AU2017228675A1 - Cells useful for immuno-based Botulinum toxin serotype A activity assays - Google Patents

Abstract

CELLS USEFUL FOR IMMUNO-BASED BOTULINUM TOXIN SEROTYPE A ACTIVITY ASSAYS Abstract: The present specification discloses clonal cell lines susceptible to BoNT/A intoxication, methods of producing such clonal cell lines, and methods of detecting Botulinum toxin serotype A activity using such clonal cell lines. H:\mm\Interwoven\NRPortbl\DCC\MM\7902079 1.docx - 10/6/15

Description

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Cells Useful for Immuno-Based Botulinum Toxin Serotype A Activity Assays [01] This patent application claims priority pursuant to 35 U.S.C. § 119(e) to U. S. Provisional Patent Application Serial No. 61/160,199 filed March 13, 2009, which is hereby incorporated by reference in its entirety.

[02] The sequences discosed in the present specification are contained in the Sequence Listing submitted with the present specification which is hereby incorporated by reference in its entirety.

[03] The ability of Clostridial toxins, such as, e.g., Botulinum neurotoxins (BoNTs), BoNT/A, BoNT/B, BoNT/C1, BoNT/D, BoNT/E, BoNT/F and BoNT/G, and Tetanus neurotoxin (TeNT), to inhibit neuronal transmission are being exploited in a wide variety of therapeutic and cosmetic applications, see e.g., William J. Lipham, Cosmetic and Clinical Applications of Botulinum Toxin (Slack, Inc., 2004). Clostridial toxins commercially available as pharmaceutical compositions include, BoNT/A preparations, such as, e.g., BOTOX® (Allergan, Inc., Irvine, CA), DYSPORT®/RELOXIN®, (Ipsen Ltd., Slough, England), PURTOX® (Mentor Corp., Santa Barbara, CA), XEOMIN® (Merz Pharmaceuticals, GmbH., Frankfurt, Germany), NEURONOX® (Medy-Tox, Inc., Ochang-myeon, South Korea), BTX-A (Biogen-tech Ltd., University, Yantai, Shandong, China); and BoNT/B preparations, such as, e.g., MYOBLOC®/NEUROBLOC® (Solstice Neurosciences, Inc., South San Francisco, CA). As an example, BOTOX® is currently approved in one or more countries for the following indications: achalasia, adult spasticity, anal fissure, back pain, blepharospasm, bruxism, cervical dystonia, essential tremor, glabellar lines or hyperkinetic facial lines, headache, hemifacial spasm, hyperactivity of bladder, hyperhidrosis, juvenile cerebral palsy, multiple sclerosis, myoclonic disorders, nasal labial lines, spasmodic dysphonia, strabismus and VII nerve disorder.

[04] At present the mouse LD50 bioassay, a lethality test, remains the “gold standard” test used by all pharmaceutical manufacturers to express the potency of their preparations. S. S. Arnon et al., JAMA 285: 1059-1070 (2001). In fact, the units on the pharmaceutical preparations’ labels are mouse LD50 units and the number of animals needed to produce statistically useful LD50 data is large. The advantage of the mouse LD50 bioassay is that it measures all the steps necessary for botulinum toxin uptake (e.g., toxin binding to a cell surface receptor, internalization of the toxin-receptor complex, light chain translocation into the cytoplasm, light chain cleavage of substrate), instead of merely determining the activity for only part of this intoxication process, such as, e.g., in vitro assays that only measure light chain enzymatic activity. Unfortunately, the mouse LD50 bioassay suffers from many drawbacks including high operational cost due to the large numbers of laboratory animals required, a lack of specificity since all BoNT serotypes will cause the same measurable end-point, and the potential for inaccuracy unless large animal groups are used. In addition, animal rights groups have exerted pressure on regulatory agencies in the United States (FDA/NICEATM/ICCVAM) and Europe (MHRA and EDQM), and on pharmaceutical companies manufacturing botulinum neurotoxin products to reduce animal testing and more importantly replace the mouse LD50 bioassay for product release. The regulatory agencies are engaging 1

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays 2017228675 15 Sep 2017 PCT/US2010/027242 18495 (BOT)/1957205.00451 WO 2010/105234 Patent Application pharmaceutical companies to apply the three “Rs” principle to the potency testing of botulinum neurotoxins: Reduce, Refine, Replace. D. Straughan, Progress in Applying the Three Rs to the Potency Testing of Botulinum Toxin Type A, Altern. Lab. Anim. 34(3): 305-313 (2006). In recent years, several steps have been already taken to reduce and refine the mouse LD50 bioassay in order to standardize the protocol and produce more consistent data using fewer animals per assay.

[05] Thus, a simple, reliable, validated and governmental agency acceptable botulinum toxin activity assay that can evaluate the integrity of all the steps necessary in botulinum toxin uptake would be of significant value because such a non-animal based assay would alleviate the need for animal testing and all the disadvantages, costs and ethical concerns associated with this type of animal-based assay. Companion patent application Ester Fernandez-Salas, et al., Immuno-Based Botulinum Toxin Serotype A Activity Assays, U.S. Patent Application Serial No: 12/403,531, provides novel compositions, cells, and methods for assaying the activity of a BoNT/A useful for various industries, such as, e.g., the pharmaceutical and food industries. Such compositions, cells, and methods do not use live animals or tissues taken from live animals, but can evaluate all the steps necessary for neurotoxin action, namely, binding and cellular uptake of toxin, translocation into the cell cytosol, and protease activity.

[06] One of the necessary components for the methods disclosed in U.S. Patent Application Serial No: 12/403,531 is the use of cells from an established cell line that are susceptible to low levels of BoNT/A intoxication because the amount of BoNT/A contained within a commercially-available pharmaceutical composition is very low. For example, approximately 4-5 ng of a BoNT/A complex is contained in the pharmaceutical composition sold as BOTOX®. Thus, there is a need to identify and create established cell lines comprising cells that are susceptible to BoNT/A intoxication when only very low levels of the neurotoxin is present in the sample. The present specification provides novel cells and cell compositions, that are susceptible to BoNT/A intoxication when only very low amounts of BoNT/A is present and thus allow assaying of commercially-available pharmaceutical composition comprising BoNT/A.

BRIEF DESCRIPTION OF THE DRAWINGS

[07] FIG. 1 shows a schematic of the current paradigm of neurotransmitter release and Clostridial toxin intoxication in a central and peripheral neuron. FIG. 1A shows a schematic for the neurotransmitter release mechanism of a central and peripheral neuron. The release process can be described as comprising two steps: 1) vesicle docking, where the vesicle-bound SNARE protein of a vesicle containing neurotransmitter molecules associates with the membrane-bound SNARE proteins located at the plasma membrane; and 2) neurotransmitter release, where the vesicle fuses with the plasma membrane and the neurotransmitter molecules are exocytosed. FIG. 1B shows a schematic of the intoxication mechanism for tetanus and botulinum toxin activity in a central and peripheral neuron. This intoxication process can be described as comprising four steps: 1) receptor binding, where Clostridial toxin binding to a Clostridial receptor complex and initiates the intoxication process; 2) complex internalization, where after toxin binding, a vesicle containing a toxin/receptor system complex is endocytosed into the cell; 3) light chain 2

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays 2017228675 15 Sep 2017 PCT/US2010/027242 18495 (BOT)/1957205.00451 WO 2010/105234 Patent Application translocation, where multiple events are thought to occur, including changes in the internal pH of the vesicle, formation of a channel pore comprising the HN domain of Clostridial toxin heavy chain, separation of the Clostridial toxin light chain from the heavy chain, and release of the light chain and 4) enzymatic target modification, where the light chain of Clostridial toxin proteolytically cleaves its target SNARE substrates, such as, e.g., SNAP-25, VAMP or Syntaxin, thereby preventing vesicle docking and neurotransmitter release.

[08] FIG. 2 shows volcano plots of genes that are more than 4-fold (log2(4) = 2) up or down regulated in BB10 and H1 cell lines as compared to the 2D6 cell line. FIG. 2A shows the genes that are up regulated in the BB10 cell line as compared to the 2D6 cell line. FIG2B shows the genes that are up regulated in the H1 cell line as compared to the 2D6 cell line. FIG2C shows the genes that are up regulated in the BB10 cell line as compared to the parental SiMa cell line (PA). FIG2D shows the genes that are up regulated in the H1 cell line as compared to the parental SiMa cell line (PA). FIG2E shows the genes that are up regulated in the parental SiMa cell line (PA) as compared to the 2D6 cell line. FIG. 2F shows the genes that are down regulated in the BB10 cell line as compared to the 2D6 cell line. FIG2G shows the genes that are down regulated in the H1 cell line as compared to the 2D6 cell line. FIG2H shows the genes that are down regulated in the parental SiMa cell line (PA) as compared to the2D6 cell line. Each dot represents a probe set. The dashed line marks the 95 % confidence interval, p < 0.05. Most of the genes that are over expressed in BB10 and H1 compared to 2D6 (A and B) are also over or underexpressed in BB10 compared to PA (C), in H1 compared to PA (D), and in PA compared to 2D6 (E), however a number of them are less than 4-fold over-expressed and/or do not pass the 95 % confidence interval.

[09] FIG. 3 shows normalized BIAcore SPR curves of 7.8 nM of the antibodies 2E2A6, 1D3B8, 3C1A5 and 2C9B10 and commercial MC-6050 and MC-6053. FIG. 3A shows the normalized data for the on-rate of each antibody. FIG. 3B shows the normalized data for the off-rate of each antibody.

DETAILED DESCRIPTION

[010] The present specification provides novel cells and cell compositions that are susceptible to BoNT/A intoxication to allow assaying of BoNT/A and BoNT/A compositions such as, e.g., commercially-available pharmaceutical composition comprising BoNT/A. The cell and cell compositions disclosed in the present specification are useful to conduct methods that can detect picomolar quantities of BoNT/A in a sample, such as the methods disclosed in, e.g., Ester Fernandez-Salas, et al., Immuno-Based Botulinum Toxin Serotype A Activity Assays, U.S. Patent Application Serial No: 12/403,531, which is hereby incorporated by reference in its entirety. The cells and cell compositions, and their use in methods of detecting BoNT/A activity reduce the need for animal toxicity studies, yet serve to analyze the multiple steps of BoNT/A intoxication, namely, binding and cellular uptake of toxin, translocation into the cell cytosol, and protease activity. As discussed further below, the novel cells and cell compositions of the present specification can be used in assays that analyze crude and bulk samples as well as highly 3

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 purified di-chain toxins and formulated toxin products and further are amenable to automated high throughput assay formats.

[011] Thus, aspects of the present specification provide a cell composition comprising cells from a clonal cell line that are susceptible to BoNT/A intoxication.

[012] Other aspects of the present specification provide a method of detecting BoNT/A activity using the clonal cell lines disclosed in the present specification.

[013] Clostridia toxins produced by Clostridium botulinum, Clostridium tetani, Clostridium baratii and Clostridium butyricum are the most widely used in therapeutic and cosmetic treatments of humans and other mammals. Strains of C. botulinum produce seven antigenically-distinct serotypes of botulinum toxins (BoNTs), which have been identified by investigating botulism outbreaks in man (BoNT/A, BoNT/B, BoNT/E and BoNT/F), animals (BoNT/C1 and BoNT/D), or isolated from soil (BoNT/G). While all seven botulinum toxin serotypes have similar structure and biological properties, each also displays heterogeneous characteristics, such as, e.g., different pharmacological properties. In contrast, tetanus toxin (TeNT) is produced by a uniform group of C. tetani. Two other species of Clostridia, C. baratii and C. butyricum, also produce toxins similar to BoNT/F and BoNT/E, respectively.

[014] Clostridial toxins are each translated as a single chain polypeptide of approximately 150 kDa that is subsequently cleaved by proteolytic scission within a disulfide loop by a naturally-occurring protease, such as, e.g., an endogenous Clostridial toxin protease ora naturally-occurring protease produced in the environment. This posttranslational processing yields a di-chain molecule comprising an approximately 50 kDa light chain (LC) and an approximately 100 kDa heavy chain (HC) held together by a single disulfide bond and noncovalent interactions. Each mature di-chain molecule comprises three functionally distinct domains: 1) an enzymatic domain located in the LC that includes a metalloprotease region containing a zinc-dependent endopeptidase activity which specifically targets core components of the neurotransmitter release apparatus; 2) a translocation domain contained within the amino-terminal half of the HC (Hn) that facilitates release of the LC from intracellular vesicles into the cytoplasm of the target cell; and 3) a binding domain found within the carboxyl-terminal half of the HC (Hc) that determines the binding activity and binding specificity of the toxin to the receptor complex located at the surface of the target cell.

[015] The binding, translocation and enzymatic activity of these three functional domains are all necessary for toxicity. While all details of this process are not yet precisely known, the overall cellular intoxication mechanism whereby Clostridial toxins enter a neuron and inhibit neurotransmitter release is similar, regardless of serotype or subtype. Although the applicants have no wish to be limited by the following description, the intoxication mechanism can be described as comprising at least four steps: 1) receptor binding, 2) complex internalization, 3) light chain translocation, and 4) enzymatic target modification (FIG. 1). The process is initiated when the Hc binding domain of a Clostridial toxin binds to a 4 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays toxin-specific receptor system located on the plasma membrane surface of a target cell. The binding specificity of a receptor complex is thought to be achieved, in part, by specific combinations of gangliosides and protein receptors that appear to distinctly comprise each Clostridial toxin receptor complex. Once bound, the toxin/receptor complexes are internalized by endocytosis and the internalized vesicles are sorted to specific intracellular routes. The translocation step appears to be triggered by the acidification of the vesicle compartment. This process seems to initiate important pH-dependent structural rearrangements that increase hydrophobicity, promote pore formation, and facilitate separation of the heavy and light chains of the toxin. Once separated, the light chain endopeptidase of the toxin is released from the intracellular vesicle into the cytosol where it appears to specifically target core components of the neurotransmitter release apparatus. These core proteins, vesicle-associated membrane protein (VAMP)/synaptobrevin, synaptosomal-associated protein of 25 kDa (SNAP-25) and Syntaxin, are necessary for synaptic vesicle docking and fusion at the nerve terminal and constitute members of the soluble N-ethylmaleimide-sensitive factor-attachment protein-receptor (SNARE) family. BoNT/A and BoNT/E cleave SNAP-25 in the carboxyl terminal region, releasing a nine or twenty six amino acid fragment, respectively, and BoNT/C1 also cleaves SNAP-25 near the carboxyl terminus releasing an eight amino acid fragment. The botulinum serotypes BoNT/B, BoNT/D, BoNT/F and BoNT/G, and tetanus toxin, act on the conserved central portion of VAMP, and release the amino terminal portion of VAMP into the cytosol. BoNT/C1 cleaves syntaxin at a single site near the cytosolic membrane surface. The selective proteolysis of synaptic SNAREs accounts for the block of neurotransmitter release caused by Clostridial toxins in vivo. The SNARE protein targets of Clostridial toxins are common to exocytosis in a variety of non-neuronal types; in these cells, as in neurons, light chain peptidase activity inhibits exocytosis, see, e.g., Yann Humeau et al., How Botulinum and Tetanus Neurotoxins Block Neurotransmitter Release, 82(5) Biochimie. 427-446 (2000); Kathryn Turton et al., Botulinum and Tetanus Neurotoxins: Structure, Function and Therapeutic Utility, 27(11) Trends Biochem. Sci. 552-558. (2002); Giovanna Lalli et al., The Journey of Tetanus and Botulinum Neurotoxins in Neurons, 11(9) Trends Microbiol. 431-437, (2003).

[016] Aspects of the present disclosure comprise, in part, a cell from an established cell line. As used herein, the term "cell" refers to any eukaryotic cell susceptible to BoNT/A intoxication by a BoNT/A or any eukaryotic cell that can uptake a BoNT/A. The term cell encompasses cells from a variety of organisms, such as, e.g., murine, rat, porcine, bovine, equine, primate and human cells; from a variety of cell types such as, e g., neuronal and non-neuronal; and can be isolated from or part of a heterogeneous cell population, tissue or organism. As used herein, the term "established cell line" is synonymous with “immortal cell line,” or “transformed cell line” and refers to a cell culture of cells selected for indefinite propagation from a cell population derived from an organism, tissue, or organ source. By definition, an established cell line excludes a cell culture of primary cells. As used herein, the term “primary cells” are cells harvested directly from fresh tissues or organs and do not have the potential to propagate indefinitely. An established cell line can comprise a heterogeneous population of cells or a uniform population of cells. An established cell line derived from a single cell is referred to as a clonal cell line. An established cell line can be one whose cells endogenously express all component necessary for the 5

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 cells to undergo the overall cellular mechanism whereby a BoNT/A proteolytically cleaves a SNAP-25 substrate and encompasses the binding of a BoNT/A to a BoNT/A receptor, the internalization of the neurotoxin/receptor complex, the translocation of the BoNT/A light chain from an intracellular vesicle into the cytoplasm and the proteolytic cleavage of a SNAP-25. Alternatively, an established cell line can be one whose cells have had introduced from an exogenous source at least one component necessary for the cells to undergo the overall cellular mechanism whereby a BoNT/A proteolytically cleaves a SNAP-25 substrate and encompasses the binding of a BoNT/A to a BoNT/A receptor, the internalization of the neurotoxin/receptor complex, the translocation of the BoNT/A light chain from an intracellular vesicle into the cytoplasm and the proteolytic cleavage of a SNAP-25. Also referred to as a genetically-engineered cell line, cells from such an established cell line may, e.g., express an exogenous FGFR2, an exogenous FGFR3, an exogenous SV2, an exogenous SNAP-25, or any combination thereof. As used herein, the term “established clonal cell line” or “clonal cell line” refers to a cell culture of cells selected from a heterogenous population of cell types comprising an established cell line, which can also be referred to as a parental cell line. Thus, as a non-limiting example, the cells from the A6, A7, A9, A10, A11, B5, B10, C5, C11, C12, D7, D11, E11, F10, H1, H3, H8, H10, 1E3, 2B9, 2E4, 3B8, 3D5, 3G10, 4B5, 4C8, 5F3, AC9, AF4, BB3, BB10, BE3, BF8, CC11, CD6, CE6, CG8, CG10, DC4, DD10, DE7, YF5, and H1 1.4 clonal cell lines were selected from the heterogenous population of cell types comprising the SiMa cell line (or parental SiMa cell line) DSMZ ACC 164.

[017] Aspects of the present disclosure comprise, in part, a cell from an established clonal cell line susceptible to BoNT/A intoxication. As used herein, the terms “cell(s) susceptible to BoNT/A intoxication,” “cell(s) susceptible to BoNT/A intoxication by a BoNT/A,” or “cell(s) from an established clonal cell line susceptible to BoNT/A intoxication by a BoNT/A” refer to cell(s) that can undergo the overall cellular mechanism whereby a BoNT/A proteolytically cleaves a SNAP-25 substrate and encompasses the binding of a BoNT/A to a BoNT/A receptor, the internalization of the neurotoxin/receptor complex, the translocation of the BoNT/A light chain from an intracellular vesicle into the cytoplasm and the proteolytic cleavage of a SNAP-25. By definition, cell(s) susceptible to BoNT/A intoxication must express, or be engineered to express, at least one BoNT/A receptor and at least one SNAP-25 substrate. Non-limiting examples of a cell or cells from an established clonal cell line susceptible to BoNT/A intoxication, include A6, A7, A9, A10, A11, B5, B10, C5, C11, C12, D7, D11, E11, F10, H1, H3, H8, H10, 1E3, 2B9, 2D2, 2D6, 2E4, 3B8, 3D5, 3G10, 4B5, 4C8, 4D3, 5C10, 5F3, AC9, AF4, BB3, BB10, BE3, BF8, CC11, CD6, CE6, CG8, CG10, DC4, DD10, DE7, DF5, YB7, YF5, and H1 1.4 clonal cell lines. As used herein, the terms “cell(s) that can uptake BoNT/A” or “cell(s) comprising an established clonal cell line that can uptake BoNT/A” refer to cells that can undergo the overall cellular mechanism whereby a BoNT/A proteolytically cleaves a SNAP-25 substrate and encompasses the binding of a BoNT/A to a BoNT/A receptor, the internalization of the neurotoxin/receptor complex, the translocation of the BoNT/A light chain from an intracellular vesicle into the cytoplasm and the proteolytic cleavage of a SNAP-25. By definition, cell(s) that can uptake BoNT/A must express, or be engineered to express, at least one BoNT/A receptor and at least one SNAP-25 substrate. Non-limiting examples of a cell or cells from an established clonal cell line that can uptake BoNT/A, include A6, A7, A9, A10, A11, B5, B10, C5, C11, C12, D7, D11, E11, F10, H1, 6 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays H3, H8, H10, 1E3, 2B9, 2D2, 2D6, 2E4, 3B8, 3D5, 3G10, 4B5, 4C8, 4D3, 5C10, 5F3, AC9, AF4, BB3, BB10, BE3, BF8, CC11, CD6, CE6, CG8, CG10, DC4, DD10, DE7, DF5, YB7, YF5, and H1 1.4 clonal cell lines. Cell lines comprising cell(s) from an established clonal cell line susceptible to BoNT/A intoxication or cell(s) that can uptake BoNT/A are referred to as a “responder cell line.” [018] Aspects of the present disclosure comprise, in part, cells from an established clonal cell line more susceptible to BoNT/A intoxication. As used herein, the terms “cell(s) more susceptible to BoNT/A intoxication,” “cell(s) more susceptible to BoNT/A intoxication by a BoNT/A,” or “cell(s) from an established clonal cell line more susceptible to BoNT/A intoxication by a BoNT/A” refer to cell(s) that undergo the overall cellular mechanism whereby a BoNT/A proteolytically cleaves a SNAP-25 substrate to a greater degree as compared to a cell(s) comprising a parental SIMa cell line, such as, e.g., parental SiMa cell line DSMZ ACC 164. Non-limiting examples of a cell or cells from an established clonal cell line more susceptible to BoNT/A intoxication, include a cell or cells from a A10, H1,2E4, 3B8, 3D5, 5F3, AF4, BB3, BB10, DC4, or H1 1.4 clonal cell lines. As used herein, the terms “cell(s) that uptake BoNT/A more” or “cell(s) comprising an established clonal cell line that uptake BoNT/A more” refer to cells that undergo the overall cellular mechanism whereby a BoNT/A proteolytically cleaves a SNAP-25 substrate to a greater degree as compared to a cell(s) comprising a parental SiMa cell line, such as, e.g., parental SiMa cell line DSMZ ACC 164. Non-limiting examples of a cell or cells from an established clonal cell line that can uptake BoNT/A more, include a cell or cells from a A10, H1, 2E4, 3B8, 3D5, 5F3, AF4, BB3, BB10, DC4, or H1 1.4 clonal cell lines. Cell lines comprising cell(s) from an established clonal cell line more susceptible to BoNT/A intoxication or cell(s) that can uptake BoNT/A more are referred to as a “high responder cell line.” [019] Aspects of the present disclosure comprise, in part, cells from an established clonal cell line less susceptible to BoNT/A intoxication. As used herein, the terms “cell(s) less susceptible to BoNT/A intoxication,” “cell(s) less susceptible to BoNT/A intoxication by a BoNT/A,” or “cell(s) from an established clonal cell line less susceptible to BoNT/A intoxication by a BoNT/A" refer to cell(s) that undergo the overall cellular mechanism whereby a BoNT/A proteolytically cleaves a SNAP-25 substrate to a lesser degree as compared to a cell(s) comprising a parental SiMa cell line, such as, e.g., parental SiMa cell line DSMZ ACC 164. Non-limiting examples of a cell or cells from an established clonal cell line less susceptible to BoNT/A intoxication, include A7, B10, D11, H10, 2D2, 2D6, 4D3, 5C10, DF5, and YB7 clonal cell lines. As used herein, the terms “cell(s) that uptake BoNT/A less” or “cell(s) comprising an established clonal cell line that uptake BoNT/A less” refer to cells that undergo the overall cellular mechanism whereby a BoNT/A proteolytically cleaves a SNAP-25 substrate to a lesser degree as compared to a cell(s) comprising a parental SiMa cell line, such as, e.g., parental SiMa cell line DSMZ ACC 164. Non-limiting examples of a cell or cells from an established clonal cell line that can uptake BoNT/A less, include A7, B10, D11, H10, 2D2, 2D6, 4D3, 5C10, DF5, and YB7 clonal cell lines. Cell lines comprising cell(s) from an established clonal cell line less susceptible to BoNT/A intoxication or cell(s) that can uptake BoNT/A less are referred to as a “low responder cell line.” 7

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 [020] Aspects of the present disclosure comprise, in part, a cell from an established clonal cell line not susceptible to BoNT/A intoxication. As used herein, the terms “cell(s) not susceptible to BoNT/A intoxication,” “cell(s) not susceptible to BoNT/A intoxication by a BoNT/A,” or “cell(s) from an established clonal cell line not susceptible to BoNT/A intoxication by a BoNT/A” refer to cell(s) that cannot undergo the overall cellular mechanism whereby a BoNT/A proteolytically cleaves a SNAP-25 substrate. As used herein, the terms “cell(s) that cannot uptake BoNT/A” or “cell(s) comprising an established clonal cell line that cannot uptake BoNT/A” refer to cells that cannot undergo the overall cellular mechanism whereby a BoNT/A proteolytically cleaves a SNAP-25 substrate. Cell lines comprising cell(s) from an established clonal cell line not susceptible to BoNT/A intoxication or cell(s) that cannot uptake BoNT/A are referred to as a “non-responder cell line.” [021] Thus in an embodiment, cells from an established clonal cell line are susceptible to BoNT/A intoxication. In aspects of this embodiment, cells from an established clonal cell line are susceptible to BoNT/A intoxication by, e.g., about 500 pM or less, about 400 pM or less, about 300 pM or less, about 200 pM or less, or about 100 pM or less of a BoNT/A. In other aspects of this embodiment, cells from an established clonal cell line are susceptible to BoNT/A intoxication by, e.g., about 90 pM or less, about 80 pM or less, about 70 pM or less, about 60 pM or less, about 50 pM or less, about 40 pM or less, about 30 pM or less, about 20 pM or less, or about 10 pM or less of a BoNT/A. In still other aspects, cells from an established clonal cell line are susceptible to BoNT/A intoxication by, e.g., about 9 pM or less, about 8 pM or less, about 7 pM or less, about 6 pM or less, about 5 pM or less, about 4 pM or less, about 3 pM or less, about 2 pM or less, or about 1 pM or less of a BoNT/A. In yet other aspects, cells from an established clonal cell line are susceptible to BoNT/A intoxication by, e.g., about 0.9 pM or less, about 0.8 pM or less, about 0.7 pM or less, about 0.6 pM or less, about 0.5 pM or less, about 0.4 pM or less, about 0.3 pM or less, about 0.2 pM, or about 0.1 pM or less of a BoNT/A. As used herein, the term “about” when qualifying a value of a stated item, number, percentage, or term refers to a range of plus or minus ten percent of the value of the stated item, percentage, parameter, or term.

[022] In another embodiment, cells comprising an established clonal cell line can uptake a BoNT/A. In aspects of this embodiment, cells comprising an established clonal cell line can uptake, e.g., about 500 pM or less, about 400 pM or less, about 300 pM or less, about 200 pM or less, or about 100 pM or less of a BoNT/A. In other aspects of this embodiment, cells comprising an established clonal cell line possess the ability to uptake about 90 pM or less, about 80 pM or less, about 70 pM or less, about 60 pM or less, about 50 pM or less, about 40 pM or less, about 30 pM or less, about 20 pM or less, or about 10 pM or less of a BoNT/A. In still other aspects, cells comprising an established clonal cell line possess the ability to uptake about 9 pM or less, about 8 pM or less, about 7 pM or less, about 6 pM or less, about 5 pM or less, about 4 pM or less, about 3 pM or less, about 2 pM or less, or about 1 pM or less of a BoNT/A. In yet other aspects, cells comprising an established clonal cell line possess the ability to uptake about 0.9 pM or less, about 0.8 pM or less, about 0.7 pM or less, about 0.6 pM or less, about 0.5 pM or less, about 0.4 pM or less, about 0.3 pM or less, about 0.2 pM or less, or about 0.1 pM or less of a BoNT/A. In other aspects, cells comprising an established clonal cell line can uptake BoNT/A from, e.g., about 0.01 pM to 8

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 about 100 pM, about 0.01 pM to about 75 pM, about 0.01 pM to about 50 pM, about 0.01 pM to about 25 pM, about 0.01 pM to about 20 pM, about 0.01 pM to about 15 pM, about 0.01 pM to about 10 pM, about 0.01 pM to about 5 pM, about 0.001 pM to about 100 pM, about 0.001 pM to about 75 pM, about 0.001 pM to about 50 pM, about 0.001 pM to about 25 pM, about 0.001 pM to about 20 pM, about 0.001 pM to about 15 pM, about 0.001 pM to about 10 pM, or about 0.001 pM to about 5 pM of BoNT/A.

[023] In another embodiment, cells from an established clonal cell line are not susceptible to BoNT/A intoxication. In aspects of this embodiment, cells from an established clonal cell line are not susceptible to BoNT/A intoxication by, e.g., about 500 pM or less, about 400 pM or less, about 300 pM or less, about 200 pM or less, or about 100 pM or less of a BoNT/A. In other aspects of this embodiment, cells from an established clonal cell line are susceptible to BoNT/A intoxication by, e.g., about 90 pM or less, about 80 pM or less, about 70 pM or less, about 60 pM or less, about 50 pM or less, about 40 pM or less, about 30 pM or less, about 20 pM or less A, or about 10 pM or less of a BoNT/A. In still other aspects, cells from an established clonal cell line are not susceptible to BoNT/A intoxication by, e.g., about 9 pM or less, about 8 pM or less, about 7 pM or less, about 6 pM or less, about 5 pM or less, about 4 pM or less, about 3 pM or less, about 2 pM or less, or about 1 pM or less of a BoNT/A. In yet other aspects, cells from an established clonal cell line are not susceptible to BoNT/A intoxication by, e.g., about 0.9 pM or less, about 0.8 pM or less, about 0.7 pM or less, about 0.6 pM or less, about 0.5 pM or less, about 0.4 pM or less, about 0.3 pM or less, about 0.2 pM, or about 0.1 pM or less of a BoNT/A. In other aspects, cells from an established clonal cell line are not susceptible to BoNT/A intoxication from, e.g., about 0.01 pM to about 100 pM, about 0.01 pM to about 75 pM, about 0.01 pM to about 50 pM, about 0.01 pM to about 25 pM, about 0.01 pM to about 20 pM, about 0.01 pM to about 15 pM, about 0.01 pM to about 10 pM, about 0.01 pM to about 5 pM, about 0.001 pM to about 100 pM, about 0.001 pM to about 75 pM, about 0.001 pM to about 50 pM, about 0.001 pM to about 25 pM, about 0.001 pM to about 20 pM, about 0.001 pM to about 15 pM, about 0.001 pM to about 10 pM, or about 0.001 pM to about 5 pM of BoNT/A.

[024] Aspects of the present disclosure comprise, in part, cells from an established clonal cell line susceptible to BoNT/A intoxication that are more stable than cells from a parental SiMa cell line, such as, e.g., parental SiMa cell line DSMZ ACC 164. As used herein, the term “stable” refers to cells from an established clonal cell line for a particular passage number that exhibit a relative EC50, sensitivity, efficacy, well-defined upper asymptote, and/or a well-defined dose-response curve for BoNT/A activity that is similar to the values for relative EC50, sensitivity, efficacy, well-defined upper asymptote, and/or a well-defined dose-response curve exhibited by cells from a parental SiMa cell line, such as, e.g., parental SiMa cell line DSMZ ACC 164, at the same or similar passage number, where the same assay conditions and the same BoNT/A (or molecule) are used in both assays.

[025] Thus in an embodiment, cells from an established clonal cell line are more stable as compared to a parental SiMa cell line. In an aspect of this embodiment, cells from an established clonal cell line are more stable as compared to the parental SiMa cell line DSMZ ACC 164. In other aspects of this embodiment, cells from an established clonal cell line are more stable for, e.g., at least 5 more passages, 9

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays 2017228675 15 Sep 2017 PCT/US2010/027242 18495 (BOT)/1957205.00451 WO 2010/105234 Patent Application at least 10 more passages, at least 15 more passages, at least 20 more passages, at least 25 more passages, or at least 30 more passages, as compared to a parental SiMa cell line. In yet other aspects of this embodiment, cells from an established clonal cell line are more stable for, e.g., at least 5 more passages, at least 10 more passages, at least 15 more passages, at least 20 more passages, at least 25 more passages, or at least 30 more passages, as compared to a parental SiMa cell line DSMZ ACC 164.

[026] Aspects of the present disclosure comprise, in part, cells from an established clonal cell line susceptible to BoNT/A intoxication that are stable over a plurality of cell passages. As used herein, the term “stable” refers to cells from an established clonal cell line for a particular passage number that exhibit a relative EC50, sensitivity, efficacy, well-defined upper asymptote, and/or a well-defined dose-response curve for BoNT/A activity that is similar to the values for relative EC50, sensitivity, efficacy, well-defined upper asymptote, and/or a well-defined dose-response curve exhibited by cells from the same established clonal cell line, but from a prior passage or passages, where the same assay conditions and the same BoNT/A (or molecule) are used in both assays.

[027] Cells from an established cell line disclosed in the present specification can exhibit consistent sensitivity to BoNT/A activity over a plurality of cell passages. As used herein, the term “sensitivity to BoNT/A activity” refers to the lowest dose that an assay can measure consistently above the signal detected by a non-treatment control or background signal.

[028] Thus, in an embodiment, cells from the established clonal cell line exhibit a sensitivity for BoNT/A activity for any given passages that is e.g., 100 pM or less, about 80 pM or less, about 70 pM or less, about 60 pM or less, about 50 pM or less, about 40 pM or less, about 30 pM or less, about 20 pM or less, about 10 pM or less, about 1 pM or less, about 0.9 pM or less, about 0.8 pM or less, about 0.7 pM or less, about 0.6 pM or less, about 0.5 pM or less, about 0.4 pM or less, about 0.3 pM or less, about 0.2 pM or less, or about 0.1 pM or less of a BoNT/A. In aspects of this embodiment, cells from the established clonal cell line exhibit a sensitivity for BoNT/A activity for any given passages that is, e.g., about 0.01 pM to about 100 pM, about 0.01 pM to about 75 pM, about 0.01 pM to about 50 pM, about 0.01 pM to about 25 pM, about 0.01 pM to about 20 pM, about 0.01 pM to about 15 pM, about 0.01 pM to about 10 pM, about 0.01 pM to about 5 pM, about 0.001 pM to about 100 pM, about 0.001 pM to about 75 pM, about 0.001 pM to about 50 pM, about 0.001 pM to about 25 pM, about 0.001 pM to about 20 pM, about 0.001 pM to about 15 pM, about 0.001 pM to about 10 pM, or about 0.001 pM to about 5 pM of BoNT/A.

[029] In another embodiment, cells from the established clonal cell line exhibit a sensitivity for BoNT/A activity that is about 100 pM or less, about 75 pM or less, about 50 pM or less, about 25 pM or less, less about 20 pM or less, about 15 pM or less, about 10 pM or less, or about 1 pM or less for, e.g., 5 or more cell passages, 10 or more cell passages, 15 or more cell passages, 20 or more cell passages, 25 or more cell passages, 30 or more cell passages, 35 or more cell passages, 40 or more cell passages, 45 or more cell passages, or 50 or more cell passages. In other aspects of this embodiment, cells from the established clonal cell line exhibit a sensitivity for BoNT/A activity that is about 100 pM or less, about 75 10 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays pM or less, about 50 pM or less, about 25 pM or less, less about 20 pM or less, about 15 pM or less, about 10 pM or less, or about 1 pM or less for, e g., about 15 to about 60 passages, about 20 to about 60 passages, about 25 to about 60 passages, about 30 to about 60 passages, about 35 to about 60 passages, about 40 to about 60 passages, about 45 to about 60 passages, about 50 to about 60 passages, about 15 to about 50 passages, about 20 to about 50 passages, about 25 to about 50 passages, about 30 to about 50 passages, about 35 to about 50 passages, about 40 to about 50 passages, about 15 to about 40 passages, about 20 to about 40 passages, about 25 to about 40 passages, or about 30 to about 40 passages.

[030] Cells from an established cell line disclosed in the present specification can exhibit a consistent relative efficacy of BoNT/A uptake, BoNT/A activity, or BoNT/A intoxication over a plurality of cell passages. As used herein, the term “relative efficacy” refers to how well the upper asymptote for the BoNT/A activity detected in the current assay run compares to the upper asymptote for the BoNT/A activity detected in a reference standard, a reference molecule, or a reference passage number used on that assay. As used herein, the term “signal to noise ratio for the upper asymptote” refers to the signal detected in an assay at the upper limit of detection divided by the signal detected by a non-treatment control or background signal. The upper limit of detection is the highest dose that an assay can measure consistently before saturation of the signal occurs.

[031] Thus, in an embodiment, cells from an established cell line disclosed in the present specification can exhibit a well defined upper asymptote over a plurality of cell passages and maintain a signal to noise ratio that is consistent and adequate for the assay. In aspects of this embodiment, cells from an established cell line disclosed in the present specification must have a signal to noise ratio for the upper asymptote for BoNT/A activity of, e.g., at least 3:1, at least 4:1, at least 5:1, at least 6:1, at least 7:1, at least 8:1, at least 9:1, at least 10:1, at least 15:1, at least 20:1, at least 25:1, at least 30:1, at least 35:1, at least 40:1, at least 45:1, at least 50:1, at least 60:1, at least 70:1, at least 80:1, at least 90:1, or at least 100:1, at least 150:1, at least 200:1, at least 250:1, at least 300:1, at least 350:1, at least 400:1, at least 450:1, at least 500:1, at least 550:1, or at least 600:1, over, e.g., 5 or more cell passages, 10 or more cell passages, 15 or more cell passages, 20 or more cell passages, 25 or more cell passages, 30 or more cell passages, 35 or more cell passages, 40 or more cell passages, 45 or more cell passages, or 50 or more cell passages. In other aspects of this embodiment, cells from an established cell line disclosed in the present specification must have a signal to noise ratio for the upper asymptote for BoNT/A activity of, e.g., at least 3:1, at least 4:1, at least 5:1, at least 6:1, at least 7:1, at least 8:1, at least 9:1, at least 10:1, at least 15:1, at least 20:1, at least 25:1, at least 30:1, at least 35:1, at least 40:1, at least 45:1, at least 50:1, at least 60:1, at least 70:1, at least 80:1, at least 90:1, or at least 100:1, at least 150:1, at least 200:1, at least 250:1, at least 300:1, at least 350:1, at least 400:1, at least 450:1, at least 500:1, at least 550:1, or at least 600:1, over, e.g., about 15 to about 60 passages, about 20 to about 60 passages, about 25 to about 60 passages, about 30 to about 60 passages, about 35 to about 60 passages, about 40 to about 60 passages, about 45 to about 60 passages, about 50 to about 60 passages, about 15 to about 50 passages, about 20 to about 50 passages, about 25 to about 50 passages, about 30 to about 50 11 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays passages, about 35 to about 50 passages, about 40 to about 50 passages, about 15 to about 40 passages, about 20 to about 40 passages, about 25 to about 40 passages, or about 30 to about 40 passages.

[032] Cells from an established cell line disclosed in the present specification can exhibit a well defined dose-response curve for BoNT/A activity over a plurality of cell passages. As used herein, the term “dose-response curve” refers to the how well the raw data fits the statistical model of choice for that assay. As a non-limiting example, a sigmoidal curve with a four parameter logistics fit is a dose-response curve for an enzymatic activity assay, such as, e.g., a potency assay. As another non-limiting example, a ligand binding with one site saturation fit is a dose-response curve for a ligand/antibody binding assay.

[033] Thus, in an embodiment, cells from an established cell line disclosed in the present specification exhibit a well defined dose-response curve for BoNT/A activity over a plurality of cell passages. In aspects of this embodiment, cells from an established cell line disclosed in the present specification exhibit a well defined dose-response curve for BoNT/A activity over, e.g., 5 or more cell passages, 10 or more cell passages, 15 or more cell passages, 20 or more cell passages, 25 or more cell passages, 30 or more cell passages, 35 or more cell passages, 40 or more cell passages, 45 or more cell passages, or 50 or more cell passages. In other aspects of this embodiment, cells from an established cell line disclosed in the present specification exhibit a well defined dose-response curve for BoNT/A activity over, e.g., about 15 to about 60 passages, about 20 to about 60 passages, about 25 to about 60 passages, about 30 to about 60 passages, about 35 to about 60 passages, about 40 to about 60 passages, about 45 to about 60 passages, about 50 to about 60 passages, about 15 to about 50 passages, about 20 to about 50 passages, about 25 to about 50 passages, about 30 to about 50 passages, about 35 to about 50 passages, about 40 to about 50 passages, about 15 to about 40 passages, about 20 to about 40 passages, about 25 to about 40 passages, or about 30 to about 40 passages.

[034] Cells from an established cell line disclosed in the present specification can exhibit a consistent relative EC50 value for BoNT/A activity over a plurality of cell passages. As used herein, the term “relative EC50” or “relative EC50 value” refers to an EC50 value of BoNT/A activity that is normalized against theEC50 calculated for a reference standard, a reference molecule, or a reference passage number used on that assay.

[035] Thus, in an embodiment, cells from an established clonal cell line exhibit a consistent relative EC50 for BoNT/A activity over a plurality of cell passages. In aspects of this embodiment, cells from an established clonal cell line exhibit a consistent relative EC50 for BoNT/A activity that is, e.g., about ± 10%, about ± 20%, about ± 30%, about ± 40%, about ± 50%, about 60%, about 70%, or about ± 75%, the relative EC50 for BoNT/A activity over, e.g., 5 or more cell passages, 10 or more cell passages, 15 or more cell passages, 20 or more cell passages, 25 or more cell passages, 30 or more cell passages, 35 or more cell passages, 40 or more cell passages, 45 or more cell passages, or 50 or more cell passages. In other aspects of this embodiment, cells from an established clonal cell line exhibit a relative EC50 for 12

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays 2017228675 15 Sep 2017 PCT/US2010/027242 18495 (BOT)/1957205.00451 WO 2010/105234 Patent Application

BoNT/A activity that is, e.g., about ± 10% to about 75%, about ± 10% to about 70%, about ± 10% to about 60%, about ± 10% to about 50%, about ± 10% to about 40%, about ± 10% to about 30%, or about ± 10% to about 20% the relative EC50 for BoNT/A activity over, e.g., 5 or more cell passages, 10 or more cell passages, 15 or more cell passages, 20 or more cell passages, 25 or more cell passages, 30 or more cell passages, 35 or more cell passages, 40 or more cell passages, 45 or more cell passages, or 50 or more cell passages.

[036] Aspects of the present disclosure comprise, in part, cells from an established clonal cell line susceptible to BoNT/A intoxication that exhibit at least a 1.5-fold difference in gene expression levels of one or more genes listed in Tables 5, 6, 7, or 8 as compared to the expression levels of these genes in cells from the 2D6 cell line. In other aspects of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit a difference in gene expression levels of one or more genes listed in Tables 5, 6, 7, or 8 of, e.g., at least a 1.5-fold, at least a 2.0-fold, at least a 2.5-fold, at least a 3.0-fold, at least a 3.5-fold, at least a 4.0-fold, at least a 4.5-fold, at least a 5.0-fold, at least a 5.5-fold, at least a 6.0-fold, at least a 7.0-fold, or at least a 8.0-fold as compared to the expression levels of these genes in cells from the 2D6 cell line. In other aspects of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit a difference in gene expression levels of, e.g., 2 or more genes, 3 or more genes, 4 or more genes, 5 or more genes, 6 or more genes, 7 or more genes, 8 or more genes, 9 or more genes, 10 or more genes, 20 or more genes, 30 or more genes, 40 or more genes, 50 or more genes, 60 or more genes, 70 or more genes, 80 or more genes, 90 or more genes, or 100 or more genes listed in Tables 5, 6, 7, or 8 as compared to the expression levels of these genes in cells from the 2D6 cell line. In yet other aspects, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit a difference in gene expression levels of, e.g., about 5 genes to about 100 genes, about 10 genes to about 100 genes, about 15 genes to about 100 genes, about 20 genes to about 100 genes, about 25 genes to about 100 genes, about 5 genes to about 75 genes, about 10 genes to about 75 genes, about 15 genes to about 75 genes, about 20 genes to about 75 genes, about 25 genes to about 75 genes, about 5 genes to about 50 genes, about 10 genes to about 50 genes, about 15 genes to about 50 genes, about 20 genes to about 50 genes, or about 25 genes to about 50 genes listed in Tables 5, 6, 7, or 8 as compared to the expression levels of these genes in cells from the 2D6 cell line. The log ratio in Tables 5, 6, 7, and 8 represent log2 values where 0.585 is log2(1.5) which is a 1.5-fold difference, 1 is log2(2) which is a 2-fold difference, 1.584 is log2(3) which is a 3-fold difference, 2 is log2(4) which is a 4-fold difference, 2.321 is log2(5) which is a 5-fold difference, 2.584 is log2(6) which is a 6-fold difference, 2.807 is log2(7) which is a 7-fold difference, 3 is log2(8) which is a 8-fold difference, 3.169 is log2(9) which is a 9-fold difference, and 3.321 is log2(10) which is a 10-fold difference.

[037] In an embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes listed in Tables 5 or 7 as compared to the expression levels of these genes in cells from the 2D6 cell line. In aspects of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit an increase in gene expression levels of one or more genes listed in Tables 5 or 7 of, e g., at least a 2.0-fold, 13

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 at least a 2.5-fold, at least a 3.0-fold, at least a 3.5-fold, at least a 4.0-fold, at least a 4.5-fold, at least a 5.0-fold, at least a 5.5-fold, at least a 6.0-fold, at least a 7.0-fold, or at least a 8.0-fold as compared to the expression levels of these genes in cells from the 2D6 cell line. In other aspects of this embodiment,cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit an increase in gene expression levels of, e.g., 2 or more genes, 3 or more genes, 4 or more genes, 5 or more genes, 6 or more genes, 7 or more genes, 8 or more genes, 9 or more genes, 10 or more genes, 20 or more genes, 30 or more genes, 40 or more genes, 50 or more genes, 60 or more genes, 70 or more genes, 80 or more genes, 90 or more genes, or 100 or more genes listed in Tables 5 or 7 as compared to the expression levels of these genes in cells from the 2D6 cell line. In yet other aspects, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit an increase in gene expression levels of, e.g., about 5 genes to about 100 genes, about 10 genes to about 100 genes, about 15 genes to about 100 genes, about 20 genes to about 100 genes, about 25 genes to about 100 genes, about 5 genes to about 75 genes, about 10 genes to about 75 genes, about 15 genes to about 75 genes, about 20 genes to about 75 genes, about 25 genes to about 75 genes, about 5 genes to about 50 genes, about 10 genes to about 50 genes, about 15 genes to about 50 genes, about 20 genes to about 50 genes, or about 25 genes to about 50 genes listed in Tables 5 or 7 as compared to the expression levels of these genes in cells from the 2D6 cell line.

[038] In an embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from A2BP1, ACOI, ACOT7, ACOT9, ACTL6A, ACTL6B, ADRBK2, AGPS, AIDA, AKAP13, ALCAM, ALDH7A1, AMOTL1, ANAPC7, ANKRD13A, ANKRD54, ANKS1B, ANLN, ANP32E, ANXA6, APAF1, APBB2, APOO, ARF3, ARHGAP11A, ARHGAP24, ARHGAP24, ARHGAP6, ARHGEF3, ARHGEF6, ARL13B, ARL6, ARL6IP1, ASCL1, ASF1A, ASF1B, ASXL3, ATAD2, ATP6V1A, AURKA, AURKB, BARD1, BASP1, BAX, BCL11A, BCR, BNC2, BOK, BRCA1, BRCA2, BRD4, BRI3BP, BRIP1, BTBD3, BTG3, BUB1, BUB1B, BUB3, BVES, C10ORF58, C10ORF78, C110RF75, C120RF48, C120RF49, C14ORF106, C140RF143, C150RF23, C150RF42, C180RF54, C10RF112, C10RF183, C10RF43, C1QL1, C200RF108, C200RF20, C20ORF7, C20ORF72, C220RF28, C220RF29, C220RF39, C30RF14, C3ORF70, C40RF46, C40RF49, C50RF32, C60RF115, C9ORF100, CARHSP1, CBLB, CBWD1, CBX5, CCDC109B, CCDC117, CCDC15, CCDC21, CCDC3, CCDC34, CCDC52, CCDC86, CCDC99, CCNB1, CCNE2, CCNF, CCNYL1, CD24, CD47, CD9, CDC2, CDC25B, CDC42EP4, CDC45L, CDC5L, CDC6, CDCA2, CDCA4, CDCA5, CDCA7, CDCA8, CDH2, CDK2, CDK2AP1, CDK6, CDKAL1, CDKN2C, CDKN2D, CD01, CDS2, CECR5, CELSR3, CENPF, CENPH), CENPI, CENPJ, CENPK, CENPL, CENPM, CENPN, CENPO, CEP135, CEP152, CEP55, CEP78, CEP97, CHAF1A, CHD6, CHEK1, CHEK2, CHMP4B, CHRNA3, CHRNA7, CHST15, CIT, CKAP2, CKAP2L, CKLF, CKS1B, CLDND1, CLSTN2, CMTM7, CNN3, CNOT4, CNP, CNTN1, CNTN4, COBLL1, COQ3, CPNE4, CPT1A, CPVL, CRISPLD1, CRTAC1, CRYBG3, CRYZ, CSE1L, CSRP2, CSRP2BP, CSTF1, CTDSPL2, CTNNBL1, CTSL2, CUGBP2, CXCR4, CYTSA, DACT 1, DAZ1, DBF4B, DBH, DCLRE1B, DCPS, DDAH2, DDT, DEK, DENR, DEPDC1, DEPDC1B, DERA, DGCR14, DGKE, DHX15, DHX35, DIAPH1, DIAPH3, DKFZP434L187, DLEU2, DLGAP5, DLL3, DLX6, DNA2, DNM3, DNMT3B, DOCK10, DOK4, DOK5, 14 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays DPF1, DPYD, DPYSL3, DRAM1, DRG1, DSCC1, DSN1, DTL, DTNBP1, DTYMK, DVL2, DYNLT3, DYRK4, E2F1, E2F2, E2F7, E2F8, EAF2, EBF1, ECT2, EFNA5, EFNB2, ELAVL4, ELOVL7, EME1, EMILIN2, EMILIN3, EML1, ENC1, EPB41L5, EPOR, ERCC6L, ESC02, ESF1, ESPL1, ETS1, ETV1, EX01, EXOC5, EXOSC6, EXPH5, EZH2, FAM101B, FAM105A, FAM110A, FAM114A1, FAM118A, FAM120C, FAM129B, FAM13A, FAM162B, FAM181B, FAM19A4, FAM19A5, FAM54A, FAM64A, FAM7A3, FAM83D, FANCG, FANCI, FANCL, FANCM, FARP1, FAT1, FBLN1, FBN1, FBP1, FBX043, FBX05, FEN1, FGFR2, FH, FIGNL1, FKBP5, FNDC5, FOXD1, FOXN3, FRMD6, FRZB, FSTL1, FZD2, FZD5, FZD8, G2E3, GABBR2, GAP43, GAP43, GAS2L3, GATM, GEMIN4, GFPT2, GFRA1, GFRA2, GGCX, GINS1, GINS3, GJC1, GLDC, GMNN, GNAI1, GNASAS, GNB4, GNG11, GNG12, GNG4, GPAM, GPN3, GPR125, GPR161, GPSM2, GPX3, GRP, GSG2, GSS, GSTCD, GTSE1, GTSF1, GXYLT1, H1F0, H2AFX, HAT1, HAUS6, HDAC8, HEG1, HES6, HGF, HIC2, HMG4L, HMGB1, HMGB2, HMGB3, HMGXB4, HMMR, HOOK3, HPS4, HRH3, HS3ST2, HS6ST2, HSPB11, HTATSF1, IDH2, IFI27L1, IQGAP1, ITGA6, ITGAV, ITGB5, ITPRIP, JARID2, KCNG3, KCNJ8, KCNN1, KCTD12, KDELC2, KHDRBS3, KIAA0101, KIAA0406, KIAA1211, KIAA1524, KIF11, KIF14, KIF16B, KIF18A, KIF23, KIFC1, KLF7, KLHL13, KLHL5, KNTC1, KPNA2, LBH, LGR5, LHFPL2, LIFR, LIG3, LMF2, LMNB1, LOC100127983, LOC100128844, LOC100288551, LOC340109, LOC344595, LOC440288, LOC642597, LOC728052, LPAR1, LRFN2, LRRC1, LSM4, LUM, MAB21L1, MAB21L2, MAG EH 1, MAN1A1, MAN2A1, MAOA, MAP3K13, MAPK11, MAPK12, MAPKAPK3, MASTL, MBD2, MCAM, MCM10, MCM3, MCM4, MCM5, MCM6, MCM7, MCM8, MDC1, MDM1, MED20, MEIS1, MEIS2, MELK, MEST, MFAP2, MGAT5B, MINA, MKI67, MKL1, MLF1IP, MMD, MNS1, MPHOSPH9, MPP5, MPPED2, MRC2, MRPL35, MRPL49, MRS2, MSN, MTF2, MTHFD1, MTUS1, MVK, MYBL1, MYBL2, MYD88, MY01B, MY06, MYST1, NAAA, NAGA, NANP, NARG1, NASP, NAT 11, NAT13, NCAPD3, NCAPG, NCAPG2, NCAPH, NCAPH2, NDN, NEDD1, NEDD9, NEIL3, NELL2, NFIB, NOC4L, NOS1, NR3C1, NRG3, NRM, NRXN1, NSMCE4A, NTAN1, NUCKS1, NUDT1, NUF2, NUP107, NUP37, NUP43, NUP50, NUP93, NUSAP1, NXPH1, NXT2, ODZ3, ODZ4, OIP5, ORC1L, ORC6L, OSBPL3, PAICS, PANK2, PARP3, PASK, PBK, PCDH17, PCDH8, PCGF5, PCNA, PDCL, PDE5A, PDLIM5, PDRG1, PEG3, PELI2, PELO, PEX13, PEX26, PFKFB3, PGAM5, PGM2, PHF19, PHF20, PHF21B, PHF5A, PHLPP1, PHYHIPL, PI4KA, PIP4K2A, PIR, PKMYT1, PLCL2, PLD5, PLEKHF2, PLK2, PLK4, PLS3, PLXNA2, PLXNA4, PLXNB2, PM20D2, POLA1, POLA2, POLE, POLE2, POLQ, POSTN, PPAP2B, PPAT, PPIF, PPIL5, PPM1F, PPP1R13B, PPP1R3C, PPP2R2B, PPP3CB, PRIM1, PRIM2, PRLHR, PRPS1, PRSS12, PSMA7, PSMC3IP, PSMD5, PSMD9, PSRC1, PTER, PTGES2, PTGFRN, PTGR1, PTPRE, PTPRG, PTPRK, PTPRM, PTTG1, PVRL3, PXMP4, PXN, RAB35, RAB3B, RAD18, RAD51, RAD51C, RALY, RAN, RANBP1, RANGAP1, RASEF, RBBP7, RBBP9, RBL1, RBPMS, RBX1, RECQL4, REEP1, RELB, RELL1, REX02, RFC1, RFC2, RFC3, RFC4, RFC5, RGMA, RGS5, RILPL2, RIMBP2, RMI1, RNASEH2A, RNF182, RNF26, RNF34, RPA1, RPP30, RRM1, RRM2, RRP7A, RSRC1, S1PR3, SALL4, SAP30, SASS6, SBF2, SCD5, SCML1, SCML2, SDC1, SEC23A, SEC61A2, SELM, SEMA6A, SEMA6D, SESN3, SEZ6L, SFI1, SFRP1, SGOL2, SH3D19, SHCBP1, SHMT1, SHOX2, SIM1, SIVA1, SKA1, SKA2, SKA3, SKP2, SLC25A10, SLC26A2, SLC2A4RG, SLC2A8, SLC43A3, SLC44A5, SLC7A2, SLC8A1, SLC03A1, SLIT3, SLITRK5, SLK, SLM02, SMC1A, SMC2, SMC4, SMC6, SMO, SMYD5, SNAI2, SNAP29, SNCAIP, SNRPD3, SNX18, SNX5, SORD, SOX4, SPAG6, SPARC, SPATS2L, SPC24, SPC25, SPOCK1, SPSB4, SRGAP1, SRRD, 15 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays SRRM4, SSH2, ST8SIA1, ST8SIA2, ST8SIA4, STARD4, STIL, STK17A, STMN3, STOM, STON2, STRA6, SUSD5, SUV39H1, SVIP, SYN2, SYNE2, SYNM, SYT17, SYTL4, TBC1D1, TBX3, TCF19, TCF7L2, TCFL5, TDRKH, TEAD3, TESC, TFDP1, TFDP2, TFPI2, TH1L, THOC4, TIFA, TIMP3, TLE3, TLE4, TMCC3, TMEM107, TMEM132C, TMEM151B, TMEM170B, TMEM178, TMEM194A, TMEM38B, TMEM48, TMEM56, TMEM98, TMPO, TMSB15B, TNFAIP8, TOB2, TOMM34, TPBG, ΤΡΤΕ, TPX2, TRIM29, TRIM36, TRIM68, TRIM9, TRIP13, TROAP, TSHZ3, TSPAN14, TSPAN4, TSPAN5, TTC28, TTC9, TUBA1B, TUBB, TWIST1, TXNRD1, TYMS, TYR03, UBE2C, UBE2L3, UBE2V1, UBE3B, UCK1, UCP2, UFD1L, UHRF1, UNC119B, UNG, UQCC, USP1, USP48, UTP18, VAPB, VAV3, VPS29, VSTM2L, WDHD1, WDR51 A, WDR53, WDR62, WDR67, WEE1, WEE1, WHSC1, WRAP53, WWC3, XRCC4, XRCC6, ZAK, ZFHX4, ZFP82, ZGPAT, ZNF215, ZNF217, ZNF238, ZNF253, ZNF280B, ZNF367, ZNF43, ZNF443, ZNF503, ZNF521, ZNF560, ZNF608, ZNF626, ZNF681, ZNF71, ZNF823, ZNF85, ZNF92, ZNF93, and/or ZWINT, as compared to the expression levels of these genes in cells from the 2D6 cell line.

[039] In an aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from A2BP1, ACOT9, ALCAM, ANLN, ARHGAP24, ARHGAP6, ARHGEF3, ARHGEF6, ASCL1, ASF1B, ATAD2, AURKA, AURKB, BARD1, BASP1, BNC2, BRCA2, BRIP1, BTG3, BUB1, BUB1B, BVES, C110RF75, C120RF48, C14ORF106, C150RF42, C180RF54, C10RF112, C3ORF70, C40RF49, CCDC109B, CCDC3, CCNB1, CCNE2, CD9, CDC2, CDC25B, CDC45L, CDC6, CDCA2, CDCA5, CDCA8, CDK2, CDKN2D, CENPF, CENPI, CENPL, CENPN, CEP55, CHEK1, CHEK2, CHRNA7, CIT, CKAP2L, CLSTN2, CNTN1, CNTN4, CPVL, CRYBG3, CSRP2, CTSL2, CUGBP2, CXCR4, DAZ1, DEPDC1, DEPDC1B, DIAPH3, DLGAP5, DNA2, DOK5, DPYD, DPYSL3, DSCC1, DSN1, DTL, DYNLT3, E2F1, E2F2, E2F7, E2F8, ECT2, EFNB2, ELOVL7, EME1, EMILIN2, EMILIN3, EML1, ENC1, ERCC6L, ESC02, ESPL1, ETV1, EX01, EXPH5, FAM101B, FAM114A1, FAM54A, FAM64A, FAM7A3, FAM83D, FANCI, FAT1, FBLN1, FBP1, FBX043, FGFR2, FNDC5, FOXD1, FRMD6, FRZB, FZD5, GAS2L3, GFRA2, GINS1, GINS3, GNAI1, GNB4, GNG11, GNG12, GPSM2, GRP, GTSE1, GTSF1, HGF, HMMR, HS3ST2, ITGA6, ITPRIP, KCNG3, KCTD12, KDELC2, KIAA0101, KIAA1524, KIF11, KIF14, KIF18A, KIF23, KIFC1, LOC340109, LOC642597, LOC728052, LOC728052, LPAR1, LUM, MAB21L1, MAB21L2, MAOA, MCM10, MCM5, MELK, MINA, MKI67, MLF1IP, MPPED2, MRC2, MSN, MYBL1, MYBL2, MY06, NCAPG, NCAPH, NDN, NEDD9, NEIL3, NR3C1, NRXN1, NUF2, NUSAP1, OIP5, ORC1L, OSBPL3, PBK, PCGF5, PDE5A, PEG3, PELO, PFKFB3, PHLPP1, PLD5, PLK2, PLK4, PLS3, POLA2, POLE2, POLQ, PPAP2B, PPP1R3C, PRLHR, PRSS12, PSRC1, PTGR1, PTPRE, PTPRK, PTPRM, PTTG1, PVRL3, RAD51, RBL1, RBPMS, RELL1, RFC5, RGMA, RGS5, RNF182, RRM2, S1PR3, SGOL2, SHCBP1, SHOX2, SIM1, SKA1, SLC43A3, SLC44A5, SLC7A2, SLITRK5, SMC2, SMC6, SPAG6, SPARC, SPC24, SPC25, ST8SIA4, STK17A, SUSD5, SYN2, SYNM, SYT17, TCF19, TESC, TFDP2, TFPI2, TIMP3, TLE3, TMEM132C, TMEM178, TNFAIP8, TPBG, ΤΡΤΕ, TPX2, TRIM29, TRIM36, TRIM68, TROAP, TWIST1, TYMS, UBE2C, UBE3B, UHRF1, WDHD1, WDR51A, WDR67, WEE1, ZFP82, ZNF367, ZNF521, and/or ZWINT, as compared to the expression levels of these genes in cells from the 2D6 cell line. 16 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays [040] In another aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from A2BP1, ALCAM, ANLN, ARHGAP24, ARHGAP6, ASCL1, ASF1B, ATAD2, AURKA, AURKB, BARD1, BASP1, BNC2, BRIP1, BUB1, BVES, C110RF75, C120RF48, C14ORF106, C180RF54, C3ORF70, CCDC109B, CCDC3, CD9, CDC2, CDC45L, CDCA2, CDCA8, CDK2, CENPL, CEP55, CHEK2, CHRNA7, CKAP2L, CNTN1, CRYBG3, CUGBP2, CXCR4, DAZ1, DEPDC1, DIAPH3, DLGAP5, DOK5, DPYD, DTL, DYNLT3, E2F1, E2F7, E2F8, EFNB2, ELOVL7, EMILIN2, EML1, ENC1, ESPL1, ETV1, EX01, EXPH5, FAM54A, FAM64A, FAM7A3, FAM83D, FANCI, FAT1, FBLN1, FBX043, FGFR2, FZD5, GNAI1, GNB4, GNG11, GNG12, GPSM2, GRP, GTSE1, GTSF1, HGF, HMMR, ITGA6, ITPRIP, KCTD12, KDELC2, KIF11, KIF14, KIF18A, KIF23, KIFC1, LOC340109, LOC728052, LPAR1, LUM, MAB21L1, MAB21L2, MAOA, MCM10, MELK, MINA, MKI67, MSN, MYBL1, NCAPH, NDN, NEDD9, NEIL3, NRXN1, NUF2, NUSAP1, OIP5, ORC1L, OSBPL3, PBK, PCGF5, PEG3, PEG3, PHLPP1, PLD5, PLK2, PLK4, PLS3, POLE2, PPAP2B, PPP1R3C, PRLHR, PRSS12, PTPRE, PTPRK, PTPRM, RBPMS, RELL1, RGS5, RNF182, RRM2, S1PR3, SGOL2, SHCBP1, SHOX2, SIM1, SLC43A3, SLC44A5, SLC7A2, SLITRK5, SMC6, SPAG6, SPARC, SPC24, SPC25, ST8SIA4, STK17A, SYT17, TFPI2, TIMP3, TMEM132C, TMEM178, TPBG, ΤΡΤΕ, TPX2, TRIM36, TWIST1, UBE3B, and/or ZNF367, as compared to the expression levels of these genes in cells from the 2D6 cell line.

[041] In yet another aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from A2BP1, ARHGAP24, ARHGAP6, ASCL1, ASF1B, ATAD2, AURKA, BARD1, BASP1, BNC2, BUB1, BVES, C110RF75, CCDC3, CHEK2, CHRNA7, CKAP2L, CNTN1, CRYBG3, CUGBP2, CUGBP2, CXCR4, DAZ1, DEPDC1, DIAPH3, DLGAP5, DOK5, DPYD, DTL, DYNLT3, E2F8, EFNB2, ELOVL7, ENC1, EXPH5, FAM7A3, FANCI, FAT1, FBLN1, FGFR2, GNAI1, GNB4, GNG11, GNG12, GRP, GTSE1, GTSF1, HMMR, ITGA6, ITPRIP, KCTD12, KDELC2, LOC728052, LPAR1, LUM, MAB21L1, MAB21L2, MAOA, MCM10, MELK, MINA, MKI67, MSN, MYBL1, NDN, NEDD9, NRXN1, OSBPL3, PEG3, PLK2, PLS3, PRLHR, PRSS12, PTPRK, PTPRM, RBPMS, RGS5, RNF182, RRM2, SGOL2, SIM1, SLC43A3, SLC44A5, SLC7A2, SMC6, SPAG6, SPARC, STK17A, TFPI2, TIMP3, TMEM132C, TMEM178, and/or TPTE, as compared to the expression levels of these genes in cells from the 2D6 cell line.

[042] In another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from ADAMTS9, ATAD2, C110RF82, CDC45L, CNTN1, CNTN4, Cyclin A, Cyclin E, E2F1, E2F2, E2F7, ELOVL7, EME1, FGFR, FGFR2, KIAA1524, MELK, MYBL1, MYBL2, NDC80, NDN, ORC1L, PLS3, PRIMA1, RAD54L, RBL1, RBPMS, RRM2, S1PR3, SCLY, SLCIA3, SPC24, SPC25, ST8SIA4, TFDP1, TFP12, TK1, TMEM35, TTK, TWIST1, TYMS, TYK, and/or ZWINT, as compared to the expression levels of these genes in cells from the 2D6 cell line. 17

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 [043] In yet another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1 5-fold increase in gene expression levels of one or more genes selected from AURKB, BIRC5, BRCA1, BRCA2, BRIP1.BUB1B, CD9, DLGAP3, DYNLT3, ENC1, FBLN1, FOXM1, Θβγ, GNAI1, GNG11, GNG12, GPSM2, GUCY1B3, HGF, ITGA6, JNK, KCNJ5, KIF18A, KITLG, MMD, MSN, MYRIP, NEK2, NR3C1, NXPH1, OSBPL3, PKMYT1, PTPRM, RAD51, RAD51AP1, SLC7A2, SLC43A3, SMC6, SNAI2, SNCAIP, SSH2, STK17A, SYNP02, TOP2A, TPTE, TRAF4, TSPAN, TSPAN4, UBE3, UBE3B, and/or VAV3, as compared to the expression levels of these genes in cells from the 2D6 cell line. In still another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from ALCAM, AURKA, CHEK, CIT, CSRP2, E2F, ECT2, EFNB2, ERK, ESPL1, GNAI, GPR161, HMMR, KIF4A, KIF14, KIF15, KIF22, KIF23, KIFC1, LPAR1, MK167, OIP5, PHLPP, PP1/PP2A, PPP1R3C, PRC1, PTTG1, RACGAP, RB, RGS5, SDC2, and/or TPX2, as compared to the expression levels of these genes in cells from the 2D6 cell line.

[044] In another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from ASCL1,HES6, MAPK, NMU, PEG3, PTPRK, PRLHR, PTPRK, SGOL2, SPARC, and/or ZNF217, as compared to the expression levels of these genes in cells from the 2D6 cell line. In yet another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from ASF1B, BASP1, CHAF1A, NCAPH, PBK, PRAME, SMC2, UHRF1, and/or VRK1, as compared to the expression levels of these genes in cells from the 2D6 cell line. In still another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from C14ORF106, CEP72, KIF20A, PCNA, PEX13, PFC5, POLQ, SPAG5, SYTL4, TROAP, and/or WDR51A, as compared to the expression levels of these genes in cells from the 2D6 cell line. In a further embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from ANLN, ARHGAP24, ASPM, BUB1, CCDC99, CEP55, CKAP2, DRAM, E2F8, PLXNA2, SLC16A10, UBE2C, UBE2S, and/or WDHD1, as compared to the expression levels of these genes in cells from the 2D6 cell line.

[045] In another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from ARHGEF3, CTSL2, DIAPH3, FBP1, KIF2C, KIF11, PFKFB3, and/or PLK4, as compared to the expression levels of these genes in cells from the 2D6 cell line. In yet another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from ARHGEF3, CTSL2, DIAPH3, FBP1, KIF2C, KIF11, PFKFB3, and/or PLK4, as compared to the expression levels of these genes in cells from the 2D6 cell line. In still another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected 18

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays 2017228675 15 Sep 2017 PCT/US2010/027242 18495 (BOT)/1957205.00451 WO 2010/105234 Patent Application from FNDC5, HSPC159, MAB21L2, SLITRK5, SYN2, and/or ZNF367, as compared to the expression levels of these genes in cells from the 2D6 cell line. In a further another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from EX01, KCTD12, MY06, PHEBL1, SHCBP1, TPBG, and/or TUBB6, as compared to the expression levels of these genes in cells from the 2D6 cell line. In yet another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from BTG3, GABRA5, TR1P10, and/or ZNF521, as compared to the expression levels of these genes in cells from the 2D6 cell line. In still another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1,5-fold increase in gene expression levels of one or more genes selected from BNC2, DPYD, EMILIN2, PPIL5, and/or TACC3, as compared to the expression levels of these genes in cells from the 2D6 cell line.

[046] In another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold difference in gene expression levels of one or more genes listed in Tables 14 or 16 as compared to the expression levels levels of these genes in cells from the 2D6 cell line. In an aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1,5-fold increase in gene expression levels of one or more genes selected from ACOT9, ADAMTS9, ARHGAP24, ARHGEF3, ASCL1, BARD1, BASP1, C3ORF70, C110RF75, CCDC109B, CD9, CDCA7L, CDK2, CENPL, CLSTN2, CNTN1, CSRP2, CTSL2, CUGBP2, DEPDC1, DIAPH3, DOK5, DPYD, DYNLT3, EMILIN2, ETV1, FAM101B, FBLN1, FGFR2, FNDC5, GNAI1, GNB4, GNG11, GNG12, GPR177, GTSE1, HGF, KITLG, LPAR1, MAB21L2, MAOA, MCM10, MINA, MSN, MY06, MYRIP, PAG1, PEG3, PLK2, POLA2, PPP1R3C, PRLHR, PRSS12, PTGR1, PTPRK, PVRL3, RAB32, RBPMS, SDC2, SGOL2, SLC43A3, SLC7A2, SMC2, SMC6, SPARC, SPC25, ST8SIA4, TCF7L1, TFPI2, TMEM35, TMEM178, TNFAIP8, TPTE, TRIP10, TWIST1, and/or ZNF521, as compared to the expression levels of these genes in cells from the 2D6 cell line. In another aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5- fold increase in gene expression levels of one or more genes selected from ADAMTS9, ARHGAP24, ASCL1, BARD1, BASP1, BVES, C110RF75, CDCA7L, CNTN1, CUGBP2, DOK5, DPYD, DYNLT3, FBLN1, FGFR2, GNAI1, GNB4, GNG11, GNG12, GTSE1, GTSF1, ITPRIP, KDELC2, LOC728052, LPAR1, MAB21L2, MAOA, MINA, MSN, PEG3, PLK2, PRLHR, PRSS12, PTPRK, RBPMS, RNF182, SGOL2, SLC43A3, SLC44A5, SLC7A2, SMC6, SPARC, TFPI2, TMEM178, and/or TPTE, as compared to the expression levels of these genes in cells from the 2D6 cell line. In yet another aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5- fold increase in gene expression levels of one or more genes selected from ADAMTS9, ASCL1, BASP1, DOK5, DPYD, GNB4, GNG11, GTSF1, MAOA, MINA, MSN, PEG3, PLK2, PRSS12, RNF182, SLC44A5, SPARC, TFPI2, and/or TPTE, as compared to the expression levels of these genes in cells from the 2D6 cell line. 19

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 [047] In yet another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from ADAMTS9, ARHGAP24, ARHGEF3, ASCL1, BARD1, CD9, CDK2, CSRP2, CTSL2, DIAPH3, DOK5, DYNLT3, EMILIN2, ETV1, FBLN1, FGFR2, GNAI1, GNB4, GNG11, GNG12, HGF, KITLG, LPAR1, MCM10, MSN, PAG1, PEG3, PLK2, POLA2, PPP1R3C, PTPRK, RAB32, SDC2, SLC43A3, SLC7A2, SMC6, SPARC, SPC25, ST8SIA4, TCF7L1, TFPI2, TMEM35, TNFAIP8, TPTE, TRIP10, and/or TWIST 1, as compared to the expression levels of these genes in cells from the 2D6 cell line. In an aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from ADAMTS9, ARHGAP24, ASCL1, BARD1, DOK5, DYNLT3, FBLN1, FGFR2, GNA11, GNB4, GNG11, GNG12, LPAR1, MSN, PEG3, PLK2, PTPRK, SLC43A3, SLC7A2, SMC6, SPARC, TFPI2, and/or TPTE, as compared to the expression levels of these genes in cells from the 2D6 cell line. In another aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from ADAMTS9, ASCL1, DOK5, GNB4, GNG11, MSN, PEG3, PLK2, SPARC, TFPI2, and/or TPTE, as compared to the expression levels of these genes in cells from the 2D6 cell line.

[048] In still another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from ACOT9, BASP1, C110RF75, CCDC109B, CDCA7L, CLSTN2, CNTN1, CUGBP2, DEPDC1, DPYD, FAM101B, FNDC5, GTSE1, MAOA, MINA, MY06, MYRIP, PLK2, PRLHR, PVRL3, RBPMS, SGOL2, SMC2, TFP12, TMEM178, and/or ZNF521, as compared to the expression levels of these genes in cells from the 2D6 cell line. In an aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from BASP1, C110RF75, CDCA7L, CNTN1, CUGBP2, DPYD, GTSE1, MAOA, MINA, PLK2, PRLHR, RBPMS, SGOL2, TFPI2, and/or TMEM178, as compared to the expression levels of these genes in cells from the 2D6 cell line. In another aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from BASP1, DPYD, MAOA, MINA, PLK2, and/or TFPI2, as compared to the expression levels of these genes in cells from the 2D6 cell line.

[049] In a further embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from C3ORF70, MAB21L2, PRSS12, CENPL, GPR177, and/or PTGR1, as compared to the expression levels of these genes in cells from the 2D6 cell line. In an aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from MAB21L2 and/or PRSS12, as compared to the expression levels of these genes in cells from the 2D6 cell line. 20

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 [050] In another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold decrease in gene expression levels of one or more genes listed in Tables 6 or 8 as compared to the expression levels of these genes in cells from a 2D6 cell line. In other aspects of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit a decrease in gene expression levels of one or more genes listed in Tables 6 or 8 of, e.g., at least a 1.5-fold, at least a 2.0-fold, at least a 2.5-fold, at least a 3.0-fold, at least a 3.5-fold, at least a 4.0-fold, at least a 4.5-fold, at least a 5.0-fold, at least a 5.5-fold, at least a 6.0-fold, at least a 7.0-fold, or at least a 8.0-fold as compared to the expression levels of these genes in cells from a 2D6 cell line. In other aspects of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit a decrease in gene expression levels of, e.g., 2 or more genes, 3 or more genes, 4 or more genes, 5 or more genes, 6 or more genes, 7 or more genes, 8 or more genes, 9 or more genes, 10 or more genes, 20 or more genes, 30 or more genes, 40 or more genes, 50 or more genes, 60 or more genes, 70 or more genes, 80 or more genes, 90 or more genes, or 100 or more genes listed in Tables 6 or 8 as compared to the expression levels of these genes in cells from the 2D6 cell line. In yet other aspects of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit an decrease in gene expression levels of, e.g., about 5 genes to about 100 genes, about 10 genes to about 100 genes, about 15 genes to about 100 genes, about 20 genes to about 100 genes, about 25 genes to about 100 genes, about 5 genes to about 75 genes, about 10 genes to about 75 genes, about 15 genes to about 75 genes, about 20 genes to about 75 genes, about 25 genes to about 75 genes, about 5 genes to about 50 genes, about 10 genes to about 50 genes, about 15 genes to about 50 genes, about 20 genes to about 50 genes, or about 25 genes to about 50 genes listed in Tables 6 or 8 as compared to the expression levels of these genes in cells from the 2D6 cell line.

[051] In another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold decrease in gene expression levels of one or more genes selected from AATK, ABCA2, ABCC5, ABCC8, ABR, ABTB1, ACOT1, ACRBP, ACRV1, ACYP2, ADARB1, ADCY1, ADM, AFF1, AGAP4, AGPAT3, AGXT2L2, AHI1, AKAP9, AKIRIN1, AKT2, AMH, ANK2, ANK3, ANKHD1, ANKRD17, ANKRD50, ANKS1A, AQP1, ARF1, ARHGAP1, ARHGAP23, ARL17A, ASAM, ASPHD1, ATP2B3, ATP2B3, ATP6V0A1, ATP8B2, ATP9A, BACE1, BACH2, BLZF1, BPTF, BRUNOL4, BRUNOL5, BRWD1, BRWD2, BTBD18, BTN3A3, BZRAP1, C140RF159, C150RF24, C150RF57, C160RF52, C170RF28, C10RF21, C10RF21, C1ORF50, C210RF57, C210RF59, C210RF66, C2CD2, C2CD4A, C2ORF60, C20RF68, C30RF23, C40RF41, C50RF42, C60RF154, C60RF52, C70RF28B, C70RF54, C9ORF150, C90RF68, CACNA1D, CALY, CAMK2B, CAMK2N2, CAP2, CAPN2, CARTPT, CBS, CCDC104, CCDC50, CCDC76, CD151, CD163L1, CD302, CDC42EP1, CDH10, CDH12, CDKN1C, CDKN2A, CDS1, CFC1, CHD5, CLCN3, CLDN12, CLIP4, CLMN, CNGA3, CNNM1, CNOT6L, COL6A1, COPA, CPNE8, CRKRS, CRTC1, CRYGS, CSTB, CTSK, CUL4A, CYGB, CYLD, CYP2E1, CYP3A5, CYTL1, D4S234E, DCLK1, DCTD, DEPDC6, DHX36, DIP2A, DIS3, DKFZP547G183, DNAJC22, DTNA, DTWD1, DUSP16, DUSP5, DVL3, EFNB3, EIF3C, ELFN2, ENOSF1, ERAP1, ERBB2, ERBB4, ERMAP, ETFDH, EXOSC6, FADS3, FAM120AOS, FAM150B, FAM165B, FAM184B, FAM30A, FAM46A, FAM66C, FAT4, FBRSL1, FBXW7, FGD5, FGF13, FLJ33630, FNBP1, FOXQ6, FUBP3, GAL, GAL, 21 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays GLT25D2, GNAS, GOLGA8A, GPR123, GPX7, GRIA2, GRIP2, GRM5, GUCY1A3, H2AFY, HCG 1776018, HCG 2022304, HCN4, HEATR1, HELQ, HERC4, HERPUD2, HEXDC, HGSNAT, HIST1H2AC, HIST1H2AE, HIST1H2BD, HIST1H2BK, HIST1H3I, HIST2H2BE, HIVEP3, HNRNPM, HNRNPR, HPCAL1, HPCAL4, HSPD1, IER3, IL10RB, IL17B, INTU, JMY, KAT2B, KATNB1, KBTBD11, KCNMA1, KCNQ2, KCNS2, KCTD13, KHDC1, KIAA0125, KIAA1370, KIAA1598, KIF1A, KIF5C, KIF5C, KISS1R, KLHDC1, LCORL, LGALS3BP, LOC100130097, LOC100130360, LOC100130522, LOC100272228, LOC284408, LOC399491, LOC401320, LOC641298, LOC642852, LOC90110, LOC94431, LONRF2, LRP2BP, LRRC37A2, LRRFIP1, LTBP3, LYPLAL1, LYRM5, MAP3K5, MAP7, MAP9, MCM3AP, MCM3APAS, MCTP1, MEOX2, METTL3, MFSD4, MGAT4A, MLXIP, MRPL1, MRPS33, MST1, MUC20, MXD1, MZF1, NAMPT, NAP1L3, NBPF1, NBPF10, NCOA7, NCRNA00171, NCRNA00182, NDRG1, NDUFA4L2, NDUFV3, NEBL, NELF, NHEDC2, NHEG1, NIPAL2, NIPAL3, NLRX1, NOL3, NSMAF, NUDT19, NUP153, NUP54, OLFM3, OR7D2, OSBP, PABPC1L, PABPC4, PACRGL, PAM, PAPPA, PAQR6, PARP12, PCBD2, PCNXL2, PDCD6, PDE4C, PDE9A, PDGFRB, PDIA2, PGAP1, PHF17, PHKA1, PHKA2, PHLDA2, PIGH, PION, PKD1, PLA2G4C, PLCB4, PLEKHH1, PLP2, PLRG1, PLXNC1, PNCK, PNMA3, POFUT2, POGK, PPAPDC1A, PPAPDC1B, PPID, PPIE, PPM1K, PPP1R2, PPP2R2C, PPT1, PRKACB, PRPH, PSMB7, PTCD1, PTGER2, PTGS1, PTN, PTPRD, PTPRN, RAB11FIP3, RAB6B, RAF1, RGAG4, RGS11, RGS8, RHBDL1, RHOQ, RHOU, RLF, RNASET2, RNF13, RNF149, RNF165, RNF207, RNF41, RPL37, RSL1D1, RUNDC3A, S100A6, SCMH1, SCN2A, SERP1, SETX, SFRS18, SFXN3, SGK3, SH3BP5, SH3GL2, SH3YL1, SHC2, SHC4, SIGIRR, SIK1, SLC12A7, SLC1A2, SLC1A6, SLC22A17, SLC35F3, SLC38A5, SLC01A2, SMAGP, SMAP2, SNCA, SOBP, SORCS1, SORL1, SPINT2, SPIRE2, SPOCK2, SRR, ST8SIA3, STAR, STEAP3, STOX2, STX3, SYNJ1, SYT13, SYT5, TAF10, TANC2, TCEA1, THBS2, THSD4, TIMP1, TM2D1, TMEM111, TMEM151A, TMEM184C, TMEM41B, TMEM43, TMEM5, TMEM59L, TMIE, TNFRSF25, TNFRSF25, TOX4, TP53BP1, TPM3, TRA2A, TRIM33, TRIM73, TRIM8, TRIT1, TSR1, TTC17, TTC3, TTC39C, TUSC3, TXLNB, U2AF1, UBE2D3, UBE2G2, UBN2, UBXN6, UCN, UGP2, UNC80, UNQ1887, USP36, USPL1, VN1R1, VPS13C, VPS53, VPS8, WDFY3, WDR27, WDR85, WSB1, YJEFN3, YLPM1, ZDHHC11, ZER1, ZG16B, ZNF275, ZNF440, ZNF573, ZNF641, ZNF662, ZNF785, and/or ZNF814, as compared to the expression levels of these genes in cells from the 2D6 cell line.

[052] In an aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold decrease in gene expression levels of one or more genes selected from ACOT1, AD ARB 1, ADM, ANK2, AQP1, ASAM, C2CD4A, C30RF23, CACNA1D, CAMK2B, CAP2, CARTPT, CD163L1, CDC42EP1, CDH10, CDKN1C, CDKN2A, CFC1, CLMN, CPNE8, CYGB, CYP2E1, CYTL1, DNAJC22, DUSP5, ENOSF1, ERAP1, FGF13, FOX06, GAL, GNAS, GPX7, GRIA2, GRM5, HCG 1776018, HIST1H2AC, HIST1H2BD, HIST1H2BK, HIST2H2BE, IL17B, KIAA0125, KIAA1598, KISS1R, LRP2BP, MEOX2, NCRNA00182, NDRG1, NDUFA4L2, NIPAL2, NUDT19, PDE4C, PHKA2, PHLDA2, PTGER2, RGS11, S100A6, SCN2A, SHC4, SIGIRR, SLC1A2, SLC1A6, SLC35F3, SLC38A5, SORCS1, SYT13, SYT5, THBS2, TIMP1, and/or TMEM111, as compared to the expression levels of these genes in cells from the 2D6 cell line. 22

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 [053] In another aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold decrease in gene expression levels of one or more genes selected from ACOT1, ADARB1, ANK2, AQP1, C30RF23, CAP2, CARTPT, CD163L1, CDC42EP1, CDKN2A, CFC1, CPNE8, CYGB, CYP2E1, CYTL1, FGF13, FOX06, GNAS, GRIA2, GRM5, HIST1H2AC, IL17B, KIAA0125, KIAA1598, KISS1R, MEOX2, NDRG1, NDUFA4L2, NIPAL2, PDE4C, PHKA2, RGS11, SCN2A, SLC1A2, SLC35F3, SLC38A5, SYT13, and/or THBS2, as compared to the expression levels of these genes in cells from the 2D6 cell line.

[054] In yet another aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold decrease in gene expression levels of one or more genes selected from AQP1, CAP2, CARTPT, CD163L1, CDC42EP1, CFC1, CPNE8, CYGB, CYP2E1, CYTL1, FGF13, GNAS, GRIA2, GRM5, HIST1H2AC, IL17B, KIAA0125, MEOX2, NDUFA4L2, PDE4C, PHKA2, RGS11, SLC1A2, SLC35F3, SLC38A5, and/or SYT13, as compared to the expression levels of these genes in cells from the 2D6 cell line.

[055] In another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold decrease in gene expression levels of one or more genes selected from ANXA2, AQP1, ARHGAP9, CDH10, CDKN2A, CHPT1, CNTN2, ERAP1, and/or RGS11, as compared to the expression levels of these genes in cells from the 2D6 cell line. In yet another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5- fold decrease in gene expression levels of one or more genes selected from ABCC8, AELIM3, CAP2, IL17B, MEF2A, NEEBL, PHC, S100A6, SLC1A6, SMAD1, SMAD5, SMAD8, SYT13, and/or SYTL1, as compared to the expression levels of these genes in cells from the 2D6 cell line. In still another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5- fold decrease in gene expression levels of one or more genes selected from CSTB, GPCR, GRIM5, KISSR, SCN2A, SLC1A2, and/or THBS2, as compared to the expression levels of these genes in cells from the 2D6 cell line.

[056] In another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold decrease in gene expression levels of one or more genes selected from ADARB1, ADM, PTPPH, and/or SLC01A2, as compared to the expression levels of these genes in cells from the 2D6 cell line. In yet another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold decrease in gene expression levels of one or more genes selected from CNGA3, HIST1H3E, and/or PTGS1, as compared to the expression levels of these genes in cells from the 2D6 cell line. In still another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold decrease in gene expression levels of one or more genes selected from HIST1H2BD and/or OSCAR as compared to the expression levels of these genes in cells from the 2D6 cell line. In a further embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold decrease in gene expression levels of 23

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 one or more genes selected from CALY as compared to the expression levels of these genes in cells from the 2D6 cell line.

[057] In another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1,5-fold decrease in gene expression levels of one or more genes selected from COL5A1 and/or MICAL2 as compared to the expression levels of these genes in cells from the 2D6 cell line. In yet another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1,5-fold decrease in gene expression levels of one or more genes selected from OLFML2A and/or SIGIRR as compared to the expression levels of these genes in cells from the 2D6 cell line. In still another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1,5-fold decrease in gene expression levels of one or more genes selected from HPCAL1 and/or LPAR5 as compared to the expression levels of these genes in cells from the 2D6 cell line. In a further embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold decrease in gene expression levels of one or more genes selected from HTR1E and/or SORCS1 as compared to the expression levels of these genes in cells from the 2D6 cell line.

[058] In another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold decrease in gene expression levels of one or more genes selected from ANK2, CPNE8, CREB5, IL17B, KIAA0125, LOC100289109, LOC144571, NPAS4, SLC1A2, SORCS1, THBS2, and/or ZNF814, as compared to the expression levels of these genes in cells from the 2D6 cell line.

[059] Aspects of the present disclosure comprise, in part, cells from an established clonal cell line susceptible to BoNT/A intoxication that exhibit at least a 1.5-fold difference in gene expression levels of one or more genes listed in Tables 9, 10, 11, or 12 as compared to the expression levels of these genes in cells from a parental SiMa cell line. In aspects of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold difference in gene expression levels of one or more genes listed in Tables 9, 10, 11, or 12 as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164. In other aspects of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit a difference in gene expression levels of one or more genes listed in Tables 9, 10, 11, or 12 of, e.g., at least a 1.5-fold, at least a 2.0-fold, at least a 2.5-fold, at least a 3.0-fold, at least a 3.5-fold, at least a 4.0-fold, at least a 4.5-fold, at least a 5.0-fold, at least a 5.5-fold, at least a 6.0-fold, at least a 7.0-fold, or at least a 8.0-fold as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164. In yet other aspects of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit a difference in gene expression levels of, e.g., 2 or more genes, 3 or more genes, 4 or more genes, 5 or more genes, 6 or more genes, 7 or more genes, 8 or more genes, 9 or more genes, 10 or more genes, 20 or more genes, 30 or more genes, 40 or more genes, 50 or more genes, 60 or more genes, 70 or more genes, 80 or more genes, 90 or more genes, or 100 or more genes listed in Tables 9, 24

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 10, 11, or 12 as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164. In still other aspects of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit a difference in gene expression levels of, e.g., about 5 genes to about 100 genes, about 10 genes to about 100 genes, about 15 genes to about 100 genes, about 20 genes to about 100 genes, about 25 genes to about 100 genes, about 5 genes to about 75 genes, about 10 genes to about 75 genes, about 15 genes to about 75 genes, about 20 genes to about 75 genes, about 25 genes to about 75 genes, about 5 genes to about 50 genes, about 10 genes to about 50 genes, about 15 genes to about 50 genes, about 20 genes to about 50 genes, or about 25 genes to about 50 genes listed in Tables 9, 10, 11, or 12 as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164. The log ratio in Tables 9, 10, 11, or 12 represent log2 values where 0.585 is log2(1.5) which is a 1.5-fold difference, 1 is log2(2) which is a 2-fold difference, 1.584 is log2(3) which is a 3-fold difference, 2 is log2(4) which is a 4-fold difference, 2.321 is log2(5) which is a 5-fold difference, 2.584 is log2(6) which is a 6-fold difference, 2.807 is log2(7) which is a 7-fold difference, 3 is log2(8) which is a 8-fold difference, 3.169 is log2(9) which is a 9-fold difference, and 3.321 is log2(10) which is a 10-fold difference.

[060] In an embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold difference in gene expression levels of one or more genes selected from ACOT9, ADAMTS9, ARHGAP24, ARHGEF3, ASCL1, BARD1, BASP1, C3ORF70, C110RF75, CCDC109B, CD9, CDCA7L, CDK2, CENPL, CLSTN2, CNTN1, CSRP2, CTSL2, CUGBP2, DEPDC1, DIAPH3, DOK5, DPYD, DYNLT3, EMILIN2, ETV1, FAM101B, FBLN1, FGFR2, FNDC5, GNAI1, GNB4, GNG11, GNG12, GPR177, GTSE1, HGF, KITLG, LPAR1, MAB21L2, MAOA, MCM10, MINA, MSN, MY06, MYRIP, PAG1, PEG3, PLK2, POLA2, PPP1R3C, PRLHR, PRSS12, PTGR1, PTPRK, PVRL3, RAB32, RBPMS, SDC2, SGOL2, SLC43A3, SLC7A2, SMC2, SMC6, SPARC, SPC25, ST8SIA4, TCF7L1, TFPI2, TMEM35, TMEM178, TNFAIP8, TPTE, TRIP10, TWIST1, and/or ZNF521, as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164. In another aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold difference in gene expression levels of one or more genes selected from ADAMTS9, ARHGAP24, ASCL1, BARD1, BASP1, BVES, C110RF75, CDCA7L, CNTN1, CUGBP2, DOK5, DPYD, DYNLT3, FBLN1, FGFR2, GNAI1, GNB4, GNG11, GNG12, GTSE1, GTSF1, ITPRIP, KDELC2, LOC728052, LPAR1, MAB21L2, MAOA, MINA, MSN, PEG3, PLK2, PRLHR, PRSS12, PTPRK, RBPMS, RNF182, SGOL2, SLC43A3, SLC44A5, SLC7A2, SMC6, SPARC, TFPI2, TMEM178, and/or TPTE, as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164. In yet another aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold difference in gene expression levels of one or more genes selected from ADAMTS9, ASCL1, BASP1, DOK5, DPYD, GNB4, GNG11, GTSF1, MAOA, MINA, MSN, PEG3, PLK2, PRSS12, RNF182, SLC44A5, SPARC, TFPI2, and/or TPTE, as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164. 25

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 [061] In another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes listed in Tables 9 or 11 as compared to the expression levels of these genes in cells from a parental SiMa cell line DSMZ ACC 164. In other aspects of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit an increase in gene expression levels of one or more genes listed in Tables 9 or 11 of, e.g., at least a 1.5-fold, at least a 2.0-fold, at least a 2.5-fold, at least a 3.0-fold, at least a 3.5-fold, at least a 4.0-fold, at least a 4.5-fold, at least a 5.0-fold, at least a 5.5-fold, at least a 6.0-fold, at least a 7.0-fold, or at least a 8.0-fold as compared to the expression levels of these genes in cells from a parental SiMa cell line DSMZ ACC 164. In other aspects of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit an increase in gene expression levels of, e.g., 2 or more genes, 3 or more genes, 4 or more genes, 5 or more genes, 6 or more genes, 7 or more genes, 8 or more genes, 9 or more genes, 10 or more genes, 20 or more genes, 30 or more genes, 40 or more genes, 50 or more genes, 60 or more genes, 70 or more genes, 80 or more genes, 90 or more genes, or 100 or more genes listed in Tables 9 or 11 as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164. In yet other aspects of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit an increase in gene expression levels of, e.g., about 5 genes to about 100 genes, about 10 genes to about 100 genes, about 15 genes to about 100 genes, about 20 genes to about 100 genes, about 25 genes to about 100 genes, about 5 genes to about 75 genes, about 10 genes to about 75 genes, about 15 genes to about 75 genes, about 20 genes to about 75 genes, about 25 genes to about 75 genes, about 5 genes to about 50 genes, about 10 genes to about 50 genes, about 15 genes to about 50 genes, about 20 genes to about 50 genes, or about 25 genes to about 50 genes listed in Tables 9 or 11 as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164.

[062] In an embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from A2BP1, ADRM1, AFF4, AGAP4, ALCAM, ANAPC7, ANKRD13D, ANKRD28, API5, ARF1, ARHGAP6, ARHGEF10, ARHGEF6, ARL17A, ASCL1, ASXL1, ASXL3, ATF7IP, B3GALNT2, BASP1, BLCAP, BNC2, C10ORF58, C120RF49, C120RF51, C10RF43, C20ORF117, C20ORF7, CADM1, CADPS, CALCB, CAPN1, CAPRIN2, CBLB, CBLN2, CBWD1, CCDC150, CCDC3, CD9, CDC25B, CFDP1, CHRNA7, CIAPIN1, CLASP2, CNOT7, CPVL, CRYBG3, CSE1L, CTTNBP2NL, CUGBP2, CXCR4, DACT1, DAZ1, DBH, DCAF8, DENR, DHX35, DKFZP434L187, DLEU2, DLL1, DLL3, DYNC2H1, EAF2, EFNA5, EIF3B, EIF3C, ELOVL7, EML1, EML4, ENC1, EVL, EXOSC6, EXPH5, EZH2, FAM178A, FAM181B, FAM19A4, FAM7A3, FLJ10213, FUBP3, FUS, FZD5, GAP43, GFM1, GFRA2, GGA2, GNAI1, GNAS, GNB4, GNG11, GOLGA4, GPR125, GRM8, GRP, GSPT1, GSS, GSTCD, GULP1, HAUS2, HEG1, HNRNPL, HNRNPM, HOXA7, HOXD4, ID2, IDH3B, IL1A, INSM1, IREB2, ITGA6, ITGB5, KCTD12, KDELC2, KHDRBS3, KIAA0907, KIAA1267, KIF16B, KLC1, KLHL13, LBH, LM04, LOC100128844, LOC340109, LOC641298, LOC647190, LOC728052, LOC728153, LRPPRC, LRRFIP2, LSM3, LUM, MAB21L1, MAB21L2, MAN2A1, MAOA, MARS, MDN1, MED13L, MED22, MGC24103, MINA, MKLN1, MLEC, MMD, MORF4L2, MPZL1, MSH6, MSI2, MSN, MTMR9, MY01B, MY06, N4BP2, NAAA, NDUFS8, NEDD9, 26 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays NFIB, NKTR, NLN, NOS1, NR2C1, NUFIP2, NUPL1, OSBPL3, PAPD4, PCBP2, PCDH9, PCGF5, PCNX, PDLIM5, PDZRN3, PELI2, PFKFB3, PGP, PHF20, PLK2, PLXNA2, PLXNA4, PM20D2, POLE, POLQ, PPP2R2A, PPP2R3C, PRDX2, PSMA7, PSME4, PTGFRN, PTK2, PTPN1, PTPRE, PTPRG, QKI, RAB12, RAB35, RAB3GAP2, RAD23B, RAF1, RALGAPA1, RAN, RASEF, RBL1, RDH11, RELL1, REPS1, RGS5, RIMBP2, RNF182, RNF34, RNPEP, ROB02, RPAIN, RPL35A, RPRD1A, S1PR3, SALL4, SBNOI, SCARB2, SDHA, SEMA6A, SEZ6L, SF1, SFRS8, SIM1, SIRT2, SKIL, SLC20A1, SLC44A5, SLC7A2, SLC03A1, SLITRK5, SMAD4, SMARCC2, SMC3, SNRPB2, SNRPN, SNX5, SOX2, SPAG6, SPAG9, SPATS2L, SPON1, SR140, SSBP2, ST8SIA1, STMN3, STRA6, SYNCRIP, SYTL3, TAF15, TCF7L2, TDG, TERT, TFPI2, TGFBR1, TH1L, THOC4, TIMP3, TLE3, TMEM132C, TMEM178, TMEM181, TNRC6A, TPBG, TRA2A, TRIM29, TRIM36, TSHZ3, TXNRD1, U2AF1, UBE20, UBE2V1, UBE2Z, UBXN2A, UCHL1, USP25, USP32, USP34, VPS29, XP01, XP07, ZFAND6, ZFHX4, ZFYVE16, ZGPAT, ZNF217, ZNF451, ZNF503, and/or ZNF664, as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164.

[063] In an aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from ALCAM, ARHGAP6, ARHGEF6, ASCL1, BNC2, CBLN2, CCDC150, CCDC3, CHRNA7, CRYBG3, CUGBP2, CXCR4, DAZ1, DKFZP434L187, DLL1, EFNA5, ELOVL7, EML1, EML4, ENC1, EXPH5, FAM7A3, FZD5, GFRA2, GNAI1, GNB4, GNG11, GRP, ID2, ITGA6, KCTD12, LOC100128844, LOC340109, LOC728052, LUM, MAB21L1, MAB21L2, MAOA, MGC24103, MSN, NEDD9, NFIB, OSBPL3, PAPD4, PCDH9, PDZRN3, PLK2, POLQ, PTGFRN, PTPRE, PTPRG, RAD23B, RGS5, RNF182, ROB02, SIM1, SLC20A1, SLC44A5, SLITRK5, SPAG6, SPAG9, SR140, TFPI2, TIMP3, TMEM132C, TPBG, TRIM29, TRIM36, and/or ZFAND6, as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164.

[064] In another aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from ALCAM, ARHGAP6, ARHGEF6, CBLN2, CCDC3, CHRNA7, CRYBG3, CUGBP2, CXCR4, DAZ1, ELOVL7, EML1, EXPH5, FAM7A3, GNB4, GNG11, GRP, ITGA6, KCTD12, LOC340109, LUM, MAB21L1, MAB21L2, MGC24103, PCDH9, PLK2, POLQ, PTPRE, RGS5, RNF182, ROB02, SIM1, SLC44A5, SLITRK5, SPAG6, TIMP3, and/or TMEM132C, as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164.

[065] In yet another aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from CBLN2, CCDC3, CHRNA7, CRYBG3, CXCR4, DAZ1, EXPH5, FAM7A3, GNB4, GRP, KCTD12, LUM, MGC24103, PCDH9, PLK2, POLQ, PTPRE, RGS5, ROB02, SIM1, SLITRK5, TIMP3, and/or TMEM132C, as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164. 27

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 [066] In another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes listed in Tables 14 or 16 as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164. In aspects of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes listed in Tables 14 or 16 as compared to the expression levels of these genes in cells from a parental SiMa cell line DSMZ ACC 164. In other aspects of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit an increase in gene expression levels of one or more genes listed in Tables 14 or 16 of, e.g., at least a 1.5-fold, at least a 2.0-fold, at least a 2.5-fold, at least a 3.0-fold, at least a 3.5-fold, at least a 4.0-fold, at least a 4.5-fold, at least a 5.0-fold, at least a 5.5-fold, at least a 6.0-fold, at least a 7.0-fold, or at least a 8.0-fold as compared to the expression levels of these genes in cells from a parental SiMa cell line DSMZ ACC 164. In other aspects of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit an increase in gene expression levels of, e.g., 2 or more genes, 3 or more genes, 4 or more genes, 5 or more genes, 6 or more genes, 7 or more genes, 8 or more genes, 9 or more genes, 10 or more genes, 20 or more genes, 30 or more genes, 40 or more genes, 50 or more genes, 60 or more genes, 70 or more genes, 80 or more genes, 90 or more genes, or 100 or more genes listed in Tables 14 or 16 as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164. In yet other aspects of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit an increase in gene expression levels of, e.g., about 5 genes to about 100 genes, about 10 genes to about 100 genes, about 15 genes to about 100 genes, about 20 genes to about 100 genes, about 25 genes to about 100 genes, about 5 genes to about 75 genes, about 10 genes to about 75 genes, about 15 genes to about 75 genes, about 20 genes to about 75 genes, about 25 genes to about 75 genes, about 5 genes to about 50 genes, about 10 genes to about 50 genes, about 15 genes to about 50 genes, about 20 genes to about 50 genes, or about 25 genes to about 50 genes listed in Tables 14 or 16 as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164.

[067] In aspects of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from ACOT9, ADAMTS9, ARHGAP24, ARHGEF3, ASCL1, BARD1, BASP1, C3ORF70, C110RF75, CCDC109B, CD9, CDCA7L, CDK2, CENPL, CLSTN2, CNTN1, CSRP2, CTSL2, CUGBP2, DEPDC1, DIAPH3, DOK5, DPYD, DYNLT3, EMILIN2, ETV1, FAM101B, FBLN1, FGFR2, FNDC5, GNAI1, GNB4, GNG11, GNG12, GPR177, GTSE1, HGF, KITLG, LPAR1, MAB21L2, MAOA, MCM10, MINA, MSN, MY06, MYRIP, PAG1, PEG3, PLK2, POLA2, PPP1R3C, PRLHR, PRSS12, PTGR1, PTPRK, PVRL3, RAB32, RBPMS, SDC2, SGOL2, SLC43A3, SLC7A2, SMC2, SMC6, SPARC, SPC25, ST8SIA4, TCF7L1, TFPI2, TMEM35, TMEM178, TNFAIP8, TPTE, TRIP10, TWIST1, and/or ZNF521, as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164. In another aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1 5-fold increase in gene expression levels of one or more genes selected 28

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 from ADAMTS9, ARHGAP24, ASCL1, BARD1, BASP1, BVES, C110RF75, CDCA7L, CNTN1, CUGBP2, DOK5, DPYD, DYNLT3, FBLN1, FGFR2, GNAI1, GNB4, GNG11, GNG12, GTSE1, GTSF1, ITPRIP, KDELC2, LOC728052, LPAR1, MAB21L2, MAOA, MINA, MSN, PEG3, PLK2, PRLHR, PRSS12, PTPRK, RBPMS, RNF182, SGOL2, SLC43A3, SLC44A5, SLC7A2, SMC6, SPARC, TFPI2, TMEM178, and/or TPTE, as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164. In yet another aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from ADAMTS9, ASCL1, BASP1, DOK5, DPYD, GNB4, GNG11, GTSF1, MAOA, MINA, MSN, PEG3, PLK2, PRSS12, RNF182, SLC44A5, SPARC, TFPI2, and/or TPTE, as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164.

[068] In yet another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from ADAMTS9, ARHGAP24, ARHGEF3, ASCL1, BARD1, CD9, CDK2, CSRP2, CTSL2, DIAPH3, DOK5, DYNLT3, EMILIN2, ETV1, FBLN1, FGFR2, GNAI1, GNB4, GNG11, GNG12, HGF, KITLG, LPAR1, MCM10, MSN, PAG1, PEG3, PLK2, POLA2, PPP1R3C, PTPRK, RAB32, SDC2, SLC43A3, SLC7A2, SMC6, SPARC, SPC25, ST8SIA4, TCF7L1, TFPI2, TMEM35, TNFAIP8, TPTE, TRIP10, and/or TWIST 1, as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164. In an aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from ADAMTS9, ARHGAP24, ASCL1, BARD1, DOK5, DYNLT3, FBLN1, FGFR2, GNAI1, GNB4, GNG11, GNG12, LPAR1, MSN, PEG3, PLK2, PTPRK, SLC43A3, SLC7A2, SMC6, SPARC, TFPI2, and/or TPTE, as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164. In another aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from ADAMTS9, ASCL1, DOK5, GNB4, GNG11, MSN, PEG3, PLK2, SPARC, TFPI2, and/or TPTE, as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164.

[069] In still another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from ACOT9, BASP1, C110RF75, CCDC109B, CDCA7L, CLSTN2, CNTN1, CUGBP2, DEPDC1, DPYD, FAM101B, FNDC5, GTSE1, MAOA, MINA, MY06, MYRIP, PLK2, PRLHR, PVRL3, RBPMS, SGOL2, SMC2, TFP12, TMEM178, and/or ZNF521, as compared to the expression level of these genes in cells from the parental SiMa cell line DSMZ ACC 164. In an aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from BASP1, C110RF75, CDCA7L, CNTN1, CUGBP2, DPYD, GTSE1, MAOA, MINA, PLK2, PRLHR, RBPMS, SGOL2, TFPI2, and/or TMEM178, as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164. In another aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A 29 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from BASP1, DPYD, MAOA, MINA, PLK2, and/or TFPI2, as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164.

[070] In a further embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from C3ORF70, MAB21L2, PRSS12, CENPL, GPR177, and/or PTGR1, as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164. In an aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from MAB21L2 and/or PRSS12, as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164.

[071] In another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1,5-fold decrease in gene expression levels of one or more genes listed in Tables 10 or 12 as compared to the expression levels of these genes in cells from a parental SiMa cell line. In aspects of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1,5-fold decrease in gene expression levels of one or more genes listed in Tables 10 or 12 as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164. In other aspects of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit a decrease in gene expression levels of one or more genes listed in Tables 10 or 12 of, e.g., at least a 1.5-fold, at least a 2.0-fold, at least a 2.5-fold, at least a 3.0-fold, at least a 3.5-fold, at least a 4.0-fold, at least a 4.5-fold, at least a 5.0-fold, at least a 5.5-fold, at least a 6.0-fold, at least a 7.0-fold, or at least a 8.0-fold as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164. In other aspects cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit a decrease in gene expression levels of, e.g., 2 or more genes, 3 or more genes, 4 or more genes, 5 or more genes, 6 or more genes, 7 or more genes, 8 or more genes, 9 or more genes, 10 or more genes, 20 or more genes, 30 or more genes, 40 or more genes, 50 or more genes, 60 or more genes, 70 or more genes, 80 or more genes, 90 or more genes, or 100 or more genes listed in Tables 10 or 12 as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164. In yet other aspects cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit an decrease in gene expression levels of, e.g., about 5 genes to about 100 genes, about 10 genes to about 100 genes, about 15 genes to about 100 genes, about 20 genes to about 100 genes, about 25 genes to about 100 genes, about 5 genes to about 75 genes, about 10 genes to about 75 genes, about 15 genes to about 75 genes, about 20 genes to about 75 genes, about 25 genes to about 75 genes, about 5 genes to about 50 genes, about 10 genes to about 50 genes, about 15 genes to about 50 genes, about 20 genes to about 50 genes, or about 25 genes to about 50 genes listed in Tables 10 or 12 as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164. 30 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays [072] In an embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold decrease in gene expression levels of one or more genes selected from 1-Mar, ABCG1, ABTB1, ACOT1, ACSL1, ACVR1, ACVR2A, ACYP2, ADAMTS1, ADAMTS3, ADAMTSL1, AD ARB 1, ADCY1, ADD2, ADO, AFF3, AKAP12, ALDH1A2, ALKBH1, ALLC, AMN1, ANKH, ANKRA2, ANKRD50, ANXA5, AP3B2, ARMC10, ARMCX5, ASAM, ASB13, ASPHD1, ATG5, ATL3, ATP2B3, ATP2C1, ATRNL1, B3GALTL, BACE1, BACE2, BBS10, BBS7, BCAP29, BCL2, BCORL1, BRUNOL4, BRUNOL6, BRWD1, BTN3A3, C10ORF10, C10ORF104, C110RF57, C11ORF70, C140RF167, C150RF39, C160RF52, C170RF69, C180RF18, C1GALT1C1, C10RF21, C10RF25, C10RF97, C1RL, , C210RF57, C2CD2, C2CD4A, C20RF67, C20RF68, C30RF23, C40RF12, C40RF39, C40RF41, C50RF42, C6ORF120, C9ORF150, CADM2, CAMK2D, CAMK2N1, CAMK2N2, CAP2, CAPN2, CARTPT, CCDC126, CCDC40, CCDC50, CCNY, CD248, CD302, CDC2L6, CDC37L1, CDC42EP3, CDH12, CDKN1C, CDKN2A, CDS1, CFC1, CHMP1B, CLCN3, CLDN12, CLMN, CLN8, CNGA3, CNNM1, CNOT6L, COL27A1, COL5A1, COL6A1, COL6A2, COL6A3, COX18, COX5B, CRYGD, CRYZL1, CTPS2, CTSC, CYB5R2, CYGB, CYLD, CYP2E1, CYP2U1, CYTL1, CYYR1, D4S234E, DAB1, DBT, DCAF10, DCLK1, DCTD, DDAH1, DHRSX, DISP1, DKFZP434I0714, DKK1, DNAJC12, DNAJC24, DNASE1L1, DNER, DOPEY2, DRAM2, DSCAM, DSCR3, DTX3L, DUSP16, DUSP22, ECEL1, ECHDC3, EEF1D, EEF2K, EFEMP2, EFNB3, EMID1, ENOX2, ERAP1, ERBB2, ERBB4, ETFDH, ETS2, EYA1, FAM13C, FAM162B, FAM165B, FAM172A, FAM175A, FAM190A, FAM26F, FAM46A, FAM49A, FAM71E1, FAM76A, FAM85A, FBXL5, FBXW7, FCRLB, FGD5, FGF1, FGF13, FGF19, FGF3, FGF7, FIP1L1, FKTN, FLJ10038, FLJ35220, FLJ35390, FLJ37798, FLJ39051, FOX06, FSTL1, FUCA2, GAL, GART, GAS5, GDPD5, GLCE, GLI2, GLIS1, GLIS3, GLT25D2, GNA14, GNAS, GPR123, GPX7, GRM5, GTF2H5, GUCY1A3, H2AFJ, HCG 1776018, HDAC4, HEBP2, HELQ, HERPUD2, HHLA3, HIST1H2AC, HIST1H2BD, HIST1H2BK, HIST2H2BE, HMGCLL1, HNRNPR, HPCAL1, HPDL, HPS3, HSBP1L1, HSPA1A, HTATIP2, ICAM2, IFNAR1, IGFBP5, IGFBP7, IGSF5, IL10RB, IL13RA2, IL17D, IL20RA, IL7, IMMP2L, INSR, IRS1, ITGB1BP1, JMY, JRKL, KAT2B, KBTBD11, KCMF1, KCNMA1, KCNQ2, KCNQ5, KCTD18, KDM1A, KDSR, KHDC1, KIAA1109, KIAA1324, KIAA1598, KIAA1804, KIRREL3, KLHDC1, KRCC1, LGALS3, LGALS3BP, LIFR, LING01, LIPT1, LMAN2L, LMCD1, LOC100129195, LOC100129884, LOC100130522, LOC100130856, LOC100132167, LOC100216479, LOC100272217, LOC100287039, LOC151146, LOC153682, LOC220930, LOC254128, LOC255167, LOC283588, LOC285286, LOC285550, LOC285878, LOC286052, LOC339290, LOC401321, LOC645513, LOC80154, LOC90246, LOC93622, LOC94431, LPAR3, LPHN2, LRCH2, LRP2BP, LYRM1, LYRM5, MAGI2, MANSC1, MAP3K13, MAP3K5, MAP9, MAPKAP1, MBD5, MBLAC2, MBNL1, MCTP1, MED6, MEGF11, MEOX2, MET, METT5D1, MFSD4, MFSD6, MFSD9, MGAT4A, MORC3, MREG, MRPS18C, MRPS33, MST1, MTMR3, MTUS2, MXRA7, N4BP3, NAP1L3, NCAM1, NCAM2, NCOA7, NCRNA00081, NCRNA00117, NCRNA00171, NDUFA4L2, NDUFV3, NEAT1, NEBL, NEIL2, NET01, NFATC4, NHEDC2, NIPAL3, NLRX1, NNAT, NOTCH4, NPW, NPY, NR1H3, NR2F1, NT5E, NUDT19, NUDT6, OGFRL1, OLFM3, OMA1, OPRM1, OPTN, P4HTM, PABPC4L, PABPC5, PAK1, PAM, PAPOLG, PAPPA, PBX1, PCDHB10, PCDHB16, PCNX, PCNXL2, PDCD2, PDE4DIP, PDGFRB, PEX12, PEX6, PHKA1, PHLDB3, PIBF1, PID1, PIGH, PIGP, PIK3CB, PIWIL2, PKNOX1, PKNOX2, PLA2G12A, PLCB1, PLEKHA2, PLEKHA3, PLIN2, PLRG1, POLR3GL, POU6F1, PPAPDC1A, PPOX, PPP1R14A, PPP2R5C, 31 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays PPP3CA, PRAME, PRKACB, PRMT2, PRPH, PSD3, PSTK, PTGER2, PTGES, PTN, PTP4A3, PTPRD, PTPRN2, PTPRR, QPCT, RAB4A, RAB6B, RAC2, RAI2, RCAN1, RCC1, RDH13, RFPL1S, RG9MTD2, RGAG4, RHBDD1, RHBDF2, RHOU, RNF13, RNF41, RNLS, RPL31, RPL37, RPRD1A, RRN3, RSL1D1, RSPH3, SAP30, SAV1, SCG5, SCN5A, SERTAD4, SGMS1, SH3BGR, SH3GL2, SH3KBP1, SH3YL1, SIAE, SIGIRR, SIK1, SIK3, SIX2. SLC12A7, SLC16A14, SLC22A17, SLC22A5, SLC25A12, SLC25A4, SLC35F3, SLC6A15, SLIT1, SMARCA2, SMEK2, SNAP91, SNCA, SOCS5, SORCS2, SPATA17, SPATA7, SPIN3, SPINT1, SPINT2, SPOCK2, SPRED1, SSPN, ST8SIA3, STAC2, STAR, STEAP3, STOX2, STX12, STXBP5L, SUCLG2, SYNJ1, SYNPR, SYT13, TAF12, TAF1B, TBC1D12, TBC1D15, TCEAL2, TEX264, THAP2, TM2D1, TMCC1, TMEM182, TMEM184C, TMEM196, TMEM45B, TMEM5, TMEM59L, TMEM65, TMIE, TNC, TNFRSF10D, TNFSF4, TOX, TRAPPC9, TRHDE, TRIM61, TRIM69, TSPAN7, TSPAN9, TTC23, TTC39C, TUSC3, TXLNB, UBE2D3, UBE2W, UCN, UNC5A, UTP23, VPS37A, VSTM2A, WASF3, WDFY3, WDTC1, XPR1, XYLT1, ZBTB41, ZC3H12B, ZNF148, ZNF185, ZNF22, ZNF23, ZNF25, ZNF250, ZNF280D, ZNF285A, ZNF295, ZNF346, ZNF528, ZNF585A, ZNF610, ZNF641, ZNF662, ZNF677, and/or ZNF862, as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164.

[073] In an aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold decrease in gene expression levels of one or more genes selected from ACOT1, ADARB1, ASAM, BACE2, C11ORF70, C2CD4A, C30RF23, CADM2, CAP2, CARTPT, CDKN1C, CFC1, CNGA3, COL5A1, CYGB, CYP2E1, CYTL1, DSC AM, ECEL1, ECHDC3, FAM26F, FAM49A, FGF1, FGF13, FGF19, FLJ39051, FUCA2, GAL, GPX7, GRM5, HCG 1776018, HHLA3, HIST1H2AC, HIST1H2BD, HSPA1A, HTATIP2, ICAM2, IGFBP5, IGFBP7, IL13RA2, KCNMA1, KCNQ5, KIAA1598, KRCC1, LMCD1, LOC100216479, LOC254128, LOC339290, LPAR3, MEGF11, MEOX2, NCAM2, NDUFA4L2, NEAT 1, NNAT, NPW, NPY, PABPC4L, PAPPA, PID1, PPAPDC1A, PRAME, PRKACB, PTGER2, PTN, PTP4A3, RAC2, SLC35F3, SYT13, TCEAL2, THAP2, TMIE, TNFRSF10D, TRHDE, TXLNB, and/or ZNF662, as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164.

[074] In another aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold decrease in gene expression levels of one or more genes selected from ACOT1, ASAM, BACE2, C11ORF70, C2CD4A, C30RF23, CADM2, CAP2, CARTPT, CFC1, CNGA3, CYGB, CYP2E1, CYTL1, DSCAM, ECEL1, ECHDC3, FGF1, FGF13, FUCA2, GAL, GPX7, HSPA1A, HTATIP2, ICAM2, IGFBP5, IGFBP7, KIAA1598, KRCC1, LMCD1, LOC100216479, LOC254128, LOC339290, LPAR3, MEOX2, NDUFA4L2, NEAT1, NNAT, NPW, NPY, PAPPA, PID1, PPAPDC1A, PRAME, PTN, SLC35F3, SYT13, TCEAL2, TMIE, TNFRSF10D, TRHDE, and/or ZNF662, as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164.

[075] In yet another aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold decrease in gene expression levels of one or more genes 32 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays selected from C11ORF70, CADM2, CAP2, CARTPT, CNGA3, CYGB, CYP2E1, CYTL1, DSCAM, FGF13, FUCA2, GAL, HSPA1A, HTATIP2, ICAM2, IGFBP5, IGFBP7, LMCD1, LOC100216479, MEOX2, NDUFA4L2, NEAT1, NNAT, NPW, PID1, PRAME, SLC35F3, SYT13, TCEAL2, TMIE, TNFRSF10D, and/or ZNF662, as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZACC 164.

[076] In another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes listed in Tables 5 or 7 as compared to the expression levels of these genes in cells from the 2D6 cell line, and at least a 1.5-fold increase in gene expression levels of one or more genes listed in in Tables 9 or 11 as compared to the expression levels of these genes in cells from a parental SiMa cell line. In aspects of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes listed in Tables 5 or 7 as compared to the expression levels of these genes in cells from the 2D6 cell line, and at least a 1,5-fold increase in gene expression levels of one or more genes listed in in Tables 9 or 11 as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164. In other aspects of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit an increase in gene expression levels of one or more genes listed in Tables 5 or 7 of, e.g., at least a 1.5-fold, at least a 2.0-fold, at least a 2.5-fold, at least a 3.0-fold, at least a 3.5-fold, at least a 4.0-fold, at least a 4.5-fold, at least a 5.0-fold, at least a 5.5-fold, at least a 6.0-fold, at least 7.0-fold, or at least 8.0-fold as compared to the expression levels of these genes in cells from the 2D6 cell line, and exhibit an increase in gene expression levels of one or more genes listed in Tables 9 or 11 of, e.g., at least a 1.5-fold, at least a 2.0-fold, at least a 2.5-fold, at least a 3.0-fold, at least a 3.5-fold, at least a 4.0-fold, at least a 4.5-fold, at least a 5.0-fold, at least a 5.5-fold, at least a 6.0-fold, at least 7.0-fold, or at least 8.0-fold as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164. In other aspects of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit an increase in gene expression levels of, e.g., 2 or more genes, 3 or more genes, 4 or more genes, 5 or more genes, 6 or more genes, 7 or more genes, 8 or more genes, 9 or more genes, 10 or more genes, 20 or more genes, 30 or more genes, 40 or more genes, 50 or more genes, 60 or more genes, 70 or more genes, 80 or more genes, 90 or more genes, or 100 or more genes listed in Tables 5 or 7 as compared to the expression levels of these genes in cells from the 2D6 cell line, and listed in Tables 9 or 11 as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164. In yet other aspects cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit an increase in gene expression levels of, e.g., about 5 genes to about 100 genes, about 10 genes to about 100 genes, about 15 genes to about 100 genes, about 20 genes to about 100 genes, about 25 genes to about 100 genes, about 5 genes to about 75 genes, about 10 genes to about 75 genes, about 15 genes to about 75 genes, about 20 genes to about 75 genes, about 25 genes to about 75 genes, about 5 genes to about 50 genes, about 10 genes to about 50 genes, about 15 genes to about 50 genes, about 20 genes to about 50 genes, or about 25 genes to about 50 genes listed in Tables 5 or 7 as compared to the expression levels of these genes in cells from the 2D6 cell line, and listed in 33 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays

Tables 9 or 11 as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164.

[077] In another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from A2BP1, ALCAM, ANAPC7, ARF1, ARHGAP6, ARHGEF6, ARL17A, ASCL1, ASXL3, BASP1, BNC2, C10ORF58, C120RF49, C10RF43, C20ORF7, CBLB, CBWD1, CCDC3, CD9, CDC25B, CHRNA7, CPVL, CRYBG3, CSE1L, CUGBP2, CXCR4, DACT1, DAZ1, DBH, DHX35, DKFZP434L187, DLEU2, DLL3, EAF2, EFNA5, EIF3C, ELOVL7, EML1, ENC1, EXOSC6, EXPH5, EZH2, FAM181B, FAM19A4, FAM7A3, FUBP3, FZD5, GAP43, GFRA2, GNAI1, GNB4, GNG11, GPR125, GRP, GSS, ITGA6, ITGA6, ITGB5, KCTD12, KDELC2, KHDRBS3, KIF16B, KLHL13, LBH, LOC100128844, LOC340109, LOC641298, LOC728052, LUM, MAB21L1, MAN2A1, MAOA, MINA, MMD, MSN, MY01B, MY06, NAAA, NEDD9, NOS1, OSBPL3, PCGF5, PELI2, PFKFB3, PHF20, PLK2, PLS3, PLXNA2, PLXNA4, PM20D2, POLE, PSMA7, PTGFRN, PTPRE, PTPRG, RAB35, RAF1, RAN, RASEF, RBL1, RELL1, RGS5, RIMBP2, RNF182, RNF34, S1PR3, SALL4, SEMA6A, SEZ6L, SIM1, SLC44A5, SLC7A2, SLC03A1, SLITRK5, SPAG6, SPATS2L, ST8SIA1, STMN3, STRA6, TCF7L2, TFPI2, TH1L, THOC4, TIMP3, TLE3, TMEM132C, TMEM178, TPBG, TRA2A, TRIM29, TRIM36, TSHZ3, TXNRD1, U2AF1, UBE2V1, VPS29, ZFHX4, ZGPAT, ZNF217, and/or ZNF503, as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164.

[078] In an aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from ALCAM, ARHGAP6, ARHGEF6, ASCL1, BNC2, CCDC3, CHRNA7, CRYBG3, CUGBP2, CXCR4, DAZ1, EFNA5, ELOVL7, EML1, ENC1, EXPH5, FAM7A3, FZD5, GFRA2, GNAI1, GNB4, GNG11, GRP, ITGA6, KCTD12, LOC100128844, LOC340109, LOC728052, LUM, MAB21L1, MAB21L2, MAOA, MSN, NEDD9, OSBPL3, PLK2, PTGFRN, PTPRE, RGS5, RNF182, SIM1, SLC44A5, SLITRK5, SPAG6, TFPI2, TIMP3, TMEM132C, TPBG, TRIM29, and/or TRIM36, as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164.

[079] In another aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from ALCAM, ARHGAP6, ARHGEF6, CCDC3, CHRNA7, CRYBG3, CUGBP2, CXCR4, DAZ1, ELOVL7, EML1, EXPH5, FAM7A3, GNB4, GNG11, GRP, ITGA6, KCTD12, LOC340109, LUM, MAB21L1, MAB21L2, PLK2, PTPRE, RGS5, RNF182, SIM1, SLC44A5, SLITRK5, SPAG6, TIMP3, and/or TMEM132C, as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164.

[080] In yet another aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from CCDC3, CHRNA7, CRYBG3, CXCR4, DAZ1, EXPH5, FAM7A3, GNB4, GRP, KCTD12, 34 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays LUM, PLK2, PTPRE, RGS5, SIM1, SLITRK5, TIMP3, and/or TMEM132C, as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164.

[081] In another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from A2BP1, ALCAM, ARF1, ARL17A, ASCL1, BASP1, CD9, CUGBP2, EAF2, EIF3C, FAM181B, FUBP3, GNAI1, GNB4, GNG11, KDELC2, KHDRBS3, KLHL13, LOC641298, LOC728052, MAB21L2, MAOA, MINA, MSN, MY06, PLK2, PLS3, RAF1, RELL1, RNF182, SEZ6L, SEZ6L, SIM1, SLC44A5, SLC7A2, SLC03A1, SLITRK5, SPATS2L, TCF7L2, TFPI2, TMEM178, TRA2A, U2AF1, and/or ZNF217, as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164.

[082] In an aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from A2BP1, ALCAM, ARF1, ASCL1, BASP1, CD9, CUGBP2, EIF3C, FUBP3, GNAI1, GNB4, GNG11, KDELC2, KHDRBS3, LOC641298, LOC728052, MAB21L2, MAOA, MINA, MSN, MY06, PLK2, PLS3, RELL1, RNF182, SIM1, SLC44A5, SLC7A2, SLC03A1, SLITRK5, TCF7L2, TFPI2, TMEM178, TRA2A, and/or ZNF217, as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164.

[083] In another aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from ASCL1, CUGBP2, GNAI1, GNB4, GNG11, LOC728052, MAB21L2, MAOA, MSN, PLK2, RNF182, SIM 1, SLC44A5, SLITRK5, and/or TFPI2, as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164.

[084] In yet another aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from GNB4, GNG11, PLK2, RNF182, SIM1, SLC44A5, and/or SLITRK5, as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164.

[085] In still another aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from GNB4, PLK2, SIM1, and/or SLITRK5, as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164.

[086] In another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold decrease in gene expression levels of one or more genes listed in Tables 6 or 8 as compared to the expression levels of these genes in cells from the 2D6 cell line, and at 35

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 least a 1.5-fold decrease in gene expression levels of one or more genes listed in in Tables 10 or 12 as compared to the expression levels of these genes in cells from a parental SiMa cell line. In aspects of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold decrease in gene expression levels of one or more genes listed in Tables 6 or 8 as compared to the expression levels of these genes in cells from the 2D6 cell line, and at least a 1,5-fold decrease in gene expression levels of one or more genes listed in in Tables 10 or 12 as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164. In other aspects of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit a decrease in gene expression levels of one or more genes listed in Tables 6 or 8 of, e.g., at least a 1.5-fold, at least a 2.0-fold, at least a 2.5-fold, at least a 3.0-fold, at least a 3.5-fold, at least a 4.0-fold, at least a 4.5-fold, at least a 5.0-fold, at least a 5.5-fold, at least a 6.0-fold, at least 7.0-fold, or at least 8.0-fold as compared to the expression levels of these genes in cells from the 2D6 cell line, and a decrease in gene expression levels of one or more genes listed in Tables 10 or 12 of, e g., at least a 1.5-fold, at least a 2.0-fold, at least a 2.5-fold, at least a 3.0-fold, at least a 3.5-fold, at least a 4.0-fold, at least a 4.5-fold, at least a 5.0-fold, at least a 5.5-fold, at least a 6.0-fold, at least 7.0-fold, or at least 8.0-fold as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164. In other aspects of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit a decrease in gene expression levels of, e.g., 2 or more genes, 3 or more genes, 4 or more genes, 5 or more genes, 6 or more genes, 7 or more genes, 8 or more genes, 9 or more genes, 10 or more genes, 20 or more genes, 30 or more genes, 40 or more genes, 50 or more genes, 60 or more genes, 70 or more genes, 80 or more genes, 90 or more genes, or 100 or more genes listed in Tables 6 or 8 as compared to the expression levels of these genes in cells from the 2D6 cell line, and listed in Tables 10 or 12 as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164. In yet other aspects cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit a decrease in gene expression levels of, e.g., about 5 genes to about 100 genes, about 10 genes to about 100 genes, about 15 genes to about 100 genes, about 20 genes to about 100 genes, about 25 genes to about 100 genes, about 5 genes to about 75 genes, about 10 genes to about 75 genes, about 15 genes to about 75 genes, about 20 genes to about 75 genes, about 25 genes to about 75 genes, about 5 genes to about 50 genes, about 10 genes to about 50 genes, about 15 genes to about 50 genes, about 20 genes to about 50 genes, or about 25 genes to about 50 genes listed in Tables 6 or 8 as compared to the expression levels of these genes in cells from the 2D6 cell line, and listed in Tables 10 or 12 as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164.

[087] In an embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1,5-fold decrease in gene expression levels of one or more genes selected from ABTB1, ACOT1, ACYP2, ADARB1, ADCY1, ANKRD50, ASAM, ASPHD1, ATP2B3, BACE1, BRUNOL4, BRWD1, BTN3A3, C160RF52, C10RF21, C210RF57, C2CD2, C2CD4A, C30RF23, C9ORF150, CAMK2N2, CAP2, CAPN2, CARTPT, CD302, CDH12, CDKN2A, CDS1, CFC1, CLCN3, CLDN12, CLMN, CNGA3, CNNM1, CNOT6L, COL6A1, CYGB, CYLD, CYP2E1, CYTL1, D4S234E, DCLK1, DCTD, DUSP16, 36 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays EFNB3, ERAP1, ERBB2, ERBB4, ETFDH, FAM162B, FAM165B, FAM46A, FBXW7, FGD5, FGF13, F0X06, FSTL1, GAL, GLT25D2, GNAS, GPR123, GPX7, GRM5, GUCY1A3, HCG 1776018, HELQ, HERPUD2, HIST1H2AC, HIST1H2BD, HIST1H2BK, HIST2H2BE, HNRNPR, HPCAL1, IL10RB, JMY, KAT2B, KBTBD11, KCNMA1, KCNQ2, KHDC1, KIAA1598, KLHDC1, LGALS3BP, LIFR, LOC100130522, LOC94431, LRP2BP, LYRM5, MAP3K5, MAP9, MCTP1, MEOX2, MFSD4, MGAT4A, MRPS33, MST1, NAP1L3, NCOA7, NCRNA00171, NDUFA4L2, NDUFV3, NEBL, NHEDC2, NIPAL3, NLRX1, NUDT19, OLFM3, PAM, PAPPA, PCNXL2, PDGFRB, PHKA1, PIGH, PLRG1, PLRG1, PPAPDC1A, PRKACB, PRPH, PTGER2, PTN, PTPRD, RAB6B, RGAG4, RHOU, RNF13, RNF41, RSL1D1, SH3GL2, SH3YL1, SIGIRR, SIK1, SLC12A7, SLC22A17, SLC35F3, SNCA, SPINT2, SPOCK2, ST8SIA3, STAR, STEAP3, STOX2, SYNJ1, SYT13, TM2D1, TMEM184C, TMEM5, TMEM59L, TMIE, TTC39C, TUSC3, TXLNB, UCN, WDFY3, WDFY3, ZNF641, and/or ZNF662, as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164.

[088] In an aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold decrease in gene expression levels of one or more genes selected from ACOT1, ADARB1, ASAM, C2CD4A, C30RF23, CAP2, CARTPT, CFC1, CNGA3, CYGB, CYP2E1, CYTL1, FGF13, GAL, GPX7, GRM5, HCG 1776018, HIST1H2AC, HIST1H2BD, KCNMA1, KIAA1598, MEOX2, NDUFA4L2, PPAPDC1A, PRKACB, PTGER2, PTN, SLC35F3, SYT13, TMIE, TXLNB, and/or ZNF662, as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164.

[089] In another aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold decrease in gene expression levels of one or more genes selected from ACOT1, ASAM, C2CD4A, C30RF23, CAP2, CARTPT, CFC1, CNGA3, CYGB, CYP2E1, CYTL1, FGF13, GAL, GPX7, KIAA1598, MEOX2, NDUFA4L2, PPAPDC1A, PTN, SLC35F3, SYT13, TMIE, and/or ZNF662, as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164.

[090] In yet another aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold decrease in gene expression levels of one or more genes selected from CAP2, CARTPT, CNGA3, CYGB, CYP2E1, CYTL1, FGF13, GAL, MEOX2, NDUFA4L2, SLC35F3, SYT13, TMIE, and/or ZNF662, as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164.

[091] In another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold decrease in gene expression levels of one or more genes selected from CAP2, CDKN2A, CNGA3, FAM162B, FGF13, FOX06, FSTL1, KCNMA1, KHDC1, LIFR, MCTP1, MEOX2, P PAP DC 1 A, PTN, SYT13, TMIE, and/or ZNF662, as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164. 37

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 [092] In an aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold decrease in gene expression levels of one or more genes selected from CAP2, CDKN2A, CNGA3, FGF13, FOXO6, FSTL1, KCNMA1, KHDC1, MCTP1, MEOX2, PPAPDC1A, PTN, SYT13, TMIE, and/or ZNF662, as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164.

[093] In another aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold decrease in gene expression levels of one or more genes selected from CNGA3, FGF13, KCNMA1, MEOX2, PPAPDC1A, PTN, SYT13, TMIE, and/or ZNF662, as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164.

[094] In yet another aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold decrease in gene expression levels of one or more genes selected from CNGA3, FGF13, MEOX2, PPAPDC1A, PTN, SYT13, TMIE, and/or ZNF662, as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164.

[095] In still another aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold decrease in gene expression levels of one or more genes selected from CNGA3, FGF13, MEOX2, SYT13, TMIE, and/or ZNF662, as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164.

[096] In another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold difference in gene expression levels of one or more genes listed in Tables 14 or 16 as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164. In aspects of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold difference in gene expression levels of one or more genes listed in Tables 14 or 16 as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164. In other aspects of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit a difference in gene expression levels of one or more genes listed in Tables 14 or 16 of, e.g., at least a 1.5-fold, at least a 2.0-fold, at least a 2.5-fold, at least a 3.0-fold, at least a 3.5-fold, at least a 4.0-fold, at least a 4.5-fold, at least a 5.0-fold, at least a 5.5-fold, at least a 6.0-fold, at least a 7.0-fold, or at least a 8.0-fold as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164. In other aspects of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit an increase in gene expression levels of, e.g., 2 or more genes, 3 or more genes, 4 or more genes, 5 or more genes, 6 or more genes, 7 or more genes, 8 or more genes, 9 or more genes, 10 or more genes, 20 or more genes, 30 or more genes, 40 or more genes, 50 or more genes, 60 or more genes, 70 or more genes, 80 or more genes, 90 38

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 or more genes, or 100 or more genes listed in Tables 14 or 16 as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164. In yet other aspects cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit an increase in gene expression levels of, e.g., about 5 genes to about 100 genes, about 10 genes to about 100 genes, about 15 genes to about 100 genes, about 20 genes to about 100 genes, about 25 genes to about 100 genes, about 5 genes to about 75 genes, about 10 genes to about 75 genes, about 15 genes to about 75 genes, about 20 genes to about 75 genes, about 25 genes to about 75 genes, about 5 genes to about 50 genes, about 10 genes to about 50 genes, about 15 genes to about 50 genes, about 20 genes to about 50 genes, or about 25 genes to about 50 genes listed in Tables 14 or 16 as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164.

[097] In an embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold difference in gene expression levels of one or more genes selected from ACOT9, ADAMTS9, ARHGAP24, ARHGEF3, ASCL1, BARD1, BASP1, C3ORF70, C110RF75, CCDC109B, CD9, CDCA7L, CDK2, CENPL, CLSTN2, CNTN1, CSRP2, CTSL2, CUGBP2, DEPDC1, DIAPH3, DOK5, DPYD, DYNLT3, EMILIN2, ETV1, FAM101B, FBLN1, FGFR2, FNDC5, GNAI1, GNB4, GNG11, GNG12, GPR177, GTSE1, HGF, KITLG, LPAR1, MAB21L2, MAOA, MCM10, MINA, MSN, MY06, MYRIP, PAG1, PEG3, PLK2, POLA2, PPP1R3C, PRLHR, PRSS12, PTGR1, PTPRK, PVRL3, RAB32, RBPMS, SDC2, SGOL2, SLC43A3, SLC7A2, SMC2, SMC6, SPARC, SPC25, ST8SIA4, TCF7L1, TFPI2, TMEM35, TMEM178, TNFAIP8, TPTE, TRIP10, TWIST1, and/or ZNF521, as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164. In another aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold difference in gene expression levels of one or more genes selected from ADAMTS9, ARHGAP24, ASCL1, BARD1, BASP1, BVES, C110RF75, CDCA7L, CNTN1, CUGBP2, DOK5, DPYD, DYNLT3, FBLN1, FGFR2, GNAI1, GNB4, GNG11, GNG12, GTSE1, GTSF1, ITPRIP, KDELC2, LOC728052, LPAR1, MAB21L2, MAOA, MINA, MSN, PEG3, PLK2, PRLHR, PRSS12, PTPRK, RBPMS, RNF182, SGOL2, SLC43A3, SLC44A5, SLC7A2, SMC6, SPARC, TFPI2, TMEM178, and/or TPTE, as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164. In yet another aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold difference in gene expression levels of one or more genes selected from ADAMTS9, ASCL1, BASP1, DOK5, DPYD, GNB4, GNG11, GTSF1, MAOA, MINA, MSN, PEG3, PLK2, PRSS12, RNF182, SLC44A5, SPARC, TFPI2, and/or TPTE, as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164.

[098] In another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from ADAMTS9, ARHGAP24, ARHGEF3, ASCL1, BARD1, CD9, CDK2, CSRP2, CTSL2, DIAPH3, DOK5, DYNLT3, EMILIN2, ETV1, FBLN1, FGFR2, GNAI1, GNB4, GNG11, GNG12, HGF, KITLG, 39

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 LPAR1, MCM10, MSN, PAG1, PEG3, PLK2, POLA2, PPP1R3C, PTPRK, RAB32, SDC2, SLC43A3, SLC7A2, SMC6, SPARC, SPC25, ST8SIA4, TCF7L1, TFPI2, TMEM35, TNFAIP8, TPTE, TRIP10, and/or TWIST 1, as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164. In an aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from ADAMTS9, ARHGAP24, ASCL1, BARD1, DOK5, DYNLT3, FBLN1, FGFR2, GNAI1, GNB4, GNG11, GNG12, LPAR1, MSN, PEG3, PLK2, PTPRK, SLC43A3, SLC7A2, SMC6, SPARC, TFPI2, and/or TPTE, as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164. In another aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5- fold increase in gene expression levels of one or more genes selected from ADAMTS9, ASCL1, DOK5, GNB4, GNG11, MSN, PEG3, PLK2, SPARC, TFPI2, and/or TPTE, as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164.

[099] In yet another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from ACOT9, BASP1, C110RF75, CCDC109B, CDCA7L, CLSTN2, CNTN1, CUGBP2, DEPDC1, DPYD, FAM101B, FNDC5, GTSE1, MAOA, MINA, MY06, MYRIP, PLK2, PRLHR, PVRL3, RBPMS, SGOL2, SMC2, TFP12, TMEM178, and/or ZNF521, as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164. In an aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5- fold increase in gene expression levels of one or more genes selected from BASP1, C110RF75, CDCA7L, CNTN1, CUGBP2, DPYD, GTSE1, MAOA, MINA, PLK2, PRLHR, RBPMS, SGOL2, TFPI2, and/or TMEM178, as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164. In another aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from BASP1, DPYD, MAOA, MINA, PLK2, and/or TFPI2, as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164.

[0100] In a still another embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from C3ORF70, MAB21L2, PRSS12, CENPL, GPR177, and/or PTGR1, as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164. In an aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit at least a 1.5-fold increase in gene expression levels of one or more genes selected from MAB21L2 and/or PRSS12, as compared to the expression levels of these genes in cells from both the 2D6 cell line and the parental SiMa cell line DSMZ ACC 164. 40

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 [0101] Aspects of the present disclosure comprise, in part, cells from an established clonal cell line susceptible to BoNT/A intoxication that exhibit an equivalent or lower EC50 for BoNT/A activity relative to the EC50 for BoNT/A activity of cells from a parental SiMa cell line. In an aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit an equivalent or lower EC50 for BoNT/A activity relative to the EC50 for BoNT/A activity of cells from the parental SiMa cell line DSMZ ACC 164. In an aspect of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit an equivalent EC50 for BoNT/A activity relative to the EC50 for BoNT/A activity of cells from the parental SiMa cell line DSMZ ACC 164. In aspects of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit a lower EC50 for BoNT/A activity of, e.g., at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 100% relative to the EC50 for BoNT/A activity of cells from the parental SiMa cell line DSMZ ACC 164. In other aspects of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit a lower EC50 for BoNT/A activity of, e.g., at least 110%, at least 120%, at least 130%, at least 140%, at least 150%, at least 160%, at least 170%, at least 180%, at least 190%, or at least 200% relative to the EC50 for BoNT/A activity of cells from the parental SiMa cell line DSMZ ACC 164. In yet other aspects of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit a lower EC50 for BoNT/A activity of, e g., at least 225%, at least 250%, at least 275%, at least 300%, at least 325%, at least 350%, at least 375%, at least 400%, at least 425%, at least 450%, at least 475%, or at least 500% relative to the EC50 for BoNT/A activity of cells from the parental SiMa cell line DSMZ ACC 164. In still other aspects of this embodiment, cells from an established clonal cell line susceptible to BoNT/A intoxication exhibit an EC50 for BoNT/A activity of, e.g., 10 pM or less, 9 pM or less, 8 pM or less, 7 pM or less, 6 pM or less, 5 pM or less, 4 pM or less, 3.0 pM or less, 2.9 pM or less, 2.8 pM or less, 2.7 pM or less, 2.6 pM or less, 2.5 pM or less, 2.4 pM or less, 2.3 pM or less, 2.2 pM or less, 2.1 pM or less, 2.0 pM or less, 1.9 pM or less, 1.8 pM or less, 1.7 pM or less, 1.6 pM or less, 1.5 pM or less, 1.4 pM or less, 1.3 pM or less, 1.2 pM or less, 1.1 pM or less, 1.0 pM or less, 0.9 pM or less, 0.8 pM or less, 0.7 pM or less, 0.6 pM or less, 0.5 pM or less, 0.4 pM or less, 0.3 pM or less, 0.2 pM or less, or 0.1 pM or less.

[0102] Aspects of the present disclosure comprise, in part, a BoNT/A. As used herein, the term “BoNT/A” is synonymous with “botulinum neurotoxin serotype A” or “botulinum neurotoxin type A” and refers to both a naturally-occurring BoNT/A or a non-naturally occurring BoNT/As thereof, and includes BoNT/A complex comprising the about 150 kDa BoNT/A neurotoxin and associated non-toxin associated proteins (NAPs), as well as the about 150 kDa BoNT/A neurotoxin alone. Non-limiting examples of BoNT/A complexes include, e.g., the 900-kDa BoNT/A complex, the 500-kDa BoNT/A complex, the 300-kDa BoNT/A complex. Non-limiting examples of the about 150 kDa BoNT/A neurotoxin include, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4.

[0103] As used herein, the term “naturally occurring BoNT/A” refers to any BoNT/A produced by a naturally-occurring process, including, without limitation, BoNT/A isoforms produced from a post-translational modification, an alternatively-spliced transcript, or a spontaneous mutation, and BoNT/A 41

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 subtypes, such as, e.g., a BoNT/A1 subtype, BoNT/A2 subtype, BoNT/A3 subtype, BoNT/A4 subtype, and BoNT/A5 subtype. A naturally occurring BoNT/A includes, without limitation, SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or one that substitutes, deletes or adds, e.g., 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more, 20 or more, 30 or more, 40 or more, 50 or more, or 100 amino acids from SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. Commercially available pharmaceutical compositions of a naturally-occurring BoNT/A includes, without limitation, BOTOX® (Allergan, Inc., Irvine, CA), DYSPORT®/RELOXIN®, (Ipsen Ltd., Slough, England), PURTOX® (Mentor Corp., Santa Barbara, CA), XEOMIN® (Merz Pharmaceuticals, GmbH., Frankfurt, Germany), NEURONOX® (Medy-Tox, Inc., Ochang-myeon, South Korea), BTX-A.

[0104] As used herein, the term “non-naturally occurring BoNT/A” refers to any BoNT/A whose structure was modified with the aid of human manipulation, including, without limitation, a BoNT/A with an altered amino acid sequence produced by genetic engineering using random mutagenesis or rational design and a BoNT/A produced by in vitro chemical synthesis. Non-limiting examples of non-naturally occurring BoNT/As are described in, e.g., Steward, L.E. et al., Post-translational Modifications and Clostridial Neurotoxins, U.S. Patent 7,223,577; Dolly, J.O. et al., Activatable Clostridial Toxins, U.S. Patent No. 7,419,676; Steward, L.E. et al., Clostridial Neurotoxin Compositions and Modified Clostridial Neurotoxins, US 2004/0220386; Steward, L.E. et al., Modified Clostridial Toxins With Enhanced Targeting Capabilities For Endogenous Clostridial Toxin Receptor Systems, U.S. Patent Publication No. 2008/0096248; Steward, L.E. et al., Modified Clostridial Toxins With Altered Targeting Capabilities For Clostridial Toxin Target Cells, U.S. Patent Publication No. 2008/0161543; Steward, L.E. et al., Modified Clostridial Toxins With Enhanced Translocation Capabilities and Altered Targeting Activity For Clostridial Toxin Target Cells, U.S. Patent Publication No. 2008/0241881, each of which is hereby incorporated by reference in its entirety.

[0105] Thus in an embodiment, the BoNT/A activity being detected is from a naturally occurring BoNT/A. In aspects of this embodiment, the BoNT/A activity being detected is from a BoNT/A isoform or a BoNT/A subtype. In aspects of this embodiment, the BoNT/A activity being detected is from the BoNT/A of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In other aspects of this embodiment, the BoNT/A activity being detected is from a BoNT/A having, e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% amino acid identity with SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In other aspects of this embodiment, the BoNT/A activity being detected is from BOTOX®, DYSPORT®/RELOXIN®, PURTOX®', XEOMIN®, NEURONOX®, or BTX-A.

[0106] In another embodiment, the BoNT/A activity being detected is from a non-naturally occurring BoNT/A. In other aspects of this embodiment, the BoNT/A activity being detected is from a non-naturally occurring BoNT/A variant having, e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% amino acid identity with SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In other aspects of this embodiment, the BoNT/A activity being detected is from a non-naturally occurring BoNT/A variant having, e.g., 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 42

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays 2017228675 15 Sep 2017 PCT/US2010/027242 18495 (BOT)/1957205.00451 WO 2010/105234 Patent Application or more, 8 or more, 9 or more, 10 or more, 20 or more, 30 or more, 40 or more, 50 or more, or 100 or more non-contiguous amino acid substitutions, deletions, or additions relative to SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In yet other aspects of this embodiment, the BoNT/A activity being detected is from a non-naturally occurring BoNT/A variant having, e.g., 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more, 20 or more, 30 or more, 40 or more, 50 or more, or 100 or more contiguous amino acid substitutions, deletions, or additions relative to SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4.

[0107] Aspects of the present disclosure comprise, in part, a SNAP-25. As used herein, the term “SNAP-25” refers to a naturally-occurring SNAP-25 or a non-naturally occurring SNAP-25 which is preferentially cleaved by a BoNT/A. As used herein, the term “preferentially cleaved” refers to that the cleavage rate of a BoNT/A substrate by a BoNT/A that is at least one order of magnitude higher than the cleavage rate of any other substrate by BoNT/A. In aspects of this embodiment, the cleavage rate of a BoNT/A substrate by a BoNT/A that is at least two orders of magnitude higher, at least three orders of magnitude higher, at least four orders of magnitude higher, or at least five orders of magnitude higher than the cleavage rate of any other substrate by BoNT/A.

[0108] As used herein, the term “naturally occurring SNAP-25” refers to any SNAP-25 produced by a naturally-occurring process, including, without limitation, SNAP-25 isoforms produced from a post-translational modification, an alternatively-spliced transcript, or a spontaneous mutation, and SNAP-25 subtypes. A naturally occurring SNAP-25 includes, without limitation, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, or SEQ ID NO: 24, or one that substitutes, deletes or adds, e.g., 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more, 20 or more, 30 or more, 40 or more, 50 or more, or 100 or more amino acids from SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, or SEQ ID NO: 24.

[0109] As used herein, the term “non-naturally occurring SNAP-25” refers to any SNAP-25 whose structure was modified with the aid of human manipulation, including, without limitation, a SNAP-25 produced by genetic engineering using random mutagenesis or rational design and a SNAP-25 produced by in vitro chemical synthesis. Non-limiting examples of non-naturally occurring SNAP-25s are described in, e.g., Steward, L.E. et al., FRET Protease Assays for Clostridial Toxins, U.S. Patent 7,332,567; Fernandez-Salas et al., Lipohilic Dye-based FRET Assays for Clostridial Toxin Activity, U.S. Patent Publication 2008/0160561, each of which is hereby incorporated by reference in its entirety. A non-naturally occurring SNAP-25 may substitute, delete or add, e.g., 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more, 20 or more, 30 or more, 40 or 43 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays more, 50 or more, or 100 or more amino acids from SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, or SEQ ID NO: 24.

[0110] Thus in an embodiment, a SNAP-25 is a naturally occurring SNAP-25. In aspects of this embodiment, the SNAP-25 is a SNAP-25 isoform or a SNAP-25 subtype. In aspects of this embodiment, the naturally occurring SNAP-25 is the naturally occurring SNAP-25 of SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, or SEQ ID NO: 24. In other aspects of this embodiment, the SNAP-25 is a naturally occurring SNAP-25 having, e.g., at least 70% amino acid identity, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% amino acid identity with SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, or SEQ ID NO: 24.

[0111] In another embodiment, a SNAP-25 is a non-naturally occurring SNAP-25. In other aspects of this embodiment, the SNAP-25 is a non-naturally occurring SNAP-25 having, e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% amino acid identity with SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, or SEQ ID NO: 24. In other aspects of this embodiment, the SNAP-25 is a non-naturally occurring SNAP-25 having, e.g., 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more, 20 or more, 30 or more, 40 or more, 50 or more, or 100 or more non-contiguous amino acid substitutions, deletions, or additions relative to SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, or SEQ ID NO: 24. In yet other aspects of this embodiment, the SNAP-25 is a non-naturally occurring SNAP-25 having, e.g., 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more, 20 or more, 30 or more, 40 or more, 50 or more, or 100 or more contiguous amino acid substitutions, deletions, or additions relative to SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, or SEQ ID NO: 24. 44

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 [0112] A SNAP-25 can be an endogenous SNAP-25 or an exogenous SNAP-25. As used herein, the term “endogenous SNAP-25” refers to a SNAP-25 naturally present in the cell because it is naturally encoded within the cell’s genome, such that the cell inherently expresses the SNAP-25 without the need of an external source of SNAP-25 or an external source of genetic material encoding a SNAP-25. The expression of an endogenous SNAP-25 may be with or without environmental stimulation such as, e.g., cell differentiation. By definition, an endogenous SNAP-25 can only be a naturally-occurring SNAP-25 or variants thereof. For example, the following established cell lines express an endogenous SNAP-25: BE(2)-M17, Kelly, LA1-55n, N1E-115, N4TG3, N18, Neuro-2a, NG108-15, PC12, SH-SY5Y, SiMa, and SK-N-BE(2)-C.

[0113] As used herein, the term “exogenous SNAP-25” refers to a SNAP-25 expressed in a cell through the introduction of an external source of SNAP-25 or an external source of genetic material encoding a SNAP-25 by human manipulation. The expression of an exogenous SNAP-25 may be with or without environmental stimulation such as, e.g., cell differentiation. As a non-limiting example, cells from an established clonal cell line can express an exogenous SNAP-25 by transient or stably transfection of a SNAP-25 coding sequence. As another non-limiting example, cells from an established clonal cell line can express an exogenous SNAP-25 by protein transfection of a SNAP-25. An exogenous SNAP-25 can be a naturally-occurring SNAP-25 or variants thereof, or a non-naturally occurring SNAP-25 or variants thereof.

[0114] Thus in an embodiment, cells from an established clonal cell line express an endogenous SNAP-25. In aspects of this embodiment, the endogenous SNAP-25 expressed by cells from an established clonal cell line is a naturally-occurring SNAP-25. In other aspects of this embodiment, the endogenous SNAP-25 expressed by cells from an established clonal cell line is SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, or SEQ ID NO: 24. In yet other aspects of this embodiment, the endogenous SNAP-25 expressed by cells from an established clonal cell line is a naturally occurring SNAP-25, such as, e.g., a SNAP-25 isoform or a SNAP-25 subtype. In other aspects of this embodiment, the endogenous SNAP-25 expressed by cells from an established clonal cell line is a naturally occurring SNAP-25 having, e.g., at least 70% amino acid identity, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% amino acid identity with SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, or SEQ ID NO: 24.

[0115] In another embodiment, cells from an established clonal cell line are transiently or stably engineered to express an exogenous SNAP-25. In an aspect of this embodiment, cells from an established clonal cell line are transiently or stably engineered to express a naturally-occurring SNAP-25. In other aspects of this embodiment, cells from an established clonal cell line are transiently or stably 45

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays 2017228675 15 Sep 2017 PCT/US2010/027242 18495 (BOT)/1957205.00451 WO 2010/105234 Patent Application engineered to express the naturally-occurring SNAP-25 of SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, or SEQ ID NO: 24. In yet other aspects of this embodiment, cells from an established clonal cell line are transiently or stably engineered to express a naturally occurring SNAP-25, such as, e.g., a SNAP-25 isoform or a SNAP-25 subtype. In still other aspects of this embodiment, cells from an established clonal cell line are transiently or stably engineered to express a naturally occurring SNAP-25 having, e.g., at least 70% amino acid identity, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% amino acid identity with SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, or SEQ ID NO: 24.

[0116] In another aspect of the embodiment, cells from an established clonal cell line are transiently or stably engineered to express a non-naturally occurring SNAP-25. In other aspects of this embodiment, cells from an established clonal cell line are transiently or stably engineered to express a non-naturally occurring SNAP-25 having, e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% amino acid identity with SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, or SEQ ID NO: 24. In other aspects of this embodiment, cells from an established clonal cell line are transiently or stably engineered to express a non-naturally occurring SNAP-25 having, e.g., 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more, 20 or more, 30 or more, 40 or more, 50 or more, or 100 or more noncontiguous amino acid substitutions, deletions, or additions relative to SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, or SEQ ID NO: 24. In yet other aspects of this embodiment, cells from an established clonal cell line are transiently or stably engineered to express a non-naturally occurring SNAP-25 having, e.g., 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more, 20 or more, 30 or more, 40 or more, 50 or more, or 100 or more contiguous amino acid substitutions, deletions, or additions relative to SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, or SEQ ID NO: 24.

[0117] Assays that detect the cleavage of a BoNT/A substrate after exposure to a BoNT/A can be used to assess whether a cell is expressing an endogenous or an exogenous SNAP-25. In these assays, generation of a SNAP-25 cleavage-product would be detected in cells expressing a SNAP-25 after 46

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

BoNT/A treatment. Non-limiting examples of specific Western blot analysis, as well as well-characterized reagents, conditions and protocols are readily available from commercial vendors that include, without limitation, Amersham Biosciences, Piscataway, NJ; Bio-Rad Laboratories, Hercules, CA; Pierce Biotechnology, Inc., Rockford, IL; Promega Corporation, Madison, Wl, and Stratagene, Inc., La Jolla, CA. It is understood that these and similar assays for SNAP-25 cleavage can be useful in identifying cells expressing an endogenous or an exogenous SNAP-25.

[0118] As non-limiting examples, Western blot analysis using an antibody that recognizes BoNT/A SNAP-25-cleaved product or both the cleaved and uncleaved forms of SNAP-25 can be used to assay for uptake of BoNT/A. Examples of a-SNAP-25 antibodies useful for these assays include, without limitation, a-SNAP-25 mouse monoclonal antibody SMI-81 (Sternberger Monoclonals Inc., Lutherville, MD), mouse a-SNAP-25 monoclonal antibody Cl 71.1 (Synaptic Systems, Goettingen, Germany), a-SNAP-25 mouse monoclonal antibody Cl 71.2 (Synaptic Systems, Goettingen, Germany), a-SNAP-25 mouse monoclonal antibody SP12 (Abeam, Cambridge, MA), a-SNAP-25 rabbit polyclonal antiserum (Synaptic Systems, Goettingen, Germany), a-SNAP-25 rabbit polyclonal antiserum (Abeam, Cambridge, MA), and a-SNAP-25 rabbit polyclonal antiserum S9684 (Sigma, St Louis, MO).

[0119] Aspects of the present disclosure comprise, in part, a BoNT/A receptor. As used herein, the term “BoNT/A receptor” refers to either a naturally-occurring BoNT/A receptor or a non-naturally occurring BoNT/A receptor which preferentially interacts with BoNT/A in a manner that elicits a BoNT/A intoxication response. As used herein, the term “preferentially interacts” refers to that the equilibrium dissociation constant (KD) of BoNT/A for a BoNT/A receptor is at least one order of magnitude less than that of BoNT/A for any other receptor. The equilibrium dissociation constant, a specific type of equilibrium constant that measures the propensity of an BoNT/A-BoNT/A receptor complex to separate (dissociate) reversibly into its component molecules, namely the BoNT/A and the BoNT/A receptor complex. The disassociation constant is defined as KD=[L][R]/[C], where [L] equals the molar concentration of BoNT/A, [R] is the molar concentration of a BoNT/A receptor, and [C] is the molar concentration of the BoNT/A-BoNT/A receptor complex, and where all concentrations are of such components when the system is at equilibrium. The smaller the dissociation constant, the more tightly bound the BoNT/A is to its receptor, or the higher the binding affinity between BoNT/A and BoNT/A receptor. In aspects of this embodiment, the disassociation constant of BoNT/A for a BoNT/A receptor is at least two orders of magnitude less, at least three orders of magnitude less, at least four orders of magnitude less, or at least five orders of magnitude less than that of BoNT/A for any other receptor. In other aspects of this embodiment, the binding affinity of a BoNT/A that preferentially interacts with a BoNT/A receptor can have an equilibrium disassociation constant of, e.g., of 500 nM or less, 400 nM or less, 300 nM or less, 200 nM, or less 100 nM or less. In other aspects of this embodiment, the binding affinity of a BoNT/A that preferentially interacts with a BoNT/A receptor can have an equilibrium disassociation constant of, e.g., of 90 nM or less, 80 nM or less, 70 nM or less, 60 nM or less, 50 nM or less, 40 nM or less, 30 nM or less, 20 nM, or less 10 nM or less. As used herein, the term “elicits a BoNT/A intoxication response” refers to the ability 47

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays 2017228675 15 Sep 2017 PCT/US2010/027242 18495 (BOT)/1957205.00451 WO 2010/105234 Patent Application of a BoNT/A receptor to interact with a BoNT/A to form a neurotoxin/receptor complex and the subsequent internalization of that complex into the cell cytoplasm.

[0120] As used herein, the term “naturally occurring BoNT/A receptor” refers to any BoNT/A receptor produced by a naturally-occurring process, including, without limitation, BoNT/A receptor isoforms produced from a post-translational modification, an alternatively-spliced transcript, or a spontaneous mutation, and BoNT/A receptor subtypes. A naturally occurring BoNT/A receptor includes, without limitation, a fibroblast growth factor receptor 2 (FGFR2), a fibroblast growth factor receptor 3 (FGFR3), a synaptic vesicle glycoprotein 2 (SV2), and a complex ganglioside like GT1b, such as those described in Ester Fernandez-Salas, et al., Botulinum Toxin Screening Assays, U.S. Patent Publication 2008/0003240; Ester Fernandez-Salas, et al., Botulinum Toxin Screening Assays, U.S. Patent Publication 2008/0182799; Min Dong et al., SV2 is the Protein Receptor for Botulinum Neurotoxin A, Science (2006); S. Mahrhold et al, The Synaptic Vesicle Protein 2C Mediates the Uptake of Botulinum Neurotoxin A into Phrenic Nen/es, 580(8) FEBS Lett. 2011-2014 (2006), each of which is hereby incorporated by reference in its entirety. A naturally occurring FGFR2 includes, without limitation, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, and SEQ ID NO: 70, or one that substitutes, deletes or adds, e.g., 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more, 20 or more, 30 or more, 40 or more, 50 or more, or 100 or more amino acids from SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, and SEQ ID NO: 70. A naturally occurring FGFR3 includes, without limitation, SEQ ID NO: 25, SEQ ID NO: 26, and SEQ ID NO: 27, or one that substitutes, deletes or adds, e.g., 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more, 20 or more, 30 or more, 40 or more, 50 or more, or 100 or more amino acids from SEQ ID NO: 25, SEQ ID NO: 26, and SEQ ID NO: 27. A naturally occurring SV2 includes, without limitation, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, and SEQ ID NO: 31, or one that substitutes, deletes or adds, e.g., 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more, 20 or more, 30 or more, 40 or more, 50 or more, or 100 or more amino acids from SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, and SEQ ID NO: 31.

[0121] As used herein, the term “non-naturally occurring BoNT/A receptor variant” refers to any BoNT/A receptor produced with the aid of human manipulation or design, including, without limitation, a BoNT/A receptor produced by genetic engineering using random mutagenesis or rational design and a BoNT/A receptor produced by chemical synthesis. Non-limiting examples of non-naturally occurring BoNT/A variants include, e.g., conservative BoNT/A receptor variants, non-conservative BoNT/A receptor variants, BoNT/A receptor chimeric variants and active BoNT/A receptor fragments.

[0122] As used herein, the term “non-naturally occurring BoNT/A receptor” refers to any BoNT/A receptor whose structure was modified with the aid of human manipulation, including, without limitation, a BoNT/A receptor produced by genetic engineering using random mutagenesis or rational design and a 48

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays 2017228675 15 Sep 2017 PCT/US2010/027242 18495 (BOT)/1957205.00451 WO 2010/105234 Patent Application

BoNT/A receptor produced by in vitro chemical synthesis. Non-limiting examples of non-naturally occurring BoNT/A receptors are described in, eg., Ester Fernandez-Salas, et al., Botulinum Toxin Screening Assays, U.S. Patent Publication 2008/0003240; Ester Fernandez-Salas, et al., Botulinum Toxin Screening Assays, U.S. Patent Publication 2008/0182799, each of which is hereby incorporated by reference in its entirety. A non-naturally occurring BoNT/A receptor may substitute, delete or add, e.g., 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more, 20 or more, 30 or more, 40 or more, 50 or more, or 100 or more amino acids from SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, or SEQ ID NO: 70.

[0123] Thus in an embodiment, a BoNT/A receptor is a naturally occurring BoNT/A receptor such as, e.g., FGFR2, FGFR3 or SV2. In aspects of this embodiment, the BoNT/A receptor is a BoNT/A receptor isoform or a BoNT/A receptor subtype. In aspects of this embodiment, the naturally occurring BoNT/A receptor is the naturally occurring BoNT/A receptor of SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, or SEQ ID NO: 70. In other aspects of this embodiment, the BoNT/A receptor is a naturally occurring BoNT/A receptor having, e.g., at least 70% amino acid identity, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% amino acid identity with SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, or SEQ ID NO: 70.

[0124] In another embodiment, a BoNT/A receptor is a non-naturally occurring BoNT/A receptor, such as, e.g., a genetically-engineered FGFR2, a genetically-engineered FGFR3, or a genetically-engineered SV2. In other aspects of this embodiment, the BoNT/A receptor is a non-naturally occurring BoNT/A receptor having, e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% amino acid identity with SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, or SEQ ID NO: 70. In other aspects of this embodiment, the BoNT/A receptor is a non-naturally occurring BoNT/A receptor having, e.g., 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more, 20 or more, 30 or more, 40 or more, 50 or more, or 100 or more non-contiguous amino acid substitutions, deletions, or additions relative to SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, or SEQ ID NO: 70. In yet other aspects of this embodiment, the BoNT/A receptor is a non-naturally occurring BoNT/A receptor having, e g., 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or 49

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 more, 10 or more, 20 or more, 30 or more, 40 or more, 50 or more, or 100 or more contiguous amino acid substitutions, deletions, or additions relative to SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, or SEQ ID NO: 70.

[0125] A BoNT/A receptor can be an endogenous BoNT/A receptor or an exogenous BoNT/A receptor. As used herein, the term “endogenous BoNT/A receptor” refers to a BoNT/A receptor naturally present in the cell because it is naturally encoded within the cell’s genome, such that the cell inherently expresses the BoNT/A receptor without the need an external source of BoNT/A receptor or an external source of genetic material encoding a BoNT/A receptor. Expression of an endogenous BoNT/A receptor may be with or without environmental stimulation such as e.g., cell differentiation or promoter activation. For example, the following established clonal cell lines express at least one endogenous BoNT/A receptor: BE(2)-M17, Kelly, LA1-55n, N1E-115, N4TG3, N18, Neuro-2a, NG108-15, PC12, SH-SY5Y, SiMa, and SK-N-BE(2)-C. An endogenous BoNT/A receptor can only be a naturally-occurring BoNT/A receptor or naturally-occurring variants thereof.

[0126] As used herein, the term “exogenous BoNT/A receptor” refers to a BoNT/A receptor expressed in a cell through the introduction of an external source of BoNT/A receptor or an external source of genetic material encoding a BoNT/A receptor by human manipulation. The expression of an exogenous BoNT/A receptor may be with or without environmental stimulation such as, e.g., cell differentiation or promoter activation. As a non-limiting example, cells from an established clonal cell line can express one or more exogenous BoNT/A receptors by transient or stably transfection of a polynucleotide molecule encoding a BoNT/A receptor, such as, e.g., a FGFR2, a FGFR3, or a SV2. As another non-limiting example, cells from an established clonal cell line can express one or more exogenous BoNT/A receptors by protein transfection of the BoNT/A receptors, such as, e.g., a FGFR2, a FGFR3, or a SV2. An exogenous BoNT/A receptor can be a naturally-occurring BoNT/A receptor or naturally occurring variants thereof, or non-naturally occurring BoNT/A receptor or non-naturally occurring variants thereof.

[0127] Thus in an embodiment, cells from an established clonal cell line express an endogenous BoNT/A receptor. In aspects of this embodiment, the endogenous BoNT/A receptor expressed by cells from an established clonal cell line is a naturally-occurring BoNT/A receptor. In other aspects of this embodiment, the endogenous BoNT/A receptor expressed by cells from an established clonal cell line is SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, or SEQ ID NO: 70. In yet aspects of this embodiment, the endogenous BoNT/A receptor expressed by cells from an established clonal cell line is a naturally occurring BoNT/A receptor, such as, e.g., a BoNT/A receptor isoform or a BoNT/A receptor subtype. In other aspects of this embodiment, the endogenous BoNT/A receptor expressed by cells from an established clonal cell line is a naturally occurring BoNT/A receptor 50

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays 2017228675 15 Sep 2017 PCT/US2010/027242 18495 (BOT)/1957205.00451 WO 2010/105234 Patent Application having, e.g., at least 70% amino acid identity, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% amino acid identity with SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, or SEQ ID NO: 70.

[0128] In another embodiment, cells from an established clonal cell line are transiently or stably engineered to express an exogenous BoNT/A receptor. In an aspect of this embodiment, cells from an established clonal cell line are transiently or stably engineered to express a naturally-occurring BoNT/A receptor. In other aspects of this embodiment, cells from an established clonal cell line are transiently or stably engineered to express the naturally-occurring BoNT/A receptor of SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, or SEQ ID NO: 70. In yet other aspects of this embodiment, cells from an established clonal cell line are transiently or stably engineered to express a naturally occurring BoNT/A receptor, such as, e.g., a BoNT/A receptor isoform or a BoNT/A receptor subtype. In still other aspects of this embodiment, cells from an established clonal cell line are transiently or stably engineered to express a naturally occurring BoNT/A receptor having, e.g., at least 70% amino acid identity, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% amino acid identity with SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, or SEQ ID NO: 70.

[0129] In another aspect of the embodiment, cells from an established clonal cell line are transiently or stably engineered to express a non-naturally occurring BoNT/A receptor. In other aspects of this embodiment, cells from an established clonal cell line are transiently or stably engineered to express a non-naturally occurring BoNT/A receptor having, e.g., at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% amino acid identity with SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, or SEQ ID NO: 70. In other aspects of this embodiment, cells from an established clonal cell line are transiently or stably engineered to express a non-naturally occurring BoNT/A receptor having, e.g., 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more, 20 or more, 30 or more, 40 or more, 50 or more, or 100 or more non-contiguous amino acid substitutions, deletions, or additions relative to SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, or SEQ ID NO: 70. In yet other aspects of this embodiment, cells from an established clonal cell line are transiently or stably engineered 51

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 to express a non-naturally occurring BoNT/A receptor having, e.g., 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more, 20 or more, 30 or more, 40 or more, 50 or more, or 100 or more contiguous amino acid substitutions, deletions, or additions relative to SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, or SEQ ID NO: 70 [0130] In another embodiment, cells from an established clonal cell line are transiently or stably engineered to express an exogenous FGFR2, an exogenous FGFR3, an exogenous SV2, or any combination thereof. In aspects of this embodiment, cells from an established clonal cell line are transiently or stably engineered to express a naturally-occurring FGFR2, a naturally-occurring FGFR3, a naturally-occurring SV2, or any combination thereof. In yet other aspects of this embodiment, cells from an established clonal cell line are transiently or stably engineered to express a non-naturally-occurring FGFR2, a non-naturally-occurring FGFR3, a non-naturally-occurring SV2, or any combination thereof. In still other aspects of this embodiment, cells from an established clonal cell line are transiently or stably engineered to express either a naturally-occurring FGFR2 or a non-naturally-occurring FGFR2, a naturally-occurring FGFR3 or a non-naturally-occurring FGFR3, a naturally-occurring SV2 or a non-naturally-occurring SV2, or any combination thereof.

[0131] Cells that express one or more endogenous or exogenous BoNT/A receptors can be identified by routine methods including direct and indirect assays for toxin uptake. Assays that determine BoNT/A binding or uptake properties can be used to assess whether a cell is expressing a BoNT/A receptor. Such assays include, without limitation, cross-linking assays using labeled BoNT/A, such as, e.g., [125l] BoNT/A, see, e.g., Noriko Yokosawa et al., Binding of Clostridium botulinum type C neurotoxin to different neuroblastoma cell lines, 57(1) Infect. Immun. 272-277 (1989); Noriko Yokosawa et al., Binding of botulinum type Cl, D and E neurotoxins to neuronal cell lines and synaptosomes, 29(2) Toxicon 261-264 (1991); and Tei-ichi Nishiki et al., Identification of protein receptor for Clostridium botulinum type B neurotoxin in rat brain synaptosomes, 269(14) J. Biol. Chem. 10498-10503 (1994). Other non-limiting assays include immunocytochemical assays that detect BoNT/A binding using labeled or unlabeled antibodies, see, e.g., Atsushi Nishikawa et al., The receptor and transporter for internalization of Clostridium botulinum type C progenitor toxin into HT-29 cells, 319(2) Biochem. Biophys. Res. Commun. 327-333 (2004) and immunoprecipitation assays, see, e.g., Yukako Fujinaga et al., Molecular characterization of binding subcomponents of Clostridium botulinum type C progenitor toxin for intestinal epithelial cells and erythrocytes, 150(Pt 5) Microbiology 1529-1538 (2004), that detect bound toxin using labeled or unlabeled antibodies. Antibodies useful for these assays include, without limitation, antibodies selected against BoNT/A, antibodies selected against a BoNT/A receptor, such as, e.g., FGFR2, FGFR3, or SV2, and/or antibodies selected against a ganglioside, such as, e.g., GD1a, GD1b, GD3, GQ1b, or GT1b. If the antibody is labeled, the binding of the molecule can be detected by various means, including Western blot analysis, direct microscopic observation of the cellular location of the antibody, 52

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 measurement of cell or substrate-bound antibody following a wash step, flow cytometry, electrophoresis or capillary electrophoresis, employing techniques well-known to those of skill in the art. If the antibody is unlabeled, one may employ a labeled secondary antibody for indirect detection of the bound molecule, and detection can proceed as for a labeled antibody. It is understood that these and similar assays that determine BoNT/A uptake properties or characteristics can be useful in identifying cells expressing endogenous or exogenous BoNT/A receptors.

[0132] Assays that monitor the release of a molecule after exposure to BoNT/A can also be used to assess whether a cell is expressing one or more endogenous or exogenous BoNT/A receptors. In these assays, inhibition of the molecule’s release would occur in cells expressing a BoNT/A receptor after BoNT/A treatment. Well known assays include methods that measure inhibition of radio-labeled catecholamine release from neurons, such as, e.g., [3H] noradrenaline or [3H] dopamine release, see e.g., A Fassio et al., Evidence for calcium-dependent vesicular transmitter release insensitive to tetanus toxin and botulinum toxin type F, 90(3) Neuroscience 893-902 (1999); and Sara Stigliani et al., The sensitivity of catecholamine release to botulinum toxin C1 and E suggests selective targeting of vesicles set into the readily releasable pool, 85(2) J. Neurochem. 409-421 (2003), or measures catecholamine release using a fluorometric procedure, see, e.g., Anton de Paiva et al., A role for the interchain disulfide or its participating thiols in the internalization of botulinum neurotoxin A revealed by a toxin derivative that binds to ecto-acceptors and inhibits transmitter release intracellularly, 268(28) J. Biol. Chem. 20838-20844 (1993); Gary W. Lawrence et al., Distinct exocytotic responses of intact and permeabilised chromaffin cells after cleavage of the 25-kDa synaptosomal-associated protein (SNAP-25) or synaptobrevin by botulinum toxin A or B, 236(3) Eur. J. Biochem. 877-886 (1996); and Patrick Foran et al., Botulinum neurotoxin C1 cleaves both syntaxin and SNAP-25 in intact and permeabilized chromaffin cells: correlation with its blockade of catecholamine release, 35(8) Biochemistry 2630-2636 (1996). Other non-limiting examples include assays that measure inhibition of hormone release from endocrine cells, such as, e.g., anterior pituitary cells or ovarian cells. It is understood that these and similar assays for molecule release can be useful in identifying cells expressing endogenous or exogenous or BoNT/A receptors.

[0133] Assays that detect the cleavage of a BoNT/A substrate after exposure to a BoNT/A can also be used to assess whether a cell is expressing one or more endogenous or exogenous BoNT/A receptors. In these assays, generation of a BoNT/A substrate cleavage-product, or disappearance of the intact BoNT/A substrate, would be detected in cells expressing a BoNT/A receptor after BoNT/A treatment. Non-limiting examples of specific Western blot analysis, as well as well-characterized reagents, conditions and protocols are readily available from commercial vendors that include, without limitation, Amersham Biosciences, Piscataway, NJ; Bio-Rad Laboratories, Hercules, CA; Pierce Biotechnology, Inc., Rockford, IL; Promega Corporation, Madison, Wl, and Stratagene, Inc., La Jolla, CA. It is understood that these and similar assays for BoNT/A substrate cleavage can be useful in identifying cells expressing endogenous or exogenous BoNT/A receptors. 53

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 [0134] As non-limiting examples, Western blot analysis using an antibody that recognizes BoNT/A SNAP-25-cleaved product or both the cleaved and uncleaved forms of SNAP-25 can be used to assay for uptake of BoNT/A. Examples of a-SNAP-25 antibodies useful for these assays include, without limitation, SMI-81 a-SNAP-25 mouse monoclonal antibody (Sternberger Monoclonals Inc,, Lutherville, MD), Cl 71.1 mouse a-SNAP-25 monoclonal antibody (Synaptic Systems, Goettingen, Germany), Cl 71.2 a-SNAP-25 mouse monoclonal antibody (Synaptic Systems, Goettingen, Germany), SP12 a-SNAP-25 mouse monoclonal antibody (Abeam, Cambridge, MA), a-SNAP-25 rabbit polyclonal antiserum (Synaptic Systems, Goettingen, Germany), a-SNAP-25 rabbit polyclonal antiserum S9684 (Sigma, St. Louis, MO), and a-SNAP-25 rabbit polyclonal antiserum (Abeam, Cambridge, MA).

[0135] Aspects of the present disclosure provide cells that through genetic manipulation or recombinant engineering are made to express an exogenous SNAP-25 and/or one or more exogenous BoNT/A receptors. Cells useful to express an exogenous SNAP-25 and/or one or more exogenous BoNT/A receptors through genetic manipulation or recombinant engineering include neuronal cells and nonneuronal cells that may or may not express an endogenous SNAP-25 and/or one or more endogenous BoNT/A receptors. It is further understood that such genetically manipulated or recombinantly engineered cells may express an exogenous SNAP-25 and one or more exogenous BoNT/A receptors under control of a constitutive, tissue-specific, cell-specific or inducible promoter element, enhancer element or both. It is understood that any cell is useful as long as the cell can be genetically manipulated or recombinantly engineered to expresses an exogenous SNAP-25 and/or one or more exogenous BoNT/A receptors and is capable of undergoing BoNT/A intoxication.

[0136] Methods useful for introducing into a cell an exogenous polynucleotide molecule encoding a component necessary for the cells to undergo the overall cellular mechanism whereby a BoNT/A proteolytically cleaves a SNAP-25 substrate, such as, e.g., a SNAP-25, a FGFR2, a FGFR3, or a SV2, include, without limitation, chemical-mediated delivery methods, such as, e.g., calcium phosphate-mediated, diethyl-aminoethyl (DEAE) dextran-mediated, lipid-mediated, polyethyleneimine (PEI)-mediated, polylysine-mediated and polybrene-mediated; physical-mediated delivery methods, such as, e.g., biolistic particle delivery, microinjection, protoplast fusion and electroporation; and viral-mediated delivery methods, such as, e.g., retroviral-mediated transfection, see e.g., Introducing Cloned Genes into Cultured Mammalian Cells, pp. 16.1-16.62 (Sambrook &amp; Russell, eds., Molecular Cloning A Laboratory Manual, Vol. 3, 3rd ed. 2001); Alessia Colosimo et al., Transfer and Expression of Foreign Genes in Mammalian Cells, 29(2) Biotechniques 314-318, 320-322, 324 (2000); Philip Washbourne &amp; A. Kimberley McAllister, Techniques for Gene Transfer into Neurons, 12(5) Curr. Opin. Neurobiol. 566-573 (2002); and Current Protocols in Molecular Biology, John Wiley and Sons, pp 9.16.4-9.16.11 (2000), each of which is incorporated by reference in its entirety. One skilled in the art understands that selection of a specific method to introduce a polynucleotide molecule into a cell will depend, in part, on whether the cell will transiently or stably contain a component necessary for the cells to undergo the overall cellular mechanism whereby a BoNT/A proteolytically cleaves a SNAP-25 substrate. Non-limiting examples of polynucleotide molecule encoding a component necessary for the cells to undergo the overall cellular 54

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays 2017228675 15 Sep 2017 PCT/US2010/027242 18495 (BOT)/1957205.00451 WO 2010/105234 Patent Application mechanism whereby a BoNT/A proteolytically cleaves a SNAP-25 substrate as follows: FGFR2 polynucleotide molecule of SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQ ID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, or SEQ ID NO: 138; FGFR3 polynucleotide molecule of SEQ ID NO: 139, SEQ ID NO: 140, or SEQ ID NO: 141; SV2 polynucleotide molecule of SEQ ID NO: 142, SEQ ID NO: 143, or SEQ ID NO: 144; and SNAP-25 polynucleotide molecule of SEQ ID NO: 145, or SEQ ID NO: 146.

[0137] Chemical-mediated delivery methods are well-known to a person of ordinary skill in the art and are described in, e.g., Martin Jordan &amp; Florian Worm, Transfection of Adherent and Suspended Cells by Calcium Phosphate, 33(2) Methods 136-143 (2004); Chun Zhang et al., Polyethylenimine Strategies for Plasmid Delivery to Brain-Derived Cells, 33(2) Methods 144-150 (2004), each of which is hereby incorporated by reference in its entirety. Such chemical-mediated delivery methods can be prepared by standard procedures and are commercially available, see, e.g., CellPhect Transfection Kit (Amersham Biosciences, Piscataway, NJ); Mammalian Transfection Kit, Calcium phosphate and DEAE Dextran, (Stratagene, Inc., La Jolla, CA); Lipofectamine™ Transfection Reagent (Invitrogen, Inc., Carlsbad, CA); ExGen 500 Transfection kit (Fermentas, Inc., Hanover, MD), and SuperFect and Effectene Transfection Kits (Qiagen, Inc., Valencia, CA).

[0138] Physical-mediated delivery methods are well-known to a person of ordinary skill in the art and are described in, e.g., Jeike E. Biewenga et al., Plasmid-Mediated Gene Transfer in Neurons using the Biolistics Technique, 71(1) J. Neurosci. Methods. 67-75 (1997); John O’Brien &amp; Sarah C. R. Lummis, Biolistic and Diolistic Transfection: Using the Gene Gun to Deliver DNA and Lipophilic Dyes into Mammalian Cells, 33(2) Methods 121-125 (2004); M. Golzio et al., In Vitro and In Vivo Electric Field-Mediated Permeabilization, Gene Transfer, and Expression, 33(2) Methods 126-135 (2004); and Oliver Greschet al., New Non-Viral Method for Gene Transfer into Primary Cells, 33(2) Methods 151-163 (2004), each of which is hereby incorporated by reference in its entirety.

[0139] Viral-mediated delivery methods are well-known to a person of ordinary skill in the art and are described in, e.g., Chooi M. Lai et al., Adenovirus and Adeno-Associated Virus Vectors, 21(12) DNA Cell Biol. 895-913 (2002); Ilya Frolov et al., Alphavirus-Based Expression Vectors: Strategies and Applications, 93(21) Proc. Natl. Acad. Sci. U. S. A. 11371-11377 (1996); Roland Wolkowicz et al., Lentiviral Vectors for the Delivery of DNA into Mammalian Cells, 246 Methods Mol. Biol. 391-411 (2004); A. Huser &amp; C. Hofmann, Baculovirus Vectors: Novel Mammalian Cell Gene-Delivery Vehicles and Their Applications, 3(1) Am. J. Pharmacogenomics 53-63 (2003); Tiziana Tonini et al., Transient Production of Retroviral- and Lentiviral-Based Vectors for the Transduction of Mammalian Cells, 285 Methods Mol. Biol. 141-148 (2004); Manfred Gossen &amp; Hermann Bujard, Tight Control of Gene Expression in Eukaryotic Cells by Tetracycline-Responsive Promoters, U.S. Patent No. 5,464,758; Hermann Bujard &amp; Manfred Gossen, Methods for Regulating Gene Expression, U.S. Patent No. 5,814,618; David S. Hogness, Polynucleotides Encoding Insect Steroid Hormone Receptor Polypeptides and Cells Transformed With Same, U.S. Patent No. 5,514,578; David S. Hogness, Polynucleotide Encoding Insect Ecdysone 55

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Receptor, U.S. Patent 6,245,531; Elisabetta Vegeto et al., Progesterone Receptor Having C. Terminal Hormone Binding Domain Truncations, U.S. Patent No. 5,364,791; Elisabetta Vegeto et al., Mutated Steroid Hormone Receptors, Methods for Their Use and Molecular Switch for Gene Therapy, U.S. Patent No. 5,874,534, each of which is hereby incorporated by reference in its entirety. Such viral-mediated delivery methods can be prepared by standard procedures and are commercially available, see, e.g., VIRAPOWER™ Adenoviral Expression System (Invitrogen, Inc., Carlsbad, CA) and VIRAPOWER™ Adenoviral Expression System Instruction Manual 25-0543 version A, Invitrogen, Inc., (Jul. 15, 2002); and ADEASY™ Adenoviral Vector System (Stratagene, Inc., La Jolla, CA) and ADEASY™ Adenoviral Vector System Instruction Manual 064004f, Stratagene, Inc. Furthermore, such viral delivery systems can be prepared by standard methods and are commercially available, see, e.g., BD™ Tet-Off and Tet-On Gene Expression Systems (BD Biosciences-Clonetech, Palo Alto, CA) and BD™ Tet-Off and Tet-On Gene Expression Systems User Manual, PT3001-1, BD Biosciences Clonetech, (Mar. 14, 2003), GeneSwitch™ System (Invitrogen, Inc., Carlsbad, CA) and GENESWITCH™ System A Mifepristone-Regulated Expression System for Mammalian Cells version D, 25-0313, Invitrogen, Inc., (Nov. 4, 2002); VIRAPOWER™ Lentiviral Expression System (Invitrogen, Inc., Carlsbad, CA) and VIRAPOWER™ Lentiviral Expression System Instruction Manual 25-0501 version E, Invitrogen, Inc., (Dec. 8, 2003); and COMPLETE CONTROL® Retroviral Inducible Mammalian Expression System (Stratagene, La Jolla, CA) and COMPLETE CONTROL® Retroviral Inducible Mammalian Expression System Instruction Manual, 064005e.

[0140] As mentioned above, an exogenous component necessary for the cells to undergo the overall cellular mechanism whereby a BoNT/A proteolytically cleaves a SNAP-25 substrate, such as, e.g., a SNAP-25, a FGFR2, a FGFR3, or a SV2 disclosed in the present specification can be introduced into a cell. Any and all methods useful for introducing such an exogenous component with a delivery agent into a cell population can be useful with the proviso that this method introduce the exogenous component disclosed in the present specification in at least 50% of the cells within a given cell population. Thus, aspects of this embodiment can include a cell population in which, e.g., at least 50%, at least 60%, at least 70%, at least 80%, or at least 90% of the given cell population contains an exogenous component necessary for the cells to undergo the overall cellular mechanism whereby a BoNT/A proteolytically cleaves a SNAP-25 substrate, such as, e.g., a SNAP-25, a FGFR2, a FGFR3, or a SV2 disclosed in the present specification. As used herein, the term “delivery agent” refers to any molecule that enables or enhances internalization of a covalently-linked, non-covalently-linked or in any other manner associated with a polypeptide into a cell. Thus, the term “delivery agent” encompasses, without limitation, proteins, peptides, peptidomimetics, small molecules, polynucleotide molecules, liposomes, lipids, viruses, retroviruses and cells that, without limitation, transport a covalently or non-covalently linked molecule to the cell membrane, cell cytoplasm or nucleus. It further is understood that the term “delivery agent” encompasses molecules that are internalized by any mechanism, including delivery agents which function via receptor mediated endocytosis and those which are independent of receptor mediated endocytosis. 56

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 [0141] A delivery agent can also be an agent that enables or enhances cellular uptake of a covalently linked component, like FGFR2, FGFR3, SV2, or SNAP-25, such as, e.g., by chemical conjugation or by genetically produced fusion proteins. Methods that covalently link delivery agents and methods of using such agents are described in, e.g., Steven F. Dowdy, Protein Transduction System and Methods of Use Thereof, International Publication No WO 00/34308; Gerard Chassaing &amp; Alain Prochiantz, Peptides which can be Used as Vectors for the Intracellular Addressing of Active Molecules, U.S. Patent No. 6,080,724; Alan Frankel et al., Fusion Protein Comprising TAT-derived Transport Moiert, U.S. Patent No. 5,674,980; Alan Frankel et al., TAT-derived Transport Polypeptide Conjugates, U.S. Patent No. 5,747,641; Alan Frankel et al., TAT-derived Transport Polypeptides and Fusion Proteins, U.S. Patent No. 5,804,604; Peter F. J. O’Hare et al., Use of Transport Proteins, U.S. Patent No. 6,734,167; Yao-Zhong Lin &amp; Jack J. Hawiger, Method for Importing Biologically Active Molecules into Cells, U.S. Patent No. 5,807,746; Yao-Zhong Lin &amp; Jack J. Hawiger, Method for Importing Biologically Active Molecules into Cells, U.S. Patent No. 6,043,339; Yao-Zhong Lin et al., Sequence and Method for Genetic Engineering of Proteins with Cell Membrane Translocating Activity, U.S. Patent No. 6,248,558; Yao-Zhong Lin et al., Sequence and Method for Genetic Engineering of Proteins with Cell Membrane Translocating Activity, U.S. Patent No. 6,432,680; Jack J. Hawiger et al., Method for Importing Biologically Active Molecules into Cells, U.S. Patent No. 6,495,518; Yao-Zhong Lin et al., Sequence and Method for Genetic Engineering of Proteins with Cell Membrane Translocating Activity, U.S. Patent No. 6,780,843; Jonathan B. Rothbard &amp; Paul A Wender, Method and Composition for Enhancing Transport Across Biological Membranes, U.S. Patent No. 6,306,993; Jonathan B. Rothbard &amp; Paul A Wender, Method and Composition for Enhancing Transport Across Biological Membranes, U.S. Patent No. 6,495,663; and Pamela B. Davis et al., Fusion Proteins for Protein Delivery, U.S. Patent No. 6,287,817, each of which is incorporated by reference in its entirety.

[0142] A delivery agent can also be an agent that enables or enhances cellular uptake of a non-covalently associated component, like FGFR2, FGFR3, SV2c, or SNAP-25. Methods that function in the absence of covalent linkage and methods of using such agents are described in, e.g., Gilles Divita et al, Peptide-Mediated Transfection Agents and Methods of Use, U.S. Patent No. 6,841,535; Philip L Feigner and Olivier Zelphati, Intracellular Protein Delivery Compositions and Methods of Use, U.S. Patent Publication No. 2003/0008813; and Michael Karas, Intracellular Delivery of Small Molecules, Proteins and Nucleic Acids, U.S. Patent Publication 2004/0209797, each of which is incorporated by reference in its entirety. Such peptide delivery agents can be prepared and used by standard methods and are commercially available, see, e.g. the CHARIOT™ Reagent (Active Motif, Carlsbad, CA); BIO-PORTER® Reagent (Gene Therapy Systems, Inc., San Diego, CA), BIO TREK™ Protein Delivery Reagent (Stratagene, La Jolla, CA), and PRO-JECT™ Protein Transfection Reagent (Pierce Biotechnology Inc., Rockford, IL).

[0143] Aspects of the present disclosure can also be described as follows: 1. An established clonal cell line comprising a cell susceptible to intoxication by BoNT/A. 57 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays 2. The established clonal cell line of 1, wherein the clonal cell line is selected from a parental SiMa cell line. 3. The established clonal cell line of 1 or 2, wherein the cell is susceptible to BoNT/A intoxication by about 100 pM or less, by about 50 pM or less, by about 10 pM or less, by about 5 pM or less, by about 1 pM or less, by about 0.5 pM or less, or by about 0.1 pM or less of a BoNT/A. 4. The established clonal cell line of 1 or 2, wherein susceptibility to BoNT/A intoxication is measured before differentiation of the cell. 5. The established clonal cell line of 2, wherein in the undifferentiated state, the cell exhibits at least a 1.5- fold increase in gene expression of one or more genes relative to the expression of the one or more genes in a cell from a 2D6 cell line, the genes being taken from Table 5, or wherein the cell exhibits at least a 1.5-fold decrease in gene expression of one or more genes relative to the expression of the one or more genes in a cell from a 2D6 cell line, the genes being taken from Table 6. 6. The established clonal cell line of 2, wherein in the differentiated state, the cell exhibits at least a 1.5-fold increase in gene expression of one or more genes relative to the expression of the one or more genes in a cell from a 2D6 cell line, the genes being taken from Table 9, or wherein the cell exhibits at least a 1.5-fold decrease in gene expression of one or more genes relative to the expression of the one or more genes in a cell from a 2D6 cell line, the genes being taken from Table 10. 7. The established clonal cell line of 2, wherein in the undifferentiated state, the cell exhibits at least a 1.5- fold increase in gene expression of one or more genes relative to the expression of the one or more genes in a cell from a parental SiMa cell line, the genes being taken from Table 7, or wherein the cell exhibits at least a 1.5-fold decrease in gene expression of one or more genes relative to the expression of the one or more genes in a cell from a parental SiMa cell line, the genes being taken from Table 8. 8. The established clonal cell line of 2, wherein in the differentiated state, the cell exhibits at least a 1.5-fold increase in gene expression of one or more genes relative to the expression of the one or more genes in a cell from a parental SiMa cell line, the genes being taken from Table 11, or wherein the cell exhibits at least a 1.5-fold decrease in gene expression of one or more genes relative to the expression of the one or more genes in a cell from a parental SiMa cell line, the genes being taken from Table 12. 9. The established clonal cell line of 1 or 2, wherein the cell exhibits a sensitivity for BoNT/A activity that is 100 pM or less or about 25 pM for about 5 or more cell passages, 10 or more cell passages, 15 or 58

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 more cell passages, 20 or more cell passages, 25 or more cell passages, 30 or more cell passages, 35 or more cell passages, 40 or more cell passages, 45 or more cell passages, 50 or more cell passage, 55 or more cell passage, or 60 or more cell passage. 10. The established clonal cell line of 1 or 2, wherein the cell from an established clonal cell line exhibits a well defined signal to noise ratio for the upper asymptote for BoNT/A activity of at least 3:1, at least 4:1, at least 5:1, at least 6:1, at least 7:1, at least 8:1, at least 9:1, at least 10:1, over, e.g., 5 or more cell passages, 10 or more cell passages, 15 or more cell passages, 20 or more cell passages, 25 or more cell passages, 30 or more cell passages, 35 or more cell passages, 40 or more cell passages, 45 or more cell passages, 50 or more cell passage, 55 or more cell passage, or 60 or more cell passage. 11. An established clonal cell line comprising a cell susceptible to intoxication by BoNT/A produced from a parental SiMa cell line, wherein the cell is susceptible to BoNT/A intoxication by about 100 pM or less, by about 50 pM or less, by about 10 pM or less, by about 5 pM or less, by about 1 pM or less, by about 0.5 pM or less, or by about 0.1 pM or less of a BoNT/A. 12. An established clonal cell line comprising cells susceptible to intoxication by BoNT/A, wherein the clonal cell line is selected from a parental SiMa cell line; and wherein the the clonal cell line comprises cells susceptible to BoNT/A intoxication by about 100 pM or less of a BoNT/A. 13. The established clonal cell line of 12, wherein the parental SiMa cell line is the parental SiMa cell line DSMZ ACC 164. 14. The established clonal cell line of 12, wherein the cell exhibits a sensitivity for BoNT/A activity that is 100 pM or less or about 25 pM for about 5 or more cell passages, 10 or more cell passages, 15 or more cell passages, 20 or more cell passages, 25 or more cell passages, 30 or more cell passages, 35 or more cell passages, 40 or more cell passages, 45 or more cell passages, 50 or more cell passage, 55 or more cell passage, or 60 or more cell passage. 15. The established clonal cell line of 12, wherein the cell from an established clonal cell line exhibits a well defined signal to noise ratio for the upper asymptote for BoNT/A activity of at least 3:1, at least 4:1, at least 5:1, at least 6:1, at least 7:1, at least 8:1, at least 9:1, at least 10:1, over, e g., 5 or more cell passages, 10 or more cell passages, 15 or more cell passages, 20 or more cell passages, 25 or more cell passages, 30 or more cell passages, 35 or more cell passages, 40 or more cell passages, 45 or more cell passages, 50 or more cell passage, 55 or more cell passage, or 60 or more cell passage. 59

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 16. The established clonal cell line of 12, wherein susceptibility to BoNT/A intoxication is measured before differentiation of the cell or after differentiation of the cell. 17. An established clonal cell line comprising cells susceptible to intoxication by BoNT/A, wherein the cells exhibits at least a 1.5-fold difference in gene expression levels of three or more genes as compared to the expression levels of these genes in cells from the 2D6 cell line; wherein the gene expression levels are selected from th group ADAMTS9, ASCL1, BASP1, DOK5, DPYD, GNB4, GNG11, GTSF1, MAOA, MINA, MSN, PEG3, PLK2, PRSS12, RNF182, SLC44A5, SPARC, TFPI2, and TPTE; and wherein the the clonal cell line comprises cells susceptible to BoNT/A intoxication by about 100 pM or less of a BoNT/A. 18. The established clonal cell line of 17, wherein the cells exhibits at least a 2.0-fold difference in gene expression levels of one or more genes as compared to the expression levels of these genes in cells from the 2D6 cell line, at least a 3.0-fold difference in gene expression levels of one or more genes as compared to the expression levels of these genes in cells from the 2D6 cell line, or at least a 4.0-fold difference in gene expression levels of one or more genes as compared to the expression levels of these genes in cells from the 2D6 cell line. 19. The established clonal cell line of 17, wherein the gene expression levels are measured before differentiation of the cell or after differentiation of the cell. 20. The established clonal cell line of 17, wherein the cell exhibits a sensitivity for BoNT/A activity that is 100 pM or less or about 25 pM for about 5 or more cell passages, 10 or more cell passages, 15 or more cell passages, 20 or more cell passages, 25 or more cell passages, 30 or more cell passages, 35 or more cell passages, 40 or more cell passages, 45 or more cell passages, 50 or more cell passage, 55 or more cell passage, or 60 or more cell passage. 21. The established clonal cell line of 17, wherein the cell from an established clonal cell line exhibits a well defined signal to noise ratio for the upper asymptote for BoNT/A activity of at least 3:1, at least 4:1, at least 5:1, at least 6:1, at least 7:1, at least 8:1, at least 9:1, at least 10:1, over, e.g., 5 or more cell passages, 10 or more cell passages, 15 or more cell passages, 20 or more cell passages, 25 or more cell passages, 30 or more cell passages, 35 or more cell passages, 40 or more cell passages, 45 or more cell passages, 50 or more cell passage, 55 or more cell passage, or 60 or more cell passage. 60

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EXAMPLES

Example I

Screening for Cell Lines Comprising Cells Susceptible to BoNT/A Intoxication [0144] The following example illustrates how to identify clonal cells from a parental established cell line that are susceptible to BoNT/A intoxication or have neurotoxin uptake capacity. 1. Isolation of clonal cell lines.

[0145] Companion patent application Ester Fernandez-Salas, et al., Immuno-Based Botulinum Toxin Serotype A Activity Assays, U.S. Patent Application Serial No: 12/403,531 identified several established cell lines useful for conducting the disclosed immuno-based methods of detecting BoNT/A activity, including, e.g., LA1-55n (ECACC 06041203), N18 (ECACC 88112301), Neuro-2a (ATCC CCL-131), PC12 (ATCC CRL-1721), SH-SY5Y (ATCC CRL-2266), and SiMa (DSMZ ACC 164). During characterization of the SiMa cell line, it was discovered that the cells comprising this established cell line comprised at least five different cellular phenotypes. To determine whether any one of these phenotypically-distinet cell types was responsible for the susceptibility of this cell line to BoNT/A intoxication, two different limited-dilution screens were conducted to obtain single colony isolates for each phenotypically-distinct cell type.

[0146] In both screens, a suitable density of cells from a SiMa stock were grown in RPMI 1640 medium, having 10% fetal bovine serum, 1% Penicillin-Streptomycin, 2 mM L-Glutamine, contained in a T175 Collagen IV coated flask. After the second passage, the cells were trypsin-treated to produce a cell suspension and the cell concentration was determined. About 4.0 x 106 cells from this cell suspension was transferred into a 50 mL tube and the cells were dissociated into single cells by repeated vigorous expulsion through an 18.5 gauge needle using a 10 mL syringe. Cells from this disassociated single-cell suspension were then diluted to a concentration of 0.2 x 10® cells/mL by adding 15 mL of fresh growth medium, and 2.5 pL of this dilution was added to 50 mL of fresh growth medium to obtain a concentration of 10 cells/mL. From this final dilution stock, 100 pL of growth medium was added to each well of a 96-well Collagen IV coated plates (final average density of one cell/well), and the cells were grown undisturbed in a 37 °C incubator under 5% carbon dioxide for four weeks. A total of nineteen 96-well plates were setup for analysis. Plates were microscopically examined periodically to assess colony growth. After four weeks, each well was microscopically examined to identify growing colonies, and for each growing colony identified, 100 pL of fresh growth medium was added to each well and the cells were grown undisturbed in a 37 °C incubator under 5% carbon dioxide for two weeks. After two additional weeks of growth, the growing single colonies were trypsin-treated and transferred to a new 96-well plate for continued growth. Once colonies grew to about 1,000 cells, based on visual inspection, the cells were trypsin-treated and each cell-suspension was transferred into a new well from a 24-well Collagen IV-coated plate. The cells were grown in a 37 °C incubator under 5% carbon dioxide with fresh growth 61

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 medium being replenished every 2-3 days, if needed. The cells were grown until the culture reached approximately 60% confluence or greater, at which point the cells were trypsin-treated and each cell-suspension was transferred into a 25 cm2 Collagen IV-coated flask. The cells were grown in a 37 °C incubator under 5% carbon dioxide with fresh growth medium being replenished every 2-3 days, if needed. Once the cells in the flask reached 70-80% confluence, they were frozen and stored in liquid nitrogen until the clonal cell lines were tested to determine their susceptibility to BoNT/A intoxication. Of the 1,824 colony isolates initially setup from both screens, 130 clonal cell lines were selected based on viability and growth criteria and expanded for subsequent screening procedures. 2. Primary screen for BoNT/A intoxication susceptibility of cells from a clonal cell line using a BoNT/A complex.

[0147] One way to determine whether cells from a clonal cell line were susceptible to BoNT/A intoxication was to conduct a primary screen using a CELLTITER-GLO® luminescent cell viability assay (Promega, Madison, Wl) for normalizing the cell number in each well and an immuno-based method for determining BoNT/A activity as described in Ester Fernandez-Salas, et al., Immuno-Based Botulinum Toxin Serotype A Activity Assays, U.S. Patent Application Serial No: 12/403,531, which is hereby incorporated by reference in its entirety. Two separate 96-well plates were set up, one for the BoNT/A activity assay and the other for the cell viability assay.

[0148] To conduct the BoNT/A activity assay, a lysate was prepared from cells treated with BoNT/A by plating cells from each isolated clonal cell line into a well from a poly-D-lysine 96-well plate (BD Biosciences, Bedford, MA). The wells contained 0.1 mL of a serum-free medium comprising Minimum Essential Medium, 2 mM GlutaMAX™ I with Earle’s salts, 1 x B27 supplement, 1 x N2 supplement, 0.1 mM Non-Essential Amino Acids, 10 mM HEPES and 25 pg/mL GT1b (302-011-M005, Alexis Biochemicals, San Diego, CA). These cells were incubated in a 37 °C incubator under 5% carbon dioxide until the cells differentiated, as assessed by standard and routine morphological criteria, such as growth arrest and neurite extension (approximately 3 days). The media from the differentiated cells was aspirated from each well and replaced with fresh media containing 1 nM of a BoNT/A complex. After a 24 hrs incubation, the cells were washed by aspirating the growth media and rinsing each well with 200 pL of 1 x PBS. To harvest the cells, 1 x PBS was aspirated, the cells lysed by adding 30 pi of Lysis Buffer comprising 20 mM Tris-HCI (pH 7,5), 150 mM NaCI, 1 mM EDTA, 1 mM EGTA, 1% Triton X-100 to each well, and the plate incubated on a shaker rotating at 500 rpm for 30 minutes at 4 °C. The plate was centrifuged at 4000 rpm for 20 minutes at 4 °C to pellet cellular debris and the supernatant was transferred to a capture antibody coated 96-well plate to perform the detection step.

[0149] To prepare an a-SNAP-25 capture antibody solution, the a-SNAP-25 mouse monoclonal antibody contained in the ascites from hybridoma cell line 2E2A6 (Example VII) was purified using a standard Protein A purification protocol. 62

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 [0150] To prepare an a-SNAP-25 detection antibody solution, a-SNAP-25 rabbit polyclonal antibody S9684 (Sigma, St. Louis, MO) was conjugated to Ruthenium(ll)-tris-bipyridine-(4-methysulfonate) NHS ester labeling reagent (Meso Scale Discovery, Gaithersburg, MD) according to the manufacturer's instructions (Meso Scale Discovery, Gaithersburg, MD). The conjugation reaction was performed by adding 30 pL of distilled water reconstituted MSD SULFO-TAG™ stock solution to 200 pL of 2 mg/mL a-SNAP-25 polyclonal antibodies and incubating the reaction at room temperature for 2 hours in the dark. The labeled antibodies were purified using a standard spin column protocol and the protein concentration determined using a standard colorimetric protein assay. The absorbance of the a-SNAP-25 antibody/MSD SULFO-TAG™ conjugate was measured at 455 nm using a spectrophotometer to determine the concentration in moles per liter. The detection antibody solution was stored at 4 °C until needed.

[0151] To prepare an a-SNAP-25 solid phase support comprising an a-SNAP-25 capture antibody, approximately 5 pL of the appropriate a-SNAP-25 monoclonal antibody solution (20 pg/mL in 1 x PBS) is added to each well of a 96-well MSD High Bind plate and the solution is allowed to air dry in a biological safety cabinet for 2-3 hours in order to liquid evaporate the solution. The capture antibody-bound wells were sealed and stored at 4 °C until needed.

[0152] To detect the presence of a cleaved SNAP-25 product by ECL sandwich ELISA, the wells from an a-SNAP-25 solid phase support were then blocked by adding 150 pL of Blocking Buffer comprising 2% Amersham Blocking Reagent (GE Life Sciences, Piscataway, NJ) and 10% goat serum (VWR, West Chester, PA) at room temperature for 2 hours. The Blocking Buffer was aspirated, 25 pL of a lysate from cells treated with BoNT/A was added to each well and the plates were incubated at 4 °C for overnight. Plate wells were washed three times by aspirating the cell lysate and rinsing each well three times with 200 pL 1 x PBS, 0.1% TWEEN-20® (polyoxyethylene (20) sorbitan monolaureate). After washing, 25 pi of 5 pg/mL a-SNAP-25 detection antibody solution comprising 2% Amersham Blocking Reagent in 1 x PBS, 0.1% TWEEN-20® (polyoxyethylene (20) sorbitan monolaureate) was added to each well, sealed, and incubated at room temperature for 1 hour with shaking. After a-SNAP-25 detection antibody incubation, the wells were washed three times with 200 pL 1 x PBS, 0.1% TWEEN-20® (polyoxyethylene (20) sorbitan monolaureate). After washing 150 pL of 1 x Read Buffer (Meso Scale Discovery, Gaithersburg, MD) was added to each well and the plates were read using a SECTOR™ Imager 6000 Image Reader (Meso Scale Discovery, Gaithersburg, MD). The raw data was collected using the ECL imager.

[0153] To conduct the luminescent cell viability assay, cells from each isolated clonal cell line were plated and differentiated as described above. The media from the differentiated cells was aspirated from each well and replaced with 100 pi of the reagent mixture comprising the CELLTITER-GLO® substrate and CELLTITER-GLO® buffer according to the manufacturer’s instructions. The plate was then protected from light and mixed for two minutes on an orbital shaker. The solution from the 96-well cell plate with clear bottom was transferred to a white luminometer plate and after 10 minutes incubation was read on the luminometer. 63 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays [0154] These results indicated that the cell viability readings ranged from 9,838 to 10,423,188 and BoNT/A activity signals ranged from 84 to 27,242 (Table 1). In addition, a ratio of BoNT/A activity over cell viability was calculated to normalize the data, although there was not always a 1:1 ratio of viability and activity. Seven clonal cell lines exhibited activity/viability ratios of about 0.2 x 10'2 or greater: H1, A7, A11, F10, A9, A10, and C11 (Table 1). Nine clonal cell lines exhibited activity/viability ratios of about 0.125 x 10-2 to about 0.150 x 10 2: H3, H8, E11, H10, A6, C5, C12, D11, and B5 (Table 1). Two cell lines exhibited activity/viability ratios of about 0.100 x 10 2: D7 and B10 (Table 1). Based on these activity/viability ratios in conjunction with the cell viability and BoNT/A activity signal measurements, these 18 clonal cell lines were selected for further testing by conducting a secondary screen using a BoNT/A activity assay in order to generate a dose-response curve to BoNT/A.

Table 1. Primary Screen for Clonal Cell Lines Susceptible to BoNT/A Intoxication Using Viability and Activity Signals

Well Cell Viability Reading (RLU) BoNT/A Activity Signal (RLU) Activity/Viabi lity Ratio Well Cell Viability Reading (RLU) BoNT/A Activity Signal (RLU) Activity/Viabil ity Ratio A1 2634417 2425 0.092 x 102 A7 10132753 27242 0.269 x 102 B1 731808 198 0.027 x 10-2 B7 2977371 1642 0.055 x 10'2 C1 4258160 1641 0.039 x 10-2 C7 5746577 4878 0.085x1 O'2 D1 6554606 4885 0.075 x 102 D7 5861338 6044 0.103 x 10 2 E1 2374483 897 0.038 x 10'2 E7 2819910 1399 0.050 x 10-2 F1 2801444 1842 0.066 x 10'2 F7 23523 84 0.357 x 10-2 G1 5094510 4579 0.090 x 10-2 G7 6232344 4031 0.065 x 102 H1 3808699 10861 0.285 x 10'2 H7 4916756 2759 0.056 x 10-2 A2 9593106 7090 0.074 x 10'2 A8 5945833 5611 0.094 x 10-2 B2 5374966 5673 0.106 x 10'2 B8 4591002 2128 0.046 x 10 2 C2 4170158 2972 0.071 x 10'2 C8 5648241 8758 0.155 x10'2 D2 31283 88 0.281 x 10'2 D8 4207887 3360 0.080x10'2 E2 5706902 3743 0.066 x 10'2 E8 5894699 3844 0.065 x 10"2 F2 4884798 4568 0.094 x 10'2 F8 5585487 4651 0.083 x 10'2 G2 3552045 2190 0.062 x 10'2 G8 4758800 4545 0.096 x 10'2 H2 3743690 3421 0.091 x 10'2 H8 5439137 8017 0.147 x 10'2 A3 15372 89 0.579 x 10'2 A9 10423188 20706 0.199 x 10'2 B3 5381672 1551 0.029 x 10'2 B9 6493893 4444 0.068 x 10'2 C3 4270534 3959 0.093 x 10'2 C9 5742047 5788 0.101 x 10'2 D3 48702 97 0.199 x 10'2 D9 3424405 1848 0.054 x 10'2 E3 4707349 2671 0.057 x 10'2 E9 5771943 8064 0.140 x 10'2 F3 3053132 1539 0.050 x 10'2 F9 24524 88 0.359 x 10'2 G3 5518292 4195 0.076 x 10'2 G9 7291510 6674 0.092 x 10'2 H3 4156632 6339 0.153 x 10'2 H9 4169883 6048 0.145 x 10'2 A4 19793 89 0.450 x 10'2 A10 9050811 17617 0.195 x 10'2 B4 6224766 4299 0.069 x 10'2 B10 5590113 5175 0.093 x 10'2 C4 3212859 3202 0.100 x 10'2 C10 2325807 1713 0.074 x 10'2 D4 4376180 2367 0.054 x 10'2 D10 2644116 2589 0.098 x 10-2 64 PCT/US2010/027242 WO 2010/105234

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Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays E4 3931793 3975 0.101 x 10'2 E10 4210945 2666 0.063 x 10-2 F4 1150134 526 0.046 x 10'2 F10 2932749 6390 0.218 x 10-2 G4 19023 94 0.494 x 10"2 G10 3980127 3114 0.078 x 102 H4 3368425 2645 0.079 x 10'2 H10 4519035 6187 0.137 x 10-2 A5 8231689 7809 0.095 x 10'2 A11 9870025 24690 0.250 x 10 2 B5 5332004 6545 0.123 x 102 B11 4973892 2235 0.045 x 102 C5 3869441 5042 0.130 x 10'2 C11 3326448 6405 0.193 x 10'2 D5 2554300 1161 0.045 x 10'2 D11 5747961 7169 0.125x1 O'2 E5 3781403 764 0.020 x 10'2 E11 5831546 8432 0.145 x 102 F5 4608801 3720 0.081 x 10'2 F11 5291803 4317 0.082 x 10'2 G5 7105403 7330 0.103 x 10'2 G11 3499587 2790 0.080 x 10'2 H5 5585607 7544 0.135 x 102 H11 3225750 4518 0.140 x 10'2 A6 7698708 10152 0.132 x 10'2 A12 9838 89 0.905 x 10'2 B6 4706560 3196 0.068 x 10'2 B12 3728293 2016 0.054 x 10'2 C6 5866251 6145 0.105 x 10'2 C12 4086862 5308 0.130 x 10'2 D6 2285787 768 0.034 x 10'2 D12 5044526 3860 0.077 x 10'2 E6 2471979 1038 0.042 x 10'2 E12 4787913 2719 0.057 x 10'2 F6 10958 91 0.830x1 O'2 F12 5101695 2585 0.051 x 10'2 G6 19590 91 0.465 x 10'2 G12 2887390 1622 0.056 x 10'2 H6 2057687 2564 0.125 x 10'2 H12 2829307 5105 0.180 x10'2 [0155] To conduct BoNT/A activity assay in order to generate a dose-response curve to BoNT/A, cells from each isolated clonal cell line were seeded in a poly-D-lysine 96-well plate and differentiated as described above. Of the top 18 clonal cell lines selected for further testing, only 8 remained viable, the remaining 10 clonal cell lines failed to regrow and were lost. The media from the differentiated cells was aspirated from each well and replaced with fresh media containing either 0 (untreated sample), 0.03 pM, 0.1 pM, 0.3 pM, 0.9 pM, 2.8 pM, 8.3 pM, and 25 pM of a BoNT/A complex. After a 24 hrs treatment, the cells were washed, incubated for an additional two days in serum-free medium without toxin to allow for the cleavage of the SNAP-25 substrate, and harvested as described above. The supernatant was transferred to a capture antibody coated 96-well plate to perform the detection step.

[0156] The a-SNAP-25 capture antibody solution, the a-SNAP-25 detection antibody solution, and the a-SNAP-25 solid phase support were prepared as described above. Detection of the presence of cleaved SNAP-25 product by ECL sandwich ELISA analysis was performed as described above. The raw data obtained from the ECL imager was then transferred to SigmaPlot v. 9.0 and a 4-parameter logistics fit was used to define the dose-response curves. There were no constraints used for the 4-parameter logistic function when plotting the data. Graphical reports were generated using the following analysis: R2 (correlation coefficient), a (Max for data set), b (hillslope), and X0 ± SE (EC50 value ± standard error).

[0157] These results indicate that of the 8 clonal cell lines tested, only two were more susceptible to BoNT/A intoxication when compared to cells comprising the parental SiMa cell line (Table 2). For example, cells comprising the parental SiMa cell line exhibited an EC50 activity for BoNT/A of 2.20 pM, whereas cells comprising the H1 and A10 cell lines exhibited an EC50 activity for BoNT/A of 1.76 pM or 65 PCT/US2010/027242 WO 2010/105234

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Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays less. Conversely, cells comprising the H10 and D11 cell line exhibited an EC50 activity for BoNT/A that was higher than that observed for cells comprising the parental SiMa cell line, but less than 5.0 pM. It should be noted that any clonal cell line exhibiting an EC50 activity for BoNT/A that is 5.0 pM or less (100 U/mL or less) is useful for an immuno-based method for determining BoNT/A activity described in Ester Fernandez-Salas, et al., Immuno-Based Botulinum Toxin Serotype A Activity Assays, U.S. Patent Application Serial No: 12/403,531.

Table 2. Secondary Screen for Clonal Cell Lines Susceptible to BoNT/A Intoxication Clone BoNT/A Activity EC50 (pM) SignalMiN (RLU) SignalMAx (RLU) SiMa 2.20 123 47,611 H1 0.77 193 125,252 H3 ND ND ND B5 >25.0 115 22,277 C5 ND ND ND A6 ND ND ND A7 5.59 153 100,412 D7 ND ND ND H8 ND ND ND A9 ND ND ND A10 1.76 207 113,029 B10 6.35 147 101,935 F10 >25.0 111 32,663 H10 2.80 171 120,975 A11 ND ND ND C11 ND ND ND D11 4.4 1.84 105,527 E11 ND ND ND C12 ND ND ND ND = Not determined. 3. Primary screen for BoNT/A intoxication susceptibility of cells from a clonal cell line using a formulated BoNT/A pharmaceutical product.

[0158] Another way to determine whether cells from a clonal cell line were susceptibility to BoNT/A intoxication was to conduct a primary screen by generating a dose-response curve to BoNT/A and calculate the EC50 value using an immuno-based method for determining BoNT/A activity as described in Ester Fernandez-Salas, et al., Immuno-Based Botulinum Toxin Serotype A Activity Assays, U.S. Patent Application Serial No: 12/403,531, which is hereby incorporated by reference in its entirety.

[0159] Initially six of 35 clonal cell line isolates were examined using a full dose response to BoNT/A. To prepare a lysate from cells treated with BoNT/A, cells from six clonal cell line were seeded in a poly-D-lysine 96-well plate and differentiated as described above in Section 2 except that the serum-free medium 66 PCT/US2010/027242 WO 2010/105234

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Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays comprised 60 pg/mL GT1b. The clonal cell lines used were 3D8, YB8, 1D4, 2D6, 1E11, 2F5. The H1 and H10 clonal cell lines identified above, along with the parental SiMa cell line, were used as references to identify cell lines highly susceptible to BoNT/A intoxication. The media from the differentiated cells was aspirated from each well and replaced with fresh media containing either 0 (untreated sample), 0.98 U/mL, 1.9 U/mL, 3.91 U/mL, 7.81 U/mL, 15.6 U/mL, 31.3 U/mL, 62.5 U/mL, 125 U/mL, 250 U/mL, or 500 U/mL of a formulated BoNT/A pharmaceutical product. After a 24 hrs treatment, the cells were washed, incubated for an additional two days in serum-free medium without toxin to allow for the cleavage of the SNAP-25 substrate. To harvest the cells, 1 x PBS was aspirated, the cells lysed by adding 30 pi of Lysis Buffer comprising 20 mM Tris-HCI (pH 7,5), 150 mM NaCI, 1 mM EDTA, 1 mM EGTA, 1% Triton X-100 to each well, and the plate incubated on a shaker rotating at 500 rpm for 30 minutes at 4 °C. The plate was centrifuged at 4000 rpm for 20 minutes at 4 °C to pellet cellular debris. The protein concentration was determined using standard methods. The supernatant was transferred to a capture antibody coated 96-well plate to perform the detection step of the immuno-based method.

[0160] The a-SNAP-25 capture antibody solution, the a-SNAP-25 detection antibody solution, and the a-SNAP-25 solid phase support were prepared as described above in Section 2. Detection of the presence of SNAP-25 cleavage product by ECL sandwich ELISA analysis was performed, collected data was analyzed and the EC50 calculated as described above in Section 2, except that SigmaPlot v. 10 was used.

[0161] These results show that clonal cell line H1 comprises cells that are more susceptible to BoNT/A than the parental SIMa cell line (Table 3). In addition, results indicate that although clonal cell lines H10, 1D4, 1E11, 2D6, 2F5, 3D8, and YB8 all comprise cells that are less susceptible to BoNT/A than the parental SiMa cell line, all have an EC50 of BoNT/A activity that is below 30 U/mL (Table 3). It should be noted that any clonal cell line exhibiting an EC50 activity for BoNT/A that is 100 U/mL or less (5.0 pM or less) is useful for an immuno-based method for determining BoNT/A activity described in Ester Fernandez-Salas, et al., Immuno-Based Botulinum Toxin Serotype A Activity Assays, U.S. Patent Application Serial No: 12/403,531.

Table 3. Primary Screen for Clonal Cell Lines Susceptible to BoNT/A Intoxication Clone BoNT/A Activity EC5o (U/mL) SignalMiN (RLU) SignalMAx (RLU) SiMa 10.8 ± 1.0 10,519 253,484 H1 10.2 ±0.6 13,996 276,982 H10 22.2 ±2.0 5,379 296,168 1D4 22.4 ±0.8 6,064 239,096 1E11 14.2 ± 1.7 8,698 276,323 2D6 27.3 ± 1.8 3,347 179,454 2F5 15.8 ±0.9 7,007 265,461 3D8 13.4 ±0.6 11,658 266,279 YB8 19.7 ± 1.3 8,477 293,559 67 PCT/US2010/027242 WO 2010/105234

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Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays [0162] This initial primary screen using a dose-response curve with the 10 different BoNT/A concentrations identified three concentrations that were useful for a shortened assay using 3 different BoNT/A concentrations, with one concentration being slightly higher than the lower asymptote (8 U/mL), one concentration near the EC50 (25 U/mL), and one concentration representing about 80% of the upper asymptote (80 U/mL). In these subsequent primary screens the remaining 29 clonal cell line isolates were tested as described above except that the cells were treated with either 0 (untreated sample), 8 U/mL, 25 U/mL, or 80 U/mL of a formulated BoNT/A pharmaceutical product. The clonal cell lines tested were 1E3, 2B9, 2D2, 2E4, 3B8, 3D5, 3G10, 4B5, 4C8, 4D3, 5C10, 5F3, AC9, AF4, BB3, BB10, BE3, BF8, CC11, CD6, CE6, CG8, CG10, DC4, DD10, DE7, DF5, YB7, and YF5. In addition, the parental SiMa was used as positive control.

[0163] These results show that clonal cell lines 2E4, 3B8, 3D5, 5F3, AF4, BB3, BB10, and DC4 all comprise cells that are more susceptible to BoNT/A than the parental SiMa cell line (Table 4). In addition, these results indicate that clonal cell lines 1E3, 2B9, 3G10, 4B5, 4C8, AC9, BE3, BF8, CC11, CD6, CE6, CG8, CG10, DD10, DE7, and YF5 all comprise cells that are of similar susceptibility to BoNT/A to that of the parental SiMa cell line (Table 4). Lastly, these results reveal that clonal cell lines 2D2, 4D3, 5C10, DF5, and YB7 all comprise cells that are less susceptible to BoNT/A than the parental SiMa cell line (Table 4).

Table 4. Primary Screen for Clonal Cell Lines Susceptible to BoNT/A Intoxication Clone 8 U/mL BoNT/A 25 U/mL BoNT/A 80 U/mL BoNT/A Activity Signal (RLU) Fold Difference Activity Signal (RLU) Fold Difference Activity Signal (RLU) Fold Difference SiMa 75811/80562* — 138952/ 175685* — 173979/ 225768* — 1E3 71040 0.9 128771 0.9 155107 0.9 2B9 66962 0.9 135006 1.0 166871 1.0 2D2 60224* 0.8 136947* 0.8 199786* 0.9 2E4 103680 1.4 217980 1.6 270463 1.6 3B8 123521 1.6 227367 1.6 249218 1.4 3D5 113532 1.5 201683 1.5 270578 1.6 3G10 83049 1.1 130930 0.9 175540 1.0 4B5 74344 1.0 137604 1.0 177363 1.0 4C8 87047 1.1 144395 1.0 185115 1.1 4D3 38063 0.5 80180 0.6 101724 0.6 5C10 16024* 0.2 49030 0.3 116396* 0.6 5F3 98263* 1.7 182902* 1.4 212275* 1.5 AC9 60016* 1.0 127030* 1.0 180384* 1.4 AF4 115460 1.5 179901 1.3 190867 1.1 BB3 74668 1.3 120966 1.4 170177 1.4 BB10 152748 2.0 232406 1.7 266555 1.5 BE3 100849 1.0 199487 0.9 236415 1.0 BF8 55763* 1.0 111746* 1.0 153074* 1.3 CC11 54421* 1.0 123576* 1.0 155337* 1.2 68 PCT/US2010/027242 WO 2010/105234

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Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays CD6 74970 1.0 151862 1.1 183377 1.1 CE6 70019 0.9 146292 1.1 208184 1.2 CG8 81790* 1.0 159098* 1.0 189209* 1.3 CG10 69503 0.9 141079 1.0 185801 1.1 DC4 112085 1.5 163319 1.2 169352 1.0 DD10 116325 1.5 205445 1.5 223473 1.3 DE7 60994* 0.9 131237* 0.9 174487* 0.9 DF5 34,165* 0.5 104,696* 0.7 179,314* 0.9 YB7 50433 0.7 103707 0.7 143423 0.8 YF5 65848 0.9 122487 0.9 146263 0.4 * Two separate screens were done. In the first, the signal detected for the SiMa cell line was 75811 RLU and this value was used to determine the fold difference for clonal cell lines tested in this screen (numbers with no asterisk). For the second screen, the signal detected for the SiMa cell line was 80562 RLU and this value was used to determine the fold difference for clonal cell lines tested in this screen (numbers with asterisk).

Example II

Stability Analysis of Clonal Cell Lines [0164] The following example illustrates how to characterize the stability of cells from an established clonal cell line that are susceptible to BoNT/A intoxication or have neurotoxin uptake capacity.

[0165] During characterization of the SiMa cell line, it was determined that the parental SiMa cell line became unstable in terms of a significant loss of sensitivity to BoNT/A. For example, prior to passage 13, cells comprising the parental SiMa cell line routinely exhibited an EC50 for BoNT/A activity that was under 5.0 pM. However, after passages about 14 to about 20 passages, cells comprising the parental SiMa cell exhibited an EC50 for BoNT/A activity that was routinely over 25.0 pM. One reason for this dramatic reduction in the EC50 value may be because the SiMa cell line is heterogeneous in nature since it comprises at least five different cell types. Over time, one of these cell types could overtake the culture to the exclusion of the other four. If the overtaking cell type was less susceptible to BoNT/A intoxication, or not susceptible at all, then as this cell type became the dominant one in the cell line the EC50 for BoNT/A activity in this overtaken SiMa cell line would decrease. Thus, because the established clonal cell lines were derived from only one of these cell types, then it follows that the clonal cell line would exhibit greater stability in terms of maintaining an EC50 for BoNT/A activity that was routinely under 5.0 pM.

[0166] To determine whether the cells from the established clonal cell lines showed increased stability relative to the cells comprising the parental SiMa cell line, the EC50 for BoNT/A activity was determined for clonal cell lines BB10, H1, H10, and the parental SiMa cell line at different passage numbers using an immuno-based method for determining BoNT/A activity. The media from the differentiated cells was aspirated from each well and replaced with fresh media containing either 0 (untreated sample), 0.98 U/mL, 1.9 U/mL, 3.91 U/mL, 7.81 U/mL, 15.6 U/mL, 31.3 U/mL, 62.5 U/mL, 125 U/mL, 250 U/mL, or 500 U/mL of a formulated BoNT/A pharmaceutical product. After a 24 hrs treatment, the cells were washed, incubated for an additional two days in serum-free medium without toxin to allow for the cleavage of the 69

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 SNAP-25 substrate, and harvested as described above. The supernatant was transferred to a capture antibody coated 96-well plate to perform the detection step.

[0167] Similarly, the preparation of the a-SNAP-25 capture antibody solution, a-SNAP-25 detection antibody solution, and the solid phase support comprising an a-SNAP-25 capture antibody were as described in Section 3. Lastly, detection of the presence of SNAP-25 cleavage product by ECL sandwich ELISA was performed, collected data was analyzed, and the EC50 calculated as described above in Section 2, except that PLA v. 2 was used for the 4-parameter logistics fit.

[0168] The results from this stability experiments indicated that BB10, H1 and H10 cell lines all exhibited increase stability as compared to the parental SiMa cell line. For example, where cells from the parental SiMa cell line exhibited an EC50 for BoNT/A activity that was over 500 U/mL (or 25 pM) after passages about 14 to about 20 passages, cells comprising the BB10, H1 and H10 cell lines all exhibited an EC50 for BoNT/A activity that was below 10 U/mL (or 0.5 pM) after passage about 30.

Example III

Gene Expression Profile of Cell Lines Comprising Cells Susceptible to BoNT/A Intoxication [0169] The following example illustrates how to characterize cells from an established clonal cell line that are susceptible to BoNT/A intoxication or have neurotoxin uptake capacity by gene expression profiling.

[0170] To determine the changes in genome-wide gene transcription levels in cells susceptible to BoNT/A intoxication, gene expression analysis was performed on cells from H1, BB10, 2D6 and the parental SiMa cell line, in both differentiated and undifferentiated states using GENECHIP® U133 Plus 2 microarray technology (Affymetrix, Inc., Santa Clara, CA) according to the manufacturer’s instructions, see, e.g., GENECHIP® Expression Analysis Technical Manual, 702232, Rev. 2 (2006) which is hereby incorporated by reference in its entirety.

[0171] To prepare differentiated cells for these cell lines, a suitable density of cells from the H1, BB10, 2D6, and SiMa cell lines were seeded in separate T175 tissue culture flasks containing 50 mL of a serum-free medium comprising Enhanced Minimum Essential Medium, 10 mM HEPES, 1 mM sodium pyruvate, 0.1 mM Non-Essential Amino Acids, 1 x B27 supplement, 1 x N2 supplement, and 60 pg/mL GT1b (302-011-M005, Alexis Biochemicals, San Diego, CA). These cells were incubated in a 37 °C incubator under 5% carbon dioxide until the cells differentiated, as assessed by standard and routine morphological criteria, such as growth arrest and neurite extension, and attained 80% confluence (approximately 3 days). The cells were then washed with 50 mL of 1 x PBS, trypsin-treated for 5 min at room temperature, and then 15 mL of growth medium was added to the flask to inactivate the trypsin. The cell suspension was transferred to a 50 mL tube and centrifuge at 200 RCF for 5 min at room temperature to pellet the cells. The cell pellet was washed once in 50 mL of 1 x PBS, centrifuge at 200 RCF for 5 min at room 70

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays 2017228675 15 Sep 2017 PCT/US2010/027242 18495 (BOT)/1957205.00451 WO 2010/105234 Patent Application temperature to pellet the cells, and the supernatant was removed. The cell pellet was quick frozen on dry ice and stored at -80 °C until needed.

[0172] To prepare undifferentiated cells for these cell lines, a suitable density of cells from the H1, BB10, 2D6, and SiMa cell lines were seeded in separate T175 tissue culture flasks containing 50 mL of growth medium comprising RPMI 1640, 10% fetal bovine serum, 10 mM HEPES, 1 mM sodium pyruvate, 0.1 mM Non-Essential Amino Acids, and 60 pg/mL GT1b. These cells were incubated in a 37 °C incubator under 5% carbon dioxide until the cells attained 80% confluence (approximately 3 days). The cells were then processed as described above and the cell pellet was quick frozen on dry ice and stored at -80 °C until needed.

[0173] To prepare total RNA, cells for each cell line were lysed and total RNA isolated and purified using a RNA isolation kit (QIAGEN, Valencia, CA) according to the manufacturer’s protocols. DNA was digested using an on-column DNase I procedure (QIAGEN, Valencia, CA). RNA was quantified photospectrometrically at 260 nm and purity assessed by the A260A280 ratio using a spectrophotometer. RNA integrity was assessed using a Bioanalyser 2100 (Agilent Technologies, Inc., Santa Clara, CA). Extracted total RNA aliquots were snap-frozen in liquid nitrogen and stored at -80 °C.

[0174] To prepare cDNA probes for the gene microarray chips, about 1-15 pg was reversed transcribed using a T7-Oligo(dT) promoter primer in the first strand cDNA synthesis reaction. Following RNase IH-mediated second strand cDNA synthesis, the double-stranded cDNA was purified and served as a template for subsequent in vitro transcription reaction. The in vitro transcription reaction was carried out in the presence of T7 RNA polymerase and a biotinylated nucleotide analog/ribonucleotide mix for complementary RNA (cRNA) amplification and biotin labeling. The biotinylated cRNA targets were then cleaned up, fragmented, and hybridized to microchip expression arrays for 17 hours at 65 °C according to the manufacturer’s instructions, see, e.g., GENECHIP® Expression Analysis Technical Manual, 702232, Rev. 2 (2006) which is hereby incorporated by reference in its entirety. To identify substantial treatment-related up- or down-regulated gene expression differences compared to control cell lines, greater than 1.5-fold differences (log2 0.58) were considered significant, and only those genes that displayed consistent changes in expression in the triplicate analysis were considered (Tables 5-12).

[0175] Expression profiling for cell lines H1, BB10 and 2D6 analyzed in the undifferentiated state revealed that 1,323 genes were identified as having their expression levels increase by 1.5-fold (log2 0.58) or more in the FH1 and BB10 cell lines as compared to the gene expression levels obtained from the 2D6 cell line (Table 5). Of these, 686 genes exhibited an increase in expression levels in the FH1 and BB10 cell lines by 2-fold (log2 1.0) or more as compared to the expression level for these genes determined from the 2D6 cell line; and 231 genes exhibited an increase in expression levels in the FH1 and BB10 cell lines by 4-fold (log2 2.0) or more as compared to the expression level for these genes determined from the 2D6 cell line. With respect to decreased expression, 1,438 genes were identified as having their expression levels decreased by 1.5-fold (log2 0.58) or more in the FH 1 and BB10 cell lines as 71

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 compared to the gene expression levels obtained from the 2D6 cell line (Table 6). Of these, 668 genes exhibited a decrease in expression levels in the H1 and BB10 cell lines by 2-fold (log2 1.0) or more as compared to the expression level for these genes determined from the 2D6 cell line; and 107 genes exhibited a decrease in expression levels in the H1 and BB10 cell lines by 4-fold (log2 2.0) or more as compared to the expression level for these genes determined from the 2D6 cell line.

[0176] Expression profiling for cell lines H1, BB10 and 2D6 analyzed in the differentiated state revealed that 2,556 genes were identified as having their expression levels increased by 1.5-fold (log2 0.58) or more in the H1 and BB10 cell lines as compared to the gene expression levels obtained from the 2D6 cell line (Table 7). Of these, 1,634 genes exhibited an increase in expression levels in the H1 and BB10 cell lines by 2-fold (log2 1.0) or more as compared to the expression level for these genes determined from the 2D6 cell line; and 696 genes exhibited an increase in expression levels in the H1 and BB10 cell lines by 4-fold (log2 2.0) or more as compared to the expression level for these genes determined from the 2D6 cell line. With respect to decreased expression, 2,087 genes were identified as having their expression levels decreased by 1.5-fold (log2 0.58) or more in the H1 and BB10 cell lines as compared to the gene expression levels obtained from the 2D6 cell line (Table 8). Of these, 1,215 genes exhibited a decrease in expression levels in the H1 and BB10 cell lines by 2-fold (log2 1.0) or more as compared to the expression level for these genes determined from the 2D6 cell line; and 280 genes exhibited a decrease in expression levels in the H1 and BB10 cell lines by 4-fold (log2 2.0) or more as compared to the expression level for these genes determined from the 2D6 cell line.

[0177] Expression profiling for cell lines H1, BB10 and SiMa analyzed in the undifferentiated state revealed that 1,232 genes were identified as having their expression levels increase by 1.5-fold (log2 0.58) or more in the H1 and BB10 cell lines as compared to the gene expression levels obtained from the SiMa parental cell line (Table 9). Of these, 764 genes exhibited an increase in expression levels in the H1 and BB10 cell lines by 2-fold (log2 1.0) or more as compared to the expression level for these genes determined from the SiMa parental cell line; and 228 genes exhibited an increase in expression levels in H1 and BB10 cell lines by 4-fold (log2 2.0) or more as compared to the expression level for these genes determined from the SiMa parental cell line. With respect to decreased expression, 1,265 genes were identified as having their expression levels decreased by 1.5-fold (log2 0.58) or more in the H1 and BB10 cell lines as compared to the gene expression levels obtained from the SiMa parental cell line (Table 10). Of these, 648 genes exhibited a decrease in expression levels in the H1 and BB10 cell lines by 2-fold (log2 1.0) or more as compared to the expression level for these genes determined from the SiMa parental cell line; and 189 genes exhibited a decrease in expression levels in H1 and BB10 cell lines by 4-fold (log2 2.0) or more as compared to the expression level for these genes determined from the SiMa parental cell line.

[0178] Expression profiling for cell lines H1, BB10 and SiMa analyzed in the differentiated state revealed that 756 genes were identified as having their expression levels increase by 1.5-fold (log2 0.58) or more in the H1 and BB10 cell lines as compared to the gene expression levels obtained from the SiMa parental 72

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 cell line (Table 11). Of these, 472 genes exhibited an increase in expression levels in the H1 and BB10 cell lines by 2-fold (log2 1.0) or more as compared to the expression level for these genes determined from the SiMa parental cell line; and 150 genes exhibited an increase in expression levels in H1 and BB10 cell lines by 4-fold (log2 2.0) or more as compared to the expression level for these genes determined from the SiMa parental cell line. With respect to decreased expression, 912 genes were identified as having their expression levels decreased by 1.5-fold (log2 0.58) or more in the H1 and BB10 cell lines as compared to the gene expression levels obtained from the SiMa parental cell line (Table 12). Of these, 411 genes exhibited a decrease in expression levels in the H1 and BB10 cell lines by 2-fold (log2 1.0) or more as compared to the expression level for these genes determined from the SiMa parental cell line; and 108 genes exhibited a decrease in expression levels in H1 and BB10 cell lines by 4-fold (log2 2.0) or more as compared to the expression level for these genes determined from the SiMa parental cell line.

Example IV

Pathway Analysis of Gene Expression Profiles from Clonal Cell Lines [0179] The following example illustrates how to characterize gene expression profiles from clonal cells from an established clonal cell line that are susceptible to BoNT/A intoxication or have neurotoxin uptake capacity in order to identify biological networks or pathways associated with BoNT/A intoxication.

[0180] An Ingenuity Pathway Analysis (IPA) Core Analysis (Ingenuity Systems Inc., Redwood City, CA) was performed to characterize the RNA expression phenotype of two independently derived BoNT/A very sensitive single clone cell lines, BB10 and H1, compared to a related but much less BoNT/A sensitive single clone cell line, 2D6. The analysis was done to identify the specific gene expression phenotype of a BoNT/A sensitive cell line. The result can also be used to predict and potentially identify proteins that function to enhance BoNT/A uptake.

[0181] An Ingenuity Pathway Analysis (IPA) Core Analysis was performed that identified biologically relevant networks to BoNT/A intoxication based on connectivity among the genes from an IPA library and the genes exhibiting significant changes as determined from the expression profiling discussed above. For this analysis, all genes that exhibited an increased or decrease in expression levels in the H1 and BB10 cell lines by 4-fold (log2 2.0) or more as compared to the expression level for these genes determined from the 2D6 cell line were used, in conjunction with, selected genes with known or suspected relevance to BoNT/A intoxication, hereafter referred to as the Profile genes. The significance of the association to a given network was measured and ranked by the ratio of the number of Profile genes that mapped to the specific network divided by the total number of genes that map to that network. Fisher's exact test was used to calculate p-scores, which represent the association between the Profile genes and the network, and based on the p-scores the genes from the Profile genes were used to rank the networks. The p-scores were derived from p-values. If there are n genes in the network and f of them are Profile genes, then the p-value is the probability of finding for more Profile genes in a set of n 73 PCT/US2010/027242 WO 2010/105234

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Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays genes randomly selected from the Global Molecular Network. Since significant p-values are quite low (e g., 1 x 10"8), a p-score was defined as the component of the p-value; p-score = -log 10 (p-value). The identified networks were overlaid with differentially expressed genes which had more than 1.5-fold differential expression and a p-value < 0.001 either before or after differentiation.

[0182] Using IPA Core Analysis the differentially expressed Profile genes were connected to 26 Networks. Nineteen of these included 10 or more Profile genes (Table 13). Among these nineteen networks three overall networks groups, named A, B and C were identified (Table 13). Within the networks in these three groups there were overlapping genes and the expression for more than three genes was increased after differentiation. Group A genes include the FGFR2 receptor which has been shown to function in the BoNT/A intoxication process as a receptor for BoNT/A and are as follows: genes exhibiting a 1.5-fold or more decrease in expression levels in the H1 and BB10 cell lines as compared to their expression in cells from the 2D6 cell line, ANXA2, AQP1, ARHGAP9, CDH10, CDKN2A, CHPT1, CNTN2, ERAP1, and RGS11; genes exhibiting a 1.5-fold or more increase in expression levels in the H1 and BB10 cell lines as compared to their expression in cells from the 2D6 cell line, ADAMTS9, ATAD2, C110RF82, CDC45L, CNTN1, CNTN4, Cyclin A, Cyclin E, E2F1, E2F2, E2F7, ELOVL7, EME1, FGFR, FGFR2, KIAA1524, MELK, MYBL1, MYBL2, NDC80, NDN, ORC1L, PLS3, PRIMA1, RAD54L, RBL1, RBPMS, RRM2, S1PR3, SCLY, SLCIA3, SPC24, SPC25, ST8SIA4, TFDP1, TFP12, TK1, TMEM35, TTK, TWIST 1, TYMS, TYK, and ZWINT.

[0183] Group B genes include the EGFR, a receptor which is regulated by NGF, which has been shown to increase BoNT/A uptake in cell culture experiments and are as follows: genes exhibiting a 1.5-fold or more decrease in expression levels in the H1 and BB10 cell lines as compared to their expression in cells from the 2D6 cell line, ABCC8, AELIM3, CAP2, IL17B, MEF2A, NEEBL, PHC, S100A6, SLC1A6, SMAD1, SMAD5, SMAD8, SYT13, and SYTL1; genes exhibiting a 1.5-fold or more increase in expression levels in the H1 and BB10 cell lines as compared to their expression in cells from the 2D6 cell line, AURKB, BIRC5, BRCA1, BRCA2, BRIP1.BUB1B, CD9, DLGAP3, DYNLT3, ENC1, FBLN1, FOXM1, Gpy, GNAI1, GNG11, GNG12, GPSM2, GUCY1B3, HGF, ITGA6, JNK, KCNJ5, KIF18A, KITLG, MMD, MSN, MYRIP, NEK2, NR3C1, NXPH1, OSBPL3, PKMYT1, PTPRM, RAD51, RAD51AP1, SLC7A2, SLC43A3, SMC6, SNAI2, SNCAIP, SSH2, STK17A, SYNP02, TOP2A, TPTE, TRAF4, TSPAN, TSPAN4, UBE3, UBE3B, and VAV3.

[0184] Group C genes include a number of microtubule motor proteins of the kinesin family that may function in the intracellular trafficking of BoNT/A and are as follows: genes exhibiting a 1.5-fold or more decrease in expression levels in the H1 and BB10 cell lines as compared to their expression in cells from the 2D6 cell line, CSTB, GPCR, GRIM5, KISSR, SCN2A, SLC1A2, and THBS2; genes exhibiting a 1.5-fold or more increase in expression levels in the H1 and BB10 cell lines as compared to their expression in cells from the 2D6 cell line, ALCAM, AURKA, CHEK, CIT, CSRP2, E2F, ECT2, EFNB2, ERK, ESPL1, GNAI, GPR161, HMMR, KIF4A, KIF14, KIF15, KIF22, KIF23, KIFC1, LPAR1, MK167, OIP5, PHLPP, PP1/PP2A, PPP1R3C, PRC1, PTTG1, RACGAP, RB, RGS5, SDC2, and TPX2. 74

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 [0185] The remaining networks identified did not share common genes between any other network. For Network 3, genes exhibiting a 1.5-fold or more decrease in expression levels in the H1 and BB10 cell lines as compared to their expression in cells from the 2D6 cell line, ADARB1, ADM, PTPPH, and SLC01A2; genes exhibiting a 1.5-fold or more increase in expression levels in the H1 and BB10 cell lines as compared to their expression in cells from the 2D6 cell line, ASCL1,HES6, MAPK, NMU, PEG3, PTPRK, PRLHR, PTPRK, SGOL2, SPARC, and ZNF217. For Network 6, genes exhibiting a 1.5-fold or more decrease in expression levels in the H1 and BB10 cell lines as compared to their expression in cells from the 2D6 cell line, CNGA3, HIST1H3E and PTGS1; genes exhibiting a 1.5-fold or more increase in expression levels in the H1 and BB10 cell lines as compared to their expression in cells from the 2D6 cell line, ASF1B, BASP1, CHAF1A, NCAPH, PBK, PRAME, SMC2, UHRF1, and VRK1. For Network 9, genes exhibiting a 1.5-fold or more decrease in expression levels in the H1 and BB10 cell lines as compared to their expression in cells from the 2D6 cell line, HIST1H2BD and OSCAR; genes exhibiting a 1.5-fold or more increase in expression levels in the H1 and BB10 cell lines as compared to their expression in cells from the 2D6 cell line, C14ORF106, CEP72, KIF20A, PCNA, PEX13, PFC5, POLQ, SPAG5, SYTL4, TROAP, and WDR51 A. For Network 12, genes exhibiting a 1,5-fold or more increase in expression levels in the H1 and BB10 cell lines as compared to their expression in cells from the 2D6 cell line, ANLN, ARHGAP24, ASPM, BUB1, CCDC99, CEP55, CKAP2, DRAM, E2F8, PLXNA2, SLC16A10, UBE2C, UBE2S, and WDHD1. For Network 13, genes exhibiting a 1.5-fold or more decrease in expression levels in the H1 and BB10 cell lines as compared to their expression in cells from the 2D6 cell line, CALY; genes exhibiting a 1.5-fold or more increase in expression levels in the H1 and BB10 cell lines as compared to their expression in cells from the 2D6 cell line, ARHGEF3, CTSL2, DIAPH3, FBP1, KIF2C, KIF11, PFKFB3, and PLK4. For Network 14, genes exhibiting a 1.5-fold or more decrease in expression levels in the H1 and BB10 cell lines as compared to their expression in cells from the 2D6 cell line, COL5A1 and MICAL2; genes exhibiting a 1.5-fold or more increase in expression levels in the H1 and BB10 cell lines as compared to their expression in cells from the 2D6 cell line, FNDC5, HSPC159, MAB21L2, SLITRK5, SYN2, and ZNF367. For Network 15, genes exhibiting a 1.5-fold or more decrease in expression levels in the H1 and BB10 cell lines as compared to their expression in cells from the 2D6 cell line, OLFML2A and SIGIRR; genes exhibiting a 1.5-fold or more increase in expression levels in the H1 and BB10 cell lines as compared to their expression in cells from the 2D6 cell line, EX01, KCTD12, MY06, PHEBL1, SHCBP1, TPBG, and TUBB6. For Network 17, genes exhibiting a 1.5-fold or more decrease in expression levels in the H1 and BB10 cell lines as compared to their expression in cells from the 2D6 cell line, HPCAL1 and LPAR5; genes exhibiting a 1.5-fold or more increase in expression levels in the H1 and BB10 cell lines as compared to their expression in cells from the 2D6 cell line, BTG3, GABRA5, TR1P10, and ZNF521. For Network 19, genes exhibiting a 1.5-fold or more decrease in expression levels in the H1 and BB10 cell lines as compared to their expression in cells from the 2D6 cell line, HTR1E and SORCS1; genes exhibiting a 1.5-fold or more increase in expression levels in the H1 and BB10 cell lines as compared to their expression in cells from the 2D6 cell line, BNC2, DPYD, EMILIN2, PPIL5, and TACC3. 75 PCT/US2010/027242 WO 2010/105234

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Table 13. IPA Core Analysis of Profile Genes Group Network Proteins in Network pvalue Profile Gene Number Expression Undifferentiated State Expression Differentiated State Decreased Increased Decreased Increased A 1 ADAMTS9, ATAD2, CDC45L, CDKN2A, CNTN1, CNTN2, Cyclin A, Cyclin E, DIRAS3, E2F1, E2F2, E2F7, FGFR2, HDAC, MYBL1, MYBL2, NDC80, NDN, NFkB, ORC1L, PLS3, RAD54L, RBL1, RRM2, S1PR3, SPC24, SPC25, TFDP1, TFPI2, TK1, TNFRSF10D, TTK, TYMS, TYK, ZWINT 51 30 CDKN2A ADAMTS9, CNTN1, HDAC, NDN, PLS3, S1PR3,TFPI2 CDKN2A, CNTN2, ADAMTS9, ATAD2, CDC45L, CNTN1, Cyclin A, Cyclin E, E2F1, E2F2, E2F7, FGFR2, MYBL1, MYBL2, NDC80, NDN, ORC1L, PLS3, RAD54L, RBL1, RRM2, S1PR3, SPC24, SPC25, TFDP1, TFPI2, TK1, TTK, TYMS, TYK, ZWINT C 2 ALCAM, ANK2, ANK3, AURKA, DOK5, E2F, ERK, ESPL1, GDF15, GFRA2, HMMR, ITGA9, KIF15, KIF22, KISS1R, KPNA, KPNB, LGI1, MAFB, MAP2K1, MAP2K2, MKI67, NRG3, OIP5, PHKA2, PHLPP, POSTN, PP1/PP2A, PP2A, PPP1R3C, PPP2R2B, PPP2R2C, PTTG1, RAF1, RB, SCN2A, TPX2 46 28 ANK2, ANK3, PHKA2, PPP2R2C, SCN2A ALCAM, DOK5, ERK, GFRA2, PP1/PP2A, PP2A, PPP1R3C, PPP2R2B KISSR, SCN2A ALCAM, AURKA, E2F, ERK, ESPL1, HMMR, KIF15, KIF22, MKI67, OIP5, PHLPP, PP1/PP2A, PPP1R3C, PTTG1, RB, TPX2 76 PCT/US2010/027242 WO 2010/105234

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Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays — 3 ADARB1, ADM, AKAP12, ALP, ASCL1, BHLHB2, CRH, DLL1, FRZB, FSH, GRIA2, GRIP2, hCG, HES6, HTATIP2, IL13RA2, MAPK, NMU, PDGF BB, PDLIM3, PEG3, PLAT, PPFIA4, PRLHR, PTPRH, PTPRK, SGOL2, SLC01A2, SMAD6, SPARC, STC1, TEAD4, TGFB, VEGF, ZNF217 46 28 ADARB1, GRIP2, SLC01A2 ASCL1, DLL1, FRZB, MAPK, PEG3, PLAT, PRLHR, SMAD6, SPARC, ZNF217 AD ARB 1, ADM, PTPPH, SLC01A2 ASCL1, HES6, MAPK, NMU, PEG3, PRLHR, PTPRK, SGOL2, SPARC, ZNF217 c 4 AKT, ACTN1, ACTN2, ACTN3, ATF5, ATM/ATR, BDKRB2, CHEK1, CHEK2, CIT, CSRP2, CSTB, CTSH, ECT2, EFNB2, ELM01, GNAI, GABBR2, GPCR, GPR161, GRM5, ICAM2, KIF4A, KIF14, KIF23, KIFC1, LPAR1, MMP, PDGFA PDGFB, PRC1, RAC, RAC2, RACGAP1, RGS5, SDC2, SLC1A2, THBS2 43 27 CSTB, GPCR, GRIM5, SLC1A2 GNAI, GPR161, LPAR1, RGS5 CSTB, GPCR, GRIM5, SLC1A2, THBS2 CIT, CSRP2, ECT2, EFNB2, CHEK, GNAI, GPR161, KIF4A, KIF14, KIF23, KIFC1, LPAR1, PRC1, RACGAP, RGS5, SDC2, B 5 ABLIM3, F-ACTF, G-ACT, CD9, CXCR4, DTNA, ENC1, FNBP1, ΰβγ, GNAI1, GNG11, GNG12, GPSM2, ITG, 38 25 SYT13, S100A6 CD9, CXCR4, ENC1, GPy, GNAI1, GNG11, GNG12, ITGA6, JNK, MSN, MYRIP, STK17A AELIM3, S100A6, SYT13, SYTL1 CD9, ENC1, GPy, GNAI1, GNG11, GNG12, GPSM2, ITGA6, JNK, KCNJ4, MSN, MYRIP, 77 PCT/US2010/027242 WO 2010/105234

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ITA5, ITGA6, JNK, KCNJ4, MLC, MSN, MYRIP, NOX, NET1, NRXN1, NXPH1, PI3K, RHO, S100A6, STK17A, SYT13, SYTL1, TRAF4, TSPAN, TSPAN3, TSPAN4, VAV3 NXPH1, STK17A, TRAF4, TSPAN, TSPAN4, VAV3 — 6 ADCY, ADCY1, AP1, ASF1B, ATP2B4, BASP1, BCL11B, CAM, CAMK2B, CHAF1A, CNGA3, CYP2E1, DACH1, HIST1H3E, HISH3, HRH3, HSP90, IL1, IL12, INS, INFA, ISG20, KCNN2, LDL, MMP14, NCAPH, PBK, PDGF, PIAS1, PRAME, PTGS1, SEC31A, SMC2, UHRF1, VRK1 36 24 CAMK2B BASP1, HRH3 CNGA3, HIST1H3E, PTGS1 ASF1B, BASP1, CHAF1A, NCAPH, PBK, PRAME, SMC2, UHRF1, VRK1 B 7 BARD1, BRCA1, BRCA2, BRIP1, BUB1B, CNA, CAP2, CK2, DLGAP5, FAT, GUCY1B3, HSP70, KITLG, MEF2A, NEK2, NFAT, NR3C1, NF1, PHLDA2, PKC(s), RAD51, RAD51AP1, TOP2, SAMD4A, SLC1A6, SMC6, SNAI2, SNCAIP, 32 24 CAP2, CNA, PHLDA2, PKC(s) NR3C1, SMC6, SNCAIP, TCF7L2 CAP2, MEF2A, PKC(s), SLC1A6 BRCA1, BRCA2, BRIP1, BUB1B, DLGAP3, GUCY1B3, NEK2, KITLG, NR3C1, RAD51, RAD51AP1, SMC6, SNAI2, SNCAIP, UBE3, UBE3B 78 PCT/US2010/027242 WO 2010/105234

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STAT5a, STAT5b, TCF7L2, UBE3, UBE3B, UBN, XP01 B 8 CBP, AURKB, BIRC5, CACNA1D, CBP/p300, CD3, CREB, CREB5, DBH, EGR1, ERK1, ERK2, FBLN1, FBN1, FOXM1, HGF, INCENP, KCNMA1, LGALS1, MAOA, MEK, NDRG1, NID1, P38 MAPK, PKA, PKMYT1, PRKAC, PRKACB, RAF, RAP1, RAS, RGMA, RSK, SMAD1, SMAD5, SMAD8, SYNP02, TOP2A 30 21 KCNMA1, NDRG1, RAS ERK1, ERK2, MAOA, P38 MAPK, RGMA NDRG1, SMAD1, SMAD5, SMAD8 AURKB, BIRC5, ERK1, ERK2, FBLN1, FOXM1, HGF, MAOA, P38 MAPK, PKMYT1, SYNP02, TOP2A — 9 C14ORF106, CDKN1A, CEP72, DHX8, FKBPL, HIST1H2BD, HNF4A, KIF20A, KRT18, MTHFS, OSCAR, PCGF5, PCNA, PELO, PEX13, PFC5, POLD4, POLK, POLL, POLM, POLO, POLS, R3HDM1, RASL12, RFC5, SLC33A1, SPAG5, STAT4, SULT1A1, SULT1C2, SYTL4, TCEAL3, TROAP, VEZT, WDR51A, 19 15 — PCGF5 HIST1H2BD, OSCAR C14ORF106, CEP72, KIF20A, PCNA, PEX13, PFC5, POLQ, SPAG5, SYTL4, TROAP, WDR51A 79 PCT/US2010/027242 WO 2010/105234

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Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays ZBTB16 A 10 ARHGAP9, CDH10, CDS1, CDS2, CHPT1, CNTN4, ELOVL7, EME1, FGFR, GAS6, HAND1, IFI202B, ISL1, KIAA1524, KRT74, MIRN31, MUS81, MYF6, MYOD1, NFYB, OTX1, PRIMA1, QKI, RBM9, RBPMS, RORA, SHOX2, SLC39A8, SOX2, SOX15, ST8SIA4, STAT3, TWIST 1, VPS39, ZFHX3 18 15 CHPT1 CNTN4, ELOVL7, HAND1, ODS2, SOX2, TWIST 1 ARHGAP9, CDH10 CNTN4, ELOVL7, EME1, FGFR, KIAA1524, PRIMA1, RBPMS, ST8SIA4, TWIST1 B 11 ALDH3A2, B3GALT2, BAMBI, CNN2, CTNNAL1, CTNNB1, CTSC, CUGBP2, DYNLT3, IL13, KIF18A, LIN7C, MFI2, MPP5, MRC2, NDST1, PDGF-CC, PHLDA2, PLAU, PPM1J, PPP1CA, PTPN14, PTPRM, SLC16A3, SLC26A2, SLC43A3, SLC7A2, SSH2, STK17A, TAX1BP3, TCF7L1, TGFB1, TPTE, TSPAN8 18 15 PHLDA2 BAMBI, CUGBP2, DYNLT3, SLC7A2, SLC43A3, STK17A, TPTE — DYNLT3, KIF18A, PTPRM, SLC7A2, SLC43A3, SSH2, STK17A, TPTE — 12 AHR, AHRR, ANLN, APH1B, ARHGAP24, ASPM, BUB1, CCDC99, 17 15 HS3ST1 PDZRN3, PVRL3 — ANLN, ARHGAP24, ASPM, BUB1, CCDC99, 80 PCT/US2010/027242 WO 2010/105234

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Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays CEP55, CKAP2, DRAM, E2F8, HS3ST1, JPH1, MIRN124-1, NMT2, PDZRN3, PLXNA2, PMM1, PPP1R13L, PVRL3, RFFL, S100A2, SLC16A10, TP53, UBE2A, UBE2C, UBE2D2, UBE2S, UBE2V1, UBE2V2, UBL3, VPS37C, WDHD1 CEP55, CKAP2, DRAM, E2F8, PLXNA2, SLC16A10, UBE2C, UBE2S, WDHD1 — 13 ARHGEF3, CALY, CSH2, CTSL2, DIAPH3, ECEL1, FBP1, FFAR2, FRAT2, GSK3B, HSD17B4, IL6, IL19, KIF11, KIF2C, KNG1, LARGE, LEFTY2, LGR5, LIF, LPAR3, MPZ, MSLN, ORM2, PFKFB3, PLK4, PMP22, PRPH, PRSS8, PTGER3, SCN7A, SCNN1B, SLC4A11, TAL1 17 14 CALY ARHGEF3, GSK3B, RMP22 CALY ARHGEF3, CTSL2, DIAPH3, FBP1, KIF2C, KIF11, PFKFB3, PLK4 — 14 AGT, AGTRAP, Beta ARK, CADPS, CD160, COL5A1, CPNE8, FNDC5, HSPC159, INA, ITGA7, LIMA1, LPP, MAB21L2, 15 13 CPNE3 CADPS, FNDC5, MAB21L2, SLITRK5, ST8SIA2 COL5A1, MICAL2 FNDC5, HSPC159, MAB21L2, SLITRK5, SYN2, ZNF367 81 PCT/US2010/027242 WO 2010/105234

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Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays MAPK1, MERTK, MICAL2, MIRN294, MIRN185, MIRN352, NTN1, PLCG1, PLCG2, PTGFR, RASGEF1B, RBM4B, RSU1, SKAP1, SLITRK5, SPRED1, ST8SIA2, SYN2, TGFB3, TNS1, ZNF367 — 15 ACT1, BAG5, CPVL, EX01, GIPC1, GJC1, GPR37, HSPA5, HSPA1A, HSPBP1, IkBKB, KCTD12, MAP3K3, MAP3K14, MEKK3/NIK, MIRN30B, MY06, OLFML2A, PELI3, RHEBL1, RNF126, RPL10A, RPN1, SEC16A, SHC1, SHCBP1, SIGIRR, TJP3, TPBG, TRAF6, TRAF2-TRAF5, TRAF2-TRAF5, TRAF6, TUBB6, TUBB2B 15 13 — KCTD12, TPBG OLFML2A, SIGIRR EX01, KCTD12, MY06, PHEBL1, SHCBP1, TPBG, TUBB6 B 16 ABCC8, BACE2, CLASP1, COLEC12, CXCR7, DACT1, ENTPD5, FGD6, FM01, GSTT1, IL17B, KRT34, KYNU, LAMP3, 15 13 IL17B DACT1, PCDH8 ABCC8, IL17B, NEEBL MMD, OSBPL3, SYNP02 82 PCT/US2010/027242 WO 2010/105234

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Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays LMCD1, MIRN101B, MMD, NEBL, NFRKB, OSBPL3, PCDH8, PEMT, RASAL2, SAMD4A, ST3GAL3, SYNGR3, SYNP02, TNF, TNNC1, TXN2, YWHAG, ZNF267, ZYX — 17 ARPP-19, BTG3, CBFA2T2, CBLN1, CNGA2, EBF1, EGF, EGFR, GABA, GABRA5, GABRB3, GABRD, GABRR1, HDAC9, HPCAL1, HTT, IDS, INSL3, LPAR5, OPRL1, PCDH9, PDE10A, PDE11A, PDEIA, PDEIB, PDE2A, PDE4C, PDE6H, PPAP2B, PPP1R1B, ROB02, SH3D2C1, TRIP10, ZNF521 14 13 HPCAL1 PPAP2B HPCAL1, LPAR5 BTG3, GABRA5, TRIP10, ZNF521 A 18 ANXA2, AQP1, C110RF82, CCNI, CDKN2A, DEFB104A, DEFB4, EGLN3, ERAP1, FAM129A, GNA01, IFNG, IL1B, IL1F7, INCA, LOC729687, 14 12 AQP1, CDKN2A MINA, PDE5A ANXA2, CDKN2A, ERAP1, RGS11 C110RF82, MELK, MINA, PDE5A, SCLY, SLC1A3, TMEM35 83 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays MELK, MINA, MIRN210, MPA2L, MYC, NNAT, PDE5A, RGS11, RNASE7, RT1-B, SCLY, SCUBE1, SLC11A1, SLC14A1, SLC1A3, ST18, TSH, TMEM35, TREM3 — 19 BIRC8, BNC2, CASP5, CASP10, CASP14, CASP, CBLN2, DEDD2, DNASE1L1, DPYD, DSG3, EIF4E, EMILIN2, HTRID, HTRIE, HTRIF, HTR3A, IFT57, KHDC1, MIRN20A, MTCH1, NGFR, PLXNA4, PPIL5, RB1, RP11-257K9.7, SEMA6D, SERPINA3K, SORCS1, STK25, SYT5, TACC3, TERT 10 10 — EMILIN2, PLXNA4 HTR1E, SORCS1 BNC2, DPYD, EMILIN2, PPIL5, TACC3 — 20 EGFL7, GFI1B 2 1 — — — — — 21 AGRN, PRSS12 2 1 — — — — — 22 KCNB1, KCNG3 2 1 — — — — — 23 NUP37, NUP43 2 1 — — — — — 24 HS6ST1, HS6ST2 2 1 — — — — — 25 FUCA1, FUCA2 2 1 — — — — — 26 IQGAP, IQGAP3, MIRN339 2 1 — — — — 84

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Example V

Pathway Analysis of Gene Expression Profiles from Clonal Cell Lines [0186] The following example illustrates how to characterize gene expression profiles from clonal cells from an established clonal cell line that are susceptible to BoNT/A intoxication or have neurotoxin uptake capacity in order to identify biological networks or pathways associated with BoNT/A intoxication.

[0187] Computer analysis was performed to characterize the RNA expression phenotype of two independently derived single clone cell lines, BB10 and H1, very sensitive to BoNT/A activity and a single clone cell line, 2D6, that was less sensitive BoNT/A activity. The results are useful in identifying clonal cell lines selected from the SiMa parental cell line that are useful to practice the methods disclosed in the present specification.

[0188] To identify the specific gene expression phenotype associated with a BoNT/A sensitive cell line, the data was analyzed using JMP Genomic (SAS Institute Inc., Cary, NC). To perform a JMP Genomics analysis, the RNA expression data was imported to JMP Genomics by creating two SAS files, designated “data” and “Experiment design.” A basic expression workflow was performed, including a variance analysis and one-way analysis of variance (one-way ANOVA) to identify differences in mean expression values. The variance analysis was used to identify differences between the cell lines and the differentiation state of each cell line (differentiated or non-differentiated). The expression values of all four cell lines were compared pair wise, independent of differentiation and genes that were > 4-fold overexpressed in the H1 cell line as compared to the 2D6 cell line, in the BB10 cell line as compared to the 2D6 cell line, and in SiMa parental cell line (PA) compared to the 2D6 cell line. The variance analysis treats all factors in the study as random effects, to find out what their contribution is to the proportion of variance explained (total variance = 100%). About half of the variance, 46.9% was assigned to differences among the different cell types, while 26% was assigned to differences before and after differentiation. Only 4.6% of the variance was assigned to differences among differentiated or non-differentiated cells types, meaning that the genes that were differentially expressed after differentiation were similar for all cell types examined, suggesting that the difference in BoNT/A sensitivity among the cell lines is independent of differentiation state. As such, the focus was placed on genes that are different among the different cells types irrespective of differentiation.

[0189] Based on the results from the variance analysis, the expression values of all cell lines were compared pair wise, independent of differentiation (FIG. 2). Only gene probes that were > 4-fold overexpressed in the H1 cell line as compared to the 2D6 cell line, and in the BB10 cell line as compared to the 2D6 cell line are shown. The gene probes were plotted as expression value (Log2) on the x-axis and p-value (-log10(p-value)) on the y-axis. The red dashed line marks the 95% confidence interval. The genes probes that were > 4-fold over-expressed in the H1 cell line as compared to the 2D6 cell line (FIG. 2A), and the BB10 cell line as compared to the 2D6 cell line (FIG. 2B), were also to a large extend among 85 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based Bo NT/A Activity Assays the genes that were over-expressed in the BB10 cell line as compared to the SiMa parental cell line (PA, FIG. 2C), in the H1 cell line as compared to the SiMa parental cell line (FIG. 2D), and in the SiMa parental cell line as compared to the 2D6 cell line (FIG. 2E). These data suggest that BoNT/A sensitivity was related to a gradual increase in expression of these genes. Based on this finding, the number of gene probes was further narrowed down to 119 by including only gene probes that were also over-expressed in the SiMa parental cell line compared to the 2D6 cell line, rationalizing that gene probes that were differential expressed across one more cell line would be even more likely to be important for BoNT/A sensitivity. As such, the JMP Genomic analysis resulted in the identification of 119 gene probes, designated the JMP probe set.

[0190] The JMP probe set was exported to Ingenuity Pathway Analysis (IPA) Core Analysis (Ingenuity Systems Inc., Redwood City, CA) to further characterize the JMP probe set. Using this analysis, biologically relevant networks to BoNT/A intoxication were identified based on connectivity among the genes from an IPA library and the gene probes contained in the JMP probe set. The significance of the association to a given network was measured and ranked by the ratio of the number of gene probes from the JMP probe set that mapped to the specific network divided by the total number of genes that map to that network. Fisher's exact test was used to calculate p-scores, and based on the p-scores the genes from the JMP probe set were used to rank the networks. The p-scores were derived from p-values. If there are n genes in the network and fof them are gene probes from the JMP probe set, then the p-value is the probability of finding f or more gene probes from the JMP probe set in a set of n genes randomly selected from the Global Molecular Network. Since significant p-values are quite low (e.g., 1 x 10"8), a p-score was defined as the component of the p-value; p-score = -log 10 (p-value). The identified networks were overlaid with differentially expressed genes which had more than 1.5-fold differential expression and a p-value < 0.001 either before or after differentiation. Using IPA Core Analysis, 111 of the 119 gene probes from the JMP probe set were mapped to networks. The eight unmapped probes most likely represent either a probe with an outdated nomenclature or one representing a gene without a known gene product. The 111 gene probes corresponded to 79 genes that were greater than 4.0-fold differentially expressed in the H1 and BB10 cell lines when compared to the 2D6 cell line and that were also greater than 4.0-fold differentially expressed in the SiMa parental cell lines when compared to the 2D6 cell line, when the p-value cut off was set to 0.05 (Table 14).

Table 14. Genes Identified using IPA Core Analysis Gene Name Gene Symbol Probe ID. No. Location Type Log Ratio Achaete-scute complex homolog 1 ASCL1 209985_s_at Nucleus Transcription regulator 4.469 Achaete-scute complex homolog 1 ASCL1 209988_s_at Nucleus Transcription regulator 2.774 Achaete-scute complex homolog 1 ASCL1 213768_s_at Nucleus Transcription regulator 2.955 86 WO 2010/105234 2017228675 15 Sep 2017 PCT/US2010/027242

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Acyl-CoA thioesterase 9 ACOT9 221641_s_at Cytoplasm Enzyme 2.251 ADAM metallopeptidase with thrombospondin type 1 motif, 9 ADAMTS9 226814_at Extracellular Space Peptidase 4.034 Ankyrin 2, neuronal ANK2 216195_at Plasma Membrane Other -2.673 Ankyrin 2, neuronal ANK2 232606_at Plasma Membrane Other -2.621 Blood vessel epicardial substance BVES 228783_at Plasma Membrane Other 3.174 Brain abundant, membrane attached signal protein 1 BASP1 202391_at Plasma Membrane Other 4.549 BRCA1 associated RING domain 1 BARD1 205345_at Nucleus Transcription regulator 3.44 Calsyntenin 2 CLSTN2 219414_at Plasma Membrane T ransporter 2.024 cAMP responsive element binding protein 5 CREB5 232555_at Nucleus Transcription -2.67 Cathepsin L2 CTSL2 210074_at Cytoplasm Peptidase 2.119 CD9 molecule CD9 201005_at Plasma Membrane Other 2.887 Cell division cycle associated 7-like CDCA7L 225081_s_at Nucleus Other 3.737 Centromere protein L CENPL 1554271_a_at Unknown Other 2.582 Chromosome 11 open reading frame 75 C110RF75 219806_s_at Unknown Other 3.914 Chromosome 3 open reading frame 70 C3ORF70 242447_at Unknown Other 2.705 Coiled-coil domain containing 109B CCDC109B 218802_at Unknown Other 2.881 Contactin 1 CNTN1 211203_s_at Plasma Membrane Enzyme 3.684 Contactin 1 CNTN1 227202_at Plasma Membrane Enzyme 3.184 Contactin 1 CNTN1 227209_at Plasma Membrane Enzyme 3.188 Copine VIII CPNE8 228365_at Unknown Other -3.355 Copine VIII CPNE8 241706_at Unknown Other -2.736 CUG triplet repeat, RNA binding protein 2 CUGBP2 202157_s_at Nucleus Other 3.588 Cyclin-dependent kinase 2 CDK2 204252_at Nucleus Kinase 2.744 Cysteine and glycine-rich protein 2 CSRP2 207030_s_at Nucleus Other 2.487 87 PCT/US2010/027242 WO 2010/105234

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Cysteine and glycine-rich protein 2 CSRP2 211126_s_at Nucleus Other 2.109 DEP domain containing 1 DEPDC1 220295_x_at Unknown Other 2.795 Diaphanous homolog 3 DIAPH3 232596_at Cytoplasm Enzyme 2.434 Dihydropyrimidine dehydrogenase DPYD 204646_at Cytoplasm Enzyme 4.248 Docking protein 5 DOK5 214844_s_at Plasma Membrane Other 4.56 Dynein, light chain, Tctex-type 3 DYNLT3 203303_at Cytoplasm Other 3.449 Elastin microfibril interfacer 2 EMILIN2 224374_s_at Extracellular Space Other 2.603 Ets variant 1 ETV1 206501_x_at Nucleus Transcription regulator 2.578 Ets variant 1 ETV1 217053_x_at Nucleus Transcription regulator 2.499 Ets variant 1 ETV1 217061_s_at Nucleus Transcription regulator 2.557 Family with sequence similarity 101, member B FAM101B 226876_at Unknown Other 2.399 Fibroblast growth factor receptor 2 FGFR2 203638_s_at Plasma Membrane Kinase 2.306 Fibroblast growth factor receptor 2 FGFR2 203639_s_at Plasma Membrane Kinase 3.239 Fibroblast growth factor receptor 2 FGFR2 208228_s_at Plasma Membrane Kinase 2.151 Fibronectin type III domain containing 5 FNDC5 226096_at Unknown Other 2.054 Fibulin 1 FBLN1 201787_at Extracellular Space Other 2.801 Fibulin 1 FBLN1 202994_s_at Extracellular Space Other 2.378 Fibulin 1 FBLN1 202995_s_at Extracellular Space Other 3.733 G protein-coupled receptor 177 GPR177 221958_s_at Unknown Other 2.389 G protein-coupled receptor 177 GPR177 228950_s_at Unknown Other 2.622 G-2 and S-phase expressed 1 GTSE1 204317_at Cytoplasm Other 3.334 Gametocyte specific factor 1 GTSF1 227711_at Unknown Other 6.407 Guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 1 GNAI1 227692_at Plasma Membrane Enzyme 3.123 Guanine nucleotide binding protein (G protein), beta polypeptide 4 GNB4 225710_at Plasma Membrane Enzyme 6.066 88 PCT/US2010/027242 WO 2010/105234

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Guanine nucleotide binding protein (G protein), gamma 11 GNG11 204115_at Plasma Membrane Enzyme 4.251 Guanine nucleotide binding protein (G protein), gamma 12 GNG12 212294_at Plasma Membrane Enzyme 2.315 Guanine nucleotide binding protein (G protein), gamma 12 GNG12 222834_s_at Plasma Membrane Enzyme 3.403 Hepatocyte growth factor (hepapoietin A) HGF 209960_at Extracellular Space Growth factor 2.939 Hypothetical protein LOC100289109 LOC100289 109 216189_at Unknown Other -3.256 Hypothetical protein LOC144571 LOC 144571 1564139_at Unknown Other -2.394 Inositol 1,4,5-triphosphate receptor interacting protein ITPRIP 225582_at Unknown Other 3.522 Interleukin 17B IL17B 220273_at Extracellular Space Cytokine -4.735 KDEL (Lys-Asp-Glu-Leu) containing 2 KDELC2 225128_at Unknown Other 3.003 KIAA0125 KIAA0125 206478_at Unknown Other -8.436 KIT ligand KITLG 226534_at Extracellular Space Growth factor 2.59 LY6/PLAUR domain containing 6 LYPD6 227764_at Extracellular Space Other 2.64 Lysophosphatidic acid receptor 1 LPAR1 204036_at Plasma Membrane Receptor 3.151 MAB-21-like 2 MAB21L2 210303_at Unknown Other 3.817 Minichromosome maintenance complex component 10 MCM10 223570_at Nucleus Other 2.249 Moesin MSN 200600_at Plasma Membrane Other 5.842 Monoamine oxidase A MAOA 204388_s_at Cytoplasm Enzyme 4.029 Monoamine oxidase A MAOA 204389_at Cytoplasm Enzyme 3.355 Monoamine oxidase A MAOA 212741_at Cytoplasm Enzyme 4.157 MYC induced nuclear antigen MINA 213188_s_at Nucleus Other 4.019 MYC induced nuclear antigen MINA 213189_at Nucleus Other 4.636 Myosin VI MY06 203216_s_at Cytoplasm Other 2.406 Myosin VIIAand Rab interacting protein MYRIP 214156_at Cytoplasm Other 2.805 Neuronal PAS domain protein 4 NPAS4 1554299_at Nucleus Transcription regulator -2.515 Paternally expressed 3 PEG3 209242_at Nucleus Kinase 5.896 Paternally expressed 3 PEG3 209243_s_at Nucleus Kinase 4.556 89 PCT/US2010/027242 WO 2010/105234

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Phosphoprotein associated with glycosphingolipid microdomains 1 PAG1 225626_at Plasma Membrane Other 2.193 Poliovirus receptor-related 3 PVRL3 213325_at Plasma Membrane Other 2.325 Polo-like kinase 2 PLK2 201939_at Nucleus Kinase 4.93 Polymerase (DNA directed), alpha 2 (70kD subunit) POLA2 204441_s_at Nucleus Enzyme 2.198 Prolactin releasing hormone receptor PRLHR 231805_at Plasma Membrane Receptor 3.19 Prostaglandin reductase 1 PTGR1 228824_s_at Cytoplasm Enzyme 2.398 Prostaglandin reductase 1 PTGR1 231897_at Cytoplasm Enzyme 2.33 Protease, serine, 12 (neurotrypsin, motopsin) PRSS12 205515_at Extracellular Space Peptidase 5.146 Protein phosphatase 1, regulatory (inhibitor) subunit 3C PPP1R3C 204284_at Cytoplasm Phosphatase 2.827 Protein tyrosine phosphatase, receptor type, K PTPRK 203038_at Plasma Membrane Phosphatase 3.451 RAB32, member RAS oncogene family RAB32 204214_s_at Cytoplasm Other 2.192 RELT-like 1 RELL1 226430_at Unknown Other 2.88 Rho GTPase activating protein 24 ARHGAP24 223422_s_at Cytoplasm Other 3.043 Rho guanine nucleotide exchange factor (GEF) 3 ARHGEF3 218501_at Cytoplasm Other 2.473 Ring finger protein 182 RNF182 230720_at Unknown Other 4.746 RNA binding protein with multiple splicing RBPMS 209487_at Unknown Other 2.329 RNA binding protein with multiple splicing RBPMS 209488_s_at Unknown Other 3.292 Secreted protein, acidic, cysteine-rich (osteonectin) SPARC 200665_s_at Extracellular Space Other 4.919 Secreted protein, acidic, cysteine-rich (osteonectin) SPARC 212667_at Extracellular Space Other 4.58 Shugoshin-like 2 SGOL2 230165_at Nucleus Other 3.108 Similar to hCG2031213 LOC728052 1558795_at Unknown Other 3.402 Solute carrier family 1 (glial high affinity glutamate transporter), member 2 SLC1A2 225491_at Plasma Membrane Transporter -4.354 Solute carrier family 43, member 3 SLC43A3 210692_s_at Extracellular Space Other 3.126 Solute carrier family 43, member 3 SLC43A3 213113_s_at Extracellular Space Other 2.804 Solute carrier family 44, member SLC44A5 1569112_at Unknown Other 3.923 90 PCT/US2010/027242 WO 2010/105234

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Jacky, B., etal., Cells Useful for Immuno-Based BoNT/A Activity Assays 5 Solute carrier family 44, member 5 SLC44A5 235763_at Unknown Other 4.439 Solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 SLC7A2 225516_at Plasma Membrane T ransporter 3.23 Sortilin-related VPS10 domain containing receptor 1 SORCS1 1556891_at Plasma Membrane T ransporter -2.424 SPC25, NDC80 kinetochore complex component, homolog SPC25 209891_at Unknown Other 2.634 ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 4 ST8SIA4 230836_at Cytoplasm Enzyme 2.705 Structural maintenance of chromosomes 2 SMC2 204240_s_at Nucleus T ransporter 2.442 Structural maintenance of chromosomes 6 SMC6 218781_at Nucleus Other 3.327 Structural maintenance of chromosomes 6 SMC6 236535_at Nucleus Other 3.44 Syndecan 2 SDC2 212154_at Plasma Membrane Other 2.367 Syndecan 2 SDC2 212158_at Plasma Membrane Other 2.098 Thrombospondin 2 THBS2 203083_at Extracellular Space Other -2.81 Thyroid hormone receptor interactor 10 TRIP10 202734_at Cytoplasm Other 2.663 Tissue factor pathway inhibitor 2 TFPI2 209278_s_at Extracellular Space Other 4.666 Transcription factor 7-like 1 (T-cell specific, HMG-box) TCF7L1 221016_s_at Nucleus Transcription regulator 2.835 Transmembrane phosphatase with tensin homology TPTE 220205_at Plasma Membrane Phosphatase 6.04 Transmembrane protein 178 TMEM178 229302_at Unknown Other 3.194 Transmembrane protein 35 TMEM35 219685_at Unknown Other 2.879 Tumor necrosis factor, alpha-induced protein 8 TNFAIP8 210260_s_at Cytoplasm Other 2.389 Twist homolog 1 TWIST1 213943_at Nucleus Transcription regulator 2.573 Zinc finger protein 521 ZNF521 226676_at Nucleus Other 2.382 Zinc finger protein 521 ZNF521 226677_at Nucleus Other 2.943 Zinc finger protein 814 ZNF814 1556204_a_at Unknown Other -2.505 The log ratio represent log2 values where 0.585 is log2(1.5) which is a 1.5-fold difference, 1 is log2(2) 91 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays which is a 2-fold difference, 1.584 is log2(3) which is a 3-fold difference, 2 is log2(4) which is a 4-fold difference, 2.321 is log2(5) which is a 5-fold difference, 2.584 is log2(6) which is a 6-fold difference, 2.807 is log2(7) which is a 7-fold difference, 3 is log2(8) which is a 8-fold difference, 3.169 is log2(9) which is a 9-fold difference, and 3.321 is log2(10) which is a 10-fold difference.

[0191] Using IPA Core Analysis, 73 of the 79 genes were mapped to 5 different protein networks (Table 15). Based on overlapping gene mapping, 73 of the 79 genes that were up-regulated could be associated with two major protein network groups, named A and B (Table 15). Networks 1, 2 and 5 belong to Group A, and Networks 3 and 4 belong to Group B. Similarly, all down-regulated genes were all associated with one network, named C (Table 15).

Group A genes include the FGFR2 receptor which has been shown to function in the BoNT/A intoxication process as a receptor for BoNT/A and are as follows: genes exhibiting a 1,5-fold or more increase in expression levels in the H1 and BB10 cell lines as compared to their expression in cells from the 2D6 cell line, ADAMTS9, ARHGAP24, ARHGEF3, ASCL1, BARD1, CD9, CDK2, CSRP2, CTSL2, DIAPH3, DOK5, DYNLT3, EMILIN2, ETV1, FBLN1, FGFR2, GNAI1, GNB4, GNG11, GNG12, HGF, KITLG, LPAR1, MCM10, MSN, PAG1, PEG3, PLK2, POLA2, PPP1R3C, PTPRK, RAB32, SDC2, SLC43A3, SLC7A2, SMC6, SPARC, SPC25, ST8SIA4, TCF7L1, TFPI2, TMEM35, TNFAIP8, TPTE, TRIP10, and TWIST1.

[0192] Group B genes are as follows: genes exhibiting a 1.5-fold or more increase in expression levels in the H1 and BB10 cell lines as compared to their expression in cells from the 2D6 cell line, ACOT9, BASP1, C110RF75, CCDC109B, CDCA7L, CLSTN2, CNTN1, CUGBP2, DEPDC1, DPYD, FAM101B, FNDC5, GTSE1, MAOA, MINA, MY06, MYRIP, PLK2, PRLHR, PVRL3, RBPMS, SGOL2, SMC2, TFP12, TMEM178, and ZNF521.

[0193] Group C genes are as follows: genes exhibiting a 1.5-fold or more decrease in expression levels in the H1 and BB10 cell lines as compared to their expression in cells from the 2D6 cell line, ANK2, CPNE8, CREB5, IL17B, KIAA0125, LOC100289109, LOC144571, NPAS4, SLC1A2, SORCS1, THBS2, and/or ZNF814.

[0194] The remaining networks identified did not share common genes between any other network. Individually, however, genes exhibiting a 1.5-fold or more increase in expression levels in the H1 and BB10 cell lines as compared to their expression in cells from the 2D6 cell line were as follows: C3ORF70 (Network 6), MAB21L2 (Network 7), PRSS12 (Network 8), CENPL (Network 9), GPR177 (Network 10), and PTGR1 (Network 11). 92 PCT/US2010/027242 WO 2010/105234

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Table 15. IPA Core Analysis of Genes Network Group Proteins in Network pvalue JMP Gene Number Expression Profile Increased Decreased 1 A ADAMTS9, AKT, ASCL1, CDK2, CSRP2, CTSL2, DOK5, E2F, FBLN1, FSH, GNAI1, GNG11, hCG, HGF, KITLG, LPAR1, MAPK, MCM10, MEK, MSN, NFkB, P38, MAPK, PAG1, PDGF BB, PEG3, PLK2, RAC, RAS, SDC2, SPARC, TFPI2, TGFp, TNFAIP8, TRIP10, VEGF 48 22 ADAMTS9, ASCL1, CDK2, CSRP2, CTSL2, DOK5, FBLN1, GNAI1, GNG11, HGF, KITLG, LPAR1, MCM10, MSN, PAG1, PEG3, PLK2, SDC2, SPARC, TFPI2, TNFAIP8, TRIP10 — 2 A CASP3, Caspase 3/7, CCL6, DIAPH3, DYNLT3, EMILIN2, EPM2A, ETV1, EYA2, FAM3B, FASTK, GNAI1, GNB4, GNG10, GNG11, GNG12, GSTM2, HK1, IGFBP3, IL13, PLCE1, POLA2, PPP1R3C, PTPRK, PTPRZ1, RAB32, SLC43A3, SLC7A2, SRC, ST8SIA4. TNF, TPTE, TWIST1 35 17 DIAPH3, DYNLT3, EMILIN2, ETV1, GNAI1, GNB4, GNG11, GNG12, POLA2, PPP1R3C, PTPRK, RAB32, SLC43A3, SLC7A2, ST8SIA4, TPTE, TWIST1 — 3 B ACOT9, AR, ATXN7, BASP1, CCNE2, CCNK, CLSTN2, CNTN1, CUGBP2, DGKA, FNDC5, GTSE1, IL4, MAOA, MSH2, NOVA1, NF1, PICK1, PLK2, PNRC1, POM121, PRLHR, PTP4A1, PTP4A2, PVRL1, PVRL3, PVRL4, RBPMS, SERPINB5, SMARCA4, SPN, TFP12, TP53, ZNF521 26 14 ACOT9, BASP1, CLSTN2, CNTN1, CUGBP2, FNDC5, GTSE1, MAOA, PLK2, PRLHR, PVRL3, RBPMS, TFP12, ZNF521 — 4 B ARHGAP17, AXL, C110RF75, CAPN6, CCDC109B, CDCA7L, DEPDC1, DPYD, EIF4E, FAM101B, GRB2, HNRNPF, HTATIP2, MAOA, MINA, MIR124, MIRLET7A1, MYC, MY06, MYRIP, NCAPD3, NF2, PPP2R5A, PPP2R5D, PPP2R5E, RPS16, RPS23, SGOL2, SLC25A12, SMC2, SMC4, TMEM178, TUSC2, TXNIP, ZBTB16 24 13 C110RF75, CCDC109B, CDCA7L, DEPDC1, DPYD, FAM101B, MAOA, MINA, MY06, MYRIP, SGOL2, SMC2, TMEM178 — 5 A ARHGAP24, ARHGEF, 17 10 ARHGAP24, — 93 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays ARHGEF3, BARD1, CD9, CD53, CTNNB1, DUSP3, ERK, ERM, FGF9, FGF18, FGF21, FGF23, FGFR2, IL1, IL6, IL17RD, Integrina681, KLB, LEF/TCF, LPAR1, MIRN297-2, PI3K, RAS homolog, RNAPOLII, SLC26A2, SMC6, SPC25, SREBF1, TACC1, TCF7L1, TMEM35, TPT1, WISP1 ARHGEF3, BARD1, CD9, FGFR2, LPAR1, SMC6, SPC25, TCF7L1, TMEM35 6 — C3ORF70, MIR31 2 1 C3ORF70 — 7 — MAB21L2, MIRN294 2 1 MAB21L2 — 8 — AGPN, PRSS12 2 1 PRSS12 — 9 — CENPL, MIRN340 2 1 CENPL — 10 — GPR177, MIRN324 2 1 GPR177 — 11 — ADH, PTGR1 2 1 PTGR1 — 12 C ANK2, ATP2A2, BDNF, CEBPG, CPNE8, CREB5, GRM3, GRM5, IGFBP2, IL17B, ITPR, ITPR1, K+, L1CAM, MIRN330, Neurotrophin, NFE2L1, NGFR, NME1, NPAS4, Pro-inflammatory Cytokine, PSEN1, SCN2A, SCN3A, SCNN1B, SLC1A2, SLC8A1, SORCS1, SORT1, TGFA, THBS2, TNF, TNFAIP6 22 8 — ANK2, CPNE8, CREB5, IL17B, KIAA0125, LOC100289109, LOC144571, NPAS4, SLC1A2, SORCS1, THBS2, ZNF814 [0195] Computer analysis was performed as in Example V, except that the list of probes reflects genes that were greater than 1.5-fold differential expressed in the H1 and the BB10 cell lines when compared to both the 2D6 and SiMa parental cell lines. When the p-value cut off was set to 0.05, this analysis identified 439 gene probes that could be classified to 369 genes (Table 16).

Table 16. Genes Identified using IPA Core Analysis Gene Name Gene Symbol Probe ID. No. Location Type Log Ratio 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 PFKFB3 202464_s_at Cytoplasm kinase 1.811 achaete-scute complex homolog 1 ASCL1 209985_s_at Nucleus transcription regulator 2.429 achaete-scute complex homolog 1 ASCL1 209987_s_at Nucleus transcription regulator 2.097 achaete-scute complex homolog 1 ASCL1 209988_s_at Nucleus transcription regulator 1.446 achaete-scute complex homolog 1 ASCL1 213768_s_at Nucleus transcription regulator 1.578 activated leukocyte cell adhesion molecule ALCAM 1569362_at Plasma Membrane other 2.612 94 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., etal., Cells Useful for Immuno-Based BoNT/A Activity Assays activated leukocyte cell adhesion molecule ALCAM 201951_at Plasma Membrane other 1.774 activated leukocyte cell adhesion molecule ALCAM 201952_at Plasma Membrane other 1.521 acyl-CoA thioesterase 1 ACOT1 202982_s_at Cytoplasm enzyme -2.875 acylphosphatase 2, muscle type ACYP2 206833_s_at unknown enzyme -1.15 additional sex combs like 3 ASXL3 233536_at unknown other 1.572 adenosine deaminase, RNA-specific, B1 ADARB1 203865_s_at Nucleus enzyme -2.474 adenylate cyclase 1 ADCY1 213245_at Plasma Membrane enzyme -1.935 adipocyte-specific adhesion molecule ASAM 228082_at Plasma Membrane other -2.802 ADP-ribosylation factor 1 ARF1 1565651_at Cytoplasm enzyme 1.063 ADP-ribosylation factor-like 17A ARL17A 243899_at unknown other 0.741 anaphase promoting complex subunit 7 ANAPC7 225554_s_at unknown other 0.679 ankyrin repeat and BTB (POZ) domain containing 1 ABTB1 229164_s_at Cytoplasm translation regulator -0.656 ankyrin repeat domain 50 ANKRD50 225731_at unknown other -0.654 ankyrin repeat domain 50 ANKRD50 225735_at unknown other -1.114 aspartate beta-hydroxylase domain containing 1 ASPHD1 214993_at unknown other -0.763 ataxin 2-binding protein 1 A2BP1 1553422_s_at Cytoplasm other 1.453 ataxin 2-binding protein 1 A2BP1 221217_s_at Cytoplasm other 1.497 ATPase, Ca++ transporting, plasma membrane 3 ATP2B3 207026_s_at Plasma Membrane transporter -1.248 ATPase, Ca++ transporting, plasma membrane 3 ATP2B3 242036_x_at Plasma Membrane transporter -1.777 basonuclin 2 BNC2 220272_at Nucleus other 2.466 basonuclin 2 BNC2 230722_at Nucleus other 1.641 pycrystallin domain containing 3 CRYBG3 214030_at unknown other 4.74 β-site APP-cleaving enzyme 1 BACE1 217904_s_at Cytoplasm peptidase -1.57 brain abundant, membrane attached signal protein 1 BASP1 202391_at Plasma Membrane other 1.146 bromodomain and WD repeat domain containing 1 BRWD1 225446_at Nucleus transcription regulator -1.018 95 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays bruno-like 4, RNA binding protein BRUNOL4 238966_at Nucleus translation regulator -0.81 butyrophilin, subfamily 3, member A3 BTN3A3 38241_at unknown other -1.108 C2 calcium-dependent domain containing 2 C2CD2 212875_s_at unknown other -1.27 C2 calcium-dependent domain containing 4A C2CD4A 241031_at unknown other -2.615 cadherin 12, type 2 (N-cadherin 2) CDH12 207149_at Plasma Membrane other -1.408 calcium/calmodulin-dependent protein kinase II inhibitor 2 CAMK2N2 230706_s_at Nucleus other -0.692 calmin (calponin-like, transmembrane) CLMN 213839_at Cytoplasm other -1.911 calpain 2, (m/ll) large subunit CAPN2 208683_at Cytoplasm peptidase -1.429 CAP, adenylate cyclase-associated protein, 2 CAP2 212551_at Plasma Membrane other -1.974 CAP, adenylate cyclase-associated protein,2 CAP2 212554_at Plasma Membrane other -3.68 carboxypeptidase, vitellogenic-like CPVL 208146_s_at unknown peptidase 1.708 CART prepropeptide CARTPT 206339_at Extracellular Space other -4.676 Cas-Br-M (murine) ecotropic retroviral transforming sequence b CBLB 209682_at Nucleus other 1.032 CCR4-NOT transcription complex, subunit 6-like CNOT6L 227119_at Cytoplasm other -0.785 CD302 molecule CD302 203799_at Plasma Membrane receptor -1.518 CD9 molecule CD9 201005_at Plasma Membrane other 1.415 CDP-diacylglycerol synthase (phosphatidate cytidylyltransferase) 1 CDS1 226185_at Cytoplasm enzyme -1.74 cell division cycle 25 homolog B (S. pombe) CDC25B 201853_s_at Nucleus phosphatase 1.453 chemokine (C-X-C motif) receptor 4 CXCR4 209201_x_at Plasma Membrane receptor 4.135 chemokine (C-X-C motif) receptor 4 CXCR4 211919_s_at Plasma Membrane receptor 3.957 chemokine (C-X-C motif) receptor 4 CXCR4 217028_at Plasma Membrane receptor 3.176 96 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays chloride channel 3 CLCN3 201733_at Plasma Membrane ion channel -0.908 chloride channel 3 CLCN3 201734_at Plasma Membrane ion channel -0.987 cholinergic receptor, nicotinic, alpha 7 CHRNA7 210123_s_at Plasma Membrane receptor 3.098 chromosome 1 open reading frame 21 C10RF21 221272_s_at unknown other -0.74 chromosome 1 open reading frame 21 C10RF21 223127_s_at unknown other -0.748 chromosome 1 open reading frame 43 C10RF43 1555225_at unknown other 1.604 chromosome 10 open reading frame 58 C10ORF58 224435_at Extracellular Space other 0.918 chromosome 12 open reading frame 49 C120RF49 218867_s_at unknown other 0.692 chromosome 16 open reading frame 52 C160RF52 230721_at unknown other -0.87 chromosome 20 open reading frame 7 C20ORF7 227160_s_at unknown other 0.624 chromosome 21 open reading frame 57 C210RF57 227421_at unknown other -1.086 chromosome 21 open reading frame 57 C210RF57 239208_s_at unknown other -0.657 chromosome 3 open reading frame 23 C30RF23 1555905_a_at Cytoplasm other -2.797 chromosome 3 open reading frame 23 C30RF23 1555906_s_at Cytoplasm other -1.502 chromosome 3 open reading frame 23 C30RF23 241666_at Cytoplasm other -1.017 chromosome 9 open reading frame 150 C9ORF150 227443_at unknown other -1.773 claudin 12 CLDN12 223249_at Plasma Membrane other -0.766 COBW domain containing 1 CBWD1 226193_x_at unknown other 0.849 coiled-coil domain containing 3 CCDC3 223316_at Cytoplasm other 3.357 collagen, type VI, alpha 1 COL6A1 213428_s_at Extracellular Space other -1.638 cripto, FRL-1, cryptic family 1 CFC1 223753_s_at Extracellular Space other -2.834 cripto, FRL-1, cryptic family 1 CFC1 236724_at Extracellular Space other -1.636 97 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays CSE1 chromosome segregation 1-like CSE1L 210765_at Nucleus transporter 1.581 CUG triplet repeat, RNA binding protein 2 CUGBP2 202156_s_at Nucleus other 1.318 CUG triplet repeat, RNA binding protein 2 CUGBP2 202157_s_at Nucleus other 2.156 CUG triplet repeat, RNA binding protein 2 CUGBP2 202158_s_at Nucleus other 2.539 cyclic nucleotide gated channel alpha 3 CNGA3 207261_at Plasma Membrane ion channel -3.182 cyclin M1 CNNM1 220166_at Plasma Membrane other -1.214 cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) CDKN2A 209644_x_at Nucleus transcription regulator -1.277 cylindromatosis (turban tumor syndrome) CYLD 213295_at Nucleus transcription regulator -0.815 cytochrome P450, family 2, subfamily E, polypeptide 1 CYP2E1 1431_at Cytoplasm enzyme -4.466 cytochrome P450, family 2, subfamily E, polypeptide 1 CYP2E1 209975_at Cytoplasm enzyme -3.946 cytochrome P450, family 2, subfamily E, polypeptide 1 CYP2E1 209976_s_at Cytoplasm enzyme -3.429 cytoglobin CYGB 1553572_a_at Cytoplasm transporter -4.921 cytokine-like 1 CYTL1 219837_s_at Extracellular Space cytokine -6.33 dapper, antagonist of beta-catenin, homolog 1 DACT1 219179_at Cytoplasm other 1.682 dCMP deaminase DCTD 201572_x_at unknown enzyme -0.649 DEAH (Asp-Glu-Ala-His) box polypeptide 35 DHX35 218579_s_at unknown enzyme 0.735 deleted in azoospermia 1 DAZ1 207909_x_at Nucleus translation regulator 6.92 deleted in azoospermia 1 DAZ1 207912_s_at Nucleus translation regulator 5.558 deleted in azoospermia 1 DAZ1 208281_x_at Nucleus translation regulator 5.258 deleted in azoospermia 1 DAZ1 208282_x_at Nucleus translation regulator 7.008 deleted in azoospermia 1 DAZ1 216351_x_at Nucleus translation regulator 3.596 deleted in azoospermia 1 DAZ1 216922_x_at Nucleus translation regulator 5.185 98 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays deleted in lymphocytic leukemia 2 (non-protein coding) DLEU2 216870_x_at unknown other 1.233 delta-like 3 (Drosophila) DLL3 219537_x_at Extracellular Space other 0.779 DNA segment on chromosome 4 (unique) 234 expressed sequence D4S234E 209569_x_at Cytoplasm other -1.247 DNA segment on chromosome 4 (unique) 234 expressed sequence D4S234E 209570_s_at Cytoplasm other -1.488 DNA segment on chromosome 4 (unique) 234 expressed sequence D4S234E 213533_at Cytoplasm other -1.507 dopamine beta-hydroxylase (dopamine beta-monooxygenase) DBH 206450_at Cytoplasm enzyme 1.311 doublecortin-like kinase 1 DCLK1 215303_at Cytoplasm kinase -1.62 dual specificity phosphatase 16 DUSP16 224832_at Nucleus phosphatase -0.918 echinoderm microtubule associated protein like 1 EML1 204797_s_at Cytoplasm other 2.668 ectodermal-neural cortex (with BTB-like domain) ENC1 201340_s_at Nucleus peptidase 2.445 ectodermal-neural cortex (with BTB-like domain) ENC1 201341_at Nucleus peptidase 1.91 electron-transferring-flavoprotein dehydrogenase ETFDH 33494_at Cytoplasm enzyme -0.807 ELL associated factor 2 EAF2 219551_at Nucleus transcription regulator 0.693 ELOVL family member 7, elongation of long chain fatty acids ELOVL7 227180_at unknown other 2.644 endoplasmic reticulum aminopeptidase 1 ERAP1 214012_at Extracellular Space peptidase -1.885 enhancer of zeste homolog 2 EZH2 203358_s_at Nucleus transcription regulator 0.94 ephrin-A5 EFNA5 214036_at Plasma Membrane kinase 2.041 ephrin-A5 EFNA5 227955_s_at Plasma Membrane kinase 1.84 ephrin-A5 EFNA5 233814_at Plasma Membrane kinase 1.805 ephrin-B3 EFNB3 205031_at Plasma Membrane kinase -0.816 eukaryotic translation initiation EIF3C 236700_at Cytoplasm translation 1.378 99 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., etal., Cells Useful for Immuno-Based BoNT/A Activity Assays factor 3, subunit C regulator exophilin 5 EXPH5 214734_at unknown other 3.973 exosome component 6 EXOSC6 231916_at Nucleus other 1.057 family with sequence similarity 162, member B FAM162B 228875_at unknown other -0.743 family with sequence similarity 165, member B FAM165B 228239_at Plasma Membrane other -0.822 family with sequence similarity 181, member B FAM181B 231430_at unknown other 0.794 family with sequence similarity 19 (chemokine (C-C motif)-like), member A4 FAM19A4 242348_at Extracellular Space other 1.282 family with sequence similarity 46, member A FAM46A 224973_at unknown other -1.509 family with sequence similarity 7, member A3 FAM7A3 243356_at unknown other 3.495 far upstream element (FUSE) binding protein 3 FUBP3 239193_at Nucleus transcription regulator 1.192 F-box and WD repeat domain containing 7 FBXW7 229419_at Nucleus transcription regulator -0.921 fibroblast growth factor 13 FGF13 205110_s_at Extracellular Space growth factor -3.522 follistatin-like 1 FSTL1 208782_at Extracellular Space other -1.275 forkhead box 06 FOX06 239657_x_at Nucleus other -1.512 frizzled homolog 5 FZD5 221245_s_at Plasma Membrane receptor 2.347 FYVE, RhoGEF and PH domain containing 5 FGD5 226985_at Cytoplasm other -1.952 G protein-coupled receptor 123 GPR123 239221_at Plasma Membrane receptor -1.302 G protein-coupled receptor 125 GPR125 210473_s_at Plasma Membrane receptor 0.714 galanin prepropeptide GAL 207466_at Extracellular Space other -1.434 galanin prepropeptide GAL 214240_at Extracellular Space other -3.128 gastrin-releasing peptide GRP 206326_at Extracellular Space growth factor 4.698 GDNF family receptor alpha 2 GFRA2 205721_at Plasma Membrane receptor 1.847 GDNF family receptor alpha 2 GFRA2 205722_s_at Plasma receptor 2.265 100 WO 2010/105234 PCT/US2010/027242

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays Membrane glutamate receptor, metabotropic 5 GRM5 214217_at Plasma Membrane receptor -2.231 glutathione peroxidase 7 GPX7 213170_at Cytoplasm enzyme -2.692 glutathione synthetase GSS 211630_s_at Cytoplasm enzyme 0.599 glycosyltransferase 25 domain containing 2 GLT25D2 209883_at unknown other -1.223 GNAS complex locus GNAS 214157_at Plasma Membrane enzyme -1.794 growth associated protein 43 GAP43 204471_at Plasma Membrane other 0.869 growth associated protein 43 GAP43 216963_s_at Plasma Membrane other 1.151 guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 1 GNAI1 209576_at Plasma Membrane enzyme 2.225 guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 1 GNAI1 227692_at Plasma Membrane enzyme 2.111 guanine nucleotide binding protein (G protein), beta polypeptide 4 GNB4 225710_at Plasma Membrane enzyme 4.695 guanine nucleotide binding protein (G protein), gamma 11 GNG11 204115_at Plasma Membrane enzyme 2.587 guanylate cyclase 1, soluble, alpha 3 GUCY1A3 221942_s_at Cytoplasm enzyme -1.522 guanylate cyclase 1, soluble, alpha 3 GUCY1A3 229530_at Cytoplasm enzyme -1.696 helicase, POLQ-like HELQ 228736_at Nucleus enzyme -1.28 HERPUD family member 2 HERPUD2 236170_x_at unknown other -0.897 heterogeneous nuclear ribonucleoprotein R HNRNPR 208765_s_at Nucleus other -0.64 hippocalcin-like 1 HPCAL1 205462_s_at Cytoplasm other -1.551 hippocalcin-like 1 HPCAL1 212552_at Cytoplasm other -1.387 histone cluster 1, H2ac HIST1H2A C 215071_s_at Nucleus other -2.462 histone cluster 1, H2bd HIST1H2B D 209911_x_at Nucleus other -2.036 histone cluster 1, H2bk HIST1H2B K 209806_at Nucleus other -1.575 histone cluster 2, H2be HIST2H2B 202708_s_at Nucleus other -1.735 101 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays E hypothetical LOC100130522 LOC10013 0522 230477_at unknown other -0.928 hypothetical LOC26082 DKFZP434 L187 230861_at unknown other 0.968 hypothetical protein LOC 100128844 LOC10012 8844 229110_at unknown other 2.106 hypothetical protein LOC643401 LOC34010 9 1557765_at unknown other 2.848 integrin, alpha 6 ITGA6 201656_at Plasma Membrane other 2.822 integrin, alpha 6 ITGA6 215177_s_at Plasma Membrane other 2.024 integrin, beta 5 ITGB5 201125_s_at Plasma Membrane other 0.913 interleukin 10 receptor, beta IL10RB 209575_at Plasma Membrane transmembr ane receptor -1.444 junction mediating and regulatory protein, p53 cofactor JMY 226352_at Nucleus transcription regulator -0.744 K(lysine) acetyltransferase 2B KAT2B 203845_at Nucleus transcription regulator -0.731 KDEL (Lys-Asp-Glu-Leu) containing 2 KDELC2 225128_at unknown other 1.085 kelch domain containing 1 KLHDC1 1552733_at unknown other -0.952 kelch repeat and BTB (POZ) domain containing 11 KBTBD11 204301_at unknown other -0.733 kelch-like 13 (Drosophila) KLHL13 227875_at unknown other 0.902 KH domain containing, RNA binding, signal transduction associated 3 KHDRBS3 209781_s_at Nucleus other 1.082 KH homology domain containing 1 KHDC1 230055_at unknown other -1.656 KIAA1598 KIAA1598 221802_s_at unknown other -2.811 kinesin family member 16B KIF16B 232083_at Cytoplasm other 1.688 lectin, galactoside-binding, soluble, 3 binding protein LGALS3BP 200923_at Plasma Membrane transmembr ane receptor -1.417 leukemia inhibitory factor receptor alpha LIFR 225575_at Plasma Membrane transmembr ane receptor -0.941 limb bud and heart development homolog (mouse) LBH 221011_s_at Nucleus transcription regulator 0.788 LRP2 binding protein LRP2BP 207797_s_at unknown other -1.365 102 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays lumican LUM 201744_s_at Extracellular Space other 5.638 LYR motif containing 5 LYRM5 225469_at unknown other -0.93 mab-21-like 1 MAB21L1 206163_at unknown other 2.722 mab-21-like 2 MAB21L2 210302_s_at unknown other 2.871 mab-21-like 2 MAB21L2 210303_at unknown other 2.204 macrophage stimulating 1 (hepatocyte growth factor-like) MST1 216320_x_at Extracellular Space growth factor -1.012 major facilitator superfamily domain containing 4 MFSD4 229254_at unknown other -1.752 mannosidase, alpha, class 2A, member 1 MAN2A1 226538_at Cytoplasm enzyme 0.864 mannosyl (alpha-1,3-)-glycoprotein beta-1,4-N-acetylglucosaminyltransferase, isozyme A MGAT4A 226039_at unknown enzyme -0.904 mesenchyme homeobox 2 MEOX2 206201_s_at Nucleus transcription regulator -4.213 microtubule-associated protein 9 MAP9 220145_at unknown other -0.7 microtubule-associated protein 9 MAP9 228423_at unknown other -1.108 microtubule-associated protein 9 MAP9 235550_at unknown other -0.863 mitochondrial ribosomal protein S33 MRPS33 218654_s_at Cytoplasm other -0.609 mitogen-activated protein kinase kinase kinase 5 MAP3K5 203836_s_at Cytoplasm kinase -1.159 moesin MSN 200600_at Plasma Membrane other 2.082 monoamine oxidase A MAOA 204388_s_at Cytoplasm enzyme 2.15 monoamine oxidase A MAOA 204389_at Cytoplasm enzyme 1.88 monoamine oxidase A MAOA 212741_at Cytoplasm enzyme 2.048 monocyte to macrophage differentiation-associated MMD 244523_at Plasma Membrane other 1.045 multiple C2 domains, transmembrane 1 MCTP1 220122_at unknown other -1.597 MYC induced nuclear antigen MINA 213188_s_at Nucleus other 1.391 MYC induced nuclear antigen MINA 213189_at Nucleus other 1.641 myosin IB MY01B 212365_at Cytoplasm other 0.71 myosin VI MY06 203216_s_at Cytoplasm other 1.104 103 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays myosin VI MY06 210480_s_at Cytoplasm other 1.41 Na+/H+ exchanger domain containing 2 NHEDC2 1564746_at Plasma Membrane other -1.462 N-acylethanolamine acid amidase NAAA 214765_s_at Cytoplasm enzyme 0.911 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4-like 2 NDUFA4L2 218484_at unknown enzyme -3.507 NADH dehydrogenase (ubiquinone) flavoprotein 3, 10kDa NDUFV3 226616_s_at Cytoplasm enzyme -0.875 nebulette NEBL 203961_at Cytoplasm other -1.359 neural precursor cell expressed, developmental^ down-regulated 9 NEDD9 202150_s_at Nucleus other 2.41 NIPA-like domain containing 3 NIPAL3 225876_at unknown other -1.203 nitric oxide synthase 1 (neuronal) NOS1 239132_at Cytoplasm enzyme 1.138 nitric oxide synthase 1 (neuronal) NOS1 240911_at Cytoplasm enzyme 1.187 NLR family member X1 NLRX1 219680_at unknown other -1.541 non-protein coding RNA 171 NCRNA001 71 215985_at unknown other -0.692 nuclear receptor coactivator 7 NCOA7 225344_at Nucleus other -0.842 nucleosome assembly protein 1-like 3 NAP1L3 204749_at Nucleus other -1.53 nudix (nucleoside diphosphate linked moiety X)-type motif 19 NUDT19 235384_at Cytoplasm other -1.685 olfactomedin 3 OLFM3 1554524_a_at Cytoplasm other -0.927 oxysterol binding protein-like 3 OSBPL3 209626_s_at Cytoplasm other 2.083 pecanex-like 2 PCNXL2 1554256_a_at unknown other -0.728 pellino homolog 2 PELI2 219132_at Cytoplasm other 0.732 peptidase M20 domain containing 2 PM20D2 225421_at unknown other 1.6 peptidylglycine alpha-amidating monooxygenase PAM 202336_s_at Plasma Membrane enzyme -0.861 peripherin PRPH 213847_at Plasma Membrane other -1.417 PHD finger protein 20 PHF20 235389_at Nucleus other 0.596 104 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., etal., Cells Useful for Immuno-Based BoNT/A Activity Assays phosphatidic acid phosphatase type 2 domain containing 1A PPAPDC1 A 236044_at unknown phosphatase -2.621 phosphatidylinositol glycan anchor biosynthesis, class H PIGH 209625_at Cytoplasm enzyme -0.597 phosphoinositide-interacting regulator of transient receptor potential channels HCG 1776018 232887_at unknown other -2.019 phosphorylase kinase, alpha 1 (muscle) PHKA1 229876_at Cytoplasm kinase -1.2 plastin 3 (T isoform) PLS3 201215_at Cytoplasm other 1.068 platelet-derived growth factor receptor, beta polypeptide PDGFRB 202273_at Plasma Membrane kinase -1.373 pleiotrophin PTN 209466_x_at Extracellular Space growth factor -1.426 pleiotrophin PTN 211737_x_at Extracellular Space growth factor -2.929 pleiotropic regulator 1 PLRG1 225194_at Nucleus transcription regulator -0.701 pleiotropic regulator 1 PLRG1 227246_at Nucleus transcription regulator -1.228 plexin A2 PLXNA2 213030_s_at Plasma Membrane other 0.946 plexin A4 PLXNA4 232317_at Plasma Membrane receptor 1.368 polo-like kinase 2 PLK2 201939_at Nucleus kinase 3.606 polycomb group ring finger 5 PCGF5 227935_s_at unknown other 0.791 polymerase (DNA directed), epsilon POLE 216026_s_at Nucleus enzyme 1.053 potassium channel tetramerisation domain containing 12 KCTD12 212188_at unknown ion channel 3.396 potassium channel tetramerisation domain containing 12 KCTD12 212192_at unknown ion channel 4.806 potassium large conductance calcium-activated channel, subfamily M, alpha member 1 KCNMA1 221584_s_at Plasma Membrane ion channel -2.389 potassium voltage-gated channel, KQT-like subfamily, member 2 KCNQ2 205737_at Plasma Membrane ion channel -1.246 pregnancy-associated plasma protein A, pappalysin 1 PAPPA 201982_s_at Extracellular Space peptidase -1.672 prostaglandin E receptor 2 (subtype EP2), 53kDa PTGER2 206631_at Plasma Membrane receptor -2.328 105 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., etal., Cells Useful for Immuno-Based BoNT/A Activity Assays prostaglandin F2 receptor negative regulator PTGFRN 224937_at Plasma Membrane other 2.301 proteasome (prosome, macropain) subunit, alpha type, 7 PSMA7 216088_s_at Cytoplasm peptidase 0.658 protein kinase, cAMP-dependent, catalytic, beta PRKACB 235780_at Cytoplasm kinase -2.17 protein tyrosine phosphatase, receptor type, D PTPRD 214043_at Plasma Membrane phosphatase -1.16 protein tyrosine phosphatase, receptor type, E PTPRE 221840_at Plasma Membrane phosphatase 3.044 protein tyrosine phosphatase, receptor type, G PTPRG 204944_at Plasma Membrane phosphatase 1.237 RAB35, member RAS oncogene family RAB35 205461_at Cytoplasm enzyme 0.737 RAB6B, member RAS oncogene family RAB6B 225259_at Cytoplasm enzyme -1.229 Rac/Cdc42 guanine nucleotide exchange factor (GEF) 6 ARHGEF6 209539_at Cytoplasm other 2.719 RAN, member RAS oncogene family RAN 200750_s_at Nucleus enzyme 0.59 RAS and EF-hand domain containing RASEF 1553986_at unknown other 1.393 ras homolog gene family, member U RHOU 223168__at Cytoplasm enzyme -1.154 regulator of G-protein signaling 5 RGS5 1555725_a_at Plasma Membrane other 4.038 regulator of G-protein signaling 5 RGS5 209070_s_at Plasma Membrane other 3.729 regulator of G-protein signaling 5 RGS5 209071_s_at Plasma Membrane other 3.468 regulator of G-protein signaling 5 RGS5 218353_at Plasma Membrane other 3.65 RELT-like 1 RELL1 226430_at unknown other 1.214 retinoblastoma-like 1 (p107) RBL1 1559307_s_at Nucleus other 0.959 retrotransposon gag domain containing 4 RGAG4 227823_at unknown other -1.775 Rho GTPase activating protein 6 ARHGAP6 206167_s_at Cytoplasm other 2.809 ribosomal L1 domain containing 1 RSL1D1 213750_at Cytoplasm other -0.816 RIMS binding protein 2 RIMBP2 238817_at Plasma Membrane other 1.679 106 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays ring finger protein 13 RNF13 201780_s_at Nucleus other -0.707 ring finger protein 182 RNF182 230720_at unknown other 2.696 ring finger protein 34 RNF34 219035_s_at Cytoplasm enzyme 0.85 ring finger protein 41 RNF41 201962_s_at Cytoplasm other -0.591 RNA polymerase I transcription factor homolog pseudogene 1 LOC94431 216908_x_at unknown other -0.674 sal-like 4 SALL4 229661_at Nucleus other 1.586 salt-inducible kinase 1 SIK1 208078_s_at Cytoplasm kinase -1.403 seizure related 6 homolog (mouse)-like SEZ6L 207873_x_at Plasma Membrane other 0.866 seizure related 6 homolog (mouse)-like SEZ6L 211894_x_at Plasma Membrane other 0.797 sema domain, transmembrane domain (TM), and cytoplasmic domain, (semaphorin) 6A SEMA6A 220454_s_at Plasma Membrane other 1.356 serine peptidase inhibitor, Kunitz type, 2 SPINT2 210715_s_at Extracellular Space other -1.889 SH3 domain containing, Ysc84-like 1 SH3YL1 204019_s_at unknown other -0.859 SH3-domain GRB2-like 2 SH3GL2 205751_at Plasma Membrane enzyme -1.605 similar to hCG2031213 LOC72805 2 1558795_at unknown other 2.239 similar to hCG2031213 LOC72805 2 1558796_a_at unknown other 1.887 single immunoglobulin and toll-interleukin 1 receptor (TIR) domain SIGIRR 52940_at Plasma Membrane receptor -1.42 single-minded homolog 1 SIM1 1556300_s_at Nucleus transcription regulator 6.36 single-minded homolog 1 SIM1 206876_at Nucleus transcription regulator 5.737 SLIT and NTRK-like family, member 5 SLITRK5 214930_at unknown other 4.094 SMG1 homolog, phosphatidylinositol 3-kinase-related kinase pseudogene LOC64129 8 244766_at unknown other 1.065 solute carrier family 12 (potassium/chloride transporters), member 7 SLC12A7 218066_at Plasma Membrane transporter -1.258 solute carrier family 22, member 17 SLC22A17 218675_at Plasma Membrane transporter -0.724 107 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., etal., Cells Useful for Immuno-Based BoNT/A Activity Assays solute carrier family 35, member F3 SLC35F3 229065_at unknown other -3.048 solute carrier family 44, member 5 SLC44A5 1569112_at unknown other 2.738 solute carrier family 44, member 5 SLC44A5 235763_at unknown other 1.845 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 SLC7A2 225516_at Plasma Membrane transporter 1.892 solute carrier organic anion transporter family, member 3A1 SLC03A1 219229_at Plasma Membrane transporter 1.622 solute carrier organic anion transporter family, member 3A1 SLC03A1 227367_at Plasma Membrane transporter 1.045 sparc/osteonectin, cwcv and kazal-like domains proteoglycan (testican) 2 SPOCK2 202524_s_at Extracellular Space other -0.83 sperm associated antigen 6 SPAG6 210032_s_at Cytoplasm other 1.687 sperm associated antigen 6 SPAG6 210033_s_at Cytoplasm other 2.774 spermatogenesis associated, serine-rich 2-like SPATS2L 222154_s_at unknown other 0.907 sphingosine-1 -phosphate receptor 3 S1PR3 228176_at Plasma Membrane receptor 1.9 ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1 ST8SIA1 210073_at Cytoplasm enzyme 1.114 ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 3 ST8SIA3 230262_at Cytoplasm enzyme -1.039 stathmin-like 3 STMN3 222557_at Nucleus other 0.788 STEAP family member 3 STEAP3 218424_s_at Cytoplasm transporter -1.827 steroidogenic acute regulatory protein STAR 204548_at Cytoplasm transporter -1.093 stimulated by retinoic acid gene 6 homolog STRA6 1569334_at Plasma Membrane other 1.359 stimulated by retinoic acid gene 6 homolog STRA6 1569335_a_at Plasma Membrane other 1.167 storkhead box 2 STOX2 226822_at unknown other -0.854 synaptojanin 1 SYNJ1 212990_at Cytoplasm phosphatase -0.624 synaptotagmin XIII SYT13 226086_at unknown transporter -4.754 synuclein, alpha (non A4 component of amyloid precursor) SNCA 236081_at Cytoplasm other -0.935 taxilin beta TXLNB 227834_at Cytoplasm other -2.226 108 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays teashirt zinc finger homeobox 3 TSHZ3 223392_s_at Nucleus transcription regulator 1.472 teashirt zinc finger homeobox 3 TSHZ3 223393_s_at Nucleus transcription regulator 0.962 tetratricopeptide repeat domain 39C TTC39C 238480_at unknown other -0.824 TH 1-like TH1L 220607_x_at Nucleus other 1.027 TH 1-like TH1L 225006_x_at Nucleus other 0.884 TH 1-like TH1L 225261_x_at Nucleus other 0.883 TH 1-like TH1L 225865_x_at Nucleus other 0.904 thioredoxin reductase 1 TXNRD1 201266_at Cytoplasm enzyme 1.032 THO complex 4 THOC4 226319_s_at Nucleus transcription regulator 0.996 TIMP metallopeptidase inhibitor 3 TIMP3 201147_s_at Extracellular Space other 5.151 TIMP metallopeptidase inhibitor 3 TIMP3 201148_s_at Extracellular Space other 3.637 TIMP metallopeptidase inhibitor 3 TIMP3 201149_s_at Extracellular Space other 5.037 TIMP metallopeptidase inhibitor 3 TIMP3 201150_s_at Extracellular Space other 4.312 tissue factor pathway inhibitor 2 TFPI2 209277_at Extracellular Space other 1.592 tissue factor pathway inhibitor 2 TFPI2 209278_s_at Extracellular Space other 2.326 TM2 domain containing 1 TM2D1 213882_at Plasma Membrane receptor -0.769 transcription factor 7-like 2 (T-cell specific, HMG-box) TCF7L2 212761_at Nucleus transcription regulator 1.005 transcription factor 7-like 2 (T-cell specific, HMG-box) TCF7L2 212762_s_at Nucleus transcription regulator 1.224 transcription factor 7-like 2 (T-cell specific, HMG-box) TCF7L2 216035_x_at Nucleus transcription regulator 1.072 transcription factor 7-like 2 (T-cell specific, HMG-box) TCF7L2 216037_x_at Nucleus transcription regulator 0.81 transcription factor 7-like 2 (T-cell specific, HMG-box) TCF7L2 216511_s_at Nucleus transcription regulator 1.003 transducin-like enhancer of split 3 TLE3 212770_at Nucleus other 0.976 transformer 2 alpha homolog TRA2A 213593_s_at Nucleus other 1.12 transmembrane inner ear TMIE 1553601_a_at unknown other -3.334 109 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays transmembrane protein 132C TMEM132 C 232313_at unknown other 4.02 transmembrane protein 178 TMEM178 229302_at unknown other 1.697 transmembrane protein 184C TMEM184 C 219074_at unknown other -0.779 transmembrane protein 5 TMEM5 204808_s_at Plasma Membrane other -1.074 transmembrane protein 59-like TMEM59L 219005_at Cytoplasm other -0.845 tripartite motif-containing 29 TRIM29 211002_s_at Cytoplasm transcription regulator 2.005 tripartite motif-containing 36 TRIM36 219736_at Cytoplasm other 2.221 trophoblast glycoprotein TPBG 203476_at Plasma Membrane other 2.158 tumor suppressor candidate 3 TUSC3 232770_at Extracellular Space enzyme -1.407 U2 small nuclear RNA auxiliary factor 1 U2AF1 232141_at Nucleus other 0.776 ubiquitin-conjugating enzyme E2 variant 1 UBE2V1 201003_x_at Nucleus transcription regulator 0.663 urocortin UCN 206072_at Extracellular Space other -0.961 vacuolar protein sorting 29 homolog VPS29 223026_s_at Cytoplasm transporter 0.805 v-erb-a erythroblastic leukemia viral oncogene homolog 4 ERBB4 206794_at Plasma Membrane kinase -1.537 v-erb-a erythroblastic leukemia viral oncogene homolog 4 ERBB4 214053_at Plasma Membrane kinase -1.708 v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog ERBB2 216836_s_at Plasma Membrane kinase -0.698 v-raf-1 murine leukemia viral oncogene homolog 1 RAF1 1557675_at Cytoplasm kinase 0.696 WD repeat and FYVE domain containing 3 WDFY3 212602_at Cytoplasm enzyme -0.626 WD repeat and FYVE domain containing 3 WDFY3 212606_at Cytoplasm enzyme -0.785 zinc finger homeobox 4 ZFHX4 219779_at unknown other 1.36 zinc finger homeobox 4 ZFHX4 241700_at unknown other 1.234 zinc finger protein 217 ZNF217 203739_at Nucleus transcription regulator 1.096 110 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays zinc finger protein 503 ZNF503 227195_at Nucleus other 1.373 zinc finger protein 641 ZNF641 226509_at unknown other -1.427 zinc finger protein 662 ZNF662 228538_at unknown other -3.352 zinc finger, CCCH-type with G patch domain ZGPAT 221848_at unknown other 0.991 [0196] Computer analysis was performed as in Example V, except that the list of probes reflects genes that were greater than 1.5-fold differential expressed in the H1 cell line and the BB10 cell line when compared to both the 2D6 and SiMa parental cell lines, and also a greater than 1.5-fold differential expressed in the SiMa parental cell line when compared to the 2D6 cell line. When the p-value cut off was set to 0.05, this analysis identified 94 gene probes that could be classified to 70 genes (Table 17).

Table 17. Genes Identified using IPA Core Analysis Gene Name Gene Symbol Probe ID. No. Location Type Log Ratio achaete-scute complex homolog 1 ASCL1 209985_s_at Nucleus transcription regulator 2.429 achaete-scute complex homolog 1 ASCL1 209988_s_at Nucleus transcription regulator 1.446 achaete-scute complex homolog 1 ASCL1 213768_s_at Nucleus transcription regulator 1.578 activated leukocyte cell adhesion molecule ALCAM 201952_at Plasma Membrane other 1.521 ADP-ribosylation factor 1 ARF1 1565651_at Cytoplasm enzyme 1.063 ADP-ribosylation factor-like 17A ARL17A 243899_at unknown other 0.741 ataxin 2-binding protein 1 A2BP1 1553422_s_at Cytoplasm other 1.453 ataxin 2-binding protein 1 A2BP1 221217_s_at Cytoplasm other 1.497 brain abundant, membrane attached signal protein 1 BASP1 202391_at Plasma Membrane other 1.146 CAP, adenylate cyclase-associated protein, 2 CAP2 212551_at Plasma Membrane other -1.974 CD9 molecule CD9 201005_at Plasma Membrane other 1.415 CUG triplet repeat, RNA binding protein 2 CUGBP2 202157_s_at Nucleus other 2.156 cyclic nucleotide gated channel alpha 3 CNGA3 207261_at Plasma Membrane ion channel -3.182 cyclin-dependent kinase inhibitor 2A (melanoma, p16, CDKN2A 209644_x_at Nucleus transcription regulator -1.277

Ill PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays inhibits CDK4) ELL associated factor 2 EAF2 219551_at Nucleus transcription regulator 0.693 eukaryotic translation initiation factor 3, subunit C EIF3C 236700_at Cytoplasm translation regulator 1.378 family with sequence similarity 162, member B FAM162B 228875_at unknown other -0.743 family with sequence similarity 181, member B FAM181B 231430_at unknown other 0.794 far upstream element (FUSE) binding protein 3 FUBP3 239193_at Nucleus transcription regulator 1.192 fibroblast growth factor 13 FGF13 205110_s_at Extracellular Space growth factor -3.522 follistatin-like 1 FSTL1 208782_at Extracellular Space other -1.275 forkhead box 06 FOX06 239657_x_at Nucleus other -1.512 guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 1 GNAI1 227692_at Plasma Membrane enzyme 2.111 guanine nucleotide binding protein (G protein), beta polypeptide 4 GNB4 225710_at Plasma Membrane enzyme 4.695 guanine nucleotide binding protein (G protein), gamma 11 GNG11 204115_at Plasma Membrane enzyme 2.587 KDEL (Lys-Asp-Glu-Leu) containing 2 KDELC2 225128_at unknown other 1.085 kelch-like 13 KLHL13 227875_at unknown other 0.902 KH domain containing, RNA binding, signal transduction associated 3 KHDRBS3 209781_s_at Nucleus other 1.082 KH homology domain containing 1 KHDC1 230055_at unknown other -1.656 leukemia inhibitory factor receptor alpha LIFR 225575_at Plasma Membrane transmembra ne receptor -0.941 mab-21-like 2 MAB21L2 210303_at unknown other 2.204 mesenchyme homeobox 2 MEOX2 206201_s_at Nucleus transcription regulator -4.213 moesin MSN 200600_at Plasma Membrane other 2.082 monoamine oxidase A MAOA 204388_s_at Cytoplasm enzyme 2.15 monoamine oxidase A MAOA 204389_at Cytoplasm enzyme 1.88 112 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays monoamine oxidase A MAOA 212741_at Cytoplasm enzyme 2.048 multiple C2 domains, transmembrane 1 MCTP1 220122_at unknown other -1.597 MYC induced nuclear antigen MINA 213188_s_at Nucleus other 1.391 MYC induced nuclear antigen MINA 213189_at Nucleus other 1.641 myosin VI MY06 203216_s_at Cytoplasm other 1.104 phosphatidic acid phosphatase type 2 domain containing 1A PPAPDC1A 236044_at unknown phosphatase -2.621 plastin 3 (T isoform) PLS3 201215_at Cytoplasm other 1.068 pleiotrophin PTN 209466_x_at Extracellular Space growth factor -1.426 pleiotrophin PTN 211737_x_at Extracellular Space growth factor -2.929 polo-like kinase 2 (Drosophila) PLK2 201939_at Nucleus kinase 3.606 potassium large conductance calcium-activated channel, subfamily M, alpha member 1 KCNMA1 221584_s_at Plasma Membrane ion channel -2.389 RELT-like 1 RELL1 226430_at unknown other 1.214 ring finger protein 182 RNF182 230720_at unknown other 2.696 seizure related 6 homolog-like SEZ6L 207873_x_at Plasma Membrane other 0.866 seizure related 6 homolog (mouse)-like SEZ6L 211894_x_at Plasma Membrane other 0.797 similar to hCG2031213 LOC728052 1558795_at unknown other 2.239 single-minded homolog 1 (Drosophila) SIM1 1556300_s_at Nucleus transcription regulator 6.36 single-minded homolog 1 (Drosophila) SIM1 206876_at Nucleus transcription regulator 5.737 SLIT and NTRK-like family, member 5 SLITRK5 214930_at unknown other 4.094 SMG1 homolog, phosphatidylinositol 3-kinase-related kinase pseudogene LOC641298 244766_at unknown other 1.065 solute carrier family 44, member 5 SLC44A5 1569112_at unknown other 2.738 solute carrier family 44, member 5 SLC44A5 235763_at unknown other 1.845 solute carrier family 7 (cationic amino acid SLC7A2 225516_at Plasma Membrane transporter 1.892 113 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays transporter, y+ system), member 2 solute carrier organic anion transporter family, member 3A1 SLC03A1 219229_at Plasma Membrane transporter 1.622 spermatogenesis associated, serine-rich 2-like SPATS2L 222154_s_at unknown other 0.907 synaptotagmin XIII SYT13 226086_at unknown transporter -4.754 tissue factor pathway inhibitor 2 TFPI2 209278_s_at Extracellular Space other 2.326 transcription factor 7-like 2 (T-cell specific, HMG-box) TCF7L2 212761_at Nucleus transcription regulator 1.005 transformer 2 alpha homolog TRA2A 213593_s_at Nucleus other 1.12 transmembrane inner ear TMIE 1553601_a_at unknown other -3.334 transmembrane protein 178 TMEM178 229302_at unknown other 1.697 U2 small nuclear RNA auxiliary factor 1 U2AF1 232141_at Nucleus other 0.776 v-raf-1 murine leukemia viral oncogene homolog 1 RAF1 1557675_at Cytoplasm kinase 0.696 zinc finger protein 217 ZNF217 203739_at Nucleus transcription regulator 1.096 zinc finger protein 662 ZNF662 228538_at unknown other -3.352 The log ratio represent log2 values where 0.585 is log2(1.5) which is a 1.5-fold difference, 1 is log2(2) which is a 2-fold difference, 1.584 is log2(3) which is a 3-fold difference, 2 is log2(4) which is a 4-fold difference, 2.321 is log2(5) which is a 5-fold difference, 2.584 is log2(6) which is a 6-fold difference, 2.807 is log2(7) which is a 7-fold difference, 3 is log2(8) which is a 8-fold difference, 3.169 is log2(9) which is a 9-fold difference, and 3.321 is log2(10) which is a 10-fold difference.

Example VI

Immuno-Based Method to Detect Picomolar Amounts of BoNT/A

[0197] The following example illustrates how to perform immuno-based methods of detecting BoNT/A activity that can detect picomolar amounts of the BoNT/A pharmaceutical product, such as, e.g., BOTOX® DYSPORT®/RELOXIN®, PURTOX®', XEOMIN®, NEURONOX®, or BTX-A. 1. Immuno-based method of detecting BoNT/A using ECL sandwich ELISA.

[0198] To prepare a lysate from cells treated with a BoNT/A, approximately 150,000 cells from an established clonal cell line was plated into the wells of 96-well tissue culture poly-D-lysine plates containing 100 pL of a serum-free medium containing Minimum Essential Medium, 2 mM GlutaMAX™ I with Earle’s salts, 1 x B27 supplement, 1 x N2 supplement, 0.1 mM Non-Essential Amino Acids, 10 mM 114

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays 2017228675 15 Sep 2017 PCT/US2010/027242 18495 (BOT)/1957205.00451 WO 2010/105234 Patent Application HEPES and 60 pg/mL GT1b. The cell lines used were BB10, H1, and SiMa. These cells were incubated in a 37 °C incubator under 5% carbon dioxide until the cells differentiated, as assessed by standard and routine morphological criteria, such as growth arrest and neurite extension (approximately 3 days). The media from the differentiated cells was aspirated from each well and replaced with fresh media containing one of the following: 1) SiMa cell line, 0 (untreated), 0.98 U/mL, 1.9 U/mL, 3.91 U/mL, 7.81 U/mL, 15.6 U/mL, 31.3 U/mL, 62.5 U/mL, 125 U/mL, 250 U/mL, or 500 U/mL of a BoNT/A pharmaceutical product reconstituted in a sodium chloride free medium; 2) BB10, 0 (untreated), 0.49 U/mL, 0.98 U/mL, 1.9 U/mL, 3.91 U/mL, 7.81 U/mL, 15.6 U/mL, 31.3 U/mL, 62.5 U/mL, 125 U/mL, 250 U/mL; 3) H1, 0 (untreated), 0.3 U/mL, 1 U/mL, 3 U/mL, 9 U/mL, 28 U/mL, 83 U/mL, and 250 U/mL. Because the BoNT/A pharmaceutical product contains sodium chloride, its addition to the culture medium resulted in a hypertonic media that was detrimental to cell viability. To circumvent the hypertonicity issue, 200 pL of MEM media made without sodium chloride was used to reconstitute the BoNT/A pharmaceutical product giving a final concentration of 25 pM BoNT/A (500 U/mL). The matrix was kept constant for all concentrations along the dose-response curve by adding sodium chloride in the media used to make the dilutions match the amount of excipients present at the highest concentration used (25 pM or 500 U/mL). After a 24 hr treatment, the cells were washed, and incubated for an additional two days without toxin. To harvest the cells, 1 x PBS was aspirated, the cells lysed by adding 75 pL of Lysis Buffer comprising 50 mM HEPES, 150 mM NaCI, 1.5 mM MgCI2, 1 mM EGTA, 1% Triton X-100 to each well, and the plate incubated on a shaker rotating at 500 rpm for 30 minutes at 4 °C. The plate was centrifuged at 4000 rpm for 20 minutes at 4 °C to pellet cellular debris and the supernatant was transferred to a capture antibody coated 96-well plate to perform the detection step.

[0199] To prepare the a-SNAP-25 capture antibody solution, the a-SNAP-25 monoclonal antibody contained in the ascites from hybridoma cell line 2E2A6 (Example VII) was purified using a standard Protein A purification protocol. To prepare the a-SNAP-25 detection antibody solution, a-SNAP-25 rabbit polyclonal antibody S9684 (Sigma, St. Louis, MO) was conjugated to Ruthenium(ll)-tris-bipyridine-(4-methysulfonate) NHS ester labeling reagent (Meso Scale Discovery, Gaithersburg, MD) according to the manufacturer’s instructions (Meso Scale Discovery, Gaithersburg, MD). The conjugation reaction was performed by adding 30 pL of distilled water reconstituted MSD SULFO-TAG™ stock solution to 200 pL of 2 mg/mL a-SNAP-25 polyclonal antibodies and incubating the reaction at room temperature for 2 hours in the dark. The labeled antibodies were purified using a standard spin column protocol and the protein concentration determined using a standard colorimetric protein assay. The absorbance of the a-SNAP-25 antibody/MSD SULFO-TAG™ conjugate was measured at 455 nm using a spectrophotometer to determine the concentration in moles per liter. The detection antibody solution was stored at 4 °C until needed.

[0200] To prepare the solid phase support comprising the capture antibody that is specific for a SNAP-25 cleaved product, approximately 1 pL of a-SNAP-25 monoclonal antibody 2E2A6 solution (45 pg/mL in 1 x PBS, 750 pg/mL of BSA) was added to each well of a 96-well MSD High Bind plate (Meso Scale 115

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays 2017228675 15 Sep 2017 PCT/US2010/027242 18495 (BOT)/1957205.00451 WO 2010/105234 Patent Application

Discovery, Gaithersburg, MD) and the solution is allowed to air dry in a biological safety cabinet for 2-3 hours in order to liquid evaporate the solution, and then the plates were sealed and stored at 4 °C until needed. The dried capture antibody-bound wells were then blocked by adding 150 μΙ_ of Blocking Buffer comprising 1 x PBS, 0.05% Tween-20, 2 % ECL Blocking reagent (GE Healthcare-Amersham), and 1 % goat serum (Rockland Immunochemicals, Gilbertsville, PA) at room temperature for 2 hours with rotation at 600 rpm.

[0201] To detect the presence of a SNAP-25 cleavage product by ECL sandwich ELISA analysis, the Blocking Buffer from plates was aspirated, 25 pL of a lysate from cells treated with BoNT/A was added to each well and the plates were incubated at 4 °C for overnight. Plate wells were washed three times by aspirating the cell lysate and rinsing each well three times with 200 pL 1 x PBS, 0.1% TWEEN-20® (polyoxyethylene (20) sorbitan monolaureate). After washing, 25 pi of 5 pg/mL a-SNAP-25 detection antibody solution comprising 2% Amersham Blocking Reagent in 1 x PBS, 0.1% TWEEN-20® (polyoxyethylene (20) sorbitan monolaureate) was added to each well, the plate was sealed, and the sealed plate was incubated at room temperature for 1 hour with shaking. After a-SNAP-25 detection antibody incubation, the wells were washed three times with 250 pL 1 x PBS, 0.1% TWEEN-20® (polyoxyethylene (20) sorbitan monolaureate). After washing 150 pL of 1 x Read Buffer (Meso Scale Discovery, Gaithersburg, MD) was added to each well and the plates were read using a SECTOR™ Imager 6000 Image Reader (Meso Scale Discovery, Gaithersburg, MD). The raw data was then transferred to SigmaPlot v 10.0 and a 4-parameter logistics fit was used to define the dose-response curves. There were no constraints used for the 4-parameter logistic function when plotting the data. Graphical reports were generated using the following analysis: R2 (correlation coefficient), a (Max for data set), b (hillslope), and X0 ± SE (EC50 value ± standard error).

[0202] These results indicated that on average the cells comprising the BB10 and H1 clonal cell lines were more susceptible to BoNT/A intoxication as compared to cells comprising the parental SiMa cell line. Cells from a BB10 cell line exhibited an EC50 for BoNT/A activity of 7 U/mL, cells from a H1 cell line exhibited an EC50 for BoNT/A activity of 8 U/mL, and cells from the parental SiMa cell line exhibited an EC50 for BoNT/A activity of 13 U/mL. This method can also be performed in a multiplex fashion as described in Ester Fernandez-Salas, et al., Immuno-Based Botulinum Toxin Serotype A Activity Assays, U.S. Patent Application Serial No: 12/403,531, which is hereby incorporated by reference in its entirety.

Example VII

Transfection of BoNT/A receptor DNA into sensitive clonal cell lines further improves sensitivity

of the clonal cell line for BoNT/A

[0203] The following example illustrates how to introduce a polynucleotide molecule encoding a BoNT/A receptor into cells from a clonal cell line to further improve susceptibility to BoNT/A intoxication or improve BoNT/A uptake capacity. 116 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays [0204] To introduce an exogenous BoNT/A receptor into cells comprising an established clonal cell line, a mammalian expression construct comprising a polynucleotide molecule of SEQ ID NO: 139 encoding the FGFR3 of SEQ ID NO: 25, was transfected into cells from a H1 clonal cell line by a cationic lipid method. A suitable density (about 5 x106 cells) of cells from an established clonal cell line are plated in a 100 mm tissue culture dish containing 5 mL of complete culture media and grown in a 37 °C incubator under 5% carbon dioxide until the cells reached a density appropriate for transfection. A 3 mL transfection solution is prepared by adding 1.5 mL of OPTI-MEM® Reduced Serum Medium containing 60 pL of LIPOFECTAMINE® 2000 (Invitrogen, Carlsbad, CA) incubated at room temperature for 5 minutes to 1.5 mL of OPTI-MEM® Reduced Serum Medium containing 24 pg of an expression construct encoding the FGFR3 of SEQ ID NO: 25. This transfection mixture is incubated at room temperature for approximately 30 minutes. The complete media on the cells is replaced with the 3 mL transfection solution and the cells are incubated in a 37 °C incubator under 5% carbon dioxide for approximately 8 hours. Transfection media is replaced with 3 mL of fresh complete culture media and the cells are incubated in a 37 °C incubator under 5% carbon dioxide for approximately 24 hours. Media is replaced with 3 mL of fresh complete culture media containing approximately 1mM G418 (Invitrogen, Carlsbad, CA) for selection of transfected cells. Cells are incubated in a 37 °C incubator under 5% carbon dioxide for approximately 1 week, the old media is replaced with fresh complete culture media containing 0.5 mM G418 and the cells are plated onto one 96-well collagen IV coated plate at a plating density of 0.5 cells per well. Cell growth and viability was monitored by microscopic examination and after about 3 weeks single clones appeared in about 20% of the wells. These clones were grown for an additional 2 weeks and then transferred to duplicate 24-well collagen IV coated plates, one to maintain the clonal cell line and the other to test for BoNT/A susceptibility.

[0205] To determine the susceptibility of the cells comprising the clonal cell lines overexpressing a BoNT/A receptor, a Western blot analysis was done to determine sensitivity and an ECL sandwich ELISA was done to determine an EC50 value. A total of eight clones were tested for the FGFR3 stably transfected H1 cells.

[0206] To prepare a cell lysate for the Western blot analysis, cells from the clonal cell line were plated into two wells in a poly-D-lysine coated 96-well plate in serum-free medium containing Minimum Essential Medium, 2 mM GLUTAMAX™ I with Earle’s salts, 1 x B27 supplement, 1 x N2 supplement, 0.1 mM Non-Essential Amino Acids, 10 mM FIEPES and 25 pg/mL GT1b (Alexis Biochemicals, Lausen, Switzerland). These cells were incubated in a 37 °C incubator under 5% carbon dioxide until the cells differentiated, as assessed by standard and routine morphological criteria, such as growth arrest and neurite extension (approximately 3 days). The media from the differentiated cells was aspirated from each well and replaced with fresh media containing either 0 (untreated), 0.5 nM or 0.25 nM of a BoNT/A complex. After a 6 hr treatment, the cells were washed, and incubated for an additional 18 hr without toxin. After the incubation, the cells were washed by aspirating the growth media and rinsing each well with 200 μΙ of 1 x 117

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 PBS. To harvest the cells, the 1 x PBS was aspirated, the cells were lysed by adding 40 μΙ_ of 2 x SDS Loading Buffer and the plate was swirled for an even coating of Loading Buffer. The lysate was transferred to a new 96-well PCR plate (Axygen, Union City, CA) and the plate was heated to 95 °C for 5 min to complete cell lysis and denature proteins.

[0207] To detect for the presence of both uncleaved SNAP-25 substrate and cleaved SNAP-25 products, an aliquot from each harvested sample was analyzed by Western blot. In this analysis, a 12 pL aliquot of the harvested sample was separated by MOPS polyacrylamide gel electrophoresis using NUPAGE® Novex 12% Bis-Tris precast polyacrylamide gels (Invitrogen Inc., Carlsbad, CA) under denaturing, reducing conditions. Separated proteins were transferred from the gel onto nitrocellulose membranes (Bio-Rad Laboratories, Hercules, CA) by Western blotting using a “Transfer +4 cassettes &amp; Cooler” transfer chamber (GE Healthcare, Piscataway, NJ). Membranes were blocked by incubating at room temperature for 1 hr with gentle agitation in a solution containing Tris-Buffered Saline (TBS) (25 mM 2-amino-2-hydroxymethyl-1,3-propanediol hydrochloric acid (Tris-HCI)(pH 7.4), 137 mM sodium chloride, 2.7 mM potassium chloride), 0.1% TWEEN-20® (polyoxyethylene (20) sorbitan monolaureate), 2% Bovine Serum Albumin (BSA), 5% nonfat dry milk. Blocked membranes were incubated at 4 °C for overnight in TBS, 0.1% TWEEN-20® (polyoxyethylene (20) sorbitan monolaureate), 2% BSA, and 5% nonfat dry milk containing a 1:5,000 dilution of a-SNAP-25 rabbit polyclonal antiserum S9684 (Sigma, St. Louis, MO) as the primary antibody. The a-SNAP-25 rabbit polyclonal antibodies can detect both the uncleaved SNAP-25 substrate and the SNAP-25 cleavage product, allowing for the assessment of overall SNAP-25 expression in each cell line and the percent of SNAP-25 cleaved after BoNT/A treatment as a parameter to assess the amount of BoNT/A uptake. Primary antibody probed blots were washed three times for 5 minutes each time in TBS, TWEEN-20® (polyoxyethylene (20) sorbitan monolaureate). Washed membranes were incubated at room temperature for 2 hours in TBS, 0.1% TWEEN-20® (polyoxyethylene (20) sorbitan monolaureate), 2% BSA, and 5% nonfat dry milk containing a 1:10,000 dilution of goat polyclonal anti-rabbit immunoglobulin G, heavy and light chains (IgG, H+L) antibody conjugated to horseradish peroxidase (Invitrogen, Inc., Carlsbad, CA) as a secondary antibody. Secondary antibody-probed blots were washed five times for 5 minutes each time in TBS, 0.1% TWEEN-20® (polyoxyethylene (20) sorbitan monolaureate). Signal detection of the labeled SNAP-25 products were visualized using the ECL Plus™ Western Blot Detection System (GE Healthcare, Amersham Biosciences, Piscataway, NJ) and the membrane was imaged and the percent of cleaved SNAP-25 products quantified with a Typhoon 9410 Variable Mode Imager and Imager Analysis software (GE Healthcare, Amersham Biosciences, Piscataway, NJ). The choice of pixel size (100 to 200 pixels) and PMT voltage settings (350 to 600, normally 400) depended on the individual blot. The volumes of the bands corresponding to either intact and cleaved SNAP-25 product were quantified using Image Quant TL and the total amount of SNAP-25 and the percentage of SNAP-25 cleaved were calculated based on the intensity of these two SNAP-25 bands. 118

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 [0208] Clone H1 1.4 had a high percentage of SNAP-25 cleavage and high levels of total SNAP25 and was selected for further testing. The selected clone was first grown on a 10 cm2 dish and then in T175 flasks to ensure that enough cells were produced for both ECL sandwich ELISA assay and for freezing stocks. Frozen stocks were made with 1 x 106 cells and 1 mL of Recovery Cell Culture Freezing Media (GIBCO-Invitrogen, #12648-010 Freezing media).

[0209] To prepare a cell lysate for the ECL sandwich ELISA, approximately 50,000 cells from H1 clonal cell line and from H1 1.4 clonal cell line overexpressing FGFR3 were plated and differentiated as described above. The media from the differentiated cells was aspirated from each well and replaced with fresh media containing either (untreated), 0.27 pM, 0.82 pM, 2.47 pM, 7.4 pM, 22.2 pM, 66.6 pM, or 200 pM of a BoNT/A complex of a BoNT/A complex. After a 6 hr treatment, the cells were washed, and incubated overnight without toxin. After a 24 hr treatment, the cells were washed by aspirating the BoNT/A containing media and rinsing each well with 200 pL of 1 x PBS. Washed cells were harvested by lysing in freshly prepared Triton X-100 Lysis Buffer (150 mM NaCI, 20 mM Tris-HCI (pH 7.5), 1 mM EDTA, 1 mM EGTA, 1% Triton X-100 plus protease inhibitors) at 4°C for 30 minutes with constant agitation. Lysed cells were centrifuged at 4000 rpm for 20 min at 4°C to pellet debris.

[0210] The a-SNAP-25 capture antibody solution, the a-SNAP-25 detection antibody solution, and the solid phase support comprising the capture antibody that is specific for a SNAP-25 cleaved product were prepared as described in Example V. To detect the presence of a cleaved SNAP-25 product by ECL sandwich ELISA, the plates were processed, and the data collected and analyzed, and the EC50 calculated as described in Example VI. The EC50 for H1 1.4 cells was estimated to about 1.7 pM, compared to an EC50 about 8.7 pM for H1 cells indicating that the newly generated H1 1.4 cell line is about 5 times more sensitive than the H1 cell line for BoNT/A uptake (average of two independent experiments with similar results). The maximum signal for both cell lines was identical indicating similar efficacy towards SNAP25 cleavage. The increase in sensitivity is especially prominent at lower concentrations of BoNT/A, where the H1 1.4 cells are many times more sensitive to BoNT/A compared to H1 cells producing a very robust signal over background at the 0.27 pM concentration. Over-expression of FGFR3 was verified in a Western blot using a-FGFR3 antibodies sc-123 (Santa Cruz Biotechnologies, Santa Cruz, CA).

Example VIII

Development of a-SNAP-25 Monoclonal Antibodies that Selectively Bind a SNAP-25 Epitope Having a Free Carboxyl-terminus at the Pi Residue of the BoNT/A Cleavage Site Scissile Bond [0211] The following example illustrates how to make a-SNAP-25 monoclonal antibodies that can selectively bind to a SNAP-25 epitope having a carboxyl-terminus at the Pi residue of the BoNT/A cleavage site scissile bond. 119 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays 1. Generation of a-SNAP-25 monoclonal antibodies.

[0212] a-SNAP-25 monoclonal antibodies with higher binding affinity for a SNAP-25 cleavage product and/or a-SNAP-25 antibodies with a higher binding specificity for a SNAP-25 cleavage product were developed. In addition, because a permanent, stable and renewable source of a-SNAP-25 antibodies is preferable for an FDA-approved assay, screens to isolate monoclonal antibodies were undertaken. To develop monoclonal a-SNAP-25 antibodies the 13-residue peptide CDSNKTRIDEANQcooh (SEQ ID NO: 38) was designed as a SNAP-25 antigen having a carboxyl-terminus at the P1 residue of the BoNT/A cleavage site scissile bond. This peptide comprises a flexible linker region and a N-terminal Cysteine residue for conjugation to KLH and amino acids 186-197 of human SNAP-25 (SEQ ID NO: 5) with a carboxylated C-terminal glutamine (SEQ ID NO: 38). The generation of monoclonal antibodies to well-chosen, unique peptide sequences provides control over epitope specificity, allowing the identification of a particular subpopulation of protein among a pool of closely related isoforms. Blast searches revealed that this peptide has high homology only to SNAP-25 and almost no possible cross-reactivity with other proteins in neuronal cells. The sequence was also carefully scrutinized by utilizing computer algorithms to determine hydropathy index, protein surface probability, regions of flexibility, and favorable secondary structure, followed by proper orientation and presentation of the chosen peptide sequence. The peptide was synthesized and conjugated to Keyhole Limpet Hemocyanin (KLH) to increase immunogenicity. Six Balb/c mice were immunized with this peptide, and after three immunizations in about eight weeks, the mice were bled for testing. The blood was allowed to clot by incubating at 4 °C for 60 minutes. The clotted blood was centrifuged at 10,000x g at 4 °C for 10 minutes to pellet the cellular debris. The resulting serum sample was dispensed into 50 pL aliquots and stored at -20 °C until needed.

[0213] A similar strategy based on other SNAP-25 antigens disclosed in the present specification is used to develop a-SNAP-25 monoclonal antibodies that can selectively bind to a SNAP-25 having a carboxyl-terminus at the Pi residue of the BoNT/A cleavage site scissile bond. For example, the SNAP-25 antigen of SEQ ID NO: 45 can be conjugated to KLH instead of the SNAP-25 antigen of SEQ ID NO: 38. As another example, the amino acids 186-197 of human SNAP-25 from the SNAP-25 antigen of SEQ ID NO: 38 can be replaced with SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 147, or SEQ ID NO: 148. 2. Screening for the presence of a-SNAP-25 monoclonal antibodies.

[0214] To determine the presence of an a-SNAP-25 monoclonal antibody that can selectively bind to a SNAP-25 antigen having a carboxyl-terminus at the P1 residue of the BoNT/A cleavage site scissile bond, comparative ELISA and cell-based cleavage assay were performed using the extracted mouse serum. For comparative ELISA, two fusion proteins were constructed: BIRA-HIS TAG®-SNAP-25i34_i97 of SEQ ID NO: 48 and the BIRA-HIS TAG®-SNAP-25134-2oe of SEQ ID NO: 49. BIRA-HIS TAG®-SNAP-25i34-197 120

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 comprised a naturally-biotinylated 16 amino acid BirA peptide of SEQ ID NO: 50 amino-terminally linked to a SNAP-25 peptide comprising amino acids 134-197 of SEQ ID NO: 5. BIRA-HIS TAG®-SNAP-25134. 206 comprised a naturally-biotinylated 16 amino acid BirA peptide of SEQ ID NO: 50 amino-terminally linked to a SNAP-25 peptide comprising amino acids 134-206 of SEQ ID NO: 5. These two substrates were suspended in 1 x PBS at a concentration of 10 pg/mL BIRA-HIS TAG®-SNAP-25i34.i97 and the BIRA-HIS TAG®-SNAP-25134-206· The BIRA-HIS TAG®-SNAP-25134.197 and the BIRA-HIS TAG®-SNAP-25134.2oe were coated onto separate plates by adding approximately 100 pi of the appropriate Substrate Solution and incubating the plates at room temperature for one hour. Washed plates were incubated at 37 °C for one hour in 0.5% BSA in 1 x TBS containing a 1:10 to 1:100 dilution of an antibody-containing serum derived from one of the six immunized mice (Mouse 1, Mouse 2, Mouse 3, Mouse 4, Mouse 5, and Mouse 6). Primary antibody probed plates were washed four times for 5 minutes each time in 200 pi TBS, 0.1% TWEEN-20® (polyoxyethylene (20) sorbitan monolaureate). Washed plates were incubated at 37 °C for 1 hour in 1 x TBS containing a 1:10,000 dilution of goat polyclonal anti-mouse IgG antibody conjugated to Horseradish peroxidase (Pierce Biotechnology, Rockford, IL) as a secondary antibody. Secondary antibody-probed plates were washed four times in 200 pi TBS, 0.1% TWEEN-20® (polyoxyethylene (20) sorbitan monolaureate). Chromogenic detection of the labeled SNAP-25 products were visualized by chromogenic detection using ImmunoPure TMB substrate kit (Pierce Biotechnology, Rockford, IL). The development of a yellow color in the BIRA-HIS TAG®-SNAP-25134.197 coated plates, but not the BIRA-HIS TAG®-SNAP-25134_2oe coated plates, indicated that the a-SNAP-25 antibody preferentially recognized the SNAP-25i97 cleavage product. The resulted indicated that of the six mice used for immunization, three mice (Mouse 2, Mouse 3, and Mouse 4) had higher titers and more specificity towards a SNAP-25 antigen having a carboxyl-terminus at the Pt residue of the BoNT/A cleavage site scissile bond.

[0215] These results were confirmed using an ELISA light chain activity assay. A 96-well Reacti-Bind Streptavidin coated plates (Pierce Biotechnology, Rockford, IL) were prepared by adding approximately 100 pi of the following Substrate Solution: Rows A-C were coated with 100 pL of BIRA-HIS TAG®-SNAP-25134.197 at twelve different concentrations; Rows D-H were coated with 100 pL of BIRA-HIS TAG®-SNAP-25134_2oe at 10 pg/mL. The plates were washed by aspirating the Substrate Solution and rinsing each well three times with 200 pi TBS, 0.1% TWEEN-20® (polyoxyethylene (20) sorbitan monolaureate). Dilutions of BoNT/A were pre-reduced at 37 °C for 20 minutes in BoNT/A Incubation Buffer (50 mM HEPES, pH 7.4, 1% fetal bovine serum, 10 pM ZnCI2, 10 mM dithiothrietol) and 100 pi of the pre-reduced BoNT/A was added to the substrate-coated plates and incubated at 37 °C for 90 minutes. BoNT/A treated plates were washed by aspirating the BoNT/A Incubation Buffer and rinsing each plate three times with 200 pi TBS, 0.1% TWEEN-20® (polyoxyethylene (20) sorbitan monolaureate). Washed plates were incubated at 37 °C for one hour in 0.5% BSA in 1 x TBS containing a 1:10 to 1:100 dilution of the antibody-containing serum being tested. Primary antibody probed plates were washed four times for 5 minutes each time in 200 pi TBS, 0.1% TWEEN-20® (polyoxyethylene (20) sorbitan monolaureate). Washed plates were incubated at 37 °C for 1 hour in 1 x TBS containing a 1:10,000 dilution of goat polyclonal anti-mouse IgG 121

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays 2017228675 15 Sep 2017 PCT/US2010/027242 18495 (BOT)/1957205.00451 WO 2010/105234 Patent Application antibody conjugated to Horseradish peroxidase (Pierce Biotechnology, Rockford, IL) as a secondary antibody. Secondary antibody-probed plates were washed four times in 200 pi TBS, 0.1% TWEEN-20® (polyoxyethylene (20) sorbitan monolaureate). Chromogenic detection of the labeled SNAP-25 products were visualized by chromogenic detection using ImmunoPure TMB substrate kit (Pierce Biotechnology, Rockford, IL). The development of a yellow color, which correlated with the presence of the SNAP-25i97 cleavage product was detected in BoNT/A treated samples, but not untreated controls, using antibody-containing serum derived from all six immunized mice (Mouse 1, Mouse 2, Mouse 3, Mouse 4, Mouse 5, and Mouse 6). Thus, the comparative ELISA analysis indicated that of the mice used for immunization, three mice (Mouse 2, Mouse 3, and Mouse 4) had higher titers and more specificity towards a SNAP-25 antigen having a carboxyl-terminus at the Pi residue of the BoNT/A cleavage site scissile bond.

[0216] For cell-based cleavage assay, a suitable density of PC12 cells were plated into 60 mm2 tissue culture plates containing 3 mL of an appropriate serum medium (Table 1). The cells were grown in a 37 °C incubator under 5% carbon dioxide until cells reached the appropriate density. A 500 pL transfection solution was prepared by adding 250 pL of OPTI-MEM® Reduced Serum Medium containing 15 pL of LIPOFECTAINE® 2000 (Invitrogen Inc., Carlsbad, CA) incubated at room temperature for 5 minutes to 250 pL of OPTI-MEM® Reduced Serum Medium containing 10 pg of a pQBI-25/GFP-BoNT/A-LC expression construct (SEQ ID NO: 51). The pQBI-25/GFP-BoNT/A-LC expression construct comprises a pQBI-25 expression vector (Qbiogene Inc., Carlsbad, CA) whose promoter elements are functionally linked to a polynucleotide encoding the GFP-BoNT/A light chain of SEQ ID NO: 52. This transfection mixture was incubated at room temperature for approximately 20 minutes. The media was replaced with fresh unsupplemented media and the 500 pL transfection solution was added to the cells. The cells were then incubated in a 37 °C incubator under 5% carbon dioxide for approximately 6 to 18 hours. The cells were washed and harvested as described in Example II. To detect for the presence of the cleaved SNAP-25i97 product, an aliquot from each harvested sample was analyzed by Western blot as described in Example II, except that the primary antibody used was a 1:1,000 dilution of the antibody-containing serum and the secondary antibody used was a 1:20,000 of mouse α-lgG Horseradish Peroxidase (Pierce Biotechnology, Rockford, IL). A single band corresponding to the SNAP-25197 cleavage product was detected in BoNT/A treated samples, but not untreated controls, using antibody-containing serum derived from three mice (Mouse 2, Mouse 3, and Mouse 4). Thus, the cell-based cleavage assay indicated that of the mice used for immunization, three mice (Mouse 2, Mouse 3, and Mouse 4) had higher titers and more specificity towards a SNAP-25 antigen having a carboxyl-terminus at the P-ι residue of the BoNT/A cleavage site scissile bond. 3. Production of hybridomas.

[0217] To make hybridomas producing a-SNAP-25 monoclonal antibodies that can selectively bind to a SNAP-25 antigen having a carboxyl-terminus at the P1 residue of the BoNT/A cleavage site scissile bond, the spleen from Mouse 2 was harvested three days subsequent to a final “booster” immunization and the 122 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays spleen cells were fused with myeloma cells P3-X63 Ag8.653 using standard hybridoma protocols. These cells were plated into five 96-well plates and hybrids were selected using HAT medium. Within 8-14 days after fusion, the first screening of the approximately 480 parent clones was carried out using comparative ELISA with the BIRA-HIS TAG®-SNAP-25i34.i97 and the BIRA-HIS TAG®-SNAP-25i34.206 peptides coated in two separate plates. The comparative ELISA provided a quick screen method to identify hybridomas producing antibodies specific for the cleaved SNAP-25197. The top 18 clones were subjected to further screening using the cell-based cleavage assay described above and immunostaining of LC/A transfected cells. (Table 18).

Table 18. Analysis of Supernatants Containing a-SNAP-25 Monoclonal Antibody Clone Comparative ELISA Cell-Based Assay OD SNAP-25,97 OD SNAP-252o6 Ratio197/206 Ratio2o6,i97 SNAP-25,97 SNAP-252o6 1D3 1.805 0.225 8.02 0.13 + + + - 1F12 0.365 0.093 3.92 0.25 - - 1G10 0.590 0.137 4.31 0.23 + + - 1H1 0.335 0.121 2.77 0.36 - - 1H8 0.310 0.302 1.03 0.97 + - 2C9 0.139 0.274 0.51 1.97 - - 2E2 0.892 0.036 24.78 0.04 ++ - 2E4 0.228 0.069 3.30 0.30 + - 2F11 1.095 1.781 0.61 1.63 - - 3C1 1.268 0.053 23.92 0.04 + + - 3C3 0.809 0.052 15.56 0.06 + + - 3E1 0.086 0.155 0.55 1.80 0 - 3E8 2.048 0.053 38.64 0.03 ++ + - 3G2 0.053 0.158 0.34 2.98 - - 4D1 0.106 0.218 0.49 2.06 - - 4G6 0.061 0.159 0.38 2.61 - - 5A5 0.251 0.106 2.37 0.42 + - 5F11 0.243 0.061 3.98 0.25 - - [0218] Clones 1D3, 1G10, 2E2, 3C1, 3C3, and 3E8 were further cloned by limiting dilution because the conditioned media produced by these clones comprised a-SNAP-25 antibodies with a preferential binding specificity having a ratio197/206 of at least 4:1 for the SNAP-25,97 cleavage product relative to the SNAP-25208 uncleaved substrate and detected the SNAP-25i97-cleavage product using the cell-based cleavage assay and the immunostaining of PC12 cells transfected with GFP-LC/A. Similarly clones 2C9, 2F11, 3G2, 4D1 and 4G6 were further cloned by limiting dilution because the conditioned media produced by these clones comprised a-SNAP-25 antibodies with a preferential binding specificity having a ratio206/i97 of at least 1.5:1 for the SNAP-2520e uncleaved substrate relative to the SNAP-25i97 cleavage product and detected the SNAP-252o6-uncleaved substrate using the cell-based cleavage assay. These single-cell derived clones were screened again using comparative ELISA, cell-based cleavage, and immunostaining to confirm their affinity and specificity, and the antibodies were isotyped using standard procedures. 123 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays

Ascites were produced from clones 1D3B8 (IgM.k), 1G10A12 (lgG3.k), 2C9B10 (lgG3.k), 2E2A6 (lgG3.k), 2F11B6 (IgM.k), 3C1A5 (lgG2a.k), and 3C3E2 (lgG2a.k). Clone 3E8 stopped producing antibodies during the cloning process and could not be further evaluated. 4. Evaluation of binding specificity of a-SNAP-25 monoclonal antibodies.

[0219] To evaluate binding specificity of an a-SNAP-25 monoclonal antibody that can selectively bind to a SNAP-25 antigen having a carboxyl-terminus at the Pi residue of the BoNT/A cleavage site scissile bond, ascites from clones 1D3B8, 1G10A12, 2C9B10, 2E2A6, 2F11B6, 3C1A5, and 3C3E2 were used to detect SNAP-25 cleavage product using the cell-based activity assay, immunocytochemistry and immunoprecipitation.

[0220] For the cell-based activity assay, binding specificity was determined by analyzing the ability of a-SNAP-25 antibody-containing ascites to detect the uncleaved SNAP-252oe substrate and the cleaved SNAP-25i97 product by Western blot analysis. A suitable density of PC12 cells were plated into 60 mm2 tissue culture plates containing 3 mL of an appropriate serum medium, grown in a 37 °C incubator under 5% carbon dioxide until an appropriate cell density was reached, and transfected with the either a transfection solution lacking the pQBI-25/GFP-BoNT/A-LC expression construct (untransfected cells) or a transfection solution containing the pQBI-25/GFP-BoNT/A-LC expression construct (transfected cells) as described above. The cells were washed and harvested as described in Example I. To detect for the presence of both the uncleaved SNAP-252o6 substrate and the cleaved SNAP-25197 product, an aliquot from each harvested sample was analyzed by Western blot as described in Example I, except that the primary antibody used was a 1:100 dilution of the a-SNAP-25 monoclonal antibody-containing ascites and the secondary antibody used was a 1:20,000 of α-mouse IgG conjugated to Horseradish Peroxidase (Pierce Biotechnology, Rockford, IL). In addition, three commercially available mouse a-SNAP-25 monoclonal antibodies were tested. SMI-81 (Sternberger Monoclonals Inc., Lutherville, MD), an a-SNAP-25 antibody the manufacturer indicates detects both the uncleaved SNAP-25206 substrate and the cleaved SNAP-25197 product, was used at a 15,000 dilution according to the manufacturer’s recommendations. MC-6050 (Research &amp; Diagnostic Antibodies, Las Vegas, NV), an a-SNAP-25 antibody the manufacturer indicates detects both the uncleaved SNAP-25206 substrate and the cleaved SNAP-25i97 product, was used at a 1:100 dilution according to the manufacturer’s recommendations. MC-6053 (Research &amp; Diagnostic Antibodies, Las Vegas, NV), an a-SNAP-25 antibody the manufacturer indicates detects only the cleaved SNAP-25197 product, was used at a 1:100 dilution according to the manufacturer’s recommendations.

[0221] Table 19 indicates the a-SNAP-25 antibody-containing ascites that detected only the SNAP-25197 cleavage product. The cell-based cleavage assay indicated that ascites produced from clones 1D3B8, 2C9B10, 2E2A6, 3C1A5, and 3C3E2 synthesize an a-SNAP-25 monoclonal antibody having high binding specificity for the SNAP-25i97 cleavage product that allows for the selective recognition of this cleavage 124

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 product relative to the SNAP-252oe uncleaved substrate. Commercial antibody SMI-81 detected the SNAP-252o6 uncleaved substrate, but only poorly recognized the SNAP-25197 cleavage product (Table 19). Surprisingly, commercial antibody MC-6050 only detected the SNAP-2520e uncleaved substrate, and failed to recognize the SNAP-25i97 cleavage product (Table 19). Even more surprisingly, commercial antibody MC-6050 only detected the SNAP-2520e uncleaved substrate, and failed to recognize the SNAP-25·!^ cleavage product, even though the manufacturer advertises that this antibody selectively detects the SNAP-25197 cleavage product (Table 19). Thus, this analysis indicates that while 1D3B8, 2C9B10, 2E2A6, 3C1A5, and 3C3E2 exhibit suitable selectivity for the SNAP-25i97 cleavage product, 1G10A12 and 2F11B6 do not. In addition, commercial antibodies SMI-81, MC-6050 and MC-6053 all are unsuitable for the immuno-based methods disclosed in the present application because all failed to selectivity detect the SNAP-25197 cleavage product.

[0222] For immunocytochemistry analysis, binding specificity was determined by analyzing the ability of a-SNAP-25 antibody-containing ascites to detect the uncleaved SNAP-2520e substrate and the cleaved SNAP-25i97 product by immunostaining. See e.g., Ester Fernandez-Salas et al., Plasma Membrane Localization Signals in the Light Chain of Botulinum Neurotoxin, Proc. Natl. Acad. Sci., U.S.A. 101(9): 3208-3213 (2004). A suitable density of PC12 cells were plated, grown, and transfected with either a transfection solution lacking the pQBI-25/GFP-BoNT/A-LC expression construct (untransfected cells) or a transfection solution containing the pQBI-25/GFP-BoNT/A-LC expression construct (transfected cells) as described above. The cells were washed in 1 x PBS and fixed in 5 ml. of PAF at room temperature for 30 minutes. Fixed cells were washed in phosphate buffered saline, incubated in 5 mL of 0.5% Triton® X-100 (polyethylene glycol octylphenol ether) in 1 x PBS, washed in 1 x PBS, and permeabilized in 5 mL of methanol at -20 °C for six minutes. Permeabilized cells were blocked in 5 mL of 100 mM glycine at room temperature for 30 minutes, washed in 1 x PBS, and blocked in 5 mL of 0.5% BSA in 1 x PBS at room temperature for 30 minutes. Blocked cells were washed in 1 x PBS and incubated at room temperature for two hours in 0.5% BSA in 1 x PBS containing a 1:10 dilution of an ascites from a clonal hybridoma cell line being tested. Primary antibody probed cells were washed three times for 5 minutes each time in 1 x PBS. Washed cells were incubated at room temperature for 2 hours in 1 x PBS containing a 1:200 dilution of goat polyclonal anti-mouse immunoglobulin G, heavy and light chains (IgG, H+L) antibody conjugated to ALEXA® FLUOR 568 (Invitrogen Inc., Carlsbad, CA) as a secondary antibody. Secondary antibody-probed cells were washed three times for 5 minutes each time in 1 x PBS. Washed cells were prepared for microscopic examination by mounting in VECTASHIELD® Mounting Media (Vector Laboratories, Burlingame, CA) and coverslipped. Images of signal detection were obtained with a Leica confocal microscope using appropriate laser settings. Table 19 indicates that the a-SNAP-25 antibody-containing ascites that specifically detected the SNAP-25197-cleavage product. The immunocytochemistry analysis indicated that ascites produced from clones 1D3B8, 2C9B10, 2E2A6, 3C1A5, and 3C3E2 synthesize an a-SNAP-25 monoclonal antibody having high binding specificity for the SNAP-25i97 cleavage product that allows for the preferential recognition of this cleavage product relative to the SNAP-25206 uncleaved substrate. 125 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays [0223] For immunoprecipitation analysis, binding specificity was determined by analyzing the ability of Protein A (HiTrap™ Protein A HP Columns, GE Healthcare, Amersham, Piscataway, NJ), purified a-SNAP-25 monoclonal antibodies to precipitate the uncleaved SNAP-252o6 substrate and the cleaved SNAP-25i97 product. See e.g., Chapter 8 Storing and Purifying Antibodies, pp. 309-311, Harlow &amp; Lane, supra, 1998a. A suitable density of PC12 cells were plated, grown, and transfected with either a transfection solution containing a pQBI-25/GFP expression construct (control cells; SEQ ID NO: 53) or a transfection solution containing the pQBI-25/GFP-BoNT/A-LC expression construct (experimental cells) as described above. The pQBI-25/GFP expression construct comprises an expression vector whose promoter elements are functionally linked to a polynucleotide encoding GFP of SEQ ID NO: 54. After an overnight incubation, the cells were washed by aspirating the growth media and rinsing each well with 200 pL 1 x PBS. To harvest the cells, the PBS was aspirated, the cells were lysed by adding an Immunoprecipitation Lysis Buffer comprising 50 mM HEPES, 150 mM NaCI, 1.5 mM MgCI2, 1 mM EGDT, 10% glycerol, 1% Triton® X-100 (polyethylene glycol octylphenol ether) and a 1 x COMPLETE™ Protease inhibitor cocktail (Roche Applied Biosciences, Indianapolis, IN) and incubating at 4 °C for one hour. The lysed cells were centrifuged at 3,000 x g at 4 °C for 10 minutes to remove cellular debris and the supernatant transferred to a clean tube and diluted to a protein concentration of approximately 1 mg/mL. Approximately 5 pg of purified monoclonal antibody was added to 0.5 mL of diluted supernatant and incubated at 4 °C for two hours. After primary antibody incubation, approximately 50 pi of immobilized Protein G (Pierce Biotechnology, Rockford, IL) was added to the diluted supernatant and incubated at 4 °C for one hour. The incubated supernatant was washed three times for 30 minutes each time by adding 0.5 mL of Immunoprecipitation Lysis Buffer, centrifuging at 300 x g at 4 °C for one minute to pellet the immobilized Protein G, and decanting the supernatant. After washing, the pellet was resuspended in 30 pL of 1 x SDS Loading Buffer and the sample was heated to 95 °C for 5 minutes. To detect for the presence of both the uncleaved SNAP-252o6 substrate and the cleaved SNAP-25197 product, an aliquot from each harvested sample was analyzed by Western blot as described in Example I, except that the primary antibody used was a 1:1,000 dilution of the a-SNAP-25 polyclonal antibody serum (see Example IV) and the secondary antibody used was a 1:20,000 of rabbit α-lgG Horseradish Peroxidase (Pierce Biotechnology, Rockford, IL). Table 19 indicates the a-SNAP-25 antibody-containing ascites that specifically pulled down the SNAP-25197-cleavage product by immunoprecipitation analysis. The immunoprecipitation analysis indicated that ascites produced from clones 2E2A6 and 3C1A5 synthesize an a-SNAP-25 monoclonal antibody having high binding specificity for the SNAP-25197 cleavage product that allows for the preferential recognition of this cleavage product relative to the SNAP-2520e uncleaved substrate.

Table 19. Analysis of Clone Ascites Containing a-SNAP-25 Monoclonal Antibody Clone Cell-Based Assay Immunocytochemistry Immunoprecipitation SNAP-25197 SNAP-25206 SNAP-25i97 SNAP-25206 SNAP-25-197 SNAP-25206 1D3B8 ++ - ++ - Not Tested Not Tested 1G10A12 ++ ++ Not Tested Not Tested Not Tested Not Tested 126 PCT/US2010/027242 WO 2010/105234

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Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays 2C9B10 + + - + + - Not Tested Not Tested 2E2A6 + + - ++ - + + - 2F11B6 + + + + Not Tested Not Tested 3C1A5 + + - + + - ++ - 3C3E2 + - Not Tested Not Tested Not Tested Not Tested MC-6050 - + Not Tested Not Tested Not Tested Not Tested MC-6053 - + Not Tested Not Tested Not Tested Not Tested SMI-81 -/+ + + Not Tested Not Tested Not Tested Not Tested 5. Evaluation of binding affinity of a-SNAP-25 monoclonal antibodies.

[0225] To determine the binding affinity of an a-SNAP-25 monoclonal antibody showing high binding specificity for either the SNAP-25i97 cleavage product or the SNAP-252oe uncleaved substrate, binding affinity assays were performed on a BIACORE 3000 instrument using carboxymethyl dextran (CM5) sensor chips (BIAcore, Inc., Piscataway, NJ). Runs were conducted at 25 °C with HBS-EP buffer comprising 10 mM HEPES (pH 7.4), 150 mM sodium chloride, 3 mM EDTA, 0.005% (v/v) surfactant P20 at a flow rate of 10 μΙ/min. SNAP-25 peptides comprising amino acids 134-197 of SEQ ID NO: 5 (SNAP-25-134-197) or amino acids 134-206 of SEQ ID NO: 5 (SNAP-25i34-2oe) were covalently attached to the surface of the CM5 sensor chips using standard amine coupling. Briefly, the CM5 chips were activated by a 7 minute injection of a mixture of 0.2 M 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and 0.05 M N-hydroxysuccimide; the SNAP-25 peptides were then injected in 10 mM sodium acetate (pH 4.0) for 20 min at a flow rate of 10 pL/min; and unreacted succimide esters were blocked by a 7-min injection of 1 M ethanolamine hydrochloride, pH 8.5. The immobilized amount of SNAP-25134-|97 or SNAP-25134.206 on the chip was reflected by a 100-150 increase in response units (about 0.10-0.15 ng/mm2). Antibody samples comprising either ascites or purified monoclonal antibodies produced from clones 1D3B8, 2C9B10, 2E2A6, 3C1A5, and 3C3E2, as well as, commercially available a-SNAP-25 antibodies were passed over the surface of the CM5 chips allowing an association time of 10 min and a dissociation time of 20 min. The surfaces were regenerated between runs by a 1 minute injection of 10 mM glycine-HCI (pH 2.5) at a flow rate of 15 pL/min. Sensorgram curves were fitted to a 1:1 kinetic binding model with the BIAevaluation 3.0 software.

[0226] The results indicate that both 2E2A6 and 3C1A5 were highly specific for cleaved SNAP-25i97 product over SNAP-25 uncleaved substrate (Table 20). When compared to the binding affinities of MC-6050 and MC-6053, 1D3B6 had an approximately 10-fold higher equilibrium disassociation constant for the SNAP-25 cleavage product relative to these commercial antibodies (Table 20). Interestingly, 2E2A6 had only a slightly lower equilibrium disassociation constant for the SNAP-25 cleavage product relative to these commercial antibodies (0.405 nM versus 0.497 and 0.508)(Table 20). As neither of these commercial a-SNAP-25 antibodies selectively recognized the SNAP-25 cleavage product (Table 19), an equilibrium disassociation constant lower than about 0.5 nM appears, in part, critical to achieve such selectivity. Similarly, when compared to the binding affinities of MC-6050 and MC-6053, 2E2A6 had an 127 PCT/US2010/027242 WO 2010/105234

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Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays about at least one-fold slower off rate/dissociation constant (6.74 x 10"5 versus 8.82 x 10 4 s"1 and 1.18 x 10"3 s'1) (Table 20). This further suggests that an off rate/dissociation constant lower than about 8.82 x 10-4 appears, in part, critical to achieve selective binding for the SNAP-25 cleavage product. This result is consistent with 1D3B8, which had an off rate/dissociation constant of 5.78 x 10 5 s1 (Table 20).

Table 20. Analysis of Binding Affinity a-SNAP-25 Monoclonal Antibodies SPR Parameter 1D3B8 2E2A6 SNAP-25i97 SNAP-25206a SNAP-25,97 SNAP-252o6b Ka (M 1 s1) 1.06 x 106 — 1.70 x 106 (1.66 x 105) (-) Kd ( s'1) 5.78 x 10'5 — 1.53 x 10'4 (6.74 x 10'5) (-) KD (nM) 0.050 — 0.090 (0.405) (-) SPR Parameter 3C1A5 2C9B10 SNAP-25i97 SNAP-25206C SNAP-25,97 SNAP-252oed Ka (M'1 s'1) 2.17 x 105 — 1.15 x 104 — Kd (s'1) 2.88 x 10'4 — 3.11 x 10'4 — KD (nM) 1.33 — 27.1 — SPR Parameter MC-6050 MC-6053 SNAP-25197 S NAP-2 5206 SNAP-25,97 SNAP-252<,6 Ka (M'1 s'1) 1.78 x 106 3.06 x 102 2.32 x 106 1.06 x 102 Kd (s'1) 8.82 x 10'4 6.07 x 10'3 1.18 x 10'3 2.56 x 10'5 KD (nM) 0.497 19,800 0.508 240 a No binding was observed when up to 125 nM of a-SNAP-25 monoclonal antibody 1D3B8 was passed over the surface of the CM5 sensor chip after a 10 minute association time. b No binding was observed when up to 10 μΜ of a-SNAP-25 monoclonal antibody 2E2A6 was passed over the surface of the CM5 sensor chip after a 10 minute association time. c No binding was observed when up to 100 nM of a-SNAP-25 monoclonal antibody 3C1A5 was passed over the surface of the CM5 sensor chip after a 10 minute association time. d No binding was observed when up to 100 nM of a-SNAP-25 monoclonal antibody 2C9B10 was passed over the surface of the CM5 sensor chip after a 10 minute association time.

[0227] To compare the six different antibodies, the on-rate (ka) and off-rate (kd) for each was normalized using a program from the BIA evaluation 4.1 software. For comparison of the on-rates, the data were first individually trimmed by deleting the re-generation portion and the injection spikes, and then normalized to a 0 to 100 scale. For comparison of the off-rate, the data were normalized to the injection stop/top point. This analysis showed that 2C9B10 had a much slower on-rate than the other antibodies (FIG. 3A), and that MC-6053 has a much faster off-rate (dissociation) that the other antibodies (FIG. 3B). The fast off-rate of MC-6053 indicates that this antibody will not perform well in the methods disclosed in the present specification because this antibody will have difficulty staying bound to the substrate antigen during the washing steps. 128 PCT/US2010/027242 WO 2010/105234

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Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays 6. Sequencing of the epitope from isolated a-SNAP-25 monoclonal antibodies.

[0228] To determine the epitope of an isolated a-SNAP-25 monoclonal antibody that can selectively bind to a SNAP-25 antigen having a carboxyl-terminus at the Pi residue of the BoNT/A cleavage site scissile bond, the polynucleotide molecule encoding the variable heavy (VH) and variable light (VL) chains of the a-SNAP-25 monoclonal antibody produced by hybridomas 1D3B8, 2C9B10, 2E2A6, 3C1A5 and 3C3E2 were sequenced. mRNA was extracted and purified from each hybridoma using standard protocols and reversed transcribed into cDNA using either an oligo dT anti-sense primer or a gene-specific (murine lgG1 CH and kappa CL) anti-sense primer. Specific murine and human constant domain primers were used to amplify the cDNA by PCR after cDNA production to determine the isotype of the antibody. Degenerate VH and VL primers were used to amplify the variable domains from the cDNA. For 5’RACE, a homopolymeric dCTP tail was added to the 3’ end of the cDNA. The heavy and light chains were then amplified with an oligo dG sense primer and a gene specific (CH/KC) anti-sense primer. PCR products included the sequence of the signal peptide, variable domains and constant domains up to the anti-sense primer. The PCR products were gel purified to remove small fragments, and cloned into a blunt or TA vector for sequencing. Five independent clones for each chain were sequenced and alignments of VH and VL chains and consensus sequences were determined. Methods used to determine the VH and VL amino acid sequences are described in, e.g., Roger A. Sabbadini, et al., Novel Bioactive Lipid Derivatives and Methods of Making and Using Same, U.S. Patent Publication 2007/0281320; and Peter Amersdorfer, et al., Molecular Characterization of Murine Humoral Immune Response to Botulinum Neurotoxin Type A Binding Domain as Assessed by Using Phage Antibody Libraries, 65(9) Infect. Immun. 3743-3752, each of which is hereby incorporated by reference in its entirety. In addition, commercial services are available to sequence the variable heavy (VH) and variable light (VL) chains of an antibody and identify the CDR regions, see, e.g., Fusion Antibodies Ltd., Northern Ireland.

[0229] The polynucleotide sequence comprising the VH and VL chains of the a-SNAP-25 monoclonal antibody produced by the hybridomas disclosed in the present specification is as follows: 1D3B8 VH (SEQ ID NO: 71), 2C9B10 VH (SEQ ID NO: 73), 2E2A6 VH (SEQ ID NO: 75), 3C1A5 VH (SEQ ID NO: 77), 3C3E2 VH variant 1 (SEQ ID NO: 79), 3C3E2 VH variant 2 (SEQ ID NO: 81), 3C3E2 VH variant 3 (SEQ ID NO: 149), 1D3B8 VL (SEQ ID NO: 83), 2C9B10 VL (SEQ ID NO: 85), 2E2A6 VL (SEQ ID NO: 87), 3C1A5 VL (SEQ ID NO: 89), and 3C3E2 VL (SEQ ID NO: 91). The amino acid sequence comprising the VH and VL chains of the a-SNAP-25 monoclonal antibody produced by the hybridomas disclosed in the present specification is as follows: 1D3B8 VH (SEQ ID NO: 72), 2C9B10 VH (SEQ ID NO: 74), 2E2A6 VH (SEQ ID NO: 76), 3C1A5 VH (SEQ ID NO: 78), 3C3E2 VH variant 1 (SEQ ID NO: 80), 3C3E2 VH variant 2 (SEQ ID NO: 82); 3C3E2 VH variant 2 (SEQ ID NO: 150), 1D3B8 VL (SEQ ID NO: 84), 2C9B10 VL (SEQ ID NO: 86), 2E2A6 VL (SEQ ID NO: 88), 3C1A5 VL (SEQ ID NO: 90), and 3C3E2 VL (SEQ ID NO: 92). The amino acid sequences comprising the VH and VL CDR domains of the a-SNAP-25 monoclonal antibody produced by the hybridomas 1D3B8, 2C9B10, 2E2A6, 3C1A5, and 3C3E2 are given in Table 21. 129 PCT/US2010/027242 WO 2010/105234

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Table 21. CDR Sequences of VH and VL domains from a-SNAP-25 Monoclonal Antibodies CDR Sequence Identified In SEQ ID NO: VH CDR 1 TFTDHSIH 2E2A6 2C9B10 3C1A5 93 VH CDR 1 TFTNYVIH 3C3E2 94 VH CDR 1 IFTDHALH 1D3B8 95 VH CDR 2 YIFPGNGNIEYNDKFKG 2E2A6 96 VH CDR 2 YLFPGNGNFEYNEKFKG 2C9B10 3C1A5 97 VH CDR 2 YINPYNDGSKYNEKFKG 3C3E2 98 VH CDR 2 YIFPGNGNIEYNEKFKG 1D3B8 99 VH CDR 3 KRMGY 2E2A6 3C1A5 100 VH CDR 3 KKMDY 2C9B10 1D3B8 101 VH CDR 3 ARMDY 3C3E2var1 102 VH CDR 3 ARMGY 3C3E2var2 151 VH CDR 3 ARH LANTYYYFDY 3C3E2var3 152 VL CDR 1 RSSQSIVHSNGNTYLE 1D3B8 103 VL CDR 1 RTTENIYSYFV 2C9B10 104 VL CDR 1 KSSQSLLYTNGKTYLT 2E2A6 105 VL CDR 1 KSSQSLLNTNGKTYLT 3C1A5 106 VL CDR 1 RASQNIGNYLH 3C3E2 107 VL CDR 2 KVSNRFS 1D3B8 108 VL CDR 2 NAKSLAE 2C9B10 109 VL CDR 2 LVSELDS 2E2A6 110 VL CDR 2 LVSKLDS 3C1A5 111 VL CDR 2 YASQSIS 3C3E2 112 VL CDR 3 FQGSHVPPT 1D3B8 113 VL CDR 3 QHHYGTPYT 2C9B10 114 VL CDR 3 LQSAHFPFT 2E2A6 115 VL CDR 3 LQSSHFPFT 3C1A5 116 VL CDR 3 QQSDTWPLT 3C3E2 117 [0230] Non-limiting examples of amino acid sequences comprising VH CDR domain variants of the a-SNAP-25 monoclonal antibody produced by the hybridomas disclosed in the present specification include VH CDR1 variant SEQ ID NO: 118 for 1D3B8; VH CDR1 variant SEQ ID NO: 119 for 2C9B10, 2E2A6 and 3C1A5 VH; VH CDR1 variant SEQ ID NO: 120 for 3C1A5 VH and 3C3E2 variant 3; VH CDR2 variant SEQ ID NO: 121 for 1D3B8 and 2E2A6; VH CDR2 variant SEQ ID NO: 122 for 2C9B10 and 3C1A5 VH; VH CDR2 variant SEQ ID NO: 123 for 3C1A5 VH and 3C3E2 variant 3; VH CDR3 variant MDY for 1D3B8 and 2C9B10; VH CDR3 variant MGY for 2E2A6 and 3C1A5 VH; and VH CDR3 variant SEQ ID NO: 124 for 3C1A5 VH and 3C3E2 variant 3. Non-limiting examples of amino acid sequences comprising VL CDR domain variants of the a-SNAP-25 monoclonal antibody produced by the hybridomas disclosed in the 130

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays 2017228675 15 Sep 2017 PCT/US2010/027242 18495 (BOT)/1957205.00451 WO 2010/105234 Patent Application present specification include VL CDR1 variant SEQ ID NO: 125 for 1D3B8; VL CDR1 variant SEQ ID NO: 126 for 2C9B10; VL CDR1 variant SEQ ID NO: 127 for 2E2A6; VL CDR1 variant SEQ ID NO: 128 for 3C1A5; VL CDR1 variant SEQ ID NO: 129 for 3C3E2; VL CDR2 variant KVS for 1D3B8; VL CDR2 variant NAK for 2C9B10; VL CDR2 variant LVS for 2E2A6; VL CDR2 variant YAT for 3C1A5; and VL CDR2 variant YAS for 3C3E2.

Example IX

Development of a-SNAP-25 Polyclonal Antibodies that Selectively Bind a SNAP-25 Epitope Having a Free Carboxyl-terminus at the Pi Residue of the BoNT/A Cleavage Site Scissile Bond [0231] The following example illustrates how to make a-SNAP-25 polyclonal antibodies that can selectively bind to a SNAP-25 epitope having a carboxyl-terminus at the P-ι residue of the BoNT/A cleavage site scissile bond.

[0232] To develop a-SNAP-25 polyclonal antibodies that bind an epitope comprising a carboxyl-terminus at the P1 residue from the BoNT/A cleavage site scissile bond from a SNAP-25 cleavage product, the 10-residue peptide CGGGRIDEANQ (SEQ ID NO: 46) was designed as a SNAP-25 cleavage product antigen. This peptide comprising a N-terminal Cysteine residue for conjugation to KLH, a G-spacer flexible spacer (GGG) linked to amino acids 191-197 of human SNAP-25 (SEQ ID NO: 5) and has a carboxylated C-terminal glutamine. Blast searches revealed that this peptide has high homology only to SNAP-25 and almost no possible cross-reactivity with other proteins in neuronal cells. The sequence was also carefully scrutinized by utilizing computer algorithms to determine hydropathy index, protein surface probability, regions of flexibility, and favorable secondary structure, followed by proper orientation and presentation of the chosen peptide sequence. The peptide was synthesized and conjugated to Keyhole Limpet Hemocyanin (KLH) to increase immunogenicity. Before the animals were immunized, na'ive rabbits were first screened against cell lysates from candidate cell lines in a Western blot in order to identify animals that had no immunoreactivity to the proteins present in the cell lysates. Two prescreened rabbits were immunized with this peptide, and after three immunizations in about eight weeks, the rabbits were bled for testing. The blood was allowed to clot by incubating at 4 °C for 60 minutes. The clotted blood was centrifuged at 10,000x g at 4 °C for 10 minutes to pellet the cellular debris. The resulting serum sample was dispensed into 50 pL aliquots and stored at -20 °C until needed.

[0233] A similar strategy based on other SNAP-25 antigens disclosed in the present specification is used to develop a-SNAP-25 polyclonal antibodies that bind an epitope comprising a carboxyl-terminus at the P1 residue from the BoNT/A cleavage site scissile bond from a SNAP-25 cleavage product. For example, the SNAP-25 antigen of SEQ ID NO: 47 can be conjugated to KLH instead of the SNAP-25 antigen of SEQ ID NO: 46. As another example, the amino acids 191-197 of human SNAP-25 from the SNAP-25 antigen of SEQ ID NO: 38 can be replaced with SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID 131

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WO 2010/105234 Patent Application PCT/US2010/027242 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017 NO: 36, SEQ ID NO: 37, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, or SEQ ID NO: 44. 2. Screening for the presence of a-SNAP-25 polyclonal antibodies.

[0234] To determine the presence of a-SNAP-25 polyclonal antibodies that can selectively bind to a SNAP-25 antigen having a carboxyl-terminus at the Pi residue of the BoNT/A cleavage site scissile bond, comparative ELISA and cell-based cleavage assays were performed using the extracted rabbit serum as described in Example VIII. The serum from both rabbits contained a-SNAP-25 polyclonal antibodies that can selectively bind to a SNAP-25 antigen having a carboxyl-terminus at the Pi residue of the BoNT/A cleavage site scissile bond. The a-SNAP-25 rabbit polyclonal antibodies were designated as NTP 22 and NTP 23. 3. Purification of a-SNAP-25 polyclonal antibodies.

[0235] To purify a-SNAP-25 polyclonal antibodies that can selectively bind to a SNAP-25 antigen having a carboxyl-terminus at the Pi residue of the BoNT/A cleavage site scissile bond, NTP 22 and NTP 23 antibodies from rabbit serum were purified using affinity columns containing the SNAP-25 antigen of SEQ ID NO: 46. 4. Evaluation of binding specificity of a-SNAP-25 polyclonal antibodies.

[0236] To evaluate binding specificity of an a-SNAP-25 polyclonal antibody that can selectively bind to a SNAP-25 antigen having a carboxyl-terminus at the Pi residue of the BoNT/A cleavage site scissile bond, purified NTP 22 and NTP 23 a-SNAP-25 polyclonal antibodies were used to detect cleavage product using the cell-based activity assay, immunnocytochemistry and immunoprecipitation as described in Example VIII. The cell-based cleavage assay, immunocytochemistry analysis and immunoprecipitation analysis all indicated that NTP 22 and NTP 23 a-SNAP-25 polyclonal antibodies did not cross-react with uncleaved SNAP-25. Thus both NTP 22 and NTP 23 have high binding specificity for the SNAP-25i97 cleavage product that allows for the preferential recognition of this cleavage product relative to the SNAP-25206 uncleaved substrate. Affinity for the antigens can be determined using SPR in the BiAcore as described in Example VIII.

[0237] Unless otherwise indicated, all numbers expressing quantities of ingredients, properties such as molecular weight, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the present invention. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of 132 PCT/US2010/027242 WO 2010/105234

Patent Application 18495 (BOT)/1957205.00451 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements.

[0238] The terms “a,” “an,” “the” and similar referents used in the context of describing the invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. Recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., “such as”) provided herein is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention otherwise claimed. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the invention.

[0239] Groupings of alternative elements or embodiments of the invention disclosed herein are not to be construed as limitations. Each group member may be referred to and claimed individually or in any combination with other members of the group or other elements found herein. It is anticipated that one or more members of a group may be included in, or deleted from, a group for reasons of convenience and/or patentability. When any such inclusion or deletion occurs, the specification is deemed to contain the group as modified thus fulfilling the written description of all Markush groups used in the appended claims.

[0240] Certain embodiments of this invention are described herein, including the best mode known to the inventors for carrying out the invention. Of course, variations on these described embodiments will become apparent to those of ordinary skill in the art upon reading the foregoing description. The inventor expects skilled artisans to employ such variations as appropriate, and the inventors intend for the invention to be practiced otherwise than specifically described herein. Accordingly, this invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Moreover, any combination of the above-described elements in all possible variations thereof is encompassed by the invention unless otherwise indicated herein or otherwise clearly contradicted by context.

[0241] Specific embodiments disclosed herein may be further limited in the claims using consisting of or consisting essentially of language. When used in the claims, whether as filed or added per amendment, 133 WO 2010/105234 Patent Application 2017228675 15 Sep 2017

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays PCT/US2010/027242 18495 (BOT)/1957205.00451 the transition term “consisting of excludes any element, step, or ingredient not specified in the claims. The transition term “consisting essentially of” limits the scope of a claim to the specified materials or steps and those that do not materially affect the basic and novel characteristic(s). Embodiments of the invention so claimed are inherently or expressly described and enabled herein. [0242] Furthermore, numerous references have been made to patents and printed publications throughout this specification. Each of the above-cited references and printed publications are individually incorporated herein by reference in their entirety. [0243] In closing, it is to be understood that the embodiments of the invention disclosed herein are illustrative of the principles of the present invention. Other modifications that may be employed are within the scope of the invention. Thus, by way of example, but not of limitation, alternative configurations of the present invention may be utilized in accordance with the teachings herein. Accordingly, the present invention is not limited to that precisely as shown and described. 134 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B„ et al., Cells Useful for Immuno-Based BoNT/A Activity Assays

Table 5. Increased Gene Expression in Cell Lines H1 and BB10 vs. Cell Line 2D6 in Undifferentiated State Using Microarray Analysis Representative Gene Symbol Probe Set ID Public ID PLS3 201215_at NM_005032 H99792 225710_at H99792 DAZ1 208282_x_at NM_020363 DAZ3 DAZ2 DAZ4 TPTE 220205_at NM_013315 DAZ1 207909_x_at U21663 DAZ3 DAZ2 DAZ4 MSN 200600 at NM 002444 CXCR4 217028_at AJ224869 NDN 209550 at U35139 FLJ32942 227711_at BG150433 AM 97932 229498 at Al 197932 PEG3 209242_at AL042588 TIMP3 201149 s at U67195 NEDD9 202149_at AL136139 TIMP3 201150 s at NM 000362 PRSS12 205515 at NM 003619 LUM 201744_s_at NM_002345 RGS5 1555725 a at AF493929 TFPI2 209278 s at L27624 CXCR4 211919 s at AF348491 RGS5 218353_at NM 025226 ASCL1 209985 s at BE797438 KCTD12 212192_at AI718937 SPARC 200665_s_at NM 003118 CXCR4 209201_x_at L01639

RefSeq Entrez Transcript ID Gene ID Log2 Ratio pvalue NM_005032 5358 6.56 2.91 E-12 — — 6.46 1.81 E-07 NM 00100537 1617 6.45 4.63E-04 5 57054 NM 00100578 57055 5 57135 NM 00100578 6 NM 004081 NM_020363 NM_020364 NM 020420 NM_013315 7179 6.44 3.16E-08 NM 199259 NM_199260 NM 199261 NM_00100537 1617 6.20 2.48E-04 5 57054 NM 00100578 57055 5 57135 NM_00100578 6 NM 004081 NM 020363 NM 020364 NM 020420 NM 002444 4478 6.11 2.92E-09 NM_00100854 π 7852 5.95 3.23E-04 u NM_003467 NM 002487 4692 5.81 3.18E-06 NM_144594 121355 5.73 8.08E-09 — — 5.59 3.21 E-08 NM 006210 5178 5.58 1.13E-07 NM 000362 7078 5.57 3.00E-05 NM_006403 4739 5.49 3.70E-09 NM_182966 NM_000362 7078 5.40 1.53E-03 NM 003619 8492 5.37 1.39E-06 NM_002345 4060 5.37 1.04E-06 NM 003617 8490 5.22 2.23E-07 NM 006528 7980 5.22 1.95E-05 NM 00100854 7852 5.18 9.56E-04 0 NM_003467 NM 003617 8490 5.15 1.82E-07 NM 004316 429 5.09 8.38E-06 NM_138444 115207 5.04 6.32E-06 NM 003118 6678 4.97 2.45E-06 NM 00100854 7852 4.97 9.51 E-04 0 NM 003467 135 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 TIMP3 Jacky, B., etal., 201147_s_at Cells Useful for Immuno-Based BoNT/A Activity Assays BF347089 NM_000362 7078 4.95 1.56E-04 DAZ1 207912_s_at NM_004081 NM 00100537 1617 4.94 1 79E-03 DAZ3 DAZ2 DAZ4 MINA 213189_at BE966695 5 NM_00100578 5 NM 00100578 6 NM_004081 NM_020363 NM 020364 NM 020420 NM_032778 57054 57055 57135 84864 4.92 1.50E-08 CUGBP2 202157_s_at U69546 NM_153182 NM_006561 10659 4.91 1 20E-06 BF000203 236385_at BF000203 — -- 4.87 6.43E-06 GRP 206326_at NM_002091 NM 002091 2922 4.82 1.83E-06 RGS5 209070_s_at Al 183997 NM_003617 8490 4.78 1.01E-07 AI183997 233858 at AU144918 — — 4.72 1.79E-05 RNF182 230720_at Al 884906 NM_152737 221687 4.72 4.74E-07 PEG3 209243_s_at AF208967 NM 006210 5178 4.69 8.13E-06 RAM2 225081_s_at AK022955 NM 018719 55536 4.52 1.18E-04 )KFZp667G21 1 214030_at BE501352 XM 376254 131544 4.52 6.37E-10 RGS5 209071 s at AF159570 NM_003617 8490 4.50 1.74E-07 VIP 206577_at NM_003381 NM_003381 7432 4.44 2.77E-04 PRSS12 213802 at AI810767 NM_194435 NM 003619 8492 4.41 1.46E-03 MGC34032 235763_at AA001450 NM_152697 204962 4.40 3.84E-08 DAZ1 208281_x_at NM_020364 NM_00100537 1617 4.39 5.53E-04 DAZ3 DAZ2 DAZ4 DAZ1 216922_x_at AF271088 5 NM 00100578 5 NM 00100578 6 NM 004081 NM_020363 NM 020364 NM 020420 NM 00100537 57054 57055 57135 1617 4.35 6.79E-04 DAZ3 DAZ2 DAZ4 SPARC 212667_at AL575922 5 NM_00100578 5 NM_00100578 6 NM_004081 NM 020363 NM_020364 NM_020420 NM 003118 57054 57055 57135 6678 4.30 4.26E-05 MAB21L2 210302 s at AF262032 NM 006439 10586 4.28 1.96E-08 CCDC3 223316_at AL136562 NM_031455 83643 4.21 1.24E-06 SLAC2-B 214734_at AB014524 NM 015065 23086 4.20 1.64E-03 ARHGAP6 206167_s_at NM_001174 NM 001174 395 4.19 1.68E-05 BASP1 202391 at NM_006317 NM_006125 NM_013422 NM_013423 NM 013427 NM 006317 10409 4.18 3.67E-08 SIM1 206876_at AL121948 NM 005068 6492 4.16 4.38E-05 136 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuho-Based BoNT/A Activity Assays SMC6L1 236535 at AW069285 NM_024624 79677 4.09 2.41 E-07 CUGBP2 202158_s_at NM 006561 NM 006561 10659 4.09 8.95E-04 FAT 201579_at NM 005245 NM_005245 2195 4.08 5.01 E-03 GNG11 204115_at NM 004126 NM 004126 2791 4.07 6.53E-04 ITGA6 201656 at NM 000210 NM_000210 3655 3.98 4.23E-09 ACATE2 221641 s at AF241787 NM 012332 23597 3.97 4.71 E-05 TCTE1L 203303_at NM 006520 NM 006520 6990 3.96 2.11 E-07 NEDD9 202150_s_at U64317 NM 006403 NM 182966 4739 3.94 1.90E-06 DOK5 214844_s_at AL050069 NM 018431 NM_177959 55816 3.83 1.64E-05 EDG2 204036_at AW269335 NM_001401 NM 057159 1902 3.82 2.36E-08 MAOA 204388_s_at NM 000240 NM 000240 4128 3.80 8.51 E-05 SPAG6 210033_s_at AF079363 NM_012443 NM_172242 9576 3.78 6.66E-06 BF476109 1556300_s_at BF476109 — — 3.78 7.77E-06 PTPRK 203038 at NM 002844 NM 002844 5796 3.75 1.34 E-03 GFRA2 205722_s_at NM 001495 NM 001495 2675 3.74 7.15E-06 PTPRE 221840_at AA775177 NM_006504 NM 130435 5791 3.72 2.12E-06 ADAMTS9 226814_at Al431730 NM_020249 NM 182920 NM 182921 56999 3.70 9.69E-05 MINA 213188_s_at AI823896 NM 032778 NM_153182 84864 3.69 3.36E-05 PLK2 201939_at NM_006622 NM_006622 10769 3.69 1.39E-06 KIAA1754 225582_at AA425726 NM_033397 85450 3.67 2.03E-04 FN5 219806_s_at NM 020179 NM 020179 56935 3.65 2.97E-04 SMC6L1 218781_at NM_024624 NM_024624 79677 3.64 1.72E-08 EML1 204797_s_at NM_004434 NM_00100870 7 NM 004434 2009 3.64 6.58E-05 ADAMTS9 1562275_at AL832835 NM_020249 NM 182920 NM 182921 56999 3.58 1.72E-06 LOC441157 1558795 at AL833240 XM_499037 441157 3.56 7.55E-06 MAOA 212741_at AA923354 NM 000240 4128 3.55 6.62E-04 TRIM29 211002_s_at AF230389 NM_012101 NM_058193 23650 3.51 2.23E-07 MAOA 204389 at NM 000240 NM 000240 4128 3.50 4.16E-07 MGC34032 1569112_at AW020413 NM 152697 204962 3.50 9.78E-06 ELOVL7 227180_at AW138767 XM_371740 79993 3.45 6.72E-04 TFPI2 209277 at AL574096 NM 006528 7980 3.43 6.92E-06 ASCL1 213768_s_at AW950513 NM_004316 429 3.36 5.80E-07 CHRNA7 CHRFAM7A 210123_s_at U62436 NM_000746 NM_139320 NM 148911 1139 89832 3.33 4.22E-06 ASCL1 209987 s at BC002341 NM_004316 429 3.33 1.82E-08 FRZB 203697_at U91903 NM 001463 2487 3.31 1.02E-05 SLC43A3 210692_s_at BC003163 NM_014096 NM 017611 NM_199329 29015 3.31 7.81 E-05 LOC253012 242601_at AA600175 NM 198151 253012 3.30 2.75E-04 CD9 201005_at NM_001769 NM_001769 928 3.26 3.31 E-04 SMAD6 207069 s at NM 005585 NM 005585 4091 3.26 6.45E-06 PCGF5 226326_at AI798098 NM_032373 84333 3.26 7.00E-07 MAB21L2 210303 at AF262032 NM 006439 10586 3.26 6.74E-05 137 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays SLC7A2 225516_at AA876372 NM 00100853 9 NM_003046 6542 3.22 1.59E-06 AL109791 233932_at AL109791 — ... 3.20 1.60E-03 MGC33926 229302 at AA058832 NM 152390 130733 3.20 1.16E-03 KCTD12 212188_at AA551075 NM 138444 115207 3.19 7.60E-05 MAFB 218559_s_at NM 005461 NM_005461 9935 3.16 7.22E-03 BNC2 220272_at NM_017637 NM 017637 54796 3.14 3.14E-03 ASCL1 209988_s_at BC001638 NM 004316 429 3.14 4.77E-08 CBLN2 242301 at R60224 NM 182511 147381 3.14 3.35E-03 ALCAM 240655_at BE502785 NM_001627 214 3.13 2.14E-04 AF131795 233139_at AF131795 — ... 3.12 8.04E-03 AI656180 242447_at AI656180 — ... 3.12 3.69E-05 LOC402524 242206 at AW590588 XM_379850 402524 3.10 5.25E-04 EDG3 228176_at AA534817 NM 005226 1903 3.10 4.81 E-04 KDELC2 225128_at AL548941 NM_153705 143888 3.09 2.21 E-04 NEGR1 243357_at AA115106 NM 173808 257194 3.09 1.42E-05 DACT1 219179 at NM_016651 NM_016651 51339 3.09 2.14E-04 DAZ1 DAZ3 DAZ2 DAZ4 216351_x_at AF248483 NM_00100537 5 NM_00100578 5 NM 00100578 6 NM_004081 NM_020363 NM 020364 NM 020420 1617 57054 57055 57135 3.06 4.06E-04 KIAA0527 214954_at BF977837 XM 171054 26032 3.03 2.02 E-04 TPBG 203476_at NM_006670 NM 006670 7162 3.02 2.88E-05 LGR5 213880_at AL524520 NM 003667 8549 3.02 2.16E-03 FLJ23091 228950_s_at AL534095 NM_00100229 2 NM 024911 79971 3.01 2.38E-03 PLXNA4 232317_at AB046770 XM 039393 XMJ379927 57671 2.99 6.60E-07 FLJ20647 218802_at NM_017918 NM 017918 55013 2.99 7.56E-03 CNTN4 229084_at R42166 NM_175607 NM 175612 NM_175613 152330 2.96 2.55E-06 RBPMS 209488_s_at D84109 NM_00100871 0 NM 00100871 1 NM 00100871 2 NM 006867 11030 2.96 5.32E-03 E2F7 228033_at AI341146 NM 203394 144455 2.94 1.26E-03 TRIM29 202504_at NM_012101 NM 012101 NM_058193 23650 2.93 6.42E-08 N26620 227503_at N26620 — ... 2.93 1.14E-04 TIMP3 201148_s_at AW338933 NM 000362 7078 2.91 1.23E-03 C2orf31 221245_s_at NM 030804 ... 81561 2.91 2.25E-05 )KFZp761O201 232313_at AL122107 XM_044062 92293 2.91 1 59E-06 BC041965 1560411_at BC041965 — — 2.91 8.58E-04 GNAI1 227692_at AU153866 NM_002069 2770 2.90 2.00E-06 GPR10 231805_at AL563031 NM_004248 2834 2.90 1.19E-04 138 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 LGR5 Jacky, B,, et al., Cells Useful for Immuno-Based BoNT/A Activity Assays 210393 at AF062006 NM_003667 8549 2.89 4.97E-05 ENC1 201340 s at AF010314 NM 003633 8507 2.89 4.72E-05 LOC51760 205613_at NM_016524 NM 016524 51760 2.88 9.54E-03 GNG12 222834_s_at N32508 NM_018841 55970 2.88 1.98E-04 BARD1 205345_at NM 000465 NM 000465 580 2.87 6.84E-03 A2BP1 1553422_s_at NM_145892 NM 018723 54715 2.86 4.30E-03 PPP1R3C 204284_at N26005 NM_145891 NM_145892 NM 145893 NM_005398 5507 2.84 1.93E-05 AF086027 1559697_a_at AF086027 — ... 2.83 1.45E-03 PMP22 210139_s_at L03203 NM_000304 5376 2.83 1.89E-04 GFRA2 205721_at U97145 NM 153321 NM 153322 NM_001495 2675 2.83 4.80E-04 PFKFB3 202464_s_at NM_004566 NM_004566 5209 2.82 3.61 E-03 BF222929 242346 x at BF222929 — — 2.82 2.87E-04 SLC43A3 213113_s_at AI630178 NM_014096 29015 2.80 1.02E-06 PEX5L 1562473_at BC037943 NM_017611 NM_199329 NM_016559 51555 2.79 1.76E-04 PELO 226731_at AA156873 53918 2.76 4.84E-03 FBN1 202765_s_at AI264196 NM_015946 NM_000138 2200 2.76 2.17E-03 PLEKHE1 212719_at AB011178 NM 194449 23239 2.75 5.65E-03 MYRIP 214156_at AL050090 NM_015460 25924 2.75 2.44E-06 BNC2 235723_at AA843242 NM 017637 54796 2.74 2.24E-03 CPVL 208146_s_at NM_031311 NM 019029 54504 2.73 2.87E-03 PLXNA4 228104_at AL117427 NM 031311 XM_039393 57671 2.72 4.31 E-04 BF940761 229427_at BF940761 XM_379927 2.69 4.80E-03 ARHGEF6 209539_at D25304 NM_004840 9459 2.68 2.81 E-04 H17657 24i444_at H17657 — — 2.67 2.17E-04 GNAI1 209576_at AL049933 NM_002069 2770 2.65 1.06E-07 LOC441157 1558796_a_at AL833240 XM 499037 441157 2.65 1.11 E-03 CADPS 1568603_at AI912173 NM 003716 8618 2.64 4.31 E-04 POSTN 210809_s_at D13665 NM 183393 NM_183394 NM 006475 10631 2.63 1.47E-03 PTPRR 210675_s_at U77917 NM_002849 5801 2.60 4.53E-03 MGC24103 232568_at AU145658 NM_130846 158295 2.59 3.96E-04 STK17A 202693 s at AW194730 NM 004760 9263 2.59 1.11 E-04 LOC440738 221697_at AF276659 NM_001004343 440738 2.58 1.85E-03 MY06 203215_s_at AA877789 NM 004999 4646 2.56 7.95E-03 CADPS 1568604_a_at AI912173 NM 003716 8618 2.56 2.70E-07 NR3C1 211671_s_at U01351 NM 183393 NM_183394 NM_000176 2908 2.56 2.36E-09 FRZB 203698_s_at NM_001463 NM 001463 2487 2.56 3.80E-04 FLJ23091 221958_s_at AA775681 NM_00100229 0 79971 2.54 5.86E-03 ADAMTS9 1554697_at AF488803 NM 024911 NM 020249 56999 2.54 1.99E-04 AW130600 226865 at AW130600 NM 182920 NM 182921 2.53 4.86E-04 139 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 ST8SIA4 Jacky, B., et al., 230836_at Cells Useful for Immuno-Based BoNT/A Activity Assays AI422986 NM_005668 7903 2.50 7.33E-03 CNTN1 211203_s_at U07820 NM 175052 NM_001843 1272 2.49 1.34E-04 EMILIN2 224374 s at AF270513 NM_175038 NM 032048 84034 2.48 1.13E-04 HGF 210997_at M77227 NM 000601 3082 2.46 4.58E-03 AI582818 229053 at Al582818 NM_00101093 1 NM 00101093 2 NM_00101093 3 NM_00101093 4 2.44 6.88E-03 LOC253981 226430 at Al394438 — 253981 2.44 3.85E-03 GNG12 212294 at BG111761 NM 018841 55970 2.42 1.06E-06 C6orf148 220513_at NM 030568 NM 030568 80759 2.41 5.89E-03 OSBPL3 209626_s_at AI202969 NM_015550 26031 2.40 9.56E-04 SEMA6D 233882_s_at AK022831 NM_145320 NM 145321 NM_145322 NM_145323 NM 145324 NM 020858 80031 2.39 1.02E-03 PCDH8 206935_at NM_002590 NM_024966 NM_153616 NM_153617 NM 153618 NMJ53619 NM_002590 5100 2.37 6.17E-07 MAB21L1 206163_at NM_005584 NM_032949 NM_005584 4081 2.36 4.98E-03 TSC 218872_at NM_017899 NM 017899 54997 2.36 1.01 E-05 PPP2R2B 213849_s_at AA974416 NM_004576 5521 2.35 2.05E-06 PDE5A 227088_at BF221547 NM_181674 NM 181675 NM_181676 NM_181677 NM_181678 NM 001083 8654 2.35 2.27E-04 ZNF521 226676_at AK021452 NM_033430 NM 033431 NM 033437 NM_015461 25925 2.34 1.55E-03 PVRL3 213325_at AA129716 NM_015480 25945 2.34 3.70E-06 ENC1 201341_at NM_003633 NM_003633 8507 2.33 3.06E-05 RGMA 223468_s_at AL136826 NM 020211 56963 2.33 1.24E-07 ST8SIA2 239537_at AW589904 NM_006011 8128 2.32 8.94E-07 140 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays FGFR2 203639_s_at M80634 NM_000141 NM 022969 NM_022970 NM_022971 NM_022972 NM 022973 NM_022974 NM_022975 NM 022976 NM 023028 NM_023029 NM 023030 NM 023031 2263 2.29 4.06E-03 BAMBI 203304_at NM 012342 NM 012342 25805 2.29 2.34E-08 ARHGAP6 1563386_at AL079282 NM_001174 NM_006125 NM 013422 NM 013423 NM_013427 395 2.27 2.07E-03 PLCL2 213309_at AL117515 NM 015184 23228 2.27 1.92E-03 A2BP1 221217_s_at NM_018723 NM 018723 NM_145891 NM 145892 NM_145893 54715 2.26 5.56E-03 LOC340109 1557765_at BC039509 XM 379322 340109 2.25 2.28E-05 SLC39A8 209267_s_at AB040120 NM 022154 64116 2.25 4.91 E-03 ITGA6 215177_s_at AV733308 NM 000210 3655 2.23 2.05E-03 CNTN1 227209_at AI091445 NM_001843 NM_175038 1272 2.23 4.31 E-03 EGLN3 219232 s at NM 022073 NM 022073 112399 2.23 7.56E-03 ZFHX4 219779_at NM_024721 NM 024721 79776 2.22 1.39E-03 AF086027 1559696_at AF086027 — — 2.21 1.05E-03 AL050204 213929_at AL050204 — — 2.20 2.15E-03 TPTE 233879_at AL137389 NM_013315 NM_199259 NM 199260 NM 199261 7179 2.20 2.76E-03 TMEM35 219685 at NM 021637 NM_021637 59353 2.20 8.17E-03 MSX2 205555_s_at D31771 NM 002449 4488 2.20 6.02E-04 GPR51 211679_x_at AF095784 NM_005458 9568 2.19 5.89E-03 BE856929 239349_at BE856929 — — 2.17 2.00E-03 SYN2 210247_at AW139618 NM_003178 NM 133625 6854 2.15 5.68E-03 COLEC12 221019_s_at NM_030781 NM 030781 NM_130386 81035 2.15 7.66E-03 TCF7L1 221016 s_at NM_031283 NM_031283 83439 2.14 1.38E-03 NRXN1 228547_at BF509242 NM_004801 NM_138735 9378 2.13 8.92E-03 CRH 205630_at NM 000756 NM 000756 1392 2.13 1.12E-03 GPR161 230369_at AI743151 NM_007369 NM_153832 23432 2.12 1.61E-04 ZNF217 203739_at NM 006526 NM 006526 7764 2.12 3.18E-04 NEDD9 233223_at AK000850 NM 006403 NM_182966 4739 2.11 4.23E-04 RASEF 235144_at AA826324 NM 152573 158158 2.09 2.92E-03 PLAT 201860_s_at NM_000930 NM 000930 NM_000931 NM 033011 5327 2.09 6.29E-04 141 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B„ et al., Cells Useful for Immuno-Based BoNT/A Activity Assays GPR51 209990_s_at AF056085 NM_005458 9568 2.05 1.33E-05 AL161982 1563494 at AL161982 — — 2.05 1.21 E-03 SEMA6D 226492_at AL036088 NM_020858 NM 024966 NM_153616 NM 153617 NM_153618 NM_153619 80031 2.05 1.22E-04 ORF1-FL49 224707_at AL522667 NM 032412 84418 2.04 2.79E-05 NID 202007_at BF940043 NM 002508 4811 2.04 2.24E-03 PCGF5 229194_at AL045882 NM_032373 84333 2.02 2.51 E-04 TCF7L2 216035_x_at AV721430 NM 030756 6934 2.02 2.84E-07 AA156721 201952_at AA156721 — — 2.02 1.05E-06 FBN1 202766 s at NM 000138 NM 000138 2200 2,02 7.81 E-04 DBH 206450 at NM_000787 NM_000787 1621 2.01 2.59E-03 PTPRR 206084_at NM_002849 NM 002849 NM 130846 5801 2.01 4.19E-03 CNTN1 227202_at AW072790 NM 001843 NM_175038 1272 2.00 1.32 E-03 ARHGEF3 218501_at NM_019555 NM_019555 50650 2.00 4.42E-05 SLITRK5 214930_at AW449813 NM 015567 26050 2.00 7.82E-06 ETV1 206501_x_at NM_004956 NM 004956 2115 1.99 3.21 E-03 SPAG6 210032_s_at AI651156 NM_012443 NM_172242 9576 1.99 2.72E-04 LCRISP1 223475_at AF142573 NM 031461 83690 1.99 3.27E-03 FGFR2 211401_s_at AB030078 NM 000141 NM 022969 NM_022970 NM 022971 NM 022972 NM_022973 NM_022974 NM 022975 NM 022976 NM 023028 NM_023029 NM 023030 NM_023031 2263 1.99 1.83E-04 FLJ30058 238047_at AA405456 NM_144967 158763 1.99 3.10E-03 BF434771 1568598_at BF434771 XM_498494 440000 1.98 2.21 E-03 TCF7L2 216511 s at AJ270770 NM 030756 6934 1.97 7.59E-05 MY06 203216_s_at NM_004999 NM 004999 4646 1.96 8.88E-05 ATP2B4 212136_at AW517686 NM_00100139 6 NM 001684 493 1.96 7.81 E-03 RAB32 204214_s_at NM_006834 NM_006834 10981 1.96 3.53E-03 AI703256 231336_at AI703256 — — 1.95 4.67E-04 FLJ40773 1563933_a_at AK091691 NM 152666 200150 1.95 1.13E-03 LOC92689 213455 at W87466 NM 138389 92689 1.95 5.71 E-04 TCF7L2 212761_at AI949687 NM 030756 6934 1.94 5.52E-05 TDRD7 213361_at AW129593 NM_014290 23424 1.93 4.13E-03 GFPT2 205100_at NM_005110 NM_005110 9945 1.92 3.68E-04 142 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays FGFR2 203638_s_at NM_022969 NM_000141 NM 022969 NM_022970 NM_022971 NM 022972 NM 022973 NM_022974 NM_022975 NM_022976 NM 023028 NM_023029 NM 023030 NM 023031 2263 1.92 3.46E-03 ALCAM 201951_at BF242905 NM 001627 214 1.91 6.46E-06 ETV1 217053_x_at X87175 NM_004956 2115 1.91 7.09E-03 NR3C1 201865_x_at AI432196 NM 000176 2908 1.90 1.19E-05. PDLIM5 203242_s_at BG054550 NM 00101151 3 NM_00101151 4 NM 00101151 5 NM 00101151 6 NM 006457 10611 1.89 7.00E-05 ST8SIA2 221285 at NM 006011 NM_006011 8128 1.89 8.94E-04 TWIST1 213943_at X99268 NM_000474 7291 1.88 3.85E-04 TLE4 216997_x_at AL358975 NM 007005 7091 1.88 7.83E-03 GPR161 214104_at AI703188 NM 007369 NM_153832 23432 1,88 5.85E-03 EDG2 204037_at BF055366 NM_001401 NM 057159 1902 1.87 9.88E-08 PDLIM5 216804_s_at AK027217 NM 00101151 3 NM_00101151 4 NM_00101151 5 NM 00101151 6 NM_006457 10611 1.87 2.39E-05 R39126 230932_at R39126 — — 1.87 2.27E-04 AI377043 230722_at AI377043 — — 1.87 1.53E-03 W93046 230068 s at W93046 — — 1.86 2.03E-03 DMN 212730_at AK026420 NM_015286 NM 145728 23336 1.86 2.15E-03 ARHGAP24 223422_s_at Al 743 534 NM 031305 83478 1.86 1.60E-03 CCNE2 211814_s_at AF112857 NM 004702 NM_057735 NM 057749 9134 1.85 5.31 E-03 NRXN1 209914_s_at AW149405 NM 004801 NM_138735 9378 1.84 2.88E-03 ETV1 217061_s_at AC004857 NM_004956 2115 1.83 4.93E-04 FAM19A5 229459_at AV723914 NM_015381 25817 1.82 1.07E-06 ITPR1 240052_at AA648993 NM 002222 3708 1.82 7.08E-04 ZAK 222757_s_at AB030034 NM 016653 NM 133646 51776 1.81 3.74E-04 143 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., etal.,' Cells Useful for Immuno-Based BoNT/A Activity Assays FGFR2 208228_s_at M87771 NM_000141 NM 022969 NM_022970 NM_022971 NM 022972 NM 022973 NM_022974 NM_022975 NM_022976 NM 023028 NM_023029 NM_023030 NM 023031 2263 1.81 1.44E-03 ZNF545 1555793 a at AL834267 NM_133466 284406 1.80 4.60E-04 AW024890 229942_at AW024890 ... ... 1.79 6.14E-05 AI733341 240911_at AI733341 — — 1.79 7.62E-04 PPAP2B 209355_s_at AB000889 NM 003713 NM 177414 8613 1.79 4.28E-04 TBX3 222917_s_at U69556 NM 005996 NM_016569 6926 1.79 9.78E-06 TRIP10 202734 at NM 004240 NM 004240 9322 1.79 8.00E-03 TCF7L2 212762_s_at Al 375916 NM 030756 6934 1.79 3.86E-07 PELO 214660_at X68742 NM_015946 53918 1.78 2.39E-03 GPR51 217077_s_at AF095723 NM 005458 9568 1.78 3.16E-04 FBLN1 202994_s_at Z95331 NM_001996 NM_006485 NM_006486 NM 006487 2192 1.77 2.59E-03 DOK5 1554863_s_at BC008992 NM 018431 NM_177959 55816 1.77 3.36E-03 NRXN1 209915_s_at AB035356 NM_004801 NM_138735 9378 1.76 7.05E-03 FLJ25067 243507_s_at AV715251 NM 152504 149840 1.76 6.53E-07 DNAPTP6 222154_s_at AK002064 NM_015535 26010 1.76 4.90E-04 MGC21654 1556429_a_at BC026969 NM_145647 93594 1.76 6.54E-03 CPNE4 228796_at BE645967 NM_130808 131034 1.75 4.64E-04 POSTN 1555778_a_at AY140646 NM_006475 10631 1.75 4.56E-05 ATOH8 228890_at BF434995 NM_032827 84913 1.75 7.05E-04 ALCAM 1569362_at BC041127 NM 001627 214 1.75 9.54E-03 HTATSF1 202601_s_at AI373539 NM_014500 27336 1.75 5.33E-05 MYD88 209124 at U70451 NM 002468 4615 1.74 3.20E-04 PPAP2B 212230_at AV725664 NM_003713 NM_177414 8613 1.74 1.11E-05 ZNF253 LOC114977 242919_at AV683221 NM_021047 114977 56242 1.73 1.13E-03 DCLRE1B 219490_s_at NM_022836 NM_022836 64858 1.73 3.54E-03 TBX3 229576_s_at N29712 NM 005996 NM_016569 6926 1.72 6.02E-07 KHDRBS3 230249 at AI650382 NM 006558 10656 1.72 3.44E-04 FLJ39609 1555980_a_at CA447406 XM 379692 284598 1.72 9.03E-03 BF110268 238178_at BF110268 — — 1.71 1.80E-04 KLF7 238482 at AL120562 NM 003709 8609 1.71 1.93E-03 ELL2 226099 at AI924426 NM 012081 22936 1.71 8.96E-04 KHDRBS3 209781_s„at AF069681 NM 006558 10656 1.71 3.55E-05 TRIM37 1569114_at BC011742 NM_00100520 7 NM_015294 4591 1.71 3.38E-03 144 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017 18495 (BOT)/1957205.00451 TPST2 AL833029 PDLIM5 TBC1D19 FZD5 PCDH9 acky, B., et al„ 222898_s_at Cells Useful for Immuno-Based BoNT/A Activity Assays BE350882 NM_016941 10683 1.70 5.19E-07 213139_at AI572079 NM 203486 NM_003068 6591 1.70 2.74E-03 229655_at N66656 NM_015381 25817 1.70 4.35E-05 1553276 at NM_152476 NM 152476 147741 1.70 2.56E-04 219682_s_at NM_016569 NM_005996 6926 1.69 1.06E-06 232083_at AB046810 NM_016569 NM_024704 55614 1.69 8.35E-06 231916 at AF131796 — — 1.69 2.15E-03 229546 at AI378035 NM 145175 151354 1.69 2.85E-08 205238_at NM_024917 NM_024917 79979 1.68 6.46E-03 205629 s at BC002599 NM 000756 1392 1.68 5.48E-03 216321 s at X03348 NM_000176 2908 1.68 5.45E-07 224937 at BF311866 NM 020440 5738 1.67 6.89E-04 226322_at BF109231 NM_031920 83857 1.67 4.14E-03 243503 at AI632740 NM_175861 NM_022463 64359 1.67 2.57E-04 202695 s at NM 004760 NM_004760 9263 1.66 2.52E-03 205413_at NM 001584 NM 001584 744 1.66 1.85E-05 229947_at AI088609 NM_015886 51050 1.66 1.62E-04 209629_s_at AF201942 NM 018698 55916 1.65 3.43E-04 201853_s_at NM_021873 NM 004358 994 1.65 4.80E-05 204079_at NM_003595 NM_021872 NM_021873 NM 021874 NM 212530 NM_00100856 ft 8459 1.65 2.97E-04 235606_at AA417117 0 NM 003595 XM_298151 344595 1.64 2.58E-05 242530_at H22448 — — 1.64 2.20E-04 214720_x_at BF981643 NM_144710 151011 1.64 1.45E-04 214791_at AK023116 NM_178584 NM_138402 93349 1.64 9.50E-05 209690_s_at BF591163 NM 018110 55715 1.64 7.06E-06 47550 at N21184 NM 021020 11178 1.63 3.08E-04 225544_at Al806338 NM 005996 6926 1.63 5.24E-06 208782 at BC000055 NM_016569 NM_007085 11167 1.63 2.00E-03 228307_at AL137580 NM 052846 90187 1.63 2.86E-03 212135_s_at AW517686 NM 00100139 6 NM_001684 493 1.63 4.64E-03 1559444 at AL833029 1.63 2.28E-03 203243_s_at NM_006457 NM_00101151 O 10611 1.62 2.91 E-05 220260 at NM_018317 0 NM_00101151 4 NM 00101151 5 NM_00101151 6 NM_006457 NM_018317 55296 1.62 6.08E-05 206136_at NM_003468 NM 003468 7855 1.62 1.51E-03 219737_s_at AI524125 NM 020403 5101 1.62 3.72E-03 NM 203487

Patent Application DLL3 SNAI2 FAM19A5 ZNF560 TBX3 C20orf23 AF131796 NSE1 CXorf34

CRH NR3C1

PTGFRN ARG99

NXN STK17A C11orf8 P115 NXT2 CDC25B LOC344595 H22448 BF981643 LOC93349 DOK4 LZTS1 TBX3 FSTL1 EMILIN3 ATP2B4 145 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B„ et al„ Cells Useful for Immuno-Based BoNT/A Activity Assays PDLIM5 212412_at AV715767 NM 00101151 .3 NM_00101151 4 NM_00101151 5 NM_00101151 6 NM_006457 10611 1.61 7.77E-04 ZNF537 223393 s at AL136805 NM_020856 57616 1.61 2.15E-03 AW052186 239942_at AW052186 — — 1.61 5.57E-03 GPR51 209991_x_at AF069755 NM_005458 9568 1.60 1.65E-06 BF509125 232198_at BF509125 — — 1.60 4.75E-03 C14orf31 225464_at N30138 NM_152330 122786 1.60 3.92E-03 PARVA 217890_s_at NM_018222 NM_018222 55742 1.59 6.06E-03 CBLB 227900_at AV701750 NM 170662 868 1.59 2.60E-03 EB-1 227441_s_at AW005572 NM 020140 NM 152788 NM_181670 56899 1.59 2.08E-04 NAGA 1555041_a_at M29276 NM_000262 4668 1.59 2.23E-06 KIAA1713 233536_at AI202664 XM 290811 80816 1.59 9.66E-04 HOMERS 215489 x at AI871287 NM_004838 9454 1.58 2.88E-04 NFIB 233304_at AU145782 NM_005596 4781 1.58 6.95E-03 SOX5 238009_at AI446064 NM_006940 NM 152989 NM 178010 6660 1.58 9.49E-06 TCF7L2 216037_x_at AA664011 NM_030756 6934 1.57 2.43E-03 LOC152573 229485_x_at AI735586 XM_496688 152573 1.57 6.34E-05 DCBLD2 213865 at AI378788 NM 080927 131566 1.57 1.25E-04 NS5ATP13TP2 1558613 at BC040647 NM 178507 220323 1.56 8.59E-03 SAMHD1 204502_at NM 015474 N M 015474 25939 1.56 9.98E-05 N50083 229110_at N50083 — — 1.56 4.18E-04 LRRN3 209840 s at AI221950 NM 018334 54674 1.55 9.99E-07 CADPS 233950_at AK000873 NM_003716 NM 183393 NM_183394 8618 1.55 1.09E-04 ELL2 226982 at AI745624 NM 012081 22936 1 55 3.35E-03 HRH3 220447_at NM_007232 NM_007232 11255 1.54 6.15E-04 LRRN3 209841_s_at AL442092 NM_018334 54674 1.54 6.25E-07 PLK4 211088 s at Z25433 NM_014264 10733 1.53 1.15E-03 NOS1 239132 at BE299830 NM 000620 4842 1.53 1.65E-03 PLEKHF2 218640_s_at NM_024613 NM_024613 79666 1.53 1.36E-03 MGC72104 243689_s_at AI681945 NM_207350 284802 1.52 1.75E-04 NOS1 207309_at NM_000620 NM 000620 4842 1.52 2.45E-04 C1orf43 1555225_at BC008306 NM 015449 NM_138740 25912 1.52 2.71 E-03 GPR161 206972_s_at NM_007369 NM_007369 NM_153832 23432 1.52 4.09E-03 ODZ3 219523_s_at NM 018104 XM 371717 55714 1.51 2.29E-04 DOK4 209691 _s_at BC003541 NM_018110 55715 1.50 1.43E-04 TRIM68 219405_at NM_018073 NM 018073 55128 1.50 2.70E-05 DPYSL3 201431 s at NM 001387 NM 001387 1809 1.50 7.17E-03 RBL1 1559307_s_at BG387892 NM_002895 NM_183404 5933 1.50 2.2 7 E-03 MY06 210480_s_at U90236 NM 004999 4646 1.50 1.85E-05 SYNGR1 210613_s_at BC000731 NM 004711 NM_145731 NM 145738 9145 1.50 8.09E-03 146 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays CD01 204154_at NM 001801 NM 001801 1036 1.50 3.73E-04 NXT2 209628_at AK023289 NM 018698 55916 1.49 1.70E-03 AC01 207071_s_at NM_002197 NM 002197 48 1.49 5.20E-03 STOM 201060_x_at AI537887 NM 004099 NM_198194 2040 1.49 3.02E-04 ZNF503 227195_at AA603467 NM 032772 84858 1.49 8.67E-07 CBX5 242069_at BE568225 NM 012117 23468 1.48 3.23E-04 PPAP2B 212226_s_at AA628586 NM_003713 NM_177414 8613 1.48 2.29E-03 C20orf102 226973 at AA206763 NM 080607 128434 1.47 1.33E-04 CDKN2C 211792_s_at U17074 NM_001262 NM_078626 1031 1.47 7.95E-03 PDZRN3 212915_at AL569804 NM 015009 23024 1.47 5.49E-04 CRYGD 207532 at NM 006891 NM_006891 1421 1.46 3.28E-03 AW207243 238617_at AW207243 — ... 1.46 3.92E-09 EIF5A2 235296_at BG500474 NM 020390 56648 1.46 5.19E-09 ANKRD5 220144_s_at NM_022096 NM 022096 NM_198798 63926 1.45 8.13E-04 UNQ470 228403_at AL541276 NM_198573 375704 1.45 3.48E-03 KCNJ8 205303_at BF514158 NM 004982 3764 1.45 5.86E-05 ID1 208937_s_at D13889 NM 002165 NM_181353 3397 1.45 1.41E-04 SALL4 229661_at NM_020436 NM 020436 57167 1.44 2.91 E-05 DPYSL3 201430_s_at W72516 NM_001387 1809 1.44 2.58E-03 MSX2 210319 x at D89377 NM 002449 4488 1.44 1.48E-03 FNDC5 226096 at AI760132 NM 153756 252995 1.44 7.61 E-04 ZNF239 206261 _at NM_005674 NM 005674 8187 1.44 6.22 E-05 COBLL1 203642_s_at NM_014900 NM 014900 22837 1.44 6.55E-03 KIAA1524 1553810 a at NM 020890 NM 020890 57650 1 44 8.59E-03 AL038824 213676_at AL038824 XM_496810 441151 1.44 6.78E-04 ARL6 235320_at AL138043 NM_032146 NM_177976 84100 1.44 4.10E-07 MGC15937 227794_at BF432254 NM_080661 92292 1.43 3.16E-03 BE671123 235798_at BE671123 — ... 1.43 4.96E-06 ARL6 223735_at AL136815 NM 032146 NM_177976 84100 1.43 7.57E-05 LOC221810 221911_at BE881590 — 221810 1.43 2.72E-03 SEZ6L 207873_x_at NM_021115 NM_021115 23544 1.42 2.45E-05 DOK4 207747 s at NM_018110 NM 018110 55715 1.42 3.44E-05 SLC1A1 206396_at NM_004170 NM_004170 6505 1.42 4.65E-03 NSE1 225667 s at AI601101 NM 145175 151354 1.42 1.15E-03 ARHGAP24 230803_s_at AI761947 NMJ53 1 305 83478 1.42 3.92E-03 C6orf152 242006_at AI379143 NMJ81714 167691 1.42 6.09E-03 LOC132671 229331_at AI559300 NM 145263 132671 1.41 1 82E-03 TH 208291 _s_at NM_000360 NM 000360 NM_199292 NM 199293 7054 1.40 7.49E-04 RBL1 1555004_a_at BC032247 NM 002895 NM_183404 5933 1.40 5.16E-03 SFRP1 202037_s_at NM 003012 NM 003012 6422 1.40 5.74E-05 CTNNA1 1558214_s_at BG330076 NM 001903 1495 1.40 5.25E-07 CPU A 210688 s at BC000185 NM_001876 1374 1.40 1 43E-03 AI917901 243140_at AI917901 — — 1.40 1.50E-04 HES1 203394_s_at BE973687 NM 005524 3280 1.40 4.39E-06 GALNT7 222587_s_at BF699855 NM 017423 51809 1.40 1.79E-03 MGC33846 231430_at AW205640 NM 175885 220382 1.39 1.42E-03 SEZ6L 211894 x at AB041736 NM_021115 23544 1.39 9.95E-07 CHML 206079 at NM 001821 NM 001821 1122 1.39 8.74E-03 147 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B„ et al., Cells Useful for Immuno-Based BoNT/A Activity Assays EGLN3 222847_s_at Al378406 NM 022073 112399 1.39 3.90E-03 MDM1 213761_at AW664850 NM 017440 NM_020128 56890 1.38 1.18E-04 SFRP1 202035_s_at AI332407 NM 003012 6422 1.38 3.39E-03 CBLN1 205747 at NM_004352 NM 004352 869 1.38 1.13E-03 PDLIM5 211681_s_at AF116705 NM 00101151 3 NM_00101151 4 NM 00101151 5 NM_00101151 6 NM_006457 10611 1.38 1.41E-04 NQ01 21-0519_s_at BC000906 NM_000903 1728 1.38 4.39E-03 ST8SIA1 210073_at L32867 NM_003034 6489 1.38 9.29E-04 AL359594 1566867_at AL359594 — — 1.38 4.68E-03 DLEU2 216870 x at AF264787 NM 006021 8847 1.38 2.48E-04 BF966021 212698_s_at BF966021 NMJ44710 NM_178584 151011 1.37 4.75E-04 C14orf125 226510_at BF435286 XM 113763 XM 370759 25938 1.37 5.78E-03 TRIM37 1554001_at BC036012 NM_00100520 7 NM 015294 4591 1.37 1.10E-05 TLE3 228340_at BE967118 NM 005078 7090 1.36 2.10E-03 SFRP1 202036_s_at AFO17987 NM 003012 6422 1.36 1.13E-03 C5orf13 222344_at AW972765 NM 004772 9315 1.36 3.74E-03 SLC8A3 1562403_a_at AK096553 NM_033262 NM_058240 NM_182932 NM_182933 NM 182936 NM_183002 6547 1.36 1.60E-04 FGFR2 208234_x_at NM_022976 NM_000141 NM 022969 NM 022970 NM_022971 NM_022972 NM_022973 NM 022974 NM_022975 NM_022976 NM 023028 NM 023029 NM_023030 NM 023031 2263 1.36 2.95E-03 DLL3 219537_x_at NM_016941 NM_016941 NM_203486 10683 1.35 4.38E-05 CUGBP2 202156 s at N36839 NM 006561 10659 1.35 2.49E-03 APBB2 213419 at U62325 NM_173075 323 1.35 5.44E-04 DOCK10 219279 at NM 017718 NM 014689 55619 1.34 5.78E-05 MAPK12 206106_at AL022328 NM 002969 6300 1.34 2.33E-06 TLE3 212770_at AW873621 NM_005078 7090 1.34 8.20E-04 BE670307 227955_s_at BE670307 — ... 1.34 1.89E-05 148 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays HGF 210998_s_at M77227 NM_000601 NM 00101093 1 NM_00101093 2 NM 00101093 3 NM_00101093 A 3082 1.34 9.86E-03 FLJ11259 218627 at NM 018370 4 NM_018370 55332 1.33 4.22E-03 AI826125 229866 at AI826125 — — 1.33 4.02E-04 SEZ6L 240709_at AW204757 NM021115 23544 1.33 5.75E-03 RAB27B 228708_at BF438386 NM_004163 5874 1.33 9.45E-03 MAP3K1 225927 at AA541479 XM_042066 4214 1.33 1 90E-03 AL040051 225481 at AL040051 — — 1.33 5.84E-04 BE967311 226225_at BE967311 — — 1.32 2.96E-05 TLE4 204872_at NM 007005 NM_007005 7091 1.32 4.50E-03 SNCAIP 219511 s at NM_005460 NM 005460 9627 1.32 3.58E-04 KIAA0376 212480_at AB002374 NM_015330 23384 1.32 2.79E-05 LZTS1 219042_at NM_021020 NM 021020 11178 1.32 3.07E-04 KIAA0318 238817_at BF063412 NM 015347 23504 1.32 5.00E-04 RNF34 219035_s_at NM_025126 NM_025126 NM_194271 80196 1.32 1.40E-03 STXBP4 244404_at AI376134 NM_178509 252983 1.31 3.35E-05 AU144956 232501_at AU144956 — — 1.31 6.46E-06 FLJ11127 219694 at NM 019018 NM 019018 54491 1.31 1.32E-03 MITF 226066_at AL117653 NM_000248 NM_006722 NM 198158 NM_198159 NMJ98177 NM_198178 4286 1.31 1.07E-03 ETS1 224833 at BE218980 NM 005238 2113 1.31 2.75E-03 NANOS1 228523_at AW970089 NM 00100955 3 NM_199461 340719 1.31 1.30E-03 FAM19A5 237094 at AI953086 NM 015381 25817 1.31 2.32E-07 LBH 221011 s at NM 030915 NM 030915 81606 1.31 1.22E-04 PEX26 219180_s_at AI817074 NM 017929 55670 1.30 3.74E-03 GALNT7 218313_s_at NM 017423 NM_017423 51809 1.30 1.80E-04 C2orf23 204365_s_at NM_022912 NM_022912 65055 1.30 5.58E-03 AL049709 216548 x at AL049709 — — 1.30 5.30E-04 MGC34032 1552782_at AK091400 NM 152697 204962 1.30 1.97E-03 DLL1 224215_s_at AF196571 NM_005618 28514 1.30 1.62E-04 TMEM20 236219 at AI452512 NM_153226 159371 1.30 3.29E-03 AW305300 238962 at AW305300 — — 1.30 4.31 E-04 C20orf23 219570_at NM_024704 NM 024704 55614 1.29 1.18E-03 DRIM 209725 at AF072718 NM_014503 27340 1.29 1.99E-03 CBLB 209682_at U26710 NM 170662 868 1.29 3.69E-03 STRA6 1569335_a_at BC015881 NM_022369 64220 1.29 9.19E-04 CRTAC1 221204_s_at NM_018058 NM_018058 55118 1.28 5.56 E-04 AF070602 216214_at AF070602 — — 1.28 5.02E-03 NAGA 202943 s at M38083 NM_000262 4668 1.28 1.26E-03 AK025909 233814_at AK025909 — — 1.27 1.16E-04 AI141426 229898_at AI141426 — — 1.27 6.87E-05 SLC8A1 241752_at AA094434 NM_021097 6546 1.27 6.10E-04 149 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays INSIG1 201625_s_at BE300521 NM 005542 NM_198336 NM_198337 3638 1.26 8.33E-03 IQGAP1 210840_s_at D29640 NM_003870 8826 1.26 2.60E-04 GAP43 204471 at NM 002045 NM 002045 2596 1.26 5.02E-04 PDLIM5 213684_s_at BF671400 NM 00101151 3 NM_00101151 4 NM 00101151 5 NM 00101151 6 NM 006457 10611 1.26 9.47E-04 GAP43 216963_s_at AF279774 NM 002045 2596 1.26 5.66E-03 KLHL5 226001_at AK002174 NM_00100707 5 NM 199039 51088 1.26 3.67E-04 RGS4 204339_s_at BC000737 NM 005613 5999 1.25 4.16E-04 AF279774 216967_at AF279774 — — 1.25 9.39E-03 PTER 218967_s_at NM_030664 NM_00100148 4 NM_030664 9317 1 25 1.22E-03 TLE3 212769_at AI567426 NM 005078 7090 1.25 3.78E-03 TLE3 206472_s_at NM_005078 NM 005078 7090 1.25 4.37E-03 RGS4 204338_s_at NM_005613 NM_005613 5999 1.25 3.77E-04 CPT1A 203634_s_at NM_001876 NM_001876' 1374 1.25 1.93E-03 ASAHL 227135_at AI436803 NM_014435 27163 1.25 9.20E-06 LOC344595 239466_at AA463827 XM 298151 344595 1.25 4.65E-05 TH1L 225006_x_at AJ238379 NM_016397 NM_198976 51497 1.24 9.26E-03 SEZ6L 216047_x_at AL050253 NM_021115 23544 1.24 1.75E-05 NSE1 234331 s at AK025063 NM 145175 151354 1.24 1.19E-04 LRRIQ2 219886_at NM_024548 NM 024548 79598 1.24 1.44E-03 GALNT10 207357_s_at NM_017540 NM 017540 NM_198321 55568 1.24 2.18E-03 BF815640 238517 at BF815640 — — 1.23 4.48E-03 SLC30A9 229500_at AI609256 NM_006345 10463 1.23 2.32E-03 LOC63929 227910_at AI635379 NM 022098 63929 1.23 1.48E-04 CSE1L 210765_at AF053640 NM 001316 NM 177436 1434 1.23 7.45E-03 BCL2L11 1558143_a_at AK027160 NM_006538 NM_138621 NM 138622 NM_138623 NM_138624 NM_138625 NM 138626 NM_138627 NM 207002 NM 207003 10018 1.23 6.27E-03 TM4SF14 221002 s at NM 030927 NM 030927 81619 1.22 4.04E-03 SLIT3 203813_s_at NM_003062 NM_003062 6586 1.22 1.58E-06 RAPGEF5 204681_s_at NM 012294 XM_499059 9771 1.22 6.58E-04 ZNF184 213452_at AI811577 NM_007149 7738 1.22 9.16E-03 PCYT2 209577_at BC000351 NM 002861 5833 1.22 2.05E-03 WDR51A 234749_s_at AL117629 NM_015426 25886 1.22 2.87E-03 MAN2A1 226538_at AV700323 NM_002372 4124 1.21 3.05E-03 150 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B„ et al., Cells Useful for Immuno-Based BoNT/A Activity Assays TLE4 233575_s_at AA705845 NM_007005 7091 1.21 2.34E-04 AW665447 230113_at AW665447 — — 1.21 3.86E-03 SAP30 204899_s_at BF247098 NM_003864 8819 1.21 2.33E-03 LOC221810 221910_at BF131965 — 221810 1.21 8.18E-03 HOMER3 204647 at NM 004838 NM_004838 9454 1.20 4.61 E-03 SLC1A1 213664_at AW235061 NM 004170 6505 1.20 5.98E-03 C20orf108 224690_at BG432350 NM_080821 116151 1.20 8.73E-03 ZNF238 207164_s_at NM_006352 NM 006352 NM_205768 10472 1.20 7.96E-03 PIR 207469 s_at NM 003662 NM 003662 8544 1.20 1.53E-05 FLRT3 219250_s_at NM_013281 NM_013281 NM_198391 23767 1.19 7.10E-04 SLIT3 203812_at ABO11538 NM 003062 6586 1.19 1.40E-03 TGIF 203313_s_at NM_003244 NM_003244 NM_170695 NM_173207 NM 173208 NM 173209 NM 173210 NM_173211 NM 174886 7050 1.19 5.40E-05 CDKN2C 204159_at NM_001262 NM_001262 NM 078626 1031 1.19 8.59E-05 MTUS1 212095_s_at BE552421 NM_00100192 4 NM_00100192 5 NM_00100192 7 NM_00100193 1 NM 020749 57509 1.19 2.48E-04 SCARA3 223842_s_at AB007830 NM 016240 NM_182826 51435 1.19 3.33E-04 HTATSF1 202602_s_at NM 014500 NM_014500 27336 1.19 2.42E-05 TRAM2 202369 s at NM_012288 NM 012288 9697 1.18 7.27E-03 PTGFRN 224950_at BF476250 NM 020440 5738 1.18 2.73E-03 DRD2 216938_x_at S69899 NM_000795 NM_016574 1813 1.18 2.02E-03 TOP3B 215781_s_at D87012 NM 003935 8940 1.18 2.21 E-03 ACY1L2 225421 at Al654133 NM_001010853 135293 1.18 7.34E-04 BC025350 1569418_at BC025350 — ... 1.18 1.04E-06 KIAA1706 225630_at AB051493 NM_030636 80820 1.18 1.55E-04 AW874669 239834 at AW874669 — — 1.18 7.57E-04 CPT1A 203633_at BF001714 NM 001876 1374 1.17 1.23E-03 C2orf23 204364_s_at BE535746 NM 022912 65055 1.17 2.59E-04 SMO 218629_at NM_005631 NM_005631 6608 1.17 3.37E-05 RPH3A 205230_at NM 014954 NM 014954 22895 1.17 6.35E-03 VIL2 208621_s_at BF663141 NM 003379 7430 1.17 8.04E-04 SEC15L2 225900_at AW294630 XM 039570 23233 1.17 7.12E-03 MCC 206132_at NM 002387 NM 002387 4163 1.17 5.91 E-04 C20orf108 224693 at Al 133137 NM 080821 116151 1.16 2.04E-05 RFC5 203209_at BC001866 NM_007370 NM 181578 5985 1.16 9.74E-03 MAPK11 211499_s_at U92268 NM_002751 MM -1-3000-3 5600 1.16 3.08E-04 NM 138993 151 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays EB-1 227439_at Al806510 NM 020140 NM_152788 NM_181670 56899 1.16 9.25E-08 FBXL7 213249_at AU145127 NM 012304 23194 1.16 5.25E-07 TTC9 213172 at AW235608 XM 027236 23508 1.16 7.95E-04 SLC40A1 223044 at AL136944 NM_014585 30061 1.16 6.08E-04 AI452715 229817_at AI452715 — -. 1.16 3.41E-03 MAN2A1 235103_at AA029155 NM 002372 4124 1.16 5.37E-04 VIL2 217234 s at AF199015 NM 003379 7430 1.16 3.24E-03 SEZ6L 213609_s_at AB023144 NM_021115 23544 1.15 2.65E-06 TLX2 207410_s_at NM016170 NM_001534 NM_016170 3196 1.15 3.55E-05 CGI-96 202937_x_at AL022316 NM 015703 27341 1.15 2.55E-03 KCNJ8 205304_s_at NM_004982 NM_004982 3764 1.14 5.54E-03 ZNF537 223392_s_at BF510588 NM_020856 57616 1.14 9.47E-06 DHX35 234728_s_at AL023803 NM_021931 60625 1.14 6.62E-06 STRA6 1569334 at BC015881 NM 022369 64220 1.14 5.40E-03 EAF2 219551_at NM_018456 NM_018456 55840 1.14 9.77E-04 ITPR1 203710_at NM_002222 NM 002222 3708 1.14 1.07E-03 LIFR 225575_at AI680541 NM_002310 3977 1.13 4.19E-06 GJA7 208460 at NM 005497 NM 005497 10052 1.13 4.63E-03 MBD2 214397_at Al 827820 NM_003927 NM_015832 8932 1.13 1.61 E-03 ANKRD13 224810_s_at AL569476 NM 033121 88455 1.13 2.65E-04 HD AC 8 223908_at AF212246 NM 018486 55869 1.13 1.96E-04 STN2 227461_at AA632295 NM_033104 85439 1.12 4.18E-03 BE464799 214036_at BE464799 — — 1.12 1.37E-04 SOX2 228038_at AI669815 NM 003106 6657 1.12 1.75E-04 GTF2E1 205930_at NM 005513 NM_005513 2960 1.12 1.67E-03 H10661 242317_at H10661 — ... 1.12 3.16E-04 HSZFP36 229732_at AI417785 XM 375568 55552 1.12 2.16E-03 RBBP9 221440_s_at NM_006606 NM 006606 NM 153328 10741 1.12 9.04E-04 DNAJB6 209015_s_at BC002446 NM_005494 NM_058246 10049 1.12 2.51 E-03 KNTC1 206316 s at NM 014708 NM 014708 9735 1.12 7.31 E-03 FUT11 238551_at BF541967 NM 173540 170384 1.12 1.14E-03 MAP2K6 205698_s_at NM_002758 NM_002758 NM_031988 5608 1.11 8.00E-03 NRM 225592 at D81048 NM 007243 11270 1.11 8.62 E-03 STMN3 222557 at AL353715 NM 015894 50861 1.11 1.13E-03 INSIG1 201626_at BG292233 NM_005542 NM_198336 NM 198337 3638 1.11 1.4 7 E-03 SH3MD2 225589_at AB040927 NM_020870 57630 1.11 3.78E-04 BCL2L11 225606_at Al949179 NM_006538 NM 138621 NM 138622 NM_138623 NM_138624 NM 138625 NM 138626 NM_138627 NM_207002 NM 207003 10018 1.11 4.77E-07 TYR03 211432_s_at U05682 NM_006293 7301 1.11 7.76E-03 152 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays APAF1 204859_s_at NM_013229 NM 001160 NM_013229 NM_181861 NM_181868 NM 181869 317 1.11 8.54E-03 LRRC1 218816_at NM_018214 NM_018214 NM_025168 55227 1.11 4.89E-03 DNM3 209839_at AL136712 NM 015569 26052 1.11 5.67E-06 MAN2A1 205105 at NM_002372 NM 002372 4124 1.11 6.81 E-03 FLJ23322 220707_s_at NM_024955 NM_024955 80020 1.10 2.15E-03 NDRG2 214279_s_at W74452 NM_016250 NM_201535 NM 201536 NM_201537 NM_201538 NM 201539 NM 201540 NM_201541 57447 1.10 5.44E-03 SCAM-1 207788 s at NM 005775 NM 005775 10174 1.10 9.08E-03 LM01 206718_at NM 002315 NM 002315 4004 1.10 5.27E-04 ITPR1 216944_s_at U23850 NM 002222 3708 1.10 8.15E-03 PCNXL2 39650_s_at AB007895 NM_014801 NM_024938 80003 1.10 9.56E-05 RBBP9 232751_at AL121893 NM 006606 NM 153328 10741 1.10 8.94E-04 AP3B1 203142_s_at NM 003664 NM_003664 8546 1.09 2.19E-03 SNAP29 222597_at AI346639 NM 004782 9342 1.09 1.46E-04 C20orf161 1553960_at CA447177 NM 033421 NM_152897 90203 1.09 2.01 E-03 LOC283464 232021_at Al864273 XM_290597 283464 1.09 1.32 E-03 AI589594 238694_at AI589594 — — 1.09 2.79E-05 SOX2 213721 at L07335 NM 003106 6657 1.08 7.40E-04 ST3GAL6 210942 s at AB022918 NM_006100 10402 1.08 2.47E-04 BG231758 227615_at BG231758 — — 1.08 5.95E-08 FLJ33814 225644_at BF060776 NM_173510 150275 1.08 2.63E-06 TYMS 1554696 s at AB077208 NM 001071 7298 1.08 7.83E-03 BOK 223349 s at BE614255 NM_032515 666 1.08 3.19E-06 C1QL1 205575_at NM_006688 NM 006688 10882 1.08 1.06E-04 GMPS 236648_at AI684467 NM_003875 8833 1.08 6.96E-04 AI733583 243235 at AI733583 — — 1.08 6.94E-03 BE066500 239729_at BE066500 — — 1.08 8.69E-04 ASAHL 232072 at AK025371 NM 014435 27163 1.08 3.73E-04 SNX5 229981_at AA131508 NM_014426 NM_152227 27131 1.08 1.66E-05 CYBA 203028_s_at NM_000101 NM_000101 1535 1.07 5.76E-04 PTER 222798_at BF112019 NM_00100148 4 NM 030664 9317 1.07 2.48E-03 LOC440820 226602_s_at T30183 XM_496519 440820 1.07 2.20E-05 AA214369 238545_at AA214369 — — 1.07 3.48E-03 ELAVL4 241424 at BF111117 NM_021952 1996 1.07 4.96E-03 C6orf189 228875 at Al540210 — 221303 1.07 1.85E-04 PARG1 203910_at NM 004815 NM_004815 9411 1.07 1.74E-04 OLFML3 218162_at NM_020190 NM_020190 56944 1.07 4.22E-03 PI4K2B 222631 at Al862887 NM 018323 55300 1.07 2.03E-03 PHYHIPL 226623 at AI829726 NM_032439 84457 1.07 5.85E-05 AA156933 236141_at AA156933 — — 1.07 9.86E-04 AI346432 229132 at Al346432 — — 1.07 3.94E-04 153 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays AI919519 235092 at AI919519 — — 1.07 8.75E-03 ELK3 221773 at AW575374 NM 005230 2004 1.07 2.45E-03 LPPR4 213496_at AW592563 NM_014839 9890 1.07 1.23E-05 EZH2 203358_s_at NM_004456 NM_004456 NM_152998 2146 1.06 5.13E-03 NS5ATP13TP2 225510 at BG033561 NM 178507 220323 1.06 1 40E-04 KIAA1102 212325_at AK027231 NM_014988 22998 1.06 1.82E-09 ZNF505 208119_s_at NM_031218 NM 00100412 6 NM 031218 81931 1.06 5.75E-03 C20orf40 231200_at BG222606 NM_144703 149986 1.06 1.73E-03 SLC8A1 238546_at BF344961 NM_021097 6546 1.06 6.63E-03 PREX1 224909 s at BF308645 NM_020820 57580 1.06 7.16E-03 MAK3 222393_s_at AU149868 NM 025146 80218 1.06 1.11E-05 TMPO 209753_s_at BG391171 NM_003276 7112 1.06 3.02E-03 AD OR A2A 205013_s_at NM_000675 NM 000675 135 1.06 9.97E-03 MGC3040 223523 at BC000568 NM_023943 66000 1.06 7.88E-07 AI700633 212812 at AI700633 — — 1.06 8.55E-03 TWSG1 219201 s at NM_020648 NM_020648 57045 1.06 9.70E-04 PPP3CB 209817_at M29550 NM_021132 5532 1.06 2.71 E-06 MAP3K13 206249 at NM_004721 NM 004721 9175 1.06 3.52E-03 SKP2 210567_s_at BC001441 NM 005983 NM 032637 6502 1.06 8.10E-04 SYN2 210315_at AF077737 NM_003178 NM_133625 6854 1.05 9.08E-03 CGI-96 33307 at AL022316 NM 015703 27341 1.05 7.16E-04 GNG12 1555240_s_at AF493879 N M 018841 55970 1.05 6.35E-04 CUTL2 213920_at AB006631 NM 015267 23316 1.04 1.63E-03 FLRT3 222853_at N71923 NM_013281 NM 198391 23767 1.04 9.61 E-07 FLJ13842 219877_at NM_024645 NM 024645 79698 1.04 6.38E-03 ADRBK2 228771_at AI651212 NM_005160 157 1.04 7.18E-05 SEC61A2 228747 at AI694646 NM 018144 55176 1.04 4.56E-03 ST3GAL6 213355_at AI989567 NM_006100 10402 1.04 1 38E-04 BF434228 235850_at BF434228 — — 1.04 4.97E-03 PCGF5 227935 s at AA522681 NM_032373 84333 1.04 8.11E-04 MYST1 214885 at AL050395 NM 032188 84148 1.04 5.82E-03 PEX13 1558163_at BC040953 NM_002618 5194 1.03 3.87E-03 INSIG1 201627_s_at NM_005542 NM 005542 NM_198336 NM 198337 3638 1.03 2.57E-06 NELL2 203413_at NM_006159 NMJ306159 4753 1.03 1.75E-03 RND3 212724_at BG054844 NM_005168 390 1.03 1.50E-03 TFDP2 203588 s at BG034328 NM_006286 7029 1.03 9.43E-03 CTNNBL1 221021_s_at NM_030877 NM 030877 56259 1.03 3.20E-03 CHML 1565951 s at AJ293392 NM_001821 1122 1.03 8.52E-03 ITPR1 211323_s_at L38019 NM_002222 3708 1.02 3.21 E-05 3KFZP564012' 202536 at AK002165 NM 014043 25978 1.02 9.94E-05 CKLF 219161 _s_at NM_016951 NM 016326 NM_016951 NM 181640 NM 181641 51192 1.02 8.63E-03 IQGAP1 213446_s_at AI679073 NM 003870 8826 1.02 1.01 E-03 C11orf8 215692_s_at BE645386 NM_001584 744 1.02 1.49E-03 AL559474 235918 x at AL559474 — — 1.02 2.13E-03 ADRBK2 204184_s_at NM 005160 NM 005160 157 1.02 3.30E-04 LOC152185 234995_at AA668779 NM_144718 152185 1.02 9.02E-04 154 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451

Jacky, B., et al., Cells Useful for I XRCC4 205071_x_at ABO17445 NM_003401 NM_022406 NM_022550 7518 1.02 3.71 E-03 GPR125 210473_s_at M37712 NM 145290 166647 1.01 1.54E-08 SLC03A1 219229_at NM_013272 NM_013272 28232 1.01 7.19E-04 POLE 216026 s at AL080203 NM_006231 5426 1.01 8.50E-03 TMOD3 223078_s_at AF177171 NM 014547 29766 1.01 2.98E-05 SKP2 203626_s_at NM_005983 NM 005983 NM_032637 6502 1.01 9.59E-08 RBPMS 207836_s_at NM_006867 NM_00100871 11030 1.00 5.05E-03 NM

NM 00100871 1 00100871 2 PHTF2 217097 s at AC004990 NM 006867 NM_020432 57157 1.00 4.53E-03 TM4SF14 223314 at BF025955 NM_030927 81619 1.00 2.72E-03 SDC2 212157_at BE048514 NM_002998 6383 1.00 6.35E-03 TP53I3 210609_s_at BC000474 NM_004881 9540 1.00 8.78E-04 AL049385 232297 at AL049385 NM_147184 1.00 1.36E-05 MTUS1 212096_s_at AL096842 NM_00100192 57509 1.00 1.43E-04 NM

NM 4 .00100192 5 .00100192 7 .00100193 1 NM KLF7 1555420_a_at BC012919 NM 020749 NM_003709 8609 1.00 1.21E-04 ZNF555 1556187 at AF052118 NM_152791 148254 0.99 7.62E-03 GPAM 225424 at AB046780 NM 020918 57678 0.99 5.06E-03 FLJ13273 1554518_at BC032942 NM_024751 79807 0.99 2.86E-04 SAP30 204900_x_at NM_003864 NM_003864 8819 0.99 3.10E-03 FBXL10 229855_at AA779208 NM_00100536 84678 0.99 1.80E-03 NEUROD4 221318 at NM_021191 D NM_032590 NM_021191 58158 0.99 2.89E-03 FLJ12649 219626 at NM 024597 XM_291344 79649 0.99 9.37E-05 TMPO 209754_s_at AF113682 NM 003276 7112 0.99 6.52E-03 RASL11B 219142_at NM_023940 NM 023940 65997 0.99 4.29E-03 ASAHL 214765 s at AK024677 NM 014435 27163 0.98 1.03E-05 ZNF238 212774_at AJ223321 NM_006352 10472 0.98 6.70E-05 ITPR2 202662 s at NM 002223 NM_205768 NM_002223 3709 0.98 8.48E-03 SEZ6L 231650 s at BE672217 NM_021115 23544 0.98 1.12E-04 C10orf47 229801 at AI640157 NM_153256 254427 0.98 7.31 E-03 SNAG1 226683_at AU146771 NM_052870 112574 0.98 1.70E-04 FGF11 227271 _at AU151265 NM_004112 2256 0.98 9.49E-03 DDT 202929 s at NM_001355 NM_001355 1652 0.98 3.16E-04 KLHL5 233866_at AK001836 NM_00100707 C 51088 0.97 7.05E-03 PVRL3 241970_at C14898 0 NM_199039 NM_015480 25945 0.97 5.02E-03 SEMA5A 205405_at NM 003966 NM 003966 9037 0.97 2.27E-03 RFC1 209085_x_at L14922 NM 002913 5981 0.97 6.24E-03 155 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays TRIM36 219736 at NM 018700 NM 018700 55521 0.97 4.06E-03 FLJ23322 231846 at AK026975 NM_024955 80020 0.97 3.27E-03 IMP-1 223689_at AF198254 NM 006546 10642 0.97 1.78E-04 MDFI 205375 at NM_005586 NM_005586 4188 0.97 7.23E-03 BE878277 212829 at BE878277 — — 0.97 1.51E-04 FLJ14451 227430 at AI969773 NM_032786 84872 0.97 8.15E-03 NARG1 226998_at AL556909 NM_057175 80155 0.96 1.89E-06 TMEM38B 222736_s_at BC000049 NM 018112 55151 0.96 3.02E-05 LAMP2 203041_s_at J04183 NM 002294 NM_013995 3920 0.96 1.13E-04 FANCL 218397_at NM 018062 N M 018062 55120 0.96 3.05E-03 APOBEC3G 204205_at NM_021822 NM_021822 60489 0.96 7.76E-03 NM 024853 220533_at NM 024853 — — 0.96 3.50E-03 UNG 202330_s_at NM_003362 NM_003362 NM_080911 7374 0.96 2.31 E-03 ACTL6A 202666_s_at NM_004301 NM 004301 NM 177989 NM_178042 86 0.96 1.28E-03 N71074 238078_at N71074 — ... 0.96 7.93E-04 FLJ40432 228810_at AW135279 NM 152523 151195 0.96 4.18E-06 KIAA1102 212327 at AK026815 NM 014988 22998 0.96 1.66E-05 C12orf2 225946_at BG484552 NM_007211 11228 0.96 4.33E-06 FLJ11539 219791_s_at NM_024748 XM_496724 79804 0.96 4.56E-04 MNS1 219703_at NM_018365 NM 018365 55329 0.96 6.11E-04 SLC8A1 235518 at Al 741439 NM 021097 6546 0.95 4.16E-03 PSMD9 209334_s_at BC002383 NM_002813 5715 0.95 5.08E-06 ACY1L2 225431_x_at BE779764 NM 001010853 135293 0.95 7.73E-04 SOD2 215223_s_at W46388 NM 000636 6648 0.95 3.07E-03 PPP1R3D 204554_at AL109928 NM_006242 5509 0.95 2.56E-03 BF056892 229024_at BF056892 — ... 0.95 1.67E-04 CHD6 225031 at AL031667 NM_032221 84181 0.95 4.37E-05 MGC7036 227983 at AI810244 NM 145058 196383 0.95 2.13E-04 CCBE1 243805 at BG035826 NM_133459 147372 0.95 1.68E-03 AL110237 232959_at AL110237 ... ... 0.95 9.01 E-04 LOC134111 226612_at H17038 XM_059689 134111 0.94 3.88E-03 ELAVL4 234904_x_at S73887 NM 021952 1996 0.94 1.21 E-04 PANK2 238856_s_at BG108346 NM_024960 NM_153637 NM 153638 NM 153639 NM_153640 NM_153641 80025 0.94 3.01 E-05 CBX5 230752_at AI638063 NM_012117 23468 0.94 6.48E-04 NDUFA6 202000_at BC002772 NM 002490 4700 0.94 5.54 E-04 HSPC117 200042_at NM_014306 NM_014306 51493 0.94 6.59E-07 TLE4 235765_at AI742932 NM_007005 7091 0.94 9.75E-04 SDC4 202071_at NM_002999 NM 002999 6385 0.94 8.2 4 E-05 CD47 211075_s_at Z25521 NM 001777 NM_198793 961 0.94 1.46E-03 EGFR 224999_at BE878463 NM_005228 NM 201282 NM 201283 NM 201284 1956 0.93 4.74E-03 TLX2 211049_at BC006356 NM_001534 NM_016170 3196 0.93 6.56E-04 VIL2 208622_s_at AA670344 NM 003379 7430 0.93 3.33E-03 JPH1 1553533_at NM 020647 NM_020647 56704 0.93 2.57E-03 TEAD3 209454_s_at AF142482 NM_003214 7005 0.93 5.72 E-03 156 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 FKBP5 Jacky, B., etal., 204560_at Cells Useful for Immuno-Based BoNT/A Activity Assays NM 004117 NM_004117 2289 0.93 2.37E-03 SEC61A2 219499_at NM_018144 NM_018144 55176 0.93 9.99E-03 PGM2 225366_at Al652855 NM 018290 55276 0.93 6.09E-04 P4HA1 207543_s_at NM 000917 NM 000917 5033 0.93 2.61 E-04 SEC23A 204344_s_at NM 006364 NM 006364 10484 0.93 3.24E-03 KIAA1102 212328_at AB029025 NM 014988 22998 0.93 1.29E-05 RANBP1 202483_s_at NM_002882 NM_002882 5902 0.93 7.82E-03 STARD4 226390_at AA628398 NM 139164 134429 0.93 1.59E-04 B4GALT8 206232 s at NM 004775 NM 004775 9331 0.93 2.63E-03 AHI1 220842_at NM_017651 NM_017651 54806 0.92 6.04E-03 MCM4 212142_at Al 936566 NM_005914 4173 0.92 7.62 E-04 CHD6 225026 at BF572029 NM 182746 NM 032221 84181 0.92 3.17E-03 HMGB2 208808_s_at BC000903 NM 002129 3148 0.92 7.83E-03 DNMT3B 220668_s_at NM_006892 NM_006892 1789 0.92 2.56E-03 AI095542 235759_at Al095542 NM 175848 NM_175849 NM_175850 0.92 4.36E-03 SLC25A1 210010 s at U25147 NM 005984 6576 0.92 2.10E-03 ELAVL4 238073 at R55745 NM_021952 1996 0.92 1.01E-03 BG149337 229814_at BG149337 — — 0.92 2.56E-03 R43103 243642_x_at R43103 — ... 0.92 3.67E-03 NEDD1 1552417_a_at NM_152905 NM 152905 121441 0.91 2.33E-03 MTUS1 212093_s_at AI695017 NM_00100192 A 57509 0.91 4.60 E-04 ALG10 1552306_at BC033730 NM 00100192 5 NM_00100192 7 NM_00100193 1 NM_020749 NM_032834 84920 0.91 7.39E-04 ELAVL4 206051_at NM 021952 NM 021952 1996 0.91 1.99E-03 MLF1 204783 at AI911434 NM 022443 4291 0.91 1.31 E-04 SLC2A8 218985_at NM 014580 NM_014580 29988 0.91 6.78E-03 ITPR2 202660_at AA834576 NM 002223 3709 0.91 9.15E-03 CISH 223377_x_at AF035947 NM 013324 1154 0.91 4.28E-03 C3orf4 1554149_at BC013610 NM 145071 NM 019895 56650 0.91 2.11E-05 LOC134111 226618_at AW572911 XM_059689 134111 0.91 5.63E-04 BE857972 243781_at BE857972 — — 0.91 1.20E-03 Cep70 224150 s at AF289495 NM 024491 80321 0.91 4.27E-03 PP2447 232706_s_at AW009248 NM 025204 80305 0.90 4.10E-03 RGS4 204337_at AL514445 NM 005613 5999 0.90 1.42E-03 KLF7 204334 at AA488672 NM 003709 8609 0.90 9.17E-04 SLC03A1 227367_at AW976431 NM_013272 28232 0.90 4.34E-03 FZD2 210220_at L37882 NM 001466 2535 0.90 2.77E-04 SESTD1 226763_at AW409611 NM 178123 91404 0.90 9.00E-04 DHX35 218579 s at NM 021931 NM 021931 60625 0.90 2.42E-05 PDLIM1 208690 s at BC000915 NM_020992 9124 0.90 6.24E-04 BICD1 1554020_at BC010091 NM 00100339 8 NM 001714 NM_018663 636 0.90 3.41 E-06 PXMP2 219076_s_at NM_018663 5827 0.90 6.61 E-03 SPOCK 202363_at AF231124 NM_004598 6695 0.90 5.89E-03 AA581439 244650 at AA581439 — — 0.89 5.83E-03 157 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., etal., Cells Useful for Immuno-Based BoNT/A Activity Assays BC003667 222487 s at BC003667 — — 0.89 8.10E-03 NFYB 218128 at AU151875 NM 006166 4801 0.89 2.19E-03 SYNJ2 212828_at AA191573 NM_003898 8871 0.89 6.92E-03 ITGB5 201124_at AL048423 NM_002213 3693 0.89 4.74E-03 SLC39A8 219869 s at NM_022154 NM_022154 64116 0.89 1.30E-03 AI333006 240432 x at Al 333006 — ... 0.89 2.24E-03 BRD4 202103_at Al 991631 NM_014299 NM_058243 23476 0.89 3.39E-03 MCM8 233560_x_at AA370141 NM 032485 NM 182802 84515 0.89 2.33E-03 PKIA 226864_at BF245954 NM 006823 NM_181839 5569 0.89 4.86E-04 FAM43A 227410_at AW264102 NM 153690 131583 0.89 4.81 E-03 ZMYM1 220206 at NM 024772 NM 024772 79830 0.89 5.27E-03 SLK 206875_s_at NM 014720 NM 014720 9748 0.89 9.22E-06 EPB41L5 225855_at AB046768 NM 020909 57669 0.89 8.39E-04 RAD18 223417_at AF169796 NM 020165 56852 0.89 2.04E-04 MEIS2 207480_s_at NM_020149 NM_002399 NM_020149 NM 170674 NM 170675 NM_170676 NM_170677 NMJ72315 NM 172316 4212 0.89 4.23E-04 NFYA 204107_at BF445142 NM_002505 NM_021705 4800 0.88 3.28E-06 SREBF2 201248_s_at NM_004599 NM_004599 6721 0.88 4.75E-03 FLJ31842 237515_at AA054642 NM_152487 148534 0.88 8.21 E-04 ZFD25 205739_x_at NM_016220 ... 51427 0.88 8.79E-03 DLEU2 215629_s_at AA905286 NM_006021 8847 0.88 6.43E-04 ZNF85 206572 x at NM 003429 NM 003429 7639 0.88 6.85E-06 PCDH17 228863_at N69091 NM 014459 27253 0.88 6.70E-03 PTPRG 204944_at NM 002841 NM 002841 5793 0.88 3.65E-03 AL833487 1562245_a_at AL833487 — — 0.88 8.59E-03 PCDH17 205656_at NM 014459 NM 014459 27253 0.88 6.19E-03 ANAPC7 225554_s_at AA131793 NM_016238 51434 0.88 8.37E-04 BE504215 228563_at BE504215 — — 0.88 1.17E-03 MLLT3 204917_s_at AV756536 NM 004529 4300 0.88 5.47E-03 CD47 213857_s_at BG230614 NM 001777 NM_198793 961 0.88 3.54 E-04 PTK7 1555324_at BC046109 NM_002821 NM_152880 NM 152881 NM_152882 NM_152883 5754 0.87 3.45 E-03 EP300 1562921 at BC040700 NM 001429 2033 0.87 3.55E-03 VPS29 223026_s_at AF201946 NM 016226 NM_057180 51699 0.87 9.51 E-03 EBF 227646_at BG435302 NM_024007 1879 0.87 6.32E-04 GPC6 223730_at AF111178 NM_005708 10082 0.87 7.72E-03 PHF5A 225309 at AL008582 NM 032758 84844 0.87 1.93E-03 FLJ31842 234980_at Al 004375 NM_152487 148534 0.87 3.12E-04 AW953794 230968 at AW953794 — — 0.87 3.09E-03 AI888657 244189 at Al 888657 — — 0.87 1.23E-03 FLJ21415 218867_s_at NM 024738 NM 024738 79794 0.87 2.65E-03 MAK3 217745_s_at NM_025146 NM_025146 80218 0.87 5.22E-04 SEC23A 212887 at Al 753659 NM_006364 10484 0.86 6.69E-03 158 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays PAX5 221969 at BF510692 NM 016734 5079 0.86 4.37E-03 UNC84B 212144_at AL021707 NM_015374 25777 0.86 9.44E-03 PRIM2A 205628 at NM_000947 NM_000947 5558 0.86 1.80E-03 ISL1 206104_at NM 002202 NM_002202 3670 0.86 2.89E-03 NAGA 202944 at NM_000262 NM 000262 4668 0.86 1.12E-04 SCD4 224901_at AL571375 NM_024906 79966 0.86 2.89E-04 PHYH 203335_at NM_006214 N M_006214 5264 0.86 3.64E-05 HMGCS1 205822_s_at NM 002130 NM_002130 3157 0.86 5.71 E-04 3ALNAC4S-6S" 203066_at NM 014863 NM 015892 51363 0.86 1.55E-04 DKFZp762A217 235775 at AI765006 NM 152588 160335 0.86 2.87E-03 ADRBK2 204183_s_at AI478542 NM 005160 157 0.85 7.45E-05 BC002942 31837_at U62317 NM_033200 91289 0.85 2.32E-03 KIAA1853 236151 at BF315452 NM 194286 84530 0.85 8.93E-03 C10orf58 228155 at BF512388 NMJ332333 84293 0.85 4.55E-08 KIAA0286 212619_at AW205215 NM_015257 23306 0.85 2.40E-03 AU146017 234082 at AU146017 — — 0.85 5.56E-03 GPR85 219898 at NM 018970 NM 018970 54329 0.85 2.12E-03 KIAA1145 235146 at N51717 NMJ320698 57458 0.85 4.62E-05 CSTF1 202190_at NM 001324 NM_001324 1477 0.85 2.75E-03 BF510533 228107_at BF510533 — — 0.85 7.13E-04 PANK2 218809_at NM_024960 NM 024960 80025 0.85 5.93E-04 NM_153637 NM_153638 NM 153639 NM 153640 NM_153641 DHX37 223364_s_at BC004463 NM_032656 57647 0.85 1.99E-03 HMGB3 203744_at NM 005342 NM 005342 3149 0.85 6.52E-03 BNIP3 201848 s at U15174 NM_004052 664 0.85 1.65E-03 LOC284244 214162_at AF070541 — 284244 0.85 2.94E-03 SV2C 216086_at AB028977 XM 043493 22987 0.85 3.24E-03 MTP18 223172_s_at AF060924 NM_00100370 A 51537 0.85 6.41 E-03 H NM_016498 SNAP29 218327_s_at NM_004782 NM 004782 9342 0.85 4.67E-03 NFYA 204109_s_at NM_002505 NM 002505 4800 0.85 4.40E-03 NM_021705 FLJ37858 227354_at BF589359 NM 00100754S 441357 0.84 6.04E-03 R58282 238557_at R58282 — — 0.84 5.38E-03 CDH2 203441 _s_at NM 001792 NM 001792 1000 0.84 1 55E-03 C20orf45 217851_s_at NM 016045 NM 016045 51012 0.84 1.50E-03 MY01B 212364_at BF432550 NMJ312223 4430 0.84 1.02 E-03 PAICS 201014_s_at NM_006452 NM 006452 10606 0.84 4.23E-04 ZNF505 215758_x_at AC007204 NM_00100412 β 81931 0.84 1.32E-04 D NM_031218 SEMA6A 215028_at AB002438 NM 020796 57556 0.84 1.21 E-04 SLIT2 209897_s at AF055585 NM 004787 9353 0.84 3.51 E-03 CELSR3 40020_at AB011536 NM_001407 1951 0.84 1.82E-06 DIRAS2 219619_at NM 017594 NM 017594 54769 0.84 9.62E-03 TOB2 222243_s_at AB051450 NM 016272 10766 0.84 3.84E-03 HAND1 220138_at NM 004821 NM 004821 9421 0.84 8.36E-04 RAD 18 224200_s_at AB035274 NM_020165 56852 0.83 3.81 E-03 LRIG3 226908_at AI627704 NM_153377 121227 0.83 9.44E-03 Al 150000 226671 at AM50000 — — 0.83 7.72 E-04 EIF5A2 235289 at AV747725 NM 020390 56648 0.83 2.77E-03 CDK2AP1 201938_at NM_004642 NM 004642 8099 0.83 8.12E-03 MLF1 204784_s_at NM_022443 NM 022443 4291 0.83 2.50E-03 159 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays MPP5 219321 at NM 022474 NM 022474 64398 0.83 1.84E-03 TXNRD1 201266_at NM_003330 NM_003330 NM 182729 NM 182742 NM 182743 7296 0.83 6.73E-05 C10orf58 224435_at BC005871 NM_032333 84293 0.82 5.15E-06 EVE1 225162_at BG285417 NM_001009556 152503 0.82 5.43E-03 RALY 201271_s_at NM_016732 NM 007367 NM_016732 22913 0.82 1.71E-03 SEC10L1 228418_at BF509391 NM_006544 10640 0.82 6.79E-06 MFAP2 203417_at NM_017459 NM_002403 NM_017459 4237 0.82 9.64E-05 MY01B 212365_at BF215996 NM 012223 4430 0.82 2.49E-04 ACAA1 214274_s_at Al 860341 NM 001607 30 0.82 5.44E-03 KIAA0701 1554292_a_at BC014891 NM_00100694 7 NM_015054 23074 0.81 5.60E-03 AK022598 232662_x_at AK022598 — — 0.81 5.55E-03 PLXNA2 213030_s_at AI688418 NM_025179 5362 0.81 6.66E-03 BE501881 227565 at BE501881 — — 0.81 2.21 E-03 BF447112 236192 at BF447112 — — 0.81 2.02E-03 LOC85028 228990_at Al 339426 XM 378848 85028 0.81 4.87E-04 BF511170 227332_at BF511170 — — 0.81 3.67E-03 KLF3 219657 s at NM 016531 NM 016531 51274 0.81 3.64E-03 GRIA1 209793 at AL567302 NM_000827 2890 0.81 3.68E-03 SUHW2 229360_at N22886 NM_080764 140883 0.81 8.50E-03 LOC401022 242042_s_at AA406052 — 401022 0.81 5.97E-04 C3orf4 208925 at AF161522 NM 019895 56650 0.81 1.42E-08 MRPL40 203152_at NM 003776 NM 003776 64976 0.81 6.67E-03 PVT1 LOC441378 1558290_a_at BG200951 XM 372058 XM_499128 441378 5820 0.81 2.88E-03 KELCHL 221837 at BG325646 NM 032775 84861 0.81 3.12E-04 CELSR3 205165_at NM_001407 NM_001407 1951 0.81 1.43E-04 RAB35 205461 at NM 006861 NM 006861 11021 0.81 6.64E-03 MGC70857 226710 at AM 99072 NM_00100179£ 414919 0.81 3.76E-05 AA446953 241749 at AA446953 XM 294592 347273 0.81 2.10E-04 PSMD5 203447_at AU157008 NM 005047 5711 0.80 8.55E-04 NUP50 222583_s_at AF116624 NM_007172 NM 153645 NM_153684 10762 0.80 2.54E-04 ARL6IP6 225707_at AL581082 NM_152522 151188 0.80 4.86E-03 H1F0 208886_at BC000145 NM_005318 3005 0.80 2.95E-04 RQCD1 1554080 at BC007102 NM_005444 9125 0.80 5.80E-03 MVK 215649_s_at AF217536 NM_000431 4598 0.80 4.39E-04 CDC5L 209055_s_at AW268817 NM_001253 988 0.80 9.38E-03 LGR4 218326 s at NM 018490 NM 018490 55366 0.80 1.35E-04 C19orf32 226597 at Al 348159 NM 138393 92840 0.80 6.56E-03 HPS4 218402_s_at NM_022081 NM_022081 NM_152840 NM 152841 NM 152842 NM_152843 89781 0.80 8.60E-04 MGC18216 243358_at BF347362 — 145815 0.79 8.83E-03 ZNF43 222136 x at AK022905 NM_003423 7594 0.79 1.19E-06 DRG1 236537 at Al 760332 NM_004147 4733 0.79 9.05E-03 SLC2A4RG 218494_s_at NM 020062 NM 020062 56731 0.79 1.26E-04 CHRNA3 211772_x_at BC006114 NM 000743 1136 0.79 5.89E-03 160 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205 00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays UBE2L3 200683_s_at BE964689 NM 003347 NMJ98157 7332 0.79 2.55E-04 NUP43 238474_at BF978064 NM_024647 NM_198887 348995 0.79 6.09E-03 EML5 1568777 at BM677635 NM_183387 161436 0.79 2.74E-03 N24703 238637 at N24703 — — 0.79 1.03E-03 CHRNA3 211587_x_at M37981 NM_000743 1136 0.79 2.09E-03 ZNF20 213916_at AU154474 NM 021143 7568 0.79 2.24E-03 VAMP1 213326_at AU150319 NM 014231 NM_016830 NM_199245 6843 0.79 2.99E-03 TMEM38B 222735_at AW452608 NM_018112 55151 0.79 1.36E-05 MAPKAPK3 202788 at NM_004635 NM 004635 7867 0.79 7.86E-03 GNB4 223488_s_at BC000873 NM_021629 59345 0.79 5.46 E-03 EPOR 209962_at M34986 NM_000121 2057 0.78 2.19E-04 C6orf115 223361_at AF116682 XM_371848 58527 0.78 1.07E-03 AK057923 1556364 at AK057923 XM 498935 440960 0.78 4.56E-03 PGM2 225367_at BF512139 NM 018290 55276 0.78 3.75E-04 CECR5 218592_s_at NM_017829 NM_017829 NM_033070 27440 0.78 4.74E-03 CHRNA3 210221_at BC000513 NM 000743 1136 0.78 2.56E-05 STMN3 218207_s_at NM_015894 NM_015894 50861 0.78 8.10E-04 UCP2 208997_s_at U82819 NM 003355 7351 0.78 3.02E-04 SFRS8 202773_s_at AI023864 NM 004592 NM_152235 6433 0.78 4.72E-03 FIGNL1 1552921_a_at NM_022116 NMJ322116 63979 0.78 5.97 E-03 MEST 202016_at NM_002402 NM_002402 NM_177524 NM_177525 4232 0.78 9.96E-03 C20orf45 222441_x_at BF032213 NM 016045 51012 0.78 2.01 E-05 PLCXD2 235230_at AW170015 NM_153268 257068 0.78 7.04E-03 UCK1 223142_s_at AF237290 NM 031432 83549 0.78 3.34E-05 SNAP29 239084_at BE896490 NM_004782 9342 0.78 7.09 E-03 SNRPD3 202567_at NM 004175 NM 004175 6634 0.78 8.05 E-03 GABPB2 204618_s_at NM_005254 NM_002041 NM 005254 NM_016654 NM_016655 NM_181427 2553 0.78 4.11E-04 RNF10 208632 at AL578551 NM 014868 9921 0.77 7.94E-04 RFC1 208021 s at NM_002913 NM_002913 5981 0.77 9.34E-03 PAPPA 240295_at AL045014 NM_002581 5069 0.77 2.94E-03 TM4SF9 225387_at AA059445 NM_005723 10098 0.77 1.49E-03 PDCL 204448 s at AF031463 NM 005388 5082 0.77 8.07E-03 GNAZ 204993_at NM_002073 NM_002073 2781 0.77 3.40E-03 STK39 202786_at NM 013233 NM 013233 27347 0.77 5.82E-03 UBE2L3 200684_s_at AI819709 NM 003347 NM 198157 7332 0.77 4.66E-06 BZRP 202096_s_at NM_000714 NM_000714 NM_007311 706 0.77 2.65E-03 ELK3 206127 at NM 005230 NM 005230 2004 0.77 2.08 E-03 ZDHHC13 219296_at NM_019028 NM_00100148 3 NM_019028 54503 0.77 9.19E-04 TIMP2 231579 s at BE968786 NM 003255 7077 0.77 2.80E-03 C8orf13 226614_s_at BE856336 NM_053279 83648 0.77 3.12E-03 161 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays BAX 208478_s_at NM_004324 NM 004324 NM_138761 NM_138762 NM 138763 NM 138764 NM_138765 581 0.77 5.20E-03 TCF8 239952_at AI743662 NM_030751 6935 0.77 2.84E-04 LOC128977 227086_at AA194312 NM_173793 128977 0.77 3.39E-03 PAICS 201013_s_at AA902652 NM 006452 10606 0.76 3.48E-03 AKAP8 203848_at AL050160 NM_005858 10270 0.76 6.90E-05 TWSG1 225406 at AA195009 NM_020648 57045 0.76 1.41E-03 PDK1 206686_at NM 002610 NM 002610 5163 0.76 4.33E-04 TIMP2 224560 at BF107565 NM_003255 7077 0.76 7.63E-03 CDS2 212862_at AL568982 NM_003818 8760 0.76 2.78E-05 384D8-2 205086_s_at NM_014551 NM_014551 NM 152299 29781 0.76 4.69E-04 DTNBP1 223445_at AF061734 NM 032122 NM 183040 NM_183041 84062 0.76 9.22E-04 BG492376 1557961 s at BG492376 — — 0.76 3.56E-03 ARL6IP6 225711 at AA654338 NM_152522 151188 0.76 8.52E-03 LRP10 201412_at NM_014045 NM_014045 26020 0.75 8.53E-03 G22P1 200792_at NM_001469 NM 001469 2547 0.75 1.40E-05 SDCBP 200958_s_at NM_005625 NM_00100706 7 NM 00100706 8 NM 00100706 9 NM_00100707 0 NM 005625 6386 0.75 8.95E-04 PELI2 219132_at NM_021255 NM_021255 57161 0.75 4.32E-04 NFYB 218129_s_at NM_006166 NM 006166 4801 0.75 6.84E-03 BTBD3 202946_s_at NM_014962 NM 014962 NM 181443 22903 0.75 2.02E-04 CSE1L 201111_at AF053641 NM001316 NM 177436 1434 0.75 9.19E-03 CAMKK1 223460_at AL136576 NM_032294 NM 172206 NM_172207 84254 0.75 6.46E-03 TFDP2 244043_at Al049624 NM_006286 7029 0.75 1.03E-03 AU154030 242141 at AU154030 — — 0.75 6.48E-03 C20orf20 218586_at NM 018270 NM 018270 55257 0.75 4.07E-04 PPAT 209434_s_at U00238 NM 002703 5471 0.75 4.18E-04 FH 203032_s_at Al363836 NM 000143 2271 0.75 3.75E-04 USP28 231837 at AB040948 NM 020886 57646 0.75 4.33E-04 COVA1 32042_at S72904 NM_006375 NM_182314 10495 0.75 1.36E-03 KIAA1432 226221_at AL138104 XM 039698 57589 0.75 1.64E-03 ZNF43 206695_x_at NM 003423 NM 003423 7594 0.75 2.70E-03 MICAL-L1 55081 at W46406 NM 033386 85377 0.75 4.38E-03 HPRP8BP 215905_s_at AL157420 NM 004814 9410 0.74 1.02E-04 MAC30 214283_at AU150186 NM 014573 27346 0.74 8.38E-06 C10orf78 238794_at N23586 NM 00100275 9 NM_145247 119392 0.74 7.02E-03 Cep70 219036_at NM_024491 NM 024491 80321 0.74 1.04E-03 162 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays CDKAL1 214877_at BE794663 NM_017774 54901 0.74 7.46E-04 CUGBP2 227178 at AI652861 NM 006561 10659 0.74 1.87E-03 SQLE 213562_s_at BF979497 NM_003129 6713 0.74 1.93E-03 RABL3 226089_at AI742028 NM_173825 285282 0.74 2.21 E-03 TRAM2 202368 s at Al 986461 NM 012288 9697 0.74 4.19E-03 CD47 227259_at BF439618 NM 001777 NM_198793 961 0.74 6.22E-03 T87730 242500_at T87730 — — 0.74 5.92E-05 DGCR2 214198_s_at AU150824 NM_005137 9993 0.74 5.08E-05 GIT2 209876_at AF124491 NM_014776 NM_057169 NM_057170 NM 139201 9815 0.74 1.42E-03 MKKS 222530_s_at AF275813 NM 018848 NM_170784 8195 0.74 8.92E-03 NFKBIE 203927_at NM_004556 NM 004556 4794 0.73 7.87E-03 PTCH 209815 at BG054916 NM_000264 5727 0.73 4.15E-07 SORT1 212807_s_at BF447105 NM 002959 6272 0.73 6.06E-04 SKP2 203625_x_at BG105365 NM_005983 NM_032637 6502 0.73 2.38E-03 B3GNT1 219326_s_at NM_006577 NM 006577 NM_033252 10678 0.73 3.66E-03 TST 209605_at D87292 NM_003312 7263 0.73 3.44E-03 RQCD1 1553510_s_at NM_005444 NM_005444 9125 0.73 7.31 E-03 LOC440928 235147 at R56118 XM 498917 440928 0.73 8.09E-05 EPB41L5 220977 x at NM 020909 NM_020909 57669 0.73 9.69E-03 B4GALT6 206233 at AF097159 NM 004775 9331 0.73 3.61 E-04 MTHFD1 202309_at NM_005956 NM_005956 4522 0.73 5.58E-03 SUHW2 230789 at Al 015954 NM 080764 140883 0.73 4.75E-03 TCF4 228837_at BE857360 NM 003199 6925 0.73 1.23E-05 C20orf22 224742 at BF570412 N M 015600 26090 0.73 5.04E-04 EIF4ENIF1 218626_at NM_019843 NM_019843 56478 0.73 3.09E-06 ZNF141 206931_at NM 003441 NM 003441 7700 0.73 1.09E-03 ZNF278 209494_s_at AI807017 NM_014323 NM_032050 NM_032051 NM_032052 23598 0.73 1.80E-03 RNF26 224947_at AL559247 NM_032015 79102 0.73 9.69E-04 GNG4 1555765_a_at AF493872 NM 004485 2786 0.73 2.53E-03 BCR 202315_s_at NM_004327 NM_004327 NM_021574 613 0.72 5.57E-03 FPGT 205140_at NM_003838 NM_003838 8790 0.72 4.20E-05 FLJ13273 235387_at AA740875 NM_024751 79807 0.72 2.00E-06 PRIM2A 215708 s at AL121975 NM_000947 5558 0.72 3.15E-03 TOMM22 217960 s at NM_020243 NM 020243 56993 0.72 3.02E-03 CDH2 203440_at M34064 NM_001792 1000 0.72 1.27E-04 DENR 234915_s at BC000925 NM 003677 8562 0.72 5.52 E-06 KIAA1280 219520_s_at NM 018458 NM 015691 55841 0.72 1.98E-03 CDC5L 209056 s at NM 001253 NM 001253 988 0.72 5.21 E-03 MYH9 211926_s_at AI827941 NM_002473 4627 0.72 5.89E-03 SLC25A13 203775_at NM_014251 NM_014251 10165 0.72 5.47E-03 SEMA6A 220454 s at NM 020796 NM 020796 57556 0.72 5.20E-04 SOX2 213722 at AW007161 NM 003106 6657 0.72 3.52 E-04 RP2 205191_at NM 006915 NM_006915 6102 0.72 1.30E-03 AI291804 242856_at AI291804 — — 0.72 6.53E-03 SLC26A2 224963 at AK025078 NM 000112 1836 0.72 3.23E-03 GRIA1 211520_s_at M64752 NM 000827 2890 0.71 6.86E-04 SCD 211162_x at AF116616 NM 005063 6319 0.71 8.56E-03 163 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays TM4SF6 209109 s at U84895 NM 003270 7105 0.71 1.07E-04 CYB5-M 201634 s at NM 030579 NM_030579 80777 0.71 8.39E-03 AW025579 213429_at AW025579 — ... 0.71 1.53E-04 CDW92 224595_at AK022549 NM 022109 NM 080546 23446 0.71 4.42E-03 KIAA1853 230010 at AA608629 NM 194286 84530 0.71 1.11E-03 GCLM 203925_at NM_002061 NM_002061 2730 0.71 2.48E-03 TLK2 228627_at AL041560 NM 006852 11011 0.71 1.99E-03 RNF144 204040 at NM 014746 NM 014746 9781 0.71 3.67E-03 PAXIP1L 212825_at AI357401 NM 007349 22976 0.71 7.70E-03 PHOX2B 207009_at NM 003924 NM 003924 8929 0.71 1.10E-05 FAM19A2 241399_at Al 142028 NM 178539 338811 0.71 3.12E-03 RSN 210716_s_at M97501 NM 002956 NM_198240 6249 0.71 1.47E-03 RB1 203132_at NM 000321 NM 000321 5925 0.71 9.52E-03 AA603344 235964_x_at AA603344 — — 0.71 5.50E-03 ZNF278 211392_s_at AF242522 NM 014323 NM_032050 NM 032051 NM_032052 23598 0.71 9.10E-03 DEK 200934 at NM 003472 NM 003472 7913 0.71 7.14E-03 GPC6 227059_at AI651255 NM_005708 10082 0.71 1.48E-03 KBTBD4 223765_s_at AF151086 NM 016506 NM_018095 55709 0.71 2.77E-04 AA521504 235952 at AA521504 — — 0.71 7.68E-03 LOC163404 231397_at AF131783 XM_375754 163404 0.71 9.06E-03 CHRNB4 207516_at NM_000750 NM 000750 1143 0.70 2.92E-04 UBE2L3 200676_s_at NM_003347 NM 003347 NMJ98157 7332 0.70 3.80E-07 MAGEH1 218573_at NM_014061 NM 014061 28986 0.70 8.04E-07 PKM2 201251_at NM_002654 NM_002654 NM 182470 NM_182471 5315 0.70 5.34E-03 DVL2 57532_at AW016304 NM 004422 1856 0.70 2.07E-03 AMMECR1 1553219_a_at NM 015365 NM 015365 9949 0.70 2.11E-03 SLA/LP 235516_at AI038867 NM 016955 NM_153825 51091 0.70 3.09E-03 PEPD 202108_at NM_000285 NM 000285 5184 0.70 7.53E-04 LDHA 200650_s_at NM_005566 NM_005566 3939 0.70 3.92E-03 MVK 204056 s at NM 000431 NM 000431 4598 0.70 3.92E-03 RAB22A 218360 at NM 020673 NM_020673 57403 0.70 2.55E-03 MAP3K7IP1 203901_at NM_006116 NM 006116 NM_153497 10454 0.70 4.29E-03 HMGCR 202540 s at NM 000859 NM 000859 3156 0.70 6.44E-04 AGPS 225113 at BF688144 NM_003659 8540 0.70 1.13E-03 ZNF305 240181_at Al 939511 NM_014724 9753 0.70 2.45E-03 SATB2 213435_at AB028957 NM_015265 23314 0.70 6.66E-03 HPS4 54037_at AL041451 NM 022081 NM_152840 NM_152841 NM 152842 NM 152843 89781 0.70 1.86E-05 B4GALT4 210540_s_at BC004523 NM_003778 NM_212543 8702 0.70 4.75E-03 ZNF555 1556188_a_at AF052118 NM_152791 148254 0.70 9.31 E-03 NEDD1 234984 at AA236927 NM_152905 121441 0.70 9.72E-03 KIAA1648 213058_at AL033538 — 284900 0.70 4.59E-03 164 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays MITF 207233_s_at NM_000248 NM 000248 NM_006722 NM 198158 NM_198159 NM 198177 NM 198178 4286 0.69 9.18E-03 TM4SF9 225388_at AI928507 NM_005723 10098 0.69 1.96E-05 GGA2 214190_x_at AI799984 NM 015044 NM 138640 23062 0.69 5.04E-04 FLJ10199 218815_s_at NM 018022 NM 018022 55092 0.69 5.48E-03 SAMHD1 234987_at AV715309 NM 015474 25939 0.69 8.34E-03 IDH3B 210418_s_at AF023265 NM_006899 NM 174855 NM_174856 3420 0.69 9.34E-05 BNIP3 201849_at NM 004052 NM_004052 664 0.69 3.88E-03 CANP 1557129_a_at AA960844 NM_198947 374393 0.69 8.06E-03 GNG4 205184 at NM 004485 NM 004485 2786 0.69 4.91 E-03 G3BP 201514_s_at NM_005754 NM_005754 NM_198395 10146 0.69 7.45E-05 B3GNT1 222870_s_at AF288208 NM 006577 NM_033252 10678 0.69 3.54E-03 CENTB2 212476_at D26069 NM_012287 23527 0.69 1.34E-03 LBR 201795_at NM_002296 NM 002296 NM 194442 3930 0.69 3.92E-04 EB-1 227440_at AW005572 NM 020140 NM_152788 NM_181670 56899 0.69 8.38E-06 LANCL1 202019_s_at AI935255 NM_006055 10314 0.69 4.49E-03 AI857788 227126_at Al 857788 — ... 0.69 9.75E-03 GPC1 202756_s_at NM_002081 NM 002081 2817 0.69 1.42E-05 RBM14 204178_s_at NM 006328 NM_006328 10432 0.69 2.67E-03 CRKL 212180_at AK000311 NM 005207 1399 0.68 3.46E-07 SMC1L1 201589 at D80000 NM 006306 8243 0.68 1.70E-03 NFIB 213032_at Al 186739 NM 005596 4781 0.68 4.95E-03 RBM14 1555639_a_at AF315633 NM 006328 10432 0.68 5.28E-04 IDH3B 210014_x_at AF023266 NM 006899 NM_174855 NM_174856 3420 0.68 2.88E-04 SC4MOL 209146_at AV704962 NM_006745 6307 0.68 1.06E-05 SLC25A15 222705_s_at BC002702 NM 014252 10166 0.68 5.67E-05 ESD 228162_at AA193515 NM_001984 2098 0.68 7.72E-03 PPAT 209433_s_at AI457120 NM 002703 5471 0.68 1.12E-03 ROD1 224618_at BF059136 NM_005156 9991 0.68 6.34E-03 ATP7A 205197_s_at BE567813 NM_000052 538 0.68 6.71 E-03 AK022438 233508_at AK022438 — ... 0.68 3.52E-03 BG337831 238065_at BG337831 — ... 0.68 8.60E-03 CDS2 212864_at Y16521 NM_003818 8760 0.68 1.15E-04 MGC34646 224996_at N30209 NM 173519 157807 0.68 1.11E-04 RECK 205407_at NM_021111 NM_021111 8434 0.67 8.99E-03 MCAM 211042_x_at BC006329 NM_006500 4162 0.67 2.11E-04 LOC128977 1553974_at BC030758 NM 173793 128977 0.67 2.13E-04 SNX5 222417_s_at AF121855 NM 014426 NM_152227 27131 0.67 7.63E-04 C20orf22 228123_s_at AW303865 NM 015600 26090 0.67 2.89E-04 PHF20 235389_at BG168139 NM_016436 51230 0.67 9.09E-03 NM_014838 204799_at NM 014838 ... ... 0.67 1.84E-04 Cep70 1554489_a_at BC016050 NM 024491 80321 0.67 5.84E-03 GCAT 205164_at NM_014291 NM_014291 23464 0.67 9.67E-03 165 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays MGC20255 225257 at AA534536 NM 052848 90324 0.67 2.25E-04 KIAA1715 225717_at AI814587 NM 030650 80856 0.67 2.65E-03 SH3MD1 224817_at W93554 NM 014631 9644 0.67 3.37E-04 NFYA 204108_at AL031778 NM_002505 NM 021705 4800 0.67 6.22E-03 MGC10854 223456_s_at BC004285 NM 032300 84260 0.67 2.49E-03 DNAJC13 212467_at AB014578 NM_173823 23317 0.67 4.58E-05 SEMA6A 223449_at AF225425 NM 020796 57556 0.67 7.98E-03 BC017932 1569283 at BC017932 XM 495940 440122 0.67 1.88E-03 CDW92 224596_at AI634866 NM 022109 NM_080546 23446 0.67 6.95E-03 HMGCS1 221750_at BG035985 NM 002130 3157 0.67 5.27E-04 IDH3B 201509_at NM_006899 NM 006899 NM_174855 NM_174856 3420 0.66 3.23E-04 CECR6 224393_s_at AF307451 NM_031890 27439 0.66 3.23E-05 IP011 222659 at AK001696 NM 016338 51194 0.66 3.34E-03 ACTL6B 206013 s at NM 016188 NM_016188 51412 0.66 5.47E-03 D15Wsu75e 212527_at BF057059 XM_039495 27351 0.66 1.32E-04 AL134573 228208_x_at AL134573 — — 0.66 1.64E-03 MLLT3 204918_s_at NM 004529 NM 004529 4300 0.66 8.51 E-03 GGA2 208913_at AA868560 NM_015044 NM_138640 23062 0.66 2.22E-03 ROD1 224617_at AI735576 NM 005156 9991 0.66 3.70E-03 SNN 218032_at AF070673 NM 003498 8303 0.66 5.14E-03 CD47 213055_at BF693956 NM_001777 NM_198793 961 0.66 2.63E-03 EN01 217294_s_at U88968 NM_001428 2023 0.66 2.43E-04 SESN3 235150 at AW376955 NM 144665 143686 0.66 7.70E-04 CRY1 209674_at D83702 NM_004075 1407 0.66 2.50E-03 NM_018243 201308_s_at NM_018243 NM 018243 55752 0.66 3.72 E-03 CBX5 241875_at AA204654 NM 012117 23468 0.66 1.75E-03 ZFYVE16 203651_at NM 014733 NM 014733 9765 0.66 1.76E-05 NRF1 204652_s_at NM_005011 NM_005011 4899 0.66 2.20E-03 GALNT2 217788_s_at NM 004481 NM 004481 2590 0.66 6.79E-06 SNX5 217792_at NM_014426 NM 014426 NM_152227 27131 0.66 1.46E-03 ALK 208212_s_at NM_004304 NMJD04304 238 0.65 2.4 7 E-03 WDR44 219297_at NM_019045 NM_019045 54521 0.65 3.28E-04 ELMOD2 1553928_at NM 153702 NM 153702 255520 0.65 1.79E-04 VAPB 202550 s at NM 004738 NM 004738 9217 0.65 3.71 E-05 LOC129285 1553955_at AY134855 NM_152994 129285 0.65 3.87E-03 MPHOSPH9 206205_at NM_022782 NM_022782 10198 0.65 7.66 E-05 SCML2 206147 x at NM 006089 NM 006089 10389 0.65 1.04 E-03 HS6ST2 230030_at AI767756 NM_147174 NM 147175 90161 0.65 3.4 3 E-03 NUP43 219007_at NM_024647 NM 024647 NM_198887 348995 0.65 6.58E-03 R12027 241836_x_at R12027 — — 0.65 6.67E-03 H16725 239138_at H16725 — — 0.65 7.65E-03 AG PS 205401_at NM 003659 NM 003659 8540 0.65 1.27E-03 DKFZP564M08: 204218 at NM 014042 NM 014042 25906 0.65 2.63E-03 MCART1 214126 at N39314 NM 033412 92014 0.65 6.73E-04 NUP50 218295_s_at NM_007172 NM 007172 NM 153645 NM 153684 10762 0.65 4.08E-04 PDK1 226452_at AU146532 NM_002610 5163 0.65 7.55E-03 GPR125 1555122 at BC026009 NM 145290 166647 0.65 1.16E-03 166 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays KIAA0692 212200 at AK025933 — 23141 0.65 3.35E-04 ZADH1 230774 at BE465894 NM_152444 145482 0.65 1.11E-03 CD24 209772_s_at X69397 NM_013230 934 0.65 3.11E-04 KIAA1715 225718_at AL133768 NM_030650 80856 0.65 2.15E-03 MANE A 222805 at AI587307 NM 024641 79694 0.65 3.26E-04 C10orf86 219067 s at NM_017615 NM_017615 54780 0.65 6.76E-03 AL524175 225479_at AL524175 — — 0.64 4.37E-05 MICAL-L1 221779_at BC001090 NM_033386 85377 0.64 1.27E-03 AI708256 229342 at Al 708256 — — 0.64 1.31 E-05 G3BP 201503_at BG500067 NM_005754 NM_198395 10146 0.64 3.53E-03 PLCXD1 222795_s_at BE675241 NM 018390 55344 0.64 2.51 E-03 CD47 226016_at AL118798 NM 001777 NM_198793 961 0.64 1.22E-07 RAB8B 219210_s_at NM 016530 NM_016530 51762 0.64 2.35E-04 RNF150 227657_at AA722069 NM_020724 57484 0.64 5.51 E-03 TEX261 212083_at BG170659 NM_144582 113419 0.64 6.37E-03 BE893995 234983_at BE893995 -- — 0.64 1.28E-03 MGC3731 222057_at AW002578 NM 024313 79159 0.64 8.73E-03 LOC284801 225762_x_at AL531683 XM_378973 284801 0.64 3.26E-03 SLC25A17 211754 s at BC005957 NM_006358 10478 0.64 9.76E-04 KIAA0692 212201_at AW274877 — 23141 0.64 2.57E-03 PCDHB2 231725_at NM 018936 NM 018936 56133 0.64 1.47E-03 ATP1A1 220948_s_at NM_000701 NM 000701 NM 00100158 6 NM 005198 NM 152253 476 0.64 2.01Έ-03 CHKB 204193_at NM_005198 1120 0.64 3.36E-03 MPHOSPH9 215731 s at X98258 NM 022782 10198 0.64 3.26E-03 KIAA0877 1560916_a_at BI461155 XM 371891 XM_374422 23333 0.64 1.49E-03 MAC30 212279 at BE779865 NM 014573 27346 0.64 1.07E-03 RPA1 201529 s at NM 002945 NM 002945 6117 0.64 4.43E-03 HADHSC 211569_s_at AF001903 NM 005327 3033 0.64 4.68E-03 HNRPC 227110_at AA126793 NM 004500 NM_031314 3183 0.64 8.86E-04 C2orf12 225269_s_at BE384529 — 192137 0.64 5.65E-05 GSK3B 209945_s_at BC000251 NM 002093 2932 0.64 8.48E-04 RCN3 61734_at AI797684 NM 020650 57333 0.64 1.45E-03 MANEA 219003 s at NM 024641 NM 024641 79694 0.63 1.47E-04 LOC339448 238010_at BF970340 NM_207356 339448 0.63 6.74E-03 U1SNRNPBP 205300_s_at NM 022717 NM_007020 NM 022717 NM 180699 NM_180703 11066 0.63 7.93E-03 AB014540 209307_at AB014540 — — 0.63 5.07E-03 MKL1 212748_at AB037859 NM 020831 57591 0.63 9.09E-04 NBS1 217299 s at AK001017 NM 002485 4683 0.63 5.38E-03 ACSL3 201662_s_at D89053 NM_004457 NM_203372 2181 0.63 3.55E-04 GALNT2 223991_s_at AF130059 NM 004481 2590 0.63 9.09E-04 FBXL10 226215_s_at Al989996 NM 00100536 6 NM_032590 84678 0.63 6.47E-03 C1orf48 230592_at BE501789 NM 015471 25936 0.63 6.21 E-03 FSCN1 210933_s_at BC004908 NM 003088 6624 0.63 7.38E-03 ALMS1 214221 at Al825212 NM_015120 7840 0.63 6.34E-03 MGC3040 223524_s_at BC000568 NM_023943 66000 0.63 8.05E-03 167 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays WDR5 223308_s_at AL521101 NM_017588 NM_052821 11091 0.63 1.08E-03 RBMS1 203748_x_at NM_016839 NM_002897 NM 016836 NM 016839 5937 0.63 4.92E-04 ACTR6 218395_at NM_022496 NM_022496 64431 0.63 1.97E-06 TOMM22 222474_s_at AB041906 NM_020243 56993 0.63 2.85E-03 LOC129138 231847 at Z97630 NM_138797 129138 0.63 1 02E-04 LOC338799 226369_at AW138760 — 338799 0.63 3.36E-03 SLC2A4RG 222650_s_at BE898559 NM_020062 56731 0.63 7.06E-04 SCOC 224786 at AL133580 NM_032547 60592 0.63 1.37E-05 MGC3731 219324_at NM_024313 NM 024313 79159 0.62 1.54E-03 C10orf6 203481 at AI655902 NM_018121 55719 0.62 2.18E-04 NUP133 233421_s_at AU146738 NM_018230 55746 0.62 7.97E-03 CSRP2BP 228543_at AA780252 NM_020536 NM_177926 57325 0.62 6.49E-04 HSPC129 1555106 a at BC035744 NM_016396 51496 0.62 1 80E-03 MGC5139 202365_at BC004815 — 84747 0.62 1.02E-04 HIC2 212964_at Al912206 NM_015094 23119 0.62 1.32E-04 FCH02 228220_at Al627666 NM 138782 115548 0.62 4.50E-03 CDK5RAP1 218315_s_at NM_016408 NM 016082 N M 016408 51654 0.62 7.08E-05 FH 214170_x_at AA669797 NM 000143 2271 0.62 9.05E-03 ENTPD6 201704 at NM 001247 NM 001247 955 0.62 1.44E-03 NUP50 213682_at AL036344 NM 007172 NM_153645 NM_153684 10762 0.62 2.73E-03 SNX5 229980_s_at AA131508 NM 014426 NM_152227 27131 0.62 1.66E-04 B4GALT6 235333_at BG503479 NM 004775 9331 0.62 4.18E-03 LOC150383 227590_at BE501980 NM_00100891 7 NM_207327 150383 0.62 1.10E-03 SYNGR1 213854_at BF511590 NM_004711 NM 145731 NM 145738 9145 0.62 3.40E-03 DZIP3 207231_at NM_014648 NM_014648 9666 0.62 5.60E-05 CSRP2BP 228544_s_at AA780252 NM 020536 NM_177926 57325 0.62 8.59E-03 SCC-112 212138 at AK021757 NM_015200 23244 0.62 2.22E-06 TEAD1 224955_at AI590088 NM_021961 7003 0.62 1.84E-03 DYRK4 212954 at AF263541 NM 003845 8798 0.62 2.89E-04 RAPH1 243012_at BF196252 NM 025252 NM_203365 NM_213589 65059 0.62 5.72E-03 SC5DL 211423_s_at D85181 NM 006918 6309 0.61 1.75E-03 BUB3 201457_x_at AF081496 NM 00100779 3 NM 004725 9184 0.61 5.81 E-03 TMEM38B 218772_x_at NM 018112 NM_018112 55151 0.61 1.91 E-03 TPARL 218095 s at NM_018475 NM 018475 55858 0.61 1.44E-03 HRPT2 235196_at AA447464 NM_024529 79577 0.61 2.37E-03 KIAA0406 212898 at AB007866 NM 014657 9675 0.61 1.44E-03 FBXO30 226541_at Al 808182 NM_032145 84085 0.61 1.59E-03 EPOR 209963_s_at M34986 NM 000121 2057 0.61 8.17E-03 AP3B1 203141_s_at AW058575 NM_003664 8546 0.61 1.23E-04 FLJ33008 228954 at AW452620 NM_152449 145748 0.61 3.98E-04 FLJ21908 1557984 s at BI464019 NM_024604 79657 0.61 1.58E-03 168 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays . ALS2CR2 223266 at AB038950 NM 018571 55437 0.61 6.51 E-05 RPP30 203436_at NM_006413 NM_006413 10556 0.61 4.85E-03 LOC388272 226608_at AW157311 NM_001001436 388272 0.61 7.08E-03 AI421677 242964_at AI421677 — — 0.61 2.28E-04 HSDL1 223248_at AK025626 NM 031463 83693 0.61 3.31 E-04 GLT25D1 222644_s_at Al924150 NM 024656 79709 0.61 3.50E-03 CBX5 209715_at L07515 NM_012117 23468 0.61 7.77E-03 SCOC 223341_s_at AF330205 NM 032547 60592 0.61 7.55E-03 FLJ22531 204922_at NM 024650 NM 024650 79703 0.61 4.70E-03 TMOD3 220800_s_at NM_014547 NM_014547 29766 0.61 1.32E-03 ZFP161 209724_s_at AL534416 NM_003409 7541 0.61 7.01 E-05 AL563613 226532_at AL563613 — — 0.61 3.89E-03 SESN3 242899 at N78412 NM 144665 143686 0.61 2.87E-03 PGM2 223738_s_at AL136705 NM 018290 55276 0.61 9.76E-05 ORC4L 203352_at NM_002552 NM 002552 NM 181741 NM 181742 5000 0.60 3.05E-03 PANK3 218433_at NM_024594 NM 024594 79646 0.60 9.11E-03 MGC13170 224468_s_at BC006151 NM 199249 NM_199250 84798 0.60 2.79E-04 HABP4 209818 s at AF241831 NM_014282 22927 0.60 5.02E-04 RBMS1 225265_at AI580100 NM_002897 NM 016836 NM 016839 5937 0.60 1.37E-03 SESN3 225123 at BE883841 NM_144665 143686 0.60 3.28E-05 RG9MTD1 223267_at AF226052 NM_017819 54931 0.60 4.25E-05 SEMA6A 225660_at W92748 NM 020796 57556 0.60 3.33E-03 PPM1F 37384 at D86995 NM 014634 9647 0.60 9.35E-04 BMP2K 219546_at NM_017593 NM_017593 NM_198892 55589 0.60 7.82E-04 SCD 211708_s_at BC005807 NM_005063 6319 0.60 3.69E-03 LOC286505 226421 at AA707320 — 286505 0.60 6.02E-03 TOMM70A 201512_s_at BC003633 NM_014820 9868 0.60 8.65E-03 ANXA11 206200_s_at NM_001157 NM 001157 NM_145868 NM_145869 311 0.60 1.86E-03 AW971254 222369_at AW971254 — ... 0.60 7.78E-04 AI754928 226347_at AI754928 — ... 0.60 4.04E-03 NHLRC2 235356_at AW297204 NM_198514 374354 0.60 4.48E-03 HDAC1 201209 at NM 004964 NM 004964 3065 0.60 2.74E-05 MGC14141 225568_at BE728983 NM_032928 85014 0.60 4.04E-04 NIT2 218557_at NM_020202 NM 020202 56954 0.59 8.84E-03 SREBF2 201247_at BE513151 NM 004599 6721 0.59 7.04E-03 MKKS 218138_at NM_018848 NM 018848 NM_170784 8195 0.59 1 60E-04 EPIM 213434_at H95263 NM_001980 NM 194356 2054 0.59 3.73E-03 NDRG3 221082_s_at NM_022477 NM_022477 NM_032013 57446 0.59 7.59E-04 TIGD7 224365_s_at AF251050 NM_033208 91151 0.59 8.93E-03 R68654 236971 at R68654 — ... 0.59 5.73E-03 BE675101 236384_at BE675101 ... — 0.59 2.31 E-04 MAC30 212281 s_at BF038366 NM_014573 27346 0.59 1.68E-04 FLJ12806 220199_s_at NM_022831 NM 022831 64853 0.59 2.17E-05 ASF1A 203427 at NM 014034 NM 014034 25842 0.59 1.25E-04 CTCF 202521_at NM_006565 NM_006565 10664 0.59 4.94E-05 PSCD3 225147 at AL521959 NM 004227 9265 0.59 9.96E-03 169 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et ai., Cells Useful for Immuno-Based BoNT/A Activity Assays IQSEC3 213834_at AB029033 XM 370667 XM_495902 440073 0.59 2.90E-04 MPHOSPH9 221965_at AI990326 NM 022782 10198 0.58 9.17E-03 DNCI2 236698_at AI823600 NM_001378 1781 0.58 1.70E-03 ZNRF3 226360 at AK022809 XM 290972 84133 0.58 2.94E-03 OSBPL11 222586_s_at AI884890 NM_022776 114885 0.58 2.49E-03 NIPSNAP3A 224436_s_at BC005935 NM_015469 25934 0.58 3.38E-03 NBS1 202906_s_at AF049895 NM_002485 4683 0.58 4.86E-03 MGC3162 218860 at NM 024078 NM 024078 79050 0.58 3.07E-04 FLJ13149 219016_at NM_021826 NM_021826 60493 0.58 8.95E-03 DIAPH1 213514_s_at AU158818 NM_005219 1729 0.58 7.31 E-03 IGSF4 209031_at AL519710 NM 014333 23705 0.58 2.03E-03 ATP6V1A 201971 s at NM 001690 NM 001690 523 0.58 4.36E-04 FLJ25952 225365_at BG249221 NM_153251 253832 0.58 2.88E-03 170 PCT/US2010/027242 WO 2010/105234 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451

Jacky, B., et al„ Cells Useful for Immuno-Based BoNT/A Activity Assays

Table 6. Decreased Gene Expression in Cell Lines H1 and BB10 vs. Cell Line 2D6 in Undifferentiated State Using Microarray Analysis

Gene Symbol Probe Set ID Representativ e Public ID RefSeq Transcript ID Entrez Gene ID Log2 Ratio pvalue KIAA0125 206478_at NM_014792 NM_014792 9834 -7.57 6.75E-06 CART 206339_at NM 004291 NM_004291 9607 -6.35 6.05E-07 CPNE8 228365_at AI765180 NM 153634 144402 -5.76 5.62E-09 MEOX2 206201_s_at NM 005924 NM 005924 4223 -5.64 6.26E-06 CYTL1 219837_s_at NM 018659 NM_018659 54360 -5.64 1.55E-10 CYGB 226632_at AL513673 NM 134268 114757 -5.63 1.66E-03 FGF13 205110_s_at NM_004114 NM 004114 2258 -5.18 1.42E-06 CPNE8 241706_at AA431782 NM_033642 NM_153634 144402 -4.70 2.99E-10 CYGB 1553572_a_at NM 134268 NM_134268 114757 -4.40 5.68E-05 BC036254 1557443_s_at BC036254 ... ... -4.26 3.10E-05 SLC1A2 225491_at AL157452 NM 004171 6506 -4.14 7.08E-13 CAP2 212554_at N90755 NM_006366 10486 -4.08 3.14E-07 AL353759 215071_s_at AL353759 — — -3.91 1.82E-05 GNAS 217057_s_at AF107846 NM 000516 2778 -3.79 5.67E-04 CFC1 223753 s_at AF312769 NM_016592 NM_080425 NM_080426 NM 032545 55997 -3.75 5.58E-06 GRM5 214217 at D60132 NM 000842 2915 -3.73 3.90E-09 CYP2E1 1431 at J02843 NM 000773 1571 -3.66 1.03E-03 LOC56901 218484 at NM 020142 NM 020142 56901 -3.66 1.04E-04 PAPPA 224942 at BG434272 NM 002581 5069 -3.64 2.15E-04 AQP1 209047_at AL518391 NM_000385 358 -3.61 1.21E-05 BG325630 234973_at BG325630 NM_198098 -3.57 9.05E-04 CDKN2A 209644_x_at U38945 NM 000077 1029 -3.30 4.00E-06 CYP2E1 209975_at AF182276 NM_058195 NM_058197 NM_000773 1571 -3.28 1.91E-03 BF432956 229057_at BF432956 — — -3.21 2.21 E-06 ANK3 237839_at BF433975 NM_001149 288 -3.19 4.55E-03 AU144437 232887 at AU144437 NM_020987 -3.17 9.97E-06 LOC158572 243017 at AA032156 XM 379705 158572 -3.12 5.87E-07 SAMD4 212845_at AB028976 NM_015589 23034 -3.12 2.46E-03 M160 223655 at AF264014 NM_174941 283316 -3.12 3.65E-05 SYT13 226086_at AB037848 NM_020826 57586 -3.11 1.85E-05 AI093492 237435 at AI093492 — — -3.03 2.14E-03 CYP2E1 209976_s_at AF182276 NM_000773 1571 -3.01 9.74E-04 N39597 1555993_at N39597 — — -2.99 1.61E-04 ASAM 226834 at BG112263 NM 024769 79827 -2.98 6.28E-03 KIAA1598 221802_s_at AU157109 NM_018330 57698 -2.94 8.29E-05 CDC42EP1 204693_at NM 007061 NM 007061 11135 -2.90 4.19E-03 N92599 241421 at N92599 NM_152243 -2.86 2.63E-05 GDF15 221577 x at AF003934 NM_004864 9518 -2.84 2.08E-03 AI341823 239657 x at Al341823 — — -2.82 2.19E-05 AW665665 237187_at AW665665 — — -2.78 1.83E-03 SLC35F3 229065 at BF968270 NM_173508 148641 -2 76 7.38E-06 AA151917 230503_at AA151917 — — -2.73 3.30E-05 PAPPA 201982_s_at NM 002581 NM_002581 5069 -2.70 2.76E-06 171 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays IL17B 220273 at NM 014443 NM_014443 27190 -2.67 2.02E-04 KIAA0125 220377_at NM_014151 NM 014792 9834 -2.65 1.07E-05 ANK2 232606_at AK021894 NM_001148 NM_020977 287 -2.65 4.00E-08 AK021495 215571_at AK021495 — ... -2.65 9.41 E-04 ANK3 239726_at Al 743588 NM_001149 NM_020987 288 -2.64 4.93E-04 ANK2 1561895_at BC030740 NM 001148 NM_020977 287 -2.63 1.24E-04 PAPPA 224940_s_at BF107618 NM_002581 5069 -2.63 4.08E-04 PAPPA 228128_x_at Al 110886 NM_002581 5069 -2.60 6.58 E-04 AW274468 242299 at AW274468 — — -2.54 9.96E-08 GRIA2 205358_at NM_000826 NM_000826 2891 -2.54 3.09E-03 PAPPA 201981__at AA148534 NM 002581 5069 -2.51 2.17E-04 ANK2 216195_at AF131823 NM 001148 NM 020977 287 -2.51 1.40E-06 PAPPA 224941_at BF107618 NM_002581 5069 -2.50 1.61E-03 LOC283404 1558195_at BG204230 — 283404 -2.49 1.03E-07 GRIP2 216481_at AF052177 XM_042936 80852 -2.44 1.03E-04 BF000047 235736_at BF000047 — ... -2.43 2.70E-05 FGF1 1552721_a_at NM_033136 NM_000800 NM 033136 NM 033137 2246 -2.43 2.69E-04 GRIA2 236538_at BE219628 NM_000826 2891 -2.40 8.42E-04 BM977131 1557478_at BM977131 — — -2.38 9.09E-05 BHLHB2 201170_s_at NM_003670 NM 003670 8553 -2.37 5.35E-03 CAP2 212551 at NM 006366 NM_006366 10486 -2.36 1.47E-03 PTN 211737 x at BC005916 NM_002825 5764 -2,35 1.99E-06 AI051127 231478_at Al 051127 — -- -2.34 3.52E-03 PHLDA2 209803_s_at AF001294 NM 003311 7262 -2.32 1.79E-05 RGS11 206107_at NM_003834 NM 003834 NM_183337 8786 -2.31 1.17E-03 EGR1 201694_s_at NM_001964 NM 001964 1958 -2.30 5.17E-03 DKK1 204602_at NM 012242 NM_012242 22943 -2.29 9.68E-04 ZAP128 202982_s_at NM 006821 NM 006821 10965 -2.29 2.38E-03 AK096401 1556204_a_at AK096401 XM_375664 400721 -2.28 4.02E-05 AI459194 227404_s_at AI459194 — — -2.28 8.03E-03 )KFZp313N062 1555905_a_at AI147556 NM 173826 285343 -2.26 6.00E-04 LOC51315 222585 x at BE326678 NM_016618 51315 -2.26 7.70E-05 HIST2H2BE 202708 s at NM_003528 NM_003528 8349 -2.25 5.90E-05 BC035768 1559987_at BC035768 — ..... -2.24 2.82 E-04 ERBB4 206794_at NM_005235 NM 005235 2066 -2.24 7.92 E-04 IL7 206693 at NM 000880 NM_000880 3574 -2.20 1.47E-04 AA601031 228919_at AA601031 — — -2.18 1.30E-03 HS3ST1 205466_s_at NM_005114 NM 005114 9957 -2.18 6.77 E-04 ANK3 215314_at AU146646 NM 001149 NM_020987 288 -2.18 3.85E-04 LOC144571 1564139_at AK056852 — 144571 -2.17 1.36E-03 ENOSF1 213645_at AF305057 NM_017512 55556 -2.16 1.79E-06 RASGEF1B 230233_at BF110534 NM 152545 153020 -2.16 7.76E-03 CREB5 205931_s_at NM_004904 NM 004904 NM_182898 NM_182899 9586 -2.15 5.67E-03 CG018 213375 s at N80918 NM_052818 90634 -2.14 7.06E-03 GAL 214240 at AL556409 NM_015973 51083 -2.12 7.95E-03 ANK2 202921 s at NM 001148 NM_001148 NM 020977 287 -2.11 3.33E-05 172 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays CAMK2B 209956_s_at U23460 NM 001220 NM_172078 NM_172079 NM_172080 NM 172081 NM_172082 NM_172083 NM_172084 816 -2.10 8.15E-06 PHKA2 1560358 at BC038597 NM_000292 5256 -2.08 2.64E-05 CACNA1D 210108_at BE550599 NM_000720 776 -2.08 2.44E-03 AW954199 239331_at AW954199 — — -2.08 1.68E-07 LOC150759 221973_at AI983904 XM_498456 XM_499585 150759 -2.05 4.18E-04 ADCY1 235049_at AA021120 NM_021116 107 -2.05 1.26E-03 AI435590 237193_s_at AI435590 — — -2.02 9.66E-04 AQP1 207542_s_at NM_000385 NM 000385 NM_198098 358 -2.02 1.79E-03 BE219849 240180_at BE219849 — — -2.00 1.75E-03 BF111884 230491_at BF111884 — — -2.00 8.24E-07 KIAA0251 1558430 at R08650 NM_015027 23042 -2.00 5.90E-03 AI810266 235456 at AI810266 — — -2.00 2.25E-07 PPP3CA 1562467 at AK097085 NM 000944 5530 -1.97 1.35E-03 SYNPR 230303_at H11380 NM 144642 132204 -1.96 6.12E-03 ADCY1 213245 at AL120173 NM 021116 107 -1.96 8.54E-05 BCAR3 239908 at AA496799 NM_003567 8412 -1.96 2.42E-03 BC025319 1568974_at BC025319 — — -1.95 6.55E-05 DDEF1 1557685_at AK054840 NM_018482 50807 -1.94 5.02E-04 NEURL 230767 at BF448300 NM 004210 9148 -1.94 4.29E-04 STAR 204548 at NM 000349 NM_000349 6770 -1.93 5.97E-05 NM_00100724 3 NAG8 210109 at AF191492 NM_014411 27099 -1.92 7.56E-03 LOC55831 215250_at AU147317 NM_018447 55831 -1.92 4.21 E-04 AI927692 228528_at AI927692 — — -1.91 1.93E-03 BC041941 1559597_at BC041941 — — -1.90 9.44E-04 CLDN10 1556687_a_at BE465772 NM 006984 NM_182848 9071 -1.90 2.11E-03 AI800713 235122_at AI800713 — — -1.88 8.12E-04 ADARB1 203865_s_at NM_015833 NM_001112 NM 015833 NM_015834 104 -1.87 6.53E-04 LOC92162 229452_at AL544576 NM_203411 92162 -1.86 1.23E-03 AL049252 216527_at AL049252 — — -1.85 4.62E-05 ARC 210090 at AF193421 NM 015193 23237 -1.85 1.06E-04 FYN 1559101_at AK090692 NM 002037 NM_153047 NM_153048 2534 -1.85 6.72 E-04 AAK1 214956_at AF090101 NM 014911 22848 -1.85 2.35E-03 FARP1 227996_at BF725250 NM_00100171 5 NM_005766 10160 -1.85 2.09E-03 PTGER2 206631 at NM 000956 NM_000956 5732 -1.84 5.50E-04 LOC360030 232744 x at BG485129 — 360030 -1.84 1.99E-03 TCEAL2 211276 at AF063606 NM_080390 140597 -1.84 4.69 E-04 SIGIRR 218921_at NM 021805 NM_021805 59307 -1.83 2.45 E-03 RAB7 239405_at Al 022632 NM_004637 7879 -1.83 1.40 E-04 173 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Ceils Useful for Immuno-Based BoNT/A Activity Assays CAMK2B 210404_x_at AF078803 NM_001220 NM_172078 NM_172079 NM 172080 NM 172081 NM_172082 NM_172083 NM 172084 816 -1.82 2.11E-06 ERBB4 214053_at AW772192 NM 005235 2066 -1.82 9.63E-05 FLJ13955 227001_at Al096706 NM_024759 79815 -1.81 1.39E-03 AI697701 243666_at AI697701 — — -1.81 1.63E-04 AK024567 234597_at AK024567 — — -1.81 4.51 E-07 RHOQ 1559582 at BC033251 NM 012249 23433 -1.81 2.02E-03 ATP2B3 207026_s_at NM_021949 NM_00100134 4 NM_021949 492 -1.81 3.94E-03 BF055351 231205 at BF055351 — — -1.79 3.90E-03 ACYP2 206833_s_at NM_001108 NM 138448 98 -1.79 1.40E-04 CAMK2B 211483_x_at AF081924 NM_001220 NM 172078 NM_172079 NM_172080 NM_172081 NM 172082 NM_172083 NM_172084 816 -1.78 7.39E-06 DUSP5 209457_at U16996 NM_004419 1847 -1.77 7.59E-04 NLF1 241031_at BE218239 NM 207322 145741 -1.77 1.06E-06 DTNA 240125_at AI697494 NM_001390 NM_001391 NM 001392 NM 032975 NM_032978 NM_032979 NM 032980 NM 032981 1837 -1.77 2.09E-03 FLJ12671 233728_at AU148213 NM_030980 81875 -1.77 1.42E-03 TM4SF2 234245_at AL162055 NM_004615 7102 -1.76 3.16E-03 MGC13040 224463 s at BC006128 NM 032930 85016 -1.76 9.67E-03 IGFBP5 211959 at AW007532 NM 000599 3488 -1.76 5.39E-03 COL9A2 213622_at AI733465 NM 001852 1298 -1.76 2.66E-03 AB088847 1555547_at AB088847 — — -1.76 4.05E-06 UGCGL2 1558467 a at BE156619 NM 020121 55757 -1.75 2.63E-03 GPX7 213170_at AA406605 NM 015696 2882 -1.75 1.66E-03 RLF 241438_at Al742686 NM_012421 6018 -1.75 3.53E-03 DUSP16 1558739_at R30807 NM_030640 80824 -1.74 1.87E-04 SORCS1 1556891 at BE328250 NM 052918 114815 -1.74 2.33E-03 ANK2 202920_at BF726212 NM_001148 NM_020977 287 -1.73 1.72E-04 AL119491 244292_at AL119491 — — -1.73 2.74E-03 ATP2B3 242036_x_at H09073 NM_00100134 4 NM_021949 492 -1.72 2.83E-03 DRD1IP 219896_at NM_015722 NM_015722 50632 -1.72 4.50E-04 174 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays KCNQ2 205737_at NM_004518 NM 004518 NM_172106 NM_172107 NM_172108 NM 172109 3785 -1.72 4 02E-06 LOC51315 233329 s at AK025986 NM_016618 51315 -1.71 4.22E-05 PNCK 229411_at AI986390 NM_198452 139728 -1.71 9.68E-05 AA007336 237586_at AA007336 — — -1.71 5.37E-04 AI681941 237663 at AI681941 — — -1.71 9.56E-04 SRPK2 242755_at BE672140 NM_182691 NM_182692 6733 -1.71 3.64E-05 C9orf3 232783_at AM47867 NM 032823 84909 -1.70 4.59E-03 RGAG4 227823_at BE348679 XM_291322 340526 -1.70 6.60E-05 AK098781 1560814 a at AK098781 — ... -1.69 7.73E-04 ERBB4 233498_at AK024204 NM_005235 2066 -1.69 1.49E-03 C9orf10 241242_at BE503118 NM_014612 23196 -1.68 1.66E-03 BF342356 238934 at BF342356 — — -1.67 6.33E-06 IER3 201631_s_at NM_003897 NM_003897 NM_052815 8870 -1.67 2.10E-06 AU147091 232818_at AU147091 XM_097622 149297 -1.67 1.82E-05 SNX27 244349 at AI807658 NM 030918 81609 -1.66 4.72E-04 ACSL4 1559663_at AF090916 NM 004458 NM_022977 2182 -1.66 4.29E-04 AA705933 239866_at AA705933 — — -1.66 1.19E-04 PRR3 244204_at W87300 NM 025263 80742 -1.66 4.53E-03 TMP21 239851_at AW629289 NM_006827 10972 -1.66 5.43E-03 DDHD1 231165_at BE857355 NM 030637 80821 -1.65 5.85E-07 BRD4 232551_at AA521443 NM 014299 NM 058243 23476 -1.65 1.19E-03 LRRC5 234148_at AK025238 NM_018103 55144 -1.65 6.30E-04 BE674309 230913_at BE674309 — — -1.64 9.40E-04 AI052447 236796 at AI052447 — — -1.64 1.69E-05 BF513468 241505 at BF513468 ... ... -1.63 7.53E-03 KIAA0754 215268_at AW663712 — 23056 -1.62 1.40E-05 FLJ10378 242153_at AW264125 NM 018078 NM 032239 NM_178043 55132 -1.62 6.22E-03 AGPAT3 223182_s_at Al337300 NM 020132 56894 -1.62 7.22E-06 C9orf150 216769_x_at AK025180 NM_203403 286343 -1.62 6.30E-03 LOC286411 1557133_at AV753446 — 286411 -1.62 1.50E-03 HNRPD 213359_at W74620 NM_00100381 0 NM 002138 NM_031369 NM_031370 3184 -1.61 9.97E-03 CKMT1 1561155_at W76548 NM 020990 1159 -1.61 1.10E-03 BF433341 235977_at BF433341 — — -1.61 3.15E-03 PRKACB 202742_s_at NM_002731 NM 002731 NM_182948 NM_207578 5567 -1.61 2.42E-03 FLJ45880 228538 at BE671164 NM 207404 389114 -1.59 3.25E-03 CRYGS 223643 at AI762135 NM 017541 1427 -1.58 2.85E-05 BACH 2 221234_s_at NM_021813 NM021813 60468 -1.58 2.32E-05 AW150212 1556038_at AW150212 — — -1.58 7.16E-03 CDH12 207149 at L33477 NM_004061 1010 -1.58 7.69E-03 AB062488 1555014 x at AB062488 — — -1.58 1.71E-03 RHOU 223168 at AL096776 NM_021205 58480 -1.57 2.07E-07 175 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays C21orf66 239407_at AI793248 NM 013329 NM_016631 NM_058191 NM_145328 94104 -1.57 4.80E-03 ENOSF1 204143_s_at NM 017512 NM_017512 55556 -1.56 4.33E-04 BE894882 235681_at BE894882 — — -1.55 4.33E-05 AW606588 239008_at AW606588 — ... -1.54 5.81 E-03 SYTL1 227134_at AI341537 NM_032872 84958 -1.54 6.41 E-03 AK025360 216173 at AK025360 — — -1.54 2.23E-04 DKFZP564D16f 231799_at AK021886 XM_371074 26115 -1.54 7.37E-03 LGALS3BP 200923_at NM_005567 NM_005567 3959 -1.54 5.18E-09 AI768374 228661_s_at AI768374 — — -1.54 1.48E-03 AA639707 243837 x at AA639707 — — -1.54 3.39E-03 AI821995 240201_at Al821995 ... ... -1.54 1.51E-04 PHGDHL1 241932_at AI073803 NM 177967 337867 -1.53 2.06E-03 LOC51315 218303_x_at NM 016618 NM 016618 51315 -1.53 2.32E-05 C10orf10 209183 s at AL136653 NM_007021 11067 -1.52 3.47E-03 AI817960 239649_at Al817960 — ... -1.52 9.05E-05 CTBP2 215377_at AK024129 NM_001329 NM_022802 1488 -1.52 3.37E-04 AI828075 230795 at AI828075 — — -1.51 3.70E-05 ARHGAP20 228368_at AI936560 NM 020809 57569 -1.51 1.86E-03 BC020585 1568817_at BC020585 — — -1.51 6.55E-04 NDRG1 200632 s at NM 006096 NM 006096 10397 -1.51 1.79E-04 SLICK 234103_at AU145191 NM 198503 343450 -1.51 8.70E-03 PROM1 204304_s_at NM_006017 NM 006017 8842 -1.51 1.53E-04 THADA 233692_at AK024928 NM_022065 NM 198554 63892 -1.51 8.55E-05 FBXL13 243057 at AI923673 NM 145032 222235 -1.50 2.27E-03 LOC54103 222150_s_at AK026747 XM 379881 XM_499340 54103 -1.50 3.51 E-04 BE552011 230208 at BE552011 — — -1.50 4.21 E-03 MGC45477 1554250 s at BC033812 — 387277 -1.50 3.37E-04 AI521273 241702_at AI521273 — — -1.49 2.58E-03 AL833239 1560082_at AL833239 — — -1.49 2.21 E-03 BACE1 217904_s_at NM_012104 NM 012104 NM_138971 NM_138972 NM_138973 23621 -1.48 3.27E-05 PRSS11 201185 at NM 002775 NM 002775 5654 -1.48 7.56 E-04 PTPRH 208300_at NM_002842 NM_002842 5794 -1.48 2.27E-03 C9orf150 227443 at Al972386 NM_203403 286343 -1.48 1.85 E-03 FLJ10159 236602 at AA833813 — 55084 -1.48 1.23E-06 GLT25D2 209883 at AF288389 NM_015101 23127 -1.47 9.47E-04 LOC133308 229491_at BF433180 NM_178833 133308 -1.47 2.89E-03 KIAA1276 233823_at AB033102 XM_039169 27146 -1.46 3.60E-04 GNRHR 1568661 at BC039430 NM 000406 2798 -1.46 8.63E-03 RAB6B 221792 at AW118072 NM_016577 51560 -1.46 2.71 E-03 FLJ12666 215029_at AL117451 NM_024595 79647 -1.45 1.46 E-04 LOC23117 238342_at BF677084 XM_290670 23117 -1.45 1.20E-05 BG430958 1559455 at BG430958 — — -1.44 7.89E-04 C6orf148 237347 at AL039379 NM 030568 80759 -1.44 3.82 E-04 MAST4 225613_at Al 096389 XM_291141 23227 -1.44 4.89E-03 AL832439 1560661_x_at AL832439 — — -1.44 3.31 E-04 AA824624 239531 at AA824624 — — -1.44 1.73E-05 AU146893 229858 at AU146893 — — -1.44 1.74E-03 NDFIP2 1568807_a_at Al 301081 NM_019080 54602 -1.43 4.05E-06 SFRS1 239384 at R18746 NM 006924 6426 -1.43 8.25E-03 176 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays STMN2 203001 s at NM 007029 NM 007029 11075 -1.43 6.36E-03 PTP4A3 209695_at BC003105 NM_007079 NM_032611 11156 -1.43 3.11E-05 BE671117 243114_at BE671117 — — -1.43 3.37E-04 AK021551 232589 at AK021551 — — -1.43 2.58E-03 SRP54 1557505_a_at AI076351 NM_003136 6729 -1.42 1.37E-03 KIAA1641 220940_at NM_025190 NM_020970 57730 -1.42 1.31E-04 AW591282 231374_at AW591282 — — -1.42 5.06E-03 MCM3AP 215581 s at AK022303 NM 003906 8888 -1.42 7.91 E-04 TPD52 239862_at W89022 NM_005079 7163 -1.42 1.59E-04 MGC15523 1563226_at BC020925 NM_138570 124565 -1.42 3.66E-04 CEBPD 203973_s_at NM_005195 NM 005195 1052 -1.42 2.21 E-03 LOC133308 1564746 at BC009732 NM_178833 133308 -1.41 9.96E-05 AI041215 242912_at Al 041215 — — -1.41 1.41 E-03 BTN3A3 BTN3A2 204820_s_at NM_006994 NM_006994 NM 007047 NM 197974 10384 11118 -1.41 3.26E-03 HIAT1 242374 at AA747563 NM_033055 64645 -1.41 1.51 E-03 KIAA0500 213839_at AW028110 — 57237 -1.40 2.08 E-04 C9orf41 1564690 at BC022435 NM_152420 138199 -1.40 2.81 E-04 AL832439 1560659 at AL832439 — — -1.40 4.57E-05 ABR 214671_s_at L19704 NM_001092 NM_021962 29 -1.40 1.63E-04 BE219187 237594_at BE219187 — — -1.40 1.72 E-03 HLCS 207833 s at NM 000411 NM 000411 3141 -1.39 7.33E-03 NFYC 1558782_a_at BG390627 NM 014223 4802 -1.39 2.59E-03 SNF1LK 208078_s_at NM 030751 NM_173354 150094 -1.39 3.83E-03 C9orf150 233112_at AW301393 NM 203403 286343 -1.39 1.07E-03 SCFD1 243525_at AA808051 NM_016106 NM_182835 23256 -1.39 5.74E-04 AA936428 244674_at AA936428 — — -1.39 1.59E-03 )KFZp761N111· 229254 at BE550027 NM_181644 148808 -1.39 3.32E-06 AI691075 229728_at AI691075 — — -1.38 1.16E-04 FLJ11710 244646_at AW972881 — 79904 -1.38 7.97E-03 AGPAT3 223183_at Al928403 NM_020132 56894 -1.38 6.88E-04 BC037911 1568981 at BC037911 — — -1.38 1.58E-05 RHOU 223169_s_at AB051826 NM_021205 58480 -1.38 6.23E-03 AW172407 240908_at AW172407 XM 373053 391733 -1.38 1.17E-04 HIST1H2BK 209806_at BC000893 NM_080593 85236 -1.38 1.12E-04 BE046461 215303_at BE046461 — — -1.38 7.47E-04 AA973100 230725_at AA973100 — — -1.38 8.35E-07 SRP54 1557504_at Al076351 NM 003136 6729 -1.38 5.06E-03 FLJ13197 219871 at NM 024614 NM_024614 79667 -1.37 8.97E-03 OR7D2 1562337_at AK095468 NM_175883 162998 -1.37 2.08E-04 TRIM32 1557315_a at AL134420 NM_012210 22954 -1.37 2.53E-03 Al394334 232696 at Al394334 — — -1.37 2.28E-03 BIRC6 242068_at AA608834 NM 016252 57448 -1.37 7.28E-03 ETFA 239830_at AW850555 NM_000126 2108 -1.37 4.23E-04 PDGFRB 202273_at NM 002609 NM_002609 5159 -1.37 1.64E-04 DDEF1 232952 at AU146493 NM_018482 50807 -1.37 3.89E-03 AI912571 228333_at AI912571 — — -1.36 9.03E-04 AW150212 1556039_s_at AW150212 — — -1.36 2.10E-04 SLC16A14 238029_s at R15072 NM_152527 151473 -1.36 3.15E-04 COL6A1 212091 s at AI141603 NM 001848 1291 -1.35 4.35E-04 TMEM1 215269 at AI922538 NM_00100172 3 7109 -1.35 7.34 E-04 NM 003274 177 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays AA262583 238534_at AA262583 — — -1.35 3.27E-03 AL037414 230055_at AL037414 — ... -1.35 3.69E-04 KIF1A 203849_s_at BG473130 NM 004321 547 -1.35 3.10E-03 KIAA1904 1559072 a at BC032083 NM 052906 114794 -1.34 4.03E-03 ACSL4 1557418_at W95007 NM 004458 NM 022977 2182 -1.34 4.22E-04 ATP1B4 243737_at AI082610 NM 012069 23439 -1.34 4.77E-03 MAP2K5 244298_at AA702999 NM 002757 NM 145160 NM_145161 NM_145162 5607 -1.34 3.13E-05 GAL 207466_at NM 015973 NM 015973 51083 -1.33 8.78E-03 DOC2A 205744_at NM 003586 NM_003586 8448 -1.33 3.98E-07 AV703843 1560775_at AV703843 — — -1.33 4.77E-03 PCTK3 214797_s_at BC000281 NM_002596 NM_212502 NM_212503 5129 -1.33 9.10E-04 )KFZp761O011 207797_s_at NM_018409 NM 018409 55805 -1.33 6.16E-03 RAC2 207419_s_at NM_002872 NM_002872 5880 -1.33 4.07E-03 STMN2 203000_at BF967657 NM 007029 11075 -1.32 8.36E-03 D4S234E 209569_x_at NM_014392 NM_014392 27065 -1.32 1.21E-06 AV709727 225996_at AV709727 — — -1.32 2.28E-03 C19orf4 219005_at NM 012109 NM_012109 25789 -1.32 6.30E-06 AI276956 230766 at AI276956 — — -1.32 5.11E-04 C13orf22 1562238_at AL832776 NM_005800 10208 -1.32 1.46E-03 CRYZL1 243091_at BF435599 NM_005111 NM 145311 NM_145858 9946 -1.32 7.89E-03 HR 241355_at BF528433 NM_005144 NMJ518411 55806 -1.32 3.52E-03 LOC285513 1564077_at AK074440 NM_198281 285513 -1.32 8.81 E-03 AI973085 239765 at Al 973 085 — — -1.32 9.72E-03 DJ462023.2 225876_at T84558 NM 020448 57185 -1.31 3.81 E-03 PKD1 216949_s_at L39891 NM_000296 NM_00100994 λ 5310 -1.31 4.56E-03 MAD 226275_at AM 88653 4 NM 002357 4084 -1.31 3.40E-03 MSI2 243579_at BF029215 NM_138962 NM_170721 124540 -1.31 4.03E-03 UGCGL2 1558466 at BE156619 NM 020121 55757 -1.31 7.77E-04 DDEF1 238193_at W87434 NM 018482 50807 -1.31 6.32E-04 KIAA1277 221886_at AL037701 NM_015689 27147 -1.31 3.41 E-07 AI056683 228171 s at AI056683 — — -1.31 8.22E-04 FYN 243006_at BG222258 NM_002037 NM 153047 NM 153048 2534 -1.31 1.31E-04 GART 236969_at Al961651 NM_000819 NM_175085 2618 -1.30 9.66E-06 FLJ32130 242272_at AI375066 NM_152458 146540 -1.30 2.75E-04 C6orf198 227834_at AL589605 XM 371849 167838 -1.30 9.19E-03 DTNA 210736 x at U46746 NM 001390 1837 -1.30 5.47E-03 NM_001391 NM_001392 NM_032975 NM_032978 NM_032979 NM_032980 NM 032981 178 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays SERP1 235475_at AI580135 NM 014445 27230 -1.30 1.39E-03 C21orf25 212875 s at AP001745 NM_199050 25966 -1.30 5.16E-05 MGC12488 211386_at BC005372 — 84786 -1.30 2.63E-03 BM989131 1558075_at BM989131 — ... -1.30 1 86E-04 ENOSF1 204142 at NM 017512 NM_017512 55556 -1.30 6.73E-04 AW014345 236229_at AW014345 — ... -1.29 1.23E-05 PKD1 202328_s_at NM_000296 NM_000296 NM_00100994 A 5310 -1.29 5.93E-03 KIAA1276 227505_at N64630 4 XM_039169 27146 -1.29 9.12E-04 AL390170 213904_at AL390170 — ... -1.29 4.93E-04 BE672499 230962_at BE672499 — ... -1.28 1.31E-05 FLJ20753 229918_at AB046860 XM 371082 55036 -1.28 1.20E-05 SIGIRR 52940_at AA085764 NM_021805 59307 -1.28 3.70E-04 S100A6 217728_at NM 014624 NM 014624 6277 -1.28 5.27E-04 UCN 206072_at NM 003353 NM_003353 7349 -1.28 1.49E-03 INSL3 214572 s at NM 005543 NM 005543 3640 -1.28 3.79E-03 TBX3 243234_at BG055137 NM_005996 NM_016569 6926 -1.28 1.16E-04 LOC349136 242452_at AI683911 NM 198285 349136 -1.28 4.80E-04 LOC440457 206088_at NM 014834 XM_496239 440457 -1.28 1.40E-03 LONP 221833_at AI971258 NM_031490 83752 -1.27 6.14E-03 LOC158301 239193_at BF060981 — 158301 -1.27 2.55E-04 AW449624 239379_at AW449624 ... ... -1.27 2.70E-03 KCTD13 45653_at AW026481 NM_178863 253980 -1.27 2.70E-06 ST7L 216123_x_at AK024158 NM 017744 NM 138727 NM 138728 NM_138729 NM_198327 NM_198328 54879 -1.27 1.64E-04 AA835417 243007_at AA835417 — ... -1.27 1.46E-03 FLJ40342 1558854 a at BG616498 NM_152347 124989 -1.27 5.60E-05 UBE2D3 233303_at AL110175 NM_003340 NM 181886 NM 181887 NMJ81888 NM_181889 NM_181890 NM 181891 NM_181892 NM 181893 7323 -1.26 6.81 E-05 ZNF365 206448_at NM_014951 NM 199450 NM 199451 NM_199452 22891 -1.26 1.40E-03 CDKN1C 213182_x_at R78668 NM_000076 1028 -1.26 1.79E-03 FLJ32130 1554769 at BC040642 NM 152458 146540 -1.26 3.10E-04 ICAM2 213620_s_at AA126728 NM_000873 3384 -1.26 5.57E-03 KIAA0256 216278_at AL109705 NM 014701 9728 -1.26 1.61 E-03 BF432875 235782_at BF432875 XM 497668 388620 -1.26 4.13E-04 PRKACB 202741_at AA130247 NM 002731 NM_182948 NM_207578 5567 -1.25 3.74E-04 BG548427 235547 at BG548427 — ... -1.25 2.88E-03 MCF2L 35147_at AB002360 NM 024979 23263 -1.25 1.29E-04 AGPAT3 223184_s_at BC004219 NM_020132 56894 -1.25 7.98E-04 HSD17B1 205829_at NM 000413 NM_000413 3292 -1.25 2.09E-03 AF086013 1556543_at AF086013 — ... -1.25 7.87E-04 179 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 FAH Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays 202862 at NM_000137 NM_000137 2184 -1.25 3.32E-03 FLJ23754 1553248_at NM_152675 NM_152675 201252 -1.25 8.02E-03 RAB6B 225259_at AI805050 NM_016577 51560 -1.25 8.67E-05 ZNF148 243559_at BF515306 NM_021964 7707 -1.25 2.25E-03 HIAT1 230868 at BF433103 NM_033055 64645 -1.24 2.21 E-03 GAD2 243265_at AW444497 NM_000818 2572 -1.24 4.66E-03 KCTD13 221889_at AW026481 NM_178863 253980 -1.24 1.81E-04 PAN 3 239597_at AA993566 NM 175854 255967 -1.24 8.71 E-03 RPIP8 206196 s at NM 006695 NM 006695 10900 -1.24 4.99E-03 FBX022 215854_at AU146050 NM_012170 26263 -1.24 8.97E-04 AI733281 239994_at AI733281 NM_147188 -1.24 8.71 E-03 COL6A1 213428_s_at AA292373 NM 001848 1291 -1.23 1.41E-05 PHC3 215521_at AK023029 NM_024947 80012 -1.23 2.90E-05 BF431902 228469_at BF431902 — ... -1.23 3.29E-03 SLC7A1 215401_at AU147698 NM 003045 6541 -1.23 4.72E-05 ABCC5 226363 at BE550362 NM 005688 10057 -1.23 1.08E-04 WDR9 225446_at AI638279 NM_00100724 54014 -1.22 4.64E-03 C21orf18 213989_x_at AB004853 0 NM 018963 NM_033656 NM_00100725 8 NM 00100725 9 NM 00100726 0 NM 00100726 1 NM 00100726 2 NM 017438 NM_019607 54093 -1.22 4.28E-04 FLJ11267 220216_at NM_019607 56260 -1.22 2.57E-04 BE217890 240046_at BE217890 — — -1.22 1.64E-03 UBE2D3 242403_at AI459177 NM 003340 7323 -1.22 7.24E-05 AI697662 231465 at AI697662 NM 181886 NMJ81887 NM 181888 NM 181889 NM 181890 NM 181891 NM 181892 NM_181893 -1.22 6.05E-06 WDR9 1553227_s_at N M 018963 NM_00100724 a 54014 -1.22 9 76E-0.3 AI985021 238918_at Al 985021 Ό NM 018963 NM_033656 -1.22 3.05E-03 LOC387904 243760_at AI739231 XM_370711 387904 -1.21 8.97E-04 GFRA3 214479 at NM 001496 NM_001496 2676 -1.21 3.99E-03 BF196060 236521_at BF196060 — ... -1.21 8.75E-04 CDKN1C 219534_x_at NM_000076 NM_000076 1028 -1.21 3.80E-04 FLJ10613 46947_at T87245 NM_019067 54552 -1.21 6.49E-03 BG288330 235028 at BG288330 — ... -1.20 3.05E-03 PPP3CA 236545_at AA532718 NM_000944 5530 -1.20 2.51 E-03 EXT1 1564378_a_at AK025101 NM_000127 2131 -1.20 9.41 E-04 Al862542 235696 at Al862542 — — -1.20 3.39E-04 180 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., etal., Cells Useful for Immuno-Based BoNT/A Activity Assays D4S234E 213533 at M98528 NM 014392 27065 -1.20 2.09E-05 AL353951 232601_at AL353951 XM_498488 439987 -1.20 9.24E-03 )KFZp434O052 1557879_at BF110506 NM 194302 255101 -1.20 1.41E-03 MCTP1 220122_at NM_024717 NM 00100279 6 NM_024717 79772 -1.20 2.83E-05 VN1R1 221412_at NM_020633 NM_020633 57191 -1.20 1.29E-03 H29132 241658 at H29132 — — -1.20 2.35E-03 MGC13057 232773_at AI932618 NM 032321 84281 -1.20 2.72E-03 LOC51619 244046_at BF939235 NM_015983 51619 -1.20 5.06E-03 HNRPR 232004_at AK001846 NM_005826 10236 -1.20 5.41 E-04 U80764 222128_at U80764 — — -1.20 1.17E-04 RAB6IP2 1557738_at BC041344 NM 015064 NM_178037 NM 178038 NM 178039 NM_178040 23085 -1.19 2.25E-03 LOC255326 239151_at BG427809 XM 497224 255326 -1.19 4.72E-04 CTBP2 233315_at AK024947 NM 001329 NM_022802 1488 -1.19 1.31E-03 MCF2L 212935 at AB002360 NM_024979 23263 -1.19 4.90E-05 BF514509 239049_at BF514509 — — -1.19 6.48E-03 AA678564 238620_at AA678564 — — -1.19 9.54E-03 AW364675 239066_at AW364675 — — -1.19 6.72E-04 BE856960 242712_x_at BE856960 ... ... -1.18 8.35E-03 TYMS 217690_at BG281679 NM_001071 7298 -1.18 3.35E-03 AL530703 231882_at AL530703 XM 498570 440156 -1.18 1.80E-06 SH3BGR 204979_s_at NM_007341 NM 00100171 3 NM_007341 6450 -1.18 6.25E-05 KIF5C 1557089_at CA449408 XM 377774 3800 -1.18 8.52E-03 AP1GBP1 243667_at AW977986 NM 007247 NM_080550 11276 -1.18 2.85 E-04 DCAMKL1 205399_at NM 004734 NM 004734 9201 -1.18 8.71 E-03 JAG2 32137_at Y14330 NM_002226 NM 145159 3714 -1.18 9.67 E-03 TNFRSF25 219423_x_at NM 003790 NM_003790 NM_148965 NM 148966 NM_148967 NM_148968 NM_148969 NM 148970 NM_148971 NM 148972 NM_148973 NM 148974 8718 -1.18 9.97E-05 R99939 239245_at R99939 XM_498488 439987 -1.18 2.96 E-03 KLF9 203542_s_at AI690205 NM_001206 687 -1.18 9.74E-05 ZC3HDC1 218543_s_at NM 022750 NM 022750 64761 -1.17 7.23E-04 IDS 1559136_s_at AU140213 NM 000202 NM 006123 3423 -1.17 9.45E-03 CDKN1C 213348_at N33167 NM 000076 1028 -1.17 3.74E-04 MLLT10 238257_at N64035 NM 00100956 9 NM 004641 8028 -1.17 8.79E-03 LRRN6A 227933_at AM93252 NM_032808 84894 -1.17 5.79E-05 IL10RB 209575_at BC001903 NM_000628 3588 -1.17 2.48E-04 181 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 KIF1A Jacky, B., et al., 225482 at Cells Useful for Immuno-Based BoNT/A Activity Assays AL533416 NM_004321 547 -1.17 1.50E-03 FAM46A 221766_s_at AW246673 NM 017633 55603 -1.17 3.00E-04 D4S234E 209570_s_at BC001745 NM 014392 27065 -1.17 3.84E-06 PDCD2 228420_at AW590850 NM_002598 5134 -1.17 2.71 E-03 )KFZp313N062 1555906_s_at AM47556 NM_144781 NM 173826 285343 -1.17 1.60E-05 TIMP1 201666_at NM 003254 NM_003254 7076 -1.17 1.45E-03 LOC401074 1559826 a at BC039495 XM_376247 401074 -1.16 6.12E-03 AW300500 228907 at AW300500 — — -1.16 9.31 E-03 BACH 2 227173_s_at AW450901 NM 021813 60468 -1.16 1.95E-04 FLJ11800 220575_at NM 024974 NM_024974 80039 -1.15 8.14E-05 AU146999 215986_at AU146999 — — -1.15 4.17E-05 FLJ10404 243047 at AV698751 NM 019057 54540 -1.15 3.32E-06 AI744451 81811_at Al 744451 XM 373053 391733 -1.15 6.74E-04 UBE2D3 240383_at AI239832 NM 003340 7323 -1.15 1.23E-03 YEATS2 236462_at AA742310 NM_181886 NM_181887 NM 181888 NM_181889 NM 181890 NM_181891 NM_181892 NM_181893 NM_018023 55689 -1.15 9.25E-03 LTBP3 219922_s_at NM_021070 NM 021070 4054 -1.15 3.83E-05 IREB2 1563130_a_at AL109710 NM_004136 3658 -1.15 6.76E-04 CRYGS 223644_s_at AF161703 NM_017541 1427 -1.15 2.33E-03 BE326951 243562_at BE326951 — — -1.15 3.70E-03 KIAA0217 241965_at BF589232 NM_015155 23185 -1.15 6.15E-04 AK024175 222152_at AK024175 XM_373053 391733 -1.15 6.88E-04 DNAJB5 207453_s_at NM 012266 NM_012266 25822 -1.14 8.99E-05 AI798680 227943 at Al798680 — — -1.14 1.60E-03 VPS13C 235023_at AA828371 NM 017684 54832 -1.14 2.37E-03 LAF4 232286_at AA572675 NM_002285 3899 -1.14 5.79E-03 AA021559 244815_at AA021559 — — -1.14 1.83E-03 AI051572 243310 at AI051572 — — -1.14 4.12E-04 PAK3 214078_at AF070581 NM 002578 5063 -1.14 2.48E-05 RNF19 230599_at AI681558 NM_015435 25897 -1.14 5.16E-03 SH3GL2 205751 at NM 003026 NM_183419 NM_003026 6456 -1.14 7.99E-04 AA779679 227805 at AA779679 — — -1.13 3.80E-04 BC009525 1568813_at BC009525 — — -1.13 2.50E-03 AA682539 235575_at AA682539 — — -1.13 2.54E-03 PSMB7 244801 at AI248671 NM 002799 5695 -1.13 3.90E-06 FARP1 239246_at AW102941 NM_00100171 c 10160 -1.13 2.54E-03 SF3B14 1561923 a at AF147425 0 NM_005766 NM 016047 51639 -1.13 1.53E-03 KATNB1 203163_at NM_005886 NM 005886 10300 -1.13 6.37E-05 FLJ 10246 220458 at NM_018038 N M 018038 55104 -1.13 1.74E-03 BE738279 242546_at BE738279 XM 498570 440156 -1.13 1.10E-07 ABR 212895_s_at AL527773 NM 001092 29 -1.13 2.07E-03 AI631833 227396_at AI631833 NM_021962 -1.12 5.31 E-03 AI424872 81737_at AI424872 XM_497487 441749 -1.12 1.92E-03 AK027225 222145_at AK027225 XM_497487 441749 -1.12 2.62E-04 BIRC1 204860_s_at AI817801 NM_004536 4671 -1.12 3.81 E-03 SLC12A7 218066 at NM_006598 NM_006598 10723 -1.12 2.90E-03 182 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et at., Cells Useful for Immuno-Based BoNT/A Activity Assays TRIO 209010 s at AI797657 NM_007118 7204 -1.12 7.12E-05 AV699781 239577 at AV699781 — ... -1.12 1.61E-03 AB037813 231969_at AB037813 — ... -1.12 9.92E-03 ABCC3 208161_s_at NM_020037 NM 003786 NM 020037 NM 020038 8714 -1.12 5.49E-03 ATP2B2 204685_s_at R52647 NM_00100133 1 NM_001683 491 -1.12 3.74E-05 FGF7 230918 at BE856598 NM_002009 2252 -1.12 7.41 E-03 MR AS 225185_at BF343625 NM 012219 22808 -1.12 4.78E-04 LOC255326 231106_at Al684591 XM 497224 255326 -1.11 2.25E-04 BTN3A3 204821_at NM_006994 NM 006994 NM_197974 10384 -1.11 3.77E-04 PPP2R5C 1557718_at AL834350 NM 002719 NM 178586 NM_178587 NMTI78588 5527 -1.11 2.73E-03 BE467577 228251_at BE467577 — ... -1.11 3.53E-03 BM983749 1558686 at BM983749 — — -1.11 5.76E-04 AK022031 1556713 at AK022031 ... ... -1.11 3.57E-03 PPP3R1 1565811_at BC033945 NM_000945 5534 -1.11 1.10E-03 AI907083 222380_s_at Al907083 XM_373053 391733 -1.11 5.00E-03 DNAH5 243938 x at AI872645 NM 001369 1767 -1.11 1.58E-03 PRPH 213847 at NM 006262 NM_006262 5630 -1.10 3.67E-03 AI796536 229810_at Al 796536 — — -1.10 1.23E-04 R3HDM 210714_at BC001217 NM_015361 23518 -1.10 5.50E-03 AA412065 242492_at AA412065 ... ... -1.10 1.37E-03 SCN2A2 206381 at NM_021007 NM_021007 6326 -1.10 5.85E-03 AU157716 227051_at AU157716 — ... -1.10 3.37E-03 LOC339047 214682_at AK023376 XM 290671 339047 -1.10 9.05E-04 CNOT4 1559347_at BI599409 NM_00100822 5 NM 013316 4850 -1.10 5.45E-03 POFUT2 209578_s_at BC000626 NM 015227 NM 133634 NM 133635 23275 -1.10 5.47E-04 PTN 209466_x_at M57399 NM_002825 5764 -1.10 2.17E-04 BF001773 241906_at BF001773 — — -1.10 3.71 E-03 TM4SF8 232632_at AU145719 NM 005724 NM_198902 10099 -1.10 3.31 E-04 CKLFSF8 234562_x_at AK000115 NM 178868 152189 -1.10 5.38E-04 PCSK7 TAGLN 232521_at AK027156 NM 00100152 2 NM_003186 NM_004716 6876 9159 -1.10 8.49E-03 HNRPD 236000_s_at AA863112 NM 00100381 0 NM 002138 NM 031369 NM 031370 3184 -1.10 1.74E-03 FARP1 235501_at AW961576 NM_00100171 5 NM_005766 10160 -1.10 2.99E-03 LOC255326 242393 x at AV708982 XM 497224 255326 -1.10 5.74E-03 IBTK 215086_at AB037838 NM 015525 25998 -1.10 8.89E-03 183 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays DTNA 211493_x_at U46744 NM 001390 NM_001391 NM_001392 NM 032975 NM 032978 NM 032979 NM_032980 NM 032981 1837 -1.10 3.03E-03 DTNA 227084_at AW339310 NM 001390 NM_001391 NM_001392 NM 032975 NM 032978 NM_032979 NM_032980 NM 032981 1837 -1.10 3.15E-03 LOC54103 213142_x_at AV700415 XM_379881 XM_499340 54103 -1.10 8.79E-03 AA088430 242556_at AA088430 — — -1.10 2.33E-04 RP42 242428_at N58513 NM 020640 54165 -1.09 9.11E-03 KIAA1731 1565830_at AL833615 XM_374922 85459 -1.09 3.43E-03 LOC284408 1558809_s_at AK094324 — 284408 -1.09 6.98E-05 LOC255326 233271_at AU145563 XM_497224 255326 -1.09 6.71 E-05 AW290940 226773 at AW290940 — — -1.09 4.20E-05 TAGLN2 200916 at NM_003564 NM_003564 8407 -1.09 2.34E-03 HIST1H2BD 209911_x_at BC002842 NM_021063 NM 138720 3017 -1.09 2.10E-03 RSNL2 242710_at AI791820 NM_024692 79745 -1.09 1.82E-03 AL833123 1559496_at AL833123 — ... -1.09 6.13E-04 AF138859 233037_at AF138859 — — -1.09 4.93E-04 DUSP16 1558740 s at R30807 NM 030640 80824 -1.09 5.64E-04 NSUN6 242239_at AW970888 NM_182543 221078 -1.09 1.80E-03 SLC39A14 1561886_a_at R00975 NM 015359 23516 -1.09 3.24E-03 FMNL2 1556656_at BF477401 NM_00100441 7 NM 00100442 1 NM 00100442 2 NM_052905 114793 -1.09 8.64E-03 MY015B 219173_at NM 024957 XR 000222 80022 -1.09 7.64E-03 MTSS1 232757_at AV705679 NM 014751 9788 -1.09 4.23E-03 BCL6B 243825_at T79768 NM_181844 255877 -1.09 2.13E-04 AK023394 232107_at AK023394 ... -1.09 4.94E-04 CDKN1C 216894_x_at D64137 NM_000076 1028 -1.09 8.38E-05 PGAP1 220576 at NM 024989 NM 024989 80055 -1.09 4.32E-03 ATP8B2 226771_at AB032963 NM_00100585 5 NM 020452 57198 -1.09 7.06E-06 PDE5A 1556257_at BC037908 NM 001083 NM 033430 NM 033431 NM 033437 8654 -1.08 5.89E-03 STK17A 241410_at Al 949081 NM 004760 9263 -1.08 7.78E-03 FBLP-1 1555480_a_at AF459643 NM 017556 54751 -1.08 4.80E-04 184 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays NDUFV3 226616_s_at NM_021075 NM 00100150 3 NM_021075 4731 -1.08 7.94E-07 PHACTR1 1561642_at AF085859 NM 030948 221692 -1.08 6.92E-03 PAK3 236277_at H23551 NM 002578 5063 -1.08 7.40E-05 TP53BP1 1569098_s_at BU508386 NM 005657 7158 -1.08 1.66E-05 FNBP1 230389_at BE046511 NM_015033 23048 -1.08 1.40E-03 AK021973 234098_at AK021973 — — -1.08 9.97E-03 N70015 236510_at N70015 — — -1.08 8.69E-04 PPP2R2C 223574_x_at AF086924 NM_020416 NM_181876 5522 -1.08 2.02E-05 JMY 226352_at BF447037 NM 152405 133746 -1.08 4.14E-03 MYT1L 1554633 a at AF036943 NM 015025 23040 -1.08 2.26E-03 AV03 237330_at AA603494 XM 380173 253260 -1.08 2.23E-03 PTPN2 240843_at N53696 NM_002828 NM 080422 NM 080423 5771 -1.07 1.44E-04 LUC7L2 242024_at T90999 NM016019 51631 -1.07 8.65E-03 AI631888 235532_at AI631888 — — -1.07 1.86E-08 PDE9A 205593_s_at NM_002606 NM_00100156 7 5152 -1.07 1.16E-05 NM_00100156 8 NM_00100156 9 NM_00100157 0 NM_00100157 1 NM_00100157 2 NM_00100157 3 NM_00100157 4 NM_00100157 5 NM_00100157 6 NM_00100157 7 NM_00100157 8 NM_00100157 9 NM_00100158 0 NM_00100158 1 NM_00100158 2 LOC92154 1555894 s at AA829283 NM 138383 92154 -1.07 1.06E-03 CUL4A 232466_at AU155661 NM_00100889 C 8451 -1.07 1.04E-04 0 NM 003589 FLJ21106 219980 at NM 025097 NM 025097 80167 -1.07 3.33E-03 GSPT1 240452_at AA580082 NM 002094 2935 -1.07 1.19E-03 PCAF 203845 at AV727449 NM 003884 8850 -1.07 9.18E-05 185 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays TIGD4 232998 at AK024235 NM 145720 201798 -1.07 1.44E-03 PCNXL2 1554256_a_at BC008300 NM_014801 80003 -1.06 3.23E-03 AI950451 240971_x_at AI950451 NM_024938 -1.06 6.35E-03 LOC57228 209679_s_at BC003379 NM 020467 57228 -1.06 5.22 E-04 ARFGEF1 236742_at AA132172 NM_006421 10565 -1.06 8.57E-04 FLJ14966 243611_at BG231646 NM 032867 84953 -1.06 3.24E-03 AK097571 1556261_a_at AK097571 — — -1.06 3.95E-03 FLJ22729 238295_at N22706 NM 024683 79736 -1.06 4.49E-05 BICD1 242052_at AW979272 NM 00100339 8 NM_001714 636 -1.06 1.94E-03 AA468422 239780_at AA468422 -1.06 5.66E-04 BF476403 230218_at BF476403 — — -1.06 9.08E-04 BIRC1 238446_at AI970117 NM_004536 441081 -1.06 3.30E-03 LOC441081 T78074 236386 at T78074 XM_496754 XM 496203 4671 440423 -1.06 3.85E-03 P15RS 231502_at BF591615 NM_018170 55197 -1.06 4.06E-03 JMJD1C 228793_at BF002296 NM 004241 221037 -1.06 2.41 E-05 TRIM33 214815_at AU136587 NM_015906 51592 -1.05 9.87E-04 WDR42A 233637_at AU146915 NM_033020 NM_015726 50717 -1.05 1.13E-03 AA757630 236724 at AA757630 — — -1.05 7.93E-03 NM 014152 220694_at NM_014152 — — -1.05 4.06E-04 AW665538 244532 x at AW665538 XM 496692 441014 -1.05 2.86E-03 MYST4 215597_x_at AU143799 NM_012330 23522 -1.05 4.35E-04 CAPZA1 238407_at AI792880 NM_006135 829 -1.05 2.34E-07 KIAA1276 235288 at AI627532 XM_039169 27146 -1.05 5.52E-05 CNNM1 220166_at NM 020348 NM 020348 26507 -1.05 2.70E-05 RPH3AL 221614_s_at BC005153 NM_006987 9501 -1.04 8.30E-04 MGC13098 60815_at AA601208 XM_379817 84820 -1.04 3.22E-05 AI003508 244114_x_at Al003508 XM 499280 XM 496690 401131 -1.04 2.52E-03 RAC2 213603_s_at BE138888 NM 002872 5880 -1.04 2.21 E-03 PLXNC1 206471 s at NM_005761 NM_005761 10154 -1.04 5.22E-03 C19orf30 223913_s_at AB058892 NM_174947 284424 -1.04 1.45E-03 BF002625 229530 at BF002625 — — -1.04 2.72E-03 ATP6V0A1 1559375_s_at AV739195 NM 005177 535 -1.04 7.96E-03 BACE1 224335_s_at AB050436 NM_012104 23621 -1.04 1.07E-03 MGC9850 224857_s_at BE378670 NM 138971 NM 138972 NM_138973 NM_152705 219404 -1.04 1.09E-03 BC035958 1569540_at BC035958 — — -1.04 3.88E-03 FLJ32130 1554770_x_at BC040642 NM_152458 146540 -1.04 1.31 E-05 GFRA3 229936_at AA694259 NM 001496 2676 -1.04 1.40E-03 FKBP11 228308_at AI452444 NM_016594 51303 -1.04 8.54E-03 AL 137290 233724 at AL137290 — — -1.04 4.79E-04 FRAS1 226145_s_at AL157471 NM_020875 80144 -1.04 3.23E-04 AU145394 215370_at AU145394 NM 025074 NM 032863 NM 206841 XM_496203 440423 -1.04 3.51 E-06 BRUNOL6 227775_at BE467313 NM 052840 60677 -1.04 1.58E-03 METAP2 240769 at AI733395 NM 006838 10988 -1.04 8.99E-03 NDP52 238560 at AI684710 NM_005831 10241 -1.04 2.82E-07 AW150065 217653 x at AW 150065 — — -1.04 2.30E-04 186 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays C21orf57 227421_at BF026326 NM_00100611 4 NM_058181 54059 -1.04 4.05E-06 CDKL3 1561190_at AF087989 NM_016508 51265 -1.03 1.48E-04 CLN8 219341 at NM_018941 NM 018941 2055 -1.03 2.97E-03 CACNA1B 235781_at AA448208 NM 000718 774 -1.03 6.51 E-04 CPEB4 242384_at AI452469 NM 030627 80315 -1.03 8.14E-03 BCAN 223632_s_at AI739071 NM_021948 NM_198427 63827 -1.03 2.54E-03 KIAA0746 212314_at AB018289 NM 015187 23231 -1.03 5.88E-05 PGAP1 233479_at AU148008 NM_024989 80055 -1.03 2.96E-03 C1orf50 219406_at NM_024097 NM_024097 79078 -1.03 7.42E-04 AF130084 1569538_at AF130084 — — -1.03 5.41 E-03 PCF11 239926 at AI675753 NM 015885 51585 -1.03 2.46E-03 FNBP1 230086_at AA937109 NM_015033 23048 -1.03 1.57E-04 AW117322 239415_at AW117322 XM_374094 389237 -1.03 5.77E-03 BC033530 1560209_at BC033530 — — -1.03 9.56E-05 AA888777 242740_at AA888777 — — -1.03 1.32 E-04 SFRS1 226419_s_at AA046439 NM 006924 6426 -1.03 8.12E-03 HNRPD 229434_at AA865357 NM_00100381 0 NM_002138 NM 031369 NM_031370 3184 -1.03 1.17E-04 LOC222070 51774 s at AW014299 — 222070 -1.03 7.32E-05 PHKA1 229876_at BE503584 NM_002637 5255 -1.02 1.73E-05 NPY 206001_at NM_000905 NM 000905 4852 -1.02 5.51 E-03 CD302 203799_at NM 014880 NM_014880 9936 -1.02 5.85E-04 UBE3A 1560741_at AL832250 NM_000462 NM_130838 NM 130839 7337 -1.02 1.28E-03 AI582773 214373_at Al 582773 XM 498956 440996 -1.02 5.09E-03 C21orf66 240105_at Al021902 NM_013329 NM 016631 NM 058191 NM_145328 94104 -1.02 3.11 E-04 ICA1 204002_s_at NM_022307 NM 004968 NM 022307 NM 022308 3382 -1.02 8.76E-05 CAPN2 208683 at M23254 NM_001748 824 -1.02 7.34E-04 CYLD 213295 at AA555096 NM_015247 1540 -1.02 8.54E-04 AK021477 232710_at AK021477 — — -1.02 9.52E-03 AV658469 244699 at AV658469 — — -1.02 6.27 E-04 GUCY1A3 221942_s_at Al 719730 NM_000856 2982 -1.02 1.00 E-03 FLJ10287 232489_at AK001149 NM 019083 54482 -1.02 1.54 E-03 PAQR6 219236_at NM_024897 NM 024897 NM_198406 79957 -1.02 6.43E-04 PELI1 232304_at AK026714 NM_020651 57162 -1.01 4.26E-04 AU152763 232939_at AU152763 — — -1.01 1.50E-03 AK021423 232890_at AK021423 — — -1.01 8.93E-05 SORL1 203509_at NM 003105 NM 003105 6653 -1.01 7.27E-03 PPIE 210502_s_at AF042386 NM 006112 NM 203456 NM 203457 10450 -1.01 7.51 E-03 FNBP1 239453_at AA262084 NM 015033 23048 -1.01 1.33E-05 C9orf126 233246_at Al 523450 NM_173690 286205 -1.01 4.78E-03 FAM13A1 232628_at Al 740629 NM_014883 10144 -1.01 2.51 E-03 187 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., etal., Cells Useful for Immuno-Based BoNT/A Activity Assays DDX31 236210_at AW628575 NM 022779 NM_138620 64794 -1.01 3.89E-03 CRABP2 202575_at NM 001878 NM_001878 1382 -1.01 3.16E-03 KIAA0746 212311_at AA522514 NM_015187 23231 -1.01 2.25E-03 PDE4C 206791 s at BF511742 NM_000923 5143 -1.01 1.92E-03 BE669703 229541 at BE669703 — — -1.01 8.81 E-05 MLL 212079_s_at AA715041 NM_005933 4297 -1.01 8.80E-04 ZDHHC11 221646 s at AF267859 NM_024786 79844 -1.01 2.90E-04 BC038589 1569311 at BC038589 — — -1.01 9.76E-04 C21orf66 1555125_at BC030539 NM 013329 NM 016631 NM_058191 NM_145328 94104 -1.00 1 94E-03 AK024879 216751 at AK024879 — — -1.00 8.95E-06 EFNB3 205031_at NM 001406 NM 001406 1949 -1.00 1.02E-03 AW188311 243281_at AW188311 — — -1.00 1.13E-03 N95363 213183 s at N95363 — — -1.00 2.68E-05 RAB6IP2 232565_at AK025052 NM_015064 NM 178037 NM_178038 NM_178039 NM_178040 23085 -1.00 3.56E-03 RASA4 FLJ21767 208534_s_at NM_006989 NM_006989 XM_376602 XM_379820 10156 401331 -1.00 1.13E-03 DCTD 210137_s_at BC001286 NM_001921 1635 -1.00 2.80E-03 EIF3S9 236274_at AW129967 NM_003751 NM_182712 8662 -1.00 7.13E-04 PTP4A3 206574_s_at NM_007079 NM 007079 NM_032611 11156 -1.00 8.68E-03 ARIH1 1558710_at BI791845 NM_005744 25820 -1.00 2.71 E-03 BF507816 240517 at BF507816 — — -1.00 3.52E-04 C10orf42 243335 at BE764796 NM_138357 90550 -0.99 5.78E-03 LNK 203320_at NM 005475 NM 005475 10019 -0.99 9.93E-05 OPTN 202073_at AV757675 NM_00100821 1 NM 00100821 2 NM_00100821 3 NM_021980 10133 -0.99 1.43E-03 AK022461 232472_at AK022461 — — -0.99 8.48E-04 GRK4 241989_at AW269179 NM_00100405 6 NM_00100405 7 NM_005307 NM 182982 2868 -0.99 1.24E-04 LOC200030 LOC400781 AG1 242191_at AI701905 NM_183372 XM 371384 XM_378897 XM 496394 200030 400781 440673 -0.99 5.68E-07 RAB3-GAP150 240234 at AI216539 NM 012414 25782 -0.99 3.46 E-03 DHX57 239311_at AI367034 NM_144995 NM 145646 NM_198963 90957 -0.99 3.00E-03 LRRN5 216167_at AK024867 NM_006338 NM 201630 10446 -0.99 3.96E-03 188 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays GART 230097_at AI207338 NMJ300819 2618 -0.99 1.29E-03 KIAA2024 1566166_at AL833423 NM_175085 NM 172070 130507 -0.99 2.85E-03 MLL3 244010_at AI057455 NM 021230 58508 -0.99 1.91E-03 GSDML 215659_at AK025174 NM_170606 NM 018530 55876 -0.99 4.78E-03 DSCAM 237268_at BE503065 NM_001389 1826 -0.99 1.16E-03 AK057701 1558515_at AK057701 NM_206887 -0.99 6.69E-03 MGC11332 213393_at AI767210 NM_032718 84804 -0.99 7.13E-04 ISYNA1 222240_s_at AL137749 NM_016368 51477 -0.99 2.38E-04 CLTC 220855_at NM 014127 NM 004859 1213 -0.99 7.98E-03 COL6A2 209156_s_at AY029208 NM 001849 1292 -0.98 2.04E-03 SUV420H1 242646_at AA702946 NM 058174 NM 058175 NM 016028 51111 -0.98 1.65E-04 KIAA1223 225735_at AL110131 NM 017635 XM 048747 57182 -0.98 5.36E-05 DNAJC12 218976_at NM_021800 NM_021800 56521 -0.98 1.57E-06 RHBDL1 207383_s_at NM_003961 NM_201262 NM_003961 9028 -0.98 6.79E-03 UBE2E1 236062_at AI742722 NM_003341 7324 -0.98 5.85E-03 HEL308 228736_at AW084661 NM_182666 NM_133636 113510 -0.98 1.68E-03 H28915 244359_s_at H28915 XM 496692 441014 -0.98 5.93E-03 BRUNOL5 232416_at AL390161 NM 021938 60680 -0.98 4.62E-03 RNF12 242121_at AW973232 NM 016120 51132 -0.98 6.21 E-03 SFRS15 222310_at AA648521 NM_183353 NM_020706 57466 -0.98 2.65E-04 ACSL4 1557419_a_at W95007 NM 004458 2182 -0.98 4.91 E-03 SPOCK2 202524 s at NM 014767 NM_022977 NM 014767 9806 -0.98 6.88E-05 KIAA0999 242920_at AW590838 NM_025164 23387 -0.97 3.05E-03 KCNK10 220727_at NM_021161 NM 021161 54207 -0.97 9.90E-03 AATK 205986_at NM 004920 NM_138317 NM_138318 9625 -0.97 2.81 E-05 SERTAD4 230660 at AU146709 NM 019605 56256 -0.97 5.49E-03 CDC2L5 242693_at AW664859 NM_003718 8621 -0.97 6.26 E-03 NM 025120 220728_at NM_025120 NM_031267 -0.97 5.32E-03 SMG1 244766_at BG180003 NM 014006 23049 -0.97 2.50E-03 KIAA0220 LOC440345 DNAJB5 212817 at AK023253 NM 015092 XM 496125 NM 012266 283846 440345 25822 -0.97 1.18E-03 HIST3H2A 221582 at BC001193 NM 033445 92815 -0.97 2.09E-03 SORL1 212560 at AV728268 NM_003105 6653 -0.97 4.84E-03 BBP 213882_at AA012917 NM 032027 83941 -0.97 7.60E-03 UGCGL2 218801_at NM 020121 NM 020121 55757 -0.96 1.53E-03 TLE1 228284_at BE302305 NM 005077 7088 -0.96 2.82E-06 CRYZL1 1552347_at NM_145311 NM 005111 9946 -0.96 8.59E-03 KIAA1223 225731_at BF196876 NM_145311 NM_145858 XM 048747 57182 -0.96 1.92E-04 CTNND1 238884 at AW195351 NM 001331 1500 -0.96 7.20E-03 FLJ10980 225327_at AB037791 NM_019600 56204 -0.96 4.11E-04 LOC255783 227325_at AW172584 — 255783 -0.96 6.35E-03 SLICK 244455_at AI732637 NM_198503 343450 -0.96 5.42E-04 189 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al„ Cells Useful for Immuno-Based BoNT/A Activity Assays MCM3AP 212269_s_at AJ010089 NM 003906 8888 -0.96 2.03E-05 EMR3 1561042_at AF086249 NM 032571 NM_152939 84658 -0.96 1.76E-03 OCIAD2 225314_at BG291649 NM 152398 132299 -0.96 6.40 E-05 BACE1 222463_s_at AF190725 NM 012104 NM 138971 NM_138972 NM 138973 23621 -0.96 5.33E-04 DNAJC12 223721_s_at AF176013 NM 021800 NM_201262 56521 -0.95 9.38E-05 CCNJ 1557830_at AW063658 NM_019084 54619 -0.95 1.55E-03 KLF12 243089_at AA551114 NM_007249 NM_016285 11278 -0.95 3.83E-03 RSL1D1 212019 at AK025446 NM_015659 26156 -0.95 2.34E-04 AK022004 233003_at AK022004 — ... -0.95 3.09E-03 FTO 215385_at AK022473 XM_051200 79068 -0.95 4.76E-03 AKAP10 236007 at AU147278 NM 007202 11216 -0.95 8.23E-04 PDXK 202671 s at NM 003681 NM 003681 8566 -0.95 3.67E-06 TRIT1 218617_at NM_017646 NM 017646 54802 -0.95 3.17E-07 MYT1L 210016_at BF223003 NM_015025 23040 -0.95 8.33E-05 AA573901 227783_at AA573901 — — -0.95 5.00E-04 AA804267 243185 at AA804267 ... — -0.95 9.14E-03 AW593330 237064_x_at AW593330 ... — -0.95 2.04E-03 HERC1 237632_at AA765387 NM_003922 8925 -0.95 3.34E-04 INPP1 202794 at NM 002194 NM 002194 3628 -0.95 1.43E-04 LOC169834 230876 at AI827906 XM 095965 169834 -0.95 1.26E-04 C21orf5 205248_at NM_005128 NM 005128 9980 -0.95 3.75E-04 FBXW7 222729_at BE551877 NM_018315 NM 033632 55294 -0.95 4.83E-05 NFASC 214799_at Al821777 NM_00100538 7 NM 00100538 8 NM_00100538 9 NM_015090 23114 -0.95 1.20E-03 LOC90639 235533 at AW021673 — 90639 -0.95 6.72E-03 BRUNOL5 230497_at BE503640 NM_021938 60680 -0.95 1.48E-06 CHPT1 1559739_at AK025141 NM_020244 56994 -0.95 1.25E-05 APOC1 204416_x_at NM_001645 NM_001645 341 -0.95 8.52E-03 TPD52 228818 at BF110792 NM 005079 7163 -0.94 2.91 E-03 HBXAP 215786_at AK022170 NM_016578 51773 -0.94 8.66E-03 ATXN1 203232 s at NM_000332 NM 000332 6310 -0.94 1.93E-03 PDXK 218019_s_at NM 021941 NM 003681 8566 -0.94 1.93E-04 FBXW7 218751_s_at NM_018315 NM 018315 NM_033632 55294 -0.94 8.91 E-05 ANKRD11 228866_at BF514864 NM 013275 29123 -0.94 9.50E-03 LOC149297 1558113 at BM545032 XM 097622 149297 -0.94 3.48E-03 FLJ20758 228512 at AW138833 NM_017952 55037 -0.94 8.02E-05 BE552208 229359_at BE552208 — — -0.94 3.55E-05 PDE4DIP 244511_at AV700591 NM_00100281 0 9659 -0.94 2.74E-03 NM_00100281 1 NM_00100281 2 NM_014644 NM 022359 190 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays MGC9850 224874 at N32181 NM_152705 219404 -0.94 2.65E-04 DUSP8 206374 at NM_004420 NM 004420 1850 -0.94 1.10E-05 LOC400729 LOC440745 243021_at AI344101 XMJ378824 XM_498840 400729 440745 -0.94 5.94E-03 AI939586 237930 at AI939586 — — -0.94 6.80E-03 PHF17 225820_at AV646599 NM 024900 NM_199320 79960 -0.94 5.13E-03 LOC222070 58900_at AW025284 — 222070 -0.93 6.09E-04 APOE 203381 s at N33009 NM_000041 348 -0.93 7.96E-03 AF086134 1561754_at AF086134 XM_498989 441057 -0.93 4.00E-03 AMH 206516_at NM_000479 NM_000479 268 -0.93 3.43E-04 SYT15 1560879_a_at AI971263 NM 031912 NM_181519 83849 -0.93 1.08E-03 KCNJ12 207110 at NM 021012 NM 021012 3768 -0.93 5.28E-03 ARHGEF4 205109_s_at NM_015320 NM_015320 NM_032995 50649 -0.93 2.32E-03 PPM1B 232580_x_at AL117553 NM_002706 NM_177968 NM_177969 5495 -0.93 7.12E-04 ZNF587 60794 f_at AI400621 NM 032828 84914 -0.93 6.69E-06 HIPK2 224016_at AF111850 NM_022740 28996 -0.93 8.37E-03 LOC133926 235628_x_at BG025030 — 133926 -0.93 4.71 E-03 AI681025 230220_at AI681025 — — -0.93 2.78E-04 LOC64744 225282_at AL137764 NM 022733 64744 -0.92 4.81 E-05 ICA1 214191_at W67992 NM 004968 NM_022307 NM_022308 3382 -0.92 2.91 E-04 )KFZp451M211 239240_at AI814116 NM 182585 285023 -0.92 9.61 E-03 SFRS15 222311 s at AA648521 NM 020706 57466 -0.92 6.79E-03 RNF111 241413_at W80457 NM_017610 54778 -0.92 5.97E-04 KATNB1 203162_s at NM_005886 NM_005886 10300 -0.92 3.97E-04 PPM1K 235061_at AV706522 NM_152542 152926 -0.92 2.02E-03 PHC3 233431 x at AU148142 NM 024947 80012 -0.92 1.61 E-03 TJP1 244476_at R39769 NM_003257 NM_175610 7082 -0.91 9.46E-04 ZDHHC11 232417 x at AU150300 NM 024786 79844 -0.91 3.90E-03 AKAP9 215483_at AK000270 NM 005751 NM_147166 NM 147171 NM_147185 10142 -0.91 3.78E-03 PLRG1 227246 at BF438014 NM_002669 5356 -0.91 4.23E-03 AL390216 234317_s_at AL390216 — — -0.91 9.52E-03 METAP2 244185 at AA921841 NM_006838 10988 -0.91 3.64E-04 PER1 36829_at AF022991 NM 002616 5187 -0.91 3.45E-03 FLJ44796 230757_at AA195276 NM 001001704 401209 -0.91 3.23E-03 R3HDM 240503_at AW274946 NM_015361 23518 -0.91 3.05E-03 NME5 206197_at NM_003551 NM_003551 8382 -0.91 1.53E-04 MGC5566 220449 at NM 024049 — 79015 -0.90 2.88E-03 MGC13098 222208_s_at W07700 XM 379817 XM_499280 84820 -0.90 1.93E-05 W90010 238271_x_at W90010 — — -0.90 3.98E-03 DCTD 201572 x at NM_001921 NM 001921 1635 -0.90 3.11 E-03 MGC42174 244304 at AW129650 NM_152383 129563 -0.90 8.32E-03 191 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays DJ328E19.C1. 1 LOC200030 MGC8902 LOC401967 AG1 214693_x_at BE732345 NM_015383 NM_173638 NM_183372 XM_371384 XM_496394 XM_496406 200030 25832 284565 401967 440673 -0.90 2.29E-04 AA714835 1556646_at AA714835 — — -0.90 8.70E-04 PPID 204186_s_at Al 014573 NM_005038 5481 -0.90 1.20E-03 ST18 206135 at NM 014682 NM 014682 9705 -0.90 1.28E-03 ZNF275 225382_at U82670 XM_372267 10838 -0.90 3.80E-03 W80446 231013_at W80446 — — -0.90 2.17E-03 AI200555 228275_at AI200555 — — -0.90 1.34E-05 CXorf43 1553646_at NM_144657 NM_144657 139324 -0.90 5.46E-04 PAPD4 222282_at AV761453 NM_173797 167153 -0.90 7.86E-03 AI015847 1568838_at AI015847 — — -0.90 3.96E-03 CTGLF1 1565620_at BG621044 NM_133446 119016 -0.90 3.42E-03 KIAA1838 241152 at BE466903 NM 032448 84498 -0.90 1.43E-03 SLC22A17 218675_at NM_020372 NM_016609 NM_020372 51310 -0.89 2.14E-04 FLJ21159 220145_at NM_024826 NM_024826 79884 -0.89 6.77E-03 TRIP12 244659 at AL120025 NM 004238 9320 -0.89 1.07E-03 FAM46A 224973_at AL078599 NM_017633 55603 -0.89 5.88E-03 PPP2R2C 228010_at Al669212 NM 020416 NMJ81876 5522 -0.89 1.10E-03 MAST4 210958_s_at BC003646 XM_291141 23227 -0.89 1.00E-03 KIDINS220 1557246 at AA992480 NM 020738 57498 -0.89 4.66E-03 NOB1P 223018_at BC000050 NM_014062 28987 -0.89 6.87E-03 AI469960 230653_at AI469960 — — -0.89 4.89E-03 HCG8 215985 at X92110 — 80869 -0.89 5.08E-03 BRUNOL4 238966_at AA678985 NM_020180 56853 -0.89 1.12E-05 C21orf51 228239_at AA148789 NM_058182 54065 -0.89 8.47E-04 MST1 216320 x at U37055 NM_020998 4485 -0.89 7.59E-03 DVL3 201908_at NM_004423 NM_004423 1857 -0.89 2.80E-03 NR2F1 209506_s_at BC004154 NM_005654 7025 -0.89 2.53E-05 STK19 243719_at AI973206 NM_004197 NM_032454 8859 -0.89 3.23E-03 KLF9 203543_s_at NM_001206 NM_001206 687 -0.89 1.00E-03 AA830545 235730_at AA830545 — — -0.89 1.23E-03 AI949265 229156 s at Al949265 XM 499089 441301 -0.89 2.40E-04 SHANK2 213307_at AF131790 NM 012309 NM_133266 22941 -0.88 1.79E-04 AI802997 235211_at AI802997 — — -0.88 8.15E-06 GPR123 239221 at AI884909 NM 032422 84435 -0.88 8.91 E-04 ABCA2 212772_s_at AL162060 NM 001606 NM_212533 20 -0.88 4.48E-04 AL049377 1562684_at AL049377 — — -0.88 5.29E-05 SAT2 225272 at AA128261 NM 133491 112483 -0.88 1.49E-03 ERMAP 219905_at NM 018538 NM 018538 114625 -0.88 1.01E-03 C20orf103 219463 at NM_012261 NM_012261 24141 -0.88 2.58E-03 CDS1 226185 at AK026697 NM_001263 1040 -0.88 1.82E-04 AI459283 231220 at AI459283 — — -0.88 1.08E-03 )KFZp313N062 226688_at AW003508 NM_173826 285343 -0.88 1.19E-03 AW235215 238913_at AW235215 — — -0.87 7.73E-03 SLC27A2 205768_s_at NM_003645 NM_003645 11001 -0.87 3.01 E-03 AA975422 242829 x at AA975422 — — -0.87 5.23E-03 DEPDC6 218858_at NM 022783 NM_022783 64798 -0.87 7.47E-04 192 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays CDC2L5 210965_x_at BC001274 NM 003718 NM 031267 8621 -0.87 1.03E-03 AHSA2 212980_at AL050376 NM_152392 130872 -0.87 8.94E-03 AK056212 1557215_at AK056212 — — -0.87 4.38E-04 BF114733 236703 at BF114733 — — -0.87 8.70E-03 AW628665 235555_at AW628665 — — -0.87 4.04E-04 FXR1 229519_at H48840 NM_005087 8087 -0.86 7.99E-03 AF5Q31 232865_at N59653 NM 014423 27125 -0.86 2.34E-03 TAF15 241885_at BF431050 NM_003487 NM_139215 8148 -0.86 2.03E-03 NM 001048 213921_at NM 001048 — — -0.86 1.92E-03 PFAAP5 214753_at AW084068 NM_014887 10443 -0.86 1.88E-03 FRMD4A 1560031 at R19413 NM_018027 55691 -0.86 1.21 E-04 NELF 221214_s_at NM_015537 NM 015537 26012 -0.86 5.19E-05 MGC11332 213403_at BF223370 NM_032718 84804 -0.86 5.38E-03 ETV3 1552423_at NM_005240 NM 005240 2117 -0.86 4.99E-04 TMF1 242243 at AI767435 NM 007114 7110 -0.86 4.40E-03 PIAS2 244633_at AA404996 NM_004671 NM_173206 9063 -0.86 6.85E-03 SLC19A1 229489_at AI681043 NM_003056 NM 194255 6573 -0.86 4.96E-03 ECE2 230706_s_at AI084921 NM_014693 9718 -0.86 7.23E-04 HNRPM 238610_s_at AI906424 NM_005968 NM_031203 4670 -0.86 2.13E-03 AW303888 1561346_at AW303888 — — -0.86 5.89E-07 HNRPM 233605_x_at AK022050 NM_005968 NM_031203 4670 -0.86 3.84E-05 FBX015 231472_at BE464323 NM_152676 201456 -0.86 5.46E-03 UBE2B 239163_at AW364833 NM_003337 7320 -0.86 1.91E-03 BE467787 243835_at BE467787 — — -0.86 3.40E-04 SORCS1 228194_s_at AI675836 NM_052918 114815 -0.86 7.48E-05 ZDHHC11 1552283 s at NM_024786 NM_024786 79844 -0.86 1.80E-04 DEADC1 227213 at AA706895 NM 182503 134637 -0.85 7.30E-04 RRAGC 218088_s_at NM_022157 NM_022157 64121 -0.85 7.96E-03 UBE3C 242673_at AA931284 NM 014671 9690 -0.85 2.73E-03 MGC13098 224517_at BC006435 XM 379817 XM 499280 84820 -0.85 2.71 E-05 FLJ23825 1555866_a_at BM980844 NM_173620 284004 -0.85 2.22E-03 SLC16A1 1560579_s_at BC023568 NM_003051 6566 -0.85 6.33E-04 RSNL2 226425 at AU144247 NM_024692 79745 -0.85 1.24E-03 LOC283922 228688 at AA843726 XM 208908 283922 -0.85 3.51 E-04 GOLGI N-67 213650_at AW006438 NM 015003 NM 181076 NM 181077 23015 -0.85 2.66E-03 FLJ37953 241825 at AI265967 NM_152382 129450 -0.85 1.32E-03 AV700050 228835_at AV700050 — — -0.85 2.40E-03 KIAA1915 1569706_at BC017579 XM 055481 114803 -0.85 6.38E-03 CEPT1 1561884_at AL833102 NM 00100779 4 NM_006090 10390 -0.85 1.37E-03 BF510762 230262_at BF510762 — — -0.85 2.02E-06 TAGLN2 210978_s at BC002616 NM_003564 8407 -0.84 3.57E-03 DUSP6 208893_s_at BC005047 NM_001946 NM_022652 1848 -0.84 1.45E-04 AI811800 241846 at AI811800 — — -0.84 3.44E-03 AA167167 243684 at AA167167 — — -0.84 3.92E-03 CNOT6L 227119_at BF103856 NM_144571 246175 -0.84 2.79E-07 ARIH1 242431 at AI656728 NM 005744 25820 -0.84 2.27E-03 193 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays BC037935 1569539 at BC037935 — — -0.84 6.55E-04 DUSP6 208891_at BC003143 NM_001946 NM_022652 1848 -0.84 3.81 E-03 C15orf28 220710_at NM_024970 — 80035 -0.84 9.94E-03 AA935515 242790 at AA935515 — — -0.84 1.15E-03 MSI2 243010_at BE000929 NM_138962 NM_170721 124540 -0.84 1.62E-03 CXorf45 205583_s_at NM_024810 NM 024810 79868 -0.84 2.89E-03 PMS2L5 242201 at AI418253 NM_174930 5383 -0.84 7.25E-04 AW000942 240230 s at AW000942 — — -0.84 6.90E-03 C9orf94 229585_at Al 803088 NM_152702 206938 -0.84 1.26E-03 FLJ20719 230712_at Al634549 XM_373827 55672 -0.84 5.27E-03 GA17 215190 at AV717062 NM 006360 10480 -0.84 6.82 E-03 CD200 209582_s_at H23979 NM 00100419 6 NM_00100419 7 NM_005944 4345 -0.84 7.62E-03 AA928506 213750 at AA928506 — — -0.84 2.15E-04 AHI1 221569_at AL136797 NM_017651 54806 -0.84 2.48E-05 RPIP8 213439 x at AM 97870 NM_006695 10900 -0.84 1.33E-06 AI929792 236081_at AI929792 — — -0.84 3.07E-04 CTNNB1 242558_at AW362945 NM_001904 1499 -0.84 1.09E-04 ELOVL5 1566079 at AL833001 NM_021814 60481 -0.83 1.76 E-03 WDR11 229694 at BF062828 NM 018117 55717 -0.83 2.23E-03 MAN2A2 219999_at NM_018621 NM_006122 4122 -0.83 4.36 E-03 AA825721 242228_at AA825721 — — -0.83 8.71 E-04 RAB12 238714 at AA504249 XM_113967 201475 -0.83 4.32E-04 KCNMA1 221584 s at U11058 NM_002247 3778 -0.83 7.71E-04 BE467087 231075_x_at BE467087 — — -0.83 4.80E-03 FGD5 226985_at AW269340 NM 152536 152273 -0.83 5.34E-03 ProSAPiPI 204447_at NM 014731 NM 014731 9762 -0.83 1.67E-04 ZNF539 1559449 a at BF679633 NM 203282 399655 -0.83 2.80E-04 NKX6-1 221366_at NM 006168 NM 006168 4825 -0.83 7.76E-03 FLJ22624 236560_at BE218020 NM_024808 79866 -0.83 7.40E-03 MGC72104 234949 at AL117574 NM 207350 284802 -0.83 1.91 E-03 GRIK2 1563754_at AJ252246 NM 021956 NM_175768 2898 -0.83 6.46E-03 AI018235 240314_at AI018235 — — -0.82 3.87E-03 ZNF518 242343 x at H57111 NM 014803 9849 -0.82 6.06 E-03 FNBP4 235101 at AV683244 NM_015308 23360 -0.82 3.49E-03 C21orf86 226995_at AV705934 NM_153454 257103 -0.82 2.10E-03 AW148862 235217_at AW148862 XM_380136 402582 -0.82 8.18E-03 AL559202 226458 at AL559202 — — -0.82 5.40E-05 JMJD2C 214861_at Al 341811 NM 015061 23081 -0.82 2.97E-03 AOF2 212348_s_at AB011173 NM_00100999 9 NM 015013 23028 -0.82 1.77E-05 TTC3 208663_s_at AI652848 NM_00100189 4 NM_003316 7267 -0.82 7.37E-05 BE327722 239840 at BE327722 — — -0.82 1.21 E-06 AK021474 215892_at AK021474 ... — -0.82 9.46E-05 BF344235 242202_at BF344235 XM_379855 402530 -0.82 5.35E-04 YLPM1 1557065_at AA927802 XM 085151 56252 -0.82 8.82E-03 CaMKIINalpha 228302 x at AW162846 NM_018584 55450 -0.81 1.09 E-03 AKT2 236664 at AA448167 NM 001626 208 -0.81 3.20E-03 194 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays PRKCD 202545_at NM_006254 NM 006254 NM_212539 5580 -0.81 2.09E-04 CYLD 39582_at AL050166 NM 015247 1540 -0.81 1.26E-03 EIF4G1 208624_s_at BE966878 NM 004953 NM 182917 NM_198241 NM_198242 NM_198244 1981 -0.81 7.60E-04 ACVR2 244332_at AW974077 NM_001616 92 -0.81 1.17E-06 AI150690 228466 at AI150690 — — -0.81 4.49E-04 AV700891 222303_at AV700891 — — -0.81 1.60E-03 C20orf13 233719_s_at AL121754 NM_017714 55617 -0.81 6.92E-04 SMURF2 230099 at AH 39993 NM 022739 64750 -0.81 2.36E-03 SHC2 213464_at AV705938 XM_375550 25759 -0.81 4.62E-06 AW167298 228116_at AW167298 XM 210856 283029 -0.80 5.41 E-03 GPR56 206582_s_at NM_005682 NM_005682 NM 201524 NM_201525 9289 -0.80 4.72E-03 ATXN7 209964_s_at AF032105 NM_000333 6314 -0.80 2.95E-03 AK000995 215349_at AK000995 — — -0.80 4.02E-03 AW086077 232800 at AW086077 — — -0.80 1.60E-03 SLC37A1 218928_s_at NM_018964 NM 018964 54020 -0.80 5.55E-03 PCNXL2 229202_at AI768826 NM 014801 NM 024938 80003 -0.80 2.18E-04 SCMH1 221216 s at NM 012236 NM_012236 22955 -0.80 5.20E-06 FLJ31951 236322_at AA830854 NM_144726 153830 -0.80 5.68E-03 CXXC5 233955_x_at AK001782 NM_016463 51523 -0.80 9.43E-05 KIAA0220 231989 s at AC003007 — 283846 -0.80 5.47E-04 POLR3C 239383_at AW023610 NM 006468 10623 -0.79 4.37E-03 SLC9A3R2 209830_s_at AF035771 NM_004785 9351 -0.79 1.09E-04 CACNA1D 207998_s_at NM 000720 NM_000720 776 -0.79 2.71 E-03 AI417268 225028_at AI417268 — — -0.79 5.37E-03 CTSB 213274_s_at AA020826 NM 001908 NM_147780 NM 147781 NM 147782 NM_147783 1508 -0.79 2.12E-04 C9orf85 1557805_at AF085969 NM 182505 NM_198394 138241 -0.79 4.15E-06 TNRC15 1560133 at BC012484 NM 015575 26058 -0.79 1.04E-04 ARSD 225280_x_at N51673 NM_001669 NM_009589 414 -0.79 8.39E-03 KLHDC1 1552733_at NM 172193 NM_172193 122773 -0.79 8.55E-05 PRO0478 220696_at NM_014129 — 29048 -0.79 7.62E-04 RAB40B 204547_at NM_006822 NM_006822 10966 -0.79 3.04E-04 ETFDH 33494_at S69232 NM_004453 2110 -0.79 1.02E-03 TGFBR1 236561_at AV700621 NM_004612 7046 -0.79 6.33E-03 GPR18 233554 at AF339764 NM 005292 2841 -0.79 2.72E-04 U2AF1 231904_at AU122448 NM_006758 7307 -0.79 1.73E-03 0KFZP434I071' 231954_at AL137273 — 54553 -0.79 1.34E-03 YAP 244803_at AI335191 NM 018253 NM 139118 NMJ39119 NM_139120 NM_139121 55249 -0.79 7.84E-05 LOC23117 238341 at BF677084 XM 290670 23117 -0.79 1.63E-03 CLASP2 212308_at AL137636 NM 015097 23122 -0.78 1.67E-03 C18orf17 238480_at Al871745 NM 153211 125488 -0.78 8.79E-04 195 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B„ et al„ Cells Useful for Immuno-Based BoNT/A Activity Assays LOC51066 206741_at NM_015931 NM 015931 51066 -0.78 3.65E-05 S100A13 202598_at NM 005979 XM 371380 6284 -0.78 4.04E-03 FLJ39653 1553145 at BC010030 NM_152684 202020 -0.78 4.89E-03 ANP32A 235954_at AA972597 NM 006305 8125 -0.78 9.06E-03 TAF15 227884_at AW296067 NM 003487 NM_139215 8148 -0.78 1.80E-03 HNRPR 208765_s_at NM_005826 NM_005826 10236 -0.78 8.21 E-05 AF194537 224549_x_at AF194537 — ... -0.78 6.16E-03 AF5Q31 1555436_a at BC025700 NM_014423 27125 -0.78 9.74E-05 MGC47869 229888 at AA861435 NM 175874 144608 -0.78 5.64E-03 MEG3 235077_at BF956762 XR_000277 55384 -0.78 2.12E-03 DKFZp547A02c 214731_at AB037854 NM_018704 55917 -0.78 1.66E-03 AI820796 217704_x_at Al 820796 — — -0.78 1.61 E-04 CCNB1IP1 217988_at NM_021178 NM 021178 NM_182849 NM 182851 NM 182852 57820 -0.77 9.59E-03 WDFY1 1562955_at BC028181 NM 020830 57590 -0.77 2.91 E-03 GPLD1 238752_at AA780295 NM_001503 NM_177483 2822 -0.77 2.12E-04 CTSB 213275_x_at W47179 NM 001908 NM_147780 NM 147781 NM 147782 NM 147783 1508 -0.77 2.40E-03 PLA2G4B 222256 s at AK000550 NM_005090 8681 -0.77 2.03E-03 BE856980 230961_at BE856980 — ... -0.77 2.41 E-03 ABTB1 229164_s_at Al 337369 NM_032548 NM 172027 NM_172028 80325 -0.77 2.25E-03 AI702720 242309_at Al 702720 ... ... -0.77 2.84E-03 MGC4707 238161_at AA813859 NM_00100367 6 NM_00100367 7 NM 00100367 8 NM_024113 79096 -0.77 2.25E-03 CD200 209583_s_at AF063591 NM_00100419 6 NM_00100419 7 NM_005944 4345 -0.77 1.43E-03 GTF3C3 1555439_at AF465407 NM 012086 9330 -0.77 3.57E-05 PTPRD 214043_at BF062299 NM_002839 NM 130391 NM_130392 NM 130393 5789 -0.77 6.45E-05 MLR1 235970 at AI807408 NM_153686 254251 -0.77 1.70E-03 AI305170 235747_at AI305170 ... ... -0.77 8.11 E-04 PLXNC1 213241_at AF035307 NM 005761 10154 -0.77 8.27E-03 SP192 1569320 at CA391618 NM 021639 60313 -0.77 2.71 E-03 LRCH3 1559490_at AL832278 NM_032773 84859 -0.77 7.53E-03 BC035170 1561079_at BC035170 — ... -0.77 3.38E-03 BC029480 1554447_at BC029480 — ... -0.77 1.93E-03 AI598222 235679 at AI598222 — — -0.77 4.88E-04 SH3KBP1 223082_at AF230904 NM_031892 30011 -0.77 9.30E-05 TNFSF13B 223502_s_at AF134715 NM_006573 10673 -0.77 2.15E-06 196 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays AP3B2 205678 at NM_004644 NM 004644 8120 -0.76 1 23E-04 MDS009 236649 at AA907927 NM 020234 56986 -0.76 6.41 E-04 CLI PR-59 212358_at AL117468 NM_015526 25999 -0.76 2.11E-03 EDG4 206723_s_at AFO11466 NM_004720 9170 -0.76 2.87E-04 RNASET2 217984 at NM 003730 NM_003730 8635 -0.76 7.52E-03 AI979338 229364_at AI979338 — — -0.76 5.81 E-03 KIAA1545 225704_at AA527531 XM_495939 57666 -0.76 8.16E-03 MGC29898 235259_at AA398590 NM_145048 133015 -0.76 3.12E-03 SIDT2 56256 at AA150165 NM_015996 51092 -0.76 8.92E-03 MGC20741 232826 at AU144129 NM_018561 25862 -0.76 2.64E-03 WBSCR19 232964_at AL137266 NM_175064 285955 -0.76 3.56E-03 ACTR2 234210_x_at AK025051 NM_00100538 6 NM_005722 10097 -0.76 2.63E-03 LOC92249 212957_s_at AU154785 XM_499179 92249 -0.76 1.06E-03 JAK1 234193_at AK025218 NM_002227 3716 -0.76 5.21 E-03 PRH1 243389 at AW663570 NM_006250 5554 -0.76 3.39E-03 AI523613 222358 x at AI523613 — — -0.76 4.89E-06 HSPA12A 214434_at AB007877 XM 048898 259217 -0.76 6.62E-03 PIK3R2 1568629_s_at BC033311 NM_005027 5296 -0.76 4.17E-03 MEG3 212732 at AI950273 XR_000277 55384 -0.76 2.60E-03 AI743452 237031_at AI743452 — — -0.76 8.51 E-03 PVT1 222087_at AW451806 XM 372058 5820 -0.76 1.17E-04 HNRPD 235999_at AA863112 NM 00100381 0 NM 002138 NM_031369 NM_031370 3184 -0.75 2.35E-03 BG253162 242585_at BG253162 — — -0.75 7.96E-04 LOC401320 238540_at AA933883 XM_379482 XM_380098 401320 -0.75 9.69E-03 AK024681 231972_at AK024681 — — -0.75 5.89E-05 FLJ14167 232289 at BF237871 — 92080 -0.75 9.36E-03 FLJ10996 244648_at AA007283 NM_019044 54520 -0.75 2.90E-03 TMEM25 226647 at AL562445 NM_032780 84866 -0.75 1.43E-03 BC003629 210230_at BC003629 — — -0.75 7.07E-03 DUSP6 208892_s_at BC003143 NM_001946 NM_022652 1848 -0.75 5.05E-03 H63 1552719_at NM_138423 NM_138423 NM_177974 113201 -0.75 2.02E-03 CXorf45 205584 at NM 024810 NM_024810 79868 -0.75 2.96E-03 BG396868 1559957_a_at BG396868 — — -0.75 1.66 E-04 CLDN12 223249_at AL136770 NM 012129 9069 -0.75 3.65E-04 UBE2G2 209042_s_at BC001738 NM 003343 NM_182688 7327 -0.75 1.16E-05 BTN3A1 209770_at U90552 NM_007048 NM_194441 11119 -0.75 8.21 E-03 MRPL1 223154 at AF212225 NM 020236 65008 -0.75 1.63E-03 SYNJ1 207594_s_at NM_003895 NM 003895 NM_203446 8867 -0.75 9.53E-03 SORBS1 218087_s_at NM_015385 NM_006434 NM 015385 10580 -0.75 9.17E-03 PORCN 219483_s_at NM_022825 NM_022825 NM_203473 NM_203474 NM 203475 NM_203476 64840 -0.75 3.19E-05 ZRANB3 244092_at AI670931 NM 032143 84083 -0.75 9.19E-03 197 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays MRPS30 231207_at AW263539 NM_016640 10884 -0.75 6.93E-04 FLJ12666 217893 s at NM 024595 NM 024595 79647 -0.74 3.79E-03 KFZp761L141' 238426_at AV707703 NM_152913 222865 -0.74 8.47E-03 AI814750 1565692 at AI814750 — — -0.74 2.10E-03 H2AFY 226840_at AW291297 NM 004893 NM 138609 NM_138610 9555 -0.74 2.05E-04 LOC388312 238678_at AI094787 XM_373704 388312 -0.74 3.88E-03 MCAM 209087_x_at AF089868 NM 006500 4162 -0.74 6.99E-03 SH3YL1 204019_s_at NM_015677 NM 015677 26751 -0.74 1.21E-03 KCNH2 210036_s_at AB044806 NM 000238 NM_172056 NM_172057 3757 -0.74 6.86E-05 AW157450 235716_at AW157450 — — -0.74 1.29E-03 LOC400099 230136_at Al 573252 XM 378399 400099 -0.74 3.10E-03 ASB13 239610_at BF509210 NM_024701 79754 -0.74 1.28E-03 POU6F1 216330 s at L14482 NM 002702 5463 -0.74 2.20E-03 SH2D3C 1552667_a_at NM_005489 NM_005489 NM_170600 10044 -0.74 7.58E-03 JAM2 219213_at NM_021219 NM_021219 58494 -0.74 3.58E-05 AW665096 214188_at AW665096 — — -0.74 2.49E-03 RIOK3 215588_x_at AK024958 NM_003831 NM_145906 8780 -0.73 2.49E-04 Al963605 230269 at Al 963605 — — -0.73 8.73E-04 BE217923 228686 at BE217923 — — -073 1.71 E-03 C6orf111 226412 at N66397 NM_032870 25957 -0.73 9.78E-03 BG109865 222459_at BG109865 — — -0.73 1.83E-03 SP3 232529_at AU144413 NM_003111 6670 -0.73 2.50E-03 RAB18 229398 at Al 769954 NM 021252 22931 -0.73 3.78E-03 KIAA1324 243349_at AI672868 NM_020775 57535 -0.73 8.70E-03 CTSB 227961_at AA130998 NM 001908 NM_147780 NM 147781 NM_147782 NM_147783 1508 -0.73 7.63 E-04 AV733292 225444 at AV733292 — — -0.73 1.88E-04 H73101 1556984 at H73101 — — -0.73 1.17E-03 MGAT4A 219797_at NM_012214 NM_012214 11320 -0.73 2.44E-03 EPOR 396_f_at X97671 NM 000121 2057 -0.73 4.18E-03 LOC401394 231406 at AW205664 XM_379512 401394 -0.73 2.54E-04 GPR153 221902 at AL567940 NM 207370 387509 -0.73 2.83E-03 KIAA0241 1563452_at AL833560 NM_015060 23080 -0.73 5.29E-04 BF114745 235459_at BF114745 — — -0.73 8.34E-03 AA553722 243594 x at AA553722 — — -0.73 9.09E-04 AL359605 227318 at AL359605 ... ... -0.73 3.65E-05 SMA4 214850 at X75940 NM_021652 11039 -0.73 1.38 E-03 ADFP 209122_at BC005127 NM_001122 123 -0.73 5.72E-04 ETS2 201329_s_at NM 005239 NM_005239 2114 -0.73 5.11 E-03 AV761014 217667_at AV761014 — — -0.73 4.49E-03 LOC283174 229734_at BF507379 NM_001001873 283174 -0.73 1.27E-04 IGBP1 242337 at Al347128 NM 001551 3476 -0.73 3.64E-03 TMEM1 209412_at U61500 NM 00100172 3 NM_003274 7109 -0.73 3.07E-03 MGEA5 223494_at AF307332 NM 012215 10724 -0.73 4.98E-03 PEX6 204545 at NM 000287 NM 000287 5190 -0.73 9.95E-03 MGC42174 242539_at AW665509 NM_152383 129563 -0.73 6.73E-04 KIF5C 203129 s at BF059313 XMJ377774 3800 -0.73 3.45E-04 198 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays GPR56 212070_at AL554008 NM_005682 NM_201524 NM_201525 9289 -0.72 1.51E-03 AMOTL2 203002_at NM_016201 NM_016201 51421 -0.72 5.43E-04 LOC440360 236838 at H11609 XM 498641 440360 -0.72 5.58E-03 MYEF2 222153_at AK023133 NM_016132 50804 -0.72 2.99E-03 T82487 241759_at T82487 — ... -0.72 2.18E-03 CSTB 201201_at NM_000100 NM_000100 1476 -0.72 9.61E-04 NGLY1 207492_at NM 025105 NM_018297 55768 -0.72 9.68E-03 DUSP8 238594 x at Al 864441 NM 004420 1850 -0.72 6.31 E-03 LUZP1 1558173_a_at AK093016 NM 033631 7798 -0.72 3.02E-04 BRUNOL4 223654_s_at BC004167 NM 020180 56853 -0.72 3.06E-04 RGS8 234297 at AL359941 NM_033345 85397 -0.72 8.24E-03 AI950023 244433_at Al 950023 — ... -0.72 5.91 E-03 AA327293 1566284_at AA327293 — — -0.72 1.66E-03 CA442342 1556097_at CA442342 — — -0.72 3.35E-03 PDE8B 243590_at AA860184 NM 003719 8622 -0.72 9.18E-03 ARHGAP1 241419_at AA709154 NM_004308 392 -0.72 4.95E-03 DKFZp547l014 207283_at NM_020217 NM 020217 56969 -0.72 2.61 E-03 DNASE1L1 203912_s_at NM_006730 NM 00100993 2 NM_00100993 3 NM_00100993 4 NM 006730 1774 -0.72 1.52 E-03 ANKRD17 225852_at BE463523 NM_032217 NM_198889 26057 -0.72 7.58E-06 AI827550 229606_at AI827550 — — -0.72 1.23E-04 AI538880 1558250_s_at AI538880 — — -0.72 7.65E-05 AI040738 240730_at AI040738 — — -0.72 7.11 E-03 FBXW7 229419_at BF222826 NM 018315 NM_033632 55294 -0.72 5.69E-04 ABCG1 204567_s_at NM_004915 NM 004915 NM_016818 NM 207174 NM_207627 NM_207628 NM_207629 NM 207630 9619 -0.72 3.49E-04 TRA2A 213593_s_at AW978896 NM_013293 29896 -0.72 4.15E-03 APC 215310_at AF038181 NM_000038 324 -0.72 3.73E-03 CXXC5 222996_s_at BC002490 NM 016463 51523 -0.71 8.07 E-04 CSNK1A1 235464_at AA010757 NM 001892 1452 -0.71 6.52 E-04 USP7 230967_s_at BF433061 NM_003470 7874 -0.71 1.6 9 E-03 TAS2R14 235762_at AI458566 NM_023922 50840 -0.71 1.07E-03 HNRPR 208766 s at BC001449 NM 005826 10236 -0.71 5.99E-04 CAPN1 232012 at AV691296 NM_005186 823 -0.71 4.07E-03 AI825987 235889_at AI825987 — — -0.71 1.70E-03 FLJ23867 226706_at BE301252 — 200058 -0.71 5.23E-03 IGF2 202410 x at NM 000612 NM_000612 3481 -0.71 2.47E-03 AI887898 228423 at AI887898 XM 374094 389237 -0.71 2.25E-03 MGC14801 224443_at BC005997 NM 032705 84791 -0.71 1.76E-03 C1orf50 62212_at W37846 NM_024097 79078 -0.71 1.18E-03 RLF 204243 at NM_012421 NM_012421 6018 -0.71 2.22E-04 AW268719 236798 at AW268719 — — -0.71 1.17E-04 AL080112 216858_x_at AL080112 — — -0.71 6.17E-04 Al022648 242972_at Al 022648 ... ... -0.71 3.82E-04 199 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays AW072078 230959 at AW072078 XM 496690 401131 -0.71 2.04E-05 PHKA1 205450_at NM_002637 NM_002637 5255 -0.71 2.60E-05 AA694209 229Q66_at AA694209 — — -0.71 1.09E-04 MAP1LC3B 208786_s_at AF183417 NM 022818 81631 -0.71 4.58E-03 PABPC4 201064_s_at NM 003819 NM 003819 8761 -0.71 2.02E-04 IGF2 210881_s_at M17863 NM_000612 3481 -0.70 3.36E-03 C5orf16 1564031_a_at AK054889 NM_173828 285613 -0.70 3.27E-03 UBXD1 223012_at AF272894 NM 025241 80700 -0.70 2.81E-03 ANKRD28 229307_at N32051 NM 015199 23243 -0.70 5.01 E-03 UNQ1912 226752_at AI816071 NM_198507 345757 -0.70 3.53E-03 ARHGAP1 202117 at BG468434 NM 004308 392 -0.70 2.81 E-03 C21orf59 218123_at NM_017835 NM 017835 NM 021254 56683 -0.70 6.33E-07 MONDOA 225157_at AW245631 NM_014938 22877 -0.70 1.12E-04 NM 024900 218517_at NM_024900 — — -0.70 8.22E-04 C6orf133 215558_at AK001118 NM 015255 23304 -0.70 6.83E-03 TRIM14 203147_s_at BE962483 NM 014788 NM 033219 NM_033220 NM_033221 9830 -0.70 7.70E-03 NM 018678 220494 s at NM_018678 — — -0.70 1.04E-03 LOC144766 243986_at BE409452 XM 378419 144766 -0.70 1.05E-03 PPP3CA 202429_s_at AL353950 NM 000944 5530 -0.70 5.44E-04 RNF41 201962_s_at NM_005785 NM 005785 NM_194358 NM_194359 10193 -0.70 4.15E-04 RPL35A 215208_x_at AK021571 NM_000996 6165 -0.70 5.45E-03 CLSTN3 204375 at NM 014718 NM 014718 9746 -0.70 4.42E-04 PTK2 241387_at AW276701 NM_005607 NM_153831 5747 -0.70 5.63E-04 SYNJ1 212990_at AB020717 NM 003895 NM 203446 8867 -0.69 1.15E-06 KIAA1276 227504_s_at N64630 XM_039169 27146 -0.69 7.28E-06 MLR1 240592_at AI939336 NM 153686 254251 -0.69 3.41 E-04 LMNA 1554600_s_at BC033088 NM 005572 NM 170707 NM_170708 4000 -0.69 9.76E-03 ZNF207 1556035_s_at AI201248 NM 003457 7756 -0.69 3.42E-03 TM4SF2 202242_at NM 004615 NM 004615 7102 -0.69 2.98E-03 AGRN 212285 s at AW008051 NM_198576 375790 -0.69 4.04E-03 AF116695 224254_x_at AF116695 — — -0.69 4.32E-03 FLJ20758 228020_at BG055431 NM_017952 55037 -0.69 3.97E-05 MYLIP 223130_s_at AF212221 NM 013262 29116 -0.69 8.41 E-03 PTPRD 213362_at N73931 NM 002839 NM_130391 NM_130392 NM_130393 5789 -0.69 4.67E-03 UNC5A 236448 at R37358 XM 030300 90249 -0.69 1.44E-05 USP36 224979_s_at AU154368 NM 025090 57602 -0.69 1.61 E-03 RBPMS2 228802_at BE348466 XM 496072 348093 -0.69 1.05E-03 SENP2 222523 at BE622841 NM 021627 59343 -0.69 4.48E-03 ATXN1 203231 s at AW235612 NM_000332 6310 -0.69 9.97E-03 AA630955 242133_s_at AA630955 — ... -0.69 1.82E-03 LOC285458 242577_at BF109197 — 285458 -0.69 9.98E-03 ZNF573 217627 at BE515346 NM 152360 126231 -0.69 5.61 E-03 APC 216933_x_at S67788 NM_000038 324 -0.69 1.03E-03 200 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B„ et a!., Cells Useful for Immuno-Based BoNT/A Activity Assays WDFY3 212598_at BE348236 NM 014991 NM 178583 NM_178585 23001 -0.69 1.37E-05 FNBP1 244286_at AI017983 NM 015033 23048 -0.69 3.21 E-03 DSCR3 203635 at NM 006052 NM 006052 10311 -0.68 1.64E-05 MONDOA 202519_at NM 014938 NM_014938 22877 -0.68 3.72E-04 AI859990 244197_x_at AI859990 — — -0.68 1.47E-03 C7orf19 1558426_x_at BC016797 NM 032831 80228 -0.68 6.95E-04 MGC20419 225642_at AL581536 NM_138417 112970 -0.68 5.44 E-03 KIAA1644 221901_at BF516072 XM_376018 85352 -0.68 3.43E-03 AI146751 242565_x_at AI146751 — — -0.68 1.09E-03 PHF17 225816_at AW138134 NM_024900 NM 199320 79960 -0.68 8.15E-04 NFASC 213438_at AA995925 NM_00100538 7 NM_00100538 8 NM 00100538 9 NM_015090 23114 -0.68 1.25E-03 AI332346 225445 at AI332346 — — -0.68 4.20E-03 PEX6 238672_at AW953952 NM_000287 5190 -0.68 1.21E-05 PALM2-AKAP2 226694_at BG540494 NM 007203 NM_147150 445815 -0.68 3.43E-04 AI821721 241223 x at AI821721 — — -0.68 5.48E-04 BF197705 230401 at BF197705 ... ... -0.68 7.84E-03 BG527339 226457_at BG527339 — — -0.68 2.91 E-04 LOC146174 230721_at BF436957 NM_173501 146174 -0.68 1.72 E-03 C1orf21 223127 s at AW003850 NM 030806 81563 -0.68 6.33E-04 FBX031 222352_at BE465371 NMJ324735 79791 -0.68 1.00E-04 TAF15 227891_s_at AU144462 NM_003487 NM_139215 8148 -0.68 9.77E-03 ZNF207 231848 x at AW192569 NM 003457 7756 -0.68 1.45E-03 ZNF37A 228711_at BF059259 NM_00100709 4 NM 003421 7587 -0.68 5.10E-04 ATP11A 1556055_at U90905 NM 015205 NM_032189 23250 -0.68 4.26 E-03 TIM14 225358_at AI003794 NM 145261 NM 201259 NM 201260 NM_201261 131118 -0.68 2.38E-03 COL5A1 212489_at AI983428 NM_000093 1289 -0.68 8.47E-03 MGC35274 226748 at AI674731 NM 153374 256586 -0.68 1.32E-05 ST7L 238512_at BF961733 NM_017744 NM_138727 NM_138728 NM 138729 NM_198327 NM_198328 54879 -0.67 2.66E-03 HUMPPA 213230_at AI422335 NM_014603 30850 -0.67 7.14E-03 Cep164 204251 s at NM 014956 NM 014956 22897 -0.67 5.51 E-03 C14orf159 218298_s_at NM_024952 NM_024952 80017 -0.67 2.50E-03 MCTP1 235740_at BG250585 NM_00100279 6 NM_024717 79772 -0.67 3.10E-03 ZNF451 215012 at AU144775 NM 015555 26036 -0.67 3.81 E-03 201 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays MAPT 225379_at AA199717 NM_005910 NM 016834 NM_016835 NM_016841 4137 -0.67 6.84E-04 SMURF2 241900_at AW195928 NM_022739 64750 -0.67 7.08E-03 FOXP1 235444_at AI417897 NM_032682 27086 -0.67 5.32E-04 ZBED3 228402_at Al679968 NM_032367 84327 -0.67 3.66E-03 ABCC8 210246 s at AF087138 NM_000352 6833 -0.67 5.10E-03 FLJ11016 219754_at NM_018301 NM_018301 55285 -0.67 4.87E-03 AI344332 227227_at Al344332 XM_373737 388397 -0.67 6.03E-05 HIS1 202814_s_at AW193511 NM_006460 10614 -0.67 5.23E-04 LOC401394 217529 at BE547674 XM 379512 401394 -0.67 1.35E-04 TMEM34 219074_at NM_018241 NM 018241 55751 -0.67 2.81E-03 PPID 204185_x_at NM 005038 NM_005038 5481 -0.67 2.92E-03 SFRS2IP 232597_x_at AK025132 NM_004719 9169 -0.67 3.06E-03 SLC35E1 227518_at AW051365 NM 024881 79939 -0.67 7.53E-03 C14orf118 229514_at AB032978 NM 017926 NM_017972 55668 -0.67 8.14E-04 KIAA0913 212359 s at W89120 NM 015037 23053 -0.67 7.72E-03 C9orf85 238912_x_at AA824363 NM 182505 NM_198394 138241 -0.67 1.86E-03 CaMKIINalpha 218309_at NM_018584 NM 018584 55450 -0.67 1.94E-07 TAF1 227205_at AW575233 NM 004606 NM 138923 6872 -0.67 3.47E-03 LOC144363 225469_at AAO15609 NM_00100166C 144363 -0.66 4.42E-03 TNKS 233152 x at AL049979 NM_003747 8658 -0.66 2.23E-03 C1orf52 228135 at AA738437 NM_198077 148423 -0.66 3.10E-03 BG502771 226397 s at BG502771 — — -0.66 6.19E-05 ELM01 204513_s_at NM 014800 NM_014800 NM_130442 9844 -0.66 6.47E-03 AI627803 236194 at AI627803 — — -0.66 2.79E-03 AA604601 1570566 at AA604601 — — -0.66 1.29E-04 RAMP1 204916 at NM005855 NM 005855 10267 -0.66 2.24E-06 AL137655 231886_at AL137655 XM_373814 388572 -0.66 1.31E-04 PCDHB16 232099_at AB046841 NM_020957 57717 -0.66 4.23E-03 KIAA0804 209553_at BC001001 NM_00100992 1 NM_015303 23355 -0.66 2.61 E-03 N63920 226179 at N63920 — — -0.66 3.55E-04 MCPH1 219592_at NM_024596 NM_024596 79648 -0.66 3.60E-03 MLLT6 224784_at BG024886 NM 005937 4302 -0.66 6.68E-04 ARRDC1 226405 s at AK001822 NM 152285 92714 -0.66 2.73E-03 RAB11FIP4 224482_s_at BC006240 NM_032932 84440 -0.66 3.11 E-03 EFNA1 202023_at NM_004428 NM_004428 NM_182685 1942 -0.66 2.72 E-03 C18orf17 1552307 a at NM 153211 NM 153211 125488 -0.66 6.53E-03 MBTD1 207115_x_at NM_017643 NM_017643 54799 -0.66 6.47E-03 ALG3 207396_s_at NM_005787 NM_00100694 0 NM 00100694 1 NM_00100694 2 NM 005787 10195 -0.66 8.88E-04 IFNAR1 225661_at AA811138 NM_000629 3454 -0.66 2.66E-03 FER1L4 222245_S_at AF218012 — 80307 -0.66 3.17E-03 DDX50 1568815_a_at AA903184 NM_024045 79009 -0.66 4.02E-03 202 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 ELK1 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays 210376 x at M25269 NM 005229 2002 -0.66 8.45E-03 FBX031 224162_s_at BC002985 NM_024735 79791 -0.66 3.15E-03 RNF13 201779_s_at AF070558 NM_007282 11342 -0.66 1.55E-03 LOC440345 238449_at BG534511 NM 183381 NM_183382 NM_183383 NM_183384 XM_496125 440345 -0.66 1.28E-03 CXXC5 224516 s at BC006428 NM 016463 51523 -0.66 1.05E-05 MKNK2 223199_at AA404592 NM_017572 2872 -0.66 2.26E-03 NFYC 202215_s_at NM_014223 NM_199054 NM_014223 4802 -0.66 4.41 E-04 RAB12 236019_at AI076335 XM 113967 201475 -0.66 1.77E-03 ETFDH 205530_at NM_004453 NM_004453 2110 -0.66 1.11E-03 LOC153364 230298_at AI692906 NM 203406 153364 -0.66 1.11 E-04 ELM03 219411_at NM_024712 NM 024712 79767 -0.66 2.82E-03 SERTAD4 229674 at AL035414 NM 019605 56256 -0.66 3.57E-04 GPRASP1 204793_at NMJ514710 NM_014710 9737 -0.65 1.35E-03 SMAD4 1565703 at AL832789 NM_005359 4089 -0.65 4.45E-03 ATP9A 216129_at AL117659 XM 030577 10079 -0.65 3.73E-03 MGC21688 232806 s at AU158601 NM 144635 131408 -0.65 3.23E-03 LOC90410 210312_s_at BC002640 NM_174887 90410 -0.65 1.34 E-04 BE348430 230235_at BE348430 — — -0.65 1.62 E-04 UBE2G2 1557053_s_at BC035653 NM 003343 7327 -0.65 1.15E-03 TRA2A 229574_at Al268231 NM 182688 NMJ313293 29896 -0.65 1.49E-03 MGC42174 238602_at AL036541 NM 152383 129563 -0.65 9.27E-03 QSCN6 201482_at NM_002826 NM 00100412 8 NM_002826 NM 020154 5768 -0.65 6.49E-03 C15orf24 217898_at NM 020154 56851 -0.65 6.93E-03 SLC01A2 211480_s_at AF085224 NM 005075 6579 -0.65 3.46E-04 ATP2C1 230387_at AL038450 NM_021094 NM_134431 NM_00100148 C 27032 -0.65 6.34E-03 AF5Q31 232864_s_at N59653 O NM 00100148 6 NM_00100148 7 NM_014382 NM_014423 27125 -0.65 1.51E-03 AL049975 234020_x_at AL049975 — — -0.64 1.81E-03 AI634543 242208 at AI634543 — — -0.64 1.23E-03 AI695743 244534_at AI695743 — ... -0.64 9.29E-03 CCNDBP1 223084_s_at AF246144 NM_012142 23582 -0.64 1.19E-03 ZBED3 235109 at AI887983 NM_037370 NM 032367 84327 -0.64 4.83E-03 BACE1 222462_s_at AI653425 NM_012104 23621 -0.64 2.24E-05 SERTAD4 235337_at AI276403 NM_138971 NM 138972 NM 138973 NM 019605 56256 -0.64 9.08 E-04 ZNF596 240324_at H50654 NM_173539 169270 -0.64 6.01 E-04 AA845825 217534 at AA845825 — — -0.64 1.19E-03 BE551142 241091_at BE551142 XM_497668 388620 -0.64 2.87E-03 KIAA1181 224576_at AK000752 NM_020462 57222 -0.64 9.10E-03 JMJD1C 221763_at AI694023 NM_004241 221037 -0.64 1.29E-04 203 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 PPP2R5B Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays 635_s_at L42374 NM_006244 5526 -0.64 7.89E-04 FLJ31438 228316_at AA905470 NM_152385 130162 -0.64 3.25E-05 Al524240 238863_x_at AI524240 — — -0.64 3.04E-05 DJ971N18.2 240094_at AL042660 NM_021156 56255 -0.64 7.59E-03 TTC3 208661_s_at AW510696 NM_00100189 λ 7267 -0.64 1.95E-04 JMJD3 41386_i_at AB002344 NM_003316 XM 043272 23135 -0.64 6.66E-03 SEC6L1 228847 at W69265 NM_007277 11336 -0.64 8.93E-03 C21orf106 227199_at AW027812 NM_015151 23181 -0.64 1.63E-03 KIAA1919 242851_at BE964989 NM_206889 NM_206890 NM_206891 NM_153369 91749 -0.64 1.22E-03 AI683552 217679 x at AI683552 — — -0.64 3.76E-03 ICA1 207949_s_at NM_004968 NM 004968 3382 -0.64 3.58E-06 AI885665 238360 s at AI885665 NM_022307 NM_022308 -0.64 3.47E-04 AW511239 229765_at AW511239 — — -0.64 7.38E-03 BI496583 1557675_at BI496583 — — -0.63 3.19E-03 LOC253982 214993_at AF070642 NM_181718 253982 -0.63 1.41E-04 ASB13 218862_at NM 024701 NM_198907 NM 024701 79754 -0.63 2.48E-03 C18orf23 230143 at BF433220 NM 152470 147341 -0.63 3.83E-03 WDFY3 212602_at AI806395 NM_014991 23001 -0.63 3.16E-04 TMEM5 204808 s at NM„014254 NM_178583 NM 178585 NM 014254 10329 -0.63 4.54E-05 SPTBN1 200671_s_at N92501 NM_003128 6711 -0.63 4.18E-04 AI216567 236754_at AI216567 NM_178313 -0.63 2.90E-03 PTPRN2 203030_s_at AF007555 NM_002847 5799 -0.63 7.43E-03 M17S2 1568857_a_at BC012591 NM_130842 NM 130843 NM_005899 4077 -0.63 6.88E-03 C6orf170 1553726 s at NM 152730 NM_031858 NM_031862 NM 152730 221322 -0.63 2.53E-04 SON 201085_s_at AA664291 NM_003103 6651 -0.63 2.20E-03 AA102332 240172 at AA102332 NM_032195 NM 058183 NM 138925 NM 138926 NM_138927 -0.63 6.39E-03 MGC15416 225861_at AW001250 NM 032371 84331 -0.63 4.24E-04 AK024602 222207_x_at AK024602 NM_138418 -0.63 1.29E-03 AW945538 239208 s at AW945538 — — -0.63 2.53E-03 AM 40364 221740_x_at AM 40364 XM 373737 388397 -0.63 1.10E-04 ARHGEF7 1562271_x_at AL831814 NM_003899 8874 -0.63 5.76E-03 AG1 215434_x_at AV684285 NM 145735 XM_371384 440673 -0.63 1.46E-03 BZRAP1 205839_s_at NM 004758 XM_496394 NM_004758 9256 -0.63 3.66E-03 C14orf149 227699 at BF511003 NM_144581 112849 -0.63 5.42E-03 U2AF1 232141 at AU144161 NM_006758 7307 -0.63 2.12E-03 204 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays CAMK2B 213276_at T15766 NM_001220 NM_172078 NM_172079 NM 172080 NM 172081 NM_172082 NM_172083 NM_172084 816 -0.63 7.05E-03 NRD1 229422 at AA448346 NM 002525 4898 -0.63 5.72E-03 C10orf18 244165_at AI809511 XM_374765 54906 -0.62 9.92E-03 TMPIT 234084_x_at AU147104 NM_031925 83862 -0.62 7.32E-04 AI334297 225961_at AI334297 — — -0.62 9.96E-03 MAPT 203929_s_at AI056359 NM 005910 NM_016834 NM_016835 NM 016841 4137 -0.62 6.17E-04 XRN1 242995_at AW976347 NM_019001 54464 -0.62 5.64E-03 NFIC 226377_at Al093722 NM_005597 NM_205843 4782 -0.62 1.82E-03 FBX09 212991_at AL137520 NM 012347 NM_033480 NM 033481 26268 -0.62 1.09E-05 OSBPL6 223805_at AF323728 NM_032523 NM_145739 114880 -0.62 1.05E-04 NRD1 242235_x_at AW978721 NM_002525 4898 -0.62 6.13E-04 ATXN7L1 227732_at AB033044 — 57485 -0.62 5.06E-03 PDPK1 32029_at AC005591 NM_002613 NM_031268 5170 -0.62 8.86E-03 BF110411 221878_at BF110411 XM_371506 388969 -0.62 4.02E-03 SNX1 1559154_at AK098001 NM_003099 NM 148955 NM_152826 6642 -0.62 2.16E-03 LOC282965 230108 at BF433475 — 282965 -0.62 7.42E-03 AA045233 224686 x at AA045233 XM_373737 388397 -0.62 1.42E-04 TIMM9 218316_at NM 012460 NM 012460 26520 -0.62 9.93E-03 PTPRN2 203029_s_at NM_002847 NM 002847 NM 130842 NM_130843 5799 -0.62 1.78E-04 MGC52110 226039 at AW006441 NM 001008215 493753 -0.62 2.08E-04 SCN5A 207413_s_at NM_000335 NM 000335 NM_198056 6331 -0.62 2.09E-03 ATF7 244473_at R37637 NM_006856 11016 -0.62 6.77E-04 AL162054 1559420 x at AL162054 — — -0.62 2.91 E-03 INHA 1569409_x_at BC037812 NM_002191 3623 -0.62 9.67E-03 CTTN 214782_at AU155105 NM_005231 NM_138565 2017 -0.62 3.85E-03 FLJ20758 228590 at AA045257 NM 017952 55037 -0.62 1.29E-06 DTX3 221835_at N92708 NM_178502 196403 -0.61 6.82E-03 AFG3L2 232919_at AU147380 NM 006796 10939 -0.61 7.83E-03 NR2F1 209505_at Al 951185 NM 005654 7025 -0.61 1.18E-04 MYLIP 228098_s_at AW292746 NM_013262 29116 -0.61 9.86E-05 FLJ00312 221971_x_at BE672818 XM_374801 399761 -0.61 2.00E-05 STAT3 235680_at AI914925 NM_003150 NM_139276 NM 213662 6774 -0.61 7.44E-04 PALM2-AKAP2 202759_s_at BE879367 NM 007203 NM_147150 445815 -0.61 1.06E-05 AI692645 230206_at AI692645 — — -0.61 7.26E-04 205 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays PPP3CA 202457 s at AA911231 NM 000944 5530 -0.61 1.76E-04 POM121 212178_s_at AK022555 NM_172020 340318 -0.61 6.29E-04 LOC340318 AK024255 232569_at AK024255 XM 290401 XM_379877 9883 -0.61 5.98E-03 TRIM8 223132_s_at AF220034 NM_030912 81603 -0.61 5.53E-05 PDLIM4 211564_s_at BC003096 NM_003687 8572 -0.61 4.83E-04 SHFM3 221519 at AF281859 NM_022039 6468 -0.61 8.52E-06 RIC3 220282 at NM 024557 NM_024557 79608 -0.61 3.26E-03 AK024881 234723_x_at AK024881 — — -0.61 7.62E-03 DKFZP434H13; 204494_s_at AW516789 NM_015492 56905 -0.61 1.22E-04 SMA3 206565_x_at NM_006780 NM_006780 10571 -0.61 8.06E-03 C21orf108 212996_s_at AI803485 — 9875 -0.61 8.23E-04 MAP1LC3B 208785_s_at BE893893 NM_022818 81631 -0.61 2.42E-03 PRKCZ 202178 at NM_002744 NM 002744 5590 -0.61 2.33E-03 BICD1 214806_at U90030 NM 00100339 8 NM_001714 NM 006301 636 -0.61 1.56E-03 MAP3K12 205447_s_at BE222201 7786 -0.61 3.86E-03 PSIP1 232363_at AK024516 NM 021144 11168 -0.61 2.71 E-03 HPCAL1 205462_s_at NM 002149 NM_033222 NM_002149 3241 -0.61 1.40E-05 PALM2-AKAP2 202760_s_at NM_007203 NM_134421 NM 007203 445815 -0.61 4.74E-03 LOC282997 222307_at AI695595 NM_147150 282997 -0.61 8.47E-03 BF339133 213296 at BF339133 — — -0.60 3.76E-03 AI791303 238890 at AI791303 — — -0.60 2.71 E-03 KIAA1881 207730 x at NM 017932 XM_375558 114782 -0.60 1.50E-03 AL355532 213845_at AL355532 — — -0.60 1.88E-04 ELOVL5 214153_at BE467941 NM 021814 60481 -0.60 2.39E-03 FLJ38991 227442 at BG283902 NM 173827 285521 -0.60 9.08E-05 C3orf6 226713_at AI247881 NM_174908 152137 -0.60 6.70E-03 FNTA 230808_at AA833870 NM_178335 NM_002027 2339 -0.60 3.58E-03 MGC54289 225228 at AI474054 NM 178454 128338 -0.60 6.20E-03 KIAA1536 209002_s_at BC003177 NM 020898 57658 -0.60 9.44E-03 CDK5R1 204995_at AL567411 NM_003885 8851 -0.60 4.65E-04 SFXN3 1559993_at AK091504 NM_030971 81855 -0.60 4.27E-03 AU157441 226511 at AU157441 — — -0.60 3.90E-03 FLJ23861 231252_at AI680874 NM_152519 151050 -0.60 5.09E-03 BE219067 243641_at BE219067 — — -0.60 2.03E-06 BC042959 1556194 a at BC042959 — — -0.60 5.58E-03 PFAAP5 221899_at AI809961 NM 014887 10443 -0.60 8.51 E-03 PPP2R2C 223573_s_at AW166283 NM_020416 5522 -0.60 4.24E-03 CLASP2 212309 at AV725315 NM_181876 NM_015097 23122 -0.60 3.17E-04 INSR 226450_at AV703054 NM_000208 3643 -0.60 8.36E-06 USP34 207365 x at NM_014709 NM_014709 9736 -0.60 8.70E-03 RUNX1 236114_at AI798118 NM_00100189 r\ 861 -0.59 5.87E-03 VPS13C 218396_at NM 017684 U NM 001754 NM_017684 54832 -0.59 6.96 E-03 KPNA1 202057_at BC002374 NM_002264 3836 -0.59 3.30E-04 RPS6KL1 223534_s_at BC004540 NM 031464 83694 -0.59 6.25E-04 CNNM3 240339_at AA829860 NM_017623 26505 -0.59 2.25E-03 AK022428 234731 at AK022428 NM_199078 -0.59 3.34 E-04 206 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays NT5C3 223298 s at AF312735 NM 016489 51251 -0.59 8.53E-04 JMJD3 213146_at AA521267 XM_043272 23135 -0.59 7.42E-03 NM_018289 219794 at NM_018289 — — -0.59 4.18E-07 FCMD 205283 at NM_006731 NM_006731 2218 -0.59 4.33E-03 C18orf17 1570552 at AF363068 NM 153211 125488 -0.59 2.11 E-03 FLJ23451 1569601_at BF106979 NM_024766 79823 -0.59 1.13E-03 BF514509 239050_s_at BF514509 — — -0.59 1.54E-03 LOC442647 229157 at AI949265 XM_499544 442647 -0.59 2.37E-03 SLC24A5 228792 at AU145100 NM_205850 283652 -0.59 1.36E-03 AI796076 243339_at AI796076 — — -0.59 2.87E-03 BE857570 235677_at BE857570 — — -0.59 2.57E-03 RALGDS 209051_s_at AF295773 NM_006266 5900 -0.59 8.43E-03 SND1 242506 at AM 38785 NM 014390 27044 -0.59 1.79E-03 BM914560 1558220_at BM914560 XM_496669 440993 -0.58 6.65E-03 SEZ6L2 218720_x_at NM_012410 NM 012410 NM_201575 26470 -0.58 3.65E-03 AW294192 228040_at AW294192 — — -0.58 3.57E-04 PCNT2 233387_s_at AK024009 NM_006031 5116 -0.58 5.43E-03 CHST5 219182_at NM_024533 NM 012126 NM_024533 23563 -0.58 9.75E-03 MGC15416 1553715_s_at NM_032371 NM_032371 NM_138418 84331 -0.58 4.55E-03 ABAT 209460_at AF237813 NM_000663 NM_020686 18 -0.58 5.91 E-03 C9orf112 225586 at BF222775 NM_138778 92715 -0.58 3.08E-03 DSCR3 2l7309_s_at AJ001867 NM_006052 10311 -0.58 6.91 E-03 IER2 202081_at NM_004907 NM_004907 9592 -0.58 6.30E-03 MGC4796 223852_s_at BC005169 NM 032017 83931 -0.58 7.87E-03 CD151 204306_s_at NM_004357 NM_004357 NM_139030 977 -0.58 1 98E-03 MACF1 208633_s_at W61052 NM_012090 NM 033044 23499 -0.58 1.19E-03 MGC16279 65585_at AA527515 NM_032916 85002 -0.58 2.75E-03 ZBTB4 225629_s at AI669498 NM 020899 57659 -0.58 4.70E-05 GRIPAP1 1557562_at AI984118 NM_020137 NM_207672 56850 -0.58 3.18E-03 AU145662 233399_x_at AU145662 XM_499131 441383 -0.58 1.90E-03 SYNGAP1 230297 x_at AW002361 NM 006772 8831 -0.58 5.57E-03 MGC15407 224968 at AL518311 NM_080667 112942 -0.58 3.50E-03 207 PCT/US2010/027242 WO 2010/105234 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays

Table 7. Increased Gene Expression in Cell Lines H1 and BB10 vs. Cell Line 2D6 in Differentiated State Using Microarray Analysis

Gene Symbol Probe Set ID Representative Public ID RefSeq Transcript ID Entrez Gene Log2 Ratio pvalue PLS3 201215_at NM 005032 NM_005032 5358 6.46 2.18E-11 PEG3 209242 at AL042588 NM_006210 5178 6.29 4.38E-07 FLJ32942 227711_at BG150433 NM_144594 121355 6.29 3.26E-08 MSN 200600 at NM 002444 NM 002444 4478 6.24 7.65E-10 )KFZp667G211 214030_at BE501352 XM 376254 131544 6.06 3.72E-05 MCM10 220651_s_at NM_018518 NM 018518 55388 5.94 2.90E-06 TPTE 220205_at NM_013315 NM 182751 NM 013315 7179 5.89 2.90E-07 DLG7 203764_at NM 014750 NM 199259 NM_199260 NM 199261 NM 014750 9787 5.79 1.58E-05 PLK2 201939_at NM 006622 NM 006622 10769 5.72 1.74E-08 HMMR 209709_s_at U29343 NM 012484 3161 5.64 2.12E-07 BUB1 209642_at AF043294 NM_012485 NM 004336 699 5.53 9.46E-06 RGS5 1555725 a at AF493929 NM 003617 8490 5.49 1.14E-04 NDN 209550_at U35139 NM_002487 4692 5.42 1.66E-05 FLJ34013 225710_at H99792 — — 5.39 6.18E-08 FAT 201579_at NM 005245 NM 005245 2195 5.36 1.20E-03 RGS5 218353_at NM_025226 NM 003617 8490 5.29 4.83E-04 KCTD12 212192_at AI718937 NM_138444 115207 5.28 1.26E-06 TFPI2 209278 s_at L27624 NM_006528 7980 5.28 1.22E-05 AI813331 229097_at AI813331 — — 5.23 3.44E-07 GNG11 204115_at NM_004126 NM_004126 2791 5.21 7.49E-06 AM 97932 229498_at Al 197932 — — 5.17 1.33E-07 RGS5 209070_s_at Al 183997 NM_003617 8490 5.14 3.20E-04 MKI67 212021 s at AU132185 NM 002417 4288 5.04 2.78E-05 PRSS12 205515_at NM_003619 NM_003619 8492 5.01 3.19E-07 MCM10 222962_s_at AB042719 NM_018518 55388 5.01 2.63E-07 BIRC5 210334 x at AB028869 NM_182751 NM_001168 332 5.00 5.51 E-05 RAMP 222680_s_at AK001261 NM_016448 51514 5.00 2.74E-05 ASF1B 218115_at NM_018154 NM_018154 55723 4.97 3.08E-05 MKI67 212023_s_at AU147044 NM_002417 4288 4.97 7.09E-06 MKI67 212020_s at AU152107 NM 002417 4288 4.97 3.98E-07 ATAD2 218782_s_at NM_014109 NM_014109 29028 4.96 7.16E-07 BIRC5 202094_at AA648913 NM_001168 332 4.96 3.70E-05 FLJ40629 229610_at AW088063 NM 152515 150468 4.96 2.93E-05 EX01 204603_at NM_003686 NM 003686 9156 4.90 1.18E-05 DEPDC1 222958_s_at AK000490 NMJ306027 NM_130398 NM 017779 55635 4.89 2.51 E-07 RGS5 209071_s_at AF159570 NM 003617 8490 4.87 1.25E-04 RRM2 209773_s_at BC001886 NMJ301034 6241 4.86 4.36E-05 KIF14 236641_at AW183154 XM_375825 9928 4.86 1.11 E-05 OIP5 213599_at BE045993 NM 007280 11339 4.85 5.98E-08 C10orf3 218542_at NM 018131 NM 018131 55165 4.85 4.79E-06 BRRN1 212949_at D38553 NM_015341 23397 4.85 2.87E-06 FLJ10719 223785_at BC004277 NM_018193 55215 4.84 6.89E-06 208 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application CHEK2 N31731 BRIP1 MELK KIF20A SPARC BUB1 BASP1 SULT1C2 GTSE1 DAZ1 DAZ3 DAZ2 DAZ4 CDC45L PRSS12 BRIP1 RNF182 SLC1A3 DAZ1 DAZ3 DAZ2 DAZ4 GTSE1 NEIL3 SPARC FN5 CENPA MYBL1 MAOA HMMR ZNF367 NMU CDCA8 FLJ10156 SHCBP1 DIAPH3 18495 (BOT)/1957205.00451

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays 210416_s_at BC004207 NM_00100573 11200 4.81 1.17E-03 D NM_007194 NM_145862 230165 at N31731 — — 4.80 2.02E-07 235609 at BF056791 NM 032043 83990 4.80 3.95E-05 204825_at NM 014791 NM 014791 9833 4.80 2.52E-04 218755_at NM 005733 NM_005733 10112 4.71 2.34E-05 200665 s at NM 003118 NM 003118 6678 4.71 6.23E-06 215509 s_at AL137654 NM 004336 699 4.69 2.73E-06 202391_at NM_006317 NM_006317 10409 4.68 5.50E-07 1553321_a_at NM 006588 NM 006588 27233 4.66 9.28E-06 204317_at BF305380 NM 016426 51512 4.64 2.33E-08 208282_x_at NM 020363 NM 00100537 1617 4.64 4.44E-03 5 57054 NM_00100578 57055 5 57135 NM_00100578 6 NM_004081 NM_020363 NM_020364 NM 020420 204126_s_at NM_003504 NM_003504 8318 4.62 2.60E-04 213802 at AI810767 NM 003619 8492 4.61 1.09E-05 221703_at AF360549 NM_032043 83990 4.60 7.21 E-06 230720 at Al884906 NM 152737 221687 4.59 1.15E-07 202800_at NM_004172 NM 004172 6507 4.55 1.78 E-06 207912 s at NM 004081 NM 00100537 1617 4.55 1.51E-03 5 57054 NM_00100578 57055 5 57135 NM_00100578 6 204315 s at AI340239 NM_004081 NM 020363 NM 020364 NM_020420 NM_016426 51512 4.54 9.21 E-06 219502 at NM 018248 NM 018248 55247 4.54 8.88E-06 212667_at AL575922 NM 003118 6678 4.53 5.72E-05 219806 s at NM 020179 NM_020179 56935 4.53 2.58E-05 204962 s at NM_001809 NM_001809 1058 4.53 1.46E-06 213906_at AW592266 XM 034274 4603 4.52 2.33E-05 212741 at AA923354 NM_000240 4128 4.52 9.33E-07 207165_at NM_012485 N M 012484 3161 4.51 5.91 E-06 229551 x at N62196 NM_012485 NM 153695 195828 4.50 2.65E-05 206023 at NM 006681 NM 006681 10874 4.50 1.75E-04 221520_s_at BC001651 NM 018101 55143 4.49 1.67E-06 221591_s_at BC005004 NM_019013 54478 4.48 1.61 E-06 219493_at NM 024745 NM 024745 79801 4.47 1.26E-05 232596_at AL354829 NM 030932 81624 4.46 1.53E-06 209 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays DAZ1 DAZ3 DAZ2 DAZ4 207909_x_at U21663 NM_00100537 5 NM_00100578 5 NM_00100578 6 NM_004081 NM 020363 NM_020364 NM 020420 1617 57054 57055 57135 4.46 3.63E-03 FOXM1 202580_x_at NM_021953 NM_021953 NM 202002 NM_202003 2305 4.44 1.30E-04 MAB21L2 210302 s at AF262032 NM 006439 10586 4.43 9.15E-04 KIF18A 221258_s_at NM_031217 NM 031217 81930 4.42 2.20E-07 STK6 204092_s_at NM_003600 NM 003600 NM 198433 NM 198434 NM 198435 NM 198436 NM 198437 6790 4.41 1.58E-06 ANLN 1552619_a_at NM 018685 NM 018685 54443 4.41 6.79E-05 MINA 213188_s_at Al 823896 NM 032778 NM_153182 84864 4.41 1.40E-04 CENPE 205046 at NM 001813 NM 001813 1062 4.40 5.00E-07 FLJ20641 227928 at AI224977 NM 017915 55010 4.40 5.48E-07 CDC2 203214_x_at NM 001786 NM_001786 NM_033379 983 4.37 1.70E-06 KIF4A 218355_at NM 012310 NM 012310 24137 4.36 5.88E-08 CDCA2 226661_at T90295 NM 152562 157313 4.34 2.67E-07 BRCA1 211851_x_at AF005068 NM_007294 NM_007295 NM 007296 NM_007297 NM_007298 NM_007299 NM 007300 NM_007301 NM 007302 NM_007303 NM 007304 NM_007305 NM 007306 672 4.34 1.52E-05 DEPDC1 235545 at Al 810054 NM 017779 55635 4.32 1.48E-07 MINA 213189_at BE966695 NM 032778 NM_153182 84864 4.31 1.18E-06 CDKN3 209714_s_at AF213033 NM_005192 1033 4.31 8.89E-05 PLK4 204887 s at NM_014264 NM 014264 10733 4.29 1.64E-04 RRM2 201890_at BE966236 NM 001034 6241 4.28 5.37E-05 RAD51 205024_s_at NM 002875 NM 002875 NM_133487 5888 4.27 1.40E-05 AURKB 209464 at ABO11446 NM 004217 9212 4.27 2.23E-05 TTK 204822 at NM_003318 NM 003318 7272 4.27 7.61 E-06 POLE2 205909 at NM 002692 NM 002692 5427 4.27 9.18E-04 210 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B„ et al., Cells Useful for Immuno-Based BoNT/A Activity Assays OSBPL3 209627_s_at AY008372 NM_015550 NM 145320 NMJ45321 NM_145322 NM_145323 NM 145324 26031 4.26 1.75E-05 PEG3 209243_s_at AF208967 NM 006210 5178 4.26 3.95E-05 KIF11 204444_at NM_004523 NM 004523 3832 4.25 4.91 E-04 Spc24 235572_at AI469788 NM 182513 147841 4.25 7.74E-09 FGFR2 203639_s_at M80634 NM_000141 NM 022969 NM_022970 NM 022971 NM_022972 NM 022973 NM_022974 NM_022975 NM 022976 NM_023028 NM_023029 NM_023030 NM 023031 2263 4.24 9.58E-06 CDCA1 223381_at AF326731 NM_031423 NM_145697 83540 4.22 1.90E-05 ANLN 222608_s_at AK023208 NM_018685 54443 4.22 2.01 E-04 MAB21L1 206163 at NM_005584 NM 005584 4081 4.21 2.65E-05 CDC6 203967_at U77949 NM_001254 990 4.20 1.21E-03 ESPL1 38158_at D79987 NM_012291 9700 4.17 1.15E-06 MCM5 201755_at NM_006739 NM_006739 4174 4.16 4.33E-04 MGC57827 225834_at AL135396 NM 207418 389835 4.16 6.28E-06 STK6 208079_s_at NM_003158 NM_003600 NM_198433 NM 198434 NM 198435 NM_198436 NM_198437 6790 4.16 1.80E-05 SLD5 211767 at BC005995 NM 032336 84296 4.16 3.72E-03 RAMP 218585_s_at NM 016448 NM 016448 51514 4.16 1.38E-04 KNTC2 204162_at NM 006101 NM 006101 10403 4.14 1.03E-06 DEPDC1 220295_x_at NM_017779 NM 017779 55635 4.14 6.26E-07 KNSL7 219306_at NM 020242 NM 020242 56992 4.14 7.68E-06 CDCA2 236957 at AI248208 NM 152562 157313 4.13 1.53E-05 MLF1IP 229305_at AA460299 NM 024629 79682 4.13 2.13E-06 CDC2 210559_s_at D88357 NM 001786 NM_033379 983 4.11 3.40E-06 CDKN3 1555758 a at AF213040 NM 005192 1033 4.10 5.09E-07 ATAD2 222740_at AI925583 NM_014109 29028 4.10 1.44E-05 FAM54A 228069_at AL138828 NM 138419 113115 4.10 8.67E-07 CDK2 204252_at M68520 NM_001798 NM_052827 1017 4.10 1.46E-06 AI377043 230722_at Al377043 — — 4.10 2.84E-08 CDC25C 205167_s_at NM_001790 NM 001790 NM_022809 995 4.09 1.38E-05 GTSE1 204318_s_at NM_016426 NM_016426 51512 4.08 6.60E-06 UHRF1 225655 at AK025578 NM_013282 29128 4.08 5.58E-05 FLJ23311 219990_at NM 024680 NM 024680 79733 4.08 1.87E-05 PBK 219148_at NM_018492 NM 018492 55872 4.08 2.74E-06 MGC34032 235763 at AA001450 NM 152697 204962 4.07 4.96E-06 211 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al„ Cells Useful for Immuno-Based BoNT/A Activity Assays Spc25 209891 at AF225416 NM 020675 57405 4.07 2.08E-04 ASPM 219918_s_at NM_018123 NM 018136 259266 4.06 1.74E-06 IQGAP3 229538_s_at AW271106 NM 178229 128239 4.04 3.66E-05 UBE3B 213822_s_at BE856776 NM_130466 NM 183414 NM_183415 89910 4.03 1.32E-06 SMC2L1 204240_s_at NM_006444 NM 006444 10592 4.02 1.45E-04 SYNP02 225720_at AW009747 NM 133477 171024 4.02 2.27E-04 FBLN1 202995_s_at NM_006486 NM_001996 NM 006485 NM_006486 NM_006487 2192 4.01 1.34E-06 ITGA6 201656_at NM 000210 NM 000210 3655 4.00 1.10E-06 CDC6 203968_s_at NM_001254 NM_001254 990 4.00 3.34E-04 TK1 1554408_a_at BC007986 NM 003258 7083 4.00 4.33E-07 FLJ25416 228281_at BF343258 NM_145018 220042 3.99 1.36E-06 ORC1L 205085 at NM 004153 NM 004153 4998 3.98 1.89E-05 CNTN1 211203_s_at U07820 NM_001843 NM 175038 1272 3.97 1.43E-05 NUSAP1 218039_at NM_016359 NMJD16359 NM 018454 51203 3.97 2.83E-06 KIF23 204709_s_at NM_004856 NM_004856 NM_138555 9493 3.96 7.58E-05 FBLN1 201787_at NM_001996 NM 001996 NM_006485 NM_006486 NM_006487 2192 3.96 1.15E-04 RAD54L 204558_at NM_003579 NM_003579 8438 3.95 6.59E-06 CENPF 209172 s at U30872 NM 016343 1063 3.95 2.98E-08 FGL1 205305_at NM_004467 NM_004467 NM_147203 NM 201552 NM_201553 2267 3.94 2.35E-05 ARHGAP24 223422_s_at AI743534 NM_031305 83478 3.94 2.71 E-05 DKFZp564A23S 1556300_s_at BF476109 — — 3.93 1.17E-03 DEPDC1 232278 s at AJ278112 NM 017779 55635 3.93 3.60E-05 GRP 206326 at NM_002091 NM_002091 2922 3.92 5.54E-05 MAOA 204388 s at NM 000240 NM 000240 4128 3.92 3.38E-07 POLQ 219510_at NM_006596 NM_006596 NM_199420 10721 3.91 8.49E-06 )KFZp762E13l: 218726 at NM 018410 NM 018410 55355 3.91 7.86E-06 GTSE1 215942_s_at BF973178 NM_016426 51512 3.90 9.11E-06 TPX2 210052_s_at AF098158 NM_012112 22974 3.90 3.85E-06 LOC440738 221697 at AF276659 NM 001004342 440738 3.90 2.27E-03 LOC340109 1557765_at BC039509 XM 379322 340109 3.89 2.74E-05 NUSAP1 219978_s_at N M 018454 NM_016359 NM_018454 51203 3.89 3.26E-06 LOC253981 226430 at Al394438 — 253981 3.88 6.06E-07 ESPL1 204817_at NM_012291 NM_012291 9700 3.85 7.34E-05 KIFC1 209680_s_at BC000712 XM 371813 3833 3.83 1.36E-06 KCTD12 212188 at AA551075 NM_138444 115207 3.82 1.05E-05 KIF14 206364 at NM 014875 XM 375825 9928 3.82 6.29E-07 SGOL2 235425_at AW965339 NM_152524 151246 3.81 3.04E-05 KIAA0186 206102_at NM 021067 XM_375911 9837 3.81 4.00E-06 C20orf129 225687_at BC001068 NM_030919 81610 3.80 4.60E-05 DNA2L 213647 at D42046 XM 166103 1763 3.79 4.96E-07 CCDC3 223316_at AL136562 NM_031455 83643 3.78 9.60E-05 CIT 212801 at Al 861788 NM_007174 11113 3.78 9.25E-05 212 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays BUB1B 203755_at NM_001211 NM 001211 701 3.78 6.66E-07 CDCA3 221436 s at NM 031299 NM 031299 83461 3.77 1.69E-04 MCM10 223570_at AL136840 NM_018518 NM_182751 55388 3.76 8.71E-06 C18orf24 217640_x_at BF038461 NM 145060 220134 3.76 7.58E-05 EMILIN2 224374 s at AF270513 NM 032048 84034 3.75 2.71 E-05 C18orf54 229442_at BF059556 NM_173529 162681 3.75 4.74E-08 MAB21L2 210303_at AF262032 NM_006439 10586 3.73 4.97E-07 BNC2 238478_at H97386 NM_017637 54796 3.73 6.40E-07 AI926924 239253 at Al 926924 — — 3.73 3.76E-04 CDC2 203213_at AL524035 NM 001786 NM_033379 983 3.73 5.41 E-06 Pfs2 221521_s_at BC003186 NM 016095 51659 3.73 2.20E-05 MGC34032 1569112_at AW020413 NM 152697 204962 3.72 5.15E-06 NEK2 204641_at NM_002497 NM_002497 4751 3.71 2.52 E-05 MGC45871 226876_at Al961778 NM 182705 359845 3.71 6.58E-06 DPYD 204646_at NM 000110 NM 000110 1806 3.70 1.06E-04 BIRC5 202095 s at NM 001168 NM 001168 332 3.70 1.51 E-06 ELOVL7 227180_at AW138767 XMJ371740 79993 3.69 9.47 E-05 BF000203 236385_at BF000203 — — 3.69 1.75E-05 STK17A 202693 s at AW194730 NM 004760 9263 3.68 3.33E-04 CHEK1 205394 at NM 001274 NM 001274 1111 3.67 2.79E-04 FLJ13912 45633_at AI421812 NM_022770 64785 3.67 3.76E-06 FLJ10719 213008_at BG403615 NM_018193 55215 3.67 4.86E-06 CENPF 207828 s at NM 005196 NM 016343 1063 3.65 1.58E-06 E2F2 228361 at AL561296 NM 004091 1870 3.65 2.93 E-06 NEGR1 243357_at AA115106 NM 173808 257194 3.65 1.29E-06 CENPA 210821_x_at BC002703 NM_001809 1058 3.65 7.15E-06 MGC40179 242560_at AA579890 NM 173472 115795 3.64 1.89E-04 SPAG6 210033_s_at AF079363 NM_012443 NM_172242 9576 3.64 3.09E-03 SLAC2-B 214734_at ABO14524 NM_015065 23086 3.64 3.42E-04 ASCL1 209985_s_at BE797438 NM 004316 429 3.63 3.48E-04 ZNF521 226677 at AF141339 NM_015461 25925 3.62 6.14E-07 NEK2 211080 sat Z25425 NM_002497 4751 3.62 4.42E-05 TK1 202338_at NM_003258 NM_003258 7083 3.62 1.03 E-05 CCNB1 214710 s_at BE407516 NM 031966 891 3.62 5.65E-07 TCF7L1 221016_s_at NM 031283 NM_031283 83439 3.61 1.36E-03 MYBL2 201710_at NM 002466 NM 002466 4605 3.60 5.06E-05 BRCA2 208368_s_at NM 000059 NM_000059 675 3.60 1.84E-05 TOP2A 201292_at AL561834 NM 001067 7153 3.60 4.23E-06 CCNE2 205034_at NM_004702 NM_004702 NM_057735 NM_057749 9134 3.60 1.96E-05 AI937080 244033 at Al 937080 — ... 3.59 1.30E-04 MKI67 212022_s_at BF001806 NM_002417 4288 3.59 3.34E-05 dJ383J4.3 1554271_a_at BC019022 NM_033319 91687 3.57 3.09 E-05 SMC6L1 236535_at AW069285 NM 024624 79677 3.56 3.19E-05 ECT2 219787 s_at NM 018098 NM 018098 1894 3.56 7.41 E-08 CDCA3 223307_at BC002551 NM 031299 83461 3.56 9.80E-05 CDCA5 224753_at BE614410 NM_080668 113130 3.56 1.86E-05 TRIP10 202734 at NM 004240 NM 004240 9322 3.55 1.98E-05 C14orf106 226630 at BF062175 NM_018353 55320 3.55 5.62E-07 TMEM35 219685_at NM_021637 NM 021637 59353 3.55 9.24E-05 POLA2 204441 _s_at NM 002689 NM_002689 23649 3.54 5.49E-06 FLJ13912 218719_s_at NM 022770 NM_022770 64785 3.52 1.92E-06 213 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays PDE5A 227088_at BF221547 NM 001083 NM 033430 NM 033431 NM_033437 8654 3.52 7.25E-04 SIM1 206876_at AL121948 NM 005068 6492 3.52 9.26E-04 WDR51A 226355_at AW001089 NM 015426 25886 3.52 2.74E-05 TFPI2 209277_at AL574096 NM_006528 7980 3.51 1.33E-04 CUGBP2 202158_s_at NM_006561 NM_006561 10659 3.51 3.91 E-03 ATAD2 235266_at AI139629 NM 014109 29028 3.49 5.52E-05 DOK5 1554863_s_at BC008992 NM 018431 NM_177959 55816 3.49 1.51 E-03 ATAD2 228401_at AI656807 NM 014109 29028 3.49 2.96E-06 WDHD1 204728_s_at NM_007086 NM 00100839 6 NM 007086 11169 3.48 1.11E-05 BC002493 223274_at BC002493 — ... 3.47 3.08E-05 BARD1 205345_at NM 000465 NM 000465 580 3.46 1.90E-03 MGC45866 230021_at AI638593 NM 152259 90381 3.46 1.66E-05 Cep152 239413_at AI130715 NM_014985 22995 3.46 2.08E-07 )KFZp761O201 232313_at AL122107 XM_044062 92293 3.46 1.14E-04 TOP2A 201291 s at AU159942 NM 001067 7153 3.45 8.58E-06 TRAF4 202871_at NM_004295 NM_004295 NM_145751 9618 3.44 2.74E-06 RBPMS 209488_s_at D84109 NM_00100871 0 NM_00100871 1 NM_00100871 2 NM 006867 11030 3.44 6.92E-04 CNTN1 227202_at AW072790 NM_001843 NM_175038 1272 3.44 1.89E-06 DCC1 219000 s at NM 024094 NM 024094 79075 3.43 2.54E-04 KIF2C 211519_s_at AY026505 NM 006845 11004 3.42 9.85E-05 SLC43A3 210692_s_at BC003163 NM_014096 NM 017611 NM_199329 29015 3.41 1.35E-04 KIAA0101 202503_s_at NM_014736 NM_014736 9768 3.40 1.33E-05 FBP1 209696_at D26054 NM_000507 2203 3.40 3.15E-04 AA224205 238075_at AA224205 — ... 3.39 1.33E-05 ADAMTS9 226814_at AI431730 NM 020249 NM_182920 NM_182921 56999 3.38 2.69E-06 FLJ10706 220840 s at NM 018186 NM 018186 55732 3.38 4.66E-05 HCAP-G 218662_s_at NM_022346 NM_022346 64151 3.37 3.87E-06 SLC7A2 225516_at AA876372 NM 00100853 9 NM_003046 6542 3.37 1.80E-08 BF477980 242775 at BF477980 — ... 3.36 1.18E-04 UBE2C 202954_at NM 007019 NM 007019 NM 181799 NM 181800 NMJ81801 NM_181802 NM 181803 11065 3.36 1.60E-06 CSRP2 207030_s_at NM_001321 NM 001321 1466 3.35 9.35E-07 214 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays PRC1 218009_s_at NM_003981 NM_003981 NM 199413 NM_199414 9055 3.35 2.53E-06 GNG12 222834_s_at N32508 NM_018841 55970 3.34 4.89E-06 AB040957 231855 at AB040957 — — 3.34 2.91 E-07 DAZ1 DAZ3 DAZ2 DAZ4 208281_x_at NM_020364 NM 00100537 5 NM_00100578 5 NM 00100578 6 NM_004081 NM 020363 NM 020364 NM 020420 1617 57054 57055 57135 3.34 4.52E-03 MCM5 216237_s_at AA807529 NM 006739 4174 3.34 1.01E-04 CCNA2 203418_at NM 001237 NM 001237 890 3.34 2.17E-04 FLJ20105 219650_at NM_017669 NM_00100995 4 NM_017669 54821 3.34 1.12E-05 BF108778 235363 at BF108778 — — 3.33 1.13E-04 BM039 222118_at AK023669 NM_018455 55839 3.33 1.47E-07 SDC2 212154_at AI380298 NM 002998 6383 3.33 5.56E-04 LOC440928 235147_at R56118 XM 498917 440928 3.33 1.32E-03 LOC146909 222039_at AA292789 XM_085634 146909 3.31 2.57E-05 RAD51AP1 204146_at BE966146 NM_006479 10635 3.31 4.07E-06 SMC6L1 218781_at NM_024624 NM 024624 79677 3.30 2.52E-08 ZWINT 204026_s_at NM_007057 NM_00100541 3 NM_00100541 4 NM 007057 NM 032997 11130 3.29 7.56E-06 KIAA1754 225582_at AA425726 NM 033397 85450 3.29 3.22E-06 CCNB1 228729 at N90191 NM 031966 891 3.29 3.59E-06 PRAME 204086_at NM_006115 NM 006115 NM_206953 NM 206954 NM_206955 NM 206956 23532 3.28 3.84E-04 BRCA1 204531_s_at NM_007295 NM_007294 NM_007295 NM_007296 NM 007297 NM_007298 NM_007299 NM_007300 NM 007301 NM_007302 NM 007303 NM_007304 NM_007305 NM 007306 672 3.28 2.73E-04 CNTN1 227209_at AI091445 NM 001843 NM 175038 1272 3.27 3.23E-05 SLC43A3 213113_s_at AI630178 NM_014096 NM 017611 NM 199329 29015 3.27 1.59E-06 215 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B„ et al., Cells Useful for Immuno-Based BoNT/A Activity Assays TIMP3 201147_s_at BF347089 NM 000362 7078 3.27 2.90E-04 LTB4DH 231897 at AL135787 NM 012212 22949 3.27 4.25E-05 FLJ22624 219544_at NM_024808 NM 024808 79866 3.27 4.96E-04 GNAI1 227692_at AU153866 NM_002069 2770 3.26 1.36E-05 BC035780 1560258 a at BC035780 — — 3.26 1.57E-07 CCNB2 202705 at NM_004701 NM 004701 9133 3.24 2.06E-06 PTTG1 203554_x_at NM_004219 NM_004219 9232 3.24 8.78E-06 LOC157570 235588_at AA740849 XM_088331 157570 3.23 2.41 E-04 BG391951 236852_at BG391951 — — 3.22 1.77E-04 MLF1IP 218883_s_at NM 024629 NM 024629 79682 3.21 1.31 E-05 MGC24665 226456_at AW138157 NM_152308 116028 3.21 6.88E-05 GNAI1 209576_at AL049933 NM_002069 2770 3.21 1.53E-06 PLK4 204886_at AL043646 NM 014264 10733 3.20 2.80E-04 GPSM2 205240_at NM 013296 NM 013296 29899 3.20 9.04E-07 TROAP 204649_at NM_005480 NM_005480 10024 3.19 2.23E-05 SYNP02 227662_at AA541622 NM 133477 171024 3.19 1.95E-03 C14orf106 206500 s at NM 018353 NM 018353 55320 3.19 5.08E-04 HCAP-G 218663_at NM_022346 NM 022346 64151 3.19 1.36E-04 FLJ10719 213007_at W74442 NM_018193 55215 3.18 1.31 E-05 LTB4DH 228824_s_at BE566894 NM 012212 22949 3.17 2.71 E-05 TRIM36 219736 at NM 018700 NM 018700 55521 3.17 4.38E-05 HGF 209960_at X16323 NM_000601 NM 00101093 3082 3.17 6.34E-04 1 NM_00101093 2 NM_00101093 3 NM_00101093 4 CHAF1A 203976_s_at NM_005483 NM_005483 10036 3.17 3.20E-04 AK022040 233445_at AK022040 — — 3.17 1.50E-06 AA938184 236312 at AA938184 — — 3.17 1.06E-04 CTSL2 210074_at AF070448 NM_001333 1515 3.17 5.51 E-04 FKSG14 222848_at BC005400 NM_022145 64105 3.16 3.35E-06 EME1 234465_at AK021607 NM 152463 146956 3.16 8.50E-06 TCTE1L 203303_at NM_006520 NM_006520 6990 3.15 2.23E-04 SBLF 213413_at BG434174 NM_006873 11037 3.15 3.72E-03 MCM6 201930_at NM_005915 NM_005915 4175 3.15 3.87E-06 LOC402524 242206_at AW590588 XM_379850 402524 3.14 1.94E-07 INCENP 242787 at AI924134 NM 020238 3619 3.14 7.83E-06 LTB4DH 228825_at BE566894 NM_012212 22949 3.12 1.25E-04 FNDC5 226096_at AI760132 NM_153756 252995 3.12 3.00E-04 P2RY5 218589 at NM 005767 NM 005767 10161 3.12 2.25E-03 GABRA5 206456_at NM 000810 NM 000810 2558 3.11 3.01 E-04 E2F1 204947_at NM_005225 NM_005225 1869 3.11 1.27E-05 E2F7 228033_at AI341146 NM 203394 144455 3.11 9.10E-05 EDG2 204036_at AW269335 NM 001401 NM 057159 1902 3.11 9.74E-05 RFC5 203210_s_at NM_007370 NM_007370 NM_181578 5985 3.09 2.74E-05 BNC2 220272 at NM_017637 NM 017637 54796 3.09 7.83E-06 DEPDC1B 226980 at AK001166 NM 018369 55789 3.09 1.82E-06 PPAP2B 209355_s_at AB000889 NM 003713 NM 177414 8613 3.09 1.33E-03 RBL1 1555004_a_at BC032247 NM 002895 NM_183404 5933 3.09 1.25E-05 LOC132671 229331_at AI559300 NM_145263 132671 3.09 2.77E-04 216 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 AI656180 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays 242447 at AI656180 — — 3.09 6.33E-05 KCNG3 1552897_a_at NM_133329 NM_133329 170850 3.09 1.62E-04 EFNB2 202668_at BF001670 NM_172344 NM_004093 1948 3.08 7.07E-04 TACC3 218308 at NM_006342 NM 006342 10460 3.07 1.21E-05 SHOX2 210135_s_at AF022654 NM 003030 6474 3.07 2.01 E-03 TYMS 1554696_s_at AB077208 NM_006884 NM 001071 7298 3.07 2.09E-06 CDK2 211804_s_at AB012305 NM_001798 1017 3.06 3.25E-06 MGC33887 213644_at Al 979276 NM_052827 NM 145036 201134 3.06 7.13E-03 BVES 228783_at AA993518 NM_007073 11149 3.06 3.06E-04 C20orf172 219512_at NM_024918 NM_147147 NM_024918 79980 3.05 1.03E-05 OSBPL3 209626_s_at AI202969 NM_015550 26031 3.05 2.81 E-04 NM_145320 NM_145321 NM_145322 NM_145323 NM 145324 CXCR4 211919_s_at AF348491 NM_00100854 Λ 7852 3.05 2.72E-03 GAS2L3 235709_at H37811 U NM_003467 NM 174942 283431 3.04 8.83E-03 CENPJ 220885 s at NM 018451 NM 018451 55835 3.04 5.23E-04 TIMP3 201149_s_at U67195 NMJD00362 7078 3.03 3.76E-05 AW271106 229490_s_at AW271106 — ... 3.03 3.24E-06 SPAG5 203145_at NM 006461 NM 006461 10615 3.03 2.06E-06 CXCR4 217028_at AJ224869 NM_00100854 Λ 7852 3.03 8.98E-04 PRIMA1 230087_at Al 823645 U NM 003467 NM 178004 145270 3.02 1.47E-05 DDA3 201896_s_at BC001425 NM_178013 NM_00100529 Λ 84722 3.02 5.61 E-06 DAZ1 216922_x_at AF271088 u NM 032636 NM_00100537 1617 3.02 8.33E-03 DAZ3 DAZ2 DAZ4 MYRIP 214156_at AL050090 5 NM_00100578 5 NM_00100578 6 NM 004081 NM 020363 NM_020364 NM_020420 NM 015460 57054 57055 57135 25924 3.02 2.47E-05 KITLG 226534_at AI446414 NM 000899 4254 3.01 4.26E-04 GAS2L3 238756_at AI860012 NM_003994 NM 174942 283431 3.00 7.34E-05 NRXN1 228547_at BF509242 NM 004801 9378 3.00 1.59E-03 ORC6L 219105_x_at NM 014321 NM_138735 NM_014321 23594 3.00 2.00E-07 CHEK1 205393_s_at NM 001274 NM_001274 1111 2.99 6.29E-05 FLJ20641 220060 s at NM 017915 NM 017915 55010 2.98 3.74E-07 SLITRK5 214930 at AW449813 NM 015567 26050 2.98 2.02E-05 BNC2 233036 at AU146418 NM 017637 54796 2.98 6.17E-03 217 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays SYNP02 225895_at AI634580 NM_133477 171024 2.98 8.59E-04 UCP2 208998 at U94592 NM 003355 7351 2.97 3.77E-05 ETV1 217061_s_at AC004857 NM_004956 2115 2.96 6.17E-07 MNS1 219703 at NM 018365 NM_018365 55329 2.96 3.49E-04 MGC11266 226118_at BE326728 NM_024322 79172 2.95 4.33E-06 AW075105 228868 x at AW075105 — — 2.95 2.52E-05 LOC91431 228859_at BF056790 NM_138698 91431 2.95 1.95E-05 OSAP 223734_at AF329088 NM 032623 84709 2.95 4.92E-04 ARHGAP11A 204492_at NM_014783 NM_014783 NM_199357 9824 2.95 3.64E-08 C6orf173 226936_at BG492359 — — 2.95 2.93E-07 HSPA2 211538 s_at U56725 NM_021979 3306 2.95 2.25E-03 MY06 203216_s_at NM 004999 NM_004999 4646 2.94 2.66E-07 MAOA 204389 at NM 000240 NM 000240 4128 2.94 4.60E-06 ZNF521 226676_at AK021452 NM_015461 25925 2.94 8.51 E-04 ASPM 232238_at AK001380 NM 018136 259266 2.94 4.78E-04 ENC1 201340 s_at AF010314 NM_003633 8507 2.94 2.73E-05 KDELC2 225128 at AL548941 NM 153705 143888 2.94 4.64E-05 SYNP02 225894_at AL589603 NM_133477 171024 2.93 8.98E-05 ENC1 201341_at NM_003633 NM 003633 8507 2.93 2.30E-05 LOC441157 1558796 a at AL833240 XM 499037 441157 2.93 2.03E-03 SDC2 212158_at AL577322 NM 002998 6383 2.92 7.40E-07 TROAP 1568596_a_at Al 199355 NM_005480 10024 2.92 8.12E-06 LOC253012 242601_at AA600175 NMJ98151 253012 2.92 1.02E-03 MGC24103 232568_at AU145658 — 158295 2.91 1.01 E-02 TFDP1 242939 at AI950069 NM 007111 7027 2.91 4.17E-05 LOC441157 1558795_at AL833240 XM 499037 441157 2.90 7.52E-07 C22orf18 218741_at NM_024053 NM_00100287 6 NM 024053 79019 2.90 2.43E-05 TYMS 202589_at NM 001071 NM 001071 7298 2.89 1.61E-06 CXCR4 209201_x_at L01639 NM 00100854 0 NM_003467 7852 2.88 5.99E-03 MGC45871 226905_at BG036514 NM_182705 359845 2.88 3.75E-04 KNTC1 206316_s_at NM 014708 NM 014708 9735 2.87 5.79E-05 PCNA 201202_at NM_002592 NM 002592 NM_182649 5111 2.87 8.09E-06 NEUROD4 221318_at NM_021191 NM 021191 58158 2.86 1.12E-04 AF15Q14 1552680_a_at NM_020380 NM_020380 NM 144508 NM_170589 57082 2.85 1.73E-04 AA699443 241838_at AA699443 — - 2.85 9.18E-05 CCNE1 213523_at AI671049 NM 001238 NM 057182 898 2.85 3.52 E-04 ST8SIA4 230836_at AI422986 NM 005668 NM_175052 7903 2.85 4.72E-06 MGC33926 229302_at AA058832 NM 152390 130733 2.84 2.64E-05 DDB2 203409 at NM 000107 NM 000107 1643 2.84 2.16E-03 TWIST1 213943_at X99268 NM 000474 7291 2.83 1.05E-05 DHRS6 218285_s_at NM_020139 NM 020139 56898 2.82 4.65E-05 DHFR 202533 s at BC003584 NM 000791 1719 2.82 4.52E-05 FLJ11029 228273 at BG165011 NM 018304 55771 2.82 6.55E-07 RNASEH2A 203022_at NM_006397 NM_006397 10535 2.82 9.96E-07 DCLRE1B 222889_at AI703304 NM_022836 64858 2.81 7.59E-05 C13orf3 227165 at AI829603 NM_145061 221150 2.81 9.72E-05 218 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays RBPMS 209487_at D84109 NM 00100871 0 NM 00100871 1 NM 00100871 2 NM_006867 11030 2.81 2.78E-06 ETV1 217053_x_at X87175 NM_004956 2115 2.80 4.43E-07 CHRNA7 CHRFAM7A 210123_s_at U62436 NM 000746 NM 139320 NM_148911 1139 89832 2.80 1.15E-04 MARLIN 1 238600_at AW157571 NM_144720 152789 2.80 1.18E-03 PLCL2 213309_at AL117515 NM 015184 23228 2.80 1.93E-04 Cep152 238535_at AW955956 NM_014985 22995 2.79 8.14E-06 RAB32 204214_s_at NM 006834 NM 006834 10981 2.79 1.16E-03 MAD2L1 1554768_a_at AF394735 NM_002358 4085 2.79 3.08E-06 ITGA6 215177 s at AV733308 NM_000210 3655 2.79 2.99E-04 ENDOG 204824_at NM 004435 NM 004435 2021 2.78 3.20E-04 TFDP2 203588_s_at BG034328 NM_006286 7029 2.78 7.51 E-05 BTG3 1556213_a_at BC028229 NM_006806 10950 2.78 5.93E-04 KIF2C 209408 at U63743 NM 006845 11004 2.77 6.84E-05 CD9 201005_at NM_001769 NM_001769 928 2.77 9.74E-06 TMPO 209754_s_at AF113682 NM 003276 7112 2.77 9.71 E-06 CDC25B 201853_s_at NM_021873 NM_004358 NM 021872 NM_021873 NM_021874 NM_212530 994 2.77 2.17E-06 TMPO 209753 s at BG391171 NM_003276 7112 2.76 7.36E-06 AURKB 239219_at N55457 NM_004217 9212 2.76 3.82E-04 TIFA 226117_at AA195074 NM 052864 92610 2.75 2.55E-05 CDCA7 224428_s_at AY029179 NM 031942 NM 145810 83879 2.75 2.27E-06 CDT1 209832_s_at AF321125 NM_030928 81620 2.75 4.06E-04 HS3ST2 219697_at NM_006043 NM_006043 9956 2.75 9.91 E-05 C18orf54 244324_at BG283921 NM 173529 162681 2.75 1.19E-05 PTPRM 1555579_s at BC029442 NM_002845 5797 2.74 5.55E-05 PLK1 202240_at NM_005030 NM 005030 5347 2.74 4.99E-06 FBLN1 202994_s_at Z95331 NM_001996 NM 006485 NM 006486 NM 006487 2192 2.74 5.20E-04 RAD54B 219494_at NM_012415 NM 012415 NM 134434 25788 2.74 3.14E-04 C14orf31 225464_at N30138 NM 152330 122786 2.74 6.69E-06 EDG3 228176_at AA534817 NM_005226 1903 2.73 2.38E-04 UBL3 243072_at AI733828 NM_007106 5412 2.72 2.94E-04 ASCL1 213768_s_at AW950513 NM 004316 429 2.71 5.62E-05 RHEBL1 1570253_a_at BC014155 NM 144593 121268 2.70 1.21 E-05 FLJ40773 1563933_a_at AK091691 NM 152666 200150 2.70 3.08E-04 ALCAM 240655_at BE502785 NM_001627 214 2.70 9.75E-04 BRCA2 214727_at X95152 NM 000059 675 2.70 4.89E-03 SCAP1 1560861 at BG210619 NM 003726 8631 2.70 9.27E-05 CCNA2 213226_at AI346350 NM 001237 890 2.69 3.29E-05 PKMYT1 204267_x_at NM_004203 NM_004203 NM_182687 9088 2.69 2.26E-05 VRK1 203856_at NM_003384 NM_003384 7443 2.69 6.68E-06 ARHGEF3 218501_at NM_019555 NM_019555 50650 2.69 2.18E-04 219 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays ASPM 239002 at AA748494 NM_018136 259266 2.69 7.18E-03 H17657 241444 at H17657 — — 2.69 3.92E-04 TNFAIP8 210260 s at BC005352 NM_014350 25816 2.68 5.03E-05 Cep72 219531_at NM_018140 NM 018140 55722 2.68 5.02E-05 FGFR2 203638_s_at NM_022969 NM 000141 NM 022969 NM 022970 NM_022971 NM_022972 NM 022973 NM_022974 NM_022975 NM 022976 NM 023028 NM_023029 NM 023030 NM 023031 2263 2.68 4.60E-05 CSRP2 211126_s_at U46006 NM 001321 1466 2.68 6.18E-07 FAM49A 208092_s_at NM_030797 NM_030797 81553 2.68 1.51E-03 CHAF1A 214426_x_at BF062223 NM_005483 10036 2.67 2.14E-07 LOC387816 241360_at BG413368 XM 370664 387816 2.67 1.92E-05 MTB 219588_s_at NM_017760 NM_017760 54892 2.67 4.22E-05 EML1 204797_s_at NM_004434 NM_00100870 7 NM 004434 2009 2.67 3.68E-03 MAD2L1 203362_s_at NM_002358 NM_002358 4085 2.67 1.55E-06 RBL1 205296_at AL365505 NM_002895 NM_183404 5933 2.66 2.73E-05 SYNP02 225721_at AI658662 NM 133477 171024 2.66 4.01 E-04 SYNE2 202761_s_at NM_015180 NM_015180 NM_182910 NM 182912 NM 182913 NM 182914 23224 2.66 1.44E-06 RASSF2 203185_at NM_014737 NM_014737 NM_170773 NM_170774 9770 2.65 1.34E-04 Al001880 242723 at AI001880 — — 2.65 9.66E-04 PTPRK 203038_at NM_002844 NM_002844 5796 2.65 5.22E-06 ETV1 206501 x at NM 004956 NM 004956 2115 2.65 2.26E-07 WDHD1 216228_s_at AK001538 NM 00100839 6 NM 007086 11169 2.64 9.95E-04 ZNF505 1569241_a_at BC020837 NM_00100412 6 NM_031218 81931 2.64 6.40E-03 SESN3 235683_at BF685808 NM_144665 143686 2.63 1.07E-03 BLM 205733 at NM 000057 NM 000057 641 2.63 3.91 E-03 MY06 210480_s_at U90236 NM_004999 4646 2.62 1.11E-06 SIL 205339_at NM_003035 NM_003035 6491 2.61 1.15E-04 CENPH 231772_x_at AL572471 NM_022909 64946 2.60 1.04E-05 GUCY1B3 211555_s at AF020340 NM 000857 2983 2.60 8.17E-05 MLF1IP 229304_s_at AA460299 NM_024629 79682 2.60 9.56E-06 ASCL1 209987_s_at BC002341 NM_004316 429 2.60 2.04E-04 BF111626 228559 at BF111626 — — 2.60 2.36E-05 GAJ 223700_at AY028916 NM 032117 84057 2.60 2.48E-05 LOC494143 235117 at AM 91897 NM_001008706 494143 2.59 9.30E-04 BG252802 229641 at BG252802 — — 2.58 2.53E-05 220 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B„ et al., Cells Useful for Immuno-Based BoNT/A Activity Assays AA406603 230002_at AA406603 — — 2.58 3.50E-06 AW024890 229942_at AW024890 — — 2.58 9.80E-04 GPR10 231805 at AL563031 NM 004248 2834 2.58 2.33E-04 Cep152 215170_s_at AB020719 NM 014985 22995 2.58 6.05E-06 EB-1 227441_s_at AW005572 NM_020140 NM_152788 NM_181670 56899 2.57 1.57E-03 TLE3 206472_s_at NM_005078 NM_005078 7090 2.57 3.99E-04 WEE1 215711_s_at AJ277546 NM_003390 7465 2.56 8.25E-05 BM039 219555_s_at NM 018455 NM 018455 55839 2.56 9.17E-08 TMSNB 205347_s_at NM_021992 NM_021992 11013 2.56 1.86E-04 KIAA1524 1553810_a_at NM 020890 NM 020890 57650 2.55 1.25E-06 ACATE2 221641 s at AF241787 NM 012332 23597 2.54 6.19E-04 AF15Q14 228323_at BF248364 NM 020380 NM_144508 NM_170589 57082 2.54 2.09E-04 CDC7 204510_at NM_003503 NM_003503 8317 2.54 7.24E-04 PTPRM 203329 at NM 002845 NM_002845 5797 2.53 383E-04 PLEKHE1 212719_at AB011178 NM_194449 23239 2.52 1.61 E-05 MY06 203215 s at AA877789 NM_004999 4646 2.51 2.63E-04 AL035461 231827 at AL035461 — — 2.51 3.24E-04 BF509125 232198 at BF509125 — — 2.51 3.41 E-03 TIMP3 201150_s_at NM_000362 NM_000362 7078 2.51 1.89E-05 NRXN1 209915_s_at AB035356 NM 004801 NM_138735 9378 2.51 9.30E-04 LOC221810 221911 at BE881590 — 221810 2.51 4.94E-06 SLC16A10 222939 s at N30257 NM 018593 117247 2.51 2.79E-04 PPAP2B 212230_at AV725664 NM_003713 NM_177414 8613 2.50 1.17E-04 C14orf143 214264 s at AI656610 NM 145231 90141 2.50 1.62E-05 FLJ11259 218627_at NM_018370 NM 018370 55332 2.50 3.56E-04 FAM46C 226811_at AL046017 NM 017709 54855 2.50 6.18E-03 CLSTN2 219414_at NM_022131 NM 022131 64084 2.50 2.54E-04 OVOS LOC440080 228245_s_at AW594320 XM 495907 XM 495909 408186 440080 2.49 1.90E-04 MCM8 224320_s_at BC005170 NM_032485 NM 182802 84515 2.49 1.61 E-05 ARG99 226322_at BF109231 NM 031920 NM_175861 83857 2.49 6.26E-04 SUV39H1 218619_s_at NM_003173 NM_003173 6839 2.49 1.39 E-03 BG109249 1558750 a at BG109249 — — 2.48 6.02 E-05 CKAP2 218252_at NM 018204 NM 018204 26586 2.48 9.73E-07 MGC17791 227420 at BF338045 NM_152362 126282 2.48 2.52E-04 AK025909 233814_at AK025909 — — 2.48 3.30E-04 MGC20533 226308_at AA099118 NM 00101169 9 NM_033417 93323 2.48 8.23E-06 GATM 216733_s_at X86401 NM_001482 2628 2.48 4.09E-04 TPBG 203476_at NM_006670 NM 006670 7162 2.47 4.81 E-05 PTER 222798_at BF112019 NM_00100148 4 NM_030664 9317 2.47 8.26E-04 221 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., etal., Cells Useful for Immuno-Based BoNT/A Activity Assays FGFR2 208228_s_at M87771 NM 000141 NM 022969 NM_022970 NM 022971 NM_022972 NM 022973 NM_022974 NM 022975 NM_022976 NM 023028 NM_023029 NM_023030 NM 023031 2263 2.47 2.00E-05 SMC4L1 201663_s_at NM_005496 NM 00100279 9 NM 00100280 0 NM_005496 10051 2.47 1.52E-06 AW963185 241700_at AW963185 — ... 2.46 2.26E-04 RFC3 204128_s_at NM_002915 NM_002915 NM_181558 5983 2.46 3.05E-05 GLDC 204836 at NM_000170 NM_000170 2731 2.46 4.48E-04 BF432331 242519_at BF432331 — — 2.46 1.67E-04 AW151660 239744_at AW151660 — — 2.46 4.79E-05 HRH3 220447 at NM 007232 NM 007232 11255 2.46 1.62E-03 VAV3 218807 at NM 006113 NM 006113 10451 2.46 6.79E-08 MCM6 238977 at R54683 NM_005915 4175 2.45 1.80E-04 KIF22 202183_s_at NM_007317 NM_007317 3835 2.44 1.23E-04 HSPC150 223229 at AB032931 NM 014176 29089 2.44 1.16E-05 QKI 212636_at AL031781 NM_006775 NM 206853 NM 206854 NM_206855 9444 2.43 4.26E-03 MGC21654 1556429_a_at BC026969 NM_145647 93594 2.43 3.09E-06 ASCL1 209988_s_at BC001638 NM_004316 429 2.43 1.00E-04 FLJ37034 229622_at H16258 — 151176 2.42 4.51 E-03 FSHPRH1 207590 s at NM 006733 NM 006733 2491 2.42 3.10E-03 PPP1R3C 204284_at N26005 NM_005398 5507 2.42 2.95E-04 MASTL 228468_at BF108964 NM 032844 84930 2.42 1.20E-05 DPYSL3 201430_s_at W72516 NM_001387 1809 2.41 3.61 E-06 AW052186 239942_at AW052186 — — 2.41 9.52E-03 RAM2 225081_s_at AK022955 NM_018719 55536 2.40 3.44E-03 PCSK1 205825_at NM_000439 NM 000439 5122 2.40 1.58E-03 TMPO 203432_at AW272611 NM 003276 7112 2.40 5.20E-05 CUGBP2 202157_s_at U69546 NM 006561 10659 2.40 6.84E-03 C19orf14 215218_s_at AC004144 NM_173636 284403 2.38 1.41 E-03 TRIM68 219405_at NM_018073 NM_018073 55128 2.38 3.90E-03 TEX15 221448 s at NM 031271 NM_031271 56154 2.38 6.78E-03 AU156421 233413_at AU156421 — ... 2.37 1.88E-03 CDKN2D 210240_s_at U20498 NM_001800 NM_079421 1032 2.36 8.95E-04 PTGFRN 224937 at BF311866 NM_020440 5738 2.36 4.21 E-05 DERA 218102_at NM 015954 NM 015954 51071 2.36 4,21 E-04 VAV3 218806_s_at AF118887 NM 006113 10451 2.35 2.50E-04 RASEF 1553986_at BC023566 NM_152573 158158 2.34 4.65E-04 TNFSF13B 223502_s_at AF134715 NM 006573 10673 2.34 3.38E-03 STN2 235852_at BE379761 NM_033104 85439 2.34 2.91 E-03 SLC4A11 223748 at AF336127 NM 032034 83959 2.34 7.89E-03 222 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays C20orf72 225890_at AI678096 NM 052865 92667 2.33 7.53E-05 CPVL 208146_s_at NM_031311 NM 019029 NM_031311 54504 2.33 1.12E-03 HMGB2 208808_s_at BC000903 NM_002129 3148 2.33 5.57E-07 FLJ13215 220466_at NM 025004 NM 025004 80071 2.32 1.61 E-04 PLK4 211088_s_at Z25433 NM 014264 10733 2.31 1.24E-05 MRC2 37408_at AB014609 NM_006039 9902 2.31 4.86E-03 ZNF488 229901_at AI056483 NM_153034 118738 2.31 3.12E-03 TM4SF7 209264_s_at AF054841 NM 003271 7106 2.31 1.36 E-04 CCNF 204827_s_at U17105 NM 001761 899 2.31 1.47 E-04 RECQL4 1553015_a_at NM_004260 NM_004260 9401 2.31 2.02 E-04 CDR2 209501_at AL582414 NM 001802 1039 2.31 1.41 E-05 HGF 210997_at M77227 NM 000601 NM_00101093 1 NM_00101093 2 NM 00101093 3 NM_00101093 λ 3082 2.30 3.55E-03 WHSC1 209052_s_at BF111870 4 NM_007331 7468 2.30 2.39E-03 NM_014919 NM_133330 NM_133331 NM_133332 NM_133333 NM_133334 NM_133335 NM_133336 CDCA7 230060_at AI277642 NM_031942 NM_145810 83879 2.30 9.28E-03 SNAI2 213139 at Al 572079 NM_003068 6591 2.30 9.13E-04 NM_004260 213520_at NM 004260 — ... 2.30 1.47 E-04 DIRAS3 215506_s_at AK021882 NM_004675 9077 2.30 2.88E-03 FLJ32363 229886 at AA502768 NM 198566 375444 2.30 4.42 E-04 KCNJ4 208359_s_at NM_004981 NM 004981 NM_152868 3761 2.30 6.70E-04 PLCXD2 235230_at AW170015 NM 153268 257068 2.29 2.14E-03 3ALNAC4S-6S" 203066_at NM 014863 NM_015892 51363 2.29 8.81 E-05 TREX2 207891 s at NM 017518 — 11219 2.29 6.18E-05 DHFR 202534_x_at NM_000791 NM 000791 1719 2.29 3.70E-05 dJ383J4.3 232065_x_at N29457 NM 033319 91687 2.29 1.75E-05 ITGA9 227297 at AI479176 NM 002207 3680 2.29 1.72E-03 NUP43 238474_at BF978064 NM_024647 NM_198887 348995 2.28 1.07E-03 SSB4 229929_at AL563476 NM 080862 92369 2.28 5.85E-04 GNG12 212294_at BG111761 NM_018841 55970 2.28 2.93E-05 POLD1 203422 at NM 002691 NM_002691 5424 2.27 8.87E-04 SHMT1 209980_s_at L23928 NM_004169 NM_148918 6470 2.27 6.54E-05 DMN 212730_at AK026420 NM 015286 NM_145728 23336 2.27 9.70E-05 EB-1 227439_at Al 806510 NM_020140 NM 152788 NM_181670 56899 2.27 3.41 E-05 SGOL1 231938_at AK024292 NM_138484 151648 2.26 2.13E-07 223 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays ARG99 226931_at AU151239 NM 031920 NM_175861 83857 2.26 3.38E-04 U79256 37577_at U79256 — — 2.26 3.97E-05 HS6ST2 1552766_at NM_147174 NM_147174 NM_147175 90161 2.26 2.22E-04 AW305300 238962 at AW305300 — — 2.25 3.89E-05 CCNF 204826_at NM 001761 NM 001761 899 2.25 6.97E-06 CNAP1 201774_s_at AK022511 NM_014865 9918 2.25 6.86E-05 AA019836 241733 at AA019836 — — 2.25 3.30E-04 SPAG6 210032_s_at AI651156 NM 012443 NM_172242 9576 2.24 1.37E-03 PEX13 1558163_at BC040953 NM_002618 5194 2.24 3.22E-04 AW953794 230968_at AW953794 — — 2.24 1.52E-03 TBPIP 213951_s_at BE964655 NM 013290 NM_016556 29893 2.24 3.20E-05 SESN3 235150_at AW376955 NM 144665 143686 2.24 4.11E-05 JPH1 229139 at ' AI202201 NM 020647 56704 2.24 3.22E-03 CTSH 202295_s_at NM_004390 NM_004390 NM_148979 1512 2.24 4.20E-03 NRG3 229233_at H05240 NM_001010848 10718 2.24 1.44E-03 DPYSL3 201431 s at NM 001387 NM 001387 1809 2.23 2.10E-06 RACGAP1 222077_s_at AU153848 NM_013277 29127 2.23 3.69E-06 BF222929 242346_x_at BF222929 — — 2.23 1.34E-03 FBX05 218875_s_at NM 012177 NM_012177 26271 2.23 3.85E-05 LOC143381 227550 at AW242720 — 143381 2.23 7.49E-03 KIAA0056 212789 at AI796581 NM 015261 23310 2.22 1.47E-05 GSG2 223759_s_at AB039834 NM 031965 83903 2.22 7.72E-05 ZNF537 223392_s_at BF510588 NM 020856 57616 2.22 4.48E-06 ADAMTS9 1554697_at AF488803 NM 020249 NM_182920 NM_182921 56999 2.21 5.03E-04 CHAF1A 203975_s_at BF000239 NM 005483 10036 2.21 6.39E-04 TEAD4 41037_at U63824 NM_003213 NM_201441 NM_201443 7004 2.21 6.00E-03 PTER 218967_s_at NM_030664 NM 00100148 4 NM_030664 9317 2.21 8.86E-03 ARHGAP20 228368_at AI936560 NM_020809 57569 2.20 2.69E-04 GMNN 218350 s at NM 015895 NM 015895 51053 2.20 1.84E-05 RAD 18 224200 s at AB035274 NM 020165 56852 2.20 8.40E-08 CCNE2 211814_s_at AF112857 NM 004702 NM_057735 NM 057749 9134 2.20 8.82E-03 RAD 18 223417_at AF169796 NM 020165 56852 2.19 2.68E-06 HGF 210755_at U46010 NM_000601 NM 00101093 1 NM_00101093 2 NM_00101093 3 NM_00101093 A 3082 2.19 4.99E-03 ALCAM 1569362 at BC041127 H NM 001627 214 2.19 3.28E-04 RFC3 204127_at BC000149 NM 002915 NM_181558 5983 2.19 1.51E-04 KIF22 216969_s_at AC002301 NM_007317 3835 2.18 7.12E-04 224 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 SALL4 Jacky, B., etal., Cells Useful for Immuno-Based BoNT/A Activity Assays 229661 at NM_020436 NM_020436 57167 2.18 3.50E-03 BNC2 235723 at AA843242 NM 017637 54796 2.18 6.54E-03 VMP 239293_at R38624 NM_080723 140767 2.18 7.44E-03 AU154486 213253_at AU154486 — ... 2.18 1.78E-04 EBF 229487 at W73890 NM 024007 1879 2.17 1.69E-03 CDC25A 204696_s_at NM_001789 NM_001789 993 2.17 7.52E-04 FLJ23091 221958_s_at AA775681 NM_201567 NM 00100229 2 NM 024911 NM_175885 79971 2.17 1.84E-06 MGC33846 231430_at AW205640 220382 2.17 4.57E-05 BG028209 230521_at BG028209 — — 2.17 1.18E-04 FLJ20920 218844 at NM 025149 NM_025149 80221 2.16 2.85E-04 AF131796 231916 at AF131796 — ... 2.16 7.81 E-05 RFC5 203209_at BC001866 NM_007370 5985 2.16 3.16E-06 ATP2B4 212136_at AW517686 NM 181578 NM_00100139 β 493 2.16 8.96E-03 AI653240 240247_at AI653240 O NM_001684 XM 496059 440261 2.16 3.06E-03 SNCAIP 219511 s at NM 005460 NM 005460 9627 2.15 6.77E-04 DHFR 48808_at AM44299 NM 000791 1719 2.14 6.65E-05 KCNN2 220116_at NM_021614 NM_021614 3781 2.14 8.09E-03 AI144156 238670_at AI144156 NM_170775 2.14 4.87E-06 C15orf20 228252_at AF108138 NM_025049 80119 2.14 6.49E-04 AA287223 238748_at AA287223 — — 2.13 7.76E-04 CKS1B 201897_s_at NM 001826 NM 001826 1163 2.13 2.30E-06 RHEBL1 1553713 a_at NM 144593 NM_144593 121268 2.13 1.90E-05 PVRL3 213325_at AA129716 NM_015480 25945 2.13 3.03E-03 H2AFX 212525_s_at AA760862 NM 002105 3014 2.13 2.86E-04 XRCC4 205071_x_at ABO17445 NM 003401 7518 2.13 6.87E-07 STK17A 202695_s_at NM_004760 NM_022406 NM_022550 NM 004760 9263 2.12 4.96E-04 MCM2 202107 s at NM 004526 NM 004526 4171 2.12 7.65E-06 DHFR 202532_s_at BC000192 NM 000791 1719 2.12 1.71E-04 INCENP 219769_at NM 020238 NM_020238 3619 2.12 7.09E-03 CBLN1 205747_at NM_004352 NM_004352 869 2.11 1.51 E-03 ZNF545 1555793 a at AL834267 NM 133466 284406 2.11 5.39E-07 GGH 203560 at NM 003878 NM_003878 8836 2.10 7.91 E-06 FLJ23091 228950_s_at AL534095 NM_00100229 o 79971 2.10 5.48E-05 TLE3 212769_at Al567426 z NM_024911 NM_005078 7090 2.09 4.14E-03 BE464799 214036_at BE464799 ___ ... 2.09 9.39E-04 ANP32E 208103_s_at NM_030920 NM_030920 81611 2.09 1.57E-05 NXPH1 232377_at N62902 NM 152745 30010 2.08 8.71 E-05 CDC25A 1555772_a_at AY137580 NM_001789 993 2.08 1.17E-03 PPAP2B 212226_s_at AA628586 NM_201567 NM 003713 8613 2.08 2.24E-03 FABP6 210445_at U19869 NM_177414 NM_001445 2172 2.08 2.58E-03 T96523 237469 at T96523 — ... 2.08 5.67E-03 KIAA0286 212621_at AB006624 NM 015257 23306 2.08 1.03E-05 DTYMK 203270 at NM 012145 NM 012145 1841 2.08 4.74E-05 NRM 225592_at D81048 NM 007243 11270 2.08 4.53E-05 FLJ25067 243507_s_at AV715251 NM 152504 149840 2.08 2.73E-04 225 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays ZNF215 220214_at NM 013250 NM 013250 7762 2.08 6.34E-05 SEMA6A 220454 s at NM 020796 NM 020796 57556 2.07 4.90E-04 SEMA6A 223449_at AF225425 NM 020796 57556 2.07 1.30E-03 PPIL5 235113_at AA742244 NM_152329 NM 203466 NM_203467 122769 2.07 2.13E-05 SMC4L1 201664_at AL136877 NM_00100279 9 NM 00100280 0 N M_005496 10051 2.06 2.53E-06 MPHOSPH1 205235_s_at NM_016195 NM 016195 9585 2.06 3.99E-06 SKP2 210567_s_at BC001441 NM 005983 NM_032637 6502 2.06 9.75E-05 ZNF537 223393_s_at AL136805 NM_020856 57616 2.06 1.76E-04 PLEKHK1 230469_at AW665138 NM_145307 219790 2.06 6.70E-04 ALCAM 201951_at BF242905 NM_001627 214 2.06 1.36 E-03 AI733341 240911_at AI733341 — ... 2.06 4.21 E-04 C14orf94 218383_at NM_017815 NM_017815 54930 2.05 4.04E-05 HES6 226446_at AW249678 NM_018645 55502 2.05 1.20 E-04 EAF2 219551_at NM 018456 NM 018456 55840 2.05 1.74 E-04 GJA7 208460_at NMJ305497 NM_005497 10052 2.05 2.33E-03 PHF21B 1560091_a_at AK092243 NM_138415 112885 2.04 6.65E-04 SEMA6A 225660_at W92748 NM_020796 57556 2.04 7.90E-04 BF593263 228018 at BF593263 — — 2.03 4.92E-03 FLJ20647 218802_at NM_017918 NM_017918 55013 2.03 1.70E-03 C20orf58 228017_s_at BF593263 NM 152864 128414 2.03 1.08E-04 NET1 201830_s_at NM 005863 NM_005863 10276 2.03 1.27E-03 FNDC5 226097_at AI686488 NM 153756 252995 2.03 1.40E-03 HSDL2 209513_s_at BC004331 NM 032303 84263 2.03 3.49E-05 NRXN1 209914_s_at AW149405 NM_004801 NM_138735 9378 2.02 6.83E-03 CXorf34 205238_at NM 024917 NM 024917 79979 2.02 5.46E-03 SYTL4 227703_s_at AL391688 NM 080737 94121 2.02 3.25E-04 FGFR2 211401_s_at AB030078 NM 000141 NM 022969 NM 022970 NM 022971 NM 022972 NM 022973 NM 022974 NM_022975 NM 022976 NM 023028 NM_023029 NM_023030 NM_023031 2263 2.01 3.92E-04 LOC440288 239792 at N75594 XM 496075 440288 2.01 5.78 E-04 TEX15 232760_at AL133653 NM_031271 56154 2.00 9.86E-04 C6orf189 228875_at Al 540210 — 221303 2.00 1.16E-05 NSE1 229546_at AI378035 NM 145175 151354 2.00 2.29E-04 KLHL13 227875_at AB037730 NM 033495 90293 2.00 3.06E-06 ARHGAP24 230803_s_at AI761947 NM 031305 83478 2.00 2.48 E-04 RFC4 204023_at NM_002916 NM 002916 NM 181573 5984 1.99 1.39E-05 TFDP2 203589_s_at NM 006286 NM 006286 7029 1.99 1.73E-06 THBS4 204776_at NM 003248 NM 003248 7060 1.99 4.42 E-03 EMILIN3 228307_at AL137580 NM 052846 90187 1.99 6.67 E-03 226 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays SESN3 242906_at BE787063 NM 144665 143686 1.99 2.42E-04 TLE4 216997 x at AL358975 NM 007005 7091 1.99 1.02E-02 MYH11 227249_at AI857685 NM 002474 NM_022844 4629 1.99 3.80E-04 SMTN 209427_at AF064238 NM 006932 NM_134269 NM_134270 6525 1.99 3.97E-03 FLJ11127 219694_at NM_019018 NM_019018 54491 1.99 1.47E-03 AA156721 201952_at AA156721 — ... 1.98 1.86E-04 LOC338773 227300_at AL521682 NM_181724 338773 1.98 1.37E-03 SDC1 201286_at Z48199 NM 00100694 6 NM 002997 6382 1.98 1.62E-04 LYN 202625_at AI356412 NM_002350 4067 1.98 1.63E-05 TLE3 212770_at AW873621 NM_005078 7090 1.98 1.14E-04 LOX 204298_s_at NM 002317 NM 002317 4015 1.96 7.97E-04 KIAA0286 212619 at AW205215 NM 015257 23306 1.96 2.89E-06 LHFPL2 212658 at N66633 NM_005779 10184 1.96 3.29E-05 C11 orf8 205413_at NM_001584 NM_001584 744 1.96 1.73E-06 Cep70 1554489_a_at BC016050 NM 024491 80321 1.96 2.05E-06 GPR155 231166_at Al 733474 NM 152529 151556 1.96 8.30E-05 POLA 204835_at NM_016937 NM 016937 5422 1.96 2.08E-04 ZAK 225665_at Al 129320 NM 016653 NM_133646 51776 1.96 2.36E-06 )KFZP564K196 223170_at AF132000 NM 015544 26022 1.96 2.12E-05 TPST2 204079_at NM_003595 NM_00100856 6 NM 003595 8459 1.95 1.43E-03 TRIP 205598 at NM 005879 NM 005879 10293 1.95 1.00E-05 TPTE 233879_at AL137389 NM_013315 NM_199259 NM 199260 NM_199261 7179 1.94 3.31 E-03 FLJ10408 220535_at NM 018088 NM_018088 55138 1.94 9.00E-03 DNAPTP6 222154_s_at AK002064 NM 015535 26010 1.94 2.39E-07 DKFZp434P05f 232398_at AK001064 NM_173466 91531 1.93 5.72E-03 FBX05 234863_x_at AK026197 NM_012177 26271 1.93 2.02E-05 STRA6 1569335_a_at BC015881 NM_022369 64220 1.93 3.41 E-04 PASK 213534_s_at D50925 NM 015148 23178 1.93 6.33E-04 DRF1 238508_at BG026951 NM 025104 NM_145663 80174 1.93 4.54E-04 R71596 229580_at R71596 ... ... 1.93 8.51 E-03 TTF2 204407_at AF080255 NM_003594 8458 1.93 3.06E-03 KIAA0635 206003_at NM 014645 NM 025009 9662 1.93 1.09E-05 OLFML3 218162 at NM_020190 NM_020190 56944 1.93 7.36E-03 GPSM2 221922_at AW 195581 NM_013296 29899 1.92 1.45E-05 AW022607 226806_s_at AW022607 — ... 1.92 6.78E-03 OPN3 219032 x at NM_014322 NM 014322 23596 1.92 2.34E-03 DTYMK 1553983 at AF258562 NM_012145 1841 1.92 1.06E-04 NY-REN-41 226287_at AI458313 NM 080654 91057 1.92 1.77E-04 RGMA 223468_s_at AL136826 NM 020211 56963 1.91 2.31 E-03 EBF 232204 at AF208502 NM 024007 1879 1.91 4.36E-05 C9orf140 225777_at AW250904 NM_178448 89958 1.91 8.55E-05 HPCA 205454_at BC001777 NM 002143 3208 1.91 2.09E-04 RFC2 1053_at M87338 NM 002914 NMJ81471 5982 1.91 2.20E-06 GUCY1B3 203817_at W93728 NM_000857 2983 1.91 1.10E-03 SEZ6L 207873_x_at NM_021115 NM_021115 23544 1.90 4.82E-07 227 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays CUGBP2 202156 s at N36839 NM 006561 10659 1.90 8.07E-04 AF15Q14 1552682_a_at NM_144508 NM_020380 NM 144508 NM_170589 57082 1.90 2.18E-04 CENPJ 223513 at AF139625 NM 018451 55835 1.90 1.64E-05 SEZ6L 211894_x_at AB041736 NM_021115 23544 1.90 1.44E-05 SDC1 201287_s_at NM_002997 NM_00100694 6 NM_002997 6382 1.90 6.29E-05 PLAUR 210845_s_at U08839 NM_00100537 6 NM_00100537 7 NM_002659 5329 1.90 5.08E-03 CBLN2 242301_at R60224 NM 182511 147381 1.90 4.25E-03 DCLRE1B 219490 s at NM_022836 NM_022836 64858 1.89 2.44E-04 ZFHX4 219779_at NM 024721 NM 024721 79776 1.89 6.77E-05 CYBA 203028_s_at NM_000101 NM_000101 1535 1.89 3.82E-05 DOCK10 219279_at NM 017718 NM 014689 55619 1.88 9.11E-04 MCM3 201555 at NM 002388 NM 002388 4172 1.88 1.06E-05 ECT2 234992 x at BG170335 NM_018098 1894 1.87 2.46E-04 ADA 204639_at NM_000022 NM_000022 100 1.87 8.91 E-04 SOX4 213668_s_at AI989477 NM_003107 6659 1.87 2.08E-04 STN2 227461 at AA632295 NM 033104 85439 1.87 6.01 E-04 HS6ST2 230030_at Al 767756 NM_147174 NM_147175 90161 1.87 6.20E-07 NAGA 1555041_a_at M29276 NM_000262 4668 1.87 2.11 E-04 GCHFR 204867_at NM 005258 NM 005258 2644 1.86 8.27E-03 KIAA1596 234733 s at AK001672 XM 048128 57697 1.86 9.32E-05 RFC2 203696_s_at NM_002914 NM_002914 NM_181471 5982 1.86 8.69E-06 HUNK 1555935_s_at T58129 NM 014586 30811 1.86 2.81 E-04 PEX13 1558164_s_at BC040953 NM_002618 5194 1.85 9.05E-05 DTYMK 1553984_s_at AF258562 NM 012145 1841 1.85 4.47E-04 TCF3 209151_x_at AA768906 NM_003200 6929 1.85 2.01 E-04 LOC91614 228293_at AJ245600 NM 139160 91614 1.85 4.22E-03 CDCA4 218399_s_at NM_017955 NM_017955 NMJ45701 55038 1.84 3.08E-04 Cep152 215882_at AK025247 NM 014985 22995 1.84 1.38E-03 TIMELESS 203046 s at NM 003920 NM 003920 8914 1.84 2.25E-04 ZNF505 208119_s_at NM_031218 NM_00100412 6 NM_031218 81931 1.84 1.87E-04 SESN3 242899 at N78412 NM 144665 143686 1.84 2.44E-03 FLJ14146 218546_at NM_024709 NM 024709 79762 1.83 4.55E-04 PHF19 225533_at AL117477 NM_00100993 6 NM_015651 26147 1.83 6.38E-04 C19orf32 226597_at Al348159 NM_138393 92840 1.83 5.57E-05 SATB2 213435_at AB028957 NM_015265 23314 1.83 9.07E-03 PASK 216945 x at U79240 NM 015148 23178 1.83 1.22E-03 MSH5 210410_s_at AF034759 NM_002441 NM_025259 NM_172165 NM 172166 4439 1.83 2.29E-04 CBLB 227900_at AV701750 NM_170662 868 1.82 5.23E-03 AI984541 235434_at AI984541 ... ... 1.82 1.15E-03 NEDD1 1552417_a_at NM_152905 NM_152905 121441 1.82 2.63E-03 228 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et a!., Cells Useful for Immuno-Based BoNT/A Activity Assays KDELR3 204017_at NM_006855 NM 006855 NM_016657 11015 1.82 4.53E-03 TYMS 228989_at AW291159 NM 001071 7298 1.82 3.40E-03 PCNXL2 39650_s_at AB007895 NM_014801 NM_024938 80003 1.82 9.16E-05 HS6ST2 1552767_a_at NMJ47174 NM 147174 NM_147175 90161 1.82 8.21 E-07 KIF23 244427_at AW192521 NM 004856 NM_138555 9493 1.81 8.25E-03 EBF 227646 at BG435302 NM_024007 1879 1.81 2.17E-05 BE466145 227041_at BE466145 — ... 1.81 5.47E-05 KCNJ8 205303_at BF514158 NM_004982 3764 1.81 1.32E-06 TRIP13 204033 at NM 004237 NM 004237 9319 1.80 1.65E-04 SMAD3 218284 at NM 015400 NM_005902 4088 1.80 2.69E-03 AI582818 229053 at AI582818 — ... 1.80 1.03E-03 TBC1D1 212350_at AB029031 NM_015173 23216 1.80 1.24E-04 FEN1 204768 s at NM 004111 NM 004111 2237 1.79 7.12E-05 HELLS 223556 at AF155827 NM_018063 3070 1.79 4.87E-04 SFI1 36545_s_at AB011114 NM_00100746 7 NM 014775 9814 1.78 8.13E-03 WASPIP 202664_at AW058622 NM_003387 7456 1.78 6.38E-03 RASEF 235144 at AA826324 NM_152573 158158 1.78 9.50E-04 NOS1 239132_at BE299830 NM 000620 4842 1.78 9.36E-04 DNMT3B 220668_s_at NM_006892 NM 006892 NM_175848 NM 175849 NM_175850 1789 1.78 3.32E-05 H10545 242137_at H10545 — — 1.77 7.47E-04 PKP4 214874_at AL050364 NM_00100547 6 NM 003628 8502 1.76 7.22E-04 T86830 227835 at T86830 XM 374317 389831 1.76 2.76E-03 HSDL2 209512„at BC004331 NM 032303 84263 1.76 1.97E-03 AH46450 228073_at AH 46450 — — 1.76 4.60E-06 BC041029 1569025 s at BC041029 XM 371697 389211 1.76 4.47E-06 AMOTL1 225459 at AU157155 NM_130847 154810 1.76 8.01 E-05 C2orf31 221245_s_at NM_030804 — 81561 1.75 5.43E-05 STK3 204068_at NM_006281 NM 006281 6788 1.75 3.93E-05 FAM19A4 242348_at AA757457 NM_00100552 7 NM_182522 151647 1.75 6.22E-07 CHTF18 226569_s_at AK024476 NM_022092 63922 1.75 5.44E-06 SOX4 201417 at AL136179 NM 003107 6659 1.75 6.42E-05 RRM1 201476_s_at AI692974 NM_001033 6240 1.74 5.08E-04 AV717623 212738_at AV717623 — — 1.74 2.87E-04 FGD4 227948_at AI949549 NM 139241 121512 1.74 3.49E-04 NTRK2 221796_at AA707199 NM_00100709 7 NM_006180 4915 1.74 2.14E-04 SOX4 201416_at BG528420 NM_003107 6659 1.73 5.20E-04 SESN3 225123 at BE883841 NM 144665 143686 1.73 4.70E-04 C6orf139 219294_at NM_018132 NM_018132 55166 1.73 3.59E-05 SRGAP1 233888_s_at AK023899 NM_020762 57522 1.73 7.93E-04 CDK6 235287 at AW192700 NM 001259 1021 1.73 2.32E-03 TNFAIP8 208296_x_at NM 014350 NM 014350 25816 1.73 9.57E-04 TUBG1 201714_at NM_001070 NM_001070 7283 1.73 1.25E-04 LOC221810 221910 at BF131965 — 221810 1.73 1.75E-04 229 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays AI220427 230696 at AI220427 — — 1.73 4.25E-03 AI685824 244565 at AI685824 XM_370580 387716 1.73 2.27E-04 AL566034 224944_at AL566034 — -- 1.72 1.01 E-05 WEE1 212533_at X62048 NM_003390 7465 1.72 1.55E-05 RRM1 201477_s_at NM 001033 NM 001033 6240 1.72 1.46E-04 EZH2 203358_s_at NM_004456 NM_004456 NM_152998 2146 1.72 4.30E-06 WHSC1 222777_s_at AI770166 NM_007331 NM_014919 NM 133330 NM_133331 NM 133332 NM 133333 NM_133334 NM_133335 NM_133336 7468 1.72 4.09E-04 H2AFX 205436 s at NM 002105 NM 002105 3014 1.72 4.53E-05 )KFZP434L011 227818_at AL133609 NM_022778 64793 1.72 2.15E-04 C9orf100 230522_s_at BG028209 NM_032818 84904 1.72 3.63E-04 ANKRD9 230972_at AW194999 NM_152326 122416 1.71 5.46E-06 ACTA2 200974 at NM 001613 NM 001613 59 1.71 1.89E-03 GALNT10 212256_at BE906572 NM 017540 NM_198321 55568 1.71 2.83E-03 Al826125 229866_at Al826125 — — 1.71 1.06E-03 LRRC20 218550_s_at NM_018205 NM_018205 NM_018239 NM_207119 55222 1.70 6.18E-03 C6orf213 1562443_at AK095527 NM 001010852 134829 1.70 2.22E-07 EDG2 204037_at BF055366 NM 001401 NM_057159 1902 1.69 2.85E-03 DLL3 222898_s_at BE350882 NM_016941 NM 203486 10683 1.69 3.90E-05 TBPIP 205956_x_at NM_013290 NM_013290 NM_016556 29893 1.69 8.09E-05 GFRA2 205721 at U97145 NM_001495 2675 1.69 3.03E-03 AI140305 228849 at AM 40305 — — 1.69 5.44E-03 MBD2 214397_at AI827820 NM_003927 NM_015832 8932 1.68 7.38E-05 POLE 216026_s_at AL080203 NM 006231 5426 1.68 1.73E-04 TIMP3 201148_s at AW338933 NM 000362 7078 1.68 3.70E-06 RBMS3 206767_at NM_014483 NM_00100379 2 NM 00100379 3 NM_014483 27303 1.68 5.38E-04 BE670307 227955_s_at BE670307 — — 1.68 3.67E-04 LAMA4 202202_s_at NM_002290 NM 002290 3910 1.68 8.97E-03 NUDT1 204766_s_at NM_002452 NM 002452 NM_198948 NM_198949 NM 198950 NM 198952 NM 198953 NM 198954 4521 1.68 4.44E-03 LOC81691 208107 s at NM 030941 NM 030941 81691 1.68 6.55E-05 PKP4 201927_s_at BG292559 NM_00100547 6 NM 003628 8502 1.68 8.23E-03 230 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays AI919519 235092 at AI919519 — — 1.68 4.50E-04 KPNA2 211762_s_at BC005978 NM_002266 3838 1.67 1.78E-06 ZNF519 1568873_at BC010705 NM_145287 162655 1.67 8.56E-03 PELO 226731_at AA156873 NM_015946 53918 1.67 5.20E-03 HIRIP3 204504 s at NM_003609 NM 003609 8479 1.67 1.47E-05 RAD54B 235846_at AI208616 NM_012415 NM_134434 25788 1.67 2.55E-03 IKFZP761M151 225355_at AK026748 — 54492 1.67 5.04E-03 SYN2 210247_at AW139618 NM_003178 NM_133625 6854 1.67 7.92E-04 SNAG1 226683_at AU146771 NM 052870 112574 1.67 1.69E-04 CDC25A 204695_at AI343459 NM 001789 NM_201567 993 1.66 4.73E-04 MEST 202016_at NM_002402 NM 002402 NM_177524 NM_177525 4232 1.66 1.55E-04 HPSE 222881_at AF155510 NM_006665 10855 1.66 3.24E-04 AI673553 203061_s_at AI673553 — — 1.66 1.97E-05 SANG 232881_at AI500353 — 149775 1.66 2.02E-04 HGF 210998_s_at M77227 NM 000601 NM 00101093 3082 1.66 6.82E-03 1 NM_00101093 2 NM_00101093 3 NM_00101093 4 SCD4 224901 at AL571375 NM_024906 79966 1.66 1.68E-03 RDH10 226021_at AW150720 NM_172037 157506 1.66 1.99E-03 SYNP02 232119_at BF984227 NM_133477 171024 1.66 5.45E-03 LSM4 202737 s at NM 012321 NM_012321 25804 1.65 5.27E-05 BE857972 243781 at BE857972 — — 1.65 7.56E-04 NET1 201829_at AW263232 NM 005863 10276 1.65 7.05E-05 LYN 210754 s at M79321 NM 002350 4067 1.65 3.45E-05 DACH1 228915_at AI650353 NM 004392 NM_080759 NM 080760 1602 1.65 6.68E-03 LIG1 202726_at NM_000234 NM_000234 3978 1.65 3.00E-04 LYN 202626 s at NM 002350 NM 002350 4067 1.64 1.87E-05 ST8SIA2 221285 at NM 006011 NM_006011 8128 1.64 2.88E-03 FLJ23322 233250_x_at AL022313 NM_024955 80020 1.64 1.54E-04 GNG12 1555240_s_at AF493879 NM_018841 55970 1.64 9.06E-05 BC025350 1569418 at BC025350 — — 1.63 1.39E-03 EVE1 225162_at BG285417 NM_001009555 152503 1.63 1.62E-03 SCML1 222747_s_at BF001786 NM_006746 6322 1.63 2.63E-04 C20orf100 228737_at AA211909 NM_032883 84969 1.63 9.04E-04 LMNB1 203276 at NM 005573 NM 005573 4001 1.63 1.56E-04 TNFSF13B 223501_at AW151360 NM 006573 10673 1.63 2.45E-03 ZAK 225662_at H28667 NM 016653 NM_133646 51776 1.63 2.26E-05 N36085 227221_at N36085 — — 1.63 2.85E-04 SOX4 201418_s_at NM_003107 NM_003107 6659 1.62 4.87E-04 LOC342892 244640_at AW440392 XM 292740 342892 1.62 9.38E-05 MCM4 222037 at AI859865 NM 005914 NM 182746 4173 1.62 4.15E-03 231 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays RAD51C 206066_s_at NM_002876 NM 002876 NM_058216 NM_058217 5889 1.62 2.63E-04 SORT1 212807_s_at BF447105 NM_002959 6272 1.62 7.88E-04 AV687517 228498 at AV687517 — — 1.62 4.00E-03 FLJ44635 227618_at AI250910 NM_207422 392490 1.62 4.08E-03 HMG2L1 212597_s_at AL079310 NM_00100368 1 NM_005487 NM_014250 10042 1.62 1.26E-04 PLXNA2 213030_s_at AI688418 NM_025179 5362 1.62 1.87E-04 ST8SIA2 239537_at AW589904 NM_006011 8128 1.61 3.33E-06 SCML1 218793 s at NM 006746 NM 006746 6322 1.61 6.46E-07 KIAA1754L 240037_at R37132 NM_00100894 9 NM 178495 150771 1.61 8.33E-03 COBLL1 203642 s at NM 014900 NM_014900 22837 1.61 1.06E-03 N26620 227503_at N26620 — ... 1.61 1.67E-03 RPA3 209507_at BC005264 NM_002947 6119 1.61 2.30E-04 RODH 205700 at NM_003725 NM 003725 8630 1.61 9.72E-03 CARHSP1 224910 at AL575747 NM_014316 23589 1.61 7.34E-03 AL049709 216548 x at AL049709 — — 1.61 2.85E-04 POLD3 212836_at D26018 NM 006591 10714 1.61 3.76E-04 BZRP 202096_s_at NM_000714 NM_000714 NM_007311 706 1.61 7.10E-03 LOC286044 222662_at W60806 — 286044 1.60 2.19E-04 MICAL3 229474_at BF055090 XM_032996 XM_032997 57553 1.60 4.74E-03 C1QL1 205575 at NM 006688 NM 006688 10882 1.60 1.17E-03 EGFR 224999_at BE878463 NM 005228 NM 201282 NM 201283 NM_201284 1956 1.60 1.02E-02 AL040051 225481_at AL040051 — — 1.60 1.85E-03 GLRX 209276_s_at AF162769 NM 002064 2745 1.59 8.29E-03 CDC25C 217010_s_at AF277724 NM 001790 NM_022809 995 1.59 8.33E-03 DNM3 209839_at AL136712 NM 015569 26052 1.59 3.88E-04 LOC81691 215215_s_at AC004381 NM_030941 81691 1.59 1.47E-05 SCD4 224018 s at BC004936 NM 024906 79966 1.59 5.27E-04 PAG 225626_at AK000680 NM_018440 55824 1.59 7.40E-03 SLC8A1 235518_at AI741439 NM_021097 6546 1.58 5.49E-04 W93046 230068_s_at W93046 — — 1.58 3.19E-03 Cep70 224150 s at AF289495 NM 024491 80321 1.58 1.32E-03 DACH1 205471_s_at AW772082 NM_004392 NM_080759 NM 080760 1602 1.58 3.93E-03 FLJ12484 219361 s at NM 022767 NM 022767 64782 1.58 3.84E-04 IMP-1 223689_at AF198254 NM_006546 10642 1.57 2.37E-03 AI697657 229128_s_at AI697657 — — 1.57 1.62E-05 LOC90139 227307 at AL565381 NM 130783 90139 1.57 2.80E-03 SEZ6L 216047 x at AL050253 NM_021115 23544 1.57 1.21E-04 CENPC1 204739_at NM 001812 NM001812 1060 1.57 4.21 E-04 CKS2 204170_s at NM 001827 NM_001827 1164 1.57 6.57E-04 LOC92689 213455 at W87466 NM_138389 92689 1.57 6.69E-04 ROR1 211057 at BC006374 NM_005012 4919 1.57 9.11 E-04 232 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B„ et al., Cells Useful for Immuno-Based BoNT/A Activity Assays PHF19 227211_at BE544837 NM 00100993 6 NM_015651 26147 1.56 3.54E-04 PHF21B 1562309_s_at AK092243 NM_138415 112885 1.56 5.12E-05 USP48 229812 at BE645018 NM_032236 84196 1.56 4.62E-03 LOC221362 213248_at AL577024 — 221362 1.56 9.52E-06 CRYZ 202950_at NM_001889 NM_001889 1429 1.56 3.29E-04 GATM 203178_at NM_001482 NM_001482 2628 1.56 1.90E-05 NM_014641 203062_s_at NM 014641 — ... 1.55 5.41 E-05 FLJ38964 235699_at H19232 NM 173527 161253 1.55 4.09E-03 SPA17 205406_s_at NM_017425 NM_017425 53340 1.55 1.75E-03 NRP1 212298_at BE620457 NM 003873 8829 1.55 7.51 E-03 NXN 243503_at AI632740 NM_022463 64359 1.55 1.68E-04 TCFL5 235694_at N49233 NM 006602 10732 1.55 7.24E-05 UNG 202330_s_at NM_003362 NM_003362 NM_080911 7374 1.54 5.21 E-06 TREX2 213334_x_at BE676218 — 11219 1.54 6.50E-04 WHSC1 209053_s_at BE793789 NM_007331 NM_014919 NM_133330 NM 133331 NM_133332 NM 133333 NM_133334 NM 133335 NM_133336 7468 1.54 1.93E-04 ITGB3BP 205176_s_at NM_014288 NM_014288 23421 1.54 1.06E-04 LSM4 202736_s_at AA112507 NM_012321 25804 1.54 8.14E-05 MPP5 226092 at BF115203 NM 022474 64398 1.54 7.77E-03 MGC21654 214061_at AI017564 NM_145647 93594 1.54 4.22E-04 C9orf76 218979_at NM_024945 NM 024945 80010 1.54 2.48E-04 KLF7 238482_at AL120562 NM_003709 8609 1.54 5.35E-03 LZTS1 47550_at N21184 NM 021020 11178 1.54 9.06E-03 SLC8A1 238546_at BF344961 NM_021097 6546 1.54 1.55E-03 FGD4 242445_at AA296351 NM 139241 121512 1.54 9.73E-03 ZNF217 203739_at NM 006526 NM 006526 7764 1.54 4.11 E-06 TM4SF14 221002 s at NM 030927 NM 030927 81619 1.54 1.44E-03 NAGA 202943_s_at M38083 NM_000262 4668 1.53 1.02E-03 RAI14 202052_s_at NM_015577 NM 015577 26064 1.53 4.59E-04 PARD6G 227204_at Al 817448 NM 032510 84552 1.53 7.67E-04 MMD 203414_at NM 012329 NM 012329 23531 1.53 7.58E-05 C15orf23 225300_at BF792864 NM_033286 90417 1.53 6.24E-04 AC01 207071_s_at NM_002197 NM_002197 48 1.53 6.67E-03 FLJ10514 218365 s at AI765051 NM 018122 55157 1.53 2.72E-03 RAB3B 227123 at AU156710 NM 002867 5865 1.52 1.25E-03 TCFL5 204849_at NM_006602 NM 006602 10732 1.52 8.79E-04 GEMIN4 205527_s_at NM_015487 NM_015721 50628 1.52 2.20E-03 CBLB 209682 at U26710 NM 170662 868 1.52 9.18E-07 HMG2L1 212596_s_at AJ010070 NM_00100368 1 NM 005487 NM 014250 10042 1.52 1.65E-04 CARHSP1 218384 at NM_014316 NM 014316 23589 1.52 1.20E-03 PTPRR 210675_s_at U77917 NM_002849 NM_130846 5801 1.51 6.84E-03 ZNF85 1554445 at BC008688 NM 003429 7639 1.51 8.78E-03 C20orf58 230668_at AI758937 NM_152864 128414 1.51 2.35E-04 AK098258 1564175 at AK098258 — — 1.51 4.42E-03 233 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays ADPN 220675 s at NM 025225 NM 025225 80339 1.51 6.52E-04 RANBP1 202483 s at NM 002882 NM 002882 5902 1.51 9.75E-06 CDK6 224851 at AW274756 NM 001259 1021 1.51 3.51 E-04 GPR161 206972_s_at NM_007369 NM_007369 NM_153832 23432 1.51 3.61 E-05 MCFP 205716 at NM 018843 NM 018843 55972 1.51 5.29E-03 RTN4IP1 224509_s_at BC006399 NMJ332730 84816 1.51 1.29E-03 RANGAP 1 212125_at NM_002883 NM_002883 5905 1.50 4.37E-04 BF057492 221871 s at BF057492 — — 1.50 2.08E-03 MMD 244523 at AW104453 NM 012329 23531 1.50 4.38E-05 PHF19 227212 s at BE544837 NM_00100993 26147 1.50 4.91 E-05 6 NM 015651 HMGB3 203744 at NM 005342 NM 005342 3149 1.50 1.38E-06 RODH 37512 at U89281 NM 003725 8630 1.50 6.29E-03 AW665447 230113_at AW665447 — — 1.50 8.13E-03 RANGAP1 1553535 a at NM 002883 NM 002883 5905 1.50 6.68E-05 PRIM1 205053 at NM 000946 NM 000946 5557 1.49 7.62E-05 FEN1 204767_s_at BC000323 NM 004111 2237 1.49 2.41 E-04 MAN1A1 208116 s at NM 005907 NM_005907 4121 1.49 2.54E-03 SLC1A1 213664 at AW235061 NM_004170 6505 1.49 1.97E-04 LOC283027 1562527_at AF519622 — 283027 1.49 6.56E-03 BUB3 201457_x_at AF081496 NM_00100779 9184 1.49 1.77E-05 GPR161 230369_at AI743151 ό NM 004725 NM_007369 23432 1.49 2.32E-04 TRIM59 235476_at AW182459 NM_153832 NM_173084 286827 1.49 9.48E-03 TLE4 204872 at NM 007005 NM_007005 7091 1.48 3.51 E-05 LOC401022 242042_s_at AA406052 — 401022 1.48 1.50E-03 ZAK 238613_at AI475164 NM_016653 51776 1.48 7.42E-03 DHRS10 228713 s at AI742586 NM_133646 NM 016246 51171 1.48 3.31 E-03 FLJ10747 222673_x_at AI582192 N M 018202 159090 1.48 4.86E-05 LOC159090 MGC13186 223272 s at BC005102 NM_145284 NM 032324 55219 84284 1.47 5.80E-03 FLJ11535 220798 x at NM 024888 NM 024888 79948 1.47 8.54 E-03 C9orf81 228774_at AW268594 XM_095991 84131 1.47 2.00 E-04 DHX35 234728_s_at AL023803 NM 021931 60625 1.47 9.46 E-04 EPOR 209962_at M34986 NM_000121 2057 1.47 4.25E-03 DUT 208955 at AB049113 NM 001948 1854 1.47 1.77 E-03 KHDRBS3 209781_s_at AF069681 NM_006558 10656 1.47 5.70E-06 AA218973 237245_at AA218973 XM 372330 390009 1.47 2.67E-03 PVT1 1558290_a_at BG200951 XM 372058 441378 1.47 4.77 E-04 LOC441378 MCM7 210983_s_at AF279900 XM 499128 NM_005916 5820 4176 1.47 5.48E-05 POLR3K 218866 s at NM 016310 NM_182776 NM 016310 51728 1.47 2.20E-03 LOC159090 225361 x at AI348001 NM_145284 159090 1.47 4.60E-05 CNP 208912_s_at BC001362 NM 033133 1267 1.47 7.89E-04 LOC201725 235088_at AI276663 NM_001008393 201725 1.46 1.25E-03 CHRNA3 211772 x at BC006114 NM 000743 1136 1.46 8.95E-04 LOC126295 1554628 at BC028974 NM_173480 126295 1.46 8.70E-03 FARP1 201911_s_at NM_005766 NM 00100171 10160 1.46 7.82E-05 PAX5 221969_at BF510692 O NM_005766 NM_016734 5079 1.46 8.27E-04 HTR2B 206638_at NM_000867 NM_000867 3357 1.46 5.49E-03 234 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays SLC25A10 218275_at NM_012140 NM_012140 1468 1.46 6.48E-03 HELLS 242890 at AI650364 NM 018063 3070 1.46 2.08E-03 CCBE1 243805 at BG035826 NM_133459 147372 1.46 3.38E-03 BE877357 228314_at BE877357 — ... 1.46 3.26E-03 MAK3 222393_s_at AU149868 NM_025146 80218 1.46 4.59E-03 BE222344 226034 at BE222344 — — 1.46 5.03E-04 FLJ10375 243230_at AA918375 NM_018075 55129 1.46 6.10E-03 BRI3BP 231810_at BG106919 NM_080626 140707 1.46 5.53E-04 LCRISP1 223475_at AF142573 NM 031461 83690 1.46 8.87E-04 ARHGAP6 206167_s_at NM_001174 NM 001174 NM_006125 NM 013422 NM_013423 NM 013427 395 1.45 6.89E-03 TLX3 208495_at NM_021025 NM_021025 30012 1.45 3.06E-04 H2AFV 202487_s_at NM_012412 NM_012412 NM 138635 NM 201436 NM 201516 NM_201517 94239 1.45 4.29E-03 BIRC5 1555826 at BQ021146 NM_001168 332 1.45 3.48E-03 AI357639 225716_at AI357639 — ... 1.44 3.04E-04 ARMC7 229906_at BF194773 NM_024585 79637 1.44 2.42E-03 OSBPL10 219073 s_at NM_017784 NM_017784 114884 1.44 1.05E-03 TUBB4 212664 at AL567012 NM 006087 10382 1.44 2.03E-03 LRRIQ2 219886 at NM 024548 NM 024548 79598 1.44 8.76E-04 CUGBP2 1557422_at R49146 NM_006561 10659 1.44 7.78E-03 SRGAP2 213329_at AA742261 XM 059095 23380 1.44 1.39E-03 NUP93 202188_at NM 014669 NM 014669 9688 1.44 2.68E-06 LOC440288 238511 at BF982733 XM_496075 440288 1.44 3.83E-04 AI346432 229132_at Al 346432 — ... 1.44 3.77E-04 HSZFP36 229732_at AI417785 XM_375568 55552 1.43 1.60E-04 DLG2 206253_at NM 001364 NM 001364 1740 1.43 7.70E-04 PTX3 206157 at NM 002852 NM 002852 5806 1.43 3.96E-04 FIGNL1 1552921_a_at NM 022116 NM 022116 63979 1.43 3.50E-04 CHML 206079_at NM_001821 NM_001821 1122 1.43 7.71 E-03 AI889959 227350 at AI889959 — — 1.43 3.94E-04 TLE4 233575 s at AA705845 NM 007005 7091 1.43 5.78E-04 LOC388272 226608_at AW157311 NM_001001436 388272 1.43 2.91 E-03 MGC2603 220011_at NM_024037 NM 024037 79000 1.43 1.24E-04 KIAA1853 230010 at AA608629 NM 194286 84530 1.43 8.35E-04 LOC51760 205613_at NM_016524 NM_016524 51760 1.42 1.17E-03 CSE1L 210766_s_at AF053640 NM_001316 NM_177436 1434 1.42 1.06E-05 FAD158 223533 at AL136919 NM 032270 84230 1.42 2.21 E-04 FAM54A 234944_s_at AL138828 NMJ38419 113115 1.42 4.74E-03 UNC84B 212144_at AL021707 NM 015374 25777 1.42 1.88E-03 BICD1 1554020_at BC010091 NM 00100339 8 NM_001714 636 1.42 9.68E-03 GNG2 1555766_a_at AF493870 NM_053064 54331 1.42 1.16E-06 WDR51A 234749 s at AL117629 NM 015426 25886 1.42 5.03E-03 EME1 234464 s at AK021607 NM 152463 146956 1.42 1.54E-05 TNFRSF19L 227060_at AW571669 NM 032871 NM_152222 84957 1.42 3.79E-03 TSC 218872 at NM 017899 NM 017899 54997 1.42 3.16 E-03 LOC201725 238015 at BE620598 NM 001008393 201725 1.42 7.24E-05 FAM33A 225686 at BE048371 NM 182620 348235 1.42 9.89E-05 235 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays GTF2E1 205930 at NM 005513 NM 005513 2960 1.42 2.50E-04 TYR03 211432 s at U05682 NM 006293 7301 1.42 1.33E-03 GFPT2 205100_at NM_005110 NM_005110 9945 1.42 1.08E-03 SNX10 218404_at NM_013322 NM_013322 29887 1.41 4.80E-04 BU077901 1557214 at BU077901 — — 1.41 2.12E-04 KPNA2 201088 at NM 002266 NM_002266 3838 1.41 1.16E-05 LZTS1 219042_at NM_021020 NM_021020 11178 1.41 5.78E-03 NOS1 207309_at NM 000620 NM_000620 4842 1.41 5.32E-04 CGI-96 33307 at AL022316 NM 015703 27341 1.41 4.76E-04 WDR34 224715_at BG338983 NM 052844 89891 1.40 1.09E-03 RAB3B 205924_at BC005035 NM 002867 5865 1.40 2.80E-03 GCH1 204224_s_at NM_000161 NM_000161 2643 1.40 2.84E-03 C14orf145 1557755_at AW028337 XM 496002 145508 1.40 1.22E-03 PDLIM5 203242_s_at BG054550 NM_00101151 3 NM_00101151 4 NM_00101151 5 NM 00101151 6 NM_006457 10611 1.40 6.09E-03 MPP5 219321_at NM_022474 NM_022474 64398 1.40 2.21 E-05 CD01 204154_at NM_001801 NM_001801 1036 1.40 3.42E-05 CHAF1B 204775_at NM 005441 NM 005441 8208 1.40 9.66E-04 RECQL 210568_s_at BC001052 NM_002907 NM_032941 5965 1.40 3.54E-03 MAPK12 206106_at AL022328 NM_002969 6300 1.40 1.10E-06 PTTG3 208511 at NM_021000 — 26255 1.39 1.10E-03 HAT1 203138_at NM_003642 NM_003642 8520 1.39 2.54E-05 MYD88 209124_at U70451 NM_002468 4615 1.39 2.89E-03 NUDT15 219347_at NM 018283 NM 018283 55270 1.39 1.29E-04 PCDH9 219737_s_at AI524125 NM 020403 NM 203487 5101 1.39 7.01 E-03 182-FIP 243119_at AA810156 NM 020772 57532 1.39 2.92E-04 MCM4 212141_at AA604621 NM 005914 NM 182746 4173 1.39 3.82E-03 RAB23 229504_at Al810826 NM 016277 NM_183227 51715 1.39 1.82 E-05 C9orf88 223019_at BC001979 NM 022833 64855 1.39 2.37E-03 DLX6 242940_x_at AA040332 XM 376652 XM_379892 1750 1.39 2.34E-06 FLJ13909 219556_at NM 025108 NM 025108 80178 1.39 5.95E-04 CDKN2C 204159_at NM_001262 NM 001262 NM_078626 1031 1.39 5.88E-04 MEIS1 1559477_s_at AL832770 NM_002398 4211 1.39 3.54E-04 STRA6 1569334 at BC015881 NM_022369 64220 1.39 6.72E-03 AW069181 223519_at AW069181 — — 1.39 9.35E-04 SEZ6L 213609 s at AB023144 NM_021115 23544 1.38 5.40E-04 FKBP14 235311_at BG110260 NM_017946 55033 1.38 1.16E-04 BG231758 227615_at BG231758 — — 1.38 1.85E-04 GEMIN4 217099_s at AF258545 NM 015721 50628 1.38 2.18E-03 H2AFV 227085_at AI823792 NM_012412 NM_138635 NM 201436 NM 201516 NM_201517 94239 1.38 1.65E-04 KLF10 202393_s_at NM_005655 NM_005655 7071 1.38 4.37E-03 236 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B„ et al., Cells Useful for Immuno-Based BoNT/A Activity Assays MRE11A 205395_s_at NM_005590 NM 005590 NM_005591 4361 1.38 9.90E-04 FDXR 207813_s_at NM_004110 NM_004110 NM_024417 2232 1.38 6.17E-04 GNG4 205184_at NM_004485 NM 004485 2786 1.38 2.86E-05 MYOHD1 219320 at NM 025109 NM 025109 80179 1.38 6.52E-04 CTL2 224609_at AI264216 NM_020428 57153 1.37 2.31 E-03 FLJ13273 235387_at AA740875 NM 024751 79807 1.37 1.76E-05 EDA2R 221399_at NM_021783 NM 021783 60401 1.37 4.37E-03 MGC10744 238590_x_at BF981428 NM 032354 NM_183065 84314 1.37 6.04E-03 ACYP1 205260_s_at NM001107 NM_001107 NM_203488 97 1.37 7.99E-03 MGC12197 1555501 s at BC010357 NM 016625 51319 1.37 1.22E-03 MGC13186 226813_at AA883980 NM 032324 84284 1.37 9.86E-04 MRE11A 242456_at AA931565 NM 005590 NM 005591 4361 1.37 6.99E-03 BCR 202315_s_at NM_004327 NM 004327 NM 021574 613 1.36 1.69E-04 CHRNA3 211587_x_at M37981 NM 000743 1136 1.36 8.91 E-04 GPR161 235961_at BF248385 NM 007369 NM 153832 23432 1.36 5.62E-05 DUSP4 204015_s_at BC002671 NM_001394 NM_057158 1846 1.36 6.68E-04 GNG4 1555765_a_at AF493872 NM 004485 2786 1.36 8.13E-05 FLJ11712 219056_at NM 024570 NM 024570 79621 1:36 2.93E-03 BUB3 209974_s_at AF047473 NM 00100779 3 NM_004725 9184 1.36 2.12E-06 LOC93081 213346 at BE748563 NM 138779 93081 1.36 2.01 E-05 UNQ470 228403_at AL541276 NM 198573 375704 1.36 9.85E-03 FLJ20364 221685_s_at AF269167 NM_017785 54908 1.36 4.22E-05 LOC283454 242715 at AA331548 — 283454 1.36 8.25E-04 LOC388272 242555 at AW578854 NM 001001436 388272 1.35 7.50E-03 SELM 226051_at BF973568 NM 080430 140606 1.35 1.09E-04 PAQR4 212858_at AL520675 NM 152341 124222 1.35 3.60E-05 C20orf7 222894_x_at AI640582 NM 024120 NM_199052 79133 1.35 1.37E-04 PKP4 201929_s_at NM 003628 NM_00100547 6 NM 003628 8502 1.35 6.66E-05 CBX5 242069_at BE568225 NM_012117 23468 1.35 1.98E-03 CPNE4 228796_at BE645967 NM 130808 131034 1.35 4.28E-03 CSE1L 201112_s_at NM_001316 NM 001316 NM_177436 1434 1.35 2.61 E-06 TBC1D1 227945_at BE882538 NM_015173 23216 1.34 4.34E-03 B4GALT1 201883_s_at D29805 NM_001497 2683 1.34 1.44E-03 TAF5 1553528_a_at NM 139052 NM 006951 6877 1.34 9.10E-04 CEP1 205642_at NM 007018 NM_007018 11064 1.34 3.35E-04 STOM 201061_s_at M81635 NM_004099 NM_198194 2040 1.34 1.41 E-04 C6orf182 1554019 s at BC033448 NM_173830 285753 1.34 1.74E-05 LOC284465 229382 at AW149270 — 284465 1.34 3.05E-03 C20orf108 224690_at BG432350 NM_080821 116151 1.34 1.10E-03 TDRD7 213361_at AW129593 NM_014290 23424 1.34 5.01 E-03 CDK6 224847 at AW051349 NM 001259 1021 1.33 2.41 E-04 C20orf102 226973 at AA206763 NM 080607 128434 1.33 2.65E-03 TMPO 227578 at H28597 NM 003276 7112 1.33 1.51 E-03 237 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays TUBB6 209191_at BC002654 NM 032525 84617 1.33 1.57E-04 ANP32E 221505 at AW612574 NM 030920 81611 1.33 1.41 E-05 FLJ20516 219258_at NM_017858 NM_017858 54962 1.33 1.05E-03 DC13 218447_at NM 020188 NM 020188 56942 1.33 3.60E-03 CKLF 219161_s_at NM_016951 NM 016326 NM 016951 NM_181640 NM 181641 51192 1.33 6.08E-05 DLL3 219537_x_at NM_016941 NM 016941 NM 203486 10683 1.33 1.14E-05 DOCK4 205003_at NM_014705 N M 014705 9732 1.33 1.67E-03 UBAP2L 201377_at NM 014847 NM_014847 9898 1.33 1.35E-05 FLJ10036 218349 s at NM 017975 NM 017975 55055 1.33 1.50E-03 SERPING1 200986 at NM_000062 NM 000062 710 1.33 3.17E-03 SCML2 206147_x_at NM 006089 NM 006089 10389 1.33 2.97E-05 BE877775 1568955_at BE877775 — — 1.33 1.57E-05 LOC440820 226602 s at T30183 XM 496519 440820 1.33 3.16E-05 FKBP5 224856 at W86302 NM 004117 2289 1.33 1.42E-03 PPM1D 230330_at AI312083 N M 003620 8493 1.33 4.50E-04 )KFZp313A243i 226278_at Al 150224 — 258010 1.32 1.69E-04 MAN1A1 221760_at BG287153 NM_005907 4121 1.32 1.75E-05 RFWD3 218564 at BC002574 ... 55159 1.32 4.99E-04 C10orf78 238794_at N23586 NM_00100275 9 NM 145247 119392 1.32 9.64E-05 NEGR1 229461 x at AI123532 NM_173808 257194 1.32 1.20E-03 DCK 203302_at NM 000788 NM_000788 1633 1.32 3.62E-05 K-ALPHA-1 211072_x_at BC006481 NM_006082 10376 1.32 6.06E-06 Al092265 228088_at AI092265 — — 1.32 9.95E-04 UCHL5 220083_x_at NM_016017 NM 015984 51377 1.32 2.96E-04 TRIM37 1554001_at BC036012 NM_00100520 7 NM 015294 4591 1.32 8.08E-04 MGC39900 214051_at BF677486 NM 194324 286527 1.32 7.28E-03 NFYB 218129_s_at NM_006166 NM 006166 4801 1.32 5.07E-03 FAS 204781_s_at NM_000043 NM 000043 NM 152871 NM 152872 NM 152873 NM 152874 NM 152875 NM_152876 NM 152877 355 1.32 1.70E-03 C2orf23 204364 s at BE535746 NM 022912 65055 1.31 8.43E-05 YPEL1 228296_at AW450686 NM_013313 29799 1.31 7.66E-03 TRAF4 211899_s_at AF082185 NM_004295 NM_145751 9618 1.31 4.10E-03 GLS 203158 s at AF097493 NM 014905 2744 1.31 9.13E-04 FARP1 201910_at BF213279 NM_00100171 5 NM 005766 10160 1.31 6.05E-04 C9orf40 222781_s_at BF590861 NM_017998 55071 1.31 1.00E-02 ADCY3 235441_at BF217471 NM_004036 109 1.31 9.61 E-03 ZNF253 LOC114977 242919_at AV683221 NM_021047 114977 56242 1.31 1.27E-03 NASP 201970_s_at NM_002482 NM_002482 NM 152298 NM 172164 4678 1.31 8.90E-05 238 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays ACTL6A 202666_s_at NM_004301 NM 004301 86 1.30 1.03E-07 HOXD3 206601_s_at BC005124 NM_177989 NM_178042 NM_006898 3232 1.30 3.02E-04 SORD 201563_at L29008 NM 003104 6652 1.30 6.16E-05 COQ3 223515_s_at AL136726 NM_017421 51805 1.30 1.20E-05 SKP2 203626_s_at NM_005983 NM_005983 6502 1.30 9.20E-03 CDK6 224848_at AA922068 NM_032637 NM_001259 1021 1.30 3.32E-03 BOK 223349 s at BE614255 NM 032515 666 1.30 4.78E-06 PCDH17 205656_at NM 014459 NM 014459 27253 1.30 1.41E-03 BCAS4 220588_at NM_017843 NM_00101097 A 55653 1.30 3.33E-04 TDP1 219715_s_at NM_018319 NM_017843 NM 198799 NM_00100874 A 55775 1.30 5.37E-05 LOC283683 217520_x_at BG396614 4 NM_018319 XM_290660 283683 1.30 9.14E-03 LOC339003 C6orf152 242006 at AI379143 NM_181714 339003 167691 1.30 2.64E-03 AA824298 222606_at AA824298 ... ... 1.30 2.38E-03 PRPS1 208447_s_at NM_002764 NM_002764 5631 1.30 1.12E-04 AA401256 230537 at AA401256 — — 1.30 2.49E-03 SUV39H2 1554572 a at BC029360 NM_024670 79723 1.29 2.41 E-05 LOC284244 214162_at AF070541 — 284244 1.29 9.39E-03 WDR53 227814_at AA789329 NM_182627 348793 1.29 5.37E-06 CPT1A 210688 s at BC000185 NM 001876 1374 1.29 5.31 E-03 RFC1 208021 s at NM_002913 NM_002913 5981 1.29 1.61E-06 MGC10812 223469_at BC004942 — 83542 1.29 3.11E-04 CSE1L 201111_at AF053641 NM_001316 1434 1.29 1.01 E-03 PPFIBP2 212841 s at AI692180 NM_177436 NM 003621 8495 1.29 4.46E-04 CHRNA3 210221_at BC000513 NM 000743 1136 1.29 6.31 E-03 RBL1 1559307_s_at BG387892 NM_002895 5933 1.29 5.93E-05 ZNF43 206695_x_at NM_003423 NM_183404 NM_003423 7594 1.28 2.30E-04 TM4SF7 209263 x at BC000389 NM 003271 7106 1.28 2.01 E-04 PDLIM5 216804_s_at AK027217 NM_00101151 o 10611 1.28 1.45E-03 KCNJ8 205304 s at NM_004982 0 NM_00101151 4 NM_00101151 5 NM_00101151 6 NM_006457 NM 004982 3764 1.28 8.99E-05 NLN 225943_at BF222737 NM_020726 57486 1.28 6.53E-03 ORF1-FL49 224707_at AL522667 NM_032412 84418 1.28 6.23E-05 AL833487 1562244_at AL833487 — — . 1.28 1.81 E-04 EB-1 227440_at AW005572 NM 020140 56899 1.28 2.28E-03 MEIS1 204069 at NM_002398 NM_152788 NM_181670 NM 002398 4211 1.28 3.15 E-04 SESTD1 226763_at AW409611 NM_178123 91404 1.27 1.35E-03 GNG2 224964_s_at AK026424 NM_053064 54331 1.27 1.89E-05 DPF1 231599_x_at AI939563 NM_004647 8193 1.27 1.45E-03 239 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., etal., Cells Useful for Immuno-Based BoNT/A Activity Assays STMN1 200783_s_at NM_005563 NM 005563 NM 203399 NM_203401 3925 1.27 5.04E-04 AF279774 216967_at AF279774 — — 1.27 8.55E-03 DUSP4 204014_at NM_001394 NM 001394 NM 057158 1846 1.27 1.77E-04 MCM4 222036_s_at AI859865 NM 005914 NM_182746 4173 1.27 2.04E-03 C6orf151 1553274 a at NM 152551 NM 152551 154007 1.27 8.31 E-03 RRM2B 223342 at AB036063 NM_015713 50484 1.27 4.55E-04 TDRKH 223530_at AF227192 NM_006862 11022 1.27 1.02E-06 PR I M2 A 215708_s_at AL121975 NM 000947 5558 1.26 1.78E-03 GPR161 214104_at AI703188 NM 007369 NM_153832 23432 1.26 1.74E-05 NR3C1 211671_s_at U01351 NM_000176 2908 1.26 1.39E-04 TCF7L2 212761_at AI949687 NM_030756 6934 1.26 8.24E-03 HECA 218603_at NM 016217 NM 016217 51696 1.26 8.85E-03 KREMEN1 227250_at BF221745 NM_032045 NM 153379 83999 1.26 3.46E-04 RBMS3 241789_at AW338699 NM_00100379 2 NM_00100379 3 NM 014483 27303 1.26 7.52E-03 PLAUR 211924_s_at AY029180 NM 00100537 6 NM_00100537 7 NM 002659 5329 1.26 2.35E-03 FLJ25059 229025_s_at AW008627 NMJ44981 196294 1.26 2.34E-03 FKBP5 204560_at NM 004117 NM 004117 2289 1.26 5.68E-03 HOMER3 215489_x_at AI871287 NM 004838 9454 1.26 3.85E-03 ZNF503 227195 at AA603467 NM_032772 84858 1.26 6.66E-04 AL833634 1562699_at AL833634 — — 1.26 8.19E-05 BAX 211833_s_at U19599 NM_004324 NM 138761 NM_138762 NM 138763 NM_138764 NM 138765 581 1.25 6.21 E-04 SUHW2 229360 at N22886 NM 080764 140883 1.25 5.46E-04 CNTN4 229084_at R42166 NM_175607 NM_175612 NM 175613 152330 1.25 9.69E-04 ZNF184 213452_at AI811577 NM_007149 7738 1.25 4.11E-05 MPP1 202974_at NM 002436 NM_002436 4354 1.25 1.81 E-03 LOC93349 214791_at AK023116 NM_138402 93349 1.25 5.56E-06 TOP3B 215781 s at D87012 NM 003935 8940 1.25 1.49E-03 RTTN 227072_at BG167480 NM_173630 25914 1.25 8.89E-06 ASK 204244_s_at NM_006716 NM_006716 10926 1.25 3.89E-05 FANCG 203564_at NM 004629 NM 004629 2189 1.25 1.29E-04 WIG1 1555609_a_at AF355465 NM 022470 NM_152240 64393 1.25 2.45E-03 RFC1 209085_x_at L14922 NM 002913 5981 1.24 3.75E-07 TRIM59 227801_at N90779 NM 173084 286827 1.24 3.52E-03 KIAA1522 224746_at AB040955 XM 036299 57648 1.24 8.59E-03 SLC17A6 220551_at NM_020346 NM_020346 57084 1.24 4.19E-04 PFKFB3 202464_s_at NM 004566 NM 004566 5209 1.24 4.76E-04 240 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., etal., Cells Useful for Immuno-Based BoNT/A Activity Assays BF110268 238178 at BF110268 — — 1.24 1.57E-03 TCF3 209152_s_at AI655986 NM_003200 6929 1.24 2.72E-03 AMOTL1 225450 at AI433831 NM 130847 154810 1.24 5.65E-06 TUBA2 210527_x_at L11645 NM_006001 NM_079836 7278 1.24 3.79E-05 AB033091 225295_at AB033091 — — 1.23 8.34E-06 Cep70 219036_at NM_024491 NM_024491 80321 1.23 6.01 E-03 RTN4IP1 1555679_a_at AF439711 NM_032730 84816 1.23 3.15E-03 HTATSF1 202601 s at AI373539 NM_014500 27336 1.23 1.15E-03 CA773938 1558517_s_at CA773938 — — 1.23 7.86E-04 RAB27A 210951_x_at AF125393 NM_004580 NM_183234 NM 183235 NM_183236 5873 1.23 4.76E-03 TLE3 228340_at BE967118 NM_005078 7090 1.23 4.90E-03 AI452715 229817 at A1452715 — — 1.23 3.71 E-03 AK022598 232662_x_at AK022598 — — 1.22 2.67E-03 RNF26 224947_at AL559247 NM_032015 79102 1.22 2.05E-04 C2orf23 204365_s_at NM_022912 NM_022912 65055 1.22 9.80E-05 KIAA0574 213997 at AB011146 — 23359 1.22 4.46E-03 K-ALPHA-1 213646_x_at BE300252 NM 006082 10376 1.22 1.24E-05 SKP2 203625_x_at BG105365 NM 005983 NM_032637 6502 1.22 4.38E-06 ZNF443 205928 at NM 005815 NM 005815 10224 1.22 2.72E-03 MAPKAPK3 202788_at NM 004635 NM 004635 7867 1.22 1.73E-04 RUSC1 206949_s_at NM_014328 NM_014328 23623 1.22 4.02E-04 FIGNL1 222843_at AK023411 NM_022116 63979 1.22 1.26E-04 SENP1 1552812 a at NM_014554 NM_014554 29843 1.22 2.44E-03 AW874669 239834 at AW874669 — ... 1.22 1.90E-04 USP1 202413_s_at NM_003368 NM_003368 7398 1.22 3.61 E-04 K1AA0318 238817_at BF063412 NM_015347 23504 1.22 1.61 E-03 MGC5576 201764 at NM 024056 NM 024056 79022 1.22 1.26E-03 MGC34032 1552782 at AK091400 NM_152697 204962 1.21 2.92E-03 septin 6 213666_at AK026589 NM 015129 NM_145799 NM 145800 NM_145802 23157 1.21 5.69E-03 AI143124 212832_s_at Al 143124 — — 1.21 2.67E-04 SLC2A4RG 218494_s_at NM_020062 NM_020062 56731 1.21 6.93E-04 ZNF423 214761 at AW149417 NM 015069 23090 1.21 8.23E-03 CSRP2BP 228543_at AA780252 NM_020536 NM_177926 57325 1.21 9.19E-06 MTUS1 212095_s_at BE552421 NM_00100192 4 NM_00100192 5 NM_00100192 7 NM_00100193 1 NM_020749 57509 1.21 2.45E-04 BF056092 242629_at BF056092 — — 1.21 6.11 E-03 HPSE 219403_sat NM 006665 NM 006665 10855 1.21 1.02E-02 BF445001 238212_at BF445001 — — 1.21 2.00E-03 SRGAP2 1568957_x_at BE877775 XM 059095 23380 1.21 1.43E-04 CDKN1A 202284_s_at NM 000389 NM_000389 NM 078467 1026 1.21 1.36E-03 241 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 RAD51C Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays 209849_s_at AF029669 NM_002876 5889 1.21 2.70E-03 GTPBP1 219357_at NM_014027 NM 058216 NM 058217 NM_004286 9567 1.20 7.29E-04 SLC25A1 210010_s_at U25147 NM 005984 6576 1.20 5.15E-04 KIAA1713 233536 at Al202664 XM 290811 80816 1.20 2.85E-03 APAF1 204859_s_at NM_013229 NM_001160 317 1.20 5.73E-05 WHSC1 222778_s_at AW024870 NM 013229 NM 181861 NMJ81868 NM 181869 NM_007331 7468 1.20 4.19E-05 T87730 242500_at T87730 NM 014919 NM_133330 NM 133331 NM 133332 NM_133333 NM_133334 NM_133335 NM_133336 1.20 1.38E-03 EHD4 209536_s_at AF320070 NM_139265 30844 1.20 5.84E-03 WIG1 219628_at NM_022470 NM_022470 64393 1.20 8.50E-04 BF977829 229067 at BF977829 NM_152240 1.20 3.26E-04 NUP62 202153_s_at NM_016553 NM_012346 23636 1.20 3.85E-04 N50083 229110_at N50083 NM_016553 NM 153718 NM_153719 1.20 1.89E-03 ARL6 223735_at AL136815 NM_032146 84100 1.20 5.56E-03 MGC2574 203119_at NM 024098 NM 177976 NM_024098 79080 1.19 1.54E-04 FLJ10407 218073_s_at N M 018087 NM 018087 55706 1.19 1.01 E-02 )KFZp313A243: 230006_s_at AI742358 — 258010 1.19 1.25E-04 C20orf7 227160_s_at AW102828 NM 024120 79133 1.19 8.46E-04 MVK 215649_s_at AF217536 NM_199052 NM 000431 4598 1.19 4.73E-03 PPP1R3D 204554_at AL109928 NM_006242 5509 1.19 9.07E-04 MGC14560 218461 at NM_016301 NM_016301 51184 1.19 2.49E-06 AC007277 216508 x at AC007277 — — 1.19 1.79E-05 EPHA2 203499_at NM 004431 NM 004431 1969 1.19 7.06E-04 UBE2L3 200684_s_at Al819709 NM 003347 7332 1.19 4.60E-07 NFS1 218455_at NM_021100 NM 198157 NM_021100 9054 1.19 2.24E-03 RELB 205205_at NM 006509 NM_181679 NM 006509 5971 1.19 8.97E-03 GAS2L1 31874_at Y07846 NM 006478 10634 1.19 1.72E-03 FLJ33814 225644_at BF060776 NM_152236 NM_152237 NM_173510 150275 1.19 2.07E-05 K-ALPHA-1 211058 x at BC006379 NM 006082 10376 1.18 1.05E-05 NUP62 207740_s_at NM_012346 NM_012346 23636 1.18 1.26E-04 K-ALPHA-1 201090_x_at NM_006082 NM_016553 NM_153718 NM 153719 NM_006082 10376 1.18 1.13E-05 NLN 225944_at AW006938 NM_020726 57486 1.18 5.24E-03 242 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B„ etal., Cells Useful for Immuno-Based BoNT/A Activity Assays ALS2CR4 1553956_at BG194770 NM_152388 65062 1.18 8.49E-04 FZD2 210220_at L37882 NM 001466 2535 1.18 2.21 E-05 RET 205879_x_at BC004257 NM_020630 NM_020975 5979 1.18 2.08E-04 FLJ23322 231846 at AK026975 NM_024955 80020 1.18 2.79E-04 BE878277 212829_at BE878277 — — 1.18 6.73E-04 ZNF286 239898_x_at AI498484 NM_020652 57335 1.18 2.96E-03 HIVEP2 243254_at T08739 NM 006734 3097 1.18 6.77E-04 SUCLG2 215772_x_at AL050226 NM_003848 8801 1.18 3.77E-04 ARF4L 203586_s_at NM 001661 NM 001661 379 1.18 3.10E-03 DDX11 213378_s_at Al 983033 NM_004399 NM_030653 NM 030655 1663 1.18 6.41 E-03 PLEKHF2 218640 s at NM_024613 NM 024613 79666 1.18 2.90E-03 MCM7 208795_s_at D55716 NM_005916 NM_182776 4176 1.18 2.26E-04 CDK6 207143_at NM 001259 NM 001259 1021 1.18 4.14E-04 BAX 208478_s_at NM_004324 NM_004324 NM_138761 NM_138762 NM 138763 NM_138764 NM_138765 581 1.17 5.30E-04 FLJ23322 220707_s_at NM_024955 NM_024955 80020 1.17 2.10E-03 LOC139886 228654_at AU145277 XM 066946 139886 1.17 1.82E-06 TANC 225308_s_at AB051515 NM 033394 85461 1.17 1.16E-03 FBX022 225736_at BE966247 NM_012170 NM_147188 26263 1.17 3.53E-05 BE504215 228563_at BE504215 — — 1.17 2.17E-04 FAM43A 227410 at AW264102 NM_153690 131583 1.17 2.24E-04 PXN 201087_at NM_002859 NM_002859 5829 1.17 5.53E-04 BCLP 225536_at AL545105 NM 033504 113452 1.16 9.28E-03 C1orf43 1555225_at BC008306 NM 015449 NM_138740 25912 1.16 4.74E-04 CABYR 219928_s_at NM_012189 NM_012189 NM 138643 NM_138644 NM_153768 NM 153769 NM 153770 26256 1.16 4.76E-04 SEZ6L 231650_s_at BE672217 NM 021115 23544 1.16 9.63E-04 USP1 202412_s_at AW499935 NM_003368 7398 1.16 9.85E-04 C21orf45 228597_at AW151538 NM 018944 54069 1.16 9.08E-04 PDLIM5 203243_s_at NM_006457 NM 00101151 3 NM00101151 4 NM 00101151 5 NM 00101151 6 NM 006457 10611 1.16 3.70E-05 LGR4 218326_s_at NM_018490 NM_018490 55366 1.16 1.79E-03 LOC284307 235773_at AW029293 NM 001010879 284307 1.16 2.08E-03 ZCCHC4 220473_s_at NM_014150 XM_376310 29063 1.16 2.21 E-04 H10661 242317_at H10661 — — 1.16 4.34E-03 MFGE8 210605_s_at BC003610 NM_005928 4240 1.16 5.08E-03 CDC5L 209055_s_at AW268817 NM_001253 988 1.16 2.21 E-06 243 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays ARL6IP 211935 at D31885 NM 015161 23204 1.16 1.46E-04 NAGA 202944 at NM 000262 NM 000262 4668 1.16 4.02E-05 RAB23 220955_x_at NM 016277 NM_016277 NM_183227 51715 1.16 5.82E-04 KCNN1 206231 at NM 002248 NM 002248 3780 1.16 4.89E-04 ch-TOG 1555278_a_at BC035554 NM 00100893 8 NM_014756 9793 1.16 1.57E-04 MPHOSPH9 206205 at NM_022782 NM_022782 10198 1.16 5.99E-04 AM 41426 229898_at AI141426 — — 1.16 4.31 E-04 POU2F1 206789 s at NM 002697 NM_002697 5451 1.15 5.40E-03 DKFZP434L187 230861_at AA889613 XM_496054 26082 1.15 5.85E-05 C14orf160 224460 s at BC006117 NM 024884 79944 1.15 3.17E-03 PPM1D 204566_at NM_003620 NM 003620 8493 1.15 1.21 E-04 KIAA1853 236151_at BF315452 NM„194286 84530 1.15 1.89E-03 GLS 203159_at NM_014905 NM_014905 2744 1.15 4.23E-03 FLJ31842 234980 at Al 004375 NM_152487 148534 1.15 5.24E-03 FLJ20512 219219_at NM_017854 NM_017854 54958 1.15 2.66E-03 C13orf7 219303_at NM_024546 NM_024546 79596 1.15 1.92E-07 ADPN 233030 at AK025665 NM_025225 80339 1.14 4.1.4E-03 FANCL 218397 at NM 018062 NM 018062 55120 1.14 1.80E-04 MAK3 217745_s_at NM_025146 NM_025146 80218 1.14 3.70E-06 H05254 244170_at H05254 — — 1.14 1.12E-03 FAM14B 230172_at AL039706 NM_145249 NM_206949 122509 1.14 5.19E-03 NR3C1 216321_s_at X03348 NM_000176 2908 1.14 4.77E-03 FH 203032_s_at AI363836 NM 000143 2271 1.14 1.19E-03 SIVA 203489_at NM_006427 NM_006427 NM_021709 10572 1.14 1.23E-04 C10orf58 224435_at BC005871 NM_032333 84293 1.14 2.67E-05 MCAM 211042_x_at BC006329 NM_006500 4162 1.14 2.97E-06 LOC144997 227289 at AU119437 — 144997 1.14 8.41 E-04 SAFB2 32099 at D50928 NM 014649 9667 1.14 1.08E-03 MTUS1 212093_s_at AI695017 NM 00100192 4 NM 00100192 5 NM_00100192 7 NM 00100193 1 NM_020749 57509 1.14 1.51 E-04 SORD 201562_s_at NM_003104 NM_003104 6652 1.14 8.56E-04 HMGB1 200679 x at BE311760 NM 002128 3146 1.14 4.89E-05 TUBB 212320_at BC001002 NM_178014 203068 1.14 1.69 E-04 CDC42EP4 218062_x_at NM012121 NM012121 23580 1.13 4.75E-04 PACSIN1 227053_at N47315 NM_020804 29993 1.13 8.60E-03 KIAA1712 228334_x at AI633734 NM_030633 80817 1.13 1.79E-03 CDK2AP1 201938_at NM_004642 NM_004642 8099 1.13 4.73E-05 AI650582 226475_at AI650582 — — 1.13 9.58E-03 ZNF626 1552643_at NM_145297 NM_145297 199777 1.13 4.93E-04 MAPKAPK3 202787_s_at U43784 NM 004635 7867 1.13 2.06E-03 BTG3 205548_s_at NM_006806 NM_006806 10950 1.13 3.73E-03 UBE2S 202779_s_at NM 014501 NM_014501 27338 1.13 1.67E-04 TP53INP1 225912 at AW341649 NM 033285 94241 1.13 6.83E-03 Cep192 218827_s_at NM_018069 NM 018069 NM_032142 55125 1.13 3.17 E-04 SUHW2 230789_at Al 015954 NM_080764 140883 1.13 1.79E-05 244 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B„ et al„ Cells Useful for Immuno-Based BoNT/A Activity Assays LOC128977 1553974_at BC030758 NM_173793 128977 1.12 4.40E-04 CDH2 203441 s at NM 001792 NM 001792 1000 1.12 5.79E-03 ST8SIA1 210073 at L32867 NM 003034 6489 1.12 1.10E-03 PTP4A1 200733_s_at U48296 NM 003463 7803 1.12 2.69E-03 RNF34 219035_s_at NM_025126 NM_025126 NM 194271 80196 1.12 2.20E-04 DDX11 208159_x_at NM_004399 NM_004399 NM_030653 NM_030655 1663 1.12 2.66E-03 PTGES2 218083_at NM_025072 NM 025072 NM_198938 NM_198939 NM_198940 80142 1.12 5.25E-05 PCCB 212694 s at NM 000532 NM 000532 5096 1.12 1.29E-03 ETV4 211603 s at U35622 NM_001986 2118 1.12 1.80E-03 MGC7036 227983_at AI810244 NM_145058 196383 1.12 1.70E-05 GAP43 204471_at NM_002045 NM 002045 2596 1.12 2.85E-05 DATF1 222595_s_at AL578222 NM 022105 NM_080796 NM_080797 11083 1.12 9.82E-04 C1orf41 215691 x at AV702994 NM 016126 51668 1.11 6.15E-03 CHES1 218031_s_at NM 018589 NM 005197 1112 1.11 3.51 E-04 LOC89944 213713_s_at R48779 NM_138342 89944 1.11 4.60E-03 Al807356 227349_at AI807356 — — 1.11 7.01 E-03 RANGAP1 212127_at BE379408 NM_002883 5905 1.11 1.65E-03 CHRNA5 206533 at NM_000745 NM 000745 1138 1.11 2.14E-03 RNF138 239143_x_at AW291944 NM_016271 NM_198128 51444 1.11 1.74E-04 LOC440145 225578_at Al885466 XM 495961 440145 1.11 2.53E-04 FGF1 1552721_a_at NM_033136 NM 000800 NM_033136 NM_033137 2246 1.11 1.39E-03 AL533234 225725_at AL533234 — — 1.11 7.91 E-04 TM7SF3 222477 s at BC005176 NM 016551 51768 1.11 5.89E-04 FLJ90430 229533_x_at AI963028 NM 178558 340252 1.11 7.02E-03 RPS27L 218007_s_at NM_015920 NM 015920 51065 1.11 3.68E-03 CRTAC1 221204 s_at NM_018058 NM 018058 55118 1.11 1.69E-03 SKD3 221845_s_at AI655698 NM 030813 81570 1.11 1.33E-04 ZNF85 206572_x_at NM 003429 NM_003429 7639 1.11 3.31 E-03 XRCC3 216299_s_at AK022829 NM 005432 7517 1.11 7.35E-05 AKAP13 222024_s_at AK022014 NM 006738 NM_007200 NM_144767 11214 1.11 5.22E-03 C9orf81 1557985_s_at AA248753 XM_095991 84131 1.11 6.85E-04 PDCL 204448 s at AF031463 NM 005388 5082 1.10 4.06E-03 RAPH1 243012_at BF196252 NM_025252 NM_203365 NM 213589 65059 1.10 2.75E-03 DEK 200934 at NM 003472 NM 003472 7913 1.10 5.01 E-06 PPIF 201490_s_at NM 005729 NM 005729 10105 1.10 3.89E-06 PTP4A1 200730_s_at BF576710 NM_003463 7803 1.10 4.25E-03 Al888657 244189_at AI888657 — — 1.10 1.81 E-05 TCF7L2 216037 x at AA664011 NM 030756 6934 1.10 1.01 E-02 SNX5 222417_s_at AF121855 NM 014426 NM_152227 27131 1.10 2.71 E-03 SSH2 226080_at BE676214 NM_033389 85464 1.10 4.02E-04 BE671123 235798_at BE671123 — — 1.10 2.84E-05 MSH6 211450_s_at D89646 NM_000179 2956 1.10 4.87E-04 245 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 PDZRN3 Jacky, B., etal., 212915_at Cells Useful for Immuno-Based BoNT/A Activity Assays AL569804 NM_015009 23024 1.10 4.32E-03 PPP3CB 209817 at M29550 NM 021132 5532 1.10 4.16E-04 FAM29A 218602_s_at NM_017645 NM 017645 54801 1.09 1.73E-04 MINA 1554774_at AB083191 NM 032778 84864 1.09 7.48E-03 SRGAP1 1569269_s_at BM912471 NM_153182 NM 020762 57522 1.09 8.29E-03 LOC152185 234995_at AA668779 NM_144718 152185 1.09 2.38E-04 LOC63929 227910_at AI635379 NM_022098 63929 1.09 2.09E-03 ITPR2 202662 s at NM_002223 NM_002223 3709 1.09 4.74E-03 PCDH17 228863 at N69091 NM 014459 27253 1.09 2.79E-04 ELAVL1 201727_s_at NM_001419 NM_001419 1994 1.09 1.03E-02 PKP4 201928_at AA194254 NM_00100547 ft 8502 1.09 5.68E-05 MTUS1 212096_s_at AL096842 o NM 003628 NM_00100192 57509 1.09 8.18E-06 4 NM_00100192 5 NM 00100192 7 NM_00100193 1 NM 020749 SPOCK 202363_at AF231124 NM_004598 6695 1.09 4.27E-04 DIAPH1 209190 s at AF051782 NM 005219 1729 1.09 3.00E-03 CKLFSF7 226017_at Al708432 NM_138410 NM_181472 112616 1.09 7.48E-04 COR06 1552301 a at NM_032854 NM_032854 84940 1.09 3.51 E-03 C18orf9 219311 at NM 024899 NM 024899 79959 1.09 7.95E-04 PDGFD 219304_s_at NM_025208 NM_025208 NM_033135 80310 1.09 1.44E-03 UBE2L3 200676_s_at NM_003347 NM 003347 NM 198157 7332 1.09 3.98E-06 SLA/LP 227982_at AI806592 NM_016955 NM_153825 51091 1.08 6.59E-03 HOMER3 204647_at NM 004838 NM 004838 9454 1.08 1.80E-04 SNRPD3 202567 at NM 004175 NM_004175 6634 1.08 1.90E-05 3ΉΕΧΟ 226416_at AL137679 NM_153332 90459 1.08 3.50E-03 LMNB2 216952_s_at M94363 NM_032737 84823 1.08 2.28E-04 CBX5 209715_at L07515 NM_012117 23468 1.08 2.29E-03 ASF1A 203428_s_at AB028628 NM 014034 25842 1.08 4.83E-05 UBE2L3 200682_s_at BG531983 NM_003347 NMJ98157 7332 1.08 7.87E-06 PDLIM5 212412_at AV715767 NM 00101151 3 NM_00101151 4 NM 00101151 5 NM_00101151 6 NM_006457 10611 1.08 2.29E-03 PLEKHG3 212823_s_at AI738980 NM 015549 26030 1.08 9.61 E-03 ASXL1 244519_at AI829840 NM 015338 171023 1.08 1.17E-03 HIST1H4C 205967_at NM 003542 NM 003542 8364 1.08 4.91 E-03 UBE2L3 200683_s_at BE964689 NM 003347 NM_198157 7332 1.07 1.25E-06 DPYSL5 222797_at BF508726 NM_020134 56896 1.07 7.59E-04 246 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 ZFP36L2 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays 201368 at U07802 NM_006887 678 1.07 1.86E-04 PUSL1 228733_at AU154793 NM_153339 126789 1.07 3.30E-03 AA973128 242294_at AA973128 — ... 1.07 3.63E-03 SAP30 204899_s_at BF247098 NM 003864 8819 1.07 7.88E-05 ETV4 1554576_a_at BC007242 NM 001986 2118 1.07 2.79E-03 RARA 203749_s_at AI806984 NM 000964 5914 1.07 3.55E-03 TUBB 211714_x_at BC005838 NM 178014 203068 1.07 3.33E-04 STARD4 226390_at AA628398 NM 139164 134429 1.07 1.71E-05 TUBA6 211750_x_at BC005946 NM 032704 84790 1.07 1.66E-05 CKLFSF8 235099 at AW080832 NM_178868 152189 1.07 5.68E-03 THOC3 224623_at BE614567 NM_032361 84321 1.07 3.08E-05 PRPS1 209440_at BC001605 NM 002764 5631 1.07 2.15E-05 PRPS2 203401 at NM 002765 NM_002765 5634 1.07 2.40E-03 CRY1 209674_at D83702 NM_004075 1407 1.06 3.45E-03 DKFZP547N04 223511_at AL512744 NM_00101098 A 83932 1.06 1.17E-03 FSTL1 208782_at BC000055 H NM 032018 NM_007085 11167 1.06 2.60E-03 NDRG2 214279_s_at W74452 NM_016250 57447 1.06 7.80E-03 FLJ13273 1554518_at BC032942 NM 201535 NM 201536 NM_201537 NM_201538 NM 201539 NM 201540 NM_201541 NM 024751 79807 1.06 4.36E-05 EPB41L1 212336_at AA912711 NM 012156 2036 1.06 6.75E-05 FAM55C 243011_at BF317081 NM 177996 NM 145037 91775 1.06 9.28E-03 TCF3 213730_x_at BE962186 NM_003200 6929 1.06 4.18E-04 PLXNB2 208890_s_at BC004542 XM_371474 23654 1.06 2.15E-04 BE218067 243662 at BE218067 — ... 1.06 6.88E-03 PDRG1 225075_at AL031658 NM 030815 81572 1.06 4.96E-03 BTG3 213134_x_at AI765445 NM_006806 10950 1.06 2.21 E-03 CDC42EP4 214721_x_at AL162074 NM 012121 23580 1.06 6.10E-04 LOC96610 1569013 s at BC033148 NM_080926 96610 1.06 2.71 E-03 BF510533 228107_at BF510533 — ... 1.06 2.14E-03 TFDP1 204147_s_at NM_007111 NM_007111 7027 1.06 2.66E-03 Al092770 230466 s at AI092770 — — 1.06 1.88E-03 SFRP1 202037_s_at NM_003012 NM_003012 6422 1.06 2.39E-04 FBX022 225734_at AW294765 NM 012170 26263 1.06 1.77E-05 TUBB 209026 x at AF141349 NM_147188 NM 178014 203068 1.06 6.65E-04 ELK3 221773 at AW575374 NM_005230 2004 1.05 1.33E-05 APG4C 228190_at BF197009 NM_032852 84938 1.05 3.09E-03 BCL11A 210347_s_at AF080216 NM 178221 NM 018014 53335 1.05 4.33E-03 MFAP2 203417_at NM_017459 NM_022893 NM_138553 NM 138559 NM 002403 4237 1.05 2.57E-04 C20orf108 224693_at AM 33137 NM 017459 NM 080821 116151 1.05 1.58E-03 CD24 209772_s_at X69397 NM_013230 934 1.05 1.98E-04 247 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., etal., Cells Useful for Immuno-Based BoNT/A Activity Assays FAS 204780_s_at AA164751 NM_000043 NM_152871 NM 152872 NM_152873 NM 152874 NM 152875 NM_152876 NM_152877 355 1.05 3.67E-04 GGCX 214005_at BE326952 NM_000821 2677 1.05 6.80E-03 SESN3 235684_s_at BF685808 NM 144665 143686 1.05 8.56E-03 ANAPC7 225554_s_at AA131793 NM_016238 51434 1.05 3.09E-06 INA 230859_at BF111276 NM 032727 9118 1.05 1.36E-03 FKBP7 223667_at AF092137 NM 016105 NM_181342 51661 1.05 1.99E-03 ESRRG 207981_s_at NM_001438 NM_001438 NM_206594 NM_206595 2104 1.05 6.81 E-03 RET 215771_x_at X15786 NM_020630 NM_020975 5979 1.05 9.85E-04 CTNNAL1 202468_s_at NM_003798 NM_003798 8727 1.05 1.23E-03 SMC1L1 201589 at D80000 NM 006306 8243 1.05 3.76E-05 NFYB 218128_at AU151875 NM_006166 4801 1.04 1.55E-04 NFYB 218127_at AI804118 NM_006166 4801 1.04 2.59E-03 EPOR 209963_s_at M34986 NM_000121 2057 1.04 9.69E-04 MGC10854 223455_at BG493862 NM 032300 84260 1.04 2.09E-03 TCF3 210776_x_at M31222 NM_003200 6929 1.04 6.32E-05 ELAVL4 238073_at R55745 NM_021952 1996 1.04 6.02E-07 N66584 230593_at N66584 — ... 1.04 1.67E-03 MGC13204 225836 s at AL528840 NM 031465 83695 1.04 4.81 E-04 NUCKS 222424 s at BC000805 NM 022731 64710 1.04 1.65E-03 FBX022 225737_s_at BE966247 NM_012170 NM_147188 26263 1.04 2.33E-04 CXorf40 228809_at AW006998 NM 178124 91966 1.04 6.72E-03 NEFL 221805 at AL537457 NM_006158 4747 1.04 3.74E-03 MTHFD1 202309_at NM_005956 NM 005956 4522 1.04 1.63E-04 SRD5A1 210959_s_at AF113128 NM 001047 6715 1.04 3.17E-03 NASP 201969_at AW003362 NM 002482 NM_152298 NMJI72164 4678 1.04 8.40E-03 Septin 10 212698_s_at BF966021 NM 144710 NM_178584 151011 1.04 4.13E-03 PLCXD1 218951_s_at NM_018390 NM 018390 55344 1.04 2.13E-03 CD24 208650_s_at BG327863 NM 013230 934 1.04 5.35E-03 ZNF92 235170_at T52999 NM 007139 NM_152626 168374 1.04 1.71 E-05 CENPF 207331_at NM_016343 NM_016343 1063 1.03 3.14E-04 AA766126 244385_at AA766126 — ... 1.03 2.59E-04 TENS1 217853_at NM_022748 NM_022748 64759 1.03 1.28E-03 AL559474 235918_x_at AL559474 — ... 1.03 7.29E-04 FLJ10407 234672_s_at AL354612 NM_018087 55706 1.03 4.74 E-05 SET8 220200_s_at NM_020382 NM_020382 387893 1.03 5.39E-04 FLJ21125 226204 at AI832193 NM 024627 79680 1.03 7.12E-03 PANK2 218809 at NM_024960 NM_024960 NM 153637 NM 153638 NM 153639 NM_153640 NM 153641 80025 1.03 5.90E-06 248 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays TAF5 210053_at AW138827 NM_006951 6877 1.03 3.76E-04 AI806853 225601_at AI806853 — — 1.03 2.08E-05 MMP11 203878_s_at NM_005940 NM_005940 4320 1.03 2.69E-03 TUBA6 209251_x_at BC004949 NM 032704 84790 1.03 2.38E-05 BCL2L11 225606_at AI949179 NM 006538 NM_138621 NM_138622 NM_138623 NM 138624 NM_138625 NM_138626 NM_138627 NM_207002 NM_207003 10018 i.03 1.11E-04 ZGPAT 221848_at AL121845 NM_032527 NM 181484 NM_181485 84619 1.03 4.13E-04 C14orf106 241816_at AW103300 NM_018353 55320 1.03 2.05E-03 BCL3 204908_s_at NM_005178 NM 005178 602 1.03 7.14E-04 CBFA2T2 209145_s_at AF068266 NM 005093 NM 175864 9139 1.03 4.72E-03 MCFP 227012_at AI823986 N M 018843 55972 1.03 1.94E-06 THAP10 219596_at NM 020147 NM_020147 56906 1.03 7.28E-04 AW511319 227167_s_at AW511319 — — 1.03 6.48E-04 C2orf7 223312 at BC005069 NM 032319 84279 1.03 8.00E-05 TTC9 213172_at AW235608 XM_027236 23508 1.03 5.24E-03 DOT1L 231297_at AI479899 NM 032482 84444 1.03 7.59E-03 TM7SF3 226478_at BF540749 NM_016551 51768 1.02 1.16E-03 NFIA 224976_at R37335 NM_005595 4774 1.02 4.91 E-03 MGC72104 243689_s_at AI681945 NM 207350 284802 1.02 6.29E-03 DGCR14 204383_at NM 022719 NM_022719 8220 1.02 2.13E-03 TUBB2 208977_x_at BC004188 NM 006088 10383 1.02 1.96E-05 ZNF505 215758_x_at AC007204 NM_00100412 6 NM_031218 81931 1.02 1.93E-03 C6orf115 223361 at AF116682 XM 371848 58527 1.02 3.11E-04 RAB3C 242328_at BG055348 NM_138453 115827 1.02 5.07E-03 CECR5 218592_s_at NM_017829 NM_017829 NM_033070 27440 1.02 1.72E-05 PSMD5 203447_at AU157008 NM 005047 5711 1.02 3.28E-06 PHF6 225501_at AK027039 NM_032335 NM_032458 84295 1.02 3.94E-05 CSRP2BP 228544_s_at AA780252 NM_020536 NM_177926 57325 1.02 3.08E-03 M96 209704_at AL523380 NM_007358 22823 1.01 2.10E-04 PELI2 219132_at NM_021255 NM_021255 57161 1.01 2.52E-05 RPA1 201529 s at NM_002945 NM_002945 6117 1.01 1.36E-04 TCF3 213811_x_at AW062341 NM 003200 6929 1.01 2.33E-03 C6orf151 226263_at AA630674 NM_152551 154007 1.01 1.66E-03 C6orf4 215411_s_at AL008730 NM_147200 NM 147686 10758 1.01 1.04E-02 DUSP6 208893_s_at BC005047 NM 001946 NM 022652 1848 1.01 4.12 E-03 PEG10 212094_at AL582836 XM 496907 XM 499343 23089 1.01 4.74E-03 CTNNBL1 221021 s at NM 030877 NM 030877 56259 1.01 1.87E-05 MPHOSPH9 237158_s_at AW449069 NM 022782 10198 1.01 8.39E-04 SCLY 221575_at BC000586 NM 016510 51540 1.01 5.24E-04 249 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al„ Cells Useful for Immuno-Based BoNT/A Activity Assays NUP50 222583_s_at AF116624 NM 007172 NMJ53645 NM_153684 10762 1.01 9.47E-04 GST02 227163_at AL162742 NM 183239 119391 1.01 9.87E-03 C20orf44 222470_S_at AA033998 NM 018244 NM 199487 NM 199513 55245 1.01 9.65E-05 N56956 227254_at N56956 — — 1.01 6.12E-03 BAGE4 BAGE2 1555408_at AF218570 NM 181704 NM 182482 85317 85319 1.01 6.41 E-03 ARL2L1 228201_at BE858032 NM 144996 NM_182896 200894 1.01 2.30E-03 TCF7L2 212762_s_at AI375916 NM 030756 6934 1.01 2.14E-03 C21orf45 219004 s at NM 018944 NM 018944 54069 1.01 1.32E-03 C10orf58 228155_at BF512388 NM 032333 84293 1.00 1.86E-05 LYK5 52169_at Al302185 NM 00100378 6 NM_00100378 7 NM 00100378 8 NM_153335 92335 1.00 6.85E-04 PGF 209652_s_at BC001422 NM_002632 5228 1.00 5.14E-03 FLJ14627 221908_at AL120375 NM_032814 84900 1.00 7.78E-04 NUP37 218622_at NM 024057 NM 024057 79023 1.00 2.06E-03 SYT3 223901 at AL136594 NMJ332298 84258 1.00 6.98E-05 NARG1 222837_s_at AF327722 NM_057175 80155 1.00 1.83E-03 RNF144 204040_at NM_014746 NM 014746 9781 1.00 1.07E-06 MRPL35 222775_s_at AK026220 NM_016622 NM_145644 51318 1.00 1.64E-03 ROR1 205805_s_at NM 005012 NM_005012 4919 1.00 3.27 E-03 POP1 213449_at D31765 NM 015029 10940 1.00 7.21 E-03 ABTB2 213497_at AL050374 NM 145804 25841 1.00 2.06 E-03 ASCC3 212815_at AA156961 NM 006828 10973 1.00 4.84E-03 HDGF 216484_x_at L24521 NM 004494 3068 1.00 1.89 E-03 DUSP6 208892_s_at BC003143 NM 001946 NM_022652 1848 1.00 2.56E-03 DCPS 218774_at NM_014026 NM_014026 28960 1.00 6.63E-03 AKIP 228800_x_at BE463815 NM 017900 54998 1.00 1.79E-03 C6orf60 220150_s_at NM 024581 NM 024581 79632 1.00 2.46E-03 NXT2 209629 s at AF201942 NM 018698 55916 1.00 6.17E-03 SEC61A2 219499_at NM_018144 NM_018144 55176 1.00 1.35E-05 AI095542 235759_at AI095542 — — 1.00 3.08E-04 RPA1 201528 at BG398414 NM 002945 6117 1.00 7.67E-06 FLJ14627 221909 at AW299700 NM_032814 84900 1.00 1.91 E-03 BE967311 226225_at BE967311 — — 0.99 6.96E-05 KIAA0841 213054_at AA845355 XM_049237 23354 0.99 5.40E-05 GNG2 224965 at AU118419 NM 053064 54331 0.99 5.01 E-05 ZNF238 207164_s_at NMJ306352 NM_006352 NM_205768 10472 0.99 3.24E-03 PSMD9 209334_s_at BC002383 NM 002813 5715 0.99 2.73E-04 SNX5 217792_at NM_014426 NM 014426 NM_152227 27131 0.99 1.19E-05 PHLDA3 218634_at NM 012396 NM_012396 23612 0.99 4.00E-04 ITGA2B 206494_s_at NM 000419 NM_000419 3674 0.99 8.82E-03 SOX2 213722_at AW007161 NM 003106 6657 0.99 7.14E-03 RALY 201271_s_at NM 016732 NM_007367 NM 016732 22913 0.99 1.03E-05 250 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B„ et al., Cells Useful for Immuno-Based BoNT/A Activity Assays PCNT1 218014 at NM 024844 NM 024844 79902 0.99 2.81 E-03 LOC400506 213237 at AI652058 XM 375305 400506 0.99 8.09E-04 SLC6A15 240419_at N25883 NM 018057 NM_182767 55117 0.99 6.25E-03 CBFA2T2 209144_s_at Al810484 NM 005093 NM 175864 9139 0.99 5.43E-03 ASMTL 36554_at Y15521 NM_004192 8623 0.99 2.79E-04 NARG1 226998_at AL556909 NM 057175 80155 0.99 2.85E-05 KLHL5 226001_at AK002174 NM_00100707 5 NM_199039 51088 0.99 5.50E-04 MGC59937 1569144_a_at BC018787 NM_199001 375791 0.98 9.69E-03 NEDD4L 212445_s_at AI357376 NM 015277 23327 0.98 3.46E-03 COVA1 32042_at S72904 NM_006375 NM_182314 10495 0.98 1.78E-04 SWAP 70 209306_s_at AM 39569 NM_015055 23075 0.98 1.45E-03 EPLIN 217892_s_at NM 016357 NM 016357 51474 0.98 1.73E-03 TEF 225840_at AA779795 NM 003216 7008 0.98 3.69E-03 KIAA0391 202713_s_at AA129755 XM 375074 9692 0.98 7.23E-05 TXNRD1 201266_at NM_003330 NM 003330 NM_182729 NM_182742 NM_182743 7296 0.98 7.52E-04 AI220627 213608_s_at AI220627 XM_377713 402055 0.98 1.61E-04 SLC25A17 211754_s_at BC005957 NM 006358 10478 0.98 1.22E-03 DDX11 208149_x_at NM_030653 NM_004399 NM_030653 NM_030655 1663 0.98 2.49E-03 CD24 266 s at L33930 NM_013230 934 0.98 9.60E-04 SNAP29 218327_s_at NM_004782 NM_004782 9342 0.98 4.38E-04 DDEFL1 219103 at NM_017707 NM_017707 55616 0.98 8.35E-03 MTAP 211363_s_at AF109294 NM 002451 4507 0.98 8.59E-03 H2AFJ 225245_x_at BG386566 NM 018267 NM_177925 55766 0.98 9.29E-03 W91876 230240_at W91876 — — 0.98 6.38E-03 FLJ38973 227973_at BF130937 NM 153689 205327 0.97 4.61 E-03 ARL6 235320_at AL138043 NM_032146 NM 177976 84100 0.97 9.35E-03 WWOX 219077_s_at NM_016373 NM_016373 NM 018560 NM 130788 NM 130790 NM 130791 NM 130792 NM_130844 51741 0.97 2.03E-03 XTP3TPA 218069_at NM_024096 NM_024096 79077 0.97 1.83E-04 NAPB 225111_s_at AK022817 NM 022080 63908 0.97 1.32E-05 MRVI1 226047_at N66571 NM 006069 NM_130385 10335 0.97 6.11 E-03 H93038 241574_s_at H93038 — — 0.97 4.24E-03 Al700633 212812_at Al700633 — — 0.97 4.71 E-04 DDAH2 215537 x at AJ012008 NM 013974 23564 0.97 4.32E-03 HSPC159 219998_at NM_014181 NM 014181 29094 0.97 7.46E-04 GRK6 202849_x_at NM_002082 NM_00100410 5 NM 00100410 6 NM 002082 2870 0.97 5.10E-03 251 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al„ Cells Useful for Immuno-Based BoNT/A Activity Assays ZNF219 219314_s_at NM 016423 NM_016423 51222 0.97 2.40E-03 KLF3 219657 s at NM_016531 NM_016531 51274 0.97 2.90E-03 K03460 216323_x_at K03460 — ... 0.96 1.11E-03 IER5 218611_at NM 016545 NM_016545 51278 0.96 1.63E-03 BC040884 1560156_at BC040884 — — 0.96 8.01 E-03 PROS1 207808_s_at NM 000313 NM_000313 5627 0.96 4.30E-03 ALDH1B1 209645_s_at NM_000692 NM_000692 219 0.96 5.95E-03 PEG10 212092_at BE858180 XM_496907 XM_499343 23089 0.96 1.83E-03 GRK6 211543_s_at AF040752 NM 00100410 5 NM_00100410 6 NM 002082 2870 0.96 4.44E-04 RPP30 203436_at NM_006413 NM_006413 10556 0.96 4.98E-04 AD-003 223369_at BC001396 NM_014064 28989 0.96 5.09E-03 BG026236 230166_at BG026236 — — 0.96 6.20E-03 KIAA2002 225913_at AK025943 XM 370878 79834 0.96 8.75E-03 CD24 208651_x_at M58664 NM 013230 934 0.96 1.62E-03 TCF3 209153_s_at M31523 NM_003200 6929 0.96 1.74E-04 NMT1 201157_s_at AF020500 NM 021079 4836 0.96 7.38E-03 SURB7 209363_s_at U46837 NM 004264 9412 0.96 1.98E-04 PHYHIPL 226623_at AI829726 NM_032439 84457 0.96 4.52E-06 HSPC117 200042_at NM_014306 NM 014306 51493 0.96 2.37E-05 ALDH7A1 208950 s at BC002515 NM 001182 501 0.96 1.54E-05 TFDP2 226157 at AI569747 NM_006286 7029 0.95 1.73E-03 SURB7 209362_at AI688580 NM_004264 9412 0.95 3.64E-04 BC003636 222756_s_at BC003636 — — 0.95 1.07E-04 SCLY 59705 at AA911739 NM_016510 51540 0.95 8.43 E-04 MGC15634 242923_at AW027457 — 84841 0.95 9.36E-03 KIBRA 216074_x_at AK001727 NM_015238 23286 0.95 6.38E-03 CASP8AP2 222201_s_at AB037736 NM 012115 9994 0.95 4.11 E-04 AARS 201000 at NM_001605 NM_001605 16 0.95 1.89E-03 LOC148203 229700 at BE966267 — 148203 0.95 3.12E-04 CBLL1 220018_at NM 024814 NM 024814 79872 0.95 1.63E-03 MRPL35 225255_at AA810707 NM_016622 NM_145644 51318 0.95 4.17E-03 FAM29A 233655 s at AK022964 NM_017645 54801 0.95 1.14E-05 0KFZP566E14^ 223989_s_at BC003502 NM_015523 25996 0.95 1.35 E-04 PHF20 235389_at BG168139 NM_016436 51230 0.95 7.86E-06 C20orf23 219570 at NM 024704 NM 024704 55614 0.95 7.76E-04 MRS2L 228542_at AI631209 NM_020662 57380 0.95 5.03E-04 GPX3 201348_at NM_002084 NM_002084 2878 0.95 6.41 E-03 PRIM2A 205628_at NM_000947 NM_000947 5558 0.95 1.53 E-04 PPAT 209433_s_at AI457120 NM 002703 5471 0.95 1.28E-06 SLC9A3R1 201349_at NM_004252 NM 004252 9368 0.95 3.16E-04 SNX5 229980_s_at AA131508 NM 014426 NM 152227 27131 0.95 2.51 E-04 C9orf122 1557014_a_at BC041970 XM 379636 158228 0.95 9.32E-03 ETV6 235056_at AV722693 NM_001987 2120 0.95 1.50E-03 ROD1 224617_at AI735576 NM 005156 9991 0.95 5.78E-04 PPP2R5D 202513_s_at NM_006245 NM 006245 NM 180976 NM_180977 5528 0.95 5.76E-03 AI392908 230352_at AI392908 — — 0.95 5.22E-03 PPAT 209434_s_at U00238 NM 002703 5471 0.95 1.94E-06 HSPC129 1555106 a at BC035744 NM 016396 51496 0.94 1.87E-04 KIAA1333 223256 at AW007694 NM 017769 55632 0.94 1.83E-05 252 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays GAP43 216963_s_at AF279774 NM 002045 2596 0.94 8.23E-05 C6orf155 226810_at BE500942 NM 024882 79940 0.94 3.25E-04 FKBP7 224002_s_at AF100751 NM_016105 NM_181342 51661 0.94 7.01 E-04 NIT2 218557_at NM_020202 NM_020202 56954 0.94 8.71 E-04 NTAN1 213061 s at AA643304 NM_173474 123803 0.94 3.59 E-03 FBXL13 243057_at AI923673 NM_145032 222235 0.94 1.12E-03 SURF5 206593_s_at NM_006752 NM_006752 NM_133640 NM_181491 6837 0.94 1.04E-03 ASMTL 209394_at BC002508 NM_004192 8623 0.94 7.15E-04 PXMP4 219428_s_at BF057649 NM_007238 NM_183397 11264 0.94 1.03E-03 IGF1R 203627_at AI830698 NM 000875 3480 0.94 5.54E-04 HN1 217755_at NMJ316185 NM_00100203 2 NM 00100203 3 NM016185 51155 0.94 1.06E-03 AL833487 1562245_a_at AL833487 — — 0.94 2.02E-03 LIG3 204123_at NM_013975 NM 002311 NM_013975 3980 0.93 1.64E-05 CSTF1 202190_at NM_001324 NM_001324 1477 0.93 1.15E-03 KIAA0406 212898_at AB007866 NM 014657 9675 0.93 4.37E-05 LIG3 207348_s_at NM_002311 NM 002311 NM_013975 3980 0.93 5.83E-05 MAML3 242794_at Al569476 NM 018717 55534 0.93 5.09E-03 SRD5A1 211056_s_at BC006373 NM 001047 6715 0.93 1.03E-02 ELAVL4 206051 at NM 021952 NM 021952 1996 0.93 8.90E-05 XRCC4 210813_s_at BC005259 NM_003401 NM_022406 NM_022550 7518 0.93 5.17E-03 ALDH7A1 208951 at BC002515 NM 001182 501 0.93 4.00E-06 SLC03A1 227367_at AW976431 NM 013272 28232 0.93 4.38E-03 OGFRL1 219582_at NM_024576 NM_024576 79627 0.93 1.65E-04 CDH2 203440_at M34064 NM_001792 1000 0.93 9.39E-06 FLJ31842 237515 at AA054642 NM 152487 148534 0.93 6.73E-04 LOC283464 226868_at BF977231 XM_290597 283464 0.93 1.55E-04 DNMT1 201697_s_at NM 001379 NM_001379 1786 0.93 1.35E-04 H2AFZ 200853_at NM_002106 NM 002106 3015 0.93 1.62E-06 GAS2L1 209729_at BC001782 NM 006478 NM_152236 NM_152237 10634 0.93 6.61 E-03 IDH2 210046 s at U52144 NM 002168 3418 0.93 2.00E-04 LOC51337 218500 at NM 016647 NM_016647 51337 0.93 2.50E-03 )KFZp313A243: 230005_at AI742358 — 258010 0.93 1.41 E-03 CKLF 223451_s_at AF096895 NM_016326 NM 016951 NM_181640 NM181641 51192 0.93 7.64E-03 APEX2 204408_at NM_014481 NM 014481 27301 0.92 5.63E-04 UBOX5 215544_s_at AL121891 NM 014948 NM_199415 22888 0.92 5.63E-03 TMEM38B 222735_at AW452608 NM_018112 55151 0.92 1.79E-03 GPX2 202831_at NM_002083 NM_002083 2877 0.92 9.43E-04 MPHOSPH9 215731 s at X98258 NM 022782 10198 0.92 1.91 E-04 HABP4 232341_x_at AK025144 NM_014282 22927 0.92 1.03E-02 253 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B„ et al., Cells Useful for Immuno-Based BoNT/A Activity Assays C20orf161 1553960_at CA447177 NM 033421 90203 0.92 8.23E-03 FKBP5 224840_at AI753747 NM_152897 NM_004117 2289 0.92 1.63E-03 MGC3162 218860_at NM_024078 NM_024078 79050 0.92 6.27E-05 )KFZp313A243: 230285 at BF447829 — 258010 0.92 4.30E-03 AA669799 36553 at AA669799 — — 0.92 2.04E-04 N93774 229671_s_at N93774 ... ... 0.92 3.48E-03 AW971254 222369 at AW971254 ... — 0.92 3.06E-03 BF516305 230728_at BF516305 — — 0.92 9.61 E-04 ALDH1A2 207016_s_at ABO15228 NM 003888 8854 0.92 7.68E-03 ZNF500 242463 x at AI620827 NM_170696 NM_170697 NM 198457 162966 0.92 6.82E-03 BUB3 201458_s_at NM_004725 NM_00100779 o 9184 0.92 3.29E-04 FZD8 227405_s_at AW340311 o NM_004725 NM 031866 8325 0.92 7.53E-04 RAD1 228535_at AI796010 NM_002853 5810 0.92 3.58E-04 GCAT 205164_at NM_014291 NM_133282 NM_133377 NM 014291 23464 0.92 4.73E-03 DKFZp761A07£ 231895_at AA501453 NM_194292 163786 0.92 1.89E-04 BE464337 229512_at BE464337 — — 0.92 2.81 E-03 AI670824 238887_at AI670824 — — 0.91 4.22E-03 USP49 212872 s at AK023092 NM 004275 9477 0.91 1.13E-04 HTATSF1 202602_s_at NM_014500 NM_014500 27336 0.91 3.64E-05 MAML3 228508_at AI828006 NM_018717 55534 0.91 2.27E-04 UCHL5 219960_s_at NM_015984 NM 015984 51377 0.91 1.62E-03 MKKS 222530_s_at AF275813 NM_018848 8195 0.91 1.32E-04 C18orf9 52285_f_at AW002970 NM_170784 NM_024899 79959 0.91 2.78E-06 ADRBK2 204183_s_at AI478542 NM_005160 157 0.91 5.18E-03 LOC90313 225605_at AL540867 NM 138349 90313 0.91 5.20E-03 FANCE 220255_at NM_021922 NM_021922 2178 0.91 1.82E-03 SH3BGRL2 225354_s_at AL035700 NM_031469 83699 0.91 3.32E-04 YEATS4 218911 at NM 006530 NM 006530 8089 0.91 7.53E-05 FKBP14 219390_at NM_017946 NM 017946 55033 0.91 3.85E-06 KIAA1712 231850_x_at AB051499 NM 030633 80817 0.91 6.64E-03 C10orf78 236027_at N23587 NM_00100275 Q 119392 0.91 4.28E-03 BG261385 225906 at BG261385 y NM_145247 XM_499448 442703 0.91 2.60E-03 LOC339903 228721_at AA225165 XM_291063 339903 0.91 2.86E-03 KIBRA 213085 s at AB020676 NM 015238 23286 0.91 5.30E-05 KIAA1333 223255 at AA642341 NM 017769 55632 0.91 1.02E-03 H2AFJ 224301_x_at BC003602 NM_018267 55766 0.91 8.07E-03 HRASLS 219984 s at NM 020386 NM_177925 NM 020386 57110 0.91 1.08E-03 TUBA3 212639_x_at AL581768 NM_006009 10376 0.91 2.50E-05 K-ALPHA-1 TOMM34 201870_at NM 006809 NM_006082 NM 006809 7846 10953 0.91 6.55E-05 RFX5 202964_s at NM 000449 NM_000449 5993 0.91 7.31 E-04 AK1 202587_s_at BC001116 NM_000476 203 0.91 7.38E-03 KATNA1 205526_s_at NM 007044 NM 007044 11104 0.91 2.54E-03 PAICS 201014_s_at NM 006452 NM_006452 10606 0.91 3.31 E-03 KIAA1576 226415_at AA156723 NM 020927 57687 0.90 4.18E-03 CHML 1565951_s_at AJ293392 NM_001821 1122 0.90 1.84E-04 SLC2A8 218985_at NM 014580 NM_014580 29988 0.90 1.85E-04 254 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays DKFZp779017i 238952 x at BF439163 XM 375606 374899 0.90 1.98E-03 FLJ43505 221477 s at BF575213 NM 207468 400823 0.90 2.64E-05 HTLF 226711_at BF590117 NM_002158 3344 0.90 2.44E-05 FLJ10385 44563_at AI858000 NM_018081 55135 0.90 1.42E-05 FLJ16517 229349 at AL039884 NM_001004317 389421 0.90 706E-04 SIX5 229009 at AA527770 NM 175875 147912 0.90 7.46E-03 STMN3 222557_at AL353715 NM_015894 50861 0.90 3.11E-03 PPP2R5D 211159_s_at AB000635 NM_006245 NM 180976 NM_180977 5528 0.90 3.08E-03 AI701857 243359_at AI701857 — — 0.90 7.55E-04 PHYH 203335_at NM 006214 NM 006214 5264 0.90 1.50E-03 UFD1L 209103 s at BC001049 NM 005659 7353 0.90 7.15E-04 RAD1 204460_s_at AF074717 NM_002853 NM_133282 NM_133377 5810 0.90 1.59E-03 MPHOSPH9 221965 at AI990326 NM 022782 10198 0.90 5.47E-04 MLF1 204783_at AI911434 NM_022443 4291 0.90 1.40E-03 THOC4 226319_s_at AF047002 NM_005782 10189 0.90 3.55E-05 TM4SF15 218693_at NM 012339 NM 012339 23555 0.90 1.06E-03 MSH6 202911 at NM 000179 NM 000179 2956 0.90 8.89E-05 ANXA6 200982_s_at NM_001155 NM_001155 NM_004033 309 0.90 2.34E-06 RAB23 223463_at AF161486 NM 016277 NM 183227 51715 0.90 1.40E-03 PCTK1 207239_s_at NM_006201 NM_006201 NM 033018 5127 0.90 2.68E-03 ZNF238 212774_at AJ223321 NM 006352 NM 205768 10472 0.90 9.30E-04 HIP1R 209558_s_at AB013384 NM_003959 9026 0.90 2.26E-04 UBAP2L 201378_s_at NM_014847 NM_014847 9898 0.90 3.17E-04 FLJ32745 235644_at BF213953 NM 144978 165055 0.90 2.95E-03 GGCX 214006 s at BE326952 NM 000821 2677 0.89 1.19E-03 HIP1 226364_at AU145049 NM 005338 3092 0.89 1.85E-04 BG496998 225684_at BG496998 — — 0.89 7.38E-05 PIGX 1563111 _a_at AK000529 NM 017861 54965 0.89 1.57E-03 RAN 200750 s at AF054183 NM_006325 5901 0.89 7.04E-07 LOC128977 227086_at AA194312 NM_173793 128977 0.89 7.56E-04 PRIM2A 1554885_a_at BC017833 NM 000947 5558 0.89 1.97E-03 ACY1L2 225421 at AI654133 NM 001010853 135293 0.89 1.02E-04 FLJ39582 239015_at BE675073 XM 498459 XM 499589 439931 0.89 4.23E-03 CDK5RAP2 233540_s_at AK025867 NM 00101164 9 NM_018249 55755 0.89 1.44E-03 HIP1 205425_at NM 005338 NM 005338 3092 0.89 3.21 E-04 RNF157 226433_at BF056204 NM_052916 114804 0.89 4.40E-04 AL832468 1560116_a_at AL832468 — — 0.89 1.66E-04 CDC5L 209056 s at NM_001253 NM_001253 988 0.89 2.06E-05 C20orf17 235616_at AI694059 NM_173485 128553 0.89 7.79E-03 STAU2 204226_at NM_014393 NM 014393 27067 0.89 4.24E-05 TUBB2 213726 x at AA515698 NM 006088 10383 0.89 1.59E-04 TMEPAI 222449_at AL035541 NM_020182 NM 199169 NM 199170 NM 199171 56937 0.89 8.38E-03 KIAA1958 239033_at AI640482 NM_133465 158405 0.89 2.35E-04 TEAD3 209454_s_at AF142482 NM_003214 7005 0.89 3.41 E-03 255 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays KIAA1211 227231_at Al 991996 XM 044178 57482 0.88 1.97E-03 TMEFF1 205122 at BF439316 NM 003692 8577 0.88 6.32E-03 SLC16A10 219915_s_at NM_018593 NM 018593 117247 0.88 7.05 E-04 ACPL2 226925_at AW069729 NM_152282 92370 0.88 5.44E-07 C1orf41 203960 s at NM 016126 NM 016126 51668 0.88 6.92E-03 VPS29 223026_s_at AF201946 NM 016226 NM 057180 51699 0.88 3.36E-04 FRAT2 209864_at AB045118 NM_012083 23401 0.88 9.56E-03 IGSF4 209031_at AL519710 NM_014333 23705 0.88 1.80E-03 PARP2 215773_x_at AJ236912 NM 005484 10038 0.88 1.31 E-03 SLC03A1 219229_at NM_013272 NM 013272 28232 0.88 8.63E-04 RNPC1 212430_at AL109955 NM_017495 NM 183425 55544 0.88 4.48E-03 STAMBP 202811_at NM_006463 NM 006463 NM_201647 NM 213622 10617 0.88 3.92E-04 RPS6KA1 203379_at NM_002953 NM_00100666 5 NM 002953 6195 0.88 2.48E-03 BUB3 201456_s_at AU160695 NM_00100779 3 NM_004725 9184 0.88 1.21 E-04 LOC375295 228564_at Al 569804 XM 374020 375295 0.88 2.04E-03 KCNQ2 210508_s_at D82346 NM 004518 NM 172106 NMJ72107 NM_172108 NM_172109 3785 0.88 1.23E-04 EIF4E 201437 s at NM_001968 NM 001968 1977 0.88 2.52E-03 AGPS 225113_at BF688144 NM 003659 8540 0.88 2.42E-03 BRD4 202103_at AI991631 NM_014299 NM_058243 23476 0.88 2.06E-03 TOX 204529_s_at Al 961231 NM_014729 9760 0.88 4.56E-03 AI032121 227422_at Al 032121 — — 0.88 5.07E-04 RAB3IP 223471_at BC002556 NM 022456 NM 175623 NM 175624 NM_175625 NM 175626 NM 175627 117177 0.87 1.10E-03 DDT 202929 s at NM 001355 NM 001355 1652 0.87 4.60E-04 C10orf77 219745_at NM_024789 NM 024789 79847 0.87 9.14E-03 NUCKS 224582_s_at H09085 NM_022731 64710 0.87 2.99E-05 FBN1 202766_s_at NM 000138 NM_000138 2200 0.87 9.90E-03 AA287457 226943 at AA287457 — ... 0.87 2.30E-03 C10orf86 219067 s at NM 017615 NM017615 54780 0.87 6.15E-05 MAGE:3604678 1555875_at BU733713 — — 0.87 7.23E-03 HSPA4L 205543 at NM 014278 NM 014278 22824 0.87 7.62E-04 PLS1 205190_at NM_002670 NM_002670 5357 0.87 7.93E-03 AW299815 241815_at AW299815 — ... 0.87 5.59E-03 MRPL42 222466_s_at AL136659 NM 014050 NM 172177 NM 172178 28977 0.87 3.61 E-06 256 PCT/US2010/027242 WO 2010/105234 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays LYK5 221554_at AF308302 NM_00100378 92335 0.87 5.17E-03 6 NM_00100378 7 NM_00100378 8 C6orf61 219673_at NM_017696 NM_153335 54844 0.87 2.34E-04 NR3C1 201865_x_at AI432196 NM_000176 2908 0.87 1.11E-03 KIAA1280 219520 s at NM 018458 NM_015691 55841 0.87 6.75E-05 HMG20B 209113 s at AF288679 NM 006339 10362 0.87 8.93E-05 KIAA1211 227230_s_at BE855799 XMJM4178 57482 0.87 4.76E-04 GAS6 202177_at NM_000820 NM 000820 2621 0.87 1.87E-03 AKAP13 221718_s_at M90360 NM_006738 11214 0.87 4.55E-04 H2AFZ 213911_s_at BF718636 NM_007200 NM_144767 NM_002106 3015 0.87 6.81 E-06 NYREN18 1569030 s at BC034716 NM 016118 51667 0.87 1.77E-03 C20orf20 218586_at NM_018270 NM_018270 55257 0.86 1.58E-04 PAICS 201013_s_at AA902652 NM 006452 10606 0.86 5.07E-04 HPS4 218402_s_at NM_022081 NM 022081 89781 0.86 9.72E-04 GSS 211630_s_at L42531 NM 152840 NM_152841 NM_152842 NM_152843 NM_000178 2937 0.86 3.22E-04 AL136980 222603_at AL136980 — — 0.86 1.97E-03 septin 11 201307_at AL534972 NM_018243 55752 0.86 6.58E-05 PDLIM7 214266_s_at AW206786 NM 005451 9260 0.86 8.67E-04 HIP1 205426 s at U79734 NM 203352 NM 203353 NM_213636 NM_005338 3092 0.86 1.59E-03 BF447112 236192 at BF447112 — ... 0.86 6.78E-04 AW161909 232697_at AW161909 ... ... 0.86 1.71E-04 SEC61A2 228747_at AI694646 NM_018144 55176 0.86 3.38E-04 PXMP2 219076 s at NM 018663 NM_018663 5827 0.86 2.72E-03 AU145336 233446 at AU145336 — — 0.86 2.61 E-03 SIVA 210792_x_at AF033111 NM 006427 10572 0.86 5.84E-04 NDUFA6 202000 at BC002772 NM_021709 NM 002490 4700 0.86 2.77E-03 HMGB1 200680_x_at NM_002128 NM_002128 3146 0.85 7.80E-05 septin 8 209000_s_at BC001329 XM 034872 23176 0.85 1.12E-03 EIF2B3 218488_at NM_020365 NM 020365 8891 0.85 2.51 E-06 DCX 204851_s_at AF040254 NM 000555 1641 0.85 1.15E-03 TBC1D16 1554701 a at BC028290 NMJ78151 NM 178152 NM_178153 NM 019020 125058 0.85 2.39E-03 CARD10 210026_s_at AY028896 NM_014550 29775 0.85 2.51 E-03 VAV2 205536_at NM_003371 NM 003371 7410 0.85 2.59E-03 NES 218678_at NM 024609 NM 006617 10763 0.85 8.46E-03 DRD2 216938_x_at S69899 NM 000795 1813 0.85 7.98E-03 PARP2 214086 s_at AK001980 NMJD16574 NM 005484 10038 0.85 2.66E-03 MGC13204 225837 at AL577977 NM_031465 83695 0.85 1.56E-03 SLC29A1 201802 at NM_004955 NM_004955 2030 0.85 4.79E-03 257 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays DONSON 221677_s_at AF232674 NM 017613 NM 145794 NM 145795 29980 0.85 3.72E-03 SLC37A4 217289_s_at AF097831 NM_001467 2542 0.85 2.49E-03 HAND1 220138_at NM_004821 NM 004821 9421 0.85 7.06E-03 ZGPAT 57539_at AA535065 NM_032527 NM_181484 NM_181485 84619 0.85 3.82E-04 CGI-96 202937 x at AL022316 NM 015703 27341 0.85 4.33E-04 NUP107 218768 at NM_020401 NM_020401 57122 0.84 7.62E-05 AL133101 228007_at AL133101 — — 0.84 1.62E-04 CALM3 200622_x_at AV685208 NM_005184 808 0.84 4.45E-03 AW450360 222072_at AW450360 — — 0.84 4.39E-03 BTBD3 202946_s_at NM_014962 NM_014962 NM_181443 22903 0.84 7.63E-04 RBBP8 203344_s_at NM_002894 NM_002894 NM 203291 NM_203292 5932 0.84 2.62E-04 FH 203033_x_at NM_000143 NM_000143 2271 0.84 2.23E-06 VAV2 226063_at AA481141 NM 003371 7410 0.84 1.78E-04 MRPL49 201717 at NM_004927 NM 004927 740 0.84 3.26E-03 TUBA3 209118_s_at AF141347 NM_006009 7846 0.84 7.92E-05 CD24 216379_x_at AK000168 NM_013230 934 0.84 4.53E-05 FLJ21415 218867_s_at NM_024738 NM_024738 79794 0.84 3.59E-03 AA004210 229835 s at AA004210 — — 0.84 1.26E-04 PIGX 1552291_at NM_017861 NM 017861 54965 0.84 2.94E-03 L3MBTL2 1555815_a_at AL136564 NM_00100368 9 NM 031488 83746 0.84 6.19E-03 SEC23A 212887_at AI753659 NM_006364 10484 0.84 2.12E-03 AI589594 238694_at AI589594 — — 0.84 6.20E-04 C20orf45 222441_x_at BF032213 NM_016045 51012 0.84 3.50E-03 C8orf20 218777 at NM_025232 NM 025232 80346 0.84 8.62E-04 PREX1 224925_at AL445192 NM_020820 57580 0.84 4.97E-03 RPA2 201756_at NM_002946 NM 002946 6118 0.84 2.53E-03 RECQL 212918_at AI962943 NM 002907 NM_032941 5965 0.83 5.17E-03 HOXD4 205522_at NM 014621 NM_014621 3233 0.83 4.47E-03 AU144918 233858_at AU144918 — — 0.83 9.47E-03 DATF1 218325_s_at NM_022105 NM 022105 NM_080796 NM 080797 11083 0.83 3.04E-03 EED 209572_s_at AF080227 NM 003797 NM_152991 8726 0.83 6.60E-06 RIMS4 227644_at AL049000 NM_182970 140730 0.83 1.04E-03 CHML 226350_at AU155565 NM_001821 1122 0.83 1.58E-03 RAD21 200607_s_at BG289967 NM_006265 5885 0.83 1.96E-03 ZNF555 1556188_a_at AF052118 NM 152791 148254 0.83 3.68E-04 FSCN1 210933 s at BC004908 NM 003088 6624 0.83 1.24E-03 KIAA1467 213234_at AB040900 XM_370682 57613 0.83 4.71 E-03 DDX54 224433_s_at BC005848 NM 024072 79039 0.83 4.90E-03 TERT 207199_at NM_003219 NM 003219 NM_198253 NM_198254 NM 198255 7015 0.83 3.88E-03 HRASLS 219983_at NM_020386 NM 020386 57110 0.83 7.17E-03 258 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays BACH 215728_s_at AL031848 NM_007274 NM 181862 NMJ81863 NM_181864 NM 181865 NM 181866 11332 0.83 3.84E-06 MSH5 221406_s_at NM_025259 NM_002441 NM 025259 NM_172165 NM 172166 4439 0.83 9.50E-03 FLJ22955 221224_s_at NM_024819 NM_024819 79877 0.83 2.19E-03 ATF7IP 218987_at NM 018179 NM 018179 55729 0.83 8.71 E-04 FLJ20508 218712_at NM_017850 NM_017850 54955 0.82 1.46E-03 PHF5A 225309 at AL008582 NM 032758 84844 0.82 1.72 E-04 C20orf27 50314_i_at AI761506 NM_017874 54976 0.82 7.41 E-04 SET8 225094_at AL578116 NM 020382 387893 0.82 8.35E-04 KCNS3 205968 at NM 002252 NM 002252 3790 0.82 9.42E-03 CHES1 222494 at ' AW051527 NM 005197 1112 0.82 1.04E-02 RCBTB1 218352_at NM_018191 NM_018191 55213 0.82 8.95E-05 NM 024601 220033_at NM_024601 — — 0.82 1.30E-03 HCN3 228741 s at AA569959 NM 020897 57657 0.82 2.94E-03 ATP6V1A 201971_s_at NM_001690 NM 001690 523 0.82 1.36E-03 RNF26 224338_s_at AB055622 NM_032015 79102 0.82 2.45E-03 BC042916 1559111_a_at BC042916 — — 0.82 8.94E-03 PINX1 223907 s at AF205718 NM_017884 54984 0.82 1.62E-04 AW771952 242434 at AW771952 — — 0.82 2.95E-03 HNRPAB 201277_s_at NM_004499 NM 004499 NM_031266 3182 0.82 1.19E-04 FH 214170 x at AA669797 NM_000143 2271 0.82 3.99E-05 LOC283852 238554 at BE501733 — 283852 0.82 5.07E-03 ZNF79 214138_at AA284829 NM 007135 7633 0.82 2.28E-04 C22orf19 209418_s_at BC003615 NM_00100287 7 NM_00100287 8 NM_00100287 9 NM_003678 8563 0.82 2.69E-04 RAD21 200608_s_at N M_006265 NM 006265 5885 0.82 1.40E-03 H1F0 208886_at BC000145 NM 005318 3005 0.82 3.44E-03 MAPKAPK5 212871_at NM_003668 NM 003668 NM_139078 8550 0.82 5.71 E-04 PPP1R13B 216347_s_at AK023188 NM 015316 23368 0.82 4.23E-04 ZNF278 211392_s_at AF242522 NM 014323 NM 032050 NM_032051 NM_032052 23598 0.81 1.59E-03 ENC2 210307_s_at AL136796 NM 022480 64410 0.81 6.42E-03 DACH1 1562342_at AL713717 NM 004392 NM_080759 NM_080760 1602 0.81 4.53E-03 ADRBK2 204184_s_at NM_005160 NM 005160 157 0.81 3.83E-04 JUP 201015_s_at NM_021991 NM_002230 NM_021991 3728 0.81 5.55E-03 KIAA1333 223258_s_at BC000973 NM_017769 55632 0.81 2.69E-03 ETAA16 219216_at NM_019002 NM 019002 54465 0.81 1.33E-03 LOC387882 225105_at BF969397 NM_207376 387882 0.81 9.88E-04 KIAA1648 213058_at AL033538 — 284900 0.81 3.45 E-03 259 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al„ Cells Useful for Immuno-Based BoNT/A Activity Assays DYRK4 212954_at AF263541 NM 003845 8798 0.81 3.72E-03 LOC200008 229605_at AI150848 NM 201546 200008 0.81 6.35E-06 GPX3 214091 s at AW149846 NM_002084 2878 0.81 1.38E-03 LRP10 201412_at NM_014045 NM 014045 26020 0.81 4.50E-03 LOC55954 218752_at NM_019103 NM 00100369 2 NM_019103 55954 0.81 9.27E-03 FLJ23441 219217_at NM_024678 NM 024678 79731 0.81 5.14E-06 TH1L 220607_x_at NM_016397 NM_016397 NM_198976 51497 0.81 1.63E-03 AD-003 223368_s_at BC001396 NM_014064 28989 0.81 2.11E-03 HIP2 202347_sat AB022435 NM 005339 3093 0.80 1.48E-04 MGAT5B 238445_x_at AI609043 NM 144677 NM_198955 146664 0.80 6.85E-04 EPOR 37986_at M60459 NM_000121 2057 0.80 5.63E-03 HIC2 212966_at AL043112 NM_015094 23119 0.80 3.15E-05 GJA7 228776_at AA430014 NM_005497 10052 0.80 4.03E-05 DNAJC9 213088_s_at BE551340 NM 015190 23234 0.80 2.60E-03 HMGN2 208668_x_at BC003689 NM_005517 3151 0.80 1.11E-03 MRPL42 217919_s_at BE782148 NM_014050 NM 172177 NM_172178 28977 0.80 2.11E-03 HSPC129 223270_at AF161543 NM_016396 51496 0.80 1.61 E-05 HNRPA2B1 205292_s_at NM_002137 NM_002137 NM_031243 3181 0.80 3.05E-04 ANXA4 201301 s at BC000182 NM 001153 307 0.80 8.27E-03 SOX13 38918_at AF083105 NM 005686 9580 0.80 3.55E-03 ACTR1A 200721_s_at NM_005736 NM 005736 10121 0.80 2.85E-03 MEIS2 207480_s_at NM_020149 NM 002399 NM_020149 NM_170674 NM_170675 NM 170676 NM_170677 NM 172315 NM_172316 4212 0.80 4.47E-04 APG3L 221492_s_at AF202092 NM 022488 64422 0.80 1.43E-03 CDYL 203099_s_at AF081258 NM_004824 NM_170751 NM_170752 9425 0.80 3.28E-03 ODZ3 219523_s_at NM 018104 XM 371717 55714 0.80 1.87E-03 VAPB 202550_s_at NM_004738 NM_004738 9217 0.80 8.33E-06 SAP30 204900_x_at NM_003864 NM_003864 8819 0.80 1.56E-05 HOXD1 205975 s at NM_024501 NM 024501 3231 0.80 1.08E-03 FLJ10385 220258 s at NM 018081 NM 018081 55135 0.80 1.71E-03 LRRC1 218816_at NM_018214 NM_018214 NM_025168 55227 0.80 5.23E-03 CD24 209771 x at AA761181 NM 013230 934 0.80 5.76E-04 SLC29A1 201801 s at AF079117 NM 004955 2030 0.80 7.75E-04 C10orf86 211376_s_at BC005212 NM_017615 54780 0.80 2.32E-05 GNAZ 204993_at NM_002073 NM_002073 2781 0.80 8.65E-05 C15orf25 229208_at AK022939 NM 018097 55142 0.80 8.67E-03 CPT1A 203633 at BF001714 NM_001876 1374 0.80 1.57E-03 LOC150383 227590_at BE501980 NM_00100891 7 NM_207327 150383 0.80 1.76E-05 MGC18216 225330 at AL044092 — 145815 0.80 7.91 E-04 260 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., etal., Cells Useful for Immuno-Based BoNT/A Activity Assays 384D8-2 205086_s_at NM_014551 NM_014551 NM_152299 29781 0.80 8.25E-05 USP28 231837_at AB040948 NM_020886 57646 0.80 4.10E-04 G22P1 200792_at NM_001469 NM 001469 2547 0.79 1.57E-06 TIMM50 224913_s_at AA877820 NM_001001563 92609 0.79 1.54E-06 OSRF 219421_at NM 012382 NM 012382 23548 0.79 1.38E-03 TIAF1 MY018A 202039_at NM_004740 NM_004740 NM 078471 NM_203318 399687 9220 0.79 7.17E-03 SNN 218032_at AF070673 NM 003498 8303 0.79 3.27E-05 HPS4 54037_at AL041451 NM_022081 NM_152840 NM 152841 NM 152842 NM_152843 89781 0.79 3.31 E-05 AI339606 222852_at Al 339606 — — 0.79 3.52E-03 CNN3 201445_at NM_001839 NM 001839 1266 0.79 2.38E-05 C16orf34 212115_at AK023154 NM 144570 90861 0.79 1.93E-04 )KFZP564K082 208091_s_at NM_030796 NM_030796 81552 0.79 4.71 E-04 LETM2 1557415_s_at AI023774 NM_144652 137994 0.79 1.29E-03 AW665227 229713 at AW665227 ... — 0.79 2.47E-05 C14orf130 218108_at NM_018108 NM_018108 NM_175748 55148 0.79 4.99E-03 NEDD1 234984_at AA236927 NM 152905 121441 0.79 3.11 E-04 LOC57168 227015_at Z99714 NM 020437 57168 0.79 4.74E-06 ZNF267 219540 at AU150728 NM 003414 10308 0.79 1.98E-03 HIC2 212964_at Al 912206 NM_015094 23119 0.79 6.64E-06 BG150301 230271_at BG150301 — ... 0.79 9.81 E-03 NM_014838 204799 at NM_014838 — — 0.79 1.18E-03 FLJ14827 221777 at BE966197 NM 032848 84934 0.79 2.97E-05 NP 201695_s_at NM 000270 NM 000270 4860 0.78 8.55E-03 BACH 208002_s_at NM_007274 NM 007274 NM 181862 NM_181863 NM_181864 NM 181865 NM 181866 11332 0.78 1.62E-04 GPR155 244509_at AW449728 NM_152529 151556 0.78 8.05E-03 EIF2S1 201144_s_at NM_004094 NM 004094 1965 0.78 4.48E-06 CLEC11A 205131_x_at NM_002975 NM 002975 6320 0.78 3.57E-03 BCL11A 219497_s_at NM_022893 NM 018014 NM_022893 NM 138553 NM 138559 53335 0.78 8.37E-05 MRPL2 229884_s_at AA187325 NM 015950 51069 0.78 6.69E-04 PRKAB2 1558027_s_at AL552001 NM_005399 5565 0.78 1.67E-03 DTX1 227336_at AW576405 NM_004416 1840 0.78 1.19E-03 M96 203347_s_at NM 007358 NM 007358 22823 0.78 8.86E-03 ACN9 218981 at NM 020186 NM 020186 57001 0.78 1.05E-03 IMP-1 227377_at AK022784 NM 006546 10642 0.78 2.10E-04 DVL2 57532_at AW016304 NM 004422 1856 0.78 1.49E-04 DKFZp547A023 239525 at AI733041 NM 018704 55917 0.78 2.26 E-04 LOC91431 1565935_at AF075091 NM 138698 91431 0.78 1.72E-03 H1FX 204805_s_at NM_006026 NM 006026 8971 0.78 2.36E-03 RNPEP 208270_s_at NM_020216 NM 020216 6051 0.78 1.53E-03 LOC400960 227969_at AI627636 XM 379102 400960 0.78 1.32E-04 PXMP4 224210_s_at BC001147 NM_007238 NM 183397 11264 0.78 7.76E-03 261 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays MAP3K7IP1 203901_at NM_006116 NM_006116 10454 0.78 2.33E-04 LSM2 209449 at AF196468 NM_153497 NM_021177 57819 0.78 2.81 E-03 ODF2 225617_at AL138382 NM 002540 4957 0.78 1.50E-03 JARID2 203297_s_at BG029530 NM_153437 NM 004973 3720 0.77 5.30E-03 C20orf27 218081_at NM_017874 NM_017874 54976 0.77 1.93E-04 FLJ35779 227267_at AI953478 NM 152408 134359 0.77 5.87E-03 FLJ38973 238974_at N47077 NM_153689 205327 0.77 3.60 E-03 LOC202181 232309 at Y13871 — 202181 0.77 9.94E-04 DDX54 219111_s_at NM 024072 NM 024072 79039 0.77 5.24E-03 NELL2 203413_at NM 006159 NM 006159 4753 0.77 1.82E-04 AZI1 214742_at AB029041 NM 00100981 1 NM_014984 NM 032859 22994 0.77 4.54E-04 C13orf6 235348_at AA404347 84945 0.77 6.35E-07 MKL1 212748_at AB037859 NM 020831 57591 0.77 1.75E-04 MLF1 204784_s_at NM 022443 NM_022443 4291 0.77 4.84 E-03 RPP25 219143 s_at NM_017793 NM_017793 54913 0.77 2.33E-03 MRPL39 218558_s_at NM_017446 NM_017446 54148 0.77 1.79E-03 MR-1 225298_at AA074597 NM 080794 NM 015488 25953 0.77 9.47 E-03 SCOC 223341_s_at AF330205 NM_022572 NM 032547 60592 0.77 5.34E-06 GAMT 1552474_a_at NM_138924 NM 000156 2593 0.77 8.68E-04 MGC61550 228791_at BF434655 NM_138924 NMJ82616 348110 0.77 5.38E-04 MGC4172 218756_s_at NM 024308 NM 024308 79154 0.76 8.18E-04 IKIP 227295_at AW182575 NM 153687 121457 0.76 1.09E-04 BCL11A 219498_s_at NM_018014 NM 201612 NM 201613 NM 201614 NM 018014 53335 0.76 6.17E-05 LOC115098 225454 at AW248770 NM_022893 NM_138553 NM_138559 NM_138442 115098 0.76 2.43E-03 NM 016534 219817_at NM_016534 ... ... 0.76 1.74E-03 H15087 238186_at H15087 ... ... 0.76 4.91 E-03 D15Wsu75e 212527_at BF057059 XM 039495 27351 0.76 5.47E-03 TMEM19 229126_at AI597651 NM 018279 55266 0.76 9.91 E-03 TCF3 215260_s_at X52078 NM_003200 6929 0.76 3.41 E-03 PEX19 201706_s_at BC000496 NM_002857 5824 0.76 6.90E-07 HSPC132 218403_at NM_016399 NM_016399 51499 0.76 1.21 E-03 TMEM33 222642 s at BC000948 NM 018126 55161 0.76 1.16E-03 LOC58489 225436 at Al 339710 XM_051862 58489 0.76 6.79E-04 RAB3D 225001_at AI744658 NM 004283 9545 0.76 1.35E-04 CBWD1 226193_x_at AV709992 NM 018491 150472 0.76 7.42E-06 CBWD2 LOC220869 DC36 C7orf31 229146_at AA778688 NM 172003 NM 201453 NM 138811 220869 389760 55871 136895 0.76 4.75E-04 ZNF569 1569366 a at BC038737 NM 152484 148266 0.76 2.84E-03 TOB2 222243_s_at AB051450 NM_016272 10766 0.76 1.66E-04 BF978778 226832_at BF978778 XM 374070 389188 0.75 2.91 E-03 SULF2 233555_s_at AL034418 NM 018837 55959 0.75 2.13E-03 D50683 208944_at D50683 NM 198596 0.75 8.75E-04 262 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays TMEFF1 205123_s_at NM 003692 NM 003692 8577 0.75 5.76E-04 CSNK2A1 206075_s_at NM_001895 NM_001895 NM 177559 NM_177560 1457 0.75 8.62E-03 MY01B 212364_at BF432550 NM_012223 4430 0.75 1.60E-05 TBL1XR1 222634_s_at AF314544 NM 024665 79718 0.75 8.23E-03 C20orf6 222765_x_at AL161659 NM 016649 51575 0.75 2.08E-03 TRA16 226839_at N25631 NM 176880 126382 0.75 4.39E-03 TH1L 225006_x_at AJ238379 NM_016397 NM_198976 51497 0.75 3.15E-03 LANCL1 202019 s at AI935255 NM 006055 10314 0.75 3.29E-04 ZFWE21 219929_s_at NM_024071 NM_024071 79038 0.75 5.24E-04 BF697865 235018_at BF697865 — — 0.75 3.31 E-05 RECQL 212917_x_at AI814728 NM_002907 NM_032941 5965 0.75 1.03E-03 GPR158 232195_at R41459 NM 020752 57512 0.75 9.00E-03 TH1L 225865_x_at AJ238374 NM_016397 NM_198976 51497 0.75 5.42E-03 AW025579 213429 at AW025579 — — 0.75 2.61 E-03 NDUFA3 218563_at NM_004542 NM_004542 4696 0.75 1.05E-03 AI857788 227126_at AI857788 — — 0.75 3.17E-04 TRIM32 203846_at BC003154 NM_012210 22954 0.75 9.18E-04 LZIC 226087 at BG180887 NM 032368 84328 0.75 5.95E-03 CBX1 201518 at NM 006807 NM 006807 10951 0.75 3.35E-03 TUB 228882_at AL042088 NM_003320 NM_177972 7275 0.75 1.66E-03 EPOR 215054_at H16758 NM_000121 2057 0.74 2.51 E-03 PDXP 223290_at BC000320 NM_020315 57026 0.74 3.77E-04 GSS 201415 at NM 000178 NM_000178 2937 0.74 8.16E-04 SEC10L1 228418_at BF509391 NM 006544 10640 0.74 1.01 E-02 DNAJC9 213092_x_at AW241779 NM 015190 23234 0.74 4.38E-03 SULF2 224724_at AL133001 NM 018837 NM_198596 55959 0.74 7.10E-04 KIAA0082 212380 at D43949 NM_015050 23070 0.74 9.43E-03 NM_003349 201003_x_at NM_003349 — — 0.74 2.17E-03 HH114 232506 s at AK026504 NM 032499 84529 0.74 2.32E-03 MAP3K13 211083_s_at Z25428 NM_004721 9175 0.74 1.51 E-03 SRR 222844_s_at AF169974 NM 021947 63826 0.74 1.66E-03 SIP1 205063_at NM_003616 NM_00100918 2 NM 00100918 3 NM_003616 8487 0.74 5.42E-03 SMPD3 219695_at NM 024703 NM 018667 55512 0.74 8.85E-03 ARL6IP6 225707_at AL581082 NM 152522 151188 0.74 3.27E-03 LOC90525 228922 at AI760446 NM 138356 90525 0.74 8.81 E-03 PARP2 204752_x_at NM_005484 NM_005484 10038 0.74 8.00E-03 EPB41L5 225855_at AB046768 NM_020909 57669 0.74 2.98E-04 BG492376 1557961_s_at BG492376 — — 0.74 8.26E-03 KLF3 225140 at BF438116 NM_016531 51274 0.74 1.89E-03 R12027 241836_x_at R12027 — — 0.74 1.13E-03 MCM8 233560_x_at AA370141 NM_032485 NM_182802 84515 0.74 7.31 E-03 TFR2 210215 at AF067864 NM 003227 7036 0.74 3.11E-04 EIF4E 201435_s_at AW268640 NM_001968 1977 0.74 4.34E-05 AK001164 232752_at AK001164 — — 0.74 3.62E-03 FLJ21839 218480 at NM 021831 NM 021831 60509 0.73 2.20E-04 DUT 209932_s_at U90223 NM_001948 1854 0.73 1.26E-03 263 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B„ et al., Cells Useful for Immuno-Based BoNT/A Activity Assays RBBP7 201092 at NM_002893 NM_002893 5931 0.73 2.45E-03 SCOC 224786 at AL133580 NM 032547 60592 0.73 1.16E-06 ELF2 210361_s_at AF256223 NM_006874 1998 0.73 1.61E-04 NM_201999 BF315093 227617_at BF315093 NM_001010866 199953 0.73 3.23E-03 C6orf125 224448_s_at BC006007 NM_032340 84300 0.73 1.18E-03 AK025512 225514_at AK025512 — — 0.73 2.88E-03 TTLL4 203702_s_at AL043927 NM_014640 9654 0.73 1.86E-03 PHOX2B 207009_at NM_003924 N M_003924 8929 0.73 6.98E-04 PAK4 33814 at AF005046 NM 005884 10298 0.73 6.87E-03 TTC8 226120_at AW293939 NM_144596 123016 0.73 8.67E-04 NM_198309 NM 198310 SSBP3 217991_x_at NM_018070 NM_00100995 23648 0.73 2.77E-03 0 NM_018070 NM 145716 PPIF 201489 at BC005020 NM_005729 10105 0.73 5.19E-05 LOC155435 226732_at AI823400 NM 001008406 155435 0.73 8.92E-03 RAD1 210216_x_at AF084513 NM_002853 5810 0.73 1.61E-04 NM 133282 NM_133377 PDE7A 223358_s_at AW269834 NM_002603 5150 0.73 1.04E-03 NM_002604 LOC284611 226568_at AI478747 NM 001010883 284611 0.73 4.22E-03 MPHOSPH9 1558369 at BC036600 NM_022782 10198 0.73 9.01 E-03 AHCY 200903_s_at NM_000687 NM_000687 191 0.73 6.38E-04 KIAA1393 221952_x_at AB037814 NM_020810 57570 0.73 1.27E-03 WDR50 203721 s at NM 016001 NM_016001 51096 0.73 2.41 E-06 NRF1 204651 at AW003022 NM 005011 4899 0.72 2.06E-05 ATP6V1A 201972_at AF113129 NM 001690 523 0.72 6.11 E-06 ATP6V1C1 202872_at AW024925 NM_00100725 λ 528 0.72 5.21 E-03 4 NM_001695 AP3M1 222517_at AU152391 NM 012095 26985 0.72 8.61 E-04 NM_207012 HIP1R 38340 at ABO14555 NM 003959 9026 0.72 9.01 E-03 CDKAL1 214877_at BE794663 NM_017774 54901 0.72 2.66E-07 C10orf119 222464_s_at BC004183 NM_024834 79892 0.72 2.58E-04 QRSL1 218949_s_at NM 018292 NM 018292 55278 0.72 1.91 E-04 HSPC129 223271 s at AF161543 NM 016396 51496 0.72 1.33E-04 MTAP 204956_at NM_002451 NM_002451 4507 0.72 9.35E-03 TNFRSF10B 210405_x_at AF153687 NM_003842 8795 0.72 1.20E-05 NM_147187 NDUFS1 203039 s at NM 005006 NM 005006 4719 0.72 3.56E-06 SRPK1 202199_s_at AW082913 NM_003137 6732 0.71 2.30E-04 B4GALT4 210540_s_at BC004523 NM_003778 8702 0.71 3.68E-03 NM_212543 RBM9 213901_x_at AW149379 NM 014309 23543 0.71 8.10E-03 DENR 234915_s_at BC000925 NM 003677 8562 0.71 1.01 E-02 CPOX 204172_at NM 000097 NM 000097 1371 0.71 4.66E-04 HSPC121 217777 s at NM_016395 NM_016395 51495 0.71 2.24E-04 RFX5 202963 at AW027312 NM 000449 5993 0.71 6.50E-03 SHD1 205449_at NM_013299 NM 013299 29901 0.71 7.97E-03 ARF3 200734_s_at BG341906 NM_001659 377 0.71 3.13E-05 264 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays ING1 208415_x_at NM_005537 NM_005537 NM 198217 NMJ98218 NM 198219 3621 0.71 1.86E-05 TH1L 225261_x_at AJ238376 NM 016397 NM 198976 51497 0.71 2.65E-03 VCL 200931_s_at NM_014000 NM_003373 NM_014000 7414 0.71 4.61 E-03 ZNF545 235176_at AA927918 NM 133466 284406 0.71 8.64E-03 UBOX5 204598_at NM_014948 NM 014948 NM_199415 22888 0.71 5.08E-03 ELAVL1 201726_at BC003376 NM_001419 1994 0.71 7.04E-03 ITGB5 201125_s_at NM 002213 NM_002213 3693 0.71 2.15E-03 NUP205 212247 at AW008531 NM 015135 23165 0.71 5.94E-04 SLC17A5 221041_s_at NM_012434 NM_012434 26503 0.71 9.98E-03 AI939588 241156_at AI939588 — ... 0.71 3.21 E-03 SCRIB 212556_at AI469403 NM 015356 NM 182706 23513 0.71 7.66E-03 SOCS4 226178_at BF446961 NM 080867 NM_199421 122809 0.71 1.73E-04 C6orf211 218195_at NM 024573 NM 024573 79624 0.71 6.55E-03 PSMA7 216088_s_at AL078633 NM 002792 NM_152255 5688 0.71 2.39E-04 AKR1B1 201272_at NM 001628 NM_001628 231 0.71 4.69E-04 HMG20B 210719_s_at BC002552 NM 006339 10362 0.71 5.46E-03 DZIP3 213186 at BG502305 NM 014648 9666 0.71 5.65E-03 MFI2 223723_at BC001875 NM 005929 NM_033316 4241 0.71 2.36 E-03 PPP1CC 200726 at NM 002710 NM 002710 5501 0.71 1.35E-03 AL521247 225046_at AL521247 XM 374317 389831 0.71 3.82E-03 KIAA0841 213053_at AW189966 XM 049237 23354 0.71 9.24E-03 PDE7A 224046_s_at U67932 NM_002603 NM 002604 5150 0.71 5.94E-03 FBXO30 226541_at Ai808182 NM 032145 84085 0.71 1.04E-02 SRC 213324_at AK024281 NM_005417 NM_198291 6714 0.70 5.83E-05 LOC57168 227014_at BE550881 NM 020437 57168 0.70 3.95E-04 CIB2 205008 s at NM 006383 NM 006383 10518 0.70 1.68E-03 GPAM 225420_at AV699379 NM 020918 57678 0.70 5.07E-03 KLF7 1555420_a_at BC012919 NM_003709 8609 0.70 6.45E-03 AA833830 230896 at AA833830 — ... 0.70 7.62E-04 BTBD14A 243431 at BF000597 NM 144653 138151 0.70 2.99E-03 MAPK11 211499_s_at U92268 NM 002751 NM_138993 5600 0.70 9.93E-03 FSCN1 201564 s at NM 003088 NM 003088 6624 0.70 2.66E-03 PLAGL2 202924 s at AL562280 NM_002657 5326 0.70 3.13E-04 USP39 217829_s_at NM 006590 NM 006590 10713 0.70 6.69E-04 ABHD10 222697_s_at Al521709 NM 018394 55347 0.70 3.65E-04 C20orf142 233061_at AL117382 XM 371399 128486 0.70 8.68E-03 GPR51 209990_s_at AF056085 NM_005458 9568 0.70 1.26E-03 CELSR3 205165_at NM 001407 NM_001407 1951 0.70 1.21 E-03 SSBP2 210829_s_at AF077048 NM 012446 23635 0.70 7.97E-04 POT1 204353 s at BC002923 NM 015450 25913 0.70 1.78E-04 B4GALT6 206233 at AF097159 NM_004775 9331 0.70 1.09E-03 265 PCT/US2010/027242 WO 2010/105234 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays /IARF (C3HC4) 210075_at AF151074 NM_00100541 51257 0.70 7.91E-03 5 NM_00100541 6 MGC4825 221620 s at AF061264 NM_016496 NM 024122 79135 0.70 9.49E-03 CBLL1 227187_at Al 824009 NM_Q24814 79872 0.70 2.62E-03 RAB11A 200864_s_at NM 004663 NM 004663 8766 0.70 7.58E-03 SLBP 206052_s at NM_006527 NM 006527 7884 0.70 1.28E-03 TBX3 229576_s_at N29712 NM 005996 6926 0.70 1.56E-03 RNF10 207801_s_at NM_014868 NM_016569 NM 014868 9921 0.69 2.04E-03 KIAA0153 1552257_a_at NM_015140 NM 015140 23170 0.69 9.62E-04 THOC4 226320_at AF047002 NM_005782 10189 0.69 2.92E-03 SDHA 201093_x_at NM_004168 NM_004168 6389 0.69 1.14E-05 FKBPL 219187_at NM_022110 NM 022110 63943 0.69 5.41 E-03 EXOSC3 223489_x_at AW015573 NM_00100226 51010 0.69 2.58E-04 9 NM 016042 COCH 1554242 a at BC007230 NM_004086 1690 0.69 4.57E-03 C16orf34 212109 at AI590869 NM 144570 90861 0.69 1.30E-04 CITED1 207144_s_at NM_004143 NM 004143 4435 0.69 6.40E-03 ZDHHC3 218077_s_at BE542551 NM_016598 51304 0.69 1.09E-03 AW611729 228744_at AW611729 — — 0.69 1.38E-03 MBD4 209580_s_at AF114784 NM 003925 8930 0.69 1.50E-04 CKLF 221058_s_at NM_016326 NM 016326 NM 016951 NM_181640 NM 181641 51192 0.69 6.66E-03 PPM1F 37384_at D86995 NM 014634 9647 0.69 9.40E-05 CSTF1 32723_at L02547 NMJ301324 1477 0.69 7.49E-04 KIAA1333 223257_at AI823905 NM 017769 55632 0.69 1.45E-04 SHB 1557458 s at BU685917 NM_003028 6461 0.69 1.46 E-03 AA608749 228095_at AA608749 — — 0.69 8.96E-03 MPST 203524 s at NM_021126 NM_021126 4357 0.69 4.69E-04 METRN 232269 x at BE965311 NM 024042 79006 0.69 7.29E-03 NUP43 219007_at NM_024647 NM 024647 NM_198887 348995 0.69 8.85E-05 ΤΤΎΗ2 223741_s_at BC004233 NM_032646 NM_052869 94015 0.69 9.46E-03 C20orf178 225119 at AW299290 NM 176812 128866 0.69 9.97E-06 GTF3A 215091_s_at BE542815 NM_002097 2971 0.69 1.55E-04 NIPSNAP1 201708_s_at AW083371 NM 003634 8508 0.69 1.45E-03 C20orf44 217935_s_at NM_018244 NM 018244 NM 199487 NM_199513 55245 0.68 2.08E-03 PNRC2 222406_s_at AV738970 NM_017761 55629 0.68 5.58E-05 IGFBP2 202718 at NM 000597 NM_000597 3485 0.68 8.62E-03 PDE6D 204091 at NM 002601 NM 002601 5147 0.68 3.97E-04 KIAA0376 212480_at AB002374 N M 015330 23384 0.68 1.42E-03 PLAGL2 202925_s_at NM_002657 NM_002657 5326 0.68 1.26E-03 C6orf18 42361_g_at AI588986 NM 019052 54535 0.68 4.87E-04 C16orf5 223960 s at AF195661 NM 013399 29965 0.68 1.19E-03 ZDHHC22 229875_at AI363193 NM_174976 283576 0.68 8.32E-03 RetSat 1566472_s_at AK098125 NM 017750 54884 0.68 8.62E-03 CD47 213857_s_at BG230614 NM 001777 NM_198793 961 0.68 1.35E-04 ADRBK2 228771_at AI651212 NM 005160 157 0.68 4.73E-04 266 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al„ Cells Useful for Immuno-Based BoNT/A Activity Assays KCTD9 218823_s_at NM_017634 NM_017634 54793 0.68 1.27E-03 H49805 239911 at H49805 — — 0.68 6.32E-03 ZA20D3 221613 s at AL136598 NM 019006 54469 0.68 2.84E-04 KELCHL 221837_at BG325646 NM_032775 84861 0.68 4.31 E-03 HMOX2 218120_s_at D21243 NM 002134 3163 0.68 2.33E-04 C22orf13 223039 at BC004144 NM 031444 83606 0.68 2.45E-03 ZNF71 226514 at W55975 NM_021216 58491 0.68 1.83E-03 MGC12466 223898_at BC005360 NM_033213 93474 0.68 6.20E-03 HMGB1 224731_at BF673940 NM 002128 3146 0.68 1.63E-03 TBC1D7 223461 _at AF151073 NM 016495 51256 0.68 8.95E-04 PDCL 204449 at NM 005388 NM_005388 5082 0.68 1.36E-03 RAD1 235253_at Al 742925 NM_002853 NM_133282 NM 133377 5810 0.68 2.51 E-03 CKB 200884_at NM_001823 NM_001823 1152 0.68 3.63E-05 SRrp35 239295_at AA889416 NM_080743 135295 0.68 5.74E-03 SARA2 218254_s_at NM_016103 NM_016103 51128 0.68 7.27E-06 CBX2 226473 at BE514414 — 876 0.68 2.77E-04 BLCAP 201032_at NM_006698 NM_006698 10904 0.68 1.40E-04 MGC5139 202365 at BC004815 — 84747 0.68 1.18E-03 HIBADH 224812_at AL577446 NM 152740 11112 0.68 4.29E-05 MOBK1B 201298 s at BC003398 NM_018221 55233 0.68 1.42E-05 NIPSNAP1 201709_s_at NM_003634 NM 003634 8508 0.67 3.88E-03 CSNK2A1 212072_s_at AL049761 NM_001895 NM_177559 NM 177560 1457 0.67 4.08E-03 DUT 208956_x_at U62891 NM 001948 1854 0.67 2.02E-03 HOOK3 224359_s_at AF241830 NM_032410 84376 0.67 9.68E-04 CSTF3 229665 at AI653037 NM_001326 1479 0.67 9.91 E-03 RUVBL1 201614 s at NM 003707 NM 003707 8607 0.67 3.37E-03 PNRC2 217779_s_at NMJD17761 NM_017761 55629 0.67 1.36E-03 KIAA1893 227975_at AW963386 NM_052899 114787 0.67 8.58E-03 KIAA1949 224927 at BG251556 — 170954 0.67 8.52E-03 PSMB2 200039 s at NM 002794 NM 002794 5690 0.67 2.36E-04 RCOR2 236030_at BF528119 NM_173587 283248 0.67 3.41 E-03 AL157484 221861_at AL157484 — — 0.67 8.93E-03 RBX1 218117 at NM_014248 NM 014248 9978 0.67 4.54E-03 SIPA1 204164_at NM_006747 NM_006747 NM_153253 6494 0.67 5.05E-03 DHRS8 217989_at NM_016245 NM_016245 51170 0.67 3.77E-03 FBX045 225100_at BF590021 XM 117294 200933 0.67 5.60E-03 C19orf25 226378 s at Al 554705 NM_152482 148223 0.67 2.15E-03 E2F3 203693_s_at NM 001949 NM 001949 1871 0.67 9.86E-04 SERAC1 232183_at AA128978 NM 032861 84947 0.67 2.83E-05 LOC129138 231847 at Z97630 NM_138797 129138 0.67 4.79E-04 AL524175 225479_at AL524175 ... ... 0.67 3.32E-04 CCDC5 225297_at AV715391 NM_138443 115106 0.67 1.96E-04 KIAA1166 225784_s_at AU150745 NM_018684 55906 0.67 4.05E-03 SH3BP4 222258 s at AF015043 NM_014521 23677 0.67 8.34E-05 YTHDF1 221741_s_at AL096828 NM_017798 54915 0.66 8.07E-04 DKFZP566E14^ 218194_at NM_015523 NM_015523 25996 0.66 9.77E-05 HADHSC 201035_s_at BC000306 NM 005327 3033 0.66 2.93E-03 GALNT4 231832_at AI890347 NM 003774 8693 0.66 6.21 E-03 FLJ90709 243709_at BG054799 NM_173514 153129 0.66 1.04E-02 SMARCB1 212167_s_at AK021419 NM_00100746 8 NM 003073 6598 0.66 3.27E-05 NDUFC1 203478_at NM 002494 NM 002494 4717 0.66 4.38E-03 267 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 ATP1A1 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays 220948 s at NM 000701 NM_000701 476 0.66 9.29E-05 KIAA0265 209256_s_at AF277177 NM 00100158 6 NM_014997 23008 0.66 5.63E-03 KIAA0153 216251_s_at BF965437 NM 015140 23170 0.66 1.12E-04 CCNG1 208796_s_at BC000196 NM 004060 900 0.66 7.05E-03 DT1P1A10 213079_at AA223871 NM_199246 NM_058163 90121 0.66 1.80E-03 FLJ32065 223443_s_at BC003669 NM 153032 201283 0.66 8.33E-04 COR01C 222409_at AL162070 NM 014325 23603 0.66 6.46E-05 GGA2 208914_at BE646414 NM 015044 23062 0.66 1.84E-03 SNRPB 208821_at J04564 NM 138640 NM 003091 6628 0.66 8.27E-05 NUCKS 224581 s at AI707721 NM_198216 NM_022731 64710 0.66 5.13E-06 FLJ40432 228810_at AW135279 NM 152523 151195 0.66 7.36E-05 G6PC3 221759_at AL583123 NM 138387 92579 0.66 9.07E-04 CAMTA1 225692 at AV756867 NM 015215 23261 0.66 1.84E-03 CBX5 212126_at BG391282 NM 012117 23468 0.66 2.40E-03 LIMK2 202193_at NM_005569 NM_005569 3985 0.66 8.69E-03 MRPL40 203152_at NM 003776 NM 016733 NM_003776 64976 0.66 7.24E-03 CBR4 244052_at AI469277 NM 032783 84869 0.66 1.00E-03 NKIRAS1 225930_at AI970120 NM_020345 28512 0.65 3.27E-04 ASH2L 209517_s_at AB020982 NM 004674 9070 0.65 4.47E-04 KRAS 204009_s_at W80678 NM_004985 3845 0.65 2.50E-04 KELCHL 221838_at N38751 NM_033360 NM 032775 84861 0.65 6.67E-04 MRPL35 218890_x_at NM_016622 NM 016622 51318 0.65 6.17E-03 NUDT3 221579_s_at AF062530 NM_145644 NM 006703 11165 0.65 6.42E-03 MAGEH1 218573_at NM_014061 NM_014061 28986 0.65 1.12E-04 CCNK 225824_at AA528091 NM_003858 317762 0.65 1.32E-04 C14orf65 CPE 201117_s_at NM_001873 NM 001873 8812 1363 0.65 5.66E-03 GAMT 205354_at NM_000156 NM 000156 2593 0.65 1.31 E-03 KIAA1423 225127 at BF217531 NM_138924 XM_376550 57583 0.65 2.39E-03 EXOSC3 227916_x_at AA747303 NM_00100226 o 51010 0.65 9.83E-03 RNF166 227726 at BF057084 y NM 016042 NM 178841 115992 0.65 8.38E-04 SFI1 213431_x_at AB011114 NM_00100746 7 9814 0.65 6.82E-03 FLJ14721 226487_at BE551088 ( NM 014775 NM 032829 84915 0.65 9.93E-04 FLJ21908 1557984 s at BI464019 NM 024604 79657 0.65 4.41 E-03 TNFRSF10B 209294 x at BC001281 NM 003842 8795 0.65 9.89E-05 FLJ14827 44065_at Al937468 NM 147187 NM 032848 84934 0.65 1.53E-04 TMEM33 218465_at NM_018126 NM 018126 55161 0.65 1.81 E-03 PDHA1 1555864_s_at AW057819 NM 000284 5160 0.65 2.47E-04 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays SDCBP 200958_s_at NM_005625 NM_00100706 7 NM_00100706 8 NM 00100706 9 NM_00100707 0 NM 005625 6386 0.65 5.40E-03 TM4SF9 225387 at AA059445 NM 005723 10098 0.65 2.21 E-04 SARA2 1554482_a_at BC002847 NM016103 51128 0.65 1.82E-04 BE138575 214020_x_at BE138575 — ... 0.65 1.59E-05 LOC440885 239624 at AA725362 XM 498906 440885 0.65 3.36E-04 MGC4308 224523 s at BC006475 NM_032359 84319 0.65 5.54E-03 SSBP2 203787_at NM_012446 NM 012446 23635 0.65 3.43E-03 ELMOD2 1553928_at NM_153702 NM_153702 255520 0.65 3.72E-03 KIAA1043 215146_s_at AB028966 — 23331 0.64 5.53E-04 BC015774 1569973 at BC015774 XM_496867 441220 0.64 7.67E-03 FLJ14166 219227_at NM_024565 NM_024565 79616 0.64 4.93E-03 BRMS1L 224484_s_at BC006250 NM 032352 84312 0.64 1.03E-02 SIP1 211115_x_at AB037703 NM_00100918 2 NM_00100918 3 NM 003616 8487 0.64 4.84E-05 RGS19 204336_s_at NM_005873 NM_005873 10287 0.64 2.62E-03 HEMK1 52159_at W93807 NM_016173 51409 0.64 4.05E-03 BCCIP 218264_at NM_016567 NM 016567 NM 078468 NM 078469 56647 0.64 2.33E-04 RPL5 LOC388650 213689_x_at AL137958 NM_000969 NM_00100660 c 388650 6125 0.64 1.28E-03 CYCS 208905_at BC005299 O NM_018947 54205 0.64 6.99E-07 ARF3 211622_s_at M33384 NM 001659 377 0.64 1.47E-04 C19orf14 1553125_x_at NM 173636 NM 173636 284403 0.64 9.52E-03 MGC10433 205740 s at NM_024321 NM 024321 79171 0.64 3.28E-04 PRKDC 208694_at U47077 NM 006904 5591 0.64 8.30E-03 SCDR10 1569905_at BC018336 NM_198533 NM 198704 NM_198705 NM_198706 NM_198707 NM 198708 374875 0.64 8.71 E-03 TGIF2 216262_s_at AL050318 NM_021809 60436 0.64 1.37E-05 LOC90268 229268_at AA723152 NM_138348 90268 0.64 3.05E-04 PARP1 208644 at M32721 NM_001618 142 0.64 6.21 E-05 RGMB LOC285705 227339_at BE206621 NM_173670 285704 285705 0.64 2.63E-04 ZNF250 213858_at BE350026 NM_021061 58500 0.64 6.68E-03 ACTR1A 200720_s_at AL532341 NM 005736 10121 0.64 3.97E-03 FBXL10 229855_at AA779208 NM 00100536 6 NM_032590 84678 0.64 5.29E-03 PIPPIN 209981 at AL023553 NM 014460 27254 0.64 8.32E-03 C22orf16 224932_at AI814909 NM_213720 400916 0.64 5.31 E-03 269 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B„ et al., Cells Useful for Immuno-Based BoNT/A Activity Assays DTNBP1 223445_at AF061734 NM_032122 NM 183040 NM 183041 84062 0.63 1.32E-03 GRWD1 221549_at AF337808 NM_031485 83743 0.63 8.09E-03 LARS2 34764_at D21851 NM_015340 23395 0.63 1.98E-03 PPP5C 201979 s at NM 006247 NM_006247 5536 0.63 5 76E-05 AW051899 242602_x_at AW051899 — ... 0.63 2.62E-03 FLJ21125 219560_at NM_024627 NM_024627 79680 0.63 9.02E-03 MRPS28 219819_s_at NM_014018 NM_014018 28957 0.63 1.73E-03 SENP1 226619_at AW665440 NM 014554 29843 0.63 3.06E-03 CENTD2 34206_at AB018325 NM_015242 NM_139181 116985 0.63 2.69E-04 TPM1 206117_at NM_000366 NM_000366 7168 0.63 1.78E-03 RAP1GDS1 209444_at BC001851 NM 021159 5910 0.63 2.24E-04 CELSR3 40020 at ABO11536 NM 001407 1951 0.63 6.88E-04 PPM1F 203063_at NM 014634 NM 014634 9647 0.63 3.60E-05 HMGB1 214938_x_at AF283771 NM_002128 3146 0.63 4.46E-04 AW294869 225227_at AW294869 — — 0.63 1.30E-03 AI417537 227739 at AI417537 XM_372169 389822 0.63 9.49E-03 GTF3A 201338_x_at NM 002097 NM 002097 2971 0.63 4.05E-04 EXOSC3 223490_s_at AF281132 NM 00100226 9 NM_016042 51010 0.63 4.03E-05 HSPA14 219212_at NM 016299 NM_016299 51182 0.63 2.58E-05 DHX15 201386_s_at AF279891 NM 001358 1665 0.63 2.26E-05 CDK5RAP2 220935_s_at NM_018249 NM 00101164 9 NM_018249 55755 0.62 1.12E-03 CBX5 231862_at AK023520 NM_012117 23468 0.62 8.64E-03 AW024563 225712 at AW024563 — — 0.62 2.41 E-03 NME4 212739_s_at AL523860 NM 005009 4833 0.62 4.02E-04 EEF2K 225545_at BF001312 NM_013302 29904 0.62 1.58E-06 ECHDC1 219974 x at NM 018479 NM 018479 55862 0.62 1.24E-03 SORT1 224818 at BE622952 NM 002959 6272 0.62 6.15E-03 FKBP7 231130_at AA683602 NM 016105 NM_181342 51661 0.62 6.59E-03 PPP4R2 225519 at AA206408 NM 174907 151987 0.62 1.07E-03 JAG1 216268 s at U77914 NM 000214 182 0.62 3.91 E-03 OSBPL1A 241693_at BF246603 NM 018030 NM 080597 NM 133268 114876 0.62 3.59E-03 AP1B1 205423_at NM_001127 NM_001127 NM 145730 162 0.62 5.15E-06 SNRPB 213175_s_at AL049650 NM_003091 NM_198216 6628 0.62 1.16E-05 MYH9 211926 s at AI827941 NM_002473 4627 0.62 7.82E-06 BICD2 213154_s_at AI934125 NM_00100380 0 NM 015250 23299 0.62 6.85E-03 SNX11 220140_s_at NM_013323 N M 013323 NM_152244 29916 0.62 6.32E-03 ZNF354A 205427_at NM_005649 NM_005649 6940 0.62 9.78E-03 270 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays ANK1 205390_s_at NM_000037 NM 000037 NM 020475 NM 020476 NM 020477 NM 020478 NM 020479 NM 020480 NM_020481 286 0.62 1.01 E-02 SNRPG 205644_s_at NM_003096 NM 003096 6637 0.62 1.58E-03 15E1.2 214711_at BE568184 NM 176818 283459 0.62 9.53E-03 PPOX 204788_s_at NM_000309 NM_000309 5498 0.62 5.07E-03 GTF2F2 209595_at BC001771 NM 004128 2963 0.62 6.89E-04 RAC 3 206103_at NM 005052 NM_005052 5881 0.62 8.05E-04 IRAKI BP 1 213074 at BG545769 NM 001010844 134728 0.62 1.38E-03 M96 203345_s_at AI566096 NM_007358 22823 0.62 1.24E-03 CHPPR 203208_s_at NM 014637 NM 014637 9650 0.62 5.77E-03 CBFB 206788_s_at AF294326 NM 001755 NM_022845 865 0.62 3.44E-03 HIVEP2 212641_at AL023584 NM_006734 3097 0.62 2.38E-03 FDPS 201275_at NM 002004 NM_002004 2224 0.62 1.13E-03 SCC-112 213983 s at AW991219 NM 015200 23244 0.62 4.84E-03 NCOR2 207760_s_at NM 006312 NM 006312 9612 0.62 2.28E-03 CIAPIN1 208424 s at NM 020313 NM 020313 57019 0.62 2.19E-05 STAT1 JMISGF3A/M97HUMISGF3A/M97 NM_007315 NM_139266 6772 0.62 9.80E-04 EIF5B 201027 s at NM 015904 NM 015904 9669 0.62 3.52E-04 FBX045 225099_at AA126446 XM_117294 200933 0.62 4.20E-03 COPS6 213504_at W63732 NM 006833 10980 0.62 7.94E-03 AC 02 200793_s_at NM_001098 NM 001098 50 0.61 1.19E-03 HADHSC 211569_s_at AF001903 NM_005327 3033 0.61 1.58E-03 M6PRBP1 202122_s_at NM_005817 NM_005817 10226 0.61 5.73E-03 GPR51 211679_x_at AF095784 NM_005458 9568 0.61 2.47E-03 LOC63929 226501 at BE966628 NM 022098 63929 0.61 5.18E-04 FLJ20331 218577_at NM 017768 NM_017768 55631 0.61 7.70E-03 AM 25670 231431_s_at AM25670 XM 373626 388114 0.61 5.65E-04 RENT1 211168_s_at D86988 NM_002911 5976 0.61 5.90E-03 COX7B 202110_at NM_001866 NM 001866 1349 0.61 1.87E-03 RBMS1 209868_s_at D28482 NM_002897 NM 016836 NM_016839 5937 0.61 1.58E-05 NAP1L4 1560339 s at AK095320 NM 005969 4676 0.61 7.56E-03 DTNBP1 223446_s_at AF061734 NM 032122 NM_183040 NM 183041 84062 0.61 1.14E-03 SUHW3 235520_at AA805654 NM 017666 55609 0.61 7.60E-03 RAD1 204461_x_at NM_002853 NM_002853 NM 133282 NM 133377 5810 0.61 8.03E-03 NAP1L4 201414 s at NM 005969 NM_005969 4676 0.61 8.91 E-03 DBN1 202806_at NM_004395 NM 004395 NM_080881 1627 0.61 6.46E-03 LSM3 202209 at NM 014463 NM 014463 27258 0.61 3.78E-04 ITGAV 202351_at AI093579 NM 002210 3685 0.61 1.45E-03 PDCD8 205512_s_at NM_004208 NM 004208 NM 145812 NM 145813 9131 0.61 3.22E-03 GLT28D1 219015_s_at NM_018466 NM_018466 55849 0.61 1.02 E-02 )KFZp586M181 224776_at BF513102 NM_178819 137964 0.61 3.28E-04 271 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays ZNF305 206507_at NM_014724 NM_014724 9753 0.61 6.84E-03 MRPL37 222993_at AF325707 NM 016491 51253 0.61 3.36E-03 MY01B 212365 at BF215996 NM 012223 4430 0.61 4.15E-06 XRCC5 208642_s_at AA205834 NMJD21141 7520 0.61 1.58E-05 AK096932 1564220_a_at AK096932 — — 0.60 2.76E-03 MGC50372 1558097_at W21283 NM 173566 253143 0.60 1.75E-03 UBE2R2 226954_at BE221883 NM_017811 54926 0.60 1.57E-04 LOC283484 1556940_at AW665184 — 283484 0.60 6.08E-03 C20orf77 225024_at AL117521 NM_021215 58490 0.60 4.10E-05 FLJ10350 217943_s_at NM_018067 NM_018067 55700 0.60 2.33E-03 LOC84661 224129 s at AF226998 NM 032574 84661 0.60 6.46E-03 SMYD5 209516_at U50383 NM 006062 10322 0.60 2.51 E-04 H2AFJ 220936_s_at NM_018267 NM_018267 NM_177925 55766 0.60 2.36E-03 XPNPEP1 208453 s at NM 006523 NM 020383 7511 0.60 2.47E-03 APG7L 218673_s_at NM_006395 NM_006395 10533 0.60 7.62E-03 RASGRP1 205590_at NM_005739 NM 005739 10125 0.60 8.56E-03 KIAA1333 223254_s_at AA887053 NM 017769 55632 0.60 1.03E-02 C6orf79 220094_s_at NM 022102 NM 022102 63933 0.60 1.45E-03 PHACTR3 227949_at AL357503 NM_080672 NM_183244 NM_183246 116154 0.60 5.45E-04 CSPG6 209259 s at AF020043 NM 005445 9126 0.60 4.65E-03 C6orf108 204238_s_at NM 006443 NM_006443 NM_199184 10591 0.60 6.02E-03 MGC15606 215968_at AF055018 NM 145037 91775 0.60 6.84E-04 MGC13017 235006_at AL571598 NM 080656 91368 0.60 6.97E-03 PA2G4 208676_s_at U87954 NM_006191 5036 0.60 2.40E-03 MRPL2 218887_at NM 015950 NM_015950 51069 0.60 4.44 E-04 FUSIP1 206095_s_at NM_006625 NM 006625 NM_054016 10772 0.60 6.03E-03 NUP98 203194_s_at AA527238 NM 005387 NM 016320 NM 139131 NMJ39132 4928 0.60 2.00E-03 G6PC3 44654 at AI669655 NM 138387 92579 0.60 2.87E-03 BCR 217223_s_at U07000 NM_004327 NM_021574 613 0.60 3.32E-03 AP3S2 202399_s_at NM_005829 NM_005829 10239 0.59 2.43E-03 ZNF589 219968_at NM_016089 NM 016089 51385 0.59 2.39E-03 AHCYL1 200850_s_at NM_006621 NM_006621 10768 0.59 5.75E-04 SIN3A 225135_at AI433017 NM 015477 25942 0.59 4.14E-03 CHCHD3 217972_at NM_017812 NM_017812 54927 0.59 2.72E-03 SSBP3 223635_s_at BC003605 NM_00100995 5 NM 018070 NMJ45716 23648 0.59 1.16E-03 Al 127452 228443_s_at Al 127452 — — 0.59 2.59E-03 LOC113174 225614 at AI815207 NM 138421 113174 0.59 4.60E-04 C20orf24 224376_s_at AF274948 NM_018840 NM_199483 NM_199484 NM 199485 55969 0.59 1.49E-04 PITPNB 202522_at AL031591 NM_012399 23760 0.59 1.72 E-04 RPE 216574_s_at J04742 NM_006916 NM_199229 6120 0.59 1.51 E-03 AF061733 223477_s_at AF061733 — — 0.59 4.14E-03 ECHDC1 223088_x_at BC003549 NM_018479 55862 0.59 2.67E-05 272 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 MRPL30 Jacky, B., et al., 223996_s_at Cells Useful for Immuno-Based BoNT/A Activity Assays AF151083 NM_016503 51263 0.59 5.32E-04 CNOT4 203291_at NM_013316 NM 145212 NM_145213 NM_00100822 C 4850 0.59 1.86E-04 MGC32020 214816_x_at BC003535 O NM 013316 NM_152266 91442 0.59 1.21E-03 SLC4A7 209884_s_at AF047033 NM 003615 9497 0.59 8.63E-03 ATXN10 208833_s_at AF119662 NM_013236 25814 0.59 1.71E-06 POP7 209482_at BC001430 NM 005837 10248 0.59 4.07E-04 LRRFIP1 223492 s at BC004958 NM 004735 9208 0.59 2.17E-03 HIG1 221896_s_at BE739519 NM_014056 25994 0.58 3.91 E-03 PBX3 204082_at NM_006195 NM_006195 5090 0.58 7.63E-03 LZTR1 203412_at NM 006767 NM 006767 8216 0.58 7.27E-03 SFI1 215699_x_at AL096768 NM_00100746 7 9814 0.58 6.00E-03 TOP3B 213660 s at AA581879 / NM_014775 NM 003935 8940 0.58 3.68 E-03 PSMD12 202352_s_at AI446530 NM_002816 5718 0.58 1.19E-03 RAB7L1 218700_s_at BC002585 NM_174871 NM_003929 8934 0.58 7.31 E-03 NM_016402 217946 s_at NM 016402 — ... 0.58 3.60E-04 SIP1 211114 x_at AB037702 NM_00100918 8487 0.58 5.55E-03 2 NM_00100918 3 NM 003616 COPS8 214260_at AI079287 NM_006710 NM_198189 10920 0.58 9.44E-03 ZNF141 206931 at NM 003441 NM 003441 7700 0.58 8.62E-05 LANCL1 202020_s_at NM_006055 NM 006055 10314 0.58 6.88E-03 PXK 225796_at Al684747 NM 017771 54899 0.58 6.08E-04 AMACR 209424_s_at Al796120 NM 014324 NM 203382 23600 0.58 8.99E-03 RPE 225040_s_at AV699857 NM 006916 NM_199229 6120 0.58 5.46E-04 GSPT1 215438_x_at BE906054 NM 002094 2935 0.58 1.02E-02 ASXL1 212234 at AL034550 NM 015338 171023 0.58 1.46E-03 EIF4ENIF1 218626_at NM_019843 NM_019843 56478 0.58 1.12E-04 RIT1 239843_at Al655057 NM_006912 6016 0.58 2.20E-03 TP53RK 225402_at BG339450 NM 033550 112858 0.58 1.38E-04 MAT2B 217993_s_at NM_013283 NM_013283 NM_182796 27430 0.58 2.85E-03 TMCC3 226489_at BG177562 NM_020698 57458 0.58 3.41 E-03 POLRMT 203782 s at NM 005035 NM_005035 5442 0.58 2.34E-03 BG109230 228567 at BG109230 — ... 0.58 2.93E-04 RBMS1 203748_x_at N M 016839 NM_002897 NM 016836 NM 016839 5937 0.58 1.17E-05 LOC96610 226802_s_at W87523 NM_080926 96610 0.58 8.19E-03 273 PCT/US2010/027242 WO 2010/105234 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays

Table 8. Decreased Gene Expression in Cell Lines H1 and BB10 vs. Cell Line 2D6 in Differentiated State Using Microarray Analysis

Gene Symbol Probe Set ID Representative Public ID RefSeq Transcript ID Entrez Gene Log2 Ratio pvalue CYTL1 219837_s_at NM_018659 NM_018659 54360 -6.87 8.62E-11 IL17B 220273_at NM_014443 NM_014443 27190 -6.24 3.55E-08 KIAA0125 206478_at NM 014792 NM 014792 9834 -5.76 4.88E-04 OLFML2A 213075_at AL050002 NM 182487 169611 -5.40 4.32E-12 GNAS 217057_s_at AF107846 NM 000516 2778 -5.37 6.02E-03 THBS2 203083 at NM 003247 NM_016592 NM_080425 NM_080426 NM 003247 7058 -5.31 9.79E-08 CAP2 212554_at N90755 NM_006366 10486 -5.29 4.85E-06 CYGB 226632_at AL513673 NM_134268 114757 -5.15 2.38E-03 MEOX2 206201 s at NM 005924 NM_005924 4223 -4.96 9.77E-08 AI051127 231478 at AI051127 — — -4.84 1.89E-03 CRH 205630 at NM 000756 NM_000756 1392 -4.78 2.26E-03 NXF 1554299 at AB049469 NM_178864 266743 -4.75 3.31 E-05 SLC1A2 225491_at AL157452 NM 004171 6506 -471 1.26E-09 FGF13 205110_s_at NM_004114 NM 004114 2258 -4.65 6.61 E-06 MICAL2 212473 s at BE965029 NM_033642 NM 014632 9645 -4.59 1.59E-05 CART 206339 at NM 004291 NM 004291 9607 -4.59 4.64E-03 ADM 202912_at NM 001124 NM_001124 133 -4.47 5.16E-07 OSCAR 1554503_a_at BC035023 NM 130771 126014 -4.38 . 3.92E-04 HTR1E 207404_s_at NM_000865 NM 133168 NM_133169 NM_206817 NM_206818 NM_000865 3354 -4.24 8.64E-04 BF681305 1561817 at BF681305 — — -4.22 5.84E-04 EGFL7 218825_at NM_016215 NM_016215 51162 -4.16 3.07E-05 SLC1A6 1554593_s_at BC028721 NM_201446 NM_005071 6511 -4.16 8.15E-04 GPR54 242517_at AI819198 NM_032551 84634 -4.15 1.40E-04 BC036254 1557443_s_at BC036254 — ... -4.14 5.46E-06 NDRG1 200632_s_at NM_006096 NM_006096 10397 -4.10 8.60E-05 LOC56901 218484_at NM 020142 NM_020142 56901 -4.10 1.79E-03 STX3A 209238 at BE966922 NM 004177 6809 -4.02 4.71 E-04 AQP1 209047_at AL518391 NM_000385 358 -4.02 1.49E-03 AA530995 213832_at AA530995 NM_198098 -4.00 2.31 E-03 AL353759 215071 s at AL353759 — ... -3.90 1.96E-05 ARHGAP9 224451_x_at BC006107 NM_032496 64333 -3.89 8.61 E-04 CAP2 212551_at NM_006366 NM_006366 10486 -3.86 4.69E-07 LOC158572 243017_at AA032156 XM_379705 158572 -3.85 1.09E-04 PDE4C 211818 s at U88712 NM 000923 5143 -3.78 3.71 E-03 RaLP 230538_at AI027957 NM_203349 399694 -3.67 1.39E-05 PTGS1 215813_s_at S36219 NM_000962 5742 -3.65 1.09E-08 CYGB 1553572_a_at NM_134268 NM_080591 NM_134268 114757 -3.65 2.42E-06 274 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 ANXA2 Jacky, B., et al., 201590_x_at Cells Useful for Immuno-Based BoNT/A Activity Assays NM_004039 NM_00100285 302 -3.65 1.12E-05 NEBL 203961_at AL157398 ! NM 00100285 8 NM 004039 NM 006393 10529 -3.63 1.91E-05 ANXA2 210427_x_at BC001388 NM 213569 NM_00100285 7 302 -3.61 1.06E-05 BE219849 240180_at BE219849 I NM 00100285 8 NM 004039 -3.60 1.29E-05 AU157716 227051 at AU157716 — — -3.56 1.17E-07 RaLP 235238 at BF676462 NM 203349 399694 -3.55 6.19E-07 RGS11 206107_at NM_003834 NM_003834 8786 -3.53 1.56E-06 AI743780 229385_s_at AI743780 NM_183337 -3.53 5.61 E-08 CRH 205629 s at BC002599 NM_000756 1392 -3.52 2.27E-03 MGC4677 225799_at BF209337 NM_052871 112597 -3.49 6.17E-05 AW954199 239331_at AW954199 — — -3.49 1.64E-05 PTGS1 205128_x_at NM_000962 NM_000962 5742 -3.48 3.62E-08 BF449053 238018_at BF449053 NM_080591 -3.48 3.99E-07 CDC42EP1 204693_at NM_007061 NM 007061 11135 -3.46 1.15E-04 CDH10 220115_s_at NM_006727 NM 152243 NM_006727 1008 -3.43 5.86E-06 AI341823 239657_x_at Al 341823 — — -3.42 9.66E-07 HPCAL1 1560154_a_at AK026500 NM_002149 3241 -3.40 3.33E-08 LOC283454 229552_at AI698128 NM_134421 283454 -3.38 1.29E-03 ABLIM3 205730_s_at NM 014945 NM_014945 22885 -3.34 4.32E-05 Al885066 239845_at AI885066 — — -3.32 1.56E-05 Al810266 235456 at AI810266 — — -3.31 6.67E-04 HIST1H3E 236278_at AV705309 NM_003532 8353 -3.26 1.95E-05 SLC35F3 229065_at BF968270 NM 173508 148641 -3.24 3.97E-06 BHLHB2 201170_s_at NM_003670 NM 003670 8553 -3.22 2.22E-03 NEBL 203962_s_at NM_006393 NM 006393 10529 -3.21 3.48E-05 ANXA2 213503_x_at BE908217 NM_213569 NM_00100285 7 302 -3.19 2.51 E-07 PHKA2 1560358 at BC038597 1 NM 00100285 8 NM_004039 NM 000292 5256 -3.18 3.38E-03 GRM5 214217 at D60132 NM_000842 2915 -3.18 2.84E-04 AL512727 215014_at AL512727 — — -3.18 8.51 E-04 STC1 204595_s_at Al 300520 NM_003155 6781 -3.16 9.00E-03 BG325630 234973 at BG325630 — — -3.15 2.18E-03 SYTL1 227134 at Al 341537 NM_032872 84958 -3.14 1.02E-05 BC002465 216189_at BC002465 — — -3.11 3.46E-03 C1orf24 217967_s_at AF288391 NM_022083 116496 -3.11 5.38E-03 PDE4C 206791 s at BF511742 NM_052966 NM_000923 5143 -3.08 2.33E-03 HIST1H2BD 209911_x_at BC002842 NM_021063 3017 -3.08 9.52E-06 SYT5 206161_s_at AI659957 NM_138720 NM 003180 6861 -3.06 3.57E-03 LAMP 3 205569_at NM_014398 NM_014398 27074 -3.06 8.91 E-03 275 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., etal., Cells Useful for Immuno-Based BoNT/A Activity Assays ADARB1 203865_s_at NM_015833 NM_001112 NM 015833 NM 015834 104 -3.06 2.79E-04 CYP2E1 1431_at J02843 NM 000773 1571 -3.05 1.50E-03 LOC150759 221973_at Al983904 XM_498456 XM_499585 150759 -3.03 2.56E-03 SORCS1 1556891_at BE328250 NM_052918 114815 -3.03 3.14E-05 CREB5 232555_at AI689210 NM 004904 NM_182898 NM 182899 9586 -3.03 1.60E-03 ISG20 204698 at NM 002201 NM_002201 3669 -3.00 1.76E-03 AA417078 238619_at AA417078 — ... -2.99 5.87E-05 AW274468 242299_at AW274468 — ... -2.98 2.44E-05 PTPRH 208300 at NM 002842 NM 002842 5794 -2.97 3.46E-04 BHLHB2 201169 s at BG326045 NM_003670 8553 -2.96 1.38E-03 AW270105 229413_s_at AW270105 — ... -2.92 9.07E-04 LOC390916 235384_at AW963217 XM 372723 390916 -2.90 9.52E-08 SLC01A2 211480_s_at AF085224 NM 005075 NM_021094 NM_134431 6579 -2.88 2.29E-05 HIST1H2BK 209806_at BC000893 NM 080593 85236 -2.88 3.64E-05 SYT5 206162_x_at NM 003180 NM 003180 6861 -2.86 6.38E-04 )KFZp761O011 207797 s at NM_018409 NM_018409 55805 -2.86 2.54E-05 CDKN1C 219534_x_at NM 000076 NM 000076 1028 -2.86 3.17E-04 SCHIP1 1566772_at AL832567 NM 014575 29970 -2.85 7.20E-03 CDKN1C 213182_x_at R78668 NM_000076 1028 -2.85 3.87E-04 FLJ13955 227001_at AI096706 NM_024759 79815 -2.82 9.16E-04 SYT13 226086_at AB037848 NM_020826 57586 -2.80 7.99E-04 M160 223655_at AF264014 NM 174941 283316 -2.79 3.27E-04 CDKN2A 209644_x_at U38945 NM 000077 NM_058195 NM_058197 1029 -2.78 1.33E-06 AA954997 243436 at AA954997 — ... -2.77 1.59E-05 HIST2H2BE 202708_s_at NM 003528 NM 003528 8349 -2.75 8.53E-04 GTF2IRD2 1557289_s_at BU617476 NM 173537 84163 -2.75 3.68E-05 AI079543 236949_at Al079543 XM_498613 440283 -2.75 7.55E-03 LONP 221833 at AI971258 NM_031490 83752 -2.75 1.32E-03 AI681941 237663 at AI681941 — — -2.74 1.15E-04 BE894882 235681_at BE894882 — ... -2.73 3.37E-06 GRIA2 205358_at NM_000826 NM 000826 2891 -2.73 7.10E-03 MY015B 219173 at NM_024957 XR_000222 80022 -2.73 4.36E-05 BC042953 1561242 at BC042953 — — -2.70 6.39E-03 GRIA2 236538_at BE219628 NM_000826 2891 -2.69 3.27E-03 MY015B 59375_at AI825877 XR_000222 80022 -2.68 1.90E-06 Al927692 228528_at AI927692 — ... -2.67 6.22E-06 BC021677 1559631_at BC021677 ... ... -2.67 4.72E-04 AA088430 242556_at AA088430 ... ... -2.65 5.20E-07 AI769477 236875_at AI769477 — ... -2.65 2.18E-08 HSPA5 230031_at AW052044 NM 005347 3309 -2.64 7.69E-03 HRK 206865_at U76376 NM_003806 8739 -2.64 6.03E-03 BE671060 235901_at BE671060 — ... -2.63 9.58E-04 PLA2G4C 1554810_at BC017956 NM 003706 8605 -2.63 4.54E-05 CYP2E1 209976_s_at AF182276 NM_000773 1571 -2.63 4.37E-03 CDKN1C 213348_at N33167 NM_000076 1028 -2.62 4.09E-04 ARHGAP9 232543_x_at BE675685 NM_032496 64333 -2.62 7.93E-05 AI798680 227943_at AI798680 — ... -2.62 1.59E-05 BG430958 1559455_at BG430958 — — -2.59 1.73E-06 276 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays PPP2R2C 1562290_at AL157448 NM 020416 NM_181876 5522 -2.59 4.74E-04 ANK2 216195_at AF131823 NM 001148 NM_020977 287 -2.59 2.14E-03 CYP2E1 209975_at AF182276 NM_000773 1571 -2.58 3.47E-03 BG231712 230408_at BG231712 — — -2.58 3.02E-03 ACRBP 223717_s_at AB051833 NM_032489 84519 -2.58 1 02E-04 AU145981 232439_at AU145981 — — -2.57 3.24E-05 SIK2 233648_at AK026914 NM 015191 23235 -2.55 1.93E-03 ANK2 1561895_at BC030740 NM 001148 NM_020977 287 -2.55 9.50E-04 RHOB 1553962 s at BI668074 NM_004040 388 -2.54 1.06E-03 BC040652 1559528_at BC040652 — — -2.53 1.20E-03 CDKN1C 216894_x_at D64137 NM 000076 1028 -2.52 2.77E-04 AQP1 207542_s_at NM_000385 NM_000385 NM_198098 358 -2.52 6.49E-03 )KFZP434N181 232257_s_at AK022645 NM_032137 84077 -2.51 6.77E-03 CTBP1 243180 at AW452392 NM_001328 1487 -2.51 1.14E-05 KIAA0500 213839 at AW028110 — 57237 -2.51 5.06E-05 AW606588 239008_at AW606588 — — -2.50 5.69E-04 AA903473 235666_at AA903473 — — -2.50 1.43E-03 1KFZp313N062 1555905_a_at AH 47556 NM_173826 285343 -2.49 1.95E-04 VEGF 211527 x at M27281 NM 003376 7422 -2.49 1.00E-03 FAM46A 224973_at AL078599 NM 017633 55603 -2.48 2.76E-05 ZNF395 FBX016 223216_x_at BC001237 NM 018660 NM_172366 157574 55893 -2.48 7.42E-04 XP01 230729 at AI860764 NM_003400 7514 -2.48 1.68E-05 C20orf119 231838_at AK026760 — 80336 -2.47 1 43E-06 ANK2 232606_at AK021894 NM_001148 NM_020977 287 -2.46 1.49E-04 AV702101 238595 at AV702101 — — -2.46 3.03E-04 AW364675 239066_at AW364675 — — -2.45 3.80E-06 FAM46A 221766_s_at AW246673 NM_017633 55603 -2.45 2.44E-06 AK096401 1556204 a at AK096401 XM 375664 400721 -2.44 7.27E-04 ZNF395 221123 x at NM 018660 NM 018660 55893 -2.44 8.86E-04 PTGER2 206631 at NM 000956 NM 000956 5732 -2.43 2.99E-05 FLJ31295 226509_at AV700302 NM_152320 121274 -2.43 2.75E-05 MEF2A 239571_at AH23399 NM_005587 4205 -2.42 5.57E-04 AW298171 244346 at AW298171 — — -2.41 1.16E-05 FLJ30594 235836_at N51413 — 150622 -2.41 3.87E-03 AW205919 229830 at AW205919 — — -2.40 1.33E-04 BE671519 242236 at BE671519 — — -2.39 2.68E-03 SIGIRR 218921 at NM 021805 NM_021805 59307 -2.39 3.99E-05 AW665665 237187_at AW665665 — — -2.39 6.09E-04 GPR92 230252_at AW183080 NM_020400 57121 -2.39 1.54E-05 MGC13040 224463 s at BC006128 NM 032930 85016 -2.39 2.97E-03 ANKS1 212747_at AI990523 NM_015245 23294 -2.38 1.37E-03 ABCC8 210246_s_at AF087138 NM 000352 6833 -2.38 2.60E-04 RHOB 212099_at AI263909 NM 004040 388 -2.38 7.05E-04 SMOC2 223235 s at ABO14737 NM 022138 64094 -2.37 1 05E-03 CENTG2 1559491_at AL390180 NMJ314914 116987 -2.36 1.41E-03 ARTS-1 214012_at BE551138 NM 016442 51752 -2.36 4.64E-05 TM4SF8 232632_at AU145719 NM_005724 NM_198902 10099 -2.36 2.15E-04 U66046 215057_at U66046 — — -2.36 2.03E-04 KIAA0251 1558430_at R08650 NM 015027 23042 -2.35 5.89E-03 TIMP1 201666_at NM_003254 NM_003254 7076 -2.35 1.13E-05 AK024567 234597 at AK024567 — — -2.34 1.59E-04 277 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays PPFIA4 214978 s_at AK023365 NM 015053 8497 -2.34 1.46E-03 BCL11B 233302_at AU146285 NM 022898 64919 -2.34 1.59E-04 C21orf4 228001_at N51405 NM_138576 NM_006134 757 -2.34 7.50E-05 ATF5 204999_s_at BC005174 NM_012068 22809 -2.34 1.08E-03 COL7A1 217312_s_at L23982 NM_000094 1294 -2.33 2.40E-05 AL049252 216527_at AL049252 — — -2.33 1.19E-03 VGCNL1 228608_at N49852 NM_052867 259232 -2.32 3.07E-06 OLFM1 205591_at NM_006334 NM_006334 10439 -2.32 9.85E-03 ZNF395 232693_s_at AK021850 NM_014279 NM 058199 NM_018660 157574 -2.32 2.21 E-03 FBX016 CNTN2 230045_at BF740264 NM_172366 NM_005076 55893 6900 -2.31 5.97E-04 ZNF395 239619 at BF431867 NM_018660 55893 -2.31 2.70E-03 RASGEF1B 230233__at BF110534 NM_152545 153020 -2.31 2.05 E-03 AG PATS 223182_s_at AI337300 NM_020132 56894 -2.31 6.95E-03 ZNF395 236474 at AI797677 NM 018660 55893 -2.30 6.29E-03 MPP5 242779 at N36400 NM_022474 64398 -2.30 3.44E-08 AL512728 216813_at AL512728 — — -2.30 1.89E-03 PLEKHH1 225727_at AB033026 NM 020715 57475 -2.29 1.26E-06 PLEKHH1 225726_s_at AB033026 NM_020715 57475 -2.29 3.43E-07 AI123416 227591_at AM 23416 — — -2.29 2.47E-04 ANK2 202921_s_at NM_001148 NM_001148 287 -2.29 7.41 E-03 CKMT1 1561155 at W76548 NM_020977 NM 020990 1159 -2.28 6.30E-03 CFC1 223753 s at AF312769 NM_032545 55997 -2.27 1.79E-03 BF111884 230491_at BF111884 — — -2.27 8.21 E-06 SEC31L1 1556416_s_at AF086242 NM 014933 22872 -2.27 7.06E-05 SCN2A2 206381 at NM_021007 NM 016211 NM 021007 6326 -2.26 6.33E-06 PLEKHA5 237483_at AI990790 NM_019012 54477 -2.25 8.37E-03 EDG7 231192_at AW274018 NM 012152 23566 -2.24 1.41 E-03 DTNA 240125_at AI697494 NM 001390 1837 -2.23 6.58E-03 AF085937 1558695 at AF085937 NM_001391 NM_001392 NM_032975 NM 032978 NM_032979 NM_032980 NM_032981 -2.22 8.05E-03 AI394334 232696_at AI394334 — — -2.22 2.96 E-03 UCN 206072_at NM 003353 NM_003353 7349 -2.22 5.09E-07 DRD1IP 219896 at NM 015722 NM_015722 50632 -2.22 1.17E-04 AA412686 244608 at AA412686 — — -2.21 3.65E-03 TSAP6 218424_s_at NM_018234 NM_00100841 Λ 55240 -2.21 8.31 E-05 LOC201158 1560776_at AU121725 U NM 018234 NM 182915 NM 145301 201158 -2.21 7.37E-04 LAF4 244696 at AI033582 NM_002285 3899 -2.21 6.82 E-03 S100A6 217728_at NM 014624 NM 014624 6277 -2.20 8.83E-05 BACH 2 236307 at AA085906 NM_021813 60468 -2.20 2.30E-03 KIAA1102 241459_at AI494113 NM 014988 22998 -2.20 4.06E-03 COL5A1 212488 at N30339 NM 000093 1289 -2.20 4.18E-06 ENOSF1 213645 at AF305057 NM_017512 55556 -2.19 2.12E-04 LOC158863 232179_at AL110203 — 158863 -2.19 1.08E-05 278 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B„ et al„ Cells Useful for Immuno-Based BoNT/A Activity Assays ECEL1 219914_at NM_004826 NM_004826 9427 -2.19 1.99E-03 C21orf4 222907 x at BC000569 NM 006134 757 -2.18 3.97E-04 SMYD2 233713 at AK022181 NM 020197 56950 -2.18 6.04E-04 PDZK6 228946_at AW150229 NM_015693 27152 -2.18 3.60E-04 C21orf4 225182 at AL355685 NM_006134 757 -2.17 1.19E-03 AA601031 228919 at AA601031 — ... -2.17 3.77E-03 N95363 213183_s_at N95363 — ... -2.17 3.77E-04 ARHGAP9 226906_s_at AL548053 NM_032496 64333 -2.17 9.12E-04 ZNF395 222536 s at N36098 NM_018660 55893 -2.16 4.88E-03 FLJ12671 233728_at AU148213 NM_030980 81875 -2.16 8.06E-04 AU146864 232659 at AU146864 — ... -2.16 2.93E-04 SERPINE1 202628_s_at NM 000602 NM 000602 5054 -2.14 2.61 E-05 TYRP1 242893_at AW195492 NM_000550 7306 -2.14 1.35E-03 SLC33A1 1559232 a at BC029450 NM_004733 9197 -2.14 4.34E-03 AI695695 242051_at AI695695 — ... -2.13 1.12E-03 HRK 206864_s_at NM 003806 NM 003806 8739 -2.12 4.70E-03 RLF 241438_at AI742686 NM 012421 6018 -2.12 4.81 E-03 CUL3 237376 at BF115815 NM_003590 8452 -2.11 9.56E-06 BG704082 1556216_s_at BG704082 — — -2.11 1.16E-03 AI968130 240327_at AI968130 NM_015129 NM 145799 NM 145800 NM_145802 23157 -2.11 3.06E-04 CNGA3 207261_at NM_001298 NM_001298 1261 -2.11 6.85E-04 AI803010 239503_at AI803010 — — -2.11 1.53E-03 N73550 244112 x at N73550 — — -2.10 2.68E-03 BF110426 243237_at BF110426 XM_114222 200373 -2.10 4.35E-04 BM977131 1557478_at BM977131 — — -2.10 2.99E-03 AV685992 241376_at AV685992 — — -2.09 4.64E-03 PAN3 239393 at AW510927 NM 175854 255967 -2.08 1.36E-04 VEGF 210513_s_at AF091352 NM_003376 7422 -2.08 7.20E-03 BDKRB2 205870_at NM 000623 NM_000623 624 -2.08 2.97E-03 ZNF395 218149 s at NM 017606 NM 018660 55893 -2.07 6.79E-04 DEPDC6 218858 at NM 022783 NM_022783 64798 -2.06 5.34E-04 EVER1 214958_s_at AK021738 NM007267 11322 -2.06 2.91 E-03 LUC7L2 242024_at T90999 NM 016019 51631 -2.06 2.82 E-03 KIAA0804 1559500_at BC036005 NM 00100992 1 NM 015303 23355 -2.06 1.55E-05 FOXP4 ASCC2 229763_at BE504097 NM 032204 NM 138457 116113 84164 -2.05 6.69E-05 ATF5 204998 s at NM 012068 NM_012068 22809 -2.05 1.57E-03 AA452540 232411_at AA452540 — — -2.04 3.30E-03 FNBP1 230389 at BE046511 NM_015033 23048 -2.04 1.05E-03 AU144437 232887 at AU144437 — — -2.04 2.07E-03 IDS 1569315_s_at BC032484 NM_000202 NM_006123 3423 -2.03 1.16E-03 CSTB 236449_at AI885390 NM_000100 1476 -2.03 8.87E-05 IGF2 210881_s_at M17863 NM~000612 3481 -2.03 1.78E-04 LOC51315 222585_x_at BE326678 NM_016618 51315 -2.03 7.77E-03 TRIM66 213748_at AW271713 XM_084529 9866 -2.02 8.91 E-03 AA705933 239866_at AA705933 — — -2.02 3.47E-04 AI691075 229728 at AI691075 ... ... -2.02 7.84 E-03 HIST1H2AE 214469_at NM_021052 NM_021052 3012 -2.02 1.08E-06 LOC402617 241353_s_at AW471181 XM 380151 402617 -2.02 4.90E-04 SERPINE1 202627_s_at AL574210 NM 000602 5054 -2.01 9.89E-06 SND1 228271 at AW001186 NM_014390 27044 -2.01 5.63E-03 MIG-6 224657 at AL034417 NM 018948 54206 -2.01 2.57E-04 279 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays NM 015583 208015_at NM_015583 — — -2.01 1.80E-04 SMYD2 212921_at AF070592 NM 020197 56950 -2.01 1.62E-06 S100A4 203186_s_at NM_002961 NM 002961 6275 -2.01 6.07E-04 HIST2H2AA 214290_s_at AI313324 NMJ319554 NM_003516 8337 -2.01 7.64E-04 LOC360030 236404_at AW197320 — 360030 -2.01 7.91 E-03 AL119491 244292_at AL119491 ... ... -2.00 8.84E-03 FNBP1 230086_at AA937109 NM_015033 23048 -2.00 6.01 E-03 LGALS3 208949_s_at BC001120 NM_002306 3958 -1.99 1.10E-03 GALIG CPEB4 242384_at AI452469 NM_194327 NM_030627 81625 80315 -1.99 8.34E-03 AA278901 244055_at AA278901 — ... -1.99 1.31E-04 NSMAF 232148_at BF056507 NM_003580 8439 -1.98 6.51E-03 HIST3H2A 221582_at BC001193 NM 033445 92815 -1.98 3.01 E-04 FLJ21657 1557828 a at BE675061 NM 022483 64417 -1.98 5.30E-03 EVER1 230526_at BF515959 NM_007267 11322 -1.98 5.20E-08 SLITRK3 206732_at NM_014926 NM_014926 22865 -1.97 7.66E-05 AW973410 244310_at AW973410 XM 498613 440283 -1.97 3.35E-03 ZC3HDC1 218543_s_at NM_022750 NM 022750 64761 -1.97 2.63E-03 GPR18 244791_at AA835936 NM 005292 2841 -1.97 1.52E-03 LOC283666 226682_at AW006185 — 283666 -1.96 1.61 E-04 DUSP5 209457_at U16996 NM_004419 1847 -1.96 3.92E-06 AL048861 1559148_at AL048861 — — -1.96 2.90E-03 PKD2 240370_at AI432451 NM_000297 5311 -1.96 3.38E-04 AI963079 236411_at AI963079 — — -1.96 1.65E-03 AI758408 227235 at AI758408 — — -1.96 1.28E-03 R63578 242818 x at R63578 ... ... -1.95 2.36E-03 AW189467 230183_at AW189467 ... ... -1.95 3.15E-03 PNMA3 223621_at AL136878 NM_013364 29944 -1.95 4.80E-07 LOC286411 1557133_at AV753446 — 286411 -1.94 4.84E-04 RHOQ 1559582_at BC033251 NM_012249 23433 -1.93 1.51 E-03 AI817960 239649_at AI817960 — — -1.93 8.93E-03 FLJ10359 232414_at AA827672 XM 375853 55127 -1.92 2.24E-04 C16orf45 239971 at AI298297 NM_033201 89927 -1.92 5.46E-03 MGC29875 220251_at NM 024998 NM_014388 27042 -1.92 3.38E-03 FLJ10159 1563906_at AK090879 — 55084 -1.92 4.66E-03 FLJ10159 236602_at AA833813 — 55084 -1.92 2.30E-04 FAT4 219427 at NM_024582 NM_024582 79633 -1.92 5.03E-03 MGC45477 1554250 s at BC033812 — 387277 -1.92 2.59E-03 ARMCX4 1552327_at NM_152583 NM_152583 158947 -1.91 9.32E-07 IGF2 202410_x_at NM_000612 NM_000612 3481 -1.91 1.38E-04 PRR3 244204 at W87300 NM 025263 80742 -1.91 2.49E-03 FLJ20152 218510_x_at AI816291 NM_019000 54463 -1.90 5.85E-04 PCBD2 240846_at BF223271 NM_032151 84105 -1.90 3.18E-05 C6orf198 227834_at AL589605 XM_371849 167838 -1.90 5.03E-03 MTX3 237681_at AA699464 NM_001010891 345778 -1.89 3.91 E-03 BF514509 239049_at BF514509 — — -1.89 9.85E-04 C6orf148 237347_at AL039379 NM 030568 80759 -1.89 9.86E-05 KIAA1904 1559072_a_at BC032083 NM 052906 114794 -1.88 2.81 E-04 C6orf154 235935_at AI539370 XM 168060 221424 -1.88 2.76E-04 ATP2B3 242036_x_at H09073 NM_00100134 492 -1.88 2.12E-05 BF433341 235977 at BF433341 NM_021949 -1.88 2.48E-05 TMP21 239851_at AW629289 NM 006827 10972 -1.88 5.43E-04 GFM1 232295_at AK000780 NM 024996 85476 -1.88 3.27E-03 AAK1 214956 at AF090101 NM_014911 22848 -1.87 3.23E-03 LOC283439 238636_at BG430061 — 283439 -1.87 2.24E-03 280 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays FTHFSDC1 240552_at AA811452 NM_015440 25902 -1.87 1.82E-03 A W296421 230064_at AW296421 — — -1.87 6.51 E-03 PAPPA 240295_at AL045014 NM_002581 5069 -1.87 7.85E-05 LOC55831 215250_at AU147317 NM_018447 55831 -1.87 3.85E-03 LOC253982 238142_at AW029203 NM_181718 NM 198907 253982 -1.86 8.13E-03 NKTR 243055_at BF514072 NM_005385 4820 -1.86 2.53E-03 AW294722 240246_at AW294722 — ... -1.86 7.82E-03 AK023394 232107_at AK023394 — — -1.86 4.70E-05 VPS13C 235023_at AA828371 NM_017684 54832 -1.85 5.51 E-03 RHBDL1 207383_s_at NM 003961 NM 003961 9028 -1.85 1.70E-04 C21orf4 219600_s_at NM_006134 NM_006134 757 -1.85 1.43E-03 TPM3 238079_at AV713323 NM_152263 NM 153649 7170 -1.85 1.29E-03 BACE2 217867_x_at NM_012105 NM 012105 NM 138991 NM_138992 25825 -1.85 1.57E-03 VEGF 212171 x at H95344 NM 003376 7422 -1.84 1.68E-03 ID2 213931_at AI819238 NM 002166 3398 -1.84 3.39E-03 LOC51315 218303_x_at NM_016618 NM 016618 51315 -1.84 5.97E-03 TMIE 1553601_a_at NM_147196 NMJ47196 259236 -1.83 8.89E-04 TM4SF2 234245_at AL162055 NM_004615 7102 -1.83 7.61 E-03 FADS3 216080 s at AC004770 NM 021727 3995 -1.83 1.05E-04 SNF1LK 208078_s_at NM 030751 NM_173354 150094 -1.83 2.37E-03 FGD5 226985_at AW269340 NM 152536 152273 -1.83 1.69E-03 ATP2B3 207026_s_at NM_021949 NM_00100134 4 NM_021949 492 -1.83 1.63E-04 LOC51315 233329_s_at AK025986 NM_016618 51315 -1.83 5.27E-03 FLJ00310 1569664 at BC035915 XM 496691 375010 -1.82 5.02E-04 FNBP1 244286 at AI017983 NM_015033 23048 -1.82 1.10E-03 ASAM 228082 at BF056275 NM 024769 79827 -1.82 4.85E-03 VN1R1 221412_at NM 020633 NM_020633 57191 -1.82 4.74E-05 LOC124220 228058 at AI559190 NM 145252 124220 -1.82 5.52E-05 FLJ23754 1553248_at NM_152675 NM_152675 201252 -1.81 6.36E-03 HSD17B1 205829_at NM_000413 NM_000413 3292 -1.81 5.39E-05 ZNF407 233239_at AK024882 NM_017757 55628 -1.81 4.86E-03 ARTS-1 209788_s_at AF183569 NM 016442 51752 -1.81 5.75E-03 GBE1 203282_at NM_000158 NM_000158 2632 -1.81 2.17E-03 LONP 221834_at AV700132 NM_031490 83752 -1.81 7.26E-03 SFXN3 217226_s_at M95929 NM_030971 81855 -1.80 4.81 E-04 AK021973 234098 at AK021973 — — -1.80 1.25E-03 AA682539 235575_at AA682539 ... ... -1.80 5.79E-03 AI950023 244433_at AI950023 — — -1.80 3.52E-03 C13orf22 1562238_at AL832776 NM_005800 10208 -1.80 5.58E-04 AI828075 230795 at AI828075 — — -1.79 7.39E-05 AW172407 240908_at AW172407 XM 373053 391733 -1.79 1.54E-03 ARG2 203946 s at U75667 NM_001172 384 -1.79 8.38E-05 AI582773 214373 at AI582773 XM 498956 440996 -1.79 6.73E-03 C1orf21 221272 s at NM 030806 NM_030806 81563 -1.79 1.58E-06 BF431902 228469_at BF431902 — ... -1.79 8.24E-03 AI732874 241314_at AI732874 — — -1.79 6.26E-03 AI521273 241702 at AI521273 — — -1.79 2.16E-03 SFXN3 220974 x at NM 030971 NM_030971 81855 -1.78 5.28E-05 AA394039 229720_at AA394039 — ... -1.78 3.12E-04 AI765607 244631_at AI765607 XM 374318 389834 -1.78 7.00E-03 PHACTR1 238297 at AI884781 NM_030948 221692 -1.78 6.75E-03 BF000047 235736_at BF000047 — — -1.78 2.66E-03 281 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., etal., Cells Useful for Immuno-Based BoNT/A Activity Assays PPP1R7 1559054_a_at BC027905 NM_002712 5510 -1.78 8.88E-04 SRP54 1557504_at AI076351 NM_003136 6729 -1.77 3.30E-03 MLLT2 237006_at AA703523 NM 005935 4299 -1.77 1.07E-03 KIAA1276 235288_at AI627532 XM_039169 27146 -1.77 3.48E-04 LOC360030 1565804_at AK025161 — 360030 -1.77 7.53E-03 PAQR6 219236_at NM_024897 NM 024897 NM_198406 79957 -1.77 1.41E-03 KIAA2024 1566166_at AL833423 NM_172070 130507 -1.77 1.09E-03 FLJ20152 218532_s_at NM_019000 NM_019000 54463 -1.77 2.47E-03 ZAP128 202982_s_at NM_006821 NM_006821 10965 -1.77 2.18E-03 AM50690 228466 at AM 50690 — — -1.76 1.91E-03 AK098781 1560814_a_at AK098781 — — -1.76 9.35E-06 FLJ11267 220216_at NM 019607 NM 019607 56260 -1.76 2.56E-03 CPEB1 219578_s_at NM 030594 NM_030594 64506 -1.76 3.75E-03 NIT1 202891 at NM 005600 NM 005600 4817 -1.76 4.55E-04 ZDHHC11 221646_s_at AF267859 NM_024786 79844 -1.76 1.39E-04 LASS5 1556783_a_at AF088003 NM_147190 91012 -1.76 4.78E-03 FLJ13231 1562387_at BU189724 NM 023073 65250 -1.76 4.71 E-03 GNRHR 1568661 at BC039430 NM 000406 2798 -1.76 1.78E-03 MDH1B 1558077_s_at BG202523 NM_206892 130752 -1.75 2.90E-03 HIST1H3E 214616_at NM_003532 NM_003532 8353 -1.75 2.78E-05 PHLDA2 209803_s_at AF001294 NM_003311 7262 -1.75 1.03E-03 GRM3 240004_at BF436080 NM 000840 2913 -1.74 5.05E-03 ABU 238563_at AV762916 NM_005470 10006 -1.74 2.03E-03 RAB11FIP3 1563104_at BC009036 NM 014700 9727 -1.74 2.52E-03 C6orf52 236504 x at BE670432 XM_371798 347744 -1.74 5.49E-03 AV658469 244699 at AV658469 ... ... -1.74 6.93E-07 PLXNC1 206470_at NM_005761 NM_005761 10154 -1.74 1.25E-03 NTNG2 233072_at AI348745 NM 032536 84628 -1.74 2.30E-03 AMH 206516_at NM 000479 NM_000479 268 -1.73 4.35E-04 AI814750 1565692 at AI814750 — — -1.73 7.35E-03 NAG8 210109_at AF191492 NM 014411 27099 -1.73 8.58E-04 PLXNC1 206471_s_at NM 005761 NM_005761 10154 -1.73 1.82E-03 LOC283861 1554520 at BC009880 — 283861 -1.73 1.36E-03 HNRPM 230392_at AW298141 NM_005968 NM_031203 4670 -1.72 2.74E-04 AI802997 235211_at AI802997 — — -1.72 4.84E-03 APOC1 204416 x at NM 001645 NM 001645 341 -1.72 7.65E-05 ADCY1 213245 at AL120173 NM_021116 107 -1.71 4.24E-03 AF131805 233581_at AF 131805 — ... -1.71 2.73E-04 B3GNT5 225612_s_at BE672260 NM 032047 84002 -1.71 9.32E-03 ANK2 202920_at BF726212 NM 001148 NM_020977 287 -1.71 6.21 E-03 TTC3 1569472_s_at BC026260 NM_00100189 4 NM 003316 7267 -1.71 1.33E-03 HSPD1 241716_at BF965447 NM_002156 NM_199440 3329 -1.71 1.25E-04 RHOU 223168_at AL096776 NM_021205 58480 -1.71 1.77E-05 AI733281 239994 at AI733281 — — -1.71 1.76E-03 BC015455 1569724_at BC015455 ... ... -1.71 1.78E-04 RGS16 209324_s_at BF304996 NM_002928 6004 -1.71 4.44E-03 LOC285535 229130_at AU145323 — 285535 -1.71 3.49E-03 PDIP 206691 s at NM 006849 NM 006849 64714 -1.71 2.28E-08 BE221330 241624_at BE221330 XM_374318 389834 -1.71 4.44E-03 BF434212 237942_at BF434212 — — -1.71 2.50E-03 FLJ14966 243611 at BG231646 NM_032867 84953 -1.71 4.23E-03 MGC10850 223707_at BC004284 — 84736 -1.71 9.45E-04 282 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays H15900 239833_at H15900 ... ... -1.71 4.92E-05 SPPL3 1566897_at AL834399 NM_139015 121665 -1.71 1.54E-04 LOC256273 229466 at AU144187 — 256273 -1.70 7.69E-03 AI288679 242969_at AI288679 ... — -1.70 1.70E-04 LOC400988 230941_at AI651340 XM_379112 400988 -1.70 2.26E-05 MY015B 227743_at AI671062 XR_000222 80022 -1.70 5.37E-03 FLJ10159 229034_at BF511724 — 55084 -1.70 1.89E-03 ZNF42 40569_at M58297 NM_003422 NM_198055 7593 -1.70 8.99E-05 TMP21 238886_at BF056141 NM 006827 10972 -1.70 3.75E-03 CAMK2B 209956_s_at U23460 NM_001220 NM_172078 NM_172079 NM_172080 NM 172081 NM_172082 NM_172083 NM 172084 816 -1.69 2.99E-03 SCFD1 233229_at AU147042 NM 016106 NM_182835 23256 -1.69 1.27E-04 ERMAP 219905_at NM_018538 NM_018538 114625 -1.69 9.14E-06 AM 90292 240190_at AH 90292 — — -1.69 6.34E-04 VEGF 210512 s at AF022375 NM_003376 7422 -1.69 7.38E-04 DNAJB11 223054_at BC001144 NM 016306 51726 -1.69 6.40E-03 LOC401320 239313_at AI803568 XM_379482 XM_380098 401320 -1.69 6.47E-03 AL359574 234588_at AL359574 — — -1.68 5.27E-03 GOPC 236862_at AA279958 NM 020399 57120 -1.68 4.91 E-05 MAP3K5 203836_s_at D84476 NM_005923 4217 -1.68 3.70E-04 AW118878 230736_at AW118878 XM 373451 387647 -1.68 2.03E-04 SLC7A1 215401 at AU147698 NM 003045 6541 -1.68 3.38E-03 PDE4DIP 244511_at AV700591 NM_00100281 0 NM 00100281 1 NM_00100281 2 NM 014644 NM_022359 9659 -1.68 1.87E-04 BLCAP 1557521 a at AA653638 NM_006698 10904 -1.68 7.83E-03 PNCK 229411 at AI986390 NM 198452 139728 -1.68 1.49E-08 TUSC3 232770_at AK026149 NM_006765 NM_178234 7991 -1.67 3.31 E-04 FBXW7 222729_at BE551877 NM_018315 NM 033632 55294 -1.67 6.18E-06 1KFZP564O046 220843_s_at NM 014156 NM 015420 25879 -1.67 4.38E-03 FYN 243006_at BG222258 NM_002037 NM_153047 NM_153048 2534 -1.67 1.63E-03 PDGFA 205463_s_at NM_002607 ... 5154 -1.67 1.01E-03 ST7L 216123_x_at AK024158 NM_017744 NM_138727 NM 138728 NM_138729 NM_198327 NM_198328 54879 -1.67 2.23E-03 ZNF42 204138_s_at AI762174 NM_003422 NM 198055 7593 -1.67 1.08E-03 283 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays FNBP1 239453_at AA262084 NM 015033 23048 -1.67 5.15E-04 GNAS 214157_at AA401492 NM 000516 NM 016592 NM_080425 NM 080426 2778 -1.67 1.44E-03 BRD4 232551_at AA521443 NM 014299 NM_058243 23476 -1.67 8.62E-04 FLJ10287 232489_at AK001149 NM_019083 54482 -1.67 4.17E-03 TRIM2 214249_at AK000179 NM_015271 23321 -1.66 3.49E-03 AK021423 232890_at AK021423 ... — -1.66 1.20E-03 FARSLB 223036_at D84430 NM 005687 10056 -1.66 2.56E-03 BE891071 1569147_at BE891071 XM_496749 441078 -1.66 2.82E-03 PRKACB 235780_at BE622723 NM_002731 NM 182948 NM 207578 5567 -1.66 3.63E-04 SLC35D3 231341_at BE670584 NM_001008783 340146 -1.66 8.93E-03 N92599 241421_at N92599 — — -1.66 2.32E-03 DR1 227074_at AA524669 NM 001938 1810 -1.66 1.72E-03 KIAA0657 227573_s_at BF446688 XM 051017 23363 -1.66 3.36E-03 SLC01A2 207308_at NM 021094 NM 005075 NM 021094 NM_134431 6579 -1.65 5.88E-03 HNRPD 236000_s_at AA863112 NM_00100381 0 NM_002138 NM 031369 NM_031370 3184 -1.65 1.29E-03 LOC54103 222150_s_at AK026747 XM 379881 XM 499340 54103 -1.65 2.42E-03 RORA 1562529_s_at BC040965 NM_002943 NM_134260 NM_134261 NM_134262 6095 -1.65 6.52E-04 IUMRGE/M10(!UMRGE/M100i(-HUMRGE/M100! — — -1.65 3.90E-03 FLJ44958 229961_x_at AI871270 NM_198537 374887 -1.65 6.71 E-04 ARIH1 1558710_at BI791845 NM 005744 25820 -1.64 1.02E-03 GPX7 213170 at AA406605 NM 015696 2882 -1.64 8.64 E-04 ERBB4 206794 at NM_005235 NM_005235 2066 -1.64 1.93E-05 LOC57228 209679_s_at BC003379 NM 020467 57228 -1.64 4.85E-04 UBE2D3 233303_at AL110175 NM_003340 NM 181886 NM_181887 NM_181888 NM_181889 NM 181890 NM_181891 NM_181892 NM_181893 7323 -1.64 3.36E-03 AK000995 215349 at AK000995 — — -1.64 4.56E-03 N70015 236510_at N70015 — — -1.64 1.10E-03 BC031957 1565672_at BC031957 XM_498823 440703 -1.63 8.75E-03 FLJ36674 228482_at AV702789 NM 173622 284040 -1.63 1.14E-03 MGC43690 235576 at AW474542 NM_182552 253769 -1.63 3.31 E-12 AU153281 231937_at AU153281 — — -1.63 1.84E-05 AI807627 239734_at AI807627 — — -1.63 1.25E-03 SLC4A3 205918_at NM_005070 NM_005070 NM 201574 6508 -1.63 6.65E-04 NME5 206197_at NM 003551 NM 003551 8382 -1.63 2.24E-03 284 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays RGS16 209325_s at U94829 NM_002928 6004 -1.63 8.91 E-03 H46176 237083 at H46176 — — -1.62 2.84E-04 CDKN2A 207039_at NM_000077 NM 000077 NM_058195 NM_058197 1029 -1.62 4.13E-03 GLT25D2 209883_at AF288389 NM_015101 23127 -1.62 6.05E-05 BF002625 229530_at BF002625 — — -1.62 1 45E-03 RIPK1 209941_at U50062 NM_003804 8737 -1.62 6.97E-05 FLJ45880 228538_at BE671164 NM 207404 389114 -1.62 5.47E-06 LOC286161 228615_at AW291761 — 286161 -1.62 3.70E-03 FLJ32096 1555870 at AK056658 NM_173795 148646 -1.62 9.30E-03 NUP54 215213 at AU146949 NM_017426 53371 -1.61 3.52E-07 )KFZp313N062 1555906_s_at AM47556 NM 173826 285343 -1.61 1.21E-04 GO LG IN-67 213650_at AW006438 NM_015003 NM 181076 NM_181077 23015 -1.61 4.39E-03 AHI1 221569 at AL136797 NM_017651 54806 -1.61 1.18E-03 PLXNC1 213241_at AF035307 NM 005761 10154 -1.61 1.31 E-03 AMY2A 208498 s at NM 004038 NM_000699 279 -1.61 1.12E-05 C9orf41 1564690_at BC022435 NM_152420 138199 -1.60 3.52E-05 MGC29898 235259_at AA398590 NM_145048 133015 -1.60 1.34E-04 AV700050 228835 at AV700050 — — -1.60 3.88E-05 LGALS3BP 200923 at NM 005567 NM 005567 3959 -1.60 1 65E-06 CRYZL1 243091_at BF435599 NM_005111 NM_145311 NM 145858 9946 -1.60 1.91 E-03 ZDHHC11 1552283 s at NM 024786 NM 024786 79844 -1.60 2.31 E-05 CENTG2 233225_at AK000798 NM 014914 116987 -1.59 6.55E-03 CLCN3 240237_at H23230 NM 001829 NM_173872 1182 -1.59 6.03E-03 WASL 216094 at AK025323 NM_003941 8976 -1.59 7.27E-03 CDK3 229468 at AI885421 NM 001258 1018 -1.59 7.50E-06 PRKWNK1 216022_at AL049278 NM_018979 65125 -1.59 2.19E-03 CALR 214315 x at AI348935 NM_004343 811 -1.59 3.10E-03 NM_018289 219794_at NM_018289 — — -1.59 2.26E-07 LOC392790 243171 at AA570178 XMJ374751 392790 -1.58 5.98E-03 AA166617 230198_at AA166617 — — -1.58 3.03E-03 TP53BP1 1569098_s_at BU508386 NM 005657 7158 -1.58 5.76E-04 C21orf66 240105_at AI021902 NM_013329 NM 016631 NM_058191 NM_145328 94104 -1.58 4.09E-03 BC014200 1570061_at BC014200 — — -1.58 7.06E-05 KIAA1045 213636_at AB028968 XM_048592 23349 -1.57 2.94E-03 AK024175 222152 at AK024175 XM_373053 391733 -1.57 8.76E-03 DDHD1 231165_at BE857355 NM 030637 80821 -1.57 1.47E-03 DNAH5 243938_x_at AI872645 NM_001369 1767 -1.57 4.06 E-03 LSS 211018_at D63807 NM_00100143 8 NM_002340 4047 -1.57 2.49E-03 BC026294 1569510_at BC026294 — — -1.57 3.20E-06 FLJ32954 235349_at AI261321 NM_144713 151393 -1.57 7.97E-05 ISG20 33304 at U88964 NM 002201 3669 -1.56 1.82E-03 GPR89 1562412 at BC020562 NM_016334 51463 -1.56 5.13E-05 AL122039 234260_at AL122039 — — -1.56 3.46E-03 ARSD 225280_x_at N51673 NM_001669 NM_009589 414 -1.56 3.54E-03 MKLN1 233219_at AK023427 NM_013255 4289 -1.56 7.04E-03 285 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays LOC91526 228471_at AA744636 NM 153697 91526 -1.56 1.49E-03 PKD1 216949_s_at L39891 NM 000296 NM_00100994 A 5310 -1.56 4.32E-05 FLJ12666 215029_at AL117451 4 NM_024595 79647 -1.56 2.57E-03 BF512871 240174_at BF512871 XM 373962 388903 -1.55 2.49E-04 MGC13098 222208_s_at W07700 XMJ379817 XM499280 84820 -1.55 3.85E-03 AI271434 243668_at AI271434 — — -1.55 7.05E-03 CCPG1 221511_x_at AB033080 NM 004748 NM_020739 9236 -1.55 8.33E-03 ENOSF1 204143_s_at NM_017512 NM_017512 55556 -1.55 5.87E-03 ARG2 203945_at NM 001172 NM_001172 384 -1.55 3.00E-03 AA583038 238498_at AA583038 — — -1.55 5.09E-04 BG548427 235547_at BG548427 — — -1.55 1.16E-03 LOC338620 230930_at AI435839 ... 338620 -1.55 3.00E-03 LOC286208 1560089_at AL833509 XM_379668 286208 -1.54 2.16E-03 AA504346 242170 at AA504346 — — -1.54 7.12E-03 T77543 237530 at T77543 — ... -1.54 9.66E-04 MLSTD1 1557224_at BM682057 NM 018099 55711 -1.54 4.35E-03 SIGIRR 52940_at AA085764 NM 021805 59307 -1.54 4.74E-03 T91323 241093_at T91323 NM_015129 NM 145799 NM_145800 NM_145802 23157 -1.54 8.22E-03 GRM8 1556800 a at BC041397 NM 000845 2918 -1.54 5.54E-05 ILK 235906 at BE962235 NM_004517 3611 -1.54 5.88E-04 LOC284408 1558809_s_at AK094324 — 284408 -1.53 2.05E-03 PTPN23 1569104_a_at BE646227 NM_015466 25930 -1.53 9.23E-04 N36832 226396 at N36832 — — -1.53 1.87E-03 CALR 212953 x at BE251303 NM_004343 811 -1.53 1.01E-03 HIST1H2BN 239041 at AV747226 NM 003520 8341 -1.53 9.40E-03 KLF6 211610_at U51869 NM 00100849 0 NM_001300 1316 -1.53 7.45E-04 TTC17 232323_s_at AK026217 NM_018259 55761 -1.53 2.27E-05 HBS1L 209315_at AW297143 NM_006620 10767 -1.53 3.94E-03 AK024879 216751 at AK024879 — — -1.53 7.76E-03 WDFY3 238660_at AI732512 NM 014991 NM 178583 NM 178585 23001 -1.53 4.22E-05 FLJ20719 230712_at AI634549 XM 373827 55672 -1.52 3.20E-03 FLJ43663 243716_at Al 140617 XM 379520 XM_380146 378805 -1.52 8.90E-03 AKAP9 215483_at AK000270 NM 005751 NM_147166 NM_147171 NM_147185 10142 -1.52 1.39E-03 AL572553 241395 at AL572553 — — -1.52 4.62E-03 ZNF24 242210_at AA749167 NM_006965 7572 -1.52 5.33E-03 BE503598 1557658_at BE503598 — ... -1.52 5.96E-04 LOC440078 1570397_x_at BC034777 XM_498534 440078 -1.52 1.46E-03 BLZF1 1558560_s_at AI002966 NM_003666 8548 -1.51 3.05E-08 KCNK3 235108 at BG105700 NM_002246 3777 -1.51 1.92E-03 EVER1 204328_at NM 007267 NM 007267 11322 -1.51 7.60E-03 LOC285989 235231_at AI355709 NM_213603 285989 -1.51 9.23E-03 AW665096 214188_at AW665096 — — -1.51 1.36E-03 LTBP3 219922_s_at NM 021070 NM_021070 4054 -1.51 8.21 E-06 286 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays H2BFS 208579_x_at NM_017445 NM_017445 54145 -1.51 3.28E-04 PGAP1 220576_at NM_024989 NM 024989 80055 -1.51 4.78E-04 ACTN4 232058 at AU158358 NM 004924 81 -1.51 6.69E-03 FGD5 226984_at H09596 NM_152536 152273 -1.50 8.21 E-03 HPCAL4 219671_at AL136591 NM_016257 51440 -1.50 7.58E-05 ZNF395 232694_at AK021850 NM 018660 55893 -1.50 1 30E-05 RBM25 1557081_at AA580691 NM_021239 58517 -1.50 1.01 E-03 HPCAL1 205462_s_at NM_002149 NM_002149 NM_134421 3241 -1.50 9.84E-04 KIAA0657 227574_at BF446688 XM_051017 23363 -1.50 3.00E-03 LOC441168 229390 at AV734646 XM_496823 441168 -1.49 9.36E-03 AW241864 214353_at AW241864 — ... -1.49 4.23E-03 PTPRN 204945_at NM 002846 NM_002846 5798 -1.49 4.07E-04 N75937 240072_at N75937 — — -1.49 2.94E-03 FLJ10404 243047 at AV698751 NM 019057 54540 -1.48 2.74E-03 LOC400729 LOC440745 243021_at AI344101 XM 378824 XM_498840 400729 440745 -1.48 9.58E-03 AV709727 225996_at AV709727 — — -1.48 1.09E-03 AU159412 216029 at AU159412 — ... -1.48 8.93E-03 AU146999 215986_at AU146999 — ... -1.48 7.62E-05 MAP3K5 203837_at NM_005923 NM_005923 4217 -1.48 5.81 E-04 AW300500 228907_at AW300500 — — -1.48 3.51 E-04 SORCS1 228194_s_at AI675836 NM 052918 114815 -1.48 9.87E-06 UBE2D3 242403_at AI459177 NM_003340 NM_181886 NM 181887 NM_181888 NM 181889 NM_181890 NM 181891 NM_181892 NM181893 7323 -1.48 3.32E-04 CDK3 207188_at NM 001258 NM 001258 1018 -1.48 1.93E-05 UBE2D3 240383_at AI239832 NM 003340 NM_181886 NM_181887 NM 181888 NM 181889 NM_181890 NM 181891 NM 181892 NM 181893 7323 -1.48 1.55E-03 PRKACB 202741_at AA130247 NM_002731 NM_182948 NM_207578 5567 -1.47 3.58E-03 AA868193 244031 at AA868193 — ... -1.47 1.71 E-03 RCN1 201063_at NM_002901 NM 002901 5954 -1.47 7.39E-03 FLJ10378 242153_at AW264125 NM_018078 NM 032239 NM_178043 55132 -1.47 7.26E-03 THRAP2 216109_at AK025348 NM 015335 23389 -1.47 2.04E-04 HIAT1 242374_at AA747563 NM_033055 64645 -1.47 2.87E-03 BE552011 230208_at BE552011 — ... -1.47 1.34E-04 BG396868 1559957_a_at BG396868 — ... -1.47 8.59E-04 SMURF2 241900_at AW195928 NM_022739 64750 -1.47 3.53E-05 SERP1 235475_at AI580135 NM_014445 27230 -1.47 1.72E-03 BF347758 240222 at BF347758 — — -1.47 2.67E-04 287 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et at., Cells Useful for Immuno-Based BoNT/A Activity Assays CAMK2B 210404_x_at AF078803 NM_001220 NM 172078 NM 172079 NM_172080 NM_172081 NM 172082 NM 172083 NM_172084 816 -1.47 1.61E-03 MY09A 242512_at AI382029 NM_006901 4649 -1.47 5.15E-03 AKNA 225701_at AK024431 NM 030767 80709 -1.47 5.81 E-03 GPM6B 240286_at AL041745 NM_00100199 4 NM_00100199 5 NM 00100199 6 NM 005278 2824 -1.46 1.79E-03 STK4 223746 at BC005231 NM_006282 6789 -1.46 1.31E-04 BG178274 214757 at BG178274 — ... -1.46 2.61 E-04 AW015870 240352_at AW015870 — ... -1.46 3.79E-05 C21orf66 239407_at AI793248 NM 013329 NM_016631 NM_058191 NM_145328 94104 -1.46 4.76E-03 KIN 236887_at AA768850 NM 012311 22944 -1.46 5.23E-03 PCNXL2 229202_at AI768826 NM 014801 NM_024938 80003 -1.46 6.03E-04 KCNQ2 205737_at NM_004518 NM 004518 NM 172106 NM 172107 NM_172108 NM_172109 3785 -1.46 2.13E-04 C2orf17 222129_at AK026155 NM 024293 79137 -1.46 1.21 E-03 FBXW7 218751_s_at NM_018315 NM 018315 NM_033632 55294 -1.46 1.23E-07 U20648 216677_at U20648 — ... -1.46 7.32E-05 AGPAT3 223184_s_at BC004219 NM_020132 56894 -1.46 2.96E-03 ACYP2 206833 s at NM 001108 NM_138448 98 -1.46 1.16E-04 TTC17 224852_at BE964325 NM_018259 55761 -1.46 6.04E-05 FLJ10159 218974_at NM_018013 — 55084 -1.46 5.54E-04 ZNF160 239954_at AA701249 NM 033288 NM_198893 90338 -1.46 7.17E-03 SRP54 1557505_a_at AI076351 NM_003136 6729 -1.45 1.01 E-03 AK023798 216838_at AK023798 — ... -1.45 5.04E-04 HMGB2 243368 at AI572938 NM 002129 3148 -1.45 8.71 E-03 UBE2J1 236528 at N64079 NM_016021 51465 -1.45 2.73E-03 <FZp313N062 226688_at AW003508 NM_173826 285343 -1.45 6.50E-03 GUCY1A3 221942_s_at AI719730 NM 000856 2982 -1.45 5.82E-05 LISCH7 208190_s_at NM_015925 NM 015925 NM_205834 NM_205835 51599 -1.45 2.12E-03 AM40531 1557812_a_at AI140531 — ... -1.45 6.90E-03 KIAA1276 227505_at N64630 XM_039169 27146 -1.45 1.75E-03 BC040287 1558605_at BC040287 ... ... -1.44 4.22E-03 AI800713 235122_at AI800713 ... ... -1.44 3.58E-04 BC033530 1560209_at BC033530 ... ... -1.44 1.67E-03 HLCS 207833 s at NM 000411 NM 000411 3141 -1.44 7.21 E-03 MCF2L 239636 at W74618 NM_024979 23263 -1.44 1.41 E-03 288 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays KIAA1276 233823_at AB033102 XM 039169 27146 -1.44 3.24E-04 OR7D2 1562337 at AK095468 NM 175883 162998 -1.44 7.48E-04 JAK2 1562031_at BC043187 NM 004972 3717 -1.44 4.16E-04 PSMB7 244801_at AI248671 NM_002799 5695 -1.44 4.98E-03 KIAA1411 233730_at AL078591 NM_020819 57579 -1.43 3.20E-05 AL530703 231882_at AL530703 XM 498570 440156 -1.43 5.81 E-04 FLJ32731 227564_at BF433005 XM_372038 138050 -1.43 7.92E-05 DUSP16 1563505_at AL833073 NM_030640 80824 -1.43 4.10E-05 MGC4171 219722_s_at NM_024307 NM_024307 79153 -1.43 5.72E-03 RGAG4 227823_at BE348679 XM_291322 340526 -1.43 3.08E-05 MGC15875 226783_at Al762154 NM 032921 NM_153373 85007 -1.43 1.81E-03 FIP1L1 233405_at AU155384 NM 030917 81608 -1.43 3.48E-03 PKD1 202328_s_at NM_000296 NM 000296 5310 -1.43 1.82 E-04 NM_00100994 4 CRYGS 223643_at AI762135 NM 017541 1427 -1.43 5.80E-03 MGC42174 244304 at AW129650 NM 152383 129563 -1.43 4.62E-03 OFD1 241751 at AW292752 NM 003611 8481 -1.42 4.86E-03 PHC3 233431_x_at AU148142 NM_024947 80012 -1.42 1.22E-03 AK022100 233406_at AK022100 — — -1.42 1.03E-03 PPARG 208510_s_at NM_015869 NM_005037 NM_015869 NM_138711 NM 138712 5468 -1.42 1.45E-03 CLCN3 201733_at AA902971 NM 001829 NM_173872 1182 -1.42 1.12E-03 AW043836 239423_at AW043836 — — -1.42 2.43E-03 AF086443 1560982_at AF086443 — — -1.42 2.70E-04 R05895 239512 at R05895 — — -1.42 2.11E-03 WDR45 209217_s_at BC000464 NM_007075 11152 -1.42 3.54E-03 BF512190 235406_x_at BF512190 — ... -1.41 1.37E-03 BE738279 242546_at BE738279 XM_498570 440156 -1.41 1.24E-03 AI929077 244818 at AI929077 — — -1.41 2.46E-03 T96555 243818_at T96555 ... ... -1.41 1.37E-03 DUSP16 1558739_at R30807 NM_030640 80824 -1.41 3.84 E-04 LOC389087 243647_at AI808306 XM 374028 389087 -1.41 9.78E-03 HIST1H2BE 208527 x at NM 003523 NM_003523 8344 -1.41 3.37E-05 AU155234 233289_at AU155234 — ... -1.41 2.99E-03 AI698684 1558626_at AI698684 — ... -1.40 3.33E-04 KIAA1102 1569208_a_at BC020895 NM_014988 22998 -1.40 4.93E-03 AW150212 1556038 at AW150212 — — -1.40 1.33E-03 ABCC5 226363_at BE550362 NM_005688 10057 -1.40 4.83E-05 FLJ13105 233083_at AV706915 XM_496701 80068 -1.40 1.72E-03 Al963605 230269_at AI963605 — — -1.40 1.31E-03 ACHE 205377_s_at AM 90022 NM 000665 NM_015831 43 -1.40 2.24E-04 WDR45 209216_at BC000464 NM 007075 11152 -1.39 3.52E-03 KIAA0804 239917_at R07848 NM 00100992 1 NM 015303 23355 -1.39 2.63E-03 SIAH1 232365_at BE676461 NM 00100661 0 NM_00100661 1 NM_003031 6477 -1.39 1.23E-03 MUC20 226622_at AW084511 NM_152673 200958 -1.39 3.06E-05 289 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays TGFB1I4 237673_at BE465103 NM_006022 8848 -1.39 2.34E-03 ZNF596 240324_at H50654 NM_183422 NM 173539 169270 -1.39 3.41 E-04 NOL3 1558738_at BU785956 NM_003946 8996 -1.39 1.03E-04 CRYGS 223644_s_at AF161703 NM 017541 1427 -1.38 8.43E-03 TSGA10 1555932_at AK094208 NM 025244 80705 -1.38 2.99E-03 MST1 216320_x_at U37055 NM_182911 NM_020998 4485 -1.38 1.28E-03 LOC440722 238503_at AI142850 XM_498831 440722 -1.38 8.92E-04 FLJ10707 239957_at AW510793 XM_371614 55209 -1.38 8.78E-03 SLC37A1 218928 s at NM 018964 NM 018964 54020 -1.38 1.97E-03 SMG1 244766_at BG180003 NM_014006 23049 -1.38 8.25E-03 KIAA0220 LOC440345 CENTG2 240758 at AA706753 NM_015092 XM_496125 NM_014914 283846 440345 116987 -1.38 8.21 E-03 VPS13C 232386_at AV703288 NM_017684 54832 -1.38 1.41 E-04 ZNF42 210336_x_at AF055078 NM_003422 7593 -1.38 7.52E-05 MCCC2 1560033_at AK090834 NM_198055 NM 022132 64087 -1.37 6.91 E-05 USP40 225089_at AA127740 NM 018218 55230 -1.37 9.95E-03 ZNF589 1569108_a_at BC028160 NM_016089 51385 -1.37 3.43E-03 CITED2 207980_s_at NM_006079 NM_006079 10370 -1.37 6.11 E-03 GAL 214240 at AL556409 NM 015973 51083 -1.37 2.81 E-03 RAGE 205130_at NM_014226 NM_014226 5891 -1.37 8.58E-03 AA516469 236375_at AA516469 — — -1.37 2.01 E-03 AI915861 1557348 at AI915861 — — -1.37 7.72E-04 AI861893 242888 at AI861893 — — -1.37 5.02E-03 EDNRA 243555_at AA573452 NM_001957 1909 -1.37 2.53E-03 C14orf92 232097_at AA657818 NM_014828 9878 -1.37 1.70E-03 LOC92482 232885 at AK021501 XM_378250 92482 -1.37 7.03E-04 KIAA0999 242920 at AW590838 NM 025164 23387 -1.37 7.90E-03 KCNK12 220448_at NM_022055 NM 022055 56660 -1.37 2.31 E-05 TGFB1I4 237745_at BE670165 NM 006022 8848 -1.37 1.15E-03 CDC2L5 242693_at AW664859 NM 183422 NM_003718 8621 -1.37 7.67E-03 ZNF42 204139_x_at NM_003422 NM_031267 NM_003422 7593 -1.36 1.36E-04 BRUNOL5 232416 at AL390161 NM 198055 NM_021938 60680 -1.36 9.03E-03 AKAP12 210517_s_at AB003476 NM_005100 9590 -1.36 3.29E-03 RGS12 1555022_at AF464736 NM_144497 NM 002926 6002 -1.36 1.77E-05 LOC401320 238540_at AA933883 NM_198227 NM_198229 NM_198230 NM 198430 NM_198432 NM 198587 XM 379482 401320 -1.36 1.06E-04 CUL4A 232466_at AU155661 XM 380098 NM_00100889 C 8451 -1.36 5.42E-03 SENP6 240016 at AW273732 O NM 003589 NM 015571 26054 -1.36 2.45E-03 NBR2 1553992_s_at BC034248 NM 005821 10230 -1.36 5.37E-03 TBC1D8 221592_at BC001663 NM 007063 11138 -1.36 4.54E-03 290 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., etal., Cells Useful for Immuno-Based BoNT/A Activity Assays MBNL1 1556658_a_at AA744622 NM_021038 NM 207292 NM_207293 NM_207294 NM_207295 NM_207296 NM 207297 4154 -1.35 6.66E-03 HIST2H2AA 218280_x_at NM_003516 NM_003516 8337 -1.35 5.61 E-04 HECTD1 242349_at AW275658 NM_015382 25831 -1.35 3.14E-05 CSGIcA-T 221799_at AB037823 NM 019015 54480 -1.35 9.13E-03 TD-60 243297 at AI498610 NM 018715 55920 -1.35 3.64E-05 AW117322 239415_at AW117322 XM_374094 389237 -1.35 5.46E-05 ERCC3 215545_at AK024185 NM_000122 2071 -1.35 7.55E-03 AW148862 235217_at AW148862 XM 380136 402582 -1.35 8.44E-03 NAP1L3 204749_at NM 004538 NM 004538 4675 -1.35 1.79E-04 HIST1H2BD 222067_x_at AL353759 NM 021063 NM_138720 3017 -1.34 1.71E-05 CITED2 209357 at AF109161 NM_006079 10370 -1.34 3.87E-03 NM 024914 220450_at NM 024914 — ... -1.34 5.65E-04 USP36 220370_s_at NM 025090 NM_025090 57602 -1.34 2.56E-03 ARMCX4 1564399_a_at AK096955 NM_152583 158947 -1.34 8.99E-04 GOLGA4 215203_at AW438464 NM_002078 2803 -1.34 1 95E-03 R92984 231088 at R92984 — — -1.34 4.79E-04 LOC200030 LOC400781 AG1 242191_at AI701905 NM_183372 XM_371384 XM 378897 XM_496394 200030 400781 440673 -1.34 1.70E-03 USP40 225085_at AA522888 NM_018218 55230 -1.34 5.51 E-03 AK026429 233038_at AK026429 — — -1.34 8.07E-03 AW977516 235172_at AW977516 ... — -1.33 1.91 E-03 AK023334 232975_at AK023334 — ... -1.33 3.06E-03 CPSF6 238651_at BF512491 NM_007007 11052 -1.33 2.21 E-03 LOC158301 239193_at BF060981 — 158301 -1.33 9.50E-03 TJP2 232017_at AK025185 NM_004817 NM_201629 9414 -1.33 4.30E-04 AW591282 231374_at AW591282 — — -1.33 1.30E-04 C21orf2 203995_at NM_004928 NM_004928 755 -1.33 2.28E-03 BF063821 230598 at BF063821 — — -1.33 2.29E-03 Al743452 237031_at Al743452 ... ... -1.33 6.25E-04 AI825068 239798_at AI825068 ... — -1.33 7.63E-03 SYVN1 225090_at AA844682 NM 032431 NM 172230 84447 -1.32 5.82E-03 FLJ32731 1557064_s_at AW328331 XMJ372038 138050 -1.32 3.89E-06 SLC12A7 218066_at NM_006598 NM_006598 10723 -1.32 7.75E-04 UBE2Q 231816_s_at AI986085 NM 017582 55585 -1.32 6.59E-03 GOLGI N-67 208797_s_at AI829170 NM 015003 NM_181076 NM_181077 23015 -1.32 1.73E-04 THRAP2 239561 at AA780679 NM 015335 23389 -1.32 1.91 E-03 PCDHB16 232099 at AB046841 NM_020957 57717 -1.32 2.25E-03 GPR123 239221_at AI884909 NM 032422 84435 -1.31 2.84E-03 C1orf21 223127_s_at AW003850 NM 030806 81563 -1.31 8.71 E-04 LOC54103 213142_x_at AV700415 XM 379881 XM_499340 54103 -1.31 2.15E-03 LOC90408 1560081_at AL702091 — 90408 -1.31 3.47E-04 HEMK1 1556092_s_at BQ025558 NM_016173 51409 -1.31 2.82E-03 AW294192 228040_at AW294192 — — -1.31 1.56E-03 ZNF207 1556035_s_at AI201248 NM_003457 7756 -1.31 6.92E-03 291 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al„ Cells Useful for Immuno-Based BoNT/A Activity Assays BU680365 1562497_at BU680365 — — -1.31 9.25E-03 MGC24132 1557991 _at AK057791 NM 152396 131965 -1.31 9.13E-04 CLCN3 201734_at AI760629 NM 001829 NM_173872 1182 -1.31 2.96E-03 PPIB 200968_s_at NM_000942 NM_000942 5479 -1.31 5.05E-03 MYNN 1566108 at AK056483 NM 018657 55892 -1.31 3.79E-03 MFN1 236417_at BE644770 NM_017927 NM_033540 55669 -1.31 5.74E-03 TTC17 224849_at AK023161 NM_018259 55761 -1.31 2.03E-04 HNRPD 229434_at AA865357 NM 00100381 0 NM 002138 NM_031369 NM_031370 3184 -1.30 4.38E-03 BE217923 228686 at BE217923 — — -1.30 1.31E-04 WDR11 229694__at BF062828 NM018117 55717 -1.30 5.51 E-03 AA703326 241863_x_at AA703326 — — -1.30 3.55E-03 ZNF117 235408 x at AW058673 NM 024498 7670 -1.30 8.70E-03 COL5A1 212489 at AI983428 NM 000093 1289 -1.30 8.41 E-03 AKAP12 241679_at AI672553 NM_005100 NM_144497 9590 -1.30 1.14E-03 DKFZp762K222 226822_at AL512713 NM_020225 56977 -1.30 1.52E-04 PTBP2 236962 at AA521018 NM 021190 58155 -1.30 3.82E-03 C7orf28B 215024_at AK000993 NM 198097 221960 -1.29 6.75E-04 EFHC1 225656_at Al564473 NM 018100 114327 -1.29 8.52E-03 KIAA1970 1568858 at BCO13247 NM 133451 124454 -1.29 1 47E-05 CAMK2B 211483_x_at AF081924 NM_001220 NM_172078 NM_172079 NM 172080 NM_172081 NM 172082 NM_172083 NM 172084 816 -1.29 6.21 E-03 LOC142678 226644_at BE222279 NMJ380875 142678 -1.29 4.59E-04 IGBP1 242337 at AI347128 NM 001551 3476 -1.29 4.53E-03 MAP7 202890 at AW242297 NM 003980 9053 -1.29 9.83E-04 AK3 230630_at Al566130 NM 00100535 3 NM_013410 NM_203464 205 -1.29 3.77E-03 AI434790 239070 at AI434790 — — -1.29 2.24E-04 CD302 203799 at NM_014880 NM_014880 9936 -1.29 1.51E-04 VPS13C 218396 at NM 017684 NM 017684 54832 -1.29 1.69E-04 CUL3 242362 at AI797788 NM_003590 8452 -1.29 3.18E-03 AW971123 236446 at AW971123 — — -1.28 3.31 E-03 FLJ13150 219504_s_at NM_024813 NM_024813 79871 -1.28 6.46E-06 EPAS1 230711_at AA777349 NM 001430 2034 -1.28 7.58E-03 LOC91526 226641_at AU157224 NM_153697 91526 -1.28 3.21 E-03 AW467480 236202_at AW467480 — ... -1.28 1.77E-03 MTHFR 226929_at AA524272 NM_005957 4524 -1.28 1.48E-04 MKLN1 1560145_at BQ942131 NM_013255 4289 -1.28 4.90E-03 ZNF207 231848 x at AW192569 NM_003457 7756 -1.28 7.40E-03 AI796536 229810_at AI796536 — ... -1.28 5.96E-04 BF724558 241722_x_at BF724558 — ... -1.28 4.4 8 E-03 AI825987 235889_at AI825987 — — -1.27 2.27E-04 TXNDC4 208958 at AI827677 NM 015051 23071 -1.27 7.53E-04 ADORA2B 205891 at NM 000676 NM_000676 136 -1.27 7.80E-03 292 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al„ Cells Useful for Immuno-Based BoNT/A Activity Assays FLJ21159 220145_at NM 024826 NM 024826 79884 -1.27 1.45E-05 WSB1 201294_s_at N24643 NM 015626 NM 134264 NM 134265 26118 -1.27 4.68E-03 AK3 225342_at AK026966 NM 00100535 3 NM_013410 NM_203464 205 -1.27 9.13E-03 PLCB4 203896_s_at NM_000933 NM_000933 NM_182797 5332 -1.27 1 40E-04 RAPGEF2 215992_s_at AL117397 XM 376350 9693 -1.27 1 92E-05 PDXK 218019_s_at NM 021941 NM_003681 8566 -1.27 9.30E-03 DUSP16 224336_s_at AB052156 NM 030640 80824 -1.27 3.94E-03 BACE2 222446_s_at AF178532 NM_012105 NM 138991 NM_138992 25825 -1.27 4.30E-04 PUM2 216121_at AL080106 NM_015317 23369 -1.27 1.02E-05 AVEN 219366_at NM_020371 NM 020371 57099 -1.27 5.67E-03 NMB 205204_at NM_021077 NM_021077 NM_205858 4828 -1.26 3.26E-05 EPOR 396_f_at X97671 NM_000121 2057 -1.26 8.71 E-04 CSRP1 200621_at NM_004078 NM_004078 1465 -1.26 9.64E-03 MYT1L 1554633_a_at AF036943 NM_015025 23040 -1.26 4.55E-03 TAPBP 208829_at AF029750 NM_003190 NM_172208 NM_172209 6892 -1.26 8.92E-06 AI741597 230302_at AI741597 — — -1.26 3.47E-03 C10orf10 209183_s_at AL136653 NM_007021 11067 -1.26 1.25E-03 FLJ31951 236322_at AA830854 NM_144726 153830 -1.26 1.23E-03 HERC4 225989 at AB046813 NM 015601 26091 -1.26 1.35E-04 PTGS1 238669_at BE613133 NM 000962 NM_080591 5742 -1.26 7.68E-05 GTPBP2 221050 s at NM 019096 NM 019096 54676 -1.26 5.82E-03 CNOT4 1559347_at BI599409 NM 00100822 5 NM_013316 4850 -1.26 4.86E-03 BM914560 1558220 at BM914560 XM 496669 440993 -1.26 9.16E-03 C6orf111 230375 at AI936531 NM 032870 25957 -1.26 1 30E-03 WBSCR19 232964_at AL137266 NM_175064 285955 -1.26 4.75E-04 AW104619 229754_at AW104619 — — -1.26 3.59E-03 DISC1 244642 at AI761381 NM 018662 27185 -1.26 7.13E-03 FLJ32130 1554770_x_at BC040642 NM 152458 146540 -1.26 1.11E-03 AW192718 1559437_at AW192718 XM 373180 392084 -1.25 5.77E-03 BC014318 1558236_at BC014318 — — -1.25 1.70E-04 EVC 219432_at NM_014556 NM_014556 NM_153717 2121 -1.25 3.41 E-03 PPAPDC1 236044_at BF130943 XM_113641 196051 -1.25 1.93E-04 AI732885 214388_at AI732885 — — -1.25 1.01 E-03 AI588962 230477_at Al588962 — — -1.25 1.64 E-04 HIST1H2BI 208523_x_at NM_003525 NM_003525 8346 -1.25 1.67E-03 HRMT1L1 216069_at AL050065 NM_001535 NM_206962 3275 -1.25 6.45E-05 0KFZP434I071' 231954 at AL137273 — 54553 -1.25 1.77E-03 ZNF654 219239_s_at NM_018293 NM_018293 55279 -1.25 8.76E-04 BC035105 1569482 at BC035105 — — -1.25 1.09E-03 ZFYVE16 240859 at N20928 NM_014733 9765 -1.25 8.54E-03 AW303371 242096 at AW303371 — — -1.25 8.48E-03 AK025360 216173 at AK025360 — — -1.25 7.46E-03 293 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays LOC440157 1558139 at BE730158 XM 495969 440157 -1.25 8.53E-03 MGC15407 224968_at AL518311 NM_080667 112942 -1.25 1.67E-04 W18186 239842 x at W18186 — — -1.25 3.42E-04 FLJ32130 1554769jat BC040642 NM_152458 146540 -1.25 1.81E-04 PER2 205251_at NM_022817 NM_003894 NM 022817 8864 -1.25 4.90E-03 NOL3 221567_at AF064599 NM_003946 8996 -1.25 1.02E-04 ORMDL1 228801_at AI809749 NM_016467 94101 -1.25 1.54E-07 FLJ23825 1555866_a_at BM980844 NM 173620 284004 -1.25 2.44E-03 ACRV1 207969_x_at NM_020109 NM 001612 NM 020069 NM_020107 NM_020108 NM 020109 NM 020110 NM 020111 NM 020113 NM 020114 NM 020115 56 -1.24 3.48E-04 CHD5 213965_s_at AL035406 NM_015557 26038 -1.24 1.51E-04 C17orf27 1569078 at AF318359 NM_020914 57674 -1.24 4.95E-03 RAPGEF2 238176_at T86196 XM 376350 9693 -1.24 9.33E-03 JMJD2B 1558448 a at BC032415 NM 015015 23030 -1.24 7.07E-03 SIPA1L2 1559469_s_at BC006013 NM_020808 57568 -1.24 5.27E-03 AI018235 240314_at AI018235 — — -1.24 4.83E-03 BC007626 1562946 at BC007626 — — -1.24 5.88E-05 TIP120A 239771_at BG399629 NM_018448 55832 -1.24 1.29E-03 BF507816 240517_at BF507816 — — -1.24 6.12E-03 T79942 228465_at T79942 — — -1.23 1.38E-03 RPIP8 206196 s at NM 006695 NM 006695 10900 -1.23 2.25E-03 SFRS12 243361 at N51597 NM 139168 140890 -1.23 4.89E-03 FBXW7 229419_at BF222826 NM 018315 NM_033632 55294 -1.23 3.99E-04 PRKCA 213093_at AI471375 NM_002737 5578 -1.23 4.72E-04 AI042344 240121_x_at AI042344 — — -1.23 3.31 E-05 ABCA2 210100_s_at AF327657 NM 001606 NM_212533 20 -1.23 2.95E-04 CHST1 205567 at NM 003654 NM 003654 8534 -1.23 4.23E-03 GRIK2 1563754_at AJ252246 NM_021956 NM_175768 2898 -1.23 1.60E-03 AI887898 228423_at AI887898 XM 374094 389237 -1.23 7.61 E-04 FADS3 204257 at NM_021727 NM_021727 3995 -1.23 4.30E-04 BE551142 241091_at BE551142 XM_497668 388620 -1.23 4.14E-03 BC014318 1558237_x_at BC014318 — — -1.23 7.31 E-04 TCEA1 1566207_at BQ286789 NM 006756 NM_201437 6917 -1.23 9.86E-06 PLCE1 205111_s_at NM 016341 N M 016341 51196 -1.23 4.76E-07 KIAA0125 220377_at NM_014151 NM_014792 9834 -1.23 3.84E-04 PIK3C2A 241905 at AA579047 NM 002645 5286 -1.22 8.81 E-03 USP15 233473_x_at AU156202 NM 006313 9958 -1.22 5.44E-03 DHX36 1559039 at AK096808 NM 020865 170506 -1.22 5.13E-03 KIAA0368 236368_at BF059292 XM_036708 23392 -1.22 1.71 E-04 AI971535 229626_at AI971535 XM 370691 387856 -1.22 3.12E-04 NOL3 221566 s at AF043244 NM 003946 8996 -1.22 9.37E-04 ADAM 8 205180 s at NM001109 NM 001109 101 -1.22 7.63E-03 FGF7 230918_at BE856598 NM 002009 2252 -1.22 1.18E-03 C21orf25 212875_s_at AP001745 NM 199050 25966 -1.22 1.75E-03 294 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays C21orf57 227421_at BF026326 NM_00100611 4 NM_058181 54059 -1.22 4.19E-04 BF061976 243499_at BF061976 — — -1.22 3.63E-03 RLF 204243_at NM_012421 NM_012421 6018 -1.21 3.24E-05 MLLT2 201924_at NM_005935 NM_005935 4299 -1.21 1.72E-03 BE467577 228251_at BE467577 — — -1.21 2.37E-03 WSB1 201295_s_at BF111821 NM_015626 NM_134264 NM_134265 26118 -1.21 2.55E-03 PR47 1560526 at BQ880034 — 266671 -1.21 402E-03 PRPH 213847_at NM_006262 NM_006262 5630 -1.21 3.82E-03 H75391 1559515_at H75391 — — -1.21 3.64E-04 AI740589 243515_at AI740589 — — -1.21 7.40E-04 OLFM3 1554526 at BC022531 NM 058170 118427 -1.21 1.84E-04 C14orf135 1563259_at AK024838 NM_022495 64430 -1.21 9.40E-04 U00954 232180_at U00954 — — -1.21 4.24E-05 AI631888 235532 at AI631888 — — -1.21 1.03E-03 EXOC7 214802 at AK022397 NM 015219 23265 -1.21 8.35E-03 SIPA1L2 225056_at AB037810 NM_020808 57568 -1.20 7.73E-03 HSPC065 222890_at BG054922 NM 014157 29070 -1.20 4.19E-03 IER3 201631_s_at NM_003897 NM 003897 NM_052815 8870 -1.20 3.48E-04 BF059537 240020_at BF059537 — ... -1.20 2.65E-04 BE503598 1557659_a_at BE503598 — — -1.20 1.58E-03 FLJ13710 222835 at BG163478 NM 024817 79875 -1.20 8.19E-03 C14orf120 216263 s at AK022215 XM 033371 25983 -1.20 5.96E-07 FNBP1 212288_at AB011126 NM 015033 23048 -1.20 9.04E-06 TTC11 244082_at BF507959 NM 016068 51024 -1.20 7.10E-03 ABR 214671_s_at L19704 NM 001092 NM_021962 29 -1.20 5.25E-03 ABTB1 229164_s_at AI337369 NM_032548 NM_172027 NM_172028 80325 -1.20 3.15E-03 TRIM50C 1554182_at BC033871 NM_198853 378108 -1.19 6.94E-05 ADAMTS1 222162_s_at AK023795 NM_006988 9510 -1.19 1.75E-03 TIGD4 232998_at AK024235 NM_145720 201798 -1.19 1.23E-04 KIAA0220 231989 s at AC003007 — 283846 -1.19 6.25E-03 AI435590 237192_at AI435590 ... ... -1.19 7.36E-04 NOL3 59625_at AI912351 NM_003946 8996 -1.19 4.25E-05 FOXR2 1569669_at BM550294 NM_198451 139628 -1.19 6.60E-03 AW628665 235555 at AW628665 — — -1.19 7.01 E-03 LOC285831 228857_at AA775731 — 285831 -1.19 2.24E-04 C15orf28 220710_at NM_024970 — 80035 -1.19 7.83E-03 KIAA1957 240721_at BE672858 NM 021174 NM_199205 57805 -1.19 4.55E-04 BRPF3 225217_s_at AB033112 NM_015695 27154 -1.19 3.39E-04 PPP3CA 236545_at AA532718 NM_000944 5530 -1.18 1.89E-03 BF514509 239050_s_at BF514509 — — -1.18 8.62E-03 AA639707 243837 x at AA639707 — — -1.18 1.88E-04 WSB1 210561_s_at AL110243 NM_015626 NM_134264 NM_134265 26118 -1.18 7.42E-04 AA888777 242740 at AA888777 — — -1.18 1.23E-03 BMPR2 238393_at AL047534 NM 001204 NM_033346 659 -1.18 5.95E-03 BACH 2 1556451 at AL833645 NM_021813 60468 -1.18 2.17E-04 CRELD1 203368_at NM_015513 NM_015513 78987 -1.18 3.92E-03 295 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays RPL37 224766_at AW008221 NM 000997 6167 -1.18 6.73E-06 CSTB 201201_at NM 000100 NM_000100 1476 -1.18 2.39E-06 MGC12458 211200_s_at BC002836 NM 032328 84288 -1.18 4.74E-03 C9orf111 228383 at AK024443 NM_152286 375775 -1.18 4.27E-03 PLRG1 227246_at BF438014 NM 002669 5356 -1.18 8.04E-04 ZFYVE9 208446_s_at NM_007323 NM_004799 NM_007323 NM_007324 9372 -1.18 3.59E-03 ZNF226 224004_at AF246126 NM_015919 NM_016444 7769 -1.17 2.52E-04 NM 015437 207799_x_at NM_015437 — — . -1.17 7.74E-04 AFTIPHILIN 244312_at AW195572 NM_00100224 3 NM_017657 NM_203437 54812 -1.17 6.11E-03 AL137378 216144_at AL137378 — ... -1.17 1.87E-03 NUP153 239948_at AA004800 NM_005124 9972 -1.17 4.63E-03 OLFM3 1554524_a_at AF397394 NM_058170 118427 -1.17 4.35E-05 N30152 229850 at N30152 — ... -1.17 1.02E-03 AI934828 227116_at AI934828 XM 375373 400547 -1.17 4.08E-03 LRRFIP2 230082_at AW137053 NM 006309 NM_017724 9209 -1.17 1.78E-03 HPCAL1 212552_at BE617588 NM 002149 NM_134421 3241 -1.17 1.73E-04 DRPLA 236961_at AI539426 NM_00100702 6 NM_001940 1822 -1.17 2.23E-03 CLCN3 201732_s_at AF029346 NM_001829 NM_173872 1182 -1.17 2.63E-03 RFX2 226872_at AK024288 NM 000635 NM_134433 5990 -1.17 2.24E-03 HNRPD 235999_at AA863112 NM 00100381 0 NM 002138 NM_031369 NM_031370 3184 -1.17 1.28E-04 WNK1 211993_at AI768512 NM 018979 65125 -1.17 1.66E-03 LOC401320 1558459_s_at BC041636 XM 379482 XM_380098 401320 -1.17 2.08E-03 NM_025033 208301_at NM_025033 — ... -1.17 9.10E-05 KIAA1040 242225_at AI569482 NM_015026 23041 -1.17 5.75E-03 C9orf68 220218 at NM_017985 NM 017985 55064 -1.16 4.90E-03 C21orf66 1555125_at BC030539 NM_013329 NM 016631 NM 058191 NM 145328 94104 -1.16 3.17E-05 GAD2 243265_at AW444497 NM 000818 2572 -1.16 1.34E-04 ABTB1 226442_at H06267 NM_032548 NM 172027 NM_172028 80325 -1.16 2.47E-05 ZNF644 1557751_at AI537913 NM 016620 NM_032186 NM 201269 84146 -1.16 6.37E-03 CENTB2 240759 at AW593931 NM_012287 23527 -1.16 5.67E-03 CAPN2 208683_at M23254 NM 001748 824 -1.16 3.02E-04 TMEM5 204808_s_at NM_014254 NM 014254 10329 -1.16 1.28E-04 HIST1H2BF 208490_x_at NM_003522 NM 003522 8343 -1.16 7.03E-04 296 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays BCAP29 230150_at N57499 NM_00100840 5 NM 00100840 6 NM_00100840 7 NM_018844 55973 -1.16 2.32E-03 PERLD1 55616_at Al703342 NM_033419 93210 -1.16 4.41 E-03 DTNA 227084_at AW339310 NM_001390 NM 001391 NM_001392 NM_032975 NM_032978 NM 032979 NM_032980 NM 032981 1837 -1.16 3.40E-03 CHD9 220586_at NM 025134 NM_025134 80205 -1.16 3.15E-03 BF478226 241684 at BF478226 — ... -1.16 3.08E-04 SLC27A3 222217_s_at BC003654 NM_024330 11000 -1.16 7.01 E-04 PLOD1 200827_at NM_000302 NM_000302 5351 -1.16 1.10E-03 AI216567 236754_at AI216567 — ... -1.15 1.78E-03 AI693178 228101_at AI693178 — ... -1.15 1.78E-06 ZNF587 242564_at AI703142 NM_032828 84914 -1.15 8.15E-04 ZDHHC11 232417_x_at AU150300 NM 024786 79844 -1.15 1.16E-03 AK3 204348_s_at NM_013410 NM 00100535 3 NM_013410 NM_203464 205 -1.15 4.21 E-03 EFNB3 205031_at NM 001406 NM 001406 1949 -1.15 1.14E-04 NYREN18 1559732_at AK056624 NM 016118 51667 -1.15 9.75E-05 SIPA1L2 233587_s_at AK022852 NM 020808 57568 -1.15 1.97E-03 AI287817 240095_at AI287817 — ... -1.15 5.78E-04 IARS 239794_at AI356405 NM_002161 NM_013417 3376 -1.15 5.87E-03 WSB1 201296_s_at NM_015626 NM_015626 NM 134264 NM_134265 26118 -1.15 2.42E-03 AB037813 231969 at AB037813 — ... -1.15 9.45E-05 AI022648 242972_at Al022648 ... ... -1.15 6.12E-03 AA651954 236626_at AA651954 — ... -1.14 1.11 E-04 TAGLN2 200916 at NM 003564 NM_003564 8407 -1.14 7.20E-03 AI263044 214376_at Al263044 — ... -1.14 4.04E-03 ZNF333 1552375_at NM_032433 NM_032433 84449 -1.14 4.08E-03 HSPB1 201841_s_at NM_001540 NM 001540 3315 -1.14 8.01 E-03 FLJ25778 238350_at AW967956 XM 376679 XM_379933 254048 -1.14 8.71 E-03 KIAA1731 1565830_at AL833615 XM 374922 85459 -1.14 4.73E-05 FLJ32130 242272_at Al375066 NM 152458 146540 -1.14 3.52E-04 FLJ39485 236728 at AW070437 NM 175920 285603 -1.14 6.01 E-03 AKAP14 228493_at T87628 NM_00100853 4 NM 00100853 5 NM 178813 158798 -1.14 3.57E-03 297 PCT/US2010/027242 WO 2010/105234 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays NEDD5 232637_at AK025163 NM_00100849 4735 -1.14 1.03E-04 1 NM_00100849 2 com 236254_at BE048857 NM 004404 NM 006155 NM_015243 157680 -1.14 9.97E-04 COLEC11 219873_at NM_024027 NM 017890 NM 152564 NM 181661 NM 184042 NM 024027 78989 -1.14 2.80E-04 TMPIT 234084 x at AU147104 NM_199235 NM 031925 83862 -1.14 4.48E-03 P4HA2 1568611_at CA418310 NM_004199 8974 -1.14 5.99E-03 APOC1 213553_x_at W79394 NM_001645 341 -1.14 2.08E-03 BI868311 1565651_at BI868311 — ... -1.14 1.59E-03 NRD1 242235 x at AW978721 NM 002525 4898 -1.13 6.03E-03 ABCA2 212772_s_at AL162060 NM_001606 20 -1.13 2.55E-04 EGLN1 1561893 at BC024172 NM_212533 NM_022051 54583 -1.13 2.07E-06 ATXN7L1 227732_at AB033044 — 57485 -1.13 9.68E-04 SSR1 226712_at BF206389 NM 003144 6745 -1.13 4.37E-03 KIAA1045 37566_at AB028968 XM 048592 23349 -1.13 1.00E-03 COPA 1559862 at BC037941 NM 004371 1314 -1.13 3.33E-04 ARGBP2 204288_s_at NM_021069 NM_003603 8470 -1.13 5.18E-04 PLCE1 205112_at NM_016341 NM_021069 NM 016341 51196 -1.13 2.45E-03 PDGFRB 202273 at NM 002609 NM 002609 5159 -1.13 4.37E-03 METAP2 240769_at AI733395 NM_006838 10988 -1.13 6.92E-06 GNPTG 224887_at AF302786 NM 032520 84572 -1.13 7.70E-05 TAGLN2 210978_s_at BC002616 NM 003564 8407 -1.13 6.34E-03 BDP1 231939 s at AJ238520 NM_018429 55814 -1.13 5.92E-04 AA524740 225249_at AA524740 — ... -1.13 5.63E-03 MCM3AP 212269_s_at AJ010089 NM_003906 8888 -1.13 7.20E-04 HEL308 228736_at AW084661 NM_133636 113510 -1.12 4.79E-04 BF540795 243043 at BF540795 — — -1.12 1.49E-03 BF339133 213296_at BF339133 — — -1.12 2.35E-03 BF940997 239857_at BF940997 — — -1.12 2.17E-03 SFRS11 237746_at AI168187 NM 004768 9295 -1.12 3.42E-03 ADAMTS1 222486_s_at AF060152 NM_006988 9510 -1.12 1.60E-03 AI654130 241936_x_at AI654130 — ... -1.12 3.27E-03 NSUN4 1559848_at BC016907 NM_199044 387338 -1.12 1.76E-03 AA830545 235730 at AA830545 — — -1.12 9.65E-03 ABR 212895_s_at AL527773 NM_001092 29 -1.12 2.02E-04 AW150212 1556039 s_at AW150212 NM 021962 -1.12 2.68E-03 ADAMTS20 220717_at NM_025003 NM 025003 80070 -1.12 3.36E-03 WDFY3 212602_at AI806395 NM_175851 NM_014991 23001 -1.12 1.05E-05 C1orf8 241018 at BF446758 NM 178583 NM 178585 NM_004872 9528 -1.12 3.93E-03 CLTC 220855_at NM 014127 NM_004859 1213 -1.11 8.87E-04 BC035773 1569665_at BC035773 — ... -1.11 8.41 E-03 KDELR2 242725 at BG026159 NM 006854 11014 -1.11 8.62E-03 SMAD4 1565703_at AL832789 NM_005359 4089 -1.11 6.90E-03 298 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B„ et al., Cells Useful for Immuno-Based BoNT/A Activity Assays SIRT5 221010_s_at NM_031244 NM_012241 NM_031244 23408 -1.11 4.63E-03 MAD 226275_at Al 188653 NM 002357 4084 -1.11 1.65E-03 ARSD 223695_s_at BC003660 NM 001669 NM 009589 414 -1.11 8.01 E-03 LOC284361 224727_at AL045545 NM 175063 NM_206538 284361 -1.11 1.48E-03 DMPK 37996_s_at L08835 NM_004409 1760 -1.11 9.75E-05 HCG8 215985_at X92110 — 80869 -1.11 6.05E-03 MGC15875 232488_at AK023470 NM 032921 NM_153373 85007 -1.11 4.98E-04 PLD3 201050_at NM_012268 NM 012268 23646 -1.11 9.93E-04 C20orf35 238470_at BF129779 NM 018478 NM_033542 55861 -1.11 8.61 E-04 AA573901 227783 at AA573901 — ... -1.11 5.51 E-04 PROX1 242119_at AW451938 NM_002763 5629 -1.11 2.23E-03 AI862542 235696_at AI862542 — ... -1.11 2.47E-03 ZNF596 232641 at AC004908 NM 173539 169270 -1.11 3.61 E-03 GOLGIN-67 210424_s_at AF163441 NM 015003 NM_181076 NM 181077 23015 -1.10 3.73E-04 JMY 226352_at BF447037 NM 152405 133746 -1.10 1.15E-05 APXL2 239435_x_at AA588854 NM_133456 134549 -1.10 2.97E-03 BC004287 223366_at BC004287 — ... -1.10 3.09E-03 NM_025120 220728_at NM_025120 ... ... -1.10 4.73E-03 BF510762 230262_at BF510762 ... ... -1.10 2.62E-04 AI741900 239140_at AI741900 ... ... -1.10 7.72E-05 INADL 223681_s_at AB044807 NM_005799 NM 170605 NM_176877 NM_176878 10207 -1.10 3.79E-04 PCDHB14 231726_at NM_018934 NM_018934 56122 -1.10 7.91 E-03 AI435590 237193 s at AI435590 — ... -1.10 9.64E-03 NPIP 204538 x at NM 006985 NM_006985 9284 -1.10 2.65E-04 SR140 236696_at BE464843 XM_031553 23350 -1.09 5.65E-03 CCNL2 221427_s_at NM_030937 NM_030937 81669 -1.09 1.71 E-03 GFRA3 214479 at NM 001496 NM 001496 2676 -1.09 9.83E-03 AM 61338 65472 at Al 161338 XM_371506 388969 -1.09 3.32E-03 AF164622 210425_x_at AF164622 — ... -1.09 5.81 E-04 SLC36A1 213119_at AW058600 NM 078483 206358 -1.09 1.68E-03 NOR1 227359_at AI911248 NM 145047 NM_206837 127700 -1.09 2.57E-03 UBXD1 220757_s_at NM 025241 NM 025241 80700 -1.09 1.00E-03 C20orf103 219463_at NM 012261 NM 012261 24141 -1.09 5.61 E-03 HERC1 240703 s at AW591969 NM 003922 8925 -1.09 1.25E-03 FLJ25952 243786_at AA454190 NM_153251 253832 -1.09 1.88E-03 AK023264 233068_at AK023264 ... ... -1.08 5.48E-03 UBE2D3 230171_at AW662789 NM 003340 NM_181886 NM_181887 NM_181888 NM 181889 NM 181890 NM_181891 NM_181892 NM 181893 7323 -1.08 3.01 E-03 299 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays PRKCSH 200707_at NM_002743 NM_00100132 Q 5589 -1.08 1.56E-03 BRUNOL5 230497_at BE503640 y NM 002743 NM_021938 60680 -1.08 1.26E-03 FLJ35390 1558123_at AK092709 — 255031 -1.08 6.65E-03 IP09 225728 at AI659533 NM 018085 55705 -1.08 2.88E-03 HNRPC 1568941_a_at BC022884 NM_004500 3183 -1.08 3.18E-03 MCM3AP 215581_s_at AK022303 NM_031314 NM_003906 8888 -1.08 1.75E-03 LOC399491 215921_at AC002544 — 399491 -1.08 2.25E-04 SMU1 228180 at AA805653 NM 018225 55234 -1.08 3.97E-03 AKT2 236664__at AA448167 NM 001626 208 -1.08 1.96E-03 JAK1 234193_at AK025218 NM 002227 3716 -1.08 2.70E-03 INADL 214705_at AJ001306 NM_005799 10207 -1.08 9.90E-04 C9orf1 OOS 1558761 a at AK093641 NM_170605 NM_176877 NM_176878 NM 198841 158293 -1.08 2.09E-05 H2AFY 226840_at AW291297 NM_004893 9555 -1.08 1.19E-03 DUSP16 224832_at AB051487 NM 138609 NM 138610 NM_030640 80824 -1.08 1.39E-04 AL390216 234317_s_at AL390216 — ... -1.07 4.32E-05 PLA2G4B 219095_at NM_005090 NM_005090 8681 -1.07 7.70E-05 AF131844 222184_at AF131844 — — -1.07 1.01E-03 AI939452 240892 at AI939452 — — -1.07 2.32E-03 ANKHD1 229457_at AU148042 NM_017747 54882 -1.07 1.15E-03 AI916303 228207_at AI916303 NM_017978 NM_024668 -1.07 4.41 E-04 AA033699 229111_at AA033699 — ... -1.07 9.78E-03 GOLGIN-67 208798_x_at AF204231 NM_015003 23015 -1.07 8.11 E-04 SYNE1 209447_at AF043290 NM 181076 NM_181077 NM 015293 23345 -1.07 2.21 E-03 AL080112 216858_x_at AL080112 NM 033071 NM 133650 NM_182961 -1.07 8.82E-03 MAP7 215471_s_at AJ242502 NM_003980 9053 -1.07 7.77E-04 BC025319 1568974 at BC025319 — — -1.06 9.12E-03 DJ328E19.C1. 214693_x_at BE732345 NM_015383 200030 -1.06 3.98E-04 1 LOC200030 MGC8902 LOC401967 AG1 PIGF 239258_at BE551407 NM 173638 NM 183372 XM 371384 XM_496394 XM 496406 NM 002643 25832 284565 401967 440673 5281 -1.06 3.15E-04 NPIP 214870_x_at AC002045 NM 173074 NM 006985 339047 -1.06 2.19E-04 LOC339047 LOC440341 KIF5C 203129 s at BF059313 XM 290671 XM 352159 XM 377774 440341 9284 3800 -1.06 2.07E-03 KCTD13 45653_at AW026481 NM_178863 253980 -1.06 5.88E-06 FLJ10287 219130_at NM 019083 NM_019083 54482 -1.06 3.45E-03 PSMD7 244515_at AI640348 NM 002811 5713 -1.06 5.80E-03 300 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al„ Cells Useful for Immuno-Based BoNT/A Activity Assays AK3 AK3L2 204347_at AI653169 NM 00100292 1 NM 00100535 3 NM 013410 NM 203464 205 387851 -1.06 8.16E-03 BACE1 217904_s_at NM_012104 NM 012104 NM_138971 NM_138972 NM 138973 23621 -1.06 1.51E-04 WDFY3 212598_at BE348236 NM_014991 NM_178583 NM 178585 23001 -1.06 4.22E-03 CLCN3 201735_s_at NM_001829 NM 001829 NM_173872 1182 -1.06 2.95E-03 PHACTR1 213638_at AW054711 NM 030948 221692 -1.06 8.09E-03 PPIE 229375_at AL526713 NM_006112 NM 203456 NM_203457 10450 -1.06 2.02E-06 C10orf57 218174_s_at NM 025125 NM_025125 80195 -1.06 8.98E-04 PEX6 238672_at AW953952 NM 000287 5190 -1.06 6.15E-04 BDH 211715_s_at BC005844 NM 004051 NM_203314 NM_203315 622 -1.06 4.14E-04 BF110411 221878_at BF110411 XM_371506 388969 -1.05 8.17E-03 R93413 236590 at R93413 — — -1.05 6.60E-04 FLJ36674 244698_at AW297656 NM_173622 284040 -1.05 4.58E-03 AA729232 241359_at AA729232 — — -1.05 9.24E-03 FLJ21159 235550_at AV751613 NM 024826 79884 -1.05 4.53E-03 SMPD1 209420_s_at M59916 NM 000543 NM_00100759 6609 -1.05 8.56E-04 AA281853 239505_at AA281853 ό ___ -1.05 8.55E-04 KCNMA1 221584 s at U11058 NM_002247 3778 -1.05 7.34E-05 LOC439928 1569519_at BC039454 XM 498427 439928 -1.05 2.09E-03 PAM 202336_s_at NM_000919 NM_000919 NM 138766 NM_138821 NM_138822 5066 -1.05 1.27E-03 DCTD 201571_s_at AI656493 NM_001921 1635 -1.05 9.35E-05 ZNF573 217627_at BE515346 NM 152360 126231 -1.05 5.34E-04 WDR19 232163_at AI982884 NM_025132 57728 -1.05 4.32E-04 ETFDH 33494_at S69232 NM 004453 2110 -1.05 1.51E-03 RRAGC 222514_at AK023373 NM_022157 64121 -1.05 7.18E-03 C14orf139 219563_at NM 024633 NM 024633 79686 -1.05 7.66E-03 DNASE1 1560536_at BC035759 NM_005223 1773 -1.05 1.80E-03 D17262 1567997_x_at D17262 — ... -1.04 5.43E-03 BTG3 215425 at AL049332 NM 006806 10950 -1.04 5.78E-04 ATE1 238252_at AI040743 NM 00100197 6 NM_007041 11101 -1.04 5.92E-04 KCTD13 221889_at AW026481 NM 178863 253980 -1.04 1.16E-05 RRAGC 218088 s at NM 022157 NM 022157 64121 -1.04 8.27E-04 ZZEF1 212601_at AB007859 NM 015113 23140 -1.04 4.08E-03 BCL11B 222895_s_at AA918317 NM 022898 NM_138576 64919 -1.04 6.07E-04 KIAA0999 1563455 at AL832068 NM_025164 23387 -1.04 9.56E-03 ZFYVE26 37943_at AB002319 NM_015346 23503 -1.04 9.36E-03 301 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays NSUN6 242239 at AW970888 NM_182543 221078 -1.04 8.03E-03 BE674309 230913_at BE674309 — — -1.04 1.59E-04 AA910371 212952 at AA910371 — — -1.04 3.15E-03 C21orf51 228239_at AA148789 NM_058182 54065 -1.04 6.43E-06 PPT1 200975_at NM 000310 NM 000310 5538 -1.04 2.75E-05 TTC3 208663_s_at AI652848 NM_00100189 4 NM_003316 7267 -1.04 9.53E-06 ZCSL3 1570048_at BC036571 NM_181706 120526 -1.04 6.02E-03 ZNF3 232497_at AF217988 NM_017715 NM_032924 7551 -1.04 7.84E-04 RRN3 230328_at BF057656 NM_018427 54700 -1.04 1.78E-03 FTH1 214211_at AA083483 NM_002032 2495 -1.03 2.78E-03 SERF2 226692_at AI092931 NM_005770 10169 -1.03 3.64E-03 MTCP1 239236 at BE465277 NM 014221 4515 -1.03 2.24E-03 PDCD2 228420_at AW590850 NM_002598 NM_144781 5134 -1.03 8.82E-03 SPOCK2 202524 s at NM_014767 NM_014767 9806 -1.03 2.19E-06 CYLD 221905 at BF516433 NM 015247 1540 -1.03 1.43E-04 IREB2 1563130_a_at AL109710 NM 004136 3658 -1.03 3.66E-03 HRMT1L1 221564_at AL570294 NM_001535 NM_206962 3275 -1.03 1.20E-06 DDOST 208674 x at BC002594 NM 005216 1650 -1.03 1.01E-03 LOC339047 214682_at AK023376 XM 290671 339047 -1.02 4.06E-03 MGC15875 226519_s_at AL561859 NM_032921 NM 153373 85007 -1.02 1.51E-03 HNRPM 233605_x_at AK022050 NM 005968 NM 031203 4670 -1.02 3.07E-03 LOC144363 225469_at AA015609 NM_00100166C 144363 -1.02 6.55E-04 ZNF346 232753 at AU147613 NM 012279 23567 -1.02 9.40E-04 C3orf6 228693_at AI681307 NM 174908 NM_178335 152137 -1.02 2.49E-03 AK024681 231972_at AK024681 — — -1.02 1.17E-03 UBXD1 223012_at AF272894 NM 025241 80700 -1.02 3.65E-04 HERC4 225988_at AI819938 NM 015601 26091 -1.02 2.15E-03 MY05A 227761_at AW235548 NM 000259 4644 -1.02 8.53E-03 LTBP3 227308_x_at AW515704 NM 021070 4054 -1.02 6.79E-07 C14orf118 229520_s_at BF060678 NM 017926 NM_017972 55668 -1.02 4.18E-03 RHOU 223169_s_at AB051826 NM 021205 58480 -1.02 9.28E-03 SH3BGR 204979_s_at NM_007341 NM 00100171 3 NM_007341 6450 -1.02 1.78E-03 BC014481 1569368_at BCO14481 — — -1.02 3.54E-03 LOC158230 243595_at AI589280 — 158230 -1.02 4.74E-04 BC031322 1555900 at BC031322 — — -1.02 1 29E-03 SPG3A 223340_at AF131801 NM_015915 NM_181598 51062 -1.02 7.49E-03 AA448858 238948_at AA448858 — — -1.02 3.09E-03 MGC33486 235614 at AI215667 NM_153266 256472 -1.01 2.05E-05 M78162 217536_x_at M78162 — — -1.01 4.51 E-03 PHKA1 229876_at BE503584 NM_002637 5255 -1.01 4.38E-04 STX6 244041_at AI884934 NM_005819 10228 -1.01 8.65E-03 FLJ23518 233400 at AU158247 NM 024725 79780 -1.01 3.50E-03 PPIE 210502_s_at AF042386 NM 006112 NM 203456 NM_203457 10450 -1.01 4.24E-03 DDOST 208675_s_at D29643 NM_005216 1650 -1.01 2.59E-03 302 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays OPTN 202073_at AV757675 NM_00100821 1 NM_00100821 2 NM_00100821 O 10133 -1.01 2.57E-05 J NM_021980 Cep164 1558953_s_at BC000602 NM_014956 22897 -1.01 1.37E-03 SLC19A2 1556602_at AW614839 NM_006996 10560 -1.00 2.90E-03 DMPK 217066 s at M87313 NM 004409 1760 -1.00 8.62E-03 SFRS15 222311 s at AA648521 NM_020706 57466 -1.00 2.57E-03 LYPLAL1 230174_at AI953360 NM_138794 127018 -1.00 3.17E-03 AK000970 215512_at AK000970 NM_005885 10299 -1.00 2.13E-03 LOC492304 202409 at X07868 NM 00100713£ 492304 -1.00 1.87E-03 PIGH 209625 at BC004100 NM_004569 5283 -1.00 6.00E-07 MEIS3 1569402_at BC014430 NM_00100981 56917 -1.00 8.61 E-03 ό NM 020160 DDX52 1570415_at BC012557 NM 007010 11056 -1.00 1.89E-03 NM_152300 DTNA 211493_x_at U46744 NM 001390 1837 -1.00 7.35 E-03 NM 001391 NM_001392 NM 032975 NM 032978 NM 032979 NM_032980 NM 032981 EIF5 208707_at BE552334 NM 001969 1983 -1.00 8.81 E-03 NM_183004 ADRBK2 ,FFX-hum_alu_< AFFX-humalu NM_000021 10001 -1.00 5.84E-04 ALDH3B1 NM 000051 10020 ALDH3A2 NM_000136 10045 ANXA2 NM_000141 10160 BIRC4 NM_000144 10197 APP NM 000202 10198 ATM NM 000227 10206 ATOX1 NM_000230 10207 ATP1B3 NM_000294 1021 ATP5D NM_000297 10225 BAD NM 000314 10277 BCAT2 NM_000356 10402 BDNF NM_000364 10457 BMPR2 NM 000382 10513 BRCA1 NM 000441 10524 C11orf3 NM_000484 10606 C21orf4 NM_000527 10609 CACNB2 NM_000554 10611 CCM1 10712 CD47 10730 CDK6 10801 CHKA 10806 CHRNB1 10848 AP3S1 10921 SLC31A1 11011 CP 11019 DJ462023.2 225876_at T84558 NM_020448 57185 -1.00 6.61 E-04 BE467087 231075_x_at BE467087 — — -1.00 8.51 E-03 303 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays ITSN1 216472_at AF003737 NM 00100113 2 NM 003024 6453 -1.00 2.41 E-03 DMWD 213231_at L19267 XM_496318 1762 -1.00 1.12E-03 RPL37 224767_at AL044126 NM_000997 6167 -1.00 1.07E-03 LM04 229537 at AI694521 NM 006769 8543 -1.00 2.20E-03 ACE 227463_at AW057540 NM 000789 NM_152830 NM_152831 1636 -1.00 1 34E-03 KIAA1345 234936_s_at AK023876 XM 106386 57545 -0.99 1 60E-03 AG1 215434_x_at AV684285 XM 371384 XM_496394 440673 -0.99 1.70E-03 BE645588 243429_at BE645588 — — -0.99 7.12E-03 PAM 214620_x_at BF038548 NM 000919 NM 138766 NM 138821 NM_138822 5066 -0.99 4.07E-03 LRRFIP1 201861_s_at BF965566 NM 004735 9208 -0.99 7.92E-06 RAD 50 238656_at AA877043 NM_005732 NM_133482 10111 -0.99 8.65E-03 LOC338758 238893_at AI377324 — 338758 -0.99 2.11 E-03 BE856007 238676_at BE856007 — — -0.99 5.32E-06 Lrp2bp 227337 at AA886870 NM 181726 353322 -0.99 6.37E-04 SMURF2 227489_at BE962027 NM 022739 64750 -0.99 4.11E-04 PGRMC2 213227 at BE879873 NM_006320 10424 -0.99 1.98E-03 TMEM41B 212623 at AU153138 — 23027 -0.99 8.63E-03 BE670056 226663_at BE670056 ... — -0.99 6.70E-03 MY09B 242742_at AI863135 NM_004145 4650 -0.99 3.16E-03 )KFZp313N062 241666_at BG493222 NM_173826 285343 -0.99 1 70E-03 HK2 202934 at AI761561 NM 000189 3099 -0.99 4.09E-03 DKFZp547l014 207283_at NM_020217 NM_020217 56969 -0.99 6.98E-04 MAP1LC3B 208786_s_at AF183417 NM 022818 81631 -0.99 3.39E-03 AKAP12 227530_at BF511276 NM_005100 NM_144497 9590 -0.99 7.30E-03 AB014532 222796_at ABO14532 — — -0.98 6.13E-04 C1orf50 219406_at NM 024097 NM 024097 79078 -0.98 2.14E-04 RPL13 1565759_at BG396520 NM 000977 NM_033251 6137 -0.98 2.65E-04 MGC43690 235298_at AW194823 NM_182552 253769 -0.98 3.94E-04 AF086554 1558504_at AF086554 XM 373889 440721 -0.98 2.45E-03 FLJ11196 218651_s_at NM_018357 NM 018357 NM 197958 55323 -0.98 1.86E-03 C17orf28 225981_at AW139549 NM_030630 283987 -0.98 3.41E-04 SFXN3 1559993_at AK091504 NM_030971 81855 -0.98 4.54E-03 C6orf111 226412 at N66397 NM 032870 25957 -0.98 1.98E-03 RPL13 229590_at AI369389 NM 000977 NM 033251 6137 -0.98 1.00E-03 LOC133308 1564746_at BC009732 NM_178833 133308 -0.98 1.21E-04 AK027185 232102 at AK027185 — — -0.98 1.28E-04 AW290940 226773 at AW290940 — — -0.98 1.34E-04 AB040946 222564_at AB040946 — — -0.98 1.34E-03 ILVBL 202993_at NM_006844 NM_006844 NM 176826 10994 -0.97 1.11 E-03 NPR2 204310_s_at NM_003995 NM_000907 NM_003995 4882 -0.97 1.05E-03 304 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al„ Cells Useful for Immuno-Based BoNT/A Activity Assays PAM 212958_x_at AI022882 NM_000919 NM 138766 NM 138821 NM_138822 5066 -0.97 2.87E-03 F11066 242973_at F11066 — — -0.97 5.82E-03 SPIN3 1554099_a_at BC032490 NM_001010862 169981 -0.97 4.95E-05 AA167167 243684_at AA167167 — — -0.97 1.78E-03 LANCL2 218219 s at NM_018697 NM_018697 55915 -0.97 9.88E-03 AFFX-BioB-3 4FFX-BioB-3_a AFFX-BioB-3 — — -0.97 1.52E-04 AHI1 220841_s_at NM 017651 NM_017651 54806 -0.97 4.15E-04 AI675308 1569154_a_at AI675308 — — -0.97 2.61 E-03 AI339837 241741_at AI339837 ... — -0.97 9.92E-03 HNLF 238525_at BF987157 NM_182547 222068 -0.97 3.73E-05 NM 024658 218305 at NM 024658 — — -0.97 8.21 E-03 FLJ30294 238867_at AI298041 NM 144632 130827 -0.97 9.74E-03 FBX09 1559096_x_at AK095307 NM_012347 NM_033480 NM_033481 26268 -0.97 6.38E-05 PLP2 201136_at NM_002668 NM 002668 5355 -0.97 1.29E-04 ZNF542 229187_at AI026708 NM_194319 147947 -0.97 7.05E-03 TTLL3 210129_s_at AF078842 NM_015644 26140 -0.97 6.31 E-03 D4S234E 213533_at M98528 NM_014392 27065 -0.97 1.57E-04 SHC2 213464 at AV705938 XM_375550 25759 -0.97 4.07E-06 GCC1 243306_s_at BE276093 NM_024523 79571 -0.97 2.70E-07 TSGA2 230093_at AI683428 NM 080860 89765 -0.97 4.32E-03 HDLBP 222916_s_at AF116718 NM 005336 NM_203346 3069 -0.97 5.58E-03 C9orf91 221865_at BF969986 NM_153045 203197 -0.96 6.15E-03 CYorf15B 223646_s_at AF332225 NM_032576 84663 -0.96 4.37E-03 LTB4R 236172 at AW206817 NM 181657 1241 -0.96 5.00E-03 MGC11332 213403_at BF223370 NM_032718 84804 -0.96 5.81 E-03 SPIRE2 227706_at AI215798 NM 032451 84501 -0.96 7.98E-05 AU146901 233264_at AU146901 — — -0.96 1.84E-03 BG000693 1559932 at BG000693 — — -0.96 1.63E-04 FLJ20758 228512_at AW138833 NM_017952 55037 -0.96 1.99E-03 UNC5D 231325_at AI802048 NM_080872 137970 -0.96 4.13E-05 THRAP2 242911_at AW999644 NM 015335 23389 -0.96 5.60E-03 CLDN15 219640_at NM_014343 NM 014343 NM_138429 24146 -0.96 1.04 E-03 DUSP16 1558740_s_at R30807 NM 030640 80824 -0.96 9.85E-03 TMEM1 209412_at U61500 NM 00100172 3 NM_003274 7109 -0.96 5.34E-03 DDX26 222239_s_at AL117626 NM_012141 26512 -0.95 1.60E-03 LOC388526 235322_at BF038869 XM 371157 388526 -0.95 1.09E-04 OS-9 215399_s_at AI683900 NM 006812 10956 -0.95 7.81 E-03 PRKCSH 214080_x_at AI815793 NM 00100132 9 NM 002743 5589 -0.95 2.14E-04 BF976290 238768_at BF976290 XM_371506 388969 -0.95 9.91 E-04 FLJ14107 207287_at NM 025026 NM 025026 80094 -0.95 1.43E-05 ARHGAP23 226638_at AV701292 XM_290799 57636 -0.95 3.20E-04 AI252004 242696 at AI252004 — — -0.95 2.67 E-03 TGFB1I1 209651_at BC001830 NM_015927 7041 -0.95 7.45 E-03 AI598222 235679_at AI598222 — — -0.95 1.26E-03 AA131302 236032_at AA131302 — — -0.95 5.35E-04 AI929792 236081 at AI929792 — — -0.95 6.74E-05 N45312 228159 at N45312 — — -0.95 5.76E-04 305 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., etal., Cells Useful for Immuno-Based BoNT/A Activity Assays MONDOA 202519_at NM 014938 NM 014938 22877 -0.95 6.48E-04 PLCB4 203895_at AL535113 NM 000933 NM_182797 5332 -0.95 8.09E-05 RNF149 225414_at AL558987 NM_173647 284996 -0.95 9.45E-03 DNASE1 1557189_at AW468509 NM_005223 1773 -0.95 4.38E-04 OS-9 200714_x_at NM_006812 NM_006812 10956 -0.95 4.30E-03 CCNL2 222999_s_at AF251294 NM 030937 81669 -0.95 5.76E-03 NPD014 209006_s_at AF247168 NM_020317 NM_207035 57035 -0.95 1.08E-03 LOC154822 243261_at BF530486 — 154822 -0.94 6.74E-03 TARSL2 227611_at AA442856 NM_152334 123283 -0.94 4.59E-03 AA827805 241364_at AA827805 — — -0.94 9.38E-03 KRT18 201596_x_at NM_000224 NM 000224 NM_199187 3875 -0.94 2.40E-03 CYLD 213295 at AA555096 NM_015247 1540 -0.94 2.37E-04 BC011119 1569723_a_at BC011119 — — -0.94 7.41 E-03 PHF17 225820_at AV646599 NM_024900 NM_199320 79960 -0.94 3.79E-03 C10orf104 229145 at AA541762 NM_173473 119504 -0.94 1.46E-03 BF062399 240141_at BF062399 — — -0.94 1.03E-03 LOC286437 239762_at AI080505 — 286437 -0.94 1.26E-04 AA714835 1556646_at AA714835 ... — -0.94 6.42E-04 MGC3222 233480 at AK026869 NM 024334 79188 -0.94 1.32E-03 NEDD4 213012_at D42055 NM_006154 NM_198400 4734 -0.94 3.31 E-03 MGC26979 232023 at AL575584 NM_153704 91147 -0.94 2.50E-03 BE669703 229541 at BE669703 — — -0.94 5.09E-04 AW665287 243725_at AW665287 — — -0.94 8.33E-04 SPG7 202104_s_at NM_003119 NM_003119 NM_199367 6687 -0.94 4.93E-03 FFX-r2-Ec-bioB=X-r2-Ec-bioB-EisiFFX-r2-Ec-bioB-i — — -0.94 1.31E-04 AG1 212854_x_at AB051480 XM 371384 XM_496394 440673 -0.94 2.84E-03 BF478154 242620 at BF478154 — — -0.94 2.31E-03 PPM1K 235061_at AV706522 NM_152542 152926 -0.94 2.87E-04 MDS010 218587_s_at NM_020231 NM_020231 NM_152305 56983 -0.94 7.79E-03 RNF13 201779_s_at AF070558 NM 007282 NM_183381 NM_183382 NM_183383 NM 183384 11342 -0.93 1.21E-06 ATP8B2 226771_at AB032963 NM_00100585 5 NM_020452 57198 -0.93 1.31E-06 DCTD 210137_s_at BC001286 NM_001921 1635 -0.93 4.45E-04 LOC286260 232420_x_at AA706480 — 286260 -0.93 3.00E-04 IDS 217432_s_at AF179281 NM_000202 NM_006123 3423 -0.93 1.24E-03 ANKRD10 223251 s at BC001727 NM_017664 55608 -0.93 6.05E-05 AK098354 1555824 a at AK098354 — — -0.93 2.66E-04 DOCK9 212538_at AL576253 NM_015296 23348 -0.93 3.70E-03 DRE1 206551 x at NM 017644 NM 017644 54800 -0.93 7.84E-04 SNF1LK2 213221 s at ABO18324 NM 015191 23235 -0.93 7.54E-03 KIAA1546 227624_at AB046766 XM_042301 57667 -0.93 7.15E-03 AI417992 240513 at AI417992 — — -0.93 7.71 E-03 U2AF1 231904_at AU122448 NM 006758 7307 -0.92 7.45E-04 KIAA0492 215109_at R02172 XMJ378914 57238 -0.92 3.40E-03 306 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays LOC158563 226273_at AA218974 ... 158563 -0.92 1.79E-04 AF130054 211452_x_at AF130054 — — -0.92 4.58E-03 NCOA7 225344_at AL035689 NM_181782 135112 -0.92 1.11E-03 LOC284356 1555842_at BM978026 — 284356 -0.92 8.07E-03 EXOSC3 242590_at BE464643 NM_00100226 9 NM_016042 51010 -0.92 4.59E-03 MALAT1 224558 s at AI446756 — 378938 -0.92 8.89E-03 C20orf44 229672_at AA707125 N M 018244 NM_199487 NM_199513 55245 -0.92 1 02E-03 N64760 212622_at N64760 — — -0.92 3.14E-04 HRMT1L1 202098_s_at NM_001535 NM 001535 NM_206962 3275 -0.92 5.36E-05 NEU1 208926 at U84246 NM_000434 4758 -0.92 6.42E-03 AF131777 215504 x at AF131777 — ... -0.92 7.86E-03 PS1TP4 226381_at AW450329 — 414327 -0.92 9.25E-03 C3orf6 235051_at BF696931 NM 174908 NM 178335 152137 -0.92 9.12E-03 MAPILC3B 208785_s_at BE893893 NM_022818 81631 -0.91 1.87E-03 NM_024900 218517_at NM 024900 — ... -0.91 8.37E-03 P4HA2 202733_at NM_004199 NM_004199 8974 -0.91 4.34E-03 MBTD1 207115 x at NM_017643 NM_017643 54799 -0.91 1.43E-03 BF476403 230218 at BF476403 — — -0.91 2.19E-03 AL080160 217446_x_at AL080160 ... ... -0.91 1.65E-03 C19orf4 219005_at NM_012109 NM_012109 25789 -0.91 5.96E-04 LOC399491 214035_x_at AA308853 — 399491 -0.91 6.27E-04 CHPT1 1559739_at AK025141 NM_020244 56994 -0.91 6.26E-03 U2AF1L1 206512_at NM_005083 — 7310 -0.91 8.01 E-03 C20orf44 244795_at AV693986 NM 018244 NM 199487 NM_199513 55245 -0.91 4.26E-04 LOC339047 221501_x_at AF229069 XM_290671 339047 -0.91 2.33E-04 FLJ35093 235125_x_at AI078279 NM 198549 374986 -0.91 2.80E-03 SLC22A17 218675_at NM_020372 NM 016609 NM_020372 51310 -0.91 2.67E-06 EIF4A1 214805_at U79273 NM_001416 1973 -0.91 7.74E-03 Cep164 204251_s_at NM 014956 NM 014956 22897 -0.91 4.21 E-03 AK2 212172_at AW277253 NM 001625 NM 013411 NM_172199 204 -0.91 1.68E-04 NFKB1 209239_at M55643 NM_003998 4790 -0.91 2.66E-03 AL833666 1566854_at AL833666 — ... -0.91 3.74E-03 BE857570 235677_at BE857570 — ... -0.91 6.67E-04 KIAA1276 227504_s_at N64630 XM_039169 27146 -0.91 9.00E-05 KIAA0590 204792 s at NM 014714 NM_014714 9742 -0.91 2.73E-03 AV733292 225444_at AV733292 — ... -0.91 9.09E-04 BF057855 236829_at BF057855 — — -0.91 4.03E-03 BC020820 1562962_at BC020820 — — -0.91 1.89E-04 FX-r2-Ec-bioB: ;X-r2-Ec-bioB-3\FFX-r2-Ec-bioB-· — — -0.91 4.89E-04 AF086478 1558948 a at AF086478 — — -0.91 5.21E-03 PHF20L1 222133_s_at AK022280 NM_016018 NM 024878 NM 032205 NMJ98513 51105 -0.90 9.98E-03 HERC4 208055_s_at NM 015601 NM_015601 26091 -0.90 1.92E-03 R42552 239718 at R42552 — — -0.90 1.67E-03 307 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., etal., Cells Useful for Immuno-Based BoNT/A Activity Assays FBX09 1559094_at AK095307 NM_012347 NM 033480 NM_033481 26268 -0.90 1.55E-04 OSBP 1563051_at BC017975 NM_002556 5007 -0.90 8.83E-03 GPR27 227769 at AI703476 NM 018971 2850 -0:90 3.33E-03 C21orf33 202217_at NM_004649 NM 004649 NM_198155 8209 -0.90 2.00E-03 RGS8 234297_at AL359941 NM_033345 85397 -0.90 4.04E-03 AFFX-BioB-M ^FFX-BioB-M_a AFFX-BioB-M — — -0.90 9.42E-05 POLR3E 233458 at AB040885 NM 018119 55718 -0.90 1.75E-03 DKFZp761B107 226139_at BE670598 NM_173463 91050 -0.90 4.14E-03 AA923289 236666_s_at AA923289 XM 372416 390205 -0.90 1.19E-03 BE247450 244443_at BE247450 XM 498623 440309 -0.90 3.66E-03 SEMA4B 234725_s_at AK026133 NM 020210 NM_198925 10509 -0.90 1.81E-03 WDFY3 212606_at AL536319 NM_014991 NM 178583 NM_178585 23001 -0.90 3.35E-04 NM 018336 205955_at NM_018336 ... — -0.90 5.74E-04 SELS 223209_s_at AF328864 NM_018445 NM_203472 55829 -0.90 2.33E-03 CDH20 243657_at AW593060 NM_031891 28316 -0.90 7.78E-03 KIAA1223 225735_at AL110131 XM_048747 57182 -0.90 7.05E-04 BE502826 231550 at BE502826 — — -0.90 5.25E-03 DDX26 218819 at NM 012141 NM 012141 26512 -0.90 1.74E-03 FLJ32731 218017 s at NM 025070 XM 372038 138050 -0.90 3.84E-07 FLJ32499 1552711_a_at NM_144607 NM_144607 124637 -0.90 6.17E-05 AFFX-BioB-5 ^FX-BioB-5_a AFFX-BioB-5 — — -0.89 2.50E-05 TMEM17 1557137 at AA084725 NM_198276 200728 -0.89 9.22E-04 R26456 243135_x_at R26456 — — -0.89 2.43E-03 FFX-r2-Ec-bioC rX-r2-Ec-bioC-3 ^FFX-r2-Ec-bioC-; — — -0.89 1.35E-04 RAB5A 215956_at AK022065 NM_004162 5868 -0.89 3.52E-03 rFX-r2-Ec-bioB:X-r2-Ec-bioB-IAFFX-r2-Ec-bioB-l\ — — -0.89 3.74E-05 NXPH4 221967 at AI933199 NM 007224 11247 -0.89 1.39E-05 PERLD1 221811_at BF033007 NM 033419 93210 -0.89 3.44E-04 WDR21 214758_at AL080157 NM_015604 NM_181340 NM_181341 26094 -0.89 2.29E-04 MDS009 236649 at AA907927 NM 020234 56986 -0.89 1.30E-03 DISP1 228184_at AK023679 NM_032890 84976 -0.89 6.47E-05 HIST1H2BH 208546 x at NM 003524 NM 003524 8345 -0.89 5.00E-03 MLR1 240592_at Al939336 NM_153686 254251 -0.89 2.34E-03 AF088033 1556228_a at AF088033 ... ... -0.89 7.95E-05 FLJ10815 228951_at AI631572 NM_018231 55238 -0.89 1.85E-03 UTP14A 221514 at BC001149 NM 006649 10813 -0.89 9.63E-03 BBP 213882_at AA012917 NM_032027 83941 -0.89 3.54E-05 NCSTN 208759_at AF240468 NM_015331 23385 -0.89 6.91 E-06 LOC283922 228688_at AA843726 XM_208908 283922 -0.88 3.60E-03 Cep164 204250 s at AI655714 NM 014956 22897 -0.88 2.74E-03 ZFWE26 213073_at AB002319 NM_015346 23503 -0.88 1.02E-03 AI525856 239016_at AI525856 — — -0.88 4.67E-05 IREB2 1555476 at BC017880 NM_004136 3658 -0.88 1.40E-03 W80462 242194 at W80462 — — -0.88 2.61 E-03 C13orf21 228044_at AI420319 NM 001010897 387923 -0.88 1.82E-03 WTAP 1560274_at BF679507 NM_004906 NM 152857 NM_152858 9589 -0.88 2.07E-04 MGC4278 220352_x_at NM_024305 ... 79151 -0.88 6.74E-03 308 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 PHF17 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays 225816_at AW138134 NM_024900 79960 -0.88 3.82E-03 NM. .199320 LOC401551 243900 at AM 90548 XM 376909 401551 -0.88 6.97E-03 FLJ35630 229603_at AA971753 NM. .152618 166379 -0.88 2.21 E-03 KIAA1008 218362_s_at NM 014953 NM 014953 22894 -0.88 7.57E-04 SON 201085_s_at AA664291 NM 003103 6651 -0.88 5.49E-03 NM 032195 NM. .058183 NM. .138925 NM. .138926 NM. .138927 AK021474 215892_at AK021474 ... ... -0.88 5.75E-03 DCTD 201572_x_at NM 001921 NM. .001921 1635 -0.88 1.87E-04 H73101 1556984_at H73101 — — -0.87 3.73E-03 USP34 230148 at AI831431 NM 014709 9736 -0.87 8.65E-03 Ufc1 217797_at NM_016406 NM. .016406 51506 -0.87 7.99E-05 BE044193 229384_at BE044193 — — -0.87 8.85E-03 VMP1 224917 at BF674052 NM 030938 81671 -0.87 8.73E-03 KIAA0711 204301 at NM 014867 NM 014867 9920 -0.87 4.26E-05 C21orf66 218515_at NM_016631 NM. 013329 94104 -0.87 2.26E-04 NM 016631 NM .058191 NM 145328 D4S234E 209569_x_at NM_014392 NM 014392 27065 -0.87 6.40E-03 TJP2 202085_at NM_004817 NM 004817 9414 -0.87 5.83E-04 NM. .201629 MAN1A2 217282_at AK001970 NM 006699 10905 -0.87 5.09E-03 C15orf17 224798_s_at Al079857 NM. .020447 57184 -0.87 5.80E-03 SLC20A2 231818_x_at AK023965 NM. .006749 6575 -0.87 8.22E-03 C14orf103 222840 at H96715 NM. .018036 55102 -0.87 2.43E-03 AFFX-BioC-3 i\FFX-BioC-3_a AFFX-BioC-3 — — -0.87 3.17E-05 MGLL 211026_s_at BC006230 NM_00100379 11343 -0.87 3.12E-03 NM *+ 007283 FZD6 203987_at NM_003506 NM. .003506 8323 -0.87 9.59E-03 AFFX-BioC-5 i\FFX-BioC-5_a AFFX-BioC-5 — ... -0.87 1.11E-04 ENPP2 210839_s_at D45421 NM. .006209 5168 -0.87 1.49E-04 DKFZP564D16C 231799 at AK021886 XM 371074 26115 -0.87 1 88E-04 ANKRD20A 1569608_x_at BC016022 NM. .032250 440841 -0.87 2.10E-03 LOC440841 XM. .496541 84210 AW341304 237332_at AW341304 — — -0.87 1.73E-03 USP36 224979_s_at AU154368 NM 025090 57602 -0.87 8.89E-04 FLJ10980 225327_at AB037791 NM. .019600 56204 -0.87 3.59E-05 AI768374 228661_s_at Al768374 — — -0.87 3.95E-04 CANX 200068_s_at M94859 NM .001746 821 -0.87 7.71 E-03 MED6 207078 at NM 005466 NM 005466 10001 -0.87 9.36E-03 C3orf6 226713_at AI247881 NM. .174908 152137 -0.87 4.87E-03 NM 178335 DJ328E19.C1 . 201104_x_at NM_015383 NM 015383 200030 -0.87 9.45E-04 1 NM. .173638 25832 LOC200030 NM 183372 284565 MGC8902 XM .371384 440673 AG1 XM 496394 CARD14 240392_at BF752351 NM. .024110 79092 -0.87 6.29E-03 NM. .052819 FKBP2 203391_at NM_004470 NM. .004470 2286 -0.86 6.91 E-03 NM. .057092 CBS 212816 s at BE613178 NM. .000071 875 -0.86 6.44E-03 309 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., etal., Cells Useful for Immuno-Based BoNT/A Activity Assays AI695743 244534_at AI695743 ... ... -0.86 1.23E-04 NGLY1 220742_s_at NM 018297 NM_018297 55768 -0.86 4.72E-04 H19 224997 x at AL575306 — 283120 -0.86 2.98E-03 DYRK1B 204954_s_at NM_004714 NM_004714 NM_006483 NM 006484 9149 -0.86 6.27E-03 IDS 202439_s_at NM_000202 NM_000202 NM_006123 3423 -0.86 1.14E-03 LOC284267 228453_at AW004076 — 284267 -0.86 6.01 E-03 JUN 201466_s_at NM_002228 NM_002228 3725 -0.86 6.35E-03 TRAP1 228929 at Al341246 NM 016292 10131 -0.86 7.28E-03 TSC1 209390 at AF013168 NM 000368 7248 -0.86 1.82E-03 NM_00100856 7 MLR1 235970_at Al807408 NM_153686 254251 -0.86 7.89E-04 AI086530 217604_at Al086530 ... ... -0.86 1.82 E-03 DVL3 201908_at NM 004423 NM_004423 1857 -0.86 2.67E-04 HIST1H3D 214522_x at NM 021065 NM_003530 8351 -0.86 4.36E-05 HUMRGE/M10IUMRGE/M100K-HUMRGE/M100 — — -0.86 2.30E-03 TPP1 200742_s_at BG231932 NM 000391 1200 -0.86 7.91 E-03 TTC3 208664_s_at AU131711 NM_00100189 4 NM 003316 7267 -0.86 7.07E-03 RFPL2 207227_x_at NM_006605 NM_006605 10739 -0.86 3.03E-03 D4S234E 209570_s_at BC001745 NM_014392 27065 -0.86 1.12E-04 LOC146174 230721 at BF436957 NM 173501 146174 -0.86 5.19E-04 C9orf68 1554708 s at BC034293 NM_017985 55064 -0.86 1.35E-03 R3HDM 240503_at AW274946 NM 015361 23518 -0.86 6.04 E-03 SNCA 204467_s_at NM_000345 NM 000345 NM_007308 6622 -0.85 9.17E-05 AK094546 1556205_at AK094546 — ... -0.85 6.76E-04 KIAA1450 225924_at AI478634 — 57600 -0.85 6.97E-03 SKP1A 200719_at BE964043 NM 006930 NM 170679 6500 -0.85 3.06E-03 PGK1 228483_s_at BE856250 NM_000291 5230 -0.85 2.17E-03 LOC200030 229447_x_at N32025 NM_183372 200030 -0.85 8.99E-04 PRKCA 1560074 at AL119889 NM_002737 5578 -0.85 1.54E-03 Al332346 225445 at AI332346 — — -0.85 1.78E-03 COG1 231813_s_at AV746580 NM_018714 9382 -0.85 1.02E-03 FLJ20203 219846_at NM_025174 NM 032292 54856 -0.85 1.98E-03 GALNS 206335_at NM_000512 NM 000512 2588 -0.85 9.33E-03 CASP9 203984_s_at U60521 NM 001229 NM_032996 842 -0.85 1.05E-03 AU147777 232145_at AU147777 XM 371506 388969 -0.85 7.96E-03 MGC52110 226039_at AW006441 NM 001008215 493753 -0.85 9.51 E-06 MACF1 208634_s_at AB029290 NM_012090 NM_033044 23499 -0.85 2.09E-03 FLJ41603 227717_at BF939317 NM 001001669 389337 -0.84 5.48E-03 FLJ12716 233558_s_at AK023390 NM 021942 NM_199053 60684 -0.84 1.27E-03 BE676062 231249_at BE676062 ... ... -0.84 2.18E-03 KIAA0415 209913_x_at AB007875 XM_166527 XM 379771 XM 499251 XM_499396 9907 -0.84 3.69E-03 PCAF 203845_at AV727449 NM 003884 8850 -0.84 4.85E-03 MONDOA 211789 s at AF312918 NM 014938 22877 -0.84 4.65E-03 C6orf70 227656_at AW968493 XM 376556 55780 -0.84 1.48E-03 310 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays PTPN21 226380_at N21442 NM 007039 11099 -0.84 1.06E-03 PNMT 206793_at NM_002686 NM 002686 5409 -0.84 2.71 E-03 ALG5 218203 at NM 013338 NM_013338 29880 -0.84 8.89E-03 LOC90110 226842_at AV694039 — 90110 -0.84 5.28E-03 CYLD 39582_at AL050166 NM_015247 1540 -0.84 4.04 E-03 LOC150271 228658_at R54042 — 150271 -0.84 6.95E-03 FER1L4 222245 s_at AF218012 — 80307 -0.84 5.44E-05 MECT1 213091_at AB014516 NM_015321 NM_025021 23373 -0.84 2.37E-04 AL359605 227318_at AL359605 — — -0.84 4.99E-06 SH3GL2 205751_at NM 003026 NM 003026 6456 -0.84 3.31 E-04 MUC1 213693_s_at AI610869 NMJD02456 NM_182741 4582 -0.84 6.09E-04 RSHL2 223713_at AF353618 NM 031924 83861 -0.84 3.80E-03 MRPS33 218654_s_at NM_016071 NM 016071 NM 053035 51650 -0.83 2.36E-03 FBLP-1 1554795_a_at BC019895 NM 017556 54751 -0.83 5.75E-03 XPOT 227117_at AW242820 NM 007235 11260 -0.83 5.63E-03 ACRV1 206776_x_at NM_001612 NM 001612 NM_020069 NM_020107 NM 020108 NM 020109 NM_020110 NM_020111 NM 020113 NM_020114 NM_020115 56 -0.83 7.51 E-03 AI334297 225961_at Al334297 — — -0.83 5.29E-04 TMEM34 219074 at NM_018241 NM_018241 55751 -0.83 1.81 E-03 AI494500 241448 at AI494500 — — -0.83 9.31 E-04 LOC440160 239010_at AI744280 XM 498571 440160 -0.83 6.65E-03 PPID 204186_s_at AI014573 NM_005038 5481 -0.83 2.63E-04 PAK3 236277 at H23551 NM 002578 5063 -0.83 1.34E-04 NPM1 221923_s_at AA191576 NM_002520 NM_199185 4869 -0.83 5.74E-03 ProSAPiPI 204447_at NM_014731 NM_014731 9762 -0.83 4.47E-04 NSMAF 232149_s_at BF056507 NM 003580 8439 -0.83 6.67E-03 MGC21881 1555874_x_at BC019880 NM_203448 389741 -0.83 1.97E-03 FLJ37953 241825_at AI265967 NM_152382 129450 -0.83 2.38E-03 INPP5A 203006_at NM_005539 NM 005539 3632 -0.83 5.00E-04 SLC25A16 210686_x_at BC001407 NM 152707 8034 -0.83 2.87E-03 CBS 1553972_a_at BC007257 NM_000071 875 -0.83 5.27E-03 KIAA0804 209553_at BC001001 NM_00100992 1 NM_015303 23355 -0.83 9.90E-04 AW945538 239208_s_at AW945538 — -0.83 3.44E-04 AK021583 232931_at AK021583 — — -0.82 4.13E-03 BDP1 224227_s_at AF298152 NM 018429 55814 -0.82 4.88E-03 SPG7 214494_s_at NM_005200 NM_003119 NM_199367 6687 -0.82 9.51 E-03 ZNF599 1558390_at BC033354 NM_00100724 7 NM_00100724 8 l ___ 148103 -0.82 1.18E-03 FX-r2-Ec-bioC-X-r2-Ec-bioC-E^FFX-r2-Ec-bioC-! ___ -0.82 2.81 E-04 KIAA0690 1559127_x_at BC042908 NM 015179 23223 -0.82 1.09E-04 KIAA1546 1569385_s_at BC019007 XMJM2301 57667 -0.82 3.51 E-04 311 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays SSR4 201004_at NM_006280 NM_006280 6748 -0.82 1.83E-03 TRIT1 218617 at NM 017646 NM 017646 54802 -0.82 5.10E-05 MAPK10 204813_at NM_002753 NM 002753 NM 138980 NM_138981 NM_138982 5602 -0.82 2.98E-03 CGI-119 219206_x_at NM_016056 NM_016056 51643 -0.82 3.02E-03 GPRASP1 204793_at NM_014710 NM_014710 9737 -0.82 2.03E-04 ARHGAP1 241419_at AA709154 NM_004308 392 -0.82 2.43E-03 KIAA0934 212504_at N31807 NM 014974 22982 -0.82 2.71 E-04 LOC51619 240014 at Al821720 NM_015983 51619 -0.82 7.64E-03 MEF2A 212535_at AA142929 NMJD05587 4205 -0.81 8.41 E-04 AI859463 242111_at AI859463 — — -0.81 3.79E-03 KLF15 231015 at AW014734 NM 014079 28999 -0.81 3.05E-03 MGC8902 AG1 213612_x_at Al800419 NM 173638 XM 371384 XM_496394 284565 440673 -0.81 1.93E-03 FLJ10038 205511_at NM 017976 — 55056 -0.81 1 24E-03 PCDHA2 210572_at BC003126 NM_018905 NM_031495 NM 031496 56146 -0.81 3.16E-04 EYA1 214608_s_at AJ000098 NM 000503 NM_172058 NM_172059 NM_172060 2138 -0.81 3.74E-03 CENTG1 229917 at BE551002 NM_014770 116986 -0.81 1 70E-03 PLRG1 225194_at NM_002669 NM_002669 5356 -0.81 2.39E-03 DUSP16 236511_at AI798976 NM_030640 80824 -0.81 8.12E-03 LRRFIP1 201862_s_at NM_004735 NM_004735 9208 -0.81 2.88E-04 AI393706 238944 at AI393706 — — -0.81 3.70E-03 TNIP1 207196 s at NM_006058 NM_006058 10318 -0.81 3.18E-03 SYNCRIP 236146_at BF593158 NM 006372 10492 -0.81 3.42E-03 TAS2R5 231757 at NM 018980 NM_018980 54429 -0.81 1.10E-03 PABPC4 201064 s at NM 003819 NMJ303819 8761 -0.81 1.63E-03 AW367380 236408_at AW367380 — — -0.81 6.92E-03 C21orf127 234676_s_at AK021678 NM 013240 NM_182749 29104 -0.81 6.83E-03 NM 018678 220494 s at NM 018678 — — -0.81 9.98E-03 AF5Q31 232864_s_at N59653 NM_014423 27125 -0.81 5.40E-03 LTB4R 216388 s_at U33448 NM_181657 1241 -0.80 3.43E-03 ENPP2 209392 at L35594 NM 006209 5168 -0.80 1.95E-05 SMURF2 205596 s at AY014180 NM 022739 64750 -0.80 2.21 E-04 STS 243858_at AA699970 NM_000351 412 -0.80 1.20E-03 KLHDC1 1552733_at NM_172193 NM 172193 122773 -0.80 1.05E-03 ASTN2 215407_s_at AK024064 NM 014010 NM_198186 NM_198187 NM_198188 23245 -0.80 2.08E-03 BQ008117 1556659 at BQ008117 — — -0.80 5.03E-03 FLJ10534 239042_at AI282511 NM_018128 55720 -0.80 2.54E-03 RABL5 218785_s_at NM_022777 NM_022777 64792 -0.80 2.32E-03 RNASET2 217983_s_at NM_003730 NM_003730 8635 -0.80 7.39E-04 BTBD14B 215587_x_at AK023891 NM 052876 112939 -0.80 3.30E-03 FALZ 232909_s_at AU146870 NM_004459 NM_182641 2186 -0.80 7.77E-03 NEUGRIN 228541_x_at AI049608 NM_016645 51335 -0.80 2.24E-03 UNC5B 213100_at AA127885 NM_170744 219699 -0.80 6.29E-03 312 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., etal., Cells Useful for Immuno-Based BoNT/A Activity Assays LOC439987 LOC439993 229609_at BF224281 XM_495841 XM 498488 439987 439993 -0.80 7.79E-04 RPIP8 213439_x_at AI197870 NM_006695 10900 -0.80 3.47E-05 LOC285949 1563781_at AK096687 — 285949 -0.80 3.61 E-03 FLJ22313 236170_x_at AI377423 NM_022373 64224 -0.80 5.62E-04 AQP3 39248 at N74607 NM 004925 360 -0.80 4.75E-03 FALZ 209271 at AB032251 NM 004459 NM_182641 2186 -0.80 9.58E-03 LOC440118 •FX-M27830 M AFFX-M27830_M XM_498554 440118 -0.80 9.04E-04 ARF1 232175_at AI972094 NM 001658 375 -0.80 1.30E-04 ERBB2 216836_s_at X03363 NM 00100586 2 NM_004448 2064 -0.80 1.70E-04 LOC440823 227168_at BF475488 XM 498878 440823 -0.80 8.41 E-03 DUSP8 206374_at NM 004420 NM_004420 1850 -0.80 9.45E-04 ARHGAP1 202117_at BG468434 NM 004308 392 -0.79 5.77E-04 CYLD 221903_s_at BE046443 NM_015247 1540 -0.79 4.50E-05 AFFX-BioDn-5 ^FFX-BioDn-5 e AFFX-BioDn-5 — — -0.79 2.95E-05 CARS 202402_s_at NM_001751 NM_001751 NM 139273 833 -0.79 7.28E-03 ASTN2 209693_at AF116574 NM_014010 NM 198186 NM_198187 NM_198188 23245 -0.79 9.79E-04 AK025546 232161_x_at AK025546 ... ... -0.79 4.20E-03 PTPRD 214043_at BF062299 NM 002839 NM_130391 NM_130392 NM_130393 5789 -0.79 8.45E-03 ATP6V0A1 212383 at AL096733 NM 005177 535 -0.79 9.12E-04 AIG1 223136_at AF151861 NM 016108 51390 -0.79 8.00E-03 ANXA7 242027_at Al 732079 NM 001156 NM 004034 310 -0.79 8.52E-04 HDLBP 225012_at BE378479 NM 005336 NM_203346 3069 -0.79 4.04E-04 C10orf51 231196_x_at AI333226 — 387644 -0.79 1.33E-05 WASL 227010_at BF438330 NM 003941 8976 -0.79 1.01 E-03 RSNL2 226425 at AU144247 NM 024692 79745 -0.79 4.96E-05 ATP9A 216129_at AL117659 XM_030577 10079 -0.79 2.42E-04 AA888098 244426_at AA888098 — — -0.79 7.13E-04 DYM 220774 at NM 017653 NM 017653 54808 -0.79 1.83E-03 C2orf17 221983 at AL040896 NM 024293 79137 -0.79 6.51 E-03 MGC4618 223462_at BC005158 NM_032326 84286 -0.78 2.33E-03 RSL1D1 212019_at AK025446 NM 015659 26156 -0.78 3.44E-03 LOC200030 MGC8902 AG1 201103_x_at BE299495 NM 173638 NM_183372 XM_371384 XM_496394 200030 284565 440673 -0.78 1.09 E-03 WDR13 222138_s_at AF158978 NM_017883 64743 -0.78 1.22E-03 SERP1 200971_s_at NM_014445 NM_014445 27230 -0.78 1.90E-03 KIAA1049 213311_s_at BF000251 NM_014972 22980 -0.78 2.49E-03 BG502771 226397_s_at BG502771 — — -0.78 2.83E-03 AI652868 225811 at AI652868 ... ... -0.78 5.96E-03 AL559202 226458 at AL559202 ... ... -0.78 8.12E-03 R15431 236440_at R15431 ... ... -0.78 1.66E-05 SLC43A1 204394_at NM 003627 NM_003627 8501 -0.78 3.44E-03 C18orf17 238480 at AI871745 NM_153211 125488 -0.78 7.85E-04 C11orf31 228331_at AA526939 NM 170746 280636 -0.78 1.80E-03 313 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays SLC9A3 226125_at BF346665 NM_004174 6550 -0.78 1.02E-03 EPC2 225838_at AK002010 NM_015630 26122 -0.78 1.65E-04 KIAA0934 212503 s at N22859 NM_014974 22982 -0.78 2.51 E-04 EFHC1 231026_at AW451135 NM_018100 114327 -0.78 9.28E-03 AA883831 244042 x at AA883831 — — -0.78 9.44E-03 NIN 225921_at AL359571 NM_016350 NM_020921 NM_182944 NM_182945 NM_182946 51199 -0.78 1.33E-04 AW502656 240800 x at AW502656 — — -0.77 2.82E-05 SMYD2 212922_s_at Al809870 NM_020197 56950 -0.77 4.17E-03 NDUFV3 226616_s_at NM_021075 NM 00100150 3 NM 021075 4731 -0.77 3.48E-03 LSS 202245_at AW084510 NM_00100143 8 NM 002340 4047 -0.77 1.95E-04 TTC3 208662_s_at Al885338 NM_00100189 4 NM_003316 7267 -0.77 1.75E-04 IL10RB 209575_at BC001903 NM 000628 3588 -0.77 1.78E-05 PLTP 202075_s_at NM_006227 NM_006227 NM_182676 5360 -0.77 6.25E-03 ANKRD17 225852_at BE463523 NM_032217 NM_198889 26057 -0.77 1.79E-05 LOC283981 232463_at T77995 — 283981 -0.77 9.63E-03 AM 46751 242565_x_at AM 46751 — — -0.77 1.83E-03 GDF1 LASS1 206397_x_at NM_001492 NM 001492 NM 021267 NM 198207 10715 2657 -0.77 1.04 E-04 FLJ10276 218004_at NM_018045 N M 018045 55108 -0.77 1.60E-03 BF223556 229376_at BF223556 — — -0.77 3.00E-03 KIAA1109 212779 at AB029032 XM_371706 84162 -0.77 8.29E-04 AI983303 237877_at AI983303 — — -0.77 2.54E-05 JMJD2A 203204_s_at BC002558 NM 014663 9682 -0.77 5.29E-03 RBM8A 217856_at AF182415 NM 005105 9939 -0.77 1.77E-03 FLJ12716 218179_s_at NM_021942 NM_021942 NM_199053 60684 -0.77 4.05E-04 CGI-119 222845_x_at AF161526 NM_016056 51643 -0.77 4.64E-05 BI520422 1559467_at BI520422 — — -0.77 6.79E-03 AA134418 232150 at AA134418 — — -0.77 3.88E-03 ZNF323 222016_s_at AW086021 NM_030899 NM_145909 64288 -0.77 3.58E-03 GLG1 214730_s_at AK025457 NM_012201 2734 -0.77 8.94E-05 AK024602 222207_x_at AK024602 — — -0.76 4.03E-03 BE964222 226589_at BE964222 — — -0.76 2.53E-04 GNAS 228173_at AA810695 NM_000516 NM 016592 NM 080425 NM_080426 2778 -0.76 5.49E-03 MONDOA 225157_at AW245631 NM 014938 22877 -0.76 3.06E-04 KIAA2010 215607_x_at AU144530 NM 017936 55671 -0.76 3.17E-03 NM 032560 314 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays DJ328E19.C1. 1 LOC200030 MGC8902 LOC439928 AG1 226740_x_at BF740216 NM_015383 NM 173638 NM_183372 XM_371384 XM_496394 XM 498427 200030 25832 284565 439928 440673 -0.76 1.09E-03 LEAP-2 1552362_a_at NM_052971 NM_052971 116842 -0.76 5.61 E-03 BRUNOL4 238966_at AA678985 NM 020180 56853 -0.76 8.60E-03 AA827878 223577_x_at AA827878 — — -0.76 5.84E-03 CDKL1 244670_at AI767697 NM_004196 8814 -0.76 4.97E-03 NALP1 218380_at NM_021730 NM 014922 NM 033004 NM 033006 NM 033007 22861 -0.76 2.51 E-03 MAN1B1 65884 at AA631254 NM 016219 11253 -0.76 3.92E-04 GOSR2 235041_at AW005457 NM 004287 NM_054022 9570 -0.76 9.63E-04 BI496583 1557675 at BI496583 — ... -0.76 7.35E-03 AA194266 238728 at AA194266 — ... -0.76 2.48E-03 EFEMP2 209356_x_at AB030655 NM_016938 30008 -0.76 5.52E-03 NM_018705 220572_at NM_018705 — — -0.76 3.25E-03 MGC2747 224712_x_at AI656658 NM 024104 79086 -0.76 2.38E-04 PIK3R1 212239_at AI680192 NM_181504 NMJ81523 NM_181524 5295 -0.76 7.57E-03 RAB11B 34478 at X79780 NM_004218 9230 -0.76 5.20E-04 FLJ23867 226706_at BE301252 — 200058 -0.76 2.32E-03 NELF 221214_s_at NM_015537 NM_015537 26012 -0.76 9.78E-05 MAP2K7 216206_x_at BC005365 NMJ45185 5609 -0.75 1.08E-03 FLJ43806 213752 at BF111846 NM 201628 399563 -0.75 3.92 E-03 CHMP1.5 218177_at AA293502 NM 020412 57132 -0.75 3.04E-04 KNDC1 230359_at N45097 NM 033404 NM 152643 85442 -0.75 6.69E-04 HNRPU 236244_at AI458297 NM 004501 NM 031844 3192 -0.75 7.10E-03 C1orf50 62212_at W37846 NM 024097 79078 -0.75 7.56E-04 KIAA0913 212359_s_at W89120 NM 015037 23053 -0.75 2.87E-05 PPP2CA 215628 x at AL049285 NM 002715 5515 -0.75 2.81 E-04 C6orf160 225155_at BG339050 XM 499041 441164 -0.75 3.83E-03 CD151 204306_s_at NM_004357 NM_004357 NM 139030 977 -0.75 1.69E-06 HLCS 209399 at D87328 NM_000411 3141 -0.75 2.42 E-04 AA017536 242270_at AA017536 — ... -0.75 2.11E-05 FLJ43663 215330_at AL049991 XM_379520 XM 380146 378805 -0.75 1.78E-05 MRRF 225126_at BF438352 NM_138777 NM_199176 NM_199177 92399 -0.75 5.23E-03 WNK1 211992 at AI445745 NM_018979 65125 -0.75 3.85E-03 AI870959 244877 at AI870959 — ... -0.75 1.78E-03 LOC94431 216908_x_at AF001549 NM_145237 94431 -0.75 2.16E-03 BG527339 226457_at BG527339 ... ... -0.75 3.79E-03 AA928506 213750 at AA928506 . — ... -0.74 4.38E-04 GP1BB 206655 s at NM_000407 NM_000407 2812 -0.74 4.60E-04 AA629075 236653_at AA629075 — ... -0.74 1.35E-04 TTC3 208661_s_at AW510696 NM_00100189 4 7267 -0.74 1.79E-05 NM 003316 315 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., etal., Cells Useful for Immuno-Based BoNT/A Activity Assays TNRC6C 227149_at AB046802 NM 018996 57690 -0.74 5.66E-03 POFUT2 209578_s_at BC000626 NM 015227 NM 133634 NM_133635 23275 -0.74 1.92E-03 CLDN12 223249_at AL136770 NM 012129 9069 -0.74 2.31 E-03 PICALM 239102_s_at AW293296 NM 00100866 0 NM 007166 8301 -0.74 3.04E-03 SKIV2L 203727_at NM_006929 NM_006929 6499 -0.74 4.08E-04 LOC125150 228719_at BE645222 — 125150 -0.74 7.64E-03 AA026666 235611 at AA026666 — ... -0.74 3.78E-03 KIAA0323 212356_at AB002321 NM_015299 23351 -0.74 1.24E-03 BC031035 1569503_at BC031035 — — -0.74 1.39E-05 UNC5B 226899 at AK022859 NM 170744 219699 -0.74 6.84E-03 KCNRG 239098_at W68737 NM 173605 NM_199464 283518 -0.74 5.28E-03 DPCD 226009_at AM 29328 NM 015448 25911 -0.74 8.18E-03 LEPREL2 204854_at NM 014262 NM_014262 10536 -0.74 3.69E-03 AW341225 1556690_s_at AW341225 ... ... -0.74 1.25E-06 DPP7 224814_at NM 013379 NM_013379 29952 -0.74 2.41 E-04 GAS5 224841_x_at BF316352 — 60674 -0.74 1.39E-03 TRIM8 223132_s_at AF220034 NM 030912 81603 -0 73 1.24E-05 BF056548 232140_at BF056548 XM 499148 441443 -0.73 8.09E-03 PPT2 EGFL8 208469_s_at NM_030652 NM_005155 NM_030652 NM 138717 NM_138934 80864 9374 -0.73 3.43E-03 SH3YL1 204019_s_at NM_015677 NM_015677 26751 -0.73 4.63E-04 EXOSC6 227696_at AI701408 NM_058219 118460 -0.73 1.43E-03 SNIP 232547_at BF062187 NM_025248 80725 -0.73 8.20E-06 AL833564 1563638_at AL833564 — ... -0.73 4.87E-05 MACF1 208633_s_at W61052 NM 012090 NM 033044 23499 -0.73 9.23E-04 CIB1 201953_at NM 006384 NM 006384 10519 -0.73 5.74E-04 RAMP1 204916_at NM_005855 NM_005855 10267 -0.73 1.63E-03 AA694209 229066_at AA694209 — — -0.73 9.44E-03 NOTCH4 205247 at Al743713 NM_004557 4855 -0.73 5.43E-03 BF000009 243952 at BF000009 — — -0.73 9.42E-03 NR2F1 209506_s_at BC004154 NM_005654 7025 -0.73 4.54E-03 LOC92154 1555894_s_at AA829283 NM_138383 92154 -0.73 9.70E-03 C9orf94 229585_at AI803088 NM 152702 206938 -0.73 2.44E-03 MAN1A2 217922 at AL157902 NM 006699 10905 -0.73 1.21 E-03 CGI-119 223892_s_at AF182414 NM_016056 51643 -0.73 1.67E-03 >TAF65(gamma 201836_s_at AU154740 NM_014860 9913 -0.73 6.03E-03 PLXNA3 203623_at AI675453 NM 017514 55558 -0.73 4.76E-04 SPATA11 223318_s_at BC004393 NM_032306 84266 -0.73 9.26E-03 BE674055 236109_at BE674055 — — -0.73 8.42E-03 KIAA2026 228446_at BF062203 XM_088551 158358 -0.73 2.23E-03 CLN3 210859_x_at AF077973 NM_000086 1201 -0.72 4.13E-03 AW129145 238992_at AW129145 — ... -0.72 3.88E-03 LOC201158 1552377_s_at NM 145301 NM_145301 201158 -0.72 2.76E-03 FLJ31265 228341_at Al809108 NM_152395 131870 -0.72 1.87E-03 BF111169 230820_at BF111169 — — -0.72 1.14E-04 D8S2298E 215983_s_at D83768 NM_005671 7993 -0.72 6.50E-03 AI424847 243218 at AI424847 — — -0.72 4.14E-03 316 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays PCDHA9 PCDHAC2 PCDHAC1 PCDHA13 PCDHA12 PCDHA11 PCDHA10 PCDHA8 PCDHA7 PCDHA6 PCDHA5 PCDHA4 PCDHA3 PCDHA2 PCDHA1 224212_s_at AF169689 NM 014005 NM 018898 NM_018899 NM_018900 NM 018901 NM 018902 NM_018903 NM_018904 NM_018905 NM 018906 NM_018907 NM_018908 NM 018909 NM 018910 NM_018911 NM 031410 NM 031411 NM 031495 56134 56135 56136 56137 56138 56139 56140 56141 56142 56143 56144 56145 56146 56147 9752 -0.72 5.55E-04 RBM5 201394_s_at U23946 NM 005778 10181 -0.72 2.11E-03 AFFX-BioDn-3 vFFX-BioDn-3 £ AFFX-BioDn-3 — — -0.72 1.31E-04 WBSCR16 1554409_at BC040695 NM 030798 NM_148842 81554 -0.72 5.09E-04 SYNJ1 212990_at AB020717 NM_003895 NM_203446 8867 -0.72 6.07E-05 C19orf2 222266_at BF796940 NM 003796 NM_134447 8725 -0.72 1.36E-03 RAPGEF2 203097_s_at NM_014247 XM 376350 9693 -0.72 7.01 E-03 PQBP1 207769_s_at NM_005710 NM_005710 NM_144494 NM_144495 10084 -0.72 2.58E-03 LOC162967 FLJ38482 1555790_a_at BC036301 NM_152681 162967 201931 -0.72 3.31 E-03 EGFL4 214778 at AB011541 NM 001410 1954 -0.72 3.38E-05 FLJ21148 219751_at NM_024860 NM__024860 79918 -0.72 3.93E-04 KIAA0773 205368_at NM_014690 NM 014690 9715 -0.72 3.08E-03 FBLP-1 1555480_a_at AF459643 NM 017556 54751 -0.71 6.08E-03 PCDHA3 211870_s_at AF 152481 NM 018906 NM_031497 56145 -0.71 8.36E-04 ULK3 225067_at AL117482 NM_015518 25989 -0.71 5.76E-04 ALS4 201965_s_at NM 015046 NM 015046 23064 -0.71 1.86E-03 RASEF 243862_at AW205358 NM 152573 158158 -0.71 2.57E-03 C16orf45 212736_at BE299456 NM 033201 89927 -0.71 9.07E-06 PAK7 213990_s_at BF056517 NM_020341 NM 177990 57144 -0.71 5.12E-03 SF3B3 200688_at D13642 NM 012426 23450 -0.71 6.09E-04 BRSK1 1552504_a_at NM_032430 NM 032430 84446 -0.71 8.13E-04 C14orf103 226684_at AI217906 NM_018036 55102 -0.71 3.88E-03 SLC35E1 229410 at AI659219 NM 024881 79939 -071 9.27E-04 NFYC 202215 s at NM 014223 NM 014223 4802 -0.71 1.98E-03 MRPL53 225523_at AV726817 NM 053050 116540 -0.71 8.44E-04 C5orf14 220495_s_at NM_024715 NM 024715 79770 -0.71 8.19E-03 RUFY1 218243_at NM 025158 NM 025158 80230 -0.71 4.37E-04 C11orf11 214128_at AB014559 NM_006133 747 -0.71 6.28E-03 ZNF404 239043_at AA084273 XM 292765 342908 -0.71 6.01 E-03 TTC3 208073_x_at NM_003316 NM_00100189 4 NM_003316 7267 -0.71 3.39E-04 RNASET2 217984_at NM_003730 NM_003730 8635 -0.71 8.81 E-04 317 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays AI200555 228275_at AI200555 — ... -0.71 1.65E-03 NM 021031 220452 x at NM 021031 — ... -0.71 1.15E-03 MGC16169 240269_at BF590274 NM 033115 93627 -0.71 5.80E-03 BF590958 226243_at BF590958 XM_372919 391356 -0.71 5.37E-05 RNF139 209510 at AF064801 NM 007218 11236 -0.71 5.26E-04 CNOT4 210203_at R64001 NM_00100822 5 NM_013316 4850 -0.71 8.35E-05 MCM3APAS 220459_at NM 018118 — 114044 -0.70 3.02E-03 MGC42090 236705_at AA017245 NM_152774 256130 -0.70 8.57E-03 KIAA2026 238490_at BG109896 XM_088551 158358 -0.70 5.75E-03 SLC35E1 235035_at BF342223 NM_024881 79939 -0.70 2.86E-03 KIAA0690 1559126_at BC042908 NM 015179 23223 -0.70 2.78E-04 TIM14 225359_at BF666961 NM_145261 NM_201259 NM_201260 NM_201261 131118 -0.70 5.32E-04 PHKA1 205450 at NM 002637 NM_002637 5255 -0.70 2.40E-03 RNF13 201780_s_at NM 007282 NM_007282 NM_183381 NM 183382 NM_183383 NM_183384 11342 -0.70 6.65E-03 CLASP2 212309_at AV725315 NM 015097 23122 -0.70 9.41 E-03 VPS11 203292_s_at NM 021729 NM_021729 55823 -0.70 2.21 E-03 AI791187 241724 x at AI791187 — ... -0.70 4.52E-03 DCTN4 233490_at AI985890 NM_016221 51164 -0.70 4.12E-03 LASS5 224951_at BE348305 NM_147190 91012 -0.70 5.49E-04 SLC35E1 227518 at AW051365 NM 024881 79939 -0.70 4.70E-03 SPPL3 224638_at AI338356 NM_139015 121665 -0.70 2.98 E-03 C11orf1 231530_s_at BG150085 NM_022761 64776 -0.70 2.09E-04 RNF103 202636_at NM_005667 NM 005667 7844 -0.69 5.99E-04 LOC134218 230893 at AI223870 NM 194283 134218 -0.69 5.69E-03 C21orf59 218123_at NM_017835 NM_017835 NM_021254 56683 -0.69 2.83E-04 C19orf12 227704_at N21279 NM 031448 83636 -0.69 4.72E-03 ZF 213584 s at AI432137 NM 021212 58487 -0.69 2.28E-04 MGC4796 223852_s_at BC005169 NM_032017 83931 -0.69 5.00E-03 C9orf112 225586_at BF222775 NM_138778 92715 -0.69 2.74E-06 AK023354 222252_x_at AK023354 — ... -0.69 9.83E-04 AW873330 225674_at AW873330 — ... -0.69 9.10E-04 INSR 213792_s_at AA485908 NM 000208 3643 -0.69 6.19E-03 C6orf111 212179_at AW157501 NM_032870 25957 -0.69 2.41 E-03 AY094612 1566887 x at AY094612 XM 499198 441699 -0.69 9.34E-03 ZNF275 225383 at BF793625 XM_372267 10838 -0.68 4.76E-03 AA811371 238098_at AA811371 — ... -0.68 6.60E-03 RABGAP1L 203020_at NM_014857 NM 014857 9910 -0.68 1.28E-04 ARHGEF2 235595 at AW299534 NM 004723 9181 -0.68 2 77E-03 C6orf52 239417 x at AW103116 XM 371798 347744 -0.68 7.21 E-05 DCL-1 232371_at AU155401 NM_014880 9936 -0.68 4.13E-03 PPID 204185_x_at NM_005038 NM 005038 5481 -0.68 1.13E-03 TP53 201746 at NM 000546 NM_000546 7157 -0.68 6.97E-03 DHRSX 225503 at AL547782 NM_145177 207063 -0.68 8.56E-05 ATF6 226941_at BF439325 NM 007348 22926 -0.68 1.77E-03 PIK3R1 212240_s_at AI679268 NM 181504 NM 181523 NM_181524 5295 -0.68 2.27E-03 FFX-r2-Ec-bioD-X-r2-Ec-bioD-E\FFX-r2-Ec-bioD- l — -0.68 7.51 E-04 318 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 CCNL1 Jacky, B., et al., 220046_s_at Cells Useful for Immuno-Based BoNT/A Activity Assays NM_020307 NM_020307 57018 -0.68 5.67E-04 BC017431 1570087_at BC017431 — ... -0.68 5.92E-03 P29 202553_s_at NM_015484 NM 015484 25949 -0.68 7.53E-03 KIAA0256 212451_at N52532 NM_207170 NM_014701 9728 -0.68 2.25E-03 PPP3CA 202425_x_at NM 000944 NM_000944 5530 -0.68 4.15E-03 QTRT1 221270_s_at NM_031209 NM_031209 81890 -0.68 7.11E-04 C21orf2 203994_s_at U84569 NM 004928 755 -0.67 4.72E-06 KCNAB1 210471_s_at U33428 NM_003471 7881 -0.67 3.93E-03 ASB6 222524_s_at AF151697 NM 172159 NMJ72160 NM 017873 140459 -0.67 1.52E-04 BF438106 228045_at BF438106 NM_177999 -0.67 9.75E-03 NFYC 211797_s_at U62296 NM_014223 4802 -0.67 5.31 E-04 AI344253 238412_at Al344253 — — -0.67 1.27E-03 ZNF551 211721_s_at BC005868 NM 138347 90233 -0.67 3.58E-03 TETRAN 209215_at L11669 NM 001120 10227 -0.67 2.16E-05 C9orf60 202452 at AI991574 NM_006336 10444 -0.67 7.13E-04 IGF2AS 220561_at NM_016412 NM_016412 51214 -0.67 8.13E-03 ER01L 225750_at BE966748 NM_014584 30001 -0.67 2.29E-06 MGC16028 226196_s_at AW827281 NM 052873 112752 -0.67 6.84E-03 KIF1A 225482 at AL533416 NM_004321 547 -0.67 2.15E-03 CAMTA1 213268_at Z98884 NM 015215 23261 -0.67 4.84E-03 MAPT 203930_s_at NM_016835 NM 005910 4137 -0.67 2.43E-03 MGC8721 200847_s_at NM_016127 NM_016834 NM_016835 NM_016841 NM_016127 51669 -0.67 2.91 E-03 LOC158563 226274_at AK025562 — 158563 -0.67 3.76E-04 MAN1B1 218636_s_at NM_016219 NM016219 11253 -0.67 1.77E-05 SFRS7 213649_at AA524053 NM_006276 6432 -0.67 7.31 E-05 AK024117 234969_s_at AK024117 — ... -0.67 8.03E-04 AF336878 211454 x at AF336878 — ... -0.67 4.04E-03 SPTBN1 212071_s_at BE968833 NM 003128 6711 -0.67 1.01 E-04 PCBD1 203557_s_at NM_000281 NM_178313 NM 000281 5092 -0.67 1.83E-04 CNOT6L 227119_at BF103856 NM 00100193 9 NM 144571 246175 -0.67 7.28E-04 SLC19A1 229489_at AI681043 NM 003056 6573 -0.67 1.83E-03 C11orf1 222785_x_at AJ250229 NM_194255 NM 022761 64776 -0.67 1.97E-04 AC 0X1 227962_at BF435852 NM_004035 51 -0.67 9.83E-03 VGLL4 214004 s at AI806207 NM_007292 NM_014667 9686 -0.67 1.59E-04 FBXL6 219189_at NM 024555 NM_012162 26233 -0.67 5.47E-04 EIF3S9 242550_at AA628539 NM_024555 NM 003751 8662 -0.67 2.25E-03 CYHR1 223421_at BC005073 NM_182712 NM 032687 50626 -0.67 2.86E-03 PQBP1 214527_s_at AB041836 NM_005710 10084 -0.67 7.86E-03 AA813998 235837_at AA813998 NM 144494 NM_144495 -0.67 9.41 E-03 MYST4 211874_s_at AF119230 NM 012330 23522 -0.66 1.12E-03 CXXC5 233955 x at AK001782 NM 016463 51523 -0.66 8.92E-03 LOC54499 208715_at BF002031 NM 019026 54499 -0.66 3.49E-04 319 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays LOC286437 229531 at AW182938 286437 -0.66 9.60E-03 LOC283970 221992_at Al925734 XM 498469 283970 -0.66 7.97E-05 PPT2 209826_at AF020544 NM 005155 9374 -0.66 6.89E-03 NM_138717 NM_138934 GPR85 234303_s_at AL161959 NM 018970 54329 -0.66 2.74E-03 KIAA0350 242728_at AA705118 NM_015226 23274 -0.66 8.55E-03 C18orf23 230143_at BF433220 NM 152470 147341 -0.66 6.22E-03 LOC493856 226689_at AI749451 NM 001008388 493856 -0.66 3.86E-04 L1CAM 204584_at AI653981 NM 000425 3897 -0.66 3.46E-03 NM_024003 FLNA 214752_x_at AI625550 NM 001456 2316 -0.66 5.06E-03 CSNK1G1 220640_at NM_022048 NM_00101166 A 53944 -0.66 7.24E-03 NM 022048 C19orf24 221587_s_at BC000890 NM 017914 55009 -0.66 1.58E-03 KIF5C 203130_s_at NM_004522 XM 377774 3800 -0.66 3.64E-03 CNOT4 210867_at AF180475 NM_00100822 4850 -0.66 2.10E-03 O NM_013316 ZNF502 229532_at AI056364 NM 033210 91392 -0.66 4.74E-03 PCDHA9 210674_s_at AF152308 NM 014005 56134 -0.66 1.36E-03 PCDHAC2 NM_018898 56135 PCDHAC1 NM_018899 56136 PCDHA13 NM 018900 56137 PCDHA12 NM 018901 56138 PCDHA11 NM_018902 56139 PCDHA10 NM 018903 56140 PCDHA8 NM 018904 56141 PCDHA7 NM 018905 56142 PCDHA6 NM_018906 56143 PCDHA5 NM 018907 56144 PCDHA4 NM 018908 56145 PCDHA3 NM 018909 56146 PCDHA2 NM_018910 56147 PCDHA1 NM_018911 9752 NM 031410 NM 031411 NM 031495 INPP5B 213804_at AI039084 NM 005540 3633 -0.66 6.73E-03 RNF41 201962_s_at NM_005785 NM 005785 10193 -0.66 3.92E-04 NM_194358 NM_194359 MLL2 227528_s_at AI394529 NM 003482 8085 -0.66 1.08E-03 EPC1 223875_s_at AF277374 NM 025209 80314 -0.66 6.07E-03 CLCN5 232127 at AK021494 NM_000084 1184 -0.66 4.77E-03 BE549909 228172_at BE549909 — ... -0.66 4.49E-03 DTX3 49049_at N92708 NM_178502 196403 -0.66 9.76E-03 AA491228 242176 at AA491228 — ... -0.66 3.24E-03 USP16 222616_s_at AI806796 NM_00100199 10600 -0.66 3.36E-03 £. NM 006447 FLJ10824 212370_x_at AL080183 NM_00100575 387680 . -0.66 2.44E-04 LOC387680 1 55747 XM_290482 NFX1 1553103_at NM_147134 NM 002504 4799 -0.66 5.66E-04 NM 147133 NM 147134 320 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 MAPRE3 Jacky, B., et al., 203841_x_at Cells Useful for Immuno-Based BoNT/A Activity Assays BG222594 NM_012326 22924 -0.66 1.69E-04 AW025023 228503_at AW025023 — ... -0.66 6.46E-03 EIF4G3 201935_s_at AI768122 NM 003760 8672 -0.65 2.11E-03 KIAA1223 225731_at BF196876 XM_048747 57182 -0.65 2.55E-03 RUFY1 233380_s_at AA429145 NM_025158 80230 -0.65 2.87E-03 TMEM43 222418_s_at AA115485 NM 024334 79188 -0.65 6.70E-03 SCMH1 221216_s_at NM 012236 NM_012236 22955 -0.65 1.81E-06 NSMAF 203269_at NM_003580 NM_003580 8439 -0.65 4.56E-03 TPP1 200743_s_at NM 000391 NM_000391 1200 -0.65 7.89E-04 BSCL2 208906_at BC004911 NM 032667 26580 -0.65 1.19E-03 SNCA 204466_s_at BG260394 NM 000345 6622 -0.65 3.00E-06 AW452971 231152_at AW452971 NM 007308 -0.65 2.61 E-03 YWHAZ 214848_at U79277 NM 003406 7534 -0.65 2.64E-04 MANSC1 220945_x_at NM_018050 NM_145690 NM 018050 54682 -0.65 8.05E-04 SELT 225561_at BF692332 NM 016275 51714 -0.65 1.05E-03 CHD2 228999_at AW514564 NM_001271 1106 -0.65 1.05E-04 AI458020 238026 at AI458020 — ... -0.65 6.28E-04 MGC35048 216135_at AK000122 NM_153208 124152 -0.65 3.59E-03 AI937687 232218_at AI937687 — ... -0.65 1.85E-03 PSENEN 218302_at NM 018468 NM 172341 55851 -0.65 3.74E-03 LEMD3 218604_at NM 014319 NM 014319 23592 -0.65 8.61 E-05 KIAA0368 212427_at AB002366 XM 036708 23392 -0.65 3.72E-04 CTSB 213275_x_at W47179 NM_001908 1508 -0.65 8.91 E-03 USP32 244871_s_at AW268357 NM 147780 NM_147781 NM_147782 NM_147783 NM_032582 84669 -0.65 2.06E-03 GAS5 224741 x at BG329175 — 60674 -0.65 2.74E-03 ATP13A1 218052_s_at NM 020410 NM_020410 57130 -0.65 1.62E-03 AA973100 230725_at AA973100 — ... -0.65 1.61 E-03 MBD3 222183_x_at AL390153 NM_003926 283579 -0.64 1.72E-03 FLJ25976 CD248 219025_at NM_020404 NM_174943 NM_020404 53615 57124 -0.64 8.85E-04 PERQ1 228755_at NM_022574 NM_022574 64599 -0.64 4.85E-03 FLJ10618 237741_at AW514168 NM 018155 55186 -0.64 7.33E-03 TGFBRAP1 205210_at NM_004257 NM_004257 9392 -0.64 3.31 E-03 SNAP91 204953_at NM_014841 NM_014841 9892 -0.64 7.24E-03 AI631833 227396_at AI631833 — ... -0.64 8.39E-03 MICAL2 212472_at BE965029 NM 014632 9645 -0.64 2.60E-04 KIAA0592 211068_x_at BC006456 NM_015262 253725 -0.64 1.32E-03 RBM8A 213852_at BG289199 NM 005105 9939 -0.64 9.90E-03 TMAP1 227326_at BE966768 NM 00100852 8 NM 00100852 9 NM 198530 NM 020236 439921 -0.64 8.06E-03 MRPL1 223154_at AF212225 65008 -0.64 1.18E-03 IDS 1559136_s_at AU140213 NM 000202 3423 -0.64 1.45E-03 TRIM8 221012_s_at NM 030912 NM_006123 NM 030912 81603 -0.64 3.17E-04 C1orf27 222720_x_at W72877 NM_017847 54953 -0.64 2.02E-04 TPP1 214196_s_at AA602532 NM_000391 1200 -0.64 2.31 E-03 PMS2L2 215412_x_at AB017007 NM_002679 5380 -0.64 9.44E-03 PTEN 225363_at AK024986 NM 000314 5728 -0.64 4.41 E-03 C15orf24 217898_at NM_020154 NM_020154 56851 -0.64 1.32E-03 321 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al„ Cells Useful for Immuno-Based BoNT/A Activity Assays SELT 217811_at NM_016275 NM 016275 51714 -0.64 1.82E-04 URB 225242_s_at AW303375 NM 199511 NM 199512 151887 -0.64 6.81 E-03 EFHC1 219833_s_at NM 018100 NM_018100 114327 -0.64 1.22E-03 AW970002 235660_at AW970002 — ... -0.64 4.41 E-03 C14orf43 225980 at AV740879 NM 194278 91748 -0.64 1 54E-03 DKFZP564J102 214890_s_at AL080065 NM_00100665 5 NM_015398 25854 -0.63 7.10E-03 STARD7 236484_at AW850611 NM 020151 NM_139267 56910 -0.63 1.49E-04 AW519141 227444_at AW519141 — ... -0.63 1.87E-03 TTC3 210645_s_at D83077 NM_00100189 4 NM_003316 7267 -0.63 2.39E-03 SCN3B 204722_at AW007335 NM 018400 55800 -0.63 5.01 E-05 ATF6 217550_at AA576497 NM 007348 22926 -0.63 5.13E-03 OFD1 203569 s at NM 003611 NM 003611 8481 -0.63 4.46E-04 ITPK1 210740_s_at AF279372 NM_014216 3705 -0.63 7.31 E-04 CCNDBP1 223084_s_at AF246144 NM_012142 NM_037370 23582 -0.63 1.14E-04 BEX2 224367_at AF251053 NM 032621 84707 -0.63 5.01E-03 KIAA1387 226230 at AA541716 NM_020463 57223 -0.63 8.30E-03 DND1 222070_at AW090043 NM_194249 373863 -0.63 9.36E-03 MLL2 227527_at AI394529 NM_003482 8085 -0.63 6.88E-03 C5orf14 227873 at BE547587 NM 024715 79770 -0.63 3.10E-03 TMED4 224680_at AL539253 NM 182547 222068 -0.63 6.32E-04 MTMR1 216095_x_at AF057354 NM_003828 NM_176789 8776 -0.63 7.62E-03 MAP3K12 205448_s_at NM 006301 NM 006301 7786 -0.63 1.84E-03 KIAA0276 243691_at AA150455 NM015115 23142 -0.63 1.60E-03 AV736334 237561_x_at AV736334 — ... -0.63 5.35E-03 LOC148189 235191_at BE780373 — 148189 -0.63 7.40E-03 FBXL2 214436_at AF176518 NM 012157 25827 -0.63 6.41 E-03 HT036 223769_x_at AF284750 NM 031207 81888 -0.63 1.42E-04 MLX 217910_x_at NM_013383 NM_170607 NM 198204 NM 198205 6945 -0.62 8.02E-03 C5orf5 218518_at NM 016603 NM_016603 51306 -0.62 3.54E-03 AI652919 230581_at AI652919 — ... -0.62 3.52E-03 BF196255 229921 at BF196255 — ... -0.62 4.55E-03 KCNF1 210263 at AF029780 NM_002236 3754 -0.62 7.86E-03 LKAP 202386_s_at N M 019081 NM_014647 NM_019081 9665 -0.62 2.93E-05 AU151222 227526_at AU151222 — ... -0.62 1.49E-04 ZNF266 214686_at AA868898 NM_006631 NM_198058 10781 -0.62 3.90E-03 MAG I-3 226770_at AI692181 NM_020965 NM_152900 260425 -0.62 8.14E-04 HNRPR 208765_s_at NM_005826 NM_005826 10236 -0.62 1.26E-03 TSTA3 36936_at U58766 NM_003313 7264 -0.62 6.42E-03 AK001513 233642_s_at AK001513 — ... -0.62 2.84E-04 OGT 212307_s_at BF001665 NM 003605 NM_181672 NM_181673 8473 -0.62 2.58E-03 POMT2 225560_at AK023804 NM 013382 29954 -0.62 4.78E-03 KIAA1340 225732_at AU146850 NM 020782 57542 -0.62 5.78E-03 FLJ21148 1554555_a_at BC022451 NM 024860 79918 -0.61 3.94E-04 322 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays ZFX 229022_at AI745209 NM 003410 7543 -0.61 5.57E-03 GPR56 212070_at AL554008 NM_005682 NM 201524 NM 201525 9289 -0.61 6.44E-03 BBS7 235007_at AI683802 NM_018190 NM_176824 55212 -0.61 9.30E-03 EIF2C4 227930_at AI669957 NM 017629 192670 -0.61 7.32E-03 FLJ13868 222190_s_at BC000822 NM_022744 64755 -0.61 6.09E-03 AI524240 238863_x_at AI524240 — — -0.61 5.90E-03 Al 140364 221740_x_at AM 40364 XM 373737 388397 -0.61 5.62E-03 PR01853 220943_s_at NM_018607 NM 018607 NM 144736 55471 -0.61 4.64E-04 FLJ20850 51200_at AI744084 NM 017967 55049 -0.61 7.02E-05 TGDS 237346_at AA976208 NM 014305 23483 -0.61 7.82E-03 COMMD10 240595 at AA928078 NM 016144 51397 -0.61 3.63E-04 FLJ31340 235301_at AI797353 NMJ 52748 222223 -0.61 4.73E-04 C2orf17 221984_s_at AL040896 NM 024293 79137 -0.61 7.61 E-03 VPS54 222627_at AK002205 NM 00100573 9 NM 016516 51542 -0.61 8.85E-03 WDR9 225446_at AI638279 NM 00100724 6 NM_018963 NM_033656 54014 -0.61 6.06E-03 LOC157697 227016_at AA767385 NM_207332 157697 -0.61 8.34E-03 SLC35E1 79005 at AA504646 NM 024881 79939 -0.61 2.09E-03 RFX1 226786_at BF507952 NM_002918 5989 -0.61 1.11 E-03 MDS028 220589_s_at NMJ)18463 NMJ318463 55846 -0.61 4.18E-04 RNF111 241413_at W80457 NM_017610 54778 -0.61 4.93E-03 RPL10 221989_at AW057781 NM 006013 6134 -0.61 8.66E-03 NR1H2 218215_s_at NM_007121 NM_007121 7376 -0.61 3.22E-05 TSPYL2 218012_at NM_022117 NM 022117 64061 -0.61 4.00E-03 COG7 213190_at R61519 NMJ 53603 91949 -0.60 1.96E-03 NM 018507 219599 at NM 018507 ... ... -0.60 7.03E-03 ZNF638 213775_x_at AI357871 NM 014497 27332 -0.60 9.27E-03 ABCD4 203981_s_at AL574660 NM 005050 NM 020323 NM_020324 NM_020325 NM_020326 5826 -0.60 1.48E-04 MKLN1 243959_at N35099 NM_013255 4289 -0.60 8.87E-04 FFX-r2-Ec-bioD: :X-r2-Ec-bioD-3 \FFX-r2-Ec-bioD- : — ... -0.60 1.47E-03 KIAA1277 53991 _at AA127623 NM 015689 27147 -0.60 1.38E-03 RAB11B 217793_at AL575337 NM 004218 9230 -0.60 8.56E-04 KRTCAP3 235148_at BF680458 NM 173853 200634 -0.60 6.87E-03 ILVBL 210624_s_at BC000109 NM_006844 NM 176826 10994 -0.60 9.87E-03 CACNB1 210185_at AB054985 NM_000723 NM_199247 NM_199248 782 -0.60 3.90E-04 ZFWE28 1569369_at BC035793 NM 020972 57732 -0.60 2.58E-05 C21orf127 220311_at NM_013240 NMJ13240 NM 182749 29104 -0.60 3.00E-03 SNAPC3 229712 at AI066599 NM_003084 6619 -0.60 8.08E-04 JAM3 212813_at AA149644 NM 032801 83700 -0.60 2.27E-05 KPNA1 202057_at BC002374 NM 002264 3836 -0.60 8.33E-03 HEL308 1554342_s_at BC011863 NM 133636 113510 -0.60 9.43E-03 ET 221192_x_at NM_024311 NM 024311 79157 -0.60 2.02E-03 323 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays SNRPB2 1561965_at BE466925 NM_003092 6629 -0.60 2.74E-03 MLL 212080 at AV714029 NM 198220 NM 005933 4297 -0.60 4.11E-03 FAIM2 203618_at AB023167 NM_012306 23017 -0.60 3.14E-03 RASA2 230669_at W38444 NM_006506 5922 -0.59 4.05E-03 GRIK5 214966_at S40369 NM 002088 2901 -0.59 4.00E-03 PARP6 234710_s_at AK021790 NM_020213 56965 -0.59 2.29E-04 DXYS155E 203624_at NM_005088 NM_020214 NM 005088 8227 -0.59 9.05E-03 DUSP3 201536_at AL048503 NM 004090 1845 -0.59 5.91 E-03 FLJ10324 223693 s at AL136731 NM 018059 55698 -0.59 4.22E-04 KATNB1 203163_at NM_005886 NM_005886 10300 -0.59 1.72E-03 C12orf10 218220_at NM_021640 NM_021640 60314 -0.59 4.83E-03 SCN3B 204723_at AB032984 NM 018400 55800 -0.59 5.81 E-04 IL17D 227401_at BE856748 NM 138284 53342 -0.59 5.23E-04 TUSC3 209228_x_at U42349 NM 006765 7991 -0.59 8.59E-05 ATP6AP1 207809 s at NM_001183 NM_178234 NM 001183 537 -0.59 3.60E-03 0KFZP564D16f 224952_at BF115054 XM 371074 26115 -0.59 7.36E-06 SFRS5 203380_x_at NM_006925 NM 006925 6430 -0.59 3.73E-03 MRX85 225867 at BE741869 NM 138440 114990 -0.59 2.02E-03 SBF2 226169_at AW276572 NM 030962 81846 -0.59 9.95E-04 CDC16 209658 at AF164598 NM 003903 8881 -0.59 7.37E-03 LOC493856 226686_at AM 88518 NM_001008388 493856 -0.59 3.94E-03 LAMB2 216264_s_at X79683 NM_002292 3913 -0.59 5.67E-03 FLJ10826 225110_at AK024314 NM 018233 55239 -0.59 4.75E-03 TLOC1 208942_s_at BE866511 NM 003262 7095 -0.59 2.74E-03 VPS24 222436_s_at AF219226 NM_00100575 O 51652 -0.59 9.34E-04 ECE2 230706 s at AI084921 o NM 016079 NM_014693 9718 -0.59 5.56E-04 ZNF292 212368_at AA972711 XM_048070 23036 -0.59 8.05E-04 AK022413 233658_at AK022413 — — -0.59 7.17E-03 FLNA 200859 x at NM_001456 NM 001456 2316 -0.59 6.02E-03 TIGD1 1553099_at NM_145702 NM_145702 200765 -0.59 5.58E-03 HUMPPA 213230_at AI422335 NM 014603 30850 -0.59 2.36E-04 NUDT13 214136_at W80642 NM_015901 25961 -0.58 8.37E-03 NMT2 215069 at AK025065 NM_004808 9397 -0.58 5.28E-03 LOC51255 223064_at AF151072 NM_016494 51255 -0.58 8.47E-04 NPD014 209007_s_at AF267856 NM_020317 57035 -0.58 6.29E-03 DGKD 208072_s_at NM_003648 NM 207035 NM 003648 8527 -0.58 5.37E-04 FLJ 10824 212929_s_at W68158 NM_152879 NM_00100575 387680 -0.58 9.32E-03 LOC387680 AL049985 215507_x_at AL049985 1 XM_290482 55747 -0.58 4.06E-03 PCNXL2 1554256_a_at BC008300 NM_014801 80003 -0.58 9.20E-03 MGC54289 225228 at AI474054 NM_024938 NM_178454 128338 -0.58 2.51 E-04 FBXL14 213145_at BF001666 NM 152441 144699 -0.58 2.17E-03 TFG 239385_at AI150613 NM_00100756 E 10342 -0.58 1.31E-03 MACF1 215222_x_at AK023406 O NM_006070 NM 012090 23499 -0.58 6.16E-03 AW268719 236798 at AW268719 NM_033044 -0.58 1.80E-04 BRUNOL6 227775_at BE467313 NM_052840 60677 -0.58 7.34E-03 324 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for immuno-Based BoNT/A Activity Assays CLN3 209275_s_at AF015593 NM 000086 1201 -0.58 5.20E-04 CKLFSF3 224733_at AL574900 NM 144601 NM 181553 NM_181554 NM 181555 123920 -0.58 6.40E-04 DSCR1 208370_s_at NM_004414 NM 004414 NM 203417 NM_203418 1827 -0.58 2.94E-03 PFDN5 210908_s_at AB055804 NM_002624 NM 145896 NM_145897 5204 -0.58 9.12E-04 AA206016 228191_at AA206016 — — -0.58 2.94E-03 IDS 212221_x_at AV703259 NM 000202 NM_006123 3423 -0.58 7.55E-06 ZNF295 225539 at AP001745 NM_020727 49854 -0.58 4.67E-03 AW292996 236330_at AW292996 — — -0.58 3.90E-03 LOC253982 214993_at AF070642 NM 181718 NM 198907 253982 -0.58 6.71 E-04 USP24 212388_at AB028980 XM_371254 23358 -0.58 1.07E-03 AW237752 229699_at AW237752 — - -0.58 7.54E-03 UNQ1912 226752_at AI816071 NM_198507 345757 -0.58 1.56E-03 PHC1 225958_at Al554106 NM_004426 1911 -0.58 2.64E-03 PAN 3 225563_at AI970788 NM 175854 255967 -0.58 1.42 E-04 325 PCT/US2010/027242 WO 2010/105234 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays

Table 9. Increased Gene Expression in Cell Lines H1 and BB10 vs. SiMa Cell Line in Undifferentiated State Using Microarray Analysis

Gene Symbol Probe Set ID Representative Public ID RefSeq Transcript ID Entrez Gene ID Log2 Ratio pvalue DAZ1 208282_x_at NM_020363 NM_00100537 1617 6.15 6.22E-05 DAZ3 DAZ2 DAZ4 BF476109 1556300_s_at BF476109 5 NM 00100578 5 NM 00100578 6 NM 004081 NM 020363 NM 020364 NM_020420 57054 57055 57135 6.07 4.58E-08 DAZ1 207909_x_at U21663 NM 00100537 1617 6.03 3.64E-05 DAZ3 DAZ2 DAZ4 TIMP3 201147 s at BF347089 5 NM 00100578 5 NM 00100578 6 NM_004081 NM_020363 NM 020364 NM_020420 NM_000362 57054 57055 57135 7078 5.78 9.00E-07 LUM 201744 s at NM 002345 NM 002345 4060 5.28 9.11E-07 SIM1 206876 at AL121948 NM 005068 6492 5.13 3.40E-06 TIMP3 201149_s_at U67195 NM 000362 7078 5.09 4.07E-05 CXCR4 209201_x_at L01639 NM_00100854 Λ 7852 4.91 1.18E-03 GRP 206326_at NM 002091 U NM 003467 NM_002091 2922 4.77 1.84E-06 MGC24103 232568_at AU145658 — 158295 4.71 1.34E-05 CXCR4 211919_s_at AF348491 NM_00100854 Λ 7852 4.65 1.78E-03 KCTD12 212192_at AI718937 U NM_003467 NM 138444 115207 4.61 1.59E-05 DAZ1 207912_s_at NM_004081 NM_00100537 1617 4.39 5.11E-04 DAZ3 DAZ2 DAZ4 5 NM_00100578 5 NM_00100578 6 NM 004081 NM_020363 NM 020364 NM 020420 57054 57055 57135 326 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays DAZ1 DAZ3 DAZ2 DAZ4 216922_x_at AF271088 NM_00100537 5 NM_00100578 5 NM 00100578 6 NM_004081 NM 020363 NM_020364 NM_020420 1617 57054 57055 57135 4.30 4.72E-04 DAZ1 DAZ3 DAZ2 DAZ4 208281_x_at NM_020364 NM_00100537 5 NM 00100578 5 NM 00100578 6 NM 004081 NM 020363 NM 020364 NM 020420 1617 57054 57055 57135 4.30 3.22E-04 PTPRE 221840_at AA775177 NMJ506504 NM_130435 5791 4.28 4.00E-07 AF086027 1559697_a_at AF086027 — — 4.28 1.11E-04 BNC2 233036 at AU146418 NM_017637 54796 4.20 2.05E-04 H99792 225710 at H99792 — ... 4.20 1.70E-06 )KFZp667G211 214030_at BE501352 XM_376254 131544 4.19 1.81E-09 AL049260 216518_at AL049260 — — 4.16 8.81 E-04 AU144918 233858 at AU144918 — ... 4.15 1.87E-05 GPC6 233090_at AU144140 NM_005708 10082 4.08 1.76E-03 TIMP3 201150_s_at NM_000362 NM 000362 7078 4.04 7.75E-05 ALCAM 240655_at BE502785 NM_001627 214 3.98 1.71E-04 SSBP2 1557813 at BF724621 NM_012446 23635 3.98 1.18E-03 C1orf1 233306_at AK021509 — 711 3.97 8.32E-06 ARHGAP6 206167_s_at NM_001174 NM 001174 NM 006125 NM 013422 NM_013423 NM_013427 395 3.91 9.85E-05 TFPI2 209278_s_at L27624 NM_006528 7980 3.87 1.53E-06 AL049337 215768 at AL049337 — — 3.87 3.23E-03 FLJ39639 243547_at BE176531 XM 370932 283876 3.83 3.19E-04 KIAA1944 236377_at AW166133 NM_133448 121256 3.80 2.79E-03 AF086027 1559696 at AF086027 — — 3.77 3.26E-05 VIP 206577_at NM_003381 NM_003381 NM_194435 7432 3.72 1.05E-03 CCDC3 223316_at AL136562 NM 031455 83643 3.72 8.39E-06 POLQ 207746_at NM_014125 NM 006596 NM_199420 10721 3.54 1.20E-04 SLAC2-B 214734_at ABO14524 NM_015065 23086 3.53 2.59E-03 GPC6 232453_at AF339813 NM 005708 10082 3.52 8.95E-04 MBNL1 241681 at AW296451 NM 021038 NM_207292 NM 207293 NM 207294 NM 207295 NM_207296 NM 207297 4154 3.50 2.40E-03 327 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays EML4 233940_at AK022801 NM_019063 27436 3.49 4.67E-03 AW974642 1558410_s_at AW974642 XM 499534 442612 3.49 1.47E-03 RGS5 1555725_a_at AF493929 NM 003617 8490 3.47 3.83E-03 TIMP3 201148_s_at AW338933 NM_000362 7078 3.46 9.21 E-03 AI939547 243004_at Al 939547 — — 3.45 6.37E-03 SLITRK5 214930 at AW449813 NM 015567 26050 3.42 1.80E-05 GFRA2 205722_s_at NM_001495 NM 001495 2675 3.38 1.70E-03 RGS5 209070_s_at AM 83997 NM_003617 8490 3.32 3.17E-03 EML1 204797_s_at NM_004434 NM_00100870 2009 3.29 2.09E-04 7 NM 004434 FBXL7 241457_at Al821935 NMJU2304 23194 3.27 1.14E-03 PLK2 201939_at NM_006622 NM_006622 10769 3.27 1.65E-06 NEGR1 243357 at AA115106 NM 173808 257194 3.26 2.19E-06 ELOVL7 227180_at AW138767 XM 371740 79993 3.26 3.23E-03 SPAG6 210033_s_at AF079363 NM 012443 9576 3.23 3.60E-05 FLJ39660 1553459 at NM 173646 NM_172242 NM 173646 284992 3.22 5.48E-03 NEDD9 202150_s_at U64317 NM_006403 4739 3.22 1.70E-04 PDZRN3 233442 at AU147500 NM_182966 NM 015009 23024 3.21 2.82E-05 TRIM29 211002_s_at AF230389 NM 012101 23650 3.18 3.79E-05 PCDH9 219737_s_at AI524125 NM 058193 NM_020403 5101 3.13 7.67E-06 FAT 201579 at NM 005245 NM_203487 NM 005245 2195 3.11 4.81 E-03 NEDD9 202149_at AL136139 NM_006403 4739 3.08 2.64E-04 ITGA6 201656_at NM_000210 NM_182966 NM 000210 3655 3.07 8.91 E-05 DAZ1 216351_x_at AF248483 NM 00100537 1617 3.06 3.84E-04 DAZ3 DAZ2 DAZ4 FLJ37266 1566948_at AL831894 5 NM_00100578 5 NM 00100578 6 NM_004081 NM_020363 NM 020364 NM_020420 NM 175892 57054 57055 57135 283225 3.06 3.09E-03 EFNA5 1559360 at AL833045 NM 001962 1946 3.03 1.65E-05 RPL10A 242188 at AI743332 NM_007104 4736 3.03 2.49E-03 BE466926 217671_at BE466926 — — 3.02 9.00E-03 PTPRG 1569323_at BU853579 NM 002841 5793 3.01 1.51 E-05 CUGBP2 202158 s at NM_006561 NM 006561 10659 3.01 8.47E-05 TULP4 232372_at AL157491 NM 00100746 6 NM_020245 56995 3.01 6.44E-03 BC043430 1558714 at BC043430 2.99 6.39E-03 LOC340109 1557765_at BC039509 XM_379322 340109 2.99 6.58E-05 )KFZp761O201 232313_at AL122107 XM 044062 92293 2.98 3.82E-05 RGS5 218353_at NM 025226 NM 003617 8490 2.96 3.43E-03 CHRNA7 210123_s_at U62436 NM 000746 1139 2.96 5.22E-06 CHRFAM7A LOC440265 1569476_at BC033224 NM_139320 NM_148911 XM_378506 89832 440265 2.90 2.51 E-03 ARHGEF6 209539 at D25304 NM_004840 9459 2.90 7.95E-05 AL049277 234839 at AL049277 — — 2.89 4.82E-03 328 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., etal., Cells Useful for Immuno-Based BoNT/A Activity Assays KIAA0265 238000_at BF195340 NM_014997 23008 2.85 2.90E-04 DACT1 219179 at NM_016651 NM_016651 51339 2.85 4.31 E-04 KCTD12 212188_at AA551075 NM 138444 115207 2.84 1.79E-04 RGS5 209071 s at AF159570 NM_003617 8490 2.84 3.29E-03 AL832561 1561689 at AL832561 — — 2.84 3.60E-05 AA872187 230332_at AA872187 — — 2.82 1.50E-03 BG542611 1556277_a_at BG542611 — — 2.81 2.09E-03 PIAS2 244633_at AA404996 NM 004671 NM_173206 9063 2.80 3.93E-05 AI630830 243150_at AI630830 —' — 2.79 2.12E-03 UCHL1 1555834_at AW974143 NM 004181 7345 2.77 3.11E-03 TRIO 235705 at BF676361 NM_007118 7204 2.76 4.51 E-04 AK022040 233445_at AK022040 — — 2.76 7.74E-04 CBLN2 242301_at R60224 NM 182511 147381 2.76 3.83E-03 MIDI 242671_at BF055144 NM 000381 NM_033290 NM_033291 4281 2.74 4.62E-04 BC041991 1561690 at BC041991 — — 2.73 2.25E-03 EML4 232587_at AI208611 NM 019063 27436 2.72 8.16E-03 TRIM29 202504_at NM_012101 NM_012101 NM_058193 23650 2.70 1.08E-03 AW139261 243934_at AW139261 — — 2.69 5.92E-03 ROB02 226709 at BE858548 XM 031246 6092 2.69 1.07E-04 MEF2A 239571_at AI123399 NM_005587 4205 2.68 1.53E-04 KIAA1128 240499 at AA482221 NM 018999 54462 2.68 8.42E-03 KLF7 239809_at BF197708 NM_003709 8609 2.65 5.01 E-03 CALCA 217561 at BF447272 NM 001741 796 2.62 2.08E-03 LOC51760 205613_at NM_016524 NM_016524 51760 2.61 5.89E-03 EDD 232264_at AK022204 NM 015902 51366 2.61 7.50E-04 LOC440161 243241_at AW341473 XM_498572 440161 2.61 2.72E-04 SCHIP1 1566772 at AL832567 NM 014575 29970 2.61 1.17E-03 TFPI2 209277_at AL574096 NM_006528 7980 2.61 6.75E-04 EML4 1556732_at BC039354 NM_019063 27436 2.59 2.34E-03 AA808231 242025_at AA808231 — — 2.59 1.52E-04 CUGBP2 202157 s at U69546 NM 006561 10659 2.59 6.58E-06 PAPD4 222282_at AV761453 NM_173797 167153 2.57 4.37E-03 MGC14161 240502_at AW015920 NM_032892 84978 2.55 2.58E-03 UBE3A 1560741_at AL832250 NM_000462 NM_130838 NM_130839 7337 2.54 5.57E-03 LRRC5 234148 at AK025238 NM 018103 55144 2.54 8.12E-04 PEX5L 1562473 at BC037943 NM 016559 51555 2.54 7.14E-04 IMP-2 218847_at NM 006548 NM_00100722 5 NM_006548 10644 2.54 9.50E-05 C2orf31 221245_s_at NM_030804 — 81561 2.51 8.63E-05 AK024882 233228_at AK024882 — — 2.50 4.73E-04 TAS2R45 234042_at AF264628 NM_176886 259291 2.50 4.78E-04 KIAA1102 241459_at AI494113 NM_014988 22998 2.48 4.62E-05 BC041965 1560411_at BC041965 — — 2.47 7.60E-03 USP31 239348_at AI285970 NM_020718 57478 2.47 5.27E-03 AU144294 215574_at AU144294 — — 2.47 3.25E-03 RNF152 233180 at AU147152 NM 173557 220441 2.46 7.81 E-03 LOC440738 221697_at AF276659 NM_001004343 440738 2.45 2.37E-03 KATNAL1 243828 at AA758906 NM 032116 84056 2.44 1.32E-03 MGC39558 1562391_at AK091497 NM 152490 148789 2.44 7.21 E-03 GNG11 204115_at NM 004126 NM 004126 2791 2.43 1.79E-04 329 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays AI076172 236355_s_at AI076172 XM_495841 439993 2.42 3.12E-03 ITPR1 240052_at AA648993 NM 002222 3708 2.42 1.52E-04 IARS 239794_at AI356405 NM_002161 NM_013417 3376 2.42 2.89E-04 PLXNA4 232317_at AB046770 XM_039393 XM_379927 57671 2.41 8.26E-05 AURKB 239219_at N55457 NMJJ04217 9212 2.41 5.13E-04 FBXL7 233276_at AU146390 NM 012304 23194 2.41 3.40E-04 CDH2 237305_at AW450381 NM_001792 1000 2.40 2.95E-03 SPRY4 1566968_at AK024556 NM_030964 81848 2.40 1.67E-05 SYT4 223529 at AB037763 NM 020783 6860 2.40 4.26E-04 PPP4R2 1560926_at AF085924 NM_174907 151987 2.38 6.45E-03 BE674460 237849_at BE674460 — — 2.38 7.15E-04 AK024956 232726_at AK024956 — — 2.37 2.24E-03 PITPNB 242074 at AA833902 NM_012399 23760 2.37 2.45E-04 KIAA0485 214295_at AW129056 — 57235 2.36 6.51 E-04 BF000203 236385 at BF000203 — — 2.33 1.55E-03 BNC2 220272_at NM_017637 NM 017637 54796 2.33 3.96E-04 SDFR1 242865_at Al 332638 NM 012428 NM_017455 27020 2.31 1.45E-04 DTNA 1557803_at AF086074 NM_001390 NM_001391 NM 001392 NM_032975 NM_032978 NM 032979 NM 032980 NM 032981 1837 2.31 3.61 E-04 NRCAM 233401_at BF723605 NM_005010 4897 2.31 1.07E-03 F0X03A 1569477_at BC025999 NM 001455 NM_201559 2309 2.31 5.92E-03 MSN 200600_at NM_002444 NM 002444 4478 2.30 1.14E-05 AL832142 1561195_at AL832142 — — 2.30 2.10E-03 EDG3 228176_at AA534817 NM 005226 1903 2.29 2.67E-03 ASCL1 209985_s_at BE797438 NM 004316 429 2.28 9.42E-05 LOC146174 233832 at AK021824 NM 173501 146174 2.27 3.37E-04 PLXNA4 228104_at AL117427 XM_039393 XM_379927 57671 2.26 7.59E-04 KIDINS220 1557246_at AA992480 NM_020738 57498 2.26 5.87E-03 GFRA2 205721_at U97145 NM_001495 2675 2.25 3.08E-03 LOC440092 1570571 at BC035168 XM 498540 440092 2.25 3.18E-05 ROB02 226766 at AB046788 XM 031246 6092 2.25 3.58E-05 GAB2 1566959_at AL049273 NM_012296 NM_080491 9846 2.24 9.27E-03 ARHGAP6 1563386_at AL079282 NM_001174 NM 006125 NM_013422 NM_013423 NM_013427 395 2.24 2.24E-03 PCNX 215175 at AB023212 NM 014982 22990 2.24 3.95E-03 C10orf18 216211_at AL049233 XM_374765 54906 2.23 1.64E-03 AI678013 240165 at AI678013 — — 2.22 1.17E-03 AI653240 240247 at Al653240 XM_496059 440261 2.21 1.90E-04 GFM1 232295 at AK000780 NM_024996 85476 2.20 4.88E-03 AF116659 210717_at AF116659 — — 2.20 2.72E-03 NM 018611 220666_at NM_018611 — — 2.20 3.83E-03 PFKFB3 202464 s at NM 004566 NM 004566 5209 2.20 1.42E-03 AI671885 230494_at AI671885 XM_379123 400999 2.20 4.83E-04 330 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays TPBG 203476_at NM_006670 NM_006670 7162 2.20 1.21E-07 ITGA6 215177_s_at AV733308 NM 000210 3655 2.19 2.48E-03 AW008791 240315 at AW008791 XM_294019 345930 2.19 7.20E-03 C10orf18 244165_at AI809511 XM_374765 54906 2.18 1.55E-03 FLJ21148 231005_at T91195 NM_024860 79918 2.18 3.18E-04 DEFB32 243311_at BE044548 NM_207469 400830 2.18 1.71E-03 THRAP2 232307_at AK021554 NM_015335 23389 2.18 7.79E-04 BF057073 231310_at BF057073 — — 2.16 3.16E-05 CFDP1 210701_at D85939 NM 006324 10428 2.16 1.15E-03 SYNE2 242774_at Al684761 NM_015180 NM 182910 NM_182912 NM_182913 NM_182914 23224 2.16 3.57E-03 RNF182 230720 at Al 884906 NM 152737 221687 2.15 1 49E-04 PAPD4 242144_at AW104325 NM_173797 167153 2.15 8.28E-03 DKFZp761D221 241872_at AM 49963 NM_032291 84251 2.15 7.56E-03 NFIB 230791_at AU146924 NM 005596 4781 2.14 1.39E-03 PTGFRN 224937 at BF311866 NM 020440 5738 2.14 1.95E-03 FOX03A 242320_at AI435586 NM 001455 NM_201559 2309 2.13 1.69E-03 SSBP2 1557814_a_at BF724621 NM 012446 23635 2.13 6.51 E-03 KLF12 243089_at AA551114 NM 007249 NM_016285 11278 2.13 1.78E-03 EXT1 232174_at AA480392 NM_000127 2131 2.13 2.01 E-04 MGC4504 219270 at NM_024111 NM 024111 79094 2.13 2.30E-03 TTL 244078 at AI438957 NM_153712 150465 2.12 1.97E-04 ODZ3 233291_at AU145618 XM 371717 55714 2.11 2.81 E-04 MSI2 239232_at AA521410 NM 138962 NM_170721 124540 2.11 7.13E-04 ZNF403 233937_at AK024883 NM 024835 79893 2.11 2.80E-04 FRZB 203698_s_at NM 001463 NMJD01463 2487 2.10 6.12E-03 ATP1B4 243737_at Al082610 NM_012069 23439 2.10 3.38E-03 AI077566 243994 at AI077566 — — 2.09 3.50E-03 GATA4 243692 at AW181962 NM 002052 2626 2.09 2.75E-03 ID2 213931_at AI819238 NM_002166 3398 2.09 3.49E-04 N21631 231329_at N21631 — — 2.08 3.60E-03 GNAI1 209576 at AL049933 NM 002069 2770 2.08 4.56E-05 ZNF292 236435 at BE219036 XM 048070 23036 2.08 7.00E-03 NEDD9 233223_at AK000850 NM_006403 NM_182966 4739 2.07 4.93E-04 UBE2E3 232528_at Al 338705 NM 006357 NM_182678 10477 2.06 7.31 E-03 PAN3 239393_at AW510927 NM 175854 255967 2.05 4.66E-03 SMARCC1 239238_at AI208857 NM 003074 6599 2.04 7.80E-04 MTMR2 231057_at AU144266 NM 016156 NM_201278 NM_201281 8898 2.04 8.90E-05 MGC33926 229302_at AA058832 NM 152390 130733 2.04 4.33E-05 DREV1 230395 at Al 536637 NM_016025 51108 2.04 3.23E-03 AF238870 215811_at AF238870 — — 2.04 1.97E-03 DMXL2 215761_at AK000156 NM_015263 23312 2.04 2.78E-04 MAOA 204388_s_at NM_000240 NM_000240 4128 2.04 7.48E-04 331 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays OSBPL3 209626_s_at AI202969 NM_015550 NM_145320 NM 145321 NM 145322 NM_145323 NM_145324 26031 2.04 1.76E-03 AL161982 1563494_at AL161982 — — 2.03 1.29E-03 SALL4 229661_at NM 020436 NM 020436 57167 2.03 2.39E-03 DJ971N18.2 240094_at AL042660 NM_021156 56255 2,03 1.10E-03 GOLPH4 233877_at AK000777 NM_014498 27333 2.02 1.37E-03 MSX2 205555_s_at D31771 NM 002449 4488 2.02 2.73E-03 SR140 236696_at BE464843 XM_031553 23350 2.02 1.40E-03 PSCD3 243752_s_at Al870144 NM 004227 9265 2.02 5.25E-05 JMJD2C 239285_at Al341227 NM_015061 23081 2.02 1.02E-03 THRAP2 238883_at AW975051 NM_015335 23389 2.01 3.31 E-03 BF508839 239907_at BF508839 — — 2.01 1.50E-03 VRK1 241737_x_at T89693 NM 003384 7443 2.01 4.67E-05 AA417878 243463_s_at AA417878 — — 2.01 4.39E-03 RAP1GDS1 237856 at AI052055 NM_021159 5910 1.99 6.70E-03 BF724206 244457 at BF724206 — — 1.99 5.28E-03 MAOA 212741_at AA923354 NM 000240 4128 1.98 7.12E-04 TPTE 233879_at AL137389 NM_013315 NM_199259 NM_199260 NM 199261 7179 1.97 6.72E-03 SPAG6 210032_s_at AI651156 NM_012443 NM_172242 9576 1.97 2.71 E-04 VDP 222316_at AW973253 NM_003715 8615 1.97 8.98E-03 FLJ35740 244297_at Al806762 NM_147195 253650 1.97 7.86E-03 SPPL3 1554565_x_at BC011943 NM_139015 121665 1.96 5.95E-04 BC028185 1569609 at BC028185 XM 496328 440546 1.96 4.09E-05 MYH10 237491_at AA700633 NM_005964 4628 1.96 3.02E-03 TMP21 238886_at BF056141 NM_006827 10972 1.96 1.48E-03 TFCP2 242859_at BE156563 NM_005653 7024 1.95 8.85E-03 BE856929 239349 at BE856929 — — 1.95 4.12E-03 LOC151878 222372_at AW971248 — 151878 1.95 1.02E-03 SEC15L2 1569202_x_at BF847120 XM 039570 23233 1.94 2.05E-05 SCFD1 243525_at AA808051 NM_016106 NM_182835 23256 1.94 1.42E-03 RTN4 243031_at N90377 NM_007008 NM_020532 NM_153828 NM_207520 NM_207521 57142 1.94 3.06E-03 TRA1 239451_at AI684643 NM 003299 7184 1.93 2.01 E-03 CSE1L 210765_at AF053640 NM_001316 NM_177436 1434 1.93 2.75 E-04 ATXN2 238589_s_at AW601184 NM_002973 6311 1.93 1.04E-03 GNAI1 227692_at AU153866 NM 002069 2770 1.93 7.06E-05 TCF12 235925_at AW057520 NM_003205 NM_207036 NM_207037 NM_207038 NM 207040 6938 1.93 2.43E-03 LASS5 238299_at AW005866 NM_147190 91012 1.93 1.53E-04 AA766886 239171_at AA766886 — — 1.92 7.67E-03 KIAA1102 1569208_a_at BC020895 NM 014988 22998 1.92 1.80E-03 SARS 237689_at BF111108 NM_006513 6301 1.92 5.62E-03 332 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B„ et al., Cells Useful for Immuno-Based BoNT/A Activity Assays VTI1A 233323_at AK024973 NM_145206 143187 1.91 6.85E-04 B4GALT5 1559391 s at Al084451 NM_004776 9334 1.91 9.95E-03 AA804267 243185_at AA804267 — — 1.91 1.67E-03 MGC34032 1569112_at AW020413 NM_152697 204962 1.90 1.85E-03 AL050204 213929 at AL050204 — — 1.90 5.32E-03 FLJ31951 236322_at AA830854 NM 144726 153830 1.89 9.55E-03 ASCL1 209987_s_at BC002341 NM_004316 429 1.89 1.70E-06 LOC441157 1558795_at AL833240 XM_499037 441157 1.89 7.22E-05 NOL7 242143_at BE674964 NM_016167 51406 1.89 1.62E-03 XP01 235927 at BE350122 NM_003400 7514 1.88 1.14E-04 FOXP1 240666_at Al 732568 NM_032682 27086 1.88 6.71 E-03 CD9 201005_at NM_001769 NM_001769 928 1.87 3.75E-03 TNKS 238108_at AI401627 NM_003747 8658 1.87 8.80E-03 NID 202007 at BF940043 NM_002508 4811 1.87 3.81 E-03 MARS 213672_at AA621558 NM_004990 4141 1.86 2.54E-04 C20orf23 232083_at AB046810 NM_024704 55614 1.86 1.17E-04 KIAA1713 233536_at AI202664 XM_290811 80816 1.86 3.15E-05 U80755 243820 at U80755 — — 1.85 8.97E-05 AA700817 241997_at AA700817 — — 1.85 4.70E-03 UBE2E1 215577_at AU 146791 NM_003341 NM_182666 7324 1.85 2.95E-03 AP2B1 233800 at AA805082 NM_001282 163 1.84 4.55E-05 AGTPBP1 242008_at BE350312 NM_015239 23287 1.83 9.60E-03 RPL4 1562440_at BC026249 NM 000968 6124 1.83 1.24E-03 LOC441157 1558796 a at AL833240 XM_499037 441157 1.83 3.63E-06 EIF3S8 236700 at AI377875 NM 003752 8663 1.82 1.24E-07 ZDHHC2 243528_at AW014108 NM 016353 51201 1.82 8.62E-05 WSB1 227501 _at AI377135 NM_015626 NM 134264 NM 134265 26118 1.82 2.98E-03 PTPN12 244356 at AL079909 NM 002835 5782 1.81 5.18E-03 RB1CC1 237626_at AI801666 NM_014781 9821 1.81 2.19E-03 PCTK2 243993 at AA436887 NM 002595 5128 1.80 9.68E-03 PIP5K1A 235646 at BF515595 NM_003557 8394 1.80 5.13E-03 AU146318 232355_at AU146318 — — 1.80 7.55E-03 N59650 244265_at N59650 — — 1.80 8.30E-03 YARS 238760 at AW452122 NM_003680 8565 1.80 4.51 E-03 RNF159 241956 at Al521883 NM_032373 84333 1.80 5.20E-05 AI820961 240331_at Al820961 — — 1.79 7.22E-03 FLJ30058 238047_at AA405456 NM_144967 158763 1.79 5.67E-03 GULP1 223837 at BC001103 NM 016315 51454 1.79 6.85E-04 CGI-26 230892_at AI912194 NM_015954 51071 1.79 1.73E-03 LRCH3 1559490_at AL832278 NM 032773 84859 1.79 6.87E-03 HIRA 240451_at AA004844 NM 003325 7290 1.79 2.21 E-05 SRPK2 239811_at BF954306 NM_182691 NM_182692 6733 1.78 5.28E-03 C9orf33 217130_at AF072164 — 90477 1.78 1.23E-04 AI916641 242471_at AI916641 — — 1.78 4.35E-04 SCC-112 241798 at AI339930 NM_015200 23244 1.78 1 62E-03 SLC33A1 1559232_a_at BC029450 NM_004733 9197 1.78 1.37E-04 ATRX 236778_at AA826176 NM_000489 NM 138270 NM 138271 546 1.78 2.50E-03 ZFYVE16 1554638„at BC032227 NM_014733 9765 1.78 1.30E-03 FLJ13089 236816_at BF110370 NM 024953 80018 1.78 9.12E-03 SLC7A2 225516_at AA876372 NM 00100853 9 6542 1.78 2.48E-06 NM 003046 333 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., i Cells Useful for Immuno-Based BoNT/A Activity Assays DBH 206450_at NM 000787 NM_000787 1621 1.77 5.25E-04 H15073 236685_at H15073 — ... 1.77 1.63E-04 R45137 238304 at R45137 — ... 1.77 4.97E-03 FBXW8 237317_at AW136338 NM 012174 NM_153348 26259 1.76 4.78E-03 MLL3 244010_at AI057455 NM 021230 NM 170606 58508 1.76 5.04E-05 SLC37A3 1569666_s_at BC035773 NM 032295 NM_207113 84255 1.76 1.21E-05 CNOT2 222313 at AW972359 NM_014515 4848 1.76 1.85E-04 NS5ATP13TP2 1558613_at BC040647 NM 178507 220323 1.75 7.91 E-04 MBNL1 1556657_at AA744622 NM_021038 NM 207292 NM 207293 NM 207294 NM_207295 NM_207296 NM_207297 4154 1.74 1.02E-04 AU152272 1556650 at AU152272 — ... 1.74 2.69E-03 AI372879 237134_at AI372879 — ... 1.73 1.97E-03 N23846 1557804_at N23846 ... ... 1.72 6.11E-03 C10orf47 229801_at Al640157 NM_153256 254427 1.72 6.95E-03 W72466 231467 at W72466 ... ... 1.72 2.85E-05 MAPRE2 1564733_at BC013931 N M 014268 10982 1.72 1.15E-03 R38403 240425_x_at R38403 — — 1.72 2.69E-03 AF090944 233995 at AF090944 — ... 1.72 3.50E-04 RANBP17 234137 s at AK022022 NM_022897 64901 1.71 3.68E-03 OAZIN 240231_at AI742383 NM_015878 NM_148174 51582 1.71 1.34E-07 L3MBTL 242637_at C14069 NM 015478 NM_032107 26013 1.71 6.68E-03 AB062477 1555303_at AB062477 — ... 1.71 6.75E-03 AA682539 235575_at AA682539 — ... 1.70 8.28E-03 AL353942 216147 at AL353942 NM 018243 55752 1.70 3.06E-04 VPS26 243316 x at AA004710 NM_004896 9559 1.70 1.14E-04 LAF4 243967_at AI424899 NM 002285 3899 1.70 8.24E-03 SEZ6L 240709_at AW204757 NM_021115 23544 1.70 9.27E-04 AV03 237330 at AA603494 XM 380173 253260 1.70 6.44E-04 TPARL 1560622 at AK000203 NM_018475 55858 1.69 1.26E-03 PDLIM5 213684_s_at BF671400 NM 00101151 3 NM 00101151 4 NM_00101151 5 NM 00101151 6 NM 006457 10611 1.69 6.08E-03 SOS2 233369 at AU146027 NM 006939 6655 1.69 9.57E-03 IREB2 1563130 a at AL109710 NM 004136 3658 1.68 7.14E-06 MPZL1 210210_at AF181660 NM_003953 NM_024569 9019 1.68 5.09E-05 AW206536 243470 at AW206536 — ... 1.68 4.56E-03 TOP1 239404 at BF840360 NM_003286 7150 1.67 5.17E-04 AA936428 244674_at AA936428 — ... 1.67 1.91E-03 PUM2 235138_at AA565051 NM 015317 23369 1.67 8.24E-04 MINA 213189_at BE966695 NM 032778 NM 153182 84864 1.67 9.49E-05 334 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B„ et al., Cells Useful for Immuno-Based BoNT/A Activity Assays LOC152185 239091_at AA497043 NM 144718 152185 1.67 4.23E-04 SEC31L1 1556416_s_at AF086242 NM 014933 NM_016211 22872 1.67 6.36E-04 MAOA 204389_at NM 000240 NM 000240 4128 1.66 2.78E-04 ALCAM 1569362_at BC041127 NM 001627 214 1.66 8.23E-03 KRT18 201596_x_at NM_000224 NM_000224 NM_199187 3875 1.66 1.32E-03 N73550 244112_x_at N73550 — — 1.66 5.23E-03 MKLN1 1560145_at BQ942131 NM 013255 4289 1.65 4.78E-03 ARHGAP5 242110 at AV735587 NM 001173 394 1.65 8.85E-03 GPI 232002_at AW843302 NM 000175 2821 1.65 6.38E-04 STAU 1569527_at BC017275 NM_004602 NM_017452 NM 017453 NM_017454 6780 1.65 2.32E-04 BF512254 242695_at BF512254 — — 1.65 2.52E-03 EIF4ENIF1 242983_at Al 806626 NM_019843 56478 1.65 4.13E-03 AU144781 233300_at AU144781 — — 1.65 2.25E-03 DKFZp547A022 214731_at AB037854 NM_018704 55917 1.65 8.41 E-03 LBH 221011_s_at NM_030915 NM_030915 81606 1.64 3.86E-05 KIAA0217 241965_at BF589232 NM_015155 23185 1.64 3.53E-04 MED31 243319_at Al274981 NM 016060 51003 1.64 2.26E-04 DLEU2 1556821 x at H48516 NM_006021 8847 1.64 8.43E-03 AA195014 243769_at AA195014 — ... 1.63 9.11 E-03 N50083 229110_at N50083 — — 1.63 1 73E-03 N46436 1556568_a_at N46436 — — 1.63 4.33E-04 RAPGEF5 204680_s_at AI263837 XM_499059 9771 1.62 1.84E-03 AW003140 227576_at AW003140 — ... 1.62 5.17E-03 AL119001 233440_at AL119001 — — 1.62 5.61 E-03 CPSF6 238651_at BF512491 NM 007007 11052 1.62 4.97E-03 RBM5 230742_at AA742596 NM 005778 10181 1.62 6.51E-03 CADPS 233950_at AK000873 NM_003716 NM 183393 NM_183394 8618 1.62 3.44E-04 SPON1 209437_s_at AB051390 NM 006108 10418 1.62 1.60E-03 SCFD1 241775_at AW298119 NM_016106 NM 182835 23256 1.61 2.89E-03 CDC14A 210742_at AF064103 NM 003672 NMJ333312 NM_033313 8556 1.61 4.92E-03 FZD5 206136 at NM_003468 NM 003468 7855 1.61 1.56E-03 ZNF451 215012 at AU144775 NM 015555 26036 1.61 9.28E-03 PCGF5 226326_at AI798098 NM 032373 84333 1.61 2.79E-05 PTGFRN 224950_at BF476250 NM 020440 5738 1.61 8.83E-03 TSC 218872 at NM 017899 NM_017899 54997 1.61 5.32E-04 GRM8 216255 s at AC000099 NM 000845 2918 1.60 3.03E-05 MGC47869 243056_at AI301111 NM_175874 144608 1.60 1.26E-03 DNAPTP6 244597_at AA701247 NM_015535 26010 1.60 2.38E-03 BC028606 1555485 s at BC028606 — — 1.60 5.40E-03 ARID1B 1558822_at AF147412 NM_017519 NM_020732 NM_175863 57492 1.60 2.93E-03 BF841212 232096 x at BF841212 — — 1.60 1.12E-03 AU144005 232797_at AU144005 — — 1.60 2.27E-03 LOC158160 244075_at BF224218 NM 182829 158160 1.60 3.37E-03 MY06 210480_s_at U90236 NM 004999 4646 1.59 6.83E-04 MBNL2 236699 at AL566294 NM 144778 10150 1.59 3.46E-03 NM 207304 335 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays BI868311 1565651_at BI868311 — — 1.59 4.00E-03 LETMD1 242424 at AA345855 NM_015416 25875 1 59 5.03E-04 N75937 240072_at N75937 — — 1.59 6.26E-03 H04482 243287_s_at H04482 — ... 1.59 3.04E-03 NFIB 233304_at AU145782 NM 005596 4781 1.59 6.80E-03 PPP3R1 1565811_at BC033945 NM 000945 5534 1.59 6.08E-05 DLEU2 216870_x_at AF264787 NM_006021 8847 1.59 2.46E-04 COBRA1 1556434_at BQ777552 NM_015456 25920 1.59 2.75E-04 C6orf60 1558523_at AJ420563 NM_024581 79632 1.58 6.89E-03 MAK3 231199_at AA701676 NM_025146 80218 1.58 3.34E-03 KIAA0485 242824 at AW191647 — 57235 1.57 3.46E-05 CTBP2 233315_at AK024947 NM_001329 NM_022802 1488 1.57 2.17E-05 AA935659 240321_at AA935659 — ... 1.57 9.78E-03 TAF15 227884_at AW296067 NM_003487 NM_139215 8148 1.56 6.85E-03 KIF5C 1557089_at CA449408 XM_377774 3800 1.56 2.83E-04 KIAA0143 232356_at AW003230 NM 015137 23167 1.56 7.00E-03 CPVL 208146_s_at NM_031311 NM_019029 NM_031311 54504 1.56 4.48E-03 DMXL1 241472_at N74444 NM 005509 1657 1.55 8.84E-04 SNX5 229981_at AA131508 NM 014426 NM_152227 27131 1.55 1.33E-05 ALCAM 201951_at BF242905 NM_001627 214 1.55 2.09E-06 ANKRD11 228866_at BF514864 NM 013275 29123 1.55 2.95E-04 ID2 201565 s at NM 002166 NM 002166 3398 1.55 9.49E-04 PFAAP5 214753 at AW084068 NM_014887 10443 1.55 8.30E-04 KIAA0318 238817_at BF063412 NM_015347 23504 1.55 8.89E-05 SR140 236431_at AI674977 XM_031553 23350 1.54 8.08E-C3 API5 229692 at AW135003 NM_006595 8539 1.54 1.07E-03 AA516469 236375 at AA516469 — ... 1.54 6.79E-03 NUPL1 241425_at AA769986 NM 00100856 4 NM 00100856 5 NM_014089 9818 1.54 4.72E-05 AI791138 242968_at AI791138 — — 1.54 8.93E-03 JAK1 234193 at AK025218 NM_002227 3716 1.54 3.33E-04 AW052186 239942_at AW052186 — ... 1.53 6.32E-03 KIF23 244427_at AW192521 NM 004856 NM_138555 9493 1.53 7.98E-03 AI800470 242836 at AI800470 — — 1.53 5.90E-04 BF509125 232198_at BF509125 ... ... 1.52 1.16E-04 SPON1 209436_at ABO18305 NM 006108 10418 1.52 2.06E-04 DLEU2 1556820_a_at H48516 NM_006021 8847 1.52 1 57E-03 AK025105 232476 at AK025105 — — 1.52 2.32E-03 AA228366 236251_at AA228366 ... ... 1.52 4.86E-03 H37807 241060_x_at H37807 — ... 1.52 4.23E-03 BNC2 238478_at H97386 NM 017637 54796 1.52 2.14E-05 CADPS 1568604_a_at AI912173 NM_003716 NM_183393 NM_183394 8618 1.51 7.84E-07 SCARB2 215754_at AU148040 NM 005506 950 1.51 1.21E-03 336 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays MBNL1 238558_at AI445833 NM 021038 NM_207292 NM 207293 NM_207294 NM 207295 NM 207296 NM_207297 4154 1.51 1.09E-03 BC003528 210920_x_at BC003528 — ... 1.51 2.78E-03 GPR18 233554_at AF339764 NM 005292 2841 1.51 8.61 E-03 UBE3B 213822_s_at BE856776 NM 130466 NM 183414 NM 183415 89910 1.51 8.72E-03 WWOX 1556595_at BQ025203 NM 016373 NM 018560 NM 130788 NM_130790 NM 130791 NM 130792 NM_130844 51741 1.51 1.78E-03 AI740589 243515_at Al740589 — ... 1.51 4.92E-04 N26620 227503_at N26620 ... ... 1.51 2.93E-03 C18965 242853_at C18965 XM 379243 401106 1.51 5.39E-03 CPNE4 239990 at Al821426 NM_130808 131034 1.50 1.95E-03 FBXL11 215191_at AW836210 NM 012308 22992 1.50 3.06E-03 CHD1L 238070_at AA573217 NM_004284 9557 1.50 8.83E-03 JARID2 232835_at AA533080 NM 004973 3720 1.50 3.50E-04 MIB1 240446_at AI798164 NM_020774 57534 1.50 4.01 E-04 Z39232 1560924_at Z39232 — ... 1.49 6.88E-04 PLEKHE1 212719_at AB011178 NM 194449 23239 1.49 2.28E-04 UBE1C 1556339_a_at BM353142 NM 003968 NM 198195 NM_198197 9039 1.49 7.82 E-04 NM 030892 220969_s_at NM 030892 — — 1.49 4.83E-04 TBX3 219682_s_at NM_016569 NM_005996 NM_016569 6926 1.48 2.65E-03 PHGDHL1 241932_at AI073803 NM_177967 337867 1.48 5.92E-03 LOC158301 239193_at BF060981 ... 158301 1.48 1 36E-03 FLJ10579 230843_at AA482037 NM 018145 55177 1.48 6.04E-04 RPL10A 234224_at AL137541 NM 007104 4736 1.48 5.43E-03 C10orf119 242167_at AA703310 NM 024834 79892 1.48 9.08E-06 C0R06 1552301 a at NM 032854 NM 032854 84940 1.48 5.48E-03 MGC15912 239635_at BF510708 NM_032886 84972 1.47 4.46E-03 DTNB 233727_at AL157472 NM 021907 NM 033147 NM 033148 NM_183360 NM_183361 1838 1.47 4.45E-03 FLJ22955 232447_at AU147405 NM_024819 79877 1.46 3.56E-03 LOC151194 236607 at Al 921882 NM_145280 151194 1.46 8.35 E-04 BC035170 1561079_at BC035170 — ... 1.46 5.42E-03 XP07 240168_at AA679589 NM 015024 23039 1.46 3.12E-03 EZH2 215006_at AK023816 NM 004456 NM 152998 2146 1.46 2.64E-03 LTB4DH 228825 at BE566894 NM_012212 22949 1.46 1.02E-03 BBX 1557240_a_at BU689085 NM 020235 56987 1.46 5.33E-03 ARIH2 1559121_s_at AI767566 NM 006321 10425 1.46 8.11 E-04 ANKRD28 229307_at N32051 NM 015199 23243 1.45 2.51E-03 337 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Ceils Useful for Immuno-Based BoNT/A Activity Assays LRRFIP2 232704_s_at AK025207 NM_006309 NM_017724 9209 1.45 2.05E-03 PHLDA1 218000_s_at NM 007350 NM_007350 22822 1.45 5.61E-03 AF070602 216214_at AF070602 — ... 1.44 3.75E-03 C6orf133 215558_at AK001118 NM_015255 23304 1.44 1.76E-04 AW083060 243274_x_at AW083060 — ... 1.44 6.61 E-03 ATOH8 228890_at BF434995 NM 032827 84913 1.43 9.99E-03 CHC1L 230292_at AA868809 NM 001268 1102 1.43 2.15E-03 SMG1 KIAA0220 LOC440345 244766_at BG180003 NM_014006 NM 015092 XM_496125 23049 283846 440345 1.43 1.93E-03 T98846 239654_at T98846 — ... 1.43 7.51 E-05 ZA20D3 222186_at AL109684 NM_019006 54469 1.43 2.35E-03 SMC5L1 1562948_at BC035661 NM 015110 23137 1.43 7.05E-03 SMC4L1 237246_at AI797163 NM_00100279 9 NM 00100280 0 NM_005496 10051 1.43 7.94E-03 SLD5 1554356_at BC027454 NM_032336 84296 1.43 1.24E-03 AW451426 244480_at AW451426 — ... 1.42 1.53E-04 ZSWIM6 1560199_x_at AU120130 XM_035299 57688 1.42 2.96E-04 H06497 243211_at H06497 ... ... 1.42 1.88E-03 ENC1 201340_s_at AF010314 NM_003633 8507 1.42 8.83E-03 AW963544 238580_at AW963544 — ... 1.42 1.14E-04 IGSF4 232793_at AL359567 NM_014333 23705 1.42 6.90E-04 AK022100 233406 at AK022100 — ... 1.41 8.65E-03 CENTB2 240759_at AW593931 NM_012287 23527 1.41 8.75E-04 PTPRK 203038_at NM_002844 NM_002844 5796 1.41 2.80E-04 LOC286109 243304_at AI733824 — 286109 1.41 8.07E-03 ASCL1 213768_s_at AW950513 NM_004316 429 1.40 2.65E-05 AW293174 244290_at AW293174 XM_499534 442612 1.40 2.89E-05 MGC15937 227794_at BF432254 NM 080661 92292 1.40 2.78E-03 PTK2 1559529_at BC043202 NM_005607 NM_153831 5747 1.40 3.63E-03 MAN2A1 205105_at NM_002372 NM_002372 4124 1.39 3.32E-04 CBLB 233614_at AU145361 NM 170662 868 1.39 9.21 E-04 K1AA0998 215898_at AK021879 NM 015072 23093 1.39 5.01 E-03 PMAIP1 204285_s_at AI857639 NM 021127 5366 1.39 3.88E-06 FNBP1L 242310_at AA665058 NM_017737 54874 1.38 4.27E-03 AI755057 233055_at AI755057 — ... 1.38 1.05 E-03 RAB3-GAP150 240234_at AI216539 NM 012414 25782 1.38 7.73E-03 ACSL4 1557418_at W95007 NM 004458 NM_022977 2182 1.38 5.61 E-04 FAM13A1 232628_at AI740629 NM 014883 10144 1.37 4.61 E-03 FLJ23451 1569601 at BF106979 NM 024766 79823 1.37 4.24E-05 ZNF217 203739_at NM_006526 NM_006526 7764 1.37 5.73E-03 BF197705 230401_at BF197705 — ... 1.37 9.92E-04 HEG 212822_at AA121502 XM 087386 57493 1.37 2.43E-04 MGC15523 1563226 at BC020925 NM_138570 124565 1.37 7.40E-03 AA156721 201952_at AA156721 ... ... 1.37 1.55E-04 AL110237 232959_at AL110237 ... ... 1.37 7.09E-03 PSME4 237180_at T97717 NM 014614 23198 1.37 1.78E-03 IGSF4 244345_at AI627453 NM_014333 23705 1.36 7.17E-03 MRPS25 244019_at T89845 NM_022497 64432 1.36 2.01 E-03 BF801735 238712_at BF801735 — ... 1.36 2.63E-03 SPRY4 221489 s at W48843 NM 030964 81848 1.35 7.35E-04 SCN7A 239984_at Al 333640 NM_002976 6332 1.35 8.33E-04 338 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 HIVEP2 Jacky, B., et al., Cells Useful for 243254 at T08739 Immuno-Based BoNT/A Activity Assays NM_006734 3097 1.35 5.09E-03 PTPN11 241930_x_at AA223204 NM_002834 5781 1.35 9.28E-04 AW235215 238913_at AW235215 — ... 1.35 9.92E-03 C10orf6 1553909 x at NM 144592 NM_018121 55719 1.35 2.80E-04 ZFHX4 219779_at NM_024721 NM 024721 79776 1.35 1.82E-05 MEST 202016_at NM_002402 NM 002402 4232 1.34 2.65E-04 TRIO 231403_at N21108 NM_177524 NM_177525 NM_007118 7204 1.34 9.69E-03 UBE3C 242673_at AA931284 NM_014671 9690 1.34 3.34E-04 PPP2R2A 236492 at Al 934447 NM 002717 5520 1.34 4.98E-03 HIAT1 230868_at BF433103 NM_033055 64645 1.34 7.24E-04 LOC440971 1556744_a_at AI732587 XM_496651 440971 1.33 3.92E-03 CUGBP2 202156_s_at N36839 NM 006561 10659 1.33 2.42E-03 CNTN4 229084_at R42166 NM 175607 152330 1.33 8.25E-03 FLJ11259 218627_at NM 018370 NM_175612 NM_175613 NM 018370 55332 1 32 4.63E-03 CEPT1 1561884_at AL833102 NM_00100779 Λ 10390 1.32 1.40E-04 AL049988 216614_at AL049988 NM_006090 1.31 9.72E-03 CSPG6 1556925_at AL360194 NM 005445 9126 1.31 8.99E-03 ASXL1 242439_s_at AI819150 NM 015338 171023 1.31 1.22E-05 PVT1 1558290_a_at BG200951 XM_372058 441378 1.31 1.11E-04 LOC441378 TUBB6 209191 at BC002654 XM_499128 NM_032525 5820 84617 1.31 5.17E-04 IRAKI BP1 233290_at AU145280 NM 001010844 134728 1.31 2.71 E-03 AL137730 226999_at AL137730 — ... 1.31 6.07E-03 PTEN 233314 at AK021487 NM 000314 5728 1.31 7.60E-03 ZNF215 220214_at NM 013250 NM_013250 7762 1,31 5.81 E-03 LRPPRC 1557360_at CA430402 NM_133259 10128 1.30 1.55E-03 DKFZP434C21; 231552 at AW451785 NM_015635 26130 1.30 5.13E-04 AI651786 237945_at Al651786 ... ... 1.30 4.28E-03 AU155234 233289 at AU155234 ... ... 1.30 9.43E-03 AA648983 240478_at AA648983 ... ... 1.30 9.77E-05 AA412686 244608_at AA412686 ... ... 1.30 4.76E-03 RBMS3 240245_at AW237264 NM_00100379 27303 1.30 6.53E-03 2 NM_00100379 3 NM 014483 AK021457 216682 s at AK021457 — — 1.30 2.30E-04 SHPRH 243964_at AI631201 NM 173082 257218 1.29 9.11 E-03 METAP2 244185_at AA921841 NM 006838 10988 1.29 5.27E-05 MAB21L2 210302_s_at AF262032 NM_006439 10586 1.29 1.50E-04 AA543084 236480_at AA543084 — — 1.29 3.14E-04 AW271626 237441_at AW271626 — ... 1.29 2.95E-05 SF3B14 1561923_a_at AF147425 NM 016047 51639 1.29 7.66E-03 PRDX6 242751 at N55072 NM 004905 9588 1.28 1.80E-03 SMU1 228180_at AA805653 NMJD18225 55234 1.28 6.63E-04 BF001773 241906_at BF001773 — ... 1.28 9.10E-03 PFAAP5 221899_at AI809961 NM 014887 10443 1.28 8.55E-03 FLJ13273 220063 at NM 024751 NM_024751 79807 1.28 4.70E-04 HM13 1560297_at BG928538 NM_030789 81502 1.28 3.78E-03 NM_178580 NM_178581 NM 178582 339 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al„ Cells Useful for Immuno-Based BoNT/A Activity Assays DRF1 206661_at NM_025104 NM_025104 NM_145663 80174 1.28 5.80E-04 LOC284219 1556425_a_at BF509747 — 284219 1.27 2.33E-03 ANXA2 213503_x_at BE908217 NM_00100285 7 NM 00100285 8 NM_004039 302 1.27 2.58E-03 SPON1 213994_s_at AI885290 NM 006108 10418 1.27 2.99E-03 M11S1 244778_x_at N63691 NM 005898 NM_203364 4076 1.27 1.16E-03 LOC253981 226430_at AI394438 — 253981 1.26 6.58E-04 FUBP1 240307_at N54783 NM_003902 8880 1.26 5.57E-04 NKTR 231235 at AA732581 NM 005385 4820 1.26 6.07E-03 ARHGAP24 223422 s at AI743534 NM 031305 83478 1.26 2.57E-03 KIAA1838 241152_at BE466903 NM 032448 84498 1.26 4.94E-03 USP34 207365_x_at NM_014709 NM 014709 9736 1.25 1.35E-04 DHX57 239311_at AI367034 NM 144995 NM_145646 NM_198963 90957 1.25 7.92E-03 UBE2H 239721_at AI280328 NM 003344 NM_182697 7328 1.25 7.22E-03 ID1 208937_s_at D13889 NM_002165 NM_181353 3397 1.25 1.45E-03 MARK3 239166_at R98192 NM 002376 4140 1.24 8.08E-04 APBB2 213419 at U62325 NM 173075 323 1.24 5.44E-04 SVH 1558748_at AL832759 NM_031905 83787 1.24 2.00E-03 ASXL1 242438_at AI819150 NM_015338 171023 1.24 6.76E-05 P15RS 228566_at AA778694 NM_018170 55197 1.24 2.39E-04 LOC115648 1558486 at BC022394 NM 145326 115648 1.24 3.07E-04 CADPS 1568603_at AI912173 NM_003716 NM 183393 NM_183394 8618 1.24 3.75E-03 AI291804 242856 at AI291804 — — 1.24 8.05E-05 TCTEL1 242109 at AI038577 NM 006519 6993 1.23 3.41 E-03 QKI 241938_at AA935633 NM_006775 NM 206853 NM 206854 NM 206855 9444 1.23 1.41E-04 SCARA3 223842_s_at AB007830 NM_016240 NM 182826 51435 1.22 3.50E-04 MRPS5 236779_at BG539414 NM_031902 64969 1.22 1.33E-03 BE670307 227955_s_at BE670307 — ... 1.22 9.05E-06 DNAPTP6 241812_at AV648669 NM_015535 26010 1.22 8.50E-03 PCGF5 229194 at AL045882 NM_032373 84333 1.22 2.28E-04 AU145679 233607_at AU145679 — — 1.21 4.54E-03 BE464799 214036_at BE464799 ... ... 1.21 5.03E-05 SLC03A1 219229_at NM_013272 NM_013272 28232 1.21 2.66E-03 BF433200 242467 at BF433200 — — 1.21 7.14E-03 PPARG 232331_at AK027107 NM_005037 NM 015869 NM 138711 NM 138712 5468 1.21 6.85E-03 FNTA 240527_at AI953011 NM_002027 2339 1.21 1.22E-03 TCF7L2 216035_x_at AV721430 NM_030756 6934 1.21 2.15E-05 POLE 216026 s at AL080203 NM 006231 5426 1.21 2.59E-03 ZA20D3 238812 at AA741296 NM 019006 54469 1.21 9.92E-03 SFRS2IP 232597 x at AK025132 NM 004719 9169 1.21 1.99E-03 340 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays TH 208291_s_at NM_000360 NM_000360 NM 199292 NM 199293 7054 1.21 8.60E-04 NKTR 202380_s_at NM_005385 NM 005385 4820 1.21 1.31 E-03 PTPN13 243792_x_at AI281371 NM 006264 NM 080683 NM_080684 NM 080685 5783 1.20 9.38E-03 UBE3B 232301_at AK022019 NM 130466 NM 183414 NM_183415 89910 1.20 1.77E-04 RAB12 238714_at AA504249 XM_113967 201475 1.20 7.92E-04 AW299775 235008_at AW299775 — — 1.20 1.71 E-03 HSD17B12 242616_at W80359 NM_016142 51144 1.19 8.50E-03 R16900 242514 at R16900 — — 1.19 2.39E-03 DST 232098_at AK025142 NM_001723 NM_015548 NM 020388 NM_183380 667 1.19 4.65E-03 0KFZP564C186 1559139_at BC009786 NM_015658 26155 1.19 3.03E-03 C9orf3 233599_at AK025151 NM_032823 84909 1.19 1.52 E-03 AI859990 244197_x_at AI859990 — ... 1.18 1.42E-03 SPON1 213993 at Al 885290 NM_006108 10418 1.18 8.98E-03 CENPF 207331_at NM_016343 NM 016343 1063 1.18 6.92E-03 CDC2L5 232266_x_at AK024379 NM_003718 NM_031267 8621 1.18 2.93E-03 EXT1 237310_at Al 743607 NM_000127 2131 1.18 4.88E-03 C1QDC1 218456_at NM_023925 NM_00100225 9 NM 023925 NM 032156 65981 1.18 2.52E-06 FLJ45645 243038_at AW292769 NM_198557 375287 1.18 6.22E-03 H43040 231108 at H43040 — — 1.18 2.07E-04 SEC63 242749 at AI022173 NM 007214 11231 1.18 3.85E-03 KLF7 238482_at AL120562 NM 003709 8609 1.17 4.23E-04 API5 214960_at AF229253 NM_006595 8539 1.17 1.28E-04 ENC1 201341_at NM 003633 NM 003633 8507 1.17 9.25E-04 SLC16A4 228455 at AI092824 NM 004696 9122 1.17 3.54E-03 ANP32A 235954_at AA972597 NM 006305 8125 1.17 4.73E-03 UBE2E1 236062_at AI742722 NM_003341 NM_182666 7324 1.17 2.49E-03 EVL 227232 at T58044 NM 016337 51466 1.17 1.12E-03 SLC6A2 210353_s_at M65105 NM 001043 6530 1.17 3.19E-03 Cep63 238170_at BE327727 NM_025180 80254 1.17 6.06E-05 AU147479 233359_at AU147479 — — 1.16 1.44E-03 AF010144 207953 at AF010144 ... — 1.16 6.11E-05 TLE3 228340_at BE967118 NM_005078 7090 1.16 2.16E-03 LOC338692 238642_at AW367571 NM 207354 338692 1.16 6.72E-03 BF981643 214720_x_at BF981643 NM_144710 NM_178584 151011 1.16 3.74E-03 AU152763 232939_at AU152763 — — 1.16 1.12E-03 COMMD10 1560349_at BC036897 NM_016144 51397 1.16 7.89E-03 MDN1 1569484_s_at AL603301 NM 014611 23195 1.16 1.37E-03 FLJ10213 219906 at NM_018029 NM_018029 55096 1.16 2.68E-04 AF5Q31 1555436_a_at BC025700 NM_014423 27125 1.16 4.10E-04 BE467787 243835_at BE467787 — — 1.16 3.16E-03 NOSTRIN 235506_at AI076788 NM_052946 115677 1.16 5.52E-03 341 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays wwox 242099_at T83938 NM_016373 51741 1.16 1.72E-03 NKTR 202379_s_at Al361805 NM 018560 NM 130788 NM_130790 NM_130791 NM 130792 NM 130844 NM_005385 4820 1.16 2.17E-03 TXNRD1 201266_at NM_003330 NM 003330 7296 1.15 1.40E-04 STRA6 1569334_at BC015881 NM 182729 NM 182742 NM_182743 NM_022369 64220 1.15 2.00E-03 DLEU2 215629_s_at AA905286 NM 006021 8847 1.15 8.95E-03 MSH3 233263_at AU147635 NM 002439 4437 1.15 3.30E-04 YAP 244803_at Al 335191 NM 018253 55249 1.14 3.17E-03 ANAPC5 235926_at AI312527 NM_139118 NM 139119 NM_139120 NM_139121 NM_016237 51433 1.14 3.93E-03 LOC152573 229485_x_at AI735586 XM 496688 152573 1.14 9.91 E-03 VPS 16 233313_at AU 158316 NM_022575 64601 1.14 1.33E-03 TNRC6 233836_at AK025277 NM 080413 NM 080414 NM 014494 27327 1.14 4.69E-03 PCGF5 227935_s_at AA522681 NM_020847 NM 032373 84333 1.13 1.23E-03 LOC255326 233271_at AU145563 XM_497224 255326 1.13 9.42E-03 KIAA1881 207730_x_at NM 017932 XM 375558 114782 1.13 8.71 E-04 NAPE-PLD 233539 at AK000801 NM_198990 222236 1.13 6.74E-03 PGAP1 220576_at NM 024989 NM_024989 80055 1.13 4.35E-04 FLJ10707 239957_at AW510793 XM 371614 55209 1.13 3.10E-03 SIVA 222030_at AW024335 NM 006427 10572 1.13 8.59E-03 MGC34032 1552782_at AK091400 NM_021709 NM 152697 204962 1.13 6.36E-03 TP53I3 210609_s_at BC000474 NM 004881 9540 1.13 6.61E-03 SYT11 232677_at AU146128 NM_147184 NM 152280 23208 1.13 3.78E-05 ZAK 1555259_at AF465843 NM 016653 51776 1.13 4.30E-04 MTBP 233436 at AK022122 NM_133646 NM 022045 27085 1.12 2.65E-03 SDHA 230077_at W90764 NM 004168 255812 1.12 7.47E-04 SDHAL2 EIF4A1 214805_at U79273 XM_171032 NM_001416 6389 1973 1.12 7.09E-03 ZNF131 1557384_at AL832081 — 7690 1.12 3.31 E-03 TJP1 244476_at R39769 NM 003257 7082 1.12 1.55E-03 NM 000575 208200 at NM 000575 NM_175610 1.12 9.29E-03 SFI1 36545_s_at AB011114 NM_00100746 7 9814 1.12 1.54E-03 GALNT7 222587 s at BF699855 I NM_014775 NM_017423 51809 1.12 1.21E-03 AA176313 1566113 at AA176313 — — 1.12 7.32E-03 RABGAP1L 1565762_at AK074233 NM 014857 9910 1.12 4.63E-03 MED6 207078_at NM_005466 NM 005466 10001 1.12 8.69E-03 NDUFS1 1559691_at BC032767 NM 005006 4719 1.11 7.49E-03 SYNCRIP 1555427_s_at AY034482 NM 006372 10492 1.11 3.11 E-03 342 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays TH1L 220607_x_at NM_016397 NM 016397 NM_198976 51497 1.11 1.11E-03 SMURF2 230099 at AM 39993 NM 022739 64750 1.11 9.53E-03 KHDRBS3 209781 s at AF069681 NM_006558 10656 1.11 6.19E-04 LOC90799 223815_at AF130069 NM 138363 90799 1.10 9.64E-03 ASCL1 209988_s_at BC001638 NM_004316 429 1.10 6.04E-04 AA192765 238172_at AA192765 — — 1.10 7.54E-04 C7orf28B 215024_at AK000993 NM 198097 221960 1.10 8.32E-03 SURF5 206593_s_at NM_006752 NM_006752 NM 133640 NM 181491 6837 1.10 8.66E-03 SNTB2 232784_at R42604 NM_006750 NM_130845 6645 1.10 1.54E-05 TD-60 243297_at AI498610 NM_018715 55920 1.10 6.95E-03 HES1 203394 s at BE973687 NM 005524 3280 1.10 9.57E-05 CAS1 239545_at Al335004 NM_022900 64921 1.10 4.20E-03 PSMB7 244801_at AI248671 NM 002799 5695 1.10 1.35E-04 MBNL2 232138_at AW276914 NM 144778 NM_207304 10150 1.10 6.31 E-04 hSyn 231087_at AL046412 NM_018157 55188 1.09 8.23E-03 LRRFIP1 238840_at AW082668 NM_004735 9208 1.09 3.75E-03 SLC7A5 201195_s_at AB018009 NM_003486 8140 1.09 1.06 E-04 RDH11 217042_at AL096716 NM 016026 51109 1.09 1.95E-03 LUC7L2 243852_at Al 963460 NM_016019 51631 1.09 4.04E-03 SEC8L1 216538_at AL049351 NM_021807 60412 1.09 2.92E-04 NM 006896 206848_at NM 006896 — — 1.09 2.52E-04 PSMD7 244515 at AI640348 NM 002811 5713 1.08 1.31E-05 SYMPK 1554595_at BC030214 NM_004819 8189 1.08 6.40E-03 ELOVL5 1566079_at AL833001 NM 021814 60481 1.08 7.71 E-03 FLJ10357 241627_x_at Al640434 NM 018071 55701 1.08 1 28E-03 PASK 213534_s_at D50925 NM 015148 23178 1.08 6.82 E-03 CALM2 235190_at BF591288 NM 001743 805 1.08 1.73 E-04 SEMA5A 205405_at NM 003966 NM 003966 9037 1.08 7.59E-05 ITSN1 215791_at AF003738 NM 00100113 2 NM_003024 6453 1.08 1.59E-03 PBX4 230536_at AJ300182 NM_025245 80714 1.07 9.77E-04 MAN2A1 226538 at AV700323 NM 002372 4124 1.07 2.26E-04 MGC2803 230213_at BE220399 NM_024038 79002 1.07 9.35E-05 ABCD1 205142_x_at NM_000033 NM 000033 215 1.07 8.99E-03 ZNF537 223392_s_at BF510588 NM_020856 57616 1.07 1.32E-04 AI733583 243235 at Al 733583 — — 1.07 3.45E-03 CROP 242389_at BE887449 NM_006107 NM_016424 51747 1.07 1.26E-03 SSH2 230590_at BE675486 NM 033389 85464 1.07 5.70E-04 NDUFS8 232169 x at AK002110 NM 002496 4728 1.06 6.64E-04 VAPA 242780_at AI332536 NM_003574 NM_194434 9218 1.06 7.88E-03 FDFT1 238666_at BF438300 NM 004462 2222 1.06 1.67E-03 NQ01 210519 s at BC000906 NM 000903 1728 1.06 4.23E-03 KLHL5 233866_at AK001836 NM_00100707 5 51088 1.06 5.76E-03 NM 199039 343 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays SLC8A3 1562403_a_at AK096553 NM_033262 NM 058240 NM 182932 NM_182933 NM_182936 NM_183002 6547 1.06 2.76E-05 DPF1 206531_at N M_004647 NM_004647 8193 1.06 4.01 E-03 MCCC2 1556345_s_at AF086534 NM_022132 64087 1.06 2.60E-03 NOS1 239132_at BE299830 NM 000620 4842 1.05 1.68E-03 DOK4 209691_s_at BC003541 NM_018110 55715 1.05 9.53E-03 SESN2 223195 s at BF131886 NM_031459 83667 1.05 7.34E-03 AK025909 233814_at AK025909 — — 1.05 2.17E-06 FBN1 202766_s_at NM 000138 NM_000138 2200 1.05 4.10E-03 UCHL1 201387_s_at NM 004181 NM 004181 7345 1.05 2.84E-03 DIAPH1 209190 s at AF051782 NM 005219 1729 1.05 3.26E-04 KIAA0152 200616_s_at BC000371 NM_014730 9761 1.04 2.72E-06 GAP43 204471_at NM_002045 NM_0O2O45 2596 1.04 4.27E-04 KIAA0528 240205_x_at AW188170 NM_014802 9847 1.04 5.35E-03 AK025343 216176 at AK025343 — — 1.04 4.13E-04 WDR45 215553_x_at AK024315 NM 007075 11152 1.04 3.37E-03 NLN 234762_x_at AK026655 NM_020726 57486 1.03 6.21 E-03 AI589594 238694_at AI589594 — ... 1.03 1.36E-04 CTSL2 210074 at AF070448 NM 001333 1515 1.03 7.07E-03 COBLL1 203642_s_at NM 014900 NM_014900 22837 1.03 7.47E-03 MGC15407 235662_at AM 25867 NM 080667 112942 1.03 8.10E-03 TRNT1 223814_at BC005184 NM 016000 NM_182916 51095 1.03 8.10E-04 AI377043 230722_at AI377043 — ... 1.03 2.26E-03 MGC45866 232475_at BC002881 NM_152259 90381 1.03 4.71 E-03 KIAA2024 1566166_at AL833423 NM_172070 130507 1.03 3.17E-04 SRGAP2 1556203 a at AI263819 XM 059095 23380 1.03 1.13E-03 CHTF18 226569_s_at AK024476 NM_022092 63922 1.02 1.51 E-03 TCF7L2 216511_s_at AJ270770 NM 030756 6934 1.02 1.84E-07 SDFR1 228723_at AL360198 NM_012428 NM_017455 27020 1.02 2.35E-04 CDCA7 230060_at AI277642 NM_031942 NM_145810 83879 1.02 6.93E-03 CIAPIN1 230838 s at AW771492 NM 020313 57019 1.02 6.62E-03 SDC4 202071 at NM 002999 NM_002999 6385 1.02 4.53E-03 STK36 234005_x_at AK022692 NM 015690 27148 1.02 9.55E-05 DLGAP4 233056_x_at AK024674 NM_014902 NM 183006 22839 1.02 5.12E-03 CNOT7 233019_at AU145061 NM_013354 NM_054026 29883 1.02 3.38E-03 SKIL 217591 at BF725121 NM 005414 6498 1.01 8.82E-06 GARNL1 215162_at AB020691 NM 014990 NM_194301 253959 1.01 3.09E-04 RFC5 203210_s_at NM_007370 NM_007370 NM_181578 5985 1.01 1.06E-03 AK024136 217152_at AK024136 — — 1.01 3.14E-03 ATP8B1 214594_x_at BG252666 NM_005603 5205 1.01 6.15E-03 AL050032 216621_at AL050032 — — 1.01 1.08E-05 CKLFSF7 1560754_at AL832450 NM 138410 NM_181472 112616 1.01 1.86E-03 KIAA1212 1562648_at BC035848 NM_018084 55704 1.01 4.98E-03 CAPN1 232012_at AV691296 NM_005186 823 1.01 1.96E-03 ZNF207 231848 x at AW192569 NM 003457 7756 1.01 7.04E-03 TRA2A 229574_at AI268231 NM_013293 29896 1.01 7.43E-03 344 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays AU146021 232478_at AU146021 — — 1.01 7.34E-03 KNTC1 206316_s_at NM_014708 NM_014708 9735 1.00 8.69E-06 DENR 238982 at AW665791 NM 003677 8562 1.00 3.31 E-03 DNCH2 1565149_at AF288405 XM_370652 79659 1.00 2.59E-06 PRDX2 215067_x_at AU147942 NM_005809 NM_181737 NM_181738 7001 1.00 5.62E-03 PRDX6 238951_at BF843343 NM_004905 9588 1.00 2.00E-04 RIOK3 215588_x_at AK024958 NM_003831 NM_145906 8780 1.00 5.41 E-04 MIDI 203636_at BE967532 NM_000381 NM_033290 NM_033291 4281 1.00 2.42E-03 E2-230K 1554814_at BC007822 NM_022066 63893 1.00 2.86E-03 ZFOC1 1558816 at BC037793 NM_152437 144348 1.00 1.23E-04 EFHC1 225656_at AI564473 NM_018100 114327 1.00 7.26E-03 KIAA0999 242920_at AW590838 NM 025164 23387 1.00 6.83E-03 GRK6 202848_s_at BG423052 NM_00100410 5 NM_00100410 6 NM_002082 2870 0.99 2.95E-03 STS 243858 at AA699970 NM 000351 412 0.99 1.31 E-03 AZI2 223846_at BC001139 NM_022461 NM_203326 64343 0.99 9.97E-05 AW069499 230886_at AW069499 — — 0.99 5.25E-04 NKTR 215338_s_at AI688640 NM 005385 4820 0.99 6.23E-03 FLJ10408 220535_at NM_018088 NM 018088 55138 0.99 2.76E-03 PDZRN3 232776 at AU145289 NM_015009 23024 0.99 5.32E-03 ACVR2 244332 at AW974077 NM_001616 92 0.99 5.39E-06 GLS 223080 at AK025021 NM 014905 2744 0.99 2.09E-03 RAB35 205461_at NM 006861 NM_006861 11021 0.99 8.15E-03 FLJ21415 218867_s_at NM 024738 NM_024738 79794 0.99 4.67E-03 MTMR9 233101 at AK022071 NM 015458 66036 0.98 3.57E-04 TDG 203742_s_at BF674842 NM_00100841 1 NM_003211 6996 0.98 2.79E-04 DKFZP434K04C 1570227_at BC016065 NM 020312 57017 0.98 7.84E-03 RBL1 1555004_a_at BC032247 NM_002895 NM_183404 5933 0.98 3.12E-03 MYST3 242480 at AA868356 NM 006766 7994 0.98 3.48E-03 TXNDC5 243405_at Al097337 NM_022085 NM_030810 81567 0.98 1.17E-03 C14orf153 232814_x_at AK024310 NM_032374 84334 0.98 2.05E-03 FLJ10569 237504 at AW002398 NM_018142 55174 0.98 5.78E-05 AW451634 229470 at AW451634 — — 0.98 2.25E-03 ATP2B1 209281_s_at M95541 NM_00100132 3 NM_001682 490 0.98 7.26E-05 CHPT1 1559739_at AK025141 NM_020244 56994 0.98 1.14E-03 PFKFB4 228499_at AL038787 NM 004567 5210 0.98 1.03E-04 AI435248 242837_at AI435248 — — 0.98 3.31 E-03 AL567118 241388 at AL567118 — — 0.97 9.39E-03 ZNF274 232436_at AI057616 NM 016324 NM_016325 NM_133502 10782 0.97 8.11 E-03 SLC03A1 229776 at AW138118 NM 013272 28232 0.97 3.95E-03 DRIM 209725_at AF072718 NM 014503 27340 0.97 6.32E-03 345 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays AARS 201000_at NM 001605 NM 001605 16 0.97 3.59E-03 BE857972 243781 at BE857972 — — 0.97 2.71 E-04 AU146017 234082_at AU146017 — — 0.97 1.73E-03 MGC20481 243513_at AA971848 NM_052849 90416 0.96 3.69E-03 CPEB4 242384_at AI452469 NM_030627 80315 0.96 8.12E-03 KDELC2 225128_at AL548941 NM_153705 143888 0.96 3.31 E-03 R84398 241993_x_at R84398 — — 0.96 3.54E-03 PR47 1560526_at BQ880034 — 266671 0.96 4.91 E-03 GTSE1 204315_s at AI340239 NM_016426 51512 0.96 1.04E-03 WDR11 229694_at BF062828 NM_018117 55717 0.96 6.59E-03 CTNNB1 242558_at AW362945 NM_001904 1499 0.96 4.14E-03 AI760298 244054_at AI760298 — — 0.96 2.18E-05 IQWD1 235613_at BF476152 NM_018442 55827 0.96 6.64E-03 AW024890 229942_at AW024890 — — 0.96 6.64E-03 DDHD1 231165_at BE857355 NM 030637 80821 0.96 8.45E-03 CDYL 240594_at W86659 NM_004824 NM_170751 NM_170752 9425 0.96 4.83E-03 U2AF1 232141 at AU144161 NM 006758 7307 0.96 2.17E-05 RAPGEF2 238176_at T86196 XM_376350 9693 0.96 9.65E-03 C14orf135 1563259_at AK024838 NM_022495 64430 0.95 1.91 E-04 GPX3 214091_s_at AW149846 NM_002084 2878 0.95 6.75E-03 DKFZp434P05E 232398 at AK001064 NM 173466 91531 0.95 1.46E-03 MATR3 242260_at BG283790 NM_018834 9782 0.95 4.52 E-04 STK36 231806_s_at AL133630 NM_015690 27148 0.95 3.18E-03 DTX1 1559618 at BQ188678 NM_004416 1840 0.95 2.32E-03 AL832061 1559436 x at AL832061 — — 0.95 1.65E-03 VPS29 223026_s_at AF201946 N M 016226 NM_057180 51699 0.95 6.16E-04 SEC61A2 228747 at Al694646 NM 018144 55176 0.95 9.12E-03 USP7 230761 at Al 972599 NM_003470 7874 0.95 4.14E-06 STK32B 219686_at NM 018401 NM_018401 55351 0.95 7.68E-03 SMO 218629 at NM_005631 NM_005631 6608 0.95 6.28E-03 TCF7L2 212761 at Al 949687 NM 030756 6934 0.95 3.71 E-03 PDK1 226452 at AU146532 NM 002610 5163 0.94 7.99E-04 MAP3K1 225927 at AA541479 XM 042066 4214 0.94 1.85E-03 PMAIP1 204286_s_at NM_021127 NM_021127 5366 0.94 9.09E-04 AL049260 216524_x_at AL049260 — — 0.94 1.42E-03 GTF2H3 222104_x_at AI569458 NM_001516 2967 0.94 2.18E-03 MGC13098 POLR2J2 214740_at BE676209 NM 032958 NM_032959 NM 145325 XM_379817 XM_499280 246721 84820 0.94 6.48E-03 FLJ31795 1566480_x_at AK096357 NM 144609 124808 0.94 1.19E-03 MIDI 203637_s_at NM_000381 NM 000381 NM_033290 NM_033291 4281 0.94 8.91 E-03 AI692624 1556352 at AI692624 — — 0.94 3.86E-03 AL035461 231827 at AL035461 — — 0.94 8.02E-03 NFKBIZ 223218_s_at AB037925 NM_00100547 4 NM_031419 64332 0.93 9.02E-03 R78413 240538 at R78413 — — 0.93 5.24E-03 UBXD4 235327_x_at BG111015 NM 181713 165324 0.93 2.26E-06 PABPC1 236907_at Al 760366 NM 002568 26986 0.93 9.37E-03 RNF34 219035 s at NM 025126 NM_025126 80196 0.93 1.26E-05 NM 194271 346 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays FLJ11539 219791_s_at NM_024748 XM_496724 79804 0.93 1.41E-03 FLJ10156 221591_s_at BC005004 NM_019013 54478 0.93 4.68E-04 CREBL1 1554487_a_at BC008394 NM_004381 1388 0.93 4.64E-05 RBBP4 239071_at AI972451 NM_005610 5928 0.93 3.91E-03 SNRPA1 242146 at AA872471 NM 003090 6627 0.93 4.37E-03 DERL3 231324_at AW452134 NM_00100286 2 NM_198440 91319 0.93 9.94E-05 DDX50 1568815_a_at AA903184 NM_024045 79009 0.93 3.15E-03 KCTD3 241903 at AI688631 NM 016121 51133 0.93 1.35E-03 TBX3 225544_at AI806338 NM_005996 NM_016569 6926 0.93 2.95E-03 EXOC7 214802 at AK022397 NM 015219 23265 0.93 6.60E-03 ZDHHC13 243250_at AI922173 NM 00100148 3 NM_019028 54503 0.93 7.75E-03 NSF 1566785_x_at AK025172 NM 006178 4905 0.92 1.01E-03 C9orf3 237716 at AA699673 NM 032823 84909 0.92 2.56E-03 GPR125 210473_s_at M37712 NM_145290 166647 0.92 5.29E-07 ZNF160 214715_x_at AK024789 NM_033288 NM_198893 90338 0.92 1.07E-03 CALU 238908_at BG392414 NM 001219 813 0.92 2.85E-05 TCF7L2 216037_x_at AA664011 NM_030756 6934 0.92 1.59E-04 MBNL2 232369_at AF339768 NM_144778 NM_207304 10150 0.92 6.38E-03 DHX36 1559039 at AK096808 NM 020865 170506 0.92 4.13E-03 BE563152 224806_at BE563152 XM_498674 440448 0.92 7.47E-03 TM4SF8 232632_at AU145719 NM_005724 NM_198902 10099 0.92 1.10E-05 BTBD14B 215587 x at AK023891 NM_052876 112939 0.92 2.11E-03 AI821721 241223_x_at AI821721 — — 0.91 3.84E-03 SREBF1 235862_at AA954908 NM_00100529 1 NM_004176 6720 0.91 1.46E-03 AI570571 236092_at Al 570571 — — 0.91 2.41 E-03 FLJ13491 219245_s_at Al 309636 NM_024623 79676 0.91 9.68E-06 MDH1 235374_at AW952547 NM 005917 4190 0.91 1.14E-03 PASK 216945 x at U79240 NM 015148 23178 0.91 3.14E-03 DTYMK 1553983_at AF258562 NM_012145 1841 0.90 9.36E-03 CLU 208792_s_at M25915 NM_001831 NM_203339 1191 0.90 3.22E-05 C20orf172 219512 at NM 024918 NM_024918 79980 0.90 1.35E-03 PTPN1 202716_at NM_002827 NM_002827 5770 0.90 4.52E-04 ENTPD6 201704_at NM 001247 NM_001247 955 0.90 9.65E-03 0KFZP564C19f 236367 at N33174 XM 498825 284649 0.90 3.20E-03 GPT2 224839_s_at BG328998 NM_133443 84706 0.89 2.50E-03 TH1L 225006_x_at AJ238379 NM_016397 NM_198976 51497 0.89 1.75E-05 AW975183 244340 x at AW975183 — — 0.89 1.08E-03 AW131450 235513_at AW131450 — — 0.89 1.09E-05 AK023783 215604_x_at AK023783 — — 0.89 6.48E-03 KIAA0582 239442_at BF589179 NM 015147 23177 0.89 1.66E-03 BTBD7 217141_at AL049394 NM 00100286 0 NM_018167 55727 0.89 2.17E-03 DNAPTP6 222154 s at AK002064 NM_015535 26010 0.89 1.33E-03 RNPEP 208270_s_at NM_020216 NM_020216 6051 0.89 9.93E-04 347 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays KIAA0232 232595_at AK023294 NM_014743 9778 0.89 2.09E-03 ZNF503 227195_at AA603467 NM 032772 84858 0.88 1.25E-04 RABL4 213784 at AL037167 NM 006860 11020 0.88 4.07E-03 KLF7 204334 at AA488672 NM_003709 8609 0.88 5.59E-04 FLJ13611 234788 x at AK024819 NM_024941 80006 0.88 4.20E-03 TFF3 204623_at NM 003226 NM_003226 7033 0.88 1.84E-03 C7orf24 239841_at AA137038 NM 024051 79017 0.88 5.49E-05 FLJ14346 220720_x_at NM 025029 NM 025029 80097 0.88 2.42E-03 PGF 215179_x_at AK023843 NM_002632 5228 0.88 6.50E-04 BTBD9 233041_x_at AK025009 NM_152733 114781 0.87 5.26E-03 ZFP64 242759_at Al 821726 NM 018197 NM 022088 ' NM 199426 NM_199427 55734 0.87 1.39E-03 AW139789 232134 at AW139789 — — 0.87 2.61 E-05 KIAA1706 1563621 at AL713724 NM 030636 80820 0.87 9.21 E-03 GNAS 228173_at AA810695 NM_000516 NM_016592 NM 080425 NM_080426 2778 0.87 1.14E-03 ESPL1 204817_at NM_012291 NM_012291 9700 0.87 4.80E-03 AI791828 237868_x_at AI791828 — — 0.87 3.13E-05 RBM6 1556672 a at AM 90489 NM 005777 10180 0.87 7.88E-04 SBN01 216161_at AK024128 NM_018183 55206 0.87 2.11 E-03 BF056892 229024_at BF056892 — — 0.87 7.14E-06 CDC42BPA 215296_at AK027000 NM 003607 NM_014826 8476 0.87 5.58E-03 BE727883 226495_at BE727883 XM 498844 440752 0.87 7.67E-03 ANK2 216195_at AF131823 NM_001148 NM 020977 287 0.86 2.02E-04 SFI1 215699_x_at AL096768 NM_00100746 7 NM 014775 9814 0.86 4.61 E-04 TH1L 225261_x_at AJ238376 NM 016397 NM 198976 51497 0.86 4.08E-05 SEMA6A 215028_at AB002438 NM 020796 57556 0.86 1.40E-04 LOC91431 228859_at BF056790 NM_138698 91431 0.86 3.09E-03 FTHFSDC1 240552 at AA811452 NM 015440 25902 0.86 8.65E-04 TRIM36 219736 at NM 018700 NM 018700 55521 0.86 8.76E-03 DDX11 208159_x_at NM_004399 NM 004399 NM_030653 NM 030655 1663 0.86 1.06E-03 NFATC2IP 212809 at AA152202 NM_032815 84901 0.86 5.06E-04 M-RIP 231255_at AI970090 NM_015134 NM_201274 23164 0.86 6.68E-04 PCNT1 218014_at NM 024844 NM 024844 79902 0.86 7.48E-05 ADAM33 233868_x_at AL117415 NM_025220 NM_153202 80332 0.85 1.87E-04 FLJ10569 229633_at AA115512 NM_018142 55174 0.85 3.01 E-04 AI734111 222284_at Al 734111 — — 0.85 2.27E-03 RPL35A 215208_x_at AK021571 NM_000996 6165 0.85 1.22E-03 SNCAIP 219511_s_at NM_005460 NM 005460 9627 0.85 1.37E-03 GRIK2 1560265_at BQ434382 NM 021956 NM 175768 2898 0.85 8.83E-04 CCND1 208711_s_at BC000076 NM_053056 595 0.85 5.90E-05 NM_003349 201003_x_at NM 003349 — — 0.85 1.49E-04 FLJ13089 225888 at N62802 NM 024953 80018 0.84 3.59E-04 SLB 226324_s_at AB033005 NM_015662 26160 0.84 6.60E-03 348 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays SFRS15 222310_at AA648521 NM_020706 57466 0.84 2.91 E-03 AP3M2 1569053_at BG110196 NM_006803 10947 0.84 9.81 E-04 STRA6 1569335_a_at BC015881 NM 022369 64220 0.83 1.47E-03 TH1L 225865_x_at AJ238374 NM_016397 51497 0.83 3.21 E-04 NM_198976 SLC2A4RG 218494_s_at NM 020062 NM_020062 56731 0.83 8.97E-05 NCOA5 239815_at R16784 NM_020967 57727 0.83 7.12E-03 AARSL 231845 at AI721172 NM_020745 57505 0.83 4.13E-04 AA767373 236327_at AA767373 — ... 0.83 1.12E-03 KIAA1434 230492_s_at BE328402 NM_019593 56261 0.83 8.78E-04 RGMA 223468_s_at AL136826 NM_020211 56963 0.83 2.26E-03 T86613 235804 at T86613 — — 0.83 9.52E-05 LM04 209205_s_at BC003600 NM_006769 8543 0.83 5.83E-04 AL044078 221860_at AL044078 — — 0.83 2.22E-04 AA824321 227547 at AA824321 — — 0.82 1 63E-03 C9orf64 223697_x_at BC004407 NM 032307 84267 0.82 8.80E-05 EIF3S9 242550_at AA628539 NM_003751 8662 0.82 2.91 E-04 NM_182712 LOC144766 243986 at BE409452 XM 378419 144766 0.82 2.37E-03 C14orf145 1557755 at AW028337 XM 496002 145508 0.82 3.02E-03 FAM19A5 237094_at AI953086 NM 015381 25817 0.82 1.93E-05 CDKN2C 211792_s_at U17074 NM_001262 1031 0.82 7.21 E-03 NM_078626 STMN3 222557 at AL353715 NM 015894 50861 0.82 3.09E-03 C6orf111 230375_at Al 936531 NM 032870 25957 0.82 6.14E-04 CBWD1 226193_x_at AV709992 NM_018491 150472 0.82 7.60E-03 CBWD2 NM 172003 220869 LOC220869 NM_201453 389760 DC36 55871 ATF3 202672_s_at NM_001674 NM_001674 467 0.82 4.70E-03 NM_004024 AW629478 244625_at AW629478 — — 0.82 1.02 E-03 RAD51C 206066_s_at NM_002876 NM_002876 5889 0.82 1.65E-03 NM 058216 NM 058217 C15orf25 220071_x_at NMJ318097 NM 018097 55142 0.82 5.19E-04 C22orf18 218741_at NM_024053 NM_00100287 79019 0.81 7.04E-03 D NM 024053 GSS 211630_s_at L42531 NM_000178 2937 0.81 4.31 E-03 IREB2 1563129_at AL109710 NM 004136 3658 0.81 5.38E-03 EPIM 213434_at H95263 NM 001980 2054 0.81 1.48E-05 NM 194356 DZIP1L 239785_at BF340245 NM 173543 199221 0.81 7.64E-03 DHX37 223364_s_at BC004463 NM 032656 57647 0.81 4.75E-03 BC041029 1569025 s at BC041029 XM 371697 389211 0.81 2.66E-03 NY-REN-7 214945_at AW514267 NM_173663 285596 0.81 9.82E-03 LOC389347 XM_371783 389347 AA778747 241941_at AA778747 — — 0.81 3.29E-04 PDE4C 206792 x at NM_000923 NM 000923 5143 0.81 3.77E-04 SYNCRIP 209025 s at AF037448 NM_006372 10492 0.81 1.94E-03 DRPLA 236961_at AI539426 NM_00100702 1822 0.80 7.80E-03 D NM_001940 ZNF611 208137_x_at NM_030972 NM_030972 81856 0.80 1.06E-03 BACH2 215907_at AK027193 NM_021813 60468 0.80 1.49E-03 AL038191 240271_at AL038191 — — 0.80 4.41 E-04 FANCC 205189_s_at NM 000136 NM_000136 2176 0.80 6.32E-04 349 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays RPL10A 232592_at AU146731 NM_007104 4736 0.80 4.23E-03 GALNT7 218313_s_at NM 017423 NM 017423 51809 0.80 5.54E-03 SCML1 222747 s at BF001786 NM 006746 6322 0.79 2.71 E-03 DERA 218102_at NM 015954 NM_015954 51071 0.79 1.87E-03 AF131796 231916_at AF131796 — — 0.79 4.14E-03 CCNE1 213523_at AI671049 NM 001238 NM_057182 898 0.79 8.53E-03 WWOX 233161_at AK022464 NM_016373 NM_018560 NM 130788 NM_130790 NM 130791 NM_130792 NM 130844 51741 0.79 2.29E-03 SRP54 1557504_at AI076351 NM_003136 6729 0.79 7.25E-03 BG149337 229814_at BG149337 — — 0.79 7.38E-03 BE676171 237156_at BE676171 — — 0.79 4.22E-03 NR2C1 210530 s at M21985 NM_003297 7181 0.79 4.35E-03 NKTR 243055_at BF514072 NM_005385 4820 0.78 9.55E-03 KIAA0152 200617_at NM_014730 NM_014730 9761 0.78 6.41 E-03 EMILIN3 228307_at AL137580 NM 052846 90187 0.78 3.72E-03 TM4SF14 221002_s_at NM 030927 NM_030927 81619 0.78 3.35E-03 AM 51104 237475 x at Al 151104 — ... 0.78 1.69E-03 NUP153 239948_at AA004800 NM_005124 9972 0.78 1.85E-03 PELI2 219132_at NM 021255 NM_021255 57161 0.78 9.97E-04 THOC4 226319_s_at AF047002 NM 005782 10189 0.78 3.97E-03 HOXD4 1552337_s_at NM_014621 NM 014621 3233 0.78 4.73E-03 PPM1B 232580_x_at AL117553 NM_002706 NM 177968 NM_177969 5495 0.78 2.42 E-03 AK000864 216290 xat AK000864 — — 0.78 9.80E-03 KIFC1 209680_s_at BC000712 XM_371813 3833 0.78 2.91 E-03 GSS 201415 at NM 000178 NM 000178 2937 0.78 7.64E-03 ACPL2 236908 at BE550429 NM_152282 92370 0.78 2.99E-03 AA348683 240198_at AA348683 — ... 0.77 1.02E-05 ORF1-FL49 224707_at AL522667 NM_032412 84418 0.77 3.79E-04 LOC340085 232455_x_at AU145408 — 340085 0.77 4.32E-04 CNP 1556053_at AL556987 NM 033133 1267 0.77 2.24E-04 AK098337 1566144_at AK098337 XM 496690 401131 0.77 1.47E-03 HEG 213069_at AM 48659 XM_087386 57493 0.77 1.93E-03 Al833186 242593_at Al833186 — — 0.77 9.83E-04 GPR51 217077 s at AF095723 NM_005458 9568 0.77 7.45E-03 KIAA1434 224826_at AK001947 NM 019593 56261 0.77 3.37E-04 TYR03 211432_s_at U05682 NM 006293 7301 0.77 1.71 E-03 GNB4 223488 s at BC000873 NM 021629 59345 0.77 9.63E-03 MPHOSPH9 237158_s_at AW449069 NM_022782 10198 0.77 6.87E-03 FBXW12 215600_x_at AK022174 NM_207102 285231 0.77 4.32E-03 PTK7 1555324_at BC046109 NM_002821 NM 152880 NM_152881 NM_152882 NM 152883 5754 0.77 9.93E-03 KLHL5 226001_at AK002174 NM 00100707 5 NM_199039 51088 0.77 7.30E-03 CRTAC1 221204_s_at NM 018058 NM_018058 55118 0.76 5.35E-03 AK021514 215978_x_at AK021514 — ... 0.76 7.15E-03 N53564 242280 x at N53564 — — 0.76 1.02E-04 350 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays OLFML3 218162_at NM_020190 NM 020190 56944 0.76 3.61E-04 PDCD2 243773_at H65902 NM_002598 NM_144781 5134 0.76 9.35E-03 H09533 239748_x_at H09533 — — 0.76 6.06E-04 SH3MD1 224817_at W93554 NM_014631 9644 0.76 1.12E-05 C9orf86 219828 at NM_024718 NM 024718 55684 0.76 2.56E-03 TBX3 243234_at BG055137 NM_005996 NM_016569 6926 0.76 4.38E-03 PHF20L1 1554472_a_at BC015211 NM_016018 51105 0.76 3.06E-03 NM_024878 NM_032205 NM 198513 FLJ10404 243047_at AV698751 NM 019057 54540 0.76 6.86E-03 SIRT2 1558331_at BG722779 NM 012237 NM_030593 22933 0.76 6.78E-03 BRI3BP 231810 at BG106919 NM 080626 140707 0.76 1.27E-03 C19orf14 215218_s_at AC004144 NM_173636 284403 0.76 9.95E-03 AFG3L1 1552287_s_at NM 001132 NM 001132 172 0.76 4.38E-03 MUM1 229033_s_at AA143060 NM 032853 84939 0.76 1.74E-04 DHX35 218579_s_at NM_021931 NM 021931 60625 0.76 1.36E-03 ESPL1 38158_at D79987 NM 012291 9700 0.75 5.71 E-03 WBSCR20C 213460_x_at N29665 NM 032158 260294 0.75 3.30E-04 NM_148936 NM_148980 NM 149379 SFI1 213431_x_at AB011114 NM_00100746 7 NM_014775 9814 0.75 3.65E-05 AI252004 242696_at AI252004 — — 0.75 1.12E-03 SLC15A4 225043 at AW304786 NM_145648 121260 0.75 9.55E-03 PME-1 243443_at AI076511 NM_016147 51400 0.75 4.15E-03 TUBGCP2 244842_x_at AA235663 NM_006659 10844 0.75 5.81E-03 AI041522 228030 at Al041522 — — 0.75 8.68E-03 KIAA0992 234135_x_at AK021652 NM_016081 23022 0.75 3.75E-04 NQ01 201467_s_at AI039874 NM_000903 1728 0.75 9.53E-03 TJP2 243148_at AA007423 NM_004817 NM_201629 9414 0.75 2.81E-03 IQGAP1 213446 s at AI679073 NM 003870 8826 0.75 1.44E-03 SEC11L3 223299 at AF212233 NM_033280 90701 0.75 7.34E-04 LOC283871 222622_at BG284709 XM_208887 283871 0.75 4.92 E-03 T96555 243818 at T96555 — ... 0.75 3.01 E-03 TCEA1 1566207_at BQ286789 NM 006756 NM_201437 6917 0.74 1.85E-03 ZNF44 233775_x_at AK023304 NM_016264 51710 0.74 1.98E-04 AK024599 233702 x at AK024599 — — 0.74 2.99E-03 C20orf44 244795_at AV693986 NM_018244 NM_199487 NM_199513 55245 0.74 9.01 E-03 N4BP2 231996_at AB037834 NM 018177 55728 0.74 6.20E-06 CLIC4 201559_s_at AF109196 NM_013943 25932 0.74 9.19E-03 SEC15L1 232599_at AF220217 NM 019053 54536 0.74 7.90E-03 AU145662 233399 x at AU 145662 XM_499131 441383 0.74 1.87E-03 RAD54L 204558_at NM_003579 NM_003579 8438 0.74 1.24E-03 SLC4A8 207056 s at NM_004858 NM_004858 9498 0.74 5.18E-03 PLS3 201215 at NM 005032 NM_005032 5358 0.74 9.88E-03 C10orf6 203482_at AL133215 NM_018121 55719 0.74 9.76E-03 351 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays PDLIM7 1569150_x_at BC023629 NM 005451 NM_203352 NM 203353 NM_213636 9260 0.73 1.56E-03 AI939447 241268_x_at AI939447 — — 0.73 2.79E-04 FLJ12649 219626_at NM 024597 XM 291344 79649 0.73 8.01 E-04 PPHLN1 234459_at AK000186 NM 016488 NM_201438 NM_201439 NM_201440 NM_201515 51535 0.73 6.98E-03 DBT 205370 x at NM 001918 NM_001918 1629 0.73 4.67E-03 CBX3 230998_at AV702506 NM_007276 NM_016587 11335 0.73 8.36E-03 ASAHL 214765 s at AK024677 NM_014435 27163 0.73 1 72E-05 AF130054 211452_x_at AF130054 — ... 0.73 5.36E-04 CHKB 204193_at NM_005198 NM_005198 NM_152253 1120 0.72 3.15E-04 IQGAP1 210840 s at D29640 NM 003870 8826 0.72 7.05E-05 ASAHL 232072_at AK025371 NM_014435 27163 0.72 1.08E-03 MDS028 220590_at NM_018463 NM_018463 55846 0.72 2.33E-04 SPCS3 222753_s_at AL136660 NM_021928 60559 0.72 6.00E-03 TERT 207199_at NM_003219 NM 003219 NM_198253 NM 198254 NM_198255 7015 0.72 3.23E-05 BI496583 1557675_at BI496583 — — 0.72 4.63E-03 KIAA1731 1565829_at BU619319 XM 374922 85459 0.72 6.04E-03 UPF3A 206958_s_at AF318575 NM_023011 NM 080687 65110 0:72 6.99E-04 GPR125 1555122 at BC026009 NM 145290 166647 0.72 4.13E-03 FMNL2 1556656_at BF477401 NM_00100441 7 NM 00100442 1 NM_00100442 2 NM 052905 114793 0.72 1.56E-03 UBE2J1 236528_at N64079 NM_016021 51465 0.72 2.03E-03 AF15Q14 1552680_a_at NM 020380 NM_020380 NM_144508 NM 170589 57082 0.71 8.46E-03 RAB11FIP3 228613_at BF183535 NM 014700 9727 0.71 5.28E-03 GARNL1 234923_at AK022988 NM_014990 NM_194301 253959 0.71 7.34E-03 TK1 1554408 a at BC007986 NM_003258 7083 0.71 4.05E-03 BE503981 229593_at BE503981 — ... 0.71 2.45E-05 MARS 201475_x_at NM_004990 NM 004990 4141 0.71 6.05E-03 IDH3B 210014_x_at AF023266 NM 006899 NM 174855 NM_174856 3420 0.71 6.81 E-03 ETV1 217061_s_at AC004857 NM_004956 2115 0.71 4.82E-03 AI829569 236671 at AI829569 — — 0.71 5.08E-04 MCM4 212141_at AA604621 NM_005914 NM_182746 4173 0.71 2.19E-03 HRPT2 215398_at AF038194 NM_024529 79577 0.70 2.72E-03 SFRS14 212001 at AV738039 NM 014884 10147 0.70 1.89E-04 GEMIN4 217099_s_at AF258545 NM_015721 50628 0.70 2.89E-03 352 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., etal., Cells Useful for Immuno-Based BoNT/A Activity Assays RRAGD 221524_s_at AF272036 NM 021244 58528 0.70 4.52E-03 PSAT1 220892_s_at NM_021154 NM 021154 NM_058179 29968 0.70 4.14E-03 NSUN5 WBSCR20B WBSCR20C 213670_x_at Al768378 NM 018044 NM_032158 NM 145645 NM_148936 NM 148956 NM_148980 NM_149379 155400 260294 55695 0.70 3.58E-05 KIAA0286 212621_at AB006624 NM 015257 23306 0.70 5.42E-03 AFG3L1 236250_at Al859065 NM 001132 172 0.70 4.29E-03 MAD2L2 223234_at AF080398 NM 006341 10459 0.70 6.48E-03 BF062155 238279_x_at BF062155 — — 0.70 1.33E-03 PSMD7 238738 at AW361702 NM 002811 5713 0.70 1 94E-03 TUBG1 201714_at NM_001070 NMJ301070 7283 0.69 9.09E-03 CSTF1 202190_at NM 001324 NM_001324 1477 0.69 3.88E-03 T71269 234033_at T71269 — — 0.69 3.53E-03 CROP 241792_x_at N36160 NM_006107 NM_016424 51747 0.69 2.36E-03 SLIT3 203813_s at NM_003062 NM_003062 6586 0.69 8.85E-03 AI857788 227126_at AI857788 — — 0.69 3.64E-04 FLJ12700 219627_at NM 024910 NM 024910 79970 0.69 5.30E-04 FLJ40432 228810_at AW135279 NM_152523 151195 0.69 9.81 E-04 DGCR8 219811_at NM_022720 NM 022720 54487 0.69 3.02E-03 SHMT1 209980_s_at L23928 NM 004169 NM 148918 6470 0.68 2.17E-03 UPF3A 217596_at AA649851 NM 023011 NM_080687 65110 0.68 3.51 E-03 PPT2 209826_at AF020544 NM 005155 NM 138717 NM_138934 9374 0.68 3.49E-04 THOC4 226320_at AF047002 NM 005782 10189 0.68 4.54E-03 NDUFA5 215850 s at AK022209 NM_005000 4698 0.68 8.18E-03 DTYMK 203270 at NM 012145 NM 012145 1841 0.68 7.28E-03 FLJ10199 218815_s_at NM_018022 NM_018022 55092 0.68 3.91 E-03 CRSP6 232483_at AK022156 NM 004268 9440 0.68 5.79E-04 PTPRF 215066_at AU158443 NM 002840 NM_130440 5792 0.68 3.31 E-03 ADD1 214736_s_at BE898639 NM_001119 NM_014189 NM 014190 NM 176801 118 0.68 1.78E-03 C9orf88 223019 at BC001979 NM_022833 64855 0.68 9.03E-04 FLJ34443 241408_at AA531337 NM 175918 285464 0.68 9.11 E-03 TK2 208246_x_at NM 017618 NM 004614 7084 0.67 5.00E-03 C10orf79 243896_at Al 809779 NM_025145 80217 0.67 4.78E-03 SRGAP2 1556202 at AI263819 XM 059095 23380 0.67 9.56E-03 PANK2 218809_at NM_024960 NM 024960 NM 153637 NM_153638 NM_153639 NM 153640 NM 153641 80025 0.67 2.17E-06 HOXD4 205522_at NM_014621 NM_014621 3233 0.67 5.20E-03 NES 218678 at NM_024609 NM 006617 10763 0.67 1.78E-03 MICAL3 229474 at BF055090 XM 032996 XM 032997 57553 0.67 3.47E-03 353 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays TCF7L2 212762_s_at AI375916 NM 030756 6934 0.67 3.83E-03 TPD52L2 201379_s_at NM_003288 NM_003288 NM 199359 NM_199360 NM 199361 NM 199362 NM_199363 7165 0.66 4.00E-03 PVRL3 213325_at AA129716 NM_015480 25945 0.66 2.59E-04 ASAHL 227135_at AI436803 NM_014435 27163 0.66 2.36E-03 AI197932 229498_at AM 97932 — ... 0.66 6.38E-03 KIAA0931 213407 at AB023148 NM 015020 23035 0.66 4.47E-03 AK057923 1556364_at AK057923 XM_498935 440960 0.66 9.42E-03 ADRBK2 204183_s_at AI478542 NM 005160 157 0.66 2.10E-04 SNX5 223666_at BC002724 NM 014426 NM_152227 27131 0.66 5.32E-03 WBSCR23 221176_x_at NM_025042 NM_025042 80112 0.66 5.53E-06 AK024901 234326_at AK024901 — ... 0.65 1.50E-04 ZNF500 41113_at Al871396 NM 021646 26048 0.65 1.77E-03 DMN 212730_at AK026420 NM 015286 NM_145728 23336 0.65 3.64E-03 ANKH 239449_at AV693734 NM_054027 56172 0.65 2.03E-03 C14orf120 216263_s_at AK022215 XM 033371 25983 0.65 1.76E-03 ZNF291 215848_at AW139369 NM 020843 49855 0.65 3.43E-03 RFC1 209085_x_at L14922 NM_002913 5981 0.65 2.64E-04 SLIT2 209897_s_at AF055585 NM_004787 9353 0.65 2.23E-03 LOC134147 234981 x at BE537881 NM 138809 134147 0.65 2.57E-03 GPR51 209991 x at AF069755 NM_005458 9568 0.65 6.51 E-04 AL037473 1557780_at AL037473 — — 0.64 9.19E-03 C14orf111 215567_at AU144919 NM_015962 51077 0.64 2.31 E-03 CBX5 241875_at AA204654 NM 012117 23468 0.64 8.07E-04 UCKL1 218533_s_at NM 017859 NM_017859 54963 0.64 7.28E-03 BG231554 243179_at BG231554 — ... 0.64 5.62E-04 PLK4 204887_s_at NM 014264 NM 014264 10733 0.64 7.56E-04 OGG1 205760_s_at NM_016821 NM 002542 NM_016819 NM 016820 NM_016821 NM 016826 NM_016827 NM 016828 NM_016829 4968 0.64 4.62E-04 PAICS 201014 s at NM 006452 NM 006452 10606 0.64 8.63E-05 RNF150 227657_at AA722069 NM_020724 57484 0.64 2.38E-03 E7V1 217053_x_at X87175 NM_004956 2115 0.64 6.17E-03 HRB2 232441_at AU147079 NM 007043 11103 0.64 8.66E-03 CTNNBL1 221021 s at NM 030877 NM 030877 56259 0.64 2.56E-04 FLJ33915 229892_at AW628843 NM_182613 347918 0.64 7.04E-03 TORC3 232879_at AK024981 NM_022769 64784 0.64 5.57E-03 IPW 213447 at AI672541 — 3653 0.64 3.46E-03 ZNF337 214760 at AL049942 NM 015655 26152 0.64 6.30E-03 SNTA1 203516_at NM_003098 NM 003098 6640 0.64 5.62E-03 STX1A 204729_s_at NM_004603 NM_004603 6804 0.64 4.16E-04 RAN 200750_s_at AF054183 NM 006325 5901 0.64 4.86E-04 FLJ11029 232215_x_at AK000296 NM 018304 55771 0.63 8.93E-04 H2AFX 205436_s_at NM_002105 NM_002105 3014 0.63 1.85E-03 LOC338799 1556042_s_at BI912454 — 338799 0.63 2.22E-03 BC022346 1570210_x_at BC022346 — — 0.63 5.53E-03 C10orf58 224435_at BC005871 NM_032333 84293 0.63 3.19E-06 354 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., etal., Cells Useful for Immuno-Based BoNT/A Activity Assays LOC338799 226369_at AW138760 — 338799 0.62 4.89E-03 C9orf81 1557985_s_at AA248753 XM_095991 84131 0.62 4.31 E-03 AK023870 233427 x at AK023870 — — 0.62 7.36E-04 FLJ10504 218296_x_at NM_018116 NM018116 55154 0.62 1.11 E-03 LOC155435 225839 at AW290882 NM_001008408 155435 0.62 7.67E-03 GNG12 212294_at BG111761 NM 018841 55970 0.62 4.81 E-04 FLJ23342 236059_at AW168168 NM 024631 79684 0.62 8.20E-03 LM07 233646_at AK027238 NM 005358 4008 0.62 7.32E-03 PHF20L1 222133_s_at AK022280 NM_016018 NM 024878 NM_032205 NM 198513 51105 0.62 1.32E-03 C14orf143 214264_s_at AI656610 NM_145231 90141 0.62 5.71 E-03 LOC157627 1556046_a_at AL832535 — 157627 0.62 4.24E-03 MAP3K13 206249_at NM_004721 NM_004721 9175 0.62 4.38E-03 VGF 205586_x_at NM_003378 NM 003378 7425 0.62 1.70E-03 BLCAP 201032_at NM 006698 NM_006698 10904 0.62 1.91 E-04 POLE2 205909_at NM_002692 NM 002692 5427 0.62 9.76E-03 ZGPAT 221848_at AL121845 NM_032527 NM 181484 NM 181485 84619 0.61 1.83E-03 STN2 227461 at AA632295 NM_033104 85439 0.61 5.56E-03 SFRS11 213742_at AW241752 NM_004768 9295 0.61 8.24E-03 GPR51 209990_s_at AF056085 NM 005458 9568 0.61 8.69E-04 TGDS 237346 at AA976208 NM 014305 23483 0.61 2.60E-03 PANK2 235130_at AV703394 NM_024960 NM_153637 NM_153638 NM 153639 NM 153640 NM 153641 80025 0.61 2.05E-03 BAX 208478_s_at NM_004324 NM_004324 NM 138761 NM_138762 NM_138763 NM_138764 NM_138765 581 0.61 2.28E-03 RNF10 207801_s_at NM_014868 NM 014868 9921 0.61 9.50E-03 SPAG5 203145_at NM_006461 NM_006461 10615 0.61 3.43E-03 TOP3A 204946_s_at NM_004618 NM_004618 7156 0.61 4.78E-04 REC14 215156 at AL109709 NM_025234 80349 0.61 9.61 E-04 MGC4308 220612_at NM_014135 NM_032359 84319 0.61 7.73E-03 AI144156 238670_at AI144156 — — 0.61 2.33E-03 TBPIP 205956_x_at NM_013290 NM 013290 NM_016556 29893 0.61 9.34E-05 AW517479 242608_x_at AW517479 — — 0.60 4.70E-03 DXS9879E 219061_s_at NM_006014 NM 006014 8270 0.60 7.83E-03 384D8-2 205086_s_at NM_014551 NM 014551 NM_152299 29781 0.60 3.91 E-03 )KFZP564K196 223170_at AF132000 NM_015544 26022 0.60 2.90E-03 SOX2 213722_at AW007161 NM_003106 6657 0.60 2.03E-03 CGI-96 33307 at AL022316 NM 015703 27341 0.60 7.39E-03 BE464132 236841 at BE464132 XM_496585 440897 0.60 1.92E-03 AK025048 1565705_x_at AK025048 — — 0.60 7.42E-03 HEXA 215155_at J04178 NM_000520 3073 0.60 8.59E-03 NY-REN-41 226287 at AI458313 NM_080654 91057 0.60 6.85E-03 AK023354 222252 x at AK023354 — — 0.60 7.20E-03 KIAA0582 1559159 at AK094069 NM_015147 23177 0.59 2.73E-03 355 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays PDE8A 212521_s_at BE568219 NM_002605 NM 173454 NM_173455 NM_173456 NM_173457 5151 0.59 7.81 E-03 BE671060 235901_at BE671060 — ... 0.59 7.80E-03 KIAA1423 225127_at BF217531 XM_376550 57583 0.59 2.86E-03 DDX54 219111 _s_at NM_024072 NM_024072 79039 0.59 5.24E-03 ADCYAP1 230237_at BE220888 NM 001117 116 0.59 4.24E-03 CDKN1A 202284_s_at NM_000389 NM 000389 NM_078467 1026 0.59 1.54E-03 PWP1 201606_s_at BE796924 NM 007062 11137 0.59 3.48E-04 ZNF505 215758_x_at AC007204 NM 00100412 6 NM_031218 81931 0.59 1.44E-03 FLJ00312 221971_x_at BE672818 XM_374801 399761 0.59 7.23E-03 IGBP1 242337_at AI347128 NM 001551 3476 0.59 9.36E-03 ANKRD11 219437 s at NM_013275 NM 013275 29123 0.59 5.45E-03 TRAF4 202871_at NM_004295 NM 004295 NM_145751 9618 0.59 3.31 E-03 FLJ10404 218920 at NM 019057 NM 019057 54540 0.59 1.51 E-03 SS18L1 213140_s_at AB014593 NM_015558 NM_198935 26039 0.59 7.09E-05 C20orf161 236514_at Al 885067 NM 033421 NM 152897 90203 0.58 6.89E-03 CTNNB1 223679_at AF130085 NM 001904 1499 0.58 7.83E-04 NSFL1C 220248_x_at NM 018839 NM_016143 NM_018839 NM 182483 55968 0.58 4.26E-03 MGC15606 215968_at AF055018 NM_145037 91775 0.58 2.12E-03 VTN 204534_at NM_000638 NM 000638 7448 0.58 1.72E-03 SNX5 217792_at NM_014426 NM_014426 NM_152227 27131 0.58 4.70E-03 LOC157627 214839_at AF052108 — 157627 0.58 4.90E-03 NSFL1C 232520_s_at AK023585 NM 016143 NM 018839 NM_182483 55968 0.58 7.68E-03 E2IG5 223193_x_at AF201944 NM 014367 26355 0.58 3.89E-04 ANKFY1 224900_at AK025960 NM 016376 NM_020740 51479 0.58 6.56E-03 HNRPA3 211931_s_at BG505670 NM 194247 220988 0.58 1.97E-03 corn 1553852_at NM_152564 NM 015243 NM 017890 NM 152564 NM 181661 NM_184042 157680 0.58 8.57E-03 ZNF305 240181_at Al 939511 NM 014724 9753 0.58 6.71 E-03 RFC5 203209 at BC001866 NM 007370 5985 0.58 7.00E-03 NM_181578 356 PCT/US2010/027242 WO 2010/105234 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451

Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays

Table 10. Decreased Gene Expression in Cell Lines H1 and BB10 vs. SiMa Cell Line in Undifferentiated State Using Microarray Analysis

Gene Symbol Probe Set ID Representative Public ID RefSeq Transcript ID Entrez Gene ID Log2 Ratio pvalue HSPA1A 200799_at NM 005345 NM_005345 3303 -6.50 8.44E-07 CYTL1 219837 s at NM 018659 NM_018659 54360 -5.69 4.29E-10 CYGB 226632_at AL513673 NM_134268 114757 -5.62 1.77E-03 SYT13 226086_at AB037848 NM_020826 57586 -5.23 2.54E-09 H39185 240433 x at H39185 — — -5.19 1.50E-07 AV724769 235118 at AV724769 — — -5.15 5.31 E-08 AW188087 226809_at AW188087 — — -5.07 1.50E-07 IGFBP7 201162_at NM_001553 NM_001553 3490 -4.97 1.64E-07 MEOX2 206201 s at NM 005924 NM 005924 4223 -4.95 5.73E-08 NNAT 204239_s_at NM_005386 NM_005386 4826 -4.84 3.41 E-07 CYGB 1553572_a_at NM_134268 NM_181689 NM_134268 114757 -4.74 1.06E-03 IGSF4D 1552754 a at AA640422 NM 153184 253559 -4.44 9.24E-10 IGFBP7 201163 s at NM 001553 NM 001553 3490 -4.43 2.10E-04 CAP2 212554_at N90755 N MO06366 10486 -4.40 7.38E-04 AF150317 243111_at AF150317 — — -4.32 6.95E-07 FGF1 1552721_a_at NM_033136 NM_000800 2246 -4.30 3.01 E-04 LMCD1 218574_s_at NM_014583 NM_033136 NM_033137 NM_014583 29995 -4.23 1.05E-04 TNFRSF10D 227345 at AI738556 NM 003840 8793 -4.09 1.08E-04 IGFBP5 211959_at AW007532 NM_000599 3488 -4.02 3.56E-04 CART 206339 at NM 004291 NM 004291 9607 -4.01 4.51 E-06 ASAM 226834_at BG112263 NM_024769 79827 -3.99 9.02E-04 Al093492 237435 at AI093492 — — -3.95 2.11 E-04 FUCA2 223120_at BC003060 NM 032020 2519 -3.94 2.55E-03 PAPPA 224942_at BG434272 NM 002581 5069 -3.81 5.43E-06 PRAME 204086_at NM_006115 NM 006115 23532 -3.67 4.15E-07 DHRS3 202481 at NM 004753 NM 206953 NM 206954 NM 206955 NM 206956 NM 004753 9249 -3.66 8.82E-07 TRHDE 219937_at NM_013381 NM_013381 29953 -3.59 4.97E-05 C9orf94 229585_at AI803088 NM 152702 206938 -3.59 2.72E-04 DSCAM 237268_at BE503065 NM 001389 1826 -3.57 1.08E-07 FGF13 205110_s_at NM_004114 NM 206887 NM 004114 2258 -3.51 5.78E-05 FGF1 205117_at X59065 NM 033642 NM 000800 2246 -3.50 1.90E-03 PTN 211737_x_at BC005916 NM_033136 NM 033137 NM 002825 5764 -3.44 5.00E-04 GNAS 217057_s_at AF107846 NM 000516 2778 -3.42 1.41E-03 FLJ45880 228538 at BE671164 NM_016592 NM 080425 NM 080426 NM 207404 389114 -3.42 1.47E-04 ADAMTS3 214913_at AB002364 NM 014243 9508 -3.41 2.23E-04 CYP2E1 1431_at J02843 NM_000773 1571 -3.38 7.97E-04 AL353759 215071_s_at AL353759 — — -3.37 9.25E-05 PAPPA 224940_s_at BF107618 NM_002581 5069 -3.36 7.36E-06 357 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays BF941609 240218_at BF941609 — ... -3.35 3.21 E-05 FGF1 208240_s_at NM_013394 NM 000800 NM 033136 NM_033137 2246 -3.35 4.91 E-04 TCEAL2 211276_at AF063606 NM_080390 140597 -3.35 4.16E-05 TncRNA 224565_at BE675516 — 283131 -3.34 1.99E-04 IGSF4D 1555544_a_at AF538973 NM_153184 253559 -3.30 7.37E-07 MGC45474 228221_at AA809640 NM_152369 126969 -3.27 7.37E-04 KIAA1598 221802_s_at AU157109 NM 018330 57698 -3.25 5.86E-06 FGL1 205305_at NM_004467 NM 004467 NM 147203 NM_201552 NM_201553 2267 -3.25 2.90E-06 AU157716 227051_at AU157716 — — -3.23 7.84E-06 TMIE 1553601 _a_at NM 147196 NM 147196 259236 -3.22 3.71 E-05 IGSF4D 1552752_a_at NM_153184 NM_153184 253559 -3.21 2.78E-04 PAPPA 224941_at BF107618 NM_002581 5069 -3.15 3.66E-05 CFC1 223753_s_at AF312769 NM 032545 55997 -3.15 1.39E-05 PAPPA 228128 x at AI110886 NM_002581 5069 -3.07 9.98E-07 AA452540 232411_at AA452540 — ... -3.05 1.2 8 E-04 AW003173 230746_s_at AW003173 — — -3.03 3.62E-03 PAPPA 201981_at AA148534 NM_002581 5069 -3.03 2.64E-07 BF432956 229057_at BF432956 — — -3.01 5.34E-06 IL7 206693_at NM_000880 NM_000880 3574 -3.01 6.79E-05 N92599 241421_at N92599 — — -3.01 2.03E-05 SAMD4 212845 at AB028976 NM_015589 23034 -2.94 1.71 E-04 N95363 213183 s at N95363 — ... -2.94 7.60E-03 PPAPDC1 236044_at BF130943 XM_113641 196051 -2.94 8.60E-08 0KFZP564IO42: 223588_at AL136607 NM_031435 83591 -2.93 1.23E-03 KCNMA1 221584_s_at U11058 NM 002247 3778 -2.92 4.15E-06 AI685824 244565_at AI685824 XM 370580 387716 -2.91 4.49E-04 LOC56901 218484_at NMJ320142 NM 020142 56901 -2.88 8.77E-04 BACE2 217867_x_at NM_012105 NM 012105 NM 138991 NM_138992 25825 -2.87 7.40E-04 BF110050 241100_at BF110050 ... ... -2.81 1.52E-03 AU144437 232887_at AU144437 — — -2.81 4.16E-03 GABRA5 206456 at NM 000810 NM 000810 2558 -2.79 1.41E-03 SYNPR 230303_at H11380 NM_144642 132204 -2.77 1.02E-03 CYP2E1 209975_at AF182276 NM_000773 1571 -2.76 3.21 E-03 GAL 214240_at AL556409 NM 015973 51083 -2.75 1.20E-03 LOC51315 222585 x at BE326678 NM 016618 51315 -2.72 1 70E-05 CDH12 207149_at L33477 NM_004061 1010 -2.72 1.51 E-05 N39597 1555993_at N39597 — — -2.70 1.39E-03 SYNP02 227662_at AA541622 NM 133477 171024 -2.69 4.62E-05 NPY 206001 at NM_000905 NM 000905 4852 -2.68 9.89E-05 FGF19 223761 _at AF110400 NM_005117 9965 -2.65 8.85E-06 SLC35F3 229065_at BF968270 NM_173508 148641 -2.64 8.85E-06 SSPN 204963_at AL136756 NM 005086 8082 -2.63 1.78E-03 CYP2E1 209976 s at AF182276 NM 000773 1571 -2.63 7.81 E-04 MGC13040 224463_s_at BC006128 NM_032930 85016 -2.62 4.90E-03 ADCY1 213245_at AL120173 NM_021116 107 -2.61 5.07E-04 PAPPA 201982_s_at NM_002581 NM_002581 5069 -2.60 4.39E-03 ERBB4 206794 at NM_005235 NM_005235 2066 -2.60 3.50E-03 Al826125 229866_at AI826125 — ... -2.60 1.64E-04 DKK1 204602_at NM_012242 NM_012242 22943 -2.56 1.78E-04 BC020585 1568817 at BC020585 — — -2.56 2.42E-05 COL5A1 212488_at N30339 NM_000093 1289 -2.55 6.89E-04 358 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays PTPRR 206084_at NM_002849 NM_002849 NM_130846 5801 -2.54 2.83E-04 BACE2 222446_s_at AF178532 NM 012105 NM_138991 NM 138992 25825 -2.54 8.21 E-05 P2RX5 210448_s_at U49396 NM 002561 NM_175080 NM_175081 5026 -2.50 4.92E-03 MBD5 227839_at AI911379 NM_018328 55777 -2.49 1 78E-03 AA243659 209683_at AA243659 — — -2.44 6.66E-07 LOC51315 233329 s at AK025986 NM 016618 51315 -2.44 4.58E-05 KIAA0774 214961_at AI818409 XM 166270 23281 -2.43 3.12E-05 DDAH1 209094 at AL078459 NM 012137 23576 -2.43 1.54E-04 FLJ20701 219093_at NM_017933 NM_017933 55022 -2.43 3.02E-03 ICAM2 204683 at NM 000873 NM_000873 3384 -2.41 3.71 E-04 AI051127 231478_at AI051127 — — -2.41 3.13E-03 LOC134466 244289 at AI242408 XM_376436 134466 -2.40 8.79E-03 AI767727 229815_at AI767727 — — -2.40 5.54E-04 BF591692 231532 at BF591692 — — -2.39 6.45E-04 GRM5 214217_at D60132 NM_000842 2915 -2.39 1.63E-06 ERBB4 214053_at AW772192 NM_005235 2066 -2.39 1.44E-04 AA854843 236777_at AA854843 — — -2.38 3.59E-03 )KFZp313N062 1555905_a_at AM47556 NM 173826 285343 -2.38 1 45E-03 LOC128153 230763_at AA905508 NM_138796 128153 -2.38 2.95E-03 ANK3 206385_s_at NM_020987 NM_001149 NM_020987 288 -2.37 4.86E-04 AI810266 235456 at AI810266 — — -2.36 7.31 E-07 LOC390916 235384_at AW963217 XM_372723 390916 -2.36 8.86E-07 AV719355 217554_at AV719355 — — -2.36 2.61 E-03 KIAA0774 1554755_a_at BC032481 XM 166270 23281 -2.36 1.10E-03 HHLA3 220387_s_at NM 007071 NM 007071 11147 -2.36 2.06E-03 SMARCA2 206542_s_at AV725365 NM_003070 NM_139045 6595 -2.35 7.68E-04 CNGA3 207261 at NM 001298 NM 001298 1261 -2.32 3.40E-05 FAM49A 230276_at AI934342 NM_030797 81553 -2.30 9.19E-08 LOC339290 217506_at H49382 XM375527 339290 -2.30 8.85E-05 HTATIP2 209448_at BC002439 NM_006410 10553 -2.30 6.50E-03 FLJ31659 1553710 at NM 153027 NM 153027 152756 -2.30 6.35E-06 LOC51315 218303 x at NM 016618 NM 016618 51315 -2.30 8.49E-07 ATRNL1 213744_at AI817331 NM 207303 26033 -2.29 8.46E-08 SMARCA2 206544_x_at NM_003070 NM 003070 NM_139045 6595 -2.27 4.88E-04 GAL 207466 at NM 015973 NM 015973 51083 -2.25 6.61 E-13 PTGER2 206631_at NM_000956 NM 000956 5732 -2.25 2.22E-05 PTPRR 210675_s_at U77917 NM 002849 NM_130846 5801 -2.23 8.91 E-04 BF000047 235736 at BF000047 — — -2.22 1.49E-04 TICAM2 228234_at AI423165 NM_021649 353376 -2.22 4.67E-04 NCAM2 205669_at NM_004540 NM_004540 4685 -2.22 2.95E-06 IRS1 204686_at NM 005544 NM 005544 3667 -2.22 2.74E-03 TRIM61 238990_x_at AI763262 XM_373038 391712 -2.21 1.88E-04 AF085995 1561759_at AF085995 — — -2.21 9.13E-03 AI732969 240173 at AI732969 — — -2.20 1.87E-05 AI819043 229228 at AI819043 — — -2.20 4.58E-04 BF432875 235782_at BF432875 XM_497668 388620 -2.20 1.92 E-05 GPX7 213170_at AA406605 NM_015696 2882 -2.19 2.99E-04 NLF1 241031_at BE218239 NM_207322 145741 -2.18 8.81 E-05 BE674309 230913 at BE674309 — — -2.18 1 83E-04 359 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application . 18495 (BOT)/1957205.00451 CAP2 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays 212551_at NM_006366 NM_006366 10486 -2.17 5.50E-04 PRO1580 213550 s at AA993683 NM 018502 55374 -2.17 4.95E-03 CYB5R2 220230_s_at NM_016229 NM_00100133 β 51700 -2.15 7.15E-04 ZAP128 202982_s_at NM 006821 O NM_016229 NM_006821 10965 -2.14 1.68E-03 RAC2 207419_s_at NM 002872 NM_002872 5880 -2.14 2.67E-03 LOC153682 232794 at AL137383 — 153682 -2.13 5.45E-03 GRIA2 236538_at BE219628 NM_000826 2891 -2.13 1.05E-03 IL20RA 219115_s_at NM_014432 NM 014432 53832 -2.12 6.78E-03 SCN5A 207413_s_at NM_000335 NM 000335 6331 -2.12 2.22E-04 TSAP6 218424_s_at NM_018234 NM 198056 NM_00100841 π 55240 -2.12 1.68E-04 FAM49A 208092_s_at NM_030797 u NM 018234 NM 182915 NM 030797 81553 -2.11 4.87E-05 HIST2H2BE 202708_s_at NM_003528 NM 003528 8349 -2.10 5.97E-05 GLI2 207034_s_at NM_030379 NM 005270 2736 -2.09 5.75E-03 LOC441422 236453 at AW243154 NM_030379 NM 030380 NM_030381 XR 000264 441422 -2.09 2.02E-04 SYNP02 225720 at AW009747 NM 133477 171024 -2.09 6.04E-03 LEPR 209894_at U50748 NM_00100367 o 3953 -2.09 3.79E-04 HNRPR 232004_at AK001846 y NM 00100368 0 NM_002303 NM_005826 10236 -2.09 1.55E-05 AI222435 230319_at AI222435 — — -2.09 7.23E-05 MGC15668 229332_at AI653050 NM_032756 84842 -2.08 1.02E-03 SCAP1 1560861_at BG210619 NM_003726 8631 -2.08 5.32E-04 LRIG1 211596_s_at AB050468 NM 015541 26018 -2.08 7.64E-03 SCN3A 210432_s_at AF225986 NM 006922 6328 -2.07 3.67E-03 ADARB1 203865_s_at NM_015833 NM_001112 104 -2.07 4.67E-06 AB051467 232738 at AB051467 NM_015833 NM_015834 -2.06 1.71E-05 CREB5 205931_s_at NM_004904 NM_004904 9586 -2.06 8.68E-04 ECHDC3 219298 at NM 024693 NM 182898 NM 182899 NM_024693 79746 -2.05 6.42E-03 CRYGD 207532_at NM_006891 NM 006891 1421 -2.05 2.10E-03 ICAM2 213620_s_at AA126728 NM 000873 3384 -2.05 3.74E-04 CIP29 217498 at BG389073 NM_033082 84324 -2.04 3.37E-04 AA700440 228329 at AA700440 — — -2.04 4.62E-07 ATRNL1 213745_at AW151108 NM 207303 26033 -2.04 9.28E-06 SLC6A15 239352_at AI368909 NM 018057 55117 -2.03 1.76E-04 RGAG4 227823_at BE348679 NM 182767 XM_291322 340526 -2.03 2.13E-04 AW136654 240802_at AW136654 — — -2.02 2.07E-03 MTL5 219786_at NM 004923 NM_004923 9633 -2.02 3.30E-04 FBI4 1562953 s at BCO19264 NM 205857 404201 -2.02 4.82E-03 ZNF91 238466_at R43486 NM_003430 7644 -2.01 8.53E-04 LOC441168 229390_at AV734646 XM_496823 441168 -2.01 1.83E-04 BF343672 227925_at BF343672 XM_378321 399972 -2.01 1.32E-04 BC014056 1561906 at BCO14056 — — -2.01 8.02E-04 360 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays FGF18 206987_x_at NM_003862 NM 003862 NM_033649 8817 -2.01 6.16E-03 CHST7 206756 at NM 019886 NM 019886 56548 -2.00 1.29E-04 RAC2 213603 s at BE138888 NM_002872 5880 -2.00 2.89E-05 MCTP1 235740_at BG250585 NM_00100279 6 NM_024717 79772 -2.00 2.38E-08 C6orf198 227834_at AL589605 XM_371849 167838 -2.00 1.53E-03 SYNP02 225894_at AL589603 NM_133477 171024 -1.99 3.38E-04 FBI4 238081_at AI694300 NM_205857 404201 -1.99 1.05E-03 GABRA5 215531 s at BF966183 NM 000810 2558 -1.98 6.28E-06 SORCS2 228720 at AB037750 NM 020777 57537 -1.98 7.96E-05 MRAS 225185_at BF343625 NM012219 22808 -1.97 6.31 E-04 BE962770 229032_at BE962770 — — -1.97 6.94E-03 ATP2B3 242036_x_at H09073 NM 00100134 4 NM_Q21949 492 -1.96 1.23E-03 SSPN 226932_at AW467136 NM_005086 8082 -1.95 4.20E-05 AA976778 230679 at AA976778 — — -1.95 3.35E-04 LOC285878 1560692_at BC037834 — 285878 -1.94 . 3.90E-04 BF114967 231067_s_at BF114967 — — -1.93 1.31 E-04 C10orf59 223824_at BC005364 NM_018363 55328 -1.93 8.06E-03 ASAM 228082_at BF056275 NM_024769 79827 -1.93 2.50E-04 OXTR 206825_at NM_000916 NM_000916 5021 -1.93 2.27E-04 CNNM1 220166_at NM 020348 NM_020348 26507 -1.92 1.23E-04 PLCD4 224505_s_at BC006355 NM 032726 84812 -1.92 2.15E-05 NEFH 33767 at X15306 NM 021076 4744 -1.92 2.20E-03 LOC339290 228160_at AI433706 XM 375527 339290 -1.92 5.10E-03 EDG7 231192_at AW274018 NM_012152 23566 -1.91 7.48E-04 BF002625 229530 at BF002625 — — -1.90 4.09E-04 COL13A1 211343_s_at M33653 NM 005203 NM_080798 NM_080799 NM 080800 NM_080801 NM_080802 NM_080803 NM 080804 NM_080805 NM 080806 NM_080807 NM 080808 NM_080809 NM 080810 NM 080811 NM 080812 NM_080813 NM 080814 NM 080815 1305 -1.90 5.01 E-06 AI015847 1568838 at AI015847 — — -1.90 6.44E-04 AA705933 239866_at AA705933 -- -- -1.89 7.57E-04 NDFIP2 1568807_a_at AI301081 NM 019080 54602 -1.89 6.50E-05 PRKACB 202742_s_at NM_002731 NM 002731 NM_182948 NM_207578 5567 -1.88 2.83E-04 FLJ20449 1570153_at BC013944 NM_017826 54937 -1.88 1.81E-03 FSTL1 208782 at BC000055 NM 007085 11167 -1.88 4.35E-03 PRSS11 201185_at NM 002775 NM_002775 5654 -1.87 2.45E-04 361 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays EBF 229487_at W73890 NM_024007 1879 -1.86 2.25E-05 SLC16A14 238029_s_at R15072 NM 152527 151473 -1.86 2.63E-05 LEPR 211356_x_at U66495 NM 00100367 9 NM_00100368 0 NM_002303 3953 -1.86 9.14E-08 LOC339290 215283 at U79248 XM_375527 339290 -1.85 3.14E-04 BE672499 230962_at BE672499 — ... -1.85 3.97E-04 AI435590 237193_s_at AI435590 — ... -1.84 4.11E-05 C10orf10 209183_s_at AL136653 NM 007021 11067 -1.84 9.62E-05 ARTS-1 214012 at BE551138 NM_016442 51752 -1.84 7.70E-04 M160 223655_at AF264014 NM_174941 283316 -1.83 4.27E-03 AI803010 239503_at AI803010 — — -1.83 6.21 E-03 GLI2 228537_at AI797248 NM 005270 NM_030379 NM_030380 NM_030381 2736 -1.83 6.30E-04 AI935541 236220_at AI935541 — ... -1.83 8.96E-04 HEBP2 203430_at NM_014320 NM_014320 23593 -1.82 6.64E-03 )KFZp313N062 226688_at AW003508 NM_173826 285343 -1.82 8.96E-06 EBF 232204_at AF208502 NM_024007 1879 -1.81 6.25E-06 NT5E 203939_at NM_002526 NM 002526 4907 -1.81 2.34E-05 D4S234E 209570_s_at BC001745 NM_014392 27065 -1.80 1.14E-04 LOC133308 229491_at BF433180 NM_178833 133308 -1.79 1.59E-03 BHLHB2 201170_s_at NM_003670 NM_003670 8553 -1.79 7.17E-03 AI768374 228661 s at Al 768374 — — -1.79 9.50E-04 AL355688 232081_at AL355688 — — -1.79 5.36E-03 RPL39L 210115_at L05096 NM 052969 116832 -1.79 6.47E-03 BCL2 203685_at NM_000633 NM 000633 NM 000657 596 -1.78 4.07E-05 LRBA 214109_at AI659561 NM_006726 987 -1.78 1.89E-03 C9orf150 227443_at AI972386 NM 203403 286343 -1.78 2.50E-04 KCNAB1 210078_s_at L39833 NM 003471 NM 172159 NM_172160 7881 -1.78 2.11 E-03 PCDHB16 232099_at AB046841 NM 020957 57717 -1.77 1.97E-03 SYNP02 225895 at AI634580 NM_133477 171024 -1.77 6.20E-04 AK000776 232060_at AK000776 ... — -1.75 1.44E-04 COL6A1 213428_s_at AA292373 NM 001848 1291 -1.75 5.72E-04 LEPR 211355_x_at U52914 NM 00100367 9 NM_00100368 0 NM 002303 3953 -1.74 2.06E-06 PABPC5 233136_at AL122118 NM_080832 140886 -1.74 7.51 E-04 PROM1 204304_s_at NM_006017 NM 006017 8842 -1.74 6.03E-04 AGPAT3 223182_s_at AI337300 NM 020132 56894 -1.73 3.62E-04 ANK3 209442_x_at AL136710 NM 001149 NM_020987 288 -1.73 1.10E-03 CACNA1D 210108_at BE550599 NM 000720 776 -1.72 3.20E-04 H2AFJ 220936_s_at NM_018267 NM_018267 NM_177925 55766 -1.71 9.12E-04 LOC285878 230117_at AI420977 ... 285878 -1.71 1.65E-04 MGC70870 244125_at AA837131 NM_203481 403340 -1.70 1.71 E-03 LDB2 206481 s at NM 001290 NM_001290 9079 -1.70 9.86E-03 AI004009 222288 at Al004009 XM_371647 389129 -1.70 6.64E-04 362 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., etal., Cells Useful for Immuno-Based BoNT/A Activity Assays OPRM1 207989_at NM 000914 NM 000914 NM 00100850 3 NM_00100850 4 NM_00100850 C 4988 -1.69 1.26E-05 OPN3 224392_s_at AF303588 0 NM_014322 23596 -1.69 6.03E-04 FGD5 226985_at AW269340 NM_152536 152273 -1.68 4.08E-06 EBF 227646_at BG435302 NM_024007 1879 -1.68 1.59E-04 KIAA0500 213839_at AW028110 — 57237 -1.68 4.44E-03 BF342356 238934 at BF342356 — — -1.68 6.92E-03 PRKCH 218764_at NM_024064 NM 006255 5583 -1.67 7.79E-05 ARSD 223696_at BC003660 NM_001669 NM 009589 414 -1.66 9.99E-03 C9orf94 239909_at AI937348 NM_152702 206938 -1.66 7.20E-03 C6orf155 226810_at BE500942 NM_024882 79940 -1.65 2.05E-03 LOC151194 1553743_at NM_145280 NM_145280 151194 -1.65 6.80E-03 SYNP02 225721 at AI658662 NM_133477 171024 -1.64 9.76E-03 AL037414 230055_at AL037414 — — -1.64 3.29E-04 AW572379 229569_at AW572379 — — -1.63 2.80E-04 FRMD4B 213056_at AU145019 XM_114303 23150 -1.63 2.55E-03 D4S234E 213533 at M98528 NM 014392 27065 -1.63 1.82E-06 PTP4A3 209695_at BC003105 NM_007079 NM_032611 11156 -1.62 4.14E-06 ACYP2 206833 s at NM 001108 NM 138448 98 -1.62 7.71 E-04 MCTP1 220122_at NM_024717 NM 00100279 6 NM 024717 79772 -1.62 6.95E-05 ALDH1A2 207016_s_at AB015228 NM 003888 NM 170696 NM_170697 8854 -1.61 4.22E-04 CD302 203799_at NM_014880 NM_014880 9936 -1.61 1.17E-05 F10269 1557746 at F10269 — — -1.61 1.03E-03 FLJ20152 218532_s_at NM_019000 NM 019000 54463 -1.61 2.67E-03 FBI4 241401_at BG496631 NM_205857 404201 -1.60 1.55E-03 BC031271 1569785_at BC031271 — — -1.60 4.07E-04 BE046461 215303 at BE046461 — — -1.60 5.17E-04 FLJ10970 219230_at NM_018286 NM_018286 55273 -1.59 1.10E-04 CA336272 1558512 at CA336272 — — -1.59 1.57E-04 PRKACB 202741_at AA130247 NM_002731 NM 182948 NM_207578 5567 -1.59 1.12E-03 PDE4DIP 213388_at H15535 NM_00100281 0 NM 00100281 1 NM_00100281 2 NM 014644 NM 022359 9659 -1.59 6.05E-04 DKFZp762H18f 226657_at H27948 — 256306 -1.59 9.18E-03 ST18 206135 at NM_014682 NM 014682 9705 -1.58 4.56E-07 DBT 231919 at AK024946 NM_001918 1629 -1.58 1.11E-03 STMN2 203001_s_at NM_007029 NM 007029 11075 -1.58 5.47E-03 SIX2 206510_at AF332197 NM 016932 10736 -1.56 2.79E-05 NEBL 203961_at AL157398 NM_006393 NM 213569 10529 -1.56 7.89E-03 363 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays PCTK3 214797_s_at BC000281 NM 002596 NM_212502 NM 212503 5129 -1.56 8.81 E-03 DOC1 1554966_a_at AF329092 NM_014890 NM_182909 11259 -1.56 5.32E-04 Al800713 235122_at AI800713 — — -1.56 7.94E-04 NEFH 204412_s_at NM_021076 NM 021076 4744 -1.55 3.87E-03 MEGF11 1552439 s_at NM 032445 NM_032445 84465 -1.55 7.12E-04 AI796536 229810_at AI796536 — -1.55 6.60E-04 MGC11332 213393_at AI767210 NM 032718 84804 -1.54 1.06E-04 RBMS3 237860_at AI821998 NM 00100379 2 NM 00100379 3 NM_014483 27303 -1.54 9.15E-03 LOC285878 236308_at D60436 — 285878 -1.53 2.60E-04 LRRN6A 227933_at AM 93252 NM_032808 84894 -1.53 5.09E-06 NHS 228933_at BF111819 NM 198270 4810 -1.53 3.83E-03 EYA1 214608_s_at AJ000098 NM 000503 NM 172058 NM 172059 NM_172060 2138 -1.53 5.85E-05 AI263044 214376 at AI263044 — — -1.53 1.69E-04 ANKH 220076_at NM_019847 NM_054027 56172 -1.52 2.18E-03 FAM38B 219602_s_at NM_022068 NM_022068 63895 -1.52 3.24E-04 LOC133308 1564746_at BC009732 NM_178833 133308 -1.52 3.24E-03 AA747287 242273 at AA747287 — ... -1.52 3.10E-04 IL10RB 209575_at BC001903 NM 000628 3588 -1.52 4.38E-05 BACE1 217904_s_at NM_012104 NM_012104 NM 138971 NM 138972 NM_138973 23621 -1.51 1.09E-04 DISP1 228184_at AK023679 NM 032890 84976 -1.51 7.96E-03 KIAA1277 221886_at AL037701 NM_015689 27147 -1.51 1 64E-03 AI276956 230766 at AI276956 — — -1.51 4.00E-04 FAM13C1 1554547_at BC036453 NM_00100197 1 NM 198215 220965 -1.51 4.02 E-03 AKAP12 227529_s_at BF511276 NM_005100 NM_144497 9590 -1.50 2.52E-04 POSTN 1555778_a_at AY140646 NM_006475 10631 -1.50 1.94E-04 BF114745 235459_at BF114745 — — -1.50 2.88E-03 TNFSF4 207426_s_at NM_003326 NM_003326 7292 -1.49 1.01 E-03 STMN2 203000_at BF967657 NM_007029 11075 -1.49 4.14E-03 NR2F1 209505_at AI951185 NM 005654 7025 -1.49 3.03E-04 PTN 209466 x at M57399 NM_002825 5764 -1.49 6.92E-06 Al821995 240201_at AI821995 — ... -1.49 2.74E-03 MGC11332 213403_at BF223370 NM_032718 84804 -1.49 1.36E-03 KCNJ6 210454_s_at U24660 NM 002240 3763 -1.49 5.76E-03 MGC15730 227154 at AL566367 NM_032880 84966 -1.48 5.19E-03 T87730 242500_at T87730 — — -1.48 1.37E-05 LAF4 227198 at AW085505 NM_002285 3899 -1.48 1.11E-04 AL137538 232679_at AL137538 — — -1.48 6.18E-03 TOX 204530 s at NM 014729 NM_014729 9760 -1.48 2.48E-03 SB145 232283_at AL122088 NM 212551 388695 -1.48 8.90E-03 PPP1R14A 227006_at AA156998 NM_033256 94274 -1.47 1.25E-04 CRABP2 202575 at NM_001878 NM_001878 1382 -1.47 1.13E-03 AV723260 1560425_s_at AV723260 — ... -1.47 8.62E-03 364 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays D4S234E 209569_x_at NM_014392 NM_014392 27065 -1.47 3.74E-05 CDKN1C 213348_at N33167 NM_000076 1028 -1.47 5.81 E-05 LOC148418 229402_at AI631824 NM_001010971 148418 -1.46 5.19E-04 DKFZP434H13i 204494_s_at AW516789 NM 015492 56905 -1.46 5.88E-04 ZNF528 215019_x_at AW474158 NM_032423 84436 -1.46 4.79E-07 GCH1 204224_s_at NM 000161 NM 000161 2643 -1.46 8.78E-04 PCSK1 205825_at NM_000439 NM_000439 5122 -1.46 1.15E-03 WDR9 225446_at AI638279 NM 00100724 6 NM_018963 NM 033656 54014 -1.44 6.32E-05 DOC1 204135_at NM_014890 NM 014890 NM_182909 11259 -1.44 6.57E-03 NDRG1 200632_s_at NM_006096 NM_006096 10397 -1.44 6.23E-06 AI028528 241804 at AI028528 — — -1.43 8.22E-04 LOC253012 242601 at AA600175 NM_198151 253012 -1.43 1.56E-03 DMD 203881_s_at NM 004010 NM_000109 NM_004006 NM 004007 NM_004009 NM_004010 NM_004011 NM 004012 NM_004013 NM 004014 NM_004015 NM 004016 NM_004017 NM_004018 NM 004019 NM 004020 NMJD04021 NM 004022 NM 004023 1756 -1.43 1.85E-03 ZFHX1B 203603_s_at NM 014795 NM 014795 9839 -1.42 9.52E-03 C21orf86 228908_s_at AW131553 NM 153454 257103 -1.42 1.26E-03 MYT1L 210016 at BF223003 NM 015025 23040 -1.42 2.69E-04 C1GALT1C1 238989_at BF749723 NM 00101155 1 NM_152692 29071 -1.42 2.08E-03 LOC402524 242206_at AW590588 XM 379850 402524 -1.42 6.10E-04 CAMK2B 209956_s_at U23460 NM 001220 NM_172078 NM 172079 NM_172080 NM 172081 NM_172082 NM 172083 NM_172084 816 -1.42 1.44E-03 ST6GALNAC5 220979_s_at NM 030965 NM_030965 81849 -1.41 5.22E-04 AI341823 239657 x_at AI341823 — — -1.41 2.83E-03 AI733281 239994 at AI733281 — — -1.41 8.41E-03 SH3GL2 205751 at NM 003026 NM_003026 6456 -1.41 6.60E-04 AW450420 236373 at AW450420 — — -1.41 5.40E-03 PH-4 222125 s at BC000580 NM_017732 NM_177938 NM 177939 54681 -1.41 2.61 E-03 365 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays CDKN2A 209644_x_at U38945 NM 000077 NM_058195 NM_058197 1029 -1.40 1.98E-05 AI912571 228333 at AI912571 — — -1.40 5.33E-03 BF059209 240214_at BF059209 — — -1.40 2.18E-03 ARSD 232423_at AU144083 NM 001669 NM_009589 414 -1.39 1.43E-03 NEDL1 243743_at AI373512 NM 015052 23072 -1.39 2.52E-03 FRAS1 226145_s_at AL157471 NM 020875 NM_025074 NM 032863 NM 206841 80144 -1.39 8.77E-06 UNC5A 236448_at R37358 XM 030300 90249 -1.38 1.31E-05 FLJ35808 230924_at AI698574 NM_173623 284076 -1.38 5.69E-04 LOC222070 51774 s at AW014299 — 222070 -1.38 4.64E-03 C6orf199 1552299 at NM 145025 NM 145025 221264 -1.38 8.50E-03 CAPN2 208683_at M23254 NM_001748 824 -1.38 1.58E-03 BE503598 1557658_at BE503598 — — -1.38 5.77E-03 HOXD10 229400 at AW299531 NM 002148 3236 -1.37 2.17E-03 GLIS3 229435_at AW025602 NM_152629 169792 -1.37 1.72E-05 NAP1L3 204749_at NM_004538 NM_004538 4675 -1.37 5.99E-03 FLJ45244 229227_at BF511219 NM_207443 400242 -1.37 6.16E-03 D59759 231560 at D59759 — — -1.37 1.31E-06 ANK2 202920_at BF726212 NM_001148 NM_020977 287 -1.35 3.09E-05 FLJ30655 236487_at AW513286 NM 144643 132320 -1.35 3.30E-03 GLIS3 230258 at AI277316 NM 152629 169792 -1.35 1.33E-03 SH3BGR 204979_s_at NM_007341 NM 00100171 3 NM 007341 6450 -1.34 1.12E-04 RAI2 219440 at NM 021785 NM 021785 10742 -1.34 2.50E-04 ATXN1 203232_s_at NM_000332 NM_000332 6310 -1.34 8.99E-05 CRSP2 215167_at BE567032 NM_004229 9282 -1.34 6.26E-03 AI740460 236856_x_at AI740460 — — -1.34 3.19E-03 MGC42090 236705 at AA017245 NM 152774 256130 -1.34 3.46E-04 SNF1LK 208078_s_at NM 030751 NM 173354 150094 -1.33 4.49E-03 N4BP3 214775_at AW139448 XM_038920 23138 -1.33 8.59E-05 AL117598 231964 at AL 117598 — — -1.33 5.64E-06 NT5E 227486 at AI086864 NM_002526 4907 -1.33 9.12E-04 AL390170 213904_at AL390170 — — -1.33 7.47E-04 N50117 240236_at N50117 — — -1.33 1.78E-03 AK095719 1556696 s at AK095719 XM_499008 441094 -1.32 6.81 E-03 W80446 231013 at W80446 — ... -1.32 9.26E-04 C21orf66 239407_at AI793248 N M 013329 NM 016631 NM 058191 NM_145328 94104 -1.32 1.06E-03 RASGEF1B 230233_at BF110534 NM_152545 153020 -1.32 5.98E-03 DCAMKL1 205399 at NM_004734 NM_004734 9201 -1.32 8.09E-04 SCOTIN 222986 s at BC001463 NM 016479 51246 -1.32 7.27E-03 C21orf5 205248_at NM_005128 NM_005128 9980 -1.32 2.95E-04 HEL308 228736_at AW084661 NM_133636 113510 -1.32 6.40E-04 HDAC4 228813_at AW206037 NM 006037 9759 -1.31 4.97E-04 366 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et at., Cells Useful for Immuno-Based BoNT/A Activity Assays ST7L 1552739_s_at NM_138729 NM_017744 NM 138727 NM_138728 NM_138729 NM 198327 NM 198328 54879 -1.31 2.31 E-03 DACH2 239738_at AW780006 NM 053281 117154 -1.30 1.49E-03 RAB3-GAP150 243851_at Al860647 NM_012414 25782 -1.29 9.51 E-03 C9orf40 218904_s_at NM_017998 NM_017998 55071 -1.29 9.53E-03 AK027226 232538_at AK027226 — ... -1.29 5.59E-03 ZSWIM5 232336 at AI479419 XM 046581 57643 -1.28 1.68E-03 CEBPD 203973_s_at NM_005195 NM_005195 1052 -1.28 2.94E-03 AA687479 242826_at AA687479 — ... -1.28 1.21E-04 SIAT7E 230482_at AF131837 NM_030965 81849 -1.28 1.28E-03 AI694767 229768 at AI694767 — — -1.28 5.06E-03 FLJ20753 229918_at AB046860 XM_371082 55036 -1.28 9.34E-04 GUCY1A3 221942_s_at AI719730 NM 000856 2982 -1.28 2.15E-03 PTP4A3 206574_s_at NM_007079 NM 007079 NM_032611 11156 -1.27 9.96E-03 AI354636 235171 at Al354636 — ... -1.27 2.80E-03 STARD13 213103_at AA128023 NM_052851 NM_178006 NM 178007 NM 178008 90627 -1.27 1.35E-05 AKAP12 227530_at BF511276 NM_005100 NM_144497 9590 -1.27 1.01E-04 AI825987 235889_at AI825987 — — -1.27 9.63E-04 KLF9 203543_s_at NM_001206 NM_001206 687 -1.27 1.17E-03 RAB6B 221792_at AW118072 NM_016577 51560 -1.27 2.69E-03 HR 241355_at BF528433 NM 005144 NM_018411 55806 -1.27 2.35E-03 BBS7 219688_at NM018190 NM_018190 NM_176824 55212 -1.27 4.54E-05 BE467383 228932_at BE467383 XM 497668 388620 -1.27 3.12E-03 HPCA 205454 at BC001777 NM_002143 3208 -1.26 1.22E-03 KIAA1223 225735_at AL110131 XM_048747 57182 -1.26 2.58E-04 AK021551 232589_at AK021551 — — -1.26 7.56E-05 BE894882 235681 at BE894882 — — -1.26 2.96E-05 TOX 204529_s_at Al961231 NM 014729 9760 -1.25 8.61 E-05 STAR 204548_at NM_000349 NM_000349 NM_00100724 O 6770 -1.25 2.94E-05 AL833383 1563776_at AL833383 0 ___ -1.25 1.41 E-03 PPP3CA 202429_s_at AL353950 NM_000944 5530 -1.25 1.86E-05 SUCLG2 215772_x_at AL050226 NM 003848 8801 -1.25 6.75E-04 RAB26 219562 at NM_014353 NM 014353 25837 -1.25 6.02E-04 GRIP2 216481_at AF052177 XM_042936 80852 -1.25 7.55E-03 AA135722 237419_at AA135722 — — -1.25 3.44E-04 PTPRD 214043_at BF062299 NM 002839 NM_130391 NM 130392 NM_130393 5789 -1.25 5.77E-06 CDS1 226185 at AK026697 NM 001263 1040 -1.24 5.63E-04 CXorf32 229234 at AW007160 NM 001010888 340554 -1.24 3.78E-03 ACAD8 238175_at Al806909 NM_014384 27034 -1.24 8.68E-03 R71596 229580_at R71596 — ... -1.24 6.01 E-03 H46176 237083 at H46176 — ... -1.24 1.64E-03 HPS3 227139_s_at AA219354 NM_032383 84343 -1.24 1.38E-04 367 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays PTPRD 213362_at N73931 NM_002839 NM 130391 NM 130392 NM_130393 5789 -1.23 1.49E-04 FLJ23861 230561_s_at AA252512 NM 152519 151050 -1.23 2.64E-04 CD200 209582_s_at H23979 NM_00100419 6 NM_00100419 7 NM_005944 4345 -1.23 2.09E-03 SDK2 242064 at N23651 NM_019064 54549 -1.23 5.82E-04 AI051572 243310_at AI051572 — — -1.23 7.64E-03 GFRA3 229936_at AA694259 NM 001496 2676 -1.22 3.88E-03 SUCLG2 212459_x_at BF593940 NM_003848 8801 -1.22 2.39E-04 POU6F1 205878 at NM 002702 NM 002702 5463 -1.22 2.77E-03 NRP2 229225_at N90777 NM_003872 NM_018534 NM_201264 NM 201266 NM_201267 NM_201279 8828 -1.22 2.35E-03 H2AFJ 228213_at AW241813 NM_018267 NM_177925 55766 -1.22 1.63E-03 BE220828 237052_x_at BE220828 — — -1.21 3.13E-05 SLC6A15 206376_at NM_018057 NM 018057 NM_182767 55117 -1.21 3.32E-03 LGALS3BP 200923 at NM 005567 NM 005567 3959 -1.21 2.42E-05 AI949265 229156_s_at Al949265 XM_499089 441301 -1.21 9.17E-05 ANXA4 201302_at NM_001153 NM_001153 307 -1.21 7.33E-03 HIST1H2BD 209911_x_at BC002842 NM 021063 NM 138720 3017 -1.21 8.46E-04 PTPRN2 203029_s_at NM_002847 NM_002847 NM 130842 NM_130843 5799 -1.20 5.18E-04 RFPL1S 214120_at AW157535 — 10740 -1.20 2.59E-05 IFNAR1 225661_at AA811138 NM_000629 3454 -1.20 4.10E-04 GLIS1 244128 x at AA872588 NM 147193 148979 -1.20 6.88E-03 AGPAT3 223183_at AI928403 NM_020132 56894 -1.20 5.35E-03 PPEF1 206547_s_at NM_006240 NM_006240 NM_152223 NM 152224 NM_152225 NM_152226 5475 -1.20 2.16E-03 BCL6B 243825 at T79768 NM 181844 255877 -1.20 2.18E-03 ABCG1 204567_s_at NM_004915 NM 004915 NM_016818 NM_207174 NM_207627 NM 207628 NM_207629 NM_207630 9619 -1.19 4.03E-05 DJ462023.2 225876_at T84558 NM 020448 57185 -1.19 3.26E-03 CD200 209583_s_at AF063591 NM 00100419 6 NM_00100419 7 NM_005944 4345 -1.19 1.77E-04 368 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays C10orf89 230129_at BF589448 NM_153336 118672 -1.19 2.60E-03 MCPH1 219592_at NM 024596 NM_024596 79648 -1.19 2.64E-03 LOC285705 226989_at BE855765 — 285705 -1.19 2.15E-04 MANSC 1 220945_x_at NM_018050 NM_018050 54682 -1.19 1.43E-03 BF057799 236325_at BF057799 — — -1.19 5.51 E-03 OIP106 226013_at AW451452 NM 014965 22906 -1.18 4.67E-03 RPL37 224763_at BF724210 NM_000997 6167 -1.18 3.75E-03 N30152 229850 at N30152 — -- -1.18 6.56 E-03 DTX3L 225415_at AA577672 NM_138287 151636 -1.18 8.51 E-04 RAB6B 225259_at AI805050 NM_016577 51560 -1.18 4.83E-03 ROR1 205805 s at NM 005012 NM 005012 4919 -1.18 2.35E-05 DKFZp762K222 226822 at AL512713 NM_020225 56977 -1.18 8.30E-04 AI631888 235532 at AI631888 — ... -1.17 3.83E-08 PDGFRB 202273_at NM_002609 NM_002609 5159 -1.17 6.86E-03 TLE1 228284 at BE302305 NM 005077 7088 -1.17 1.65E-03 APG5L 202512_s_at NM_004849 NM_004849 9474 -1.17 3.29E-03 FLJ12572 219838_at NM 022905 NM 022905 64927 -1.17 4.22E-04 BACH 2 221234_s_at NM 021813 NM 021813 60468 -1.17 1 76E-04 FLJ38964 235699_at H19232 NM_173527 161253 -1.17 4.21 E-03 BE670797 230958_s_at BE670797 — ... -1.17 5.70E-04 AW665538 244532_x_at AW665538 XM_496692 441014 -1.16 3.31 E-03 AI828075 230795_at AI828075 — — -1.16 1 67E-03 NFATC4 236270 at AI806528 NM_004554 4776 -1.16 6.47E-05 SERTAD4 230660_at AU146709 NM_019605 56256 -1.16 3.68E-03 AL833609 1561660_at AL833609 XM_377034 401612 -1.16 6.14E-03 Al097640 213484_at AI097640 — ... -1.16 6.41 E-03 CDKN1C 213182 x at R78668 NM_000076 1028 -1.16 2.89E-03 BC040901 1559534_at BC040901 — ... -1.15 6.40E-03 SLC25A12 203339_at AI887457 NM_003705 8604 -1.15 3.28E-05 TUBA1 212242 at AL565074 NM_006000 7277 -1.15 4.37E-03 RUNX1 209360_s_at D43968 NM 00100189 0 NM_001754 861 -1.15 9.21 E-03 FLJ35093 243042 at BE645144 NM_198549 374986 -1.15 8.16E-03 BE552011 230208 at BE552011 — ... -1.15 8.27E-03 MGC9850 224874_at N32181 NM_152705 219404 -1.14 5.37E-04 OKFZP434I071' 231954_at AL137273 — 54553 -1.14 3.90E-03 AF130089 221590 s at AF130089 — — -1.14 3.07E-03 OMA1 226019_at AI927931 NM_145243 115209 -1.14 7.48E-03 SH3YL1 204019_s_at NM_015677 NM 015677 26751 -1.14 4.21 E-03 PBX1 212148_at AL049381 NM 002585 5087 -1.14 4.16E-04 BID 229321_s_at AK026026 NM 001196 NM_197966 NM_197967 637 -1.14 6.39E-03 MLSTD1 239108_at H16791 NM_018099 55711 -1.14 8.13E-03 RIS1 213338_at BF062629 NM 015444 25907 -1.14 7.59E-03 CDKN1C 216894_x_at D64137 NM_000076 1028 -1.13 1.04E-03 LOC283824 213725_x_at AI693140 — 283824 -1.13 9.96E-05 BBP 213882_at AA012917 NM 032027 83941 -1.13 2.41 E-03 MLSTD1 220615 s at NM_018099 NM_018099 55711 -1.13 4.02E-03 AA045174 213158_at AA045174 — ... -1.13 1.45E-03 AKAP12 210517_s_at AB003476 NM_005100 NM 144497 9590 -1.13 3.33E-04 ZNF585A 229794_at BE550717 NM 152655 NM 199126 199704 -1.13 3.01 E-03 NUDT6 230329_s_at AI580268 NM 007083 NM_198041 11162 -1.13 7.27E-05 AU157441 226511 at AU 157441 — ... -1.13 2.71 E-03 369 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays AI056683 228171_s_at AI056683 — — -1.12 4.23E-03 OLFM3 1554526 at BC022531 NM 058170 118427 -1.12 3.96E-04 MARCH-I 229383_at AI707896 NM_017923 55016 -1.12 2.06E-03 KCNQ2 205737_at NM 004518 NM 004518 NM_172106 NM 172107 NM_172108 NM 172109 3785 -1.12 1.40E-04 SLC4A3 205918_at NM_005070 NM_005070 NM_201574 6508 -1.12 4.66E-03 ARC 210090 at AF193421 NM_015193 23237 -1.12 8.17E-03 TRAM1L1 244334_at AA169554 NM_152402 133022 -1.12 5.89E-03 EDG4 206723_s_at AFO11466 NM_004720 9170 -1.12 2.48E-05 BE552208 229359 at BE552208 — — -1.12 7.11E-03 PLXNC1 206471_s_at NM_005761 NM 005761 10154 -1.12 3.43E-05 SUHW4 221213_s_at NM_017661 NM 00100284 3 NM 00100284 4 NM 017661 54816 -1.12 2.43E-03 PALM2-AKAP2 226694_at BG540494 NM 007203 NM_147150 445815 -1.12 1.75E-04 BF058422 226311_at BF058422 — — -1.12 6.35E-03 CDKN1C 219534_x_at NM 000076 NM_000076 1028 -1.11 7.81 E-05 MGC9850 224857_s_at BE378670 NM_152705 219404 -1.11 3.87E-03 LOC157378 238045 at BG167675 NM 194291 157378 -1.11 2.92E-03 FBX03 238686_at AA130258 NM_012175 NM_033406 26273 -1.11 1.55E-03 EFEMP2 209356 x at AB030655 NM 016938 30008 -1.11 2.18E-03 )KFZp434O052 1557879_at BF110506 NM_194302 255101 -1.10 3.12E-03 AK097571 1556261_a_at AK097571 ... ... -1.10 2.59E-03 C6orf189 228875_at AI540210 — 221303 -1.10 1.14E-04 SLC1A2 225491 at AL157452 NM 004171 6506 -1.10 9.00E-03 NFIB 243933 at AI096634 NM 005596 4781 -1.10 5.38E-03 FLJ32954 235349_at AI261321 NM 144713 151393 -1.10 6.76E-03 KCNK10 220727_at NM_021161 NM_021161 NM 138317 NM 138318 54207 -1.10 5.91 E-04 SORL1 212560_at AV728268 NM_003105 6653 -1.10 4.61 E-03 AIP1 209737_at AB014605 NM_012301 9863 -1.10 3.84E-03 AI827550 229606 at AI827550 — — -1.10 6.71E-07 SH3KBP1 1554168_a_at AF542051 NM 031892 30011 -1.10 5.41E-04 OPTN 202073_at AV757675 NM 00100821 1 NM 00100821 2 NM_00100821 3 NM 021980 10133 -1.09 5.67E-03 ATF5 204998_s_at NM_012068 NM_012068 22809 -1.09 5.15E-03 LOC401264 227298_at AI806330 XM 379417 401264 -1.09 6.06E-03 NSE1 229546 at AI378035 NM 145175 151354 -1.09 5.14E-03 LOC91526 228471 at AA744636 NM 153697 91526 -1.09 4.63E-03 IL17D 228977_at AI669535 NM_138284 53342 -1.09 2.53E-03 RG9MTD2 230243_at BE671949 NM 152292 93587 -1.09 7.55E-03 PLXNC1 213241 at AF035307 NM 005761 10154 -1.09 3.36E-03 PCDHB10 223854_at AF131761 56126 -1.09 4.88E-04 NM 018930 370 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays PITPNC1 229414_at AI676095 NM_012417 NM_181671 26207 -1.08 3.16E-04 DKFZp761D221 223672 at AL 136561 NM 032291 84251 -1.08 6.25E-03 FKBP7 231130_at AA683602 NM_016105 NM_181342 51661 -1.08 3.66E-03 CSPG3 205143_at NM 004386 NM_004386 1463 -1.08 3.42E-03 INSL3 214572 s at NM_005543 NM_005543 3640 -1.08 9.70E-03 SLC12A7 218066_at NM_006598 NM_006598 10723 -1.08 2.00E-03 AI695743 244534_at AI695743 — — -1.08 4.40E-04 DNAJC12 218976_at NM_021800 NM 021800 NM 201262 56521 -1.08 9.46E-05 LOC285550 236321_at AW439843 XM_209656 285550 -1.08 4.80E-03 BF476403 230218_at BF476403 — — -1.08 8.15E-04 AI798680 227943 at AI798680 — — -1.08 2.18E-03 LOC196394 226258 at BG031897 NM_207337 196394 -1.08 7.97E-03 AB037765 226747_at AB037765 — — -1.08 2.32E-03 SIX3 242054 s at AW473656 NM_005413 6496 -1.07 3.51 E-04 Al741900 239140_at AI741900 — — -1.07 1.53E-03 FLJ33996 235969 at R40373 — 283401 -1.07 5.06E-03 SLC24A1 206081_at NM 004727 NM 004727 9187 -1.07 7.02E-03 BID 227143_s_at AA706658 NM_001196 NM_197966 NM 197967 637 -1.07 1.25E-03 LRRC14 32062_at D25216 NM_014665 9684 -1.07 1.47E-03 LOC442647 229157 at AI949265 XM 499544 442647 -1.07 1.43E-03 FBXW7 229419_at BF222826 NM 018315 NM_033632 55294 -1.07 8.90E-07 AI003508 244114_x_at AI003508 XM_496690 401131 -1.07 2.92E-03 ZNF651 226484_at AA532640 NM_145166 92999 -1.07 1.09E-03 MMS19L 229226_at BE465026 NM 022362 64210 -1.07 9.65E-05 MAP6 228943_at AW003666 NM_033063 NM_207577 4135 -1.07 6.70E-03 AA928506 213750 at AA928506 — — -1.06 2.13E-03 H16409 227623_at H16409 — — -1.06 9.62E-05 H28915 244359_s_at H28915 XM_496692 441014 -1.06 5.58E-03 USP53 230083_at AW188464 NM_019050 54532 -1.06 3.73E-03 LOC90693 228087 at AK026684 NM_138771 90693 -1.06 8.05E-03 AA194266 238728 at AA194266 — — -1.06 5.18E-03 KIAA1324 221874_at AB037745 NM_020775 57535 -1.06 6.36E-04 HNRPR 208766_s_at BC001449 NM 005826 10236 -1.06 6.35E-05 EGFR 224999_at BE878463 NM_005228 NM 201282 NM_201283 NM_201284 1956 -1.06 8.72E-03 HSPC065 222890_at BG054922 NM_014157 29070 -1.06 6.01 E-03 FLJ30655 1569495 at BC040258 NM 144643 132320 -1.06 6.57E-04 PALM2-AKAP2 202760_s_at NM 007203 NM 007203 NM_147150 445815 -1.05 1.16E-05 MCF2L 35147 at AB002360 NM 024979 23263 -1.05 1.55E-04 DACH1 228915_at AI650353 NM_004392 NM_080759 NM_080760 1602 -1.05 1.79E-03 OLFM3 1554524 a at AF397394 NM 058170 118427 -1.05 2.90E-05 LTBP3 219922_s_at NM 021070 NM_021070 4054 -1.05 5.30E-03 RPH3AL 221614_s at BC005153 NM 006987 9501 -1.05 1.97E-03 FLJ20160 225325 at AA133311 NM 017694 54842 -1.05 8.44E-05 PITPNC1 238649 at AA815089 NM_012417 NM 181671 26207 -1.05 5.05E-03 371 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 AW959771 Jacky, B., et al., 236350_at Cells Useful for Immuno-Based BoNT/A Activity Assays AW959771 — — -1.05 4.54E-03 BU689502 1557302_at BU689502 — — -1.05 1.32E-04 TXNDC4 208958 at AI827677 NM 015051 23071 -1.04 4.97E-03 SVH 1554480_a_at AY150851 NM_031905 83787 -1.04 4.17E-03 KIAA1731 1565830_at AL833615 XM 374922 85459 -1.04 8.88E-03 AGPAT3 223184_s_at BC004219 NM_020132 56894 -1.04 1.18E-03 R53065 240430_at R53065 — — -1.04 1.68E-04 LOC339290 226235_at AI051299 XM_375527 339290 -1.04 3.78E-03 GAB1 229114_at AW237741 NM_002039 2549 -1.04 3.32E-04 LOC286052 241370_at AA278233 NM_207123 286052 -1.04 1.43E-03 LRP16 219188_s_at NM_014067 NM_014067 28992 -1.04 8.11E-03 ZNF505 1568720_at BC018100 NM_00100412 β 81931 -1.04 3.98E-03 WBP11 244647_at AA233885 D NM 031218 NM_016312 51729 -1.04 6.62E-03 AW590679 229300_at AW590679 — — -1.04 6.25E-06 BBS7 235007_at AI683802 NM_018190 55212 -1.03 2.92E-03 FMNL3 238823_at AA481044 NM 176824 NM_175736 91010 -1.03 1.64E-04 PAK1 230100_x_at AU147145 NM_198900 NM 002576 5058 -1.03 4.89E-03 HPCAL1 212552_at BE617588 NM 002149 3241 -1.03 6.95E-10 PHKB 238601_at AI798207 NM_134421 NM 000293 5257 -1.03 3.11E-03 NF2 211017_s_at AF123570 NM 000268 4771 -1.02 2.45E-03 NFASC 213438_at AA995925 NM_016418 NM181825 NM_181826 NM 181827 NM_181828 NM_181829 NM_181830 NM 181831 NM_181832 NM 181833 NMJ81834 NM 181835 NM 00100538 23114 -1.02 2.89E-05 7 NM_00100538 8 NM_00100538 9 NM 015090 RBBP6 1552329_at BC029352 NM_006910 NM_018703 NM_032626 5930 -1.02 4.18E-03 BE669703 229541 at BE669703 — — -1.02 1.41E-04 CTSC 225646_at AI246687 NM_001814 NM_148170 1075 -1.02 7.92E-03 TBC1D12 221858_at N34407 XM_051081 23232 -1.02 1.15E-04 C21orf86 228909 at AW131553 NM_153454 257103 -1.02 1.26E-03 AI991451 228412_at AI991451 — — -1.01 8.75E-03 FLJ25168 1553400_a_at NM_152466 NM_152466 147081 -1.01 1.66E-03 LOC157378 241342 at BG288115 NM_194291 157378 -1.01 3.97E-06 BG150485 228754 at BG150485 — — -1.01 3.89E-04 W56760 230683 at W56760 — — -1.01 1.42E-03 372 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays BF512183 229885_at BF512183 ... ... -1.01 4.33E-04 KIAA1573 225627_s_at AK024256 NM_020925 57685 -1.01 1.13E-03 GPR123 239221 at AI884909 NM 032422 84435 -1.01 2.88E-03 IPP 241393 at R78604 NM_005897 3652 -1.01 4.60E-03 ZNF626 1552643_at NM_145297 NM_145297 199777 -1.01 2.86E-03 AV723984 230403_at AV723984 — — -1.01 9.06E-04 AI672159 226550 at AI672159 — — -1.00 3.25E-03 TMEM28 206299_at NM 015686 NM_015686 27112 -1.00 3.66E-04 AI627858 236105_at AI627858 ... ... -1.00 9.19E-03 ZNF452 244758_at AA480069 NM_052923 114821 -1.00 6.80E-05 NME7 227556_at AI094580 NM 013330 NM 197972 29922 -1.00 7.25E-03 PLRG1 227246_at BF438014 NM_002669 5356 -1.00 1.86E-03 SLIT1 213601_at AB011537 NM 003061 6585 -1.00 3.09E-04 CTMP 229253_at AI184512 NM 053055 NM_176853 117145 -1.00 9.64E-03 AK056973 1557135_at AK056973 — — -1.00 3.03E-04 LOC169834 230876_at AI827906 XM 095965 169834 -1.00 1.27E-03 FLJ22624 236560 at BE218020 NM 024808 79866 -1.00 4.76E-03 VPS41 235625_at AW963328 NM 014396 NM_080631 27072 -1.00 3.16E-03 CDC42EP3 225685_at AI801777 NM_006449 10602 -1.00 1.49E-04 LRRTM2 206408 at NM 015564 NM 015564 26045 -1.00 5.75E-03 PHF10 221787_at BF431618 NM_018288 NM_133325 55274 -1.00 3.14E-06 PHKA2 1560358_at BC038597 NM_000292 5256 -0.99 4.51 E-03 NM 015492 204495 s at NM 015492 — — -0.99 2.51E-03 AU151107 230650_at AU151107 — — -0.99 3.88E-03 SLICK 244455_at AI732637 NM_198503 343450 -0.99 1.51 E-03 FLJ30294 238867_at AI298041 NM_144632 130827 -0.99 9.15E-04 LOC340281 240194 at AA406397 — 340281 -0.99 3.47E-03 LIPT1 205571_at NM_015929 NM_015929 NM_145196 NM_145197 NM 145198 NMJ45199 51601 -0.99 6.75E-03 0KFZP434H13i 215087_at AL109730 NM_015492 56905 -0.99 7.16E-06 RAPGEF3 210051_at U78168 NM 006105 10411 -0.98 7.80E-03 BTD 214116 at AI767414 NM 000060 686 -0.98 4.23E-03 ZCCHC7 226496_at BG291039 NM_032226 84186 -0.98 5.34E-03 C10orf104 229145_at AA541762 NM_173473 119504 -0.98 9.01 E-04 LOC222070 58900_at AW025284 — 222070 -0.98 4.22E-04 ESRRG 207981_s_at NM_001438 NM 001438 NM 206594 NM_206595 2104 -0.98 6.26E-03 PRPS2 203401 at NM 002765 NM 002765 5634 -0.98 9.17E-04 TM4SF2 202242 at NM_004615 NM 004615 7102 -0.98 4.04E-05 PCAF 203845_at AV727449 NM_003884 8850 -0.98 3.42E-06 LOC284669 1559483_at AK092251 — 284669 -0.98 1.08E-03 ARMCX5 1555902 at BC022066 NM_022838 64860 -0.98 6.50E-03 AI862542 235696 at AI862542 — — -0.98 7.90E-04 PLEKHA2 225136_at BF968578 XM 496973 59339 -0.98 1.31E-03 ACSL4 202422_s_at NM_022977 NM 004458 NM 022977 2182 -0.98 1.83E-03 PIN4 243226_at N53548 NM_006223 5303 -0.97 9.48E-04 BF510890 243406_at BF510890 — — -0.97 2.52E-03 FLJ11000 235159_at AW296028 NM 018295 55281 -0.97 8.58E-03 TPMT 203672_x_at U12387 NM_000367 7172 -0.97 3.95E-03 373 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 NCOA7 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays 225344_at AL035689 NM_181782 135112 -0.97 1.02E-03 NUDT6 220183_s_at NM_007083 NM_007083 11162 -0.97 1.63E-05 CACNA1B 235781 at AA448208 NM_198041 NM 000718 774 -0.97 2.17E-03 LOC253982 214993_at AF070642 NM_181718 253982 -0.97 5.64E-03 NOTCH4 205247_at AI743713 NM_198907 NM 004557 4855 -0.96 5.91 E-03 DACH1 205472_s_at NM_004392 NM 004392 1602 -0.96 6.40E-04 C21orf25 212875_s_at AP001745 NM_080759 NM_080760 NM 199050 25966 -0.96 1.81E-04 KIAA1377 235956 at AI797063 NM_020802 57562 -0.96 2.43E-03 KIAA1729 230715_at AM 38969 NM_053042 85460 -0.96 2.87E-03 TMEM18 225487_at AI074464 NM_152834 129787 -0.96 3.04E-04 CITED2 209357 at AF109161 NM_006079 10370 -0.96 4.57E-03 AI768895 231069 at AI768895 — — -0.96 4.30E-03 )KFZp451M21 1 239240_at AI814116 NM_182585 285023 -0.96 8.59E-03 N50119 235635_at N50119 — — -0.96 3.56E-03 AI802997 235211 at AI802997 — — -0.96 4.66E-05 PRPH 213847_at NM_006262 NM_006262 5630 -0.95 1.14E-03 C14orf167 227446_s_at BF445127 — 55449 -0.95 4.86E-03 NEIL2 226585_at BE466620 NM_145043 252969 -0.95 3.33E-04 LOC401020 1560475 at AK092134 XM_379145 401020 -0.95 4.55E-03 CXorf45 205583 s at NM 024810 NM 024810 79868 -0.95 2.74E-03 MLLT4 238871_at AI086124 NM_005936 4301 -0.95 6.94E-03 PPP3CA 202457_s_at AA911231 NM 000944 5530 -0.95 7.65E-04 MTUS1 212095_s_at BE552421 NM_00100192 A 57509 -0.95 1.54E-03 CARD8 1554479_a_at AF511652 NM 00100192 5 NM_00100192 7 NM 00100193 1 NM_020749 NM_014959 22900 -0.95 1.49E-03 HS3ST5 240479_at AW449310 NM_153612 222537 -0.95 4.10E-03 CDC42EP3 209286_at AI754416 NM_006449 10602 -0.94 2.27E-05 CLDN12 223249_at AL136770 NM 012129 9069 -0.94 7.31 E-04 MGC70870 242136_x_at T66145 NM_203481 403340 -0.94 4.23E-04 LIFR 225575_at AI680541 NM_002310 3977 -0.94 2.42E-03 AA002140 241365_at AA002140 — — -0.94 3.00E-03 LOC153364 230298 at AI692906 NM 203406 153364 -0.94 5.23E-03 BRUNOL4 238966_at AA678985 NM_020180 56853 -0.94 6.55E-04 AV700050 228835_at AV700050 — — -0.94 3.53E-03 TRIM4 223384_s_at BE501464 89122 -0.94 6.97E-03 FLJ23560 219487_at NM_024685 NM 033017 NM 033091 NM_024685 79738 -0.94 1.67E-03 PDGFRL 205226 at NM 006207 NM_006207 5157 -0.94 3.47E-03 BG502771 226397 s at BG502771 — — -0.94 6.49E-05 AI392908 230352_at AI392908 — — -0.94 3.46E-03 LOC93622 225391_at AL562398 NM 138699 93622 -0.94 5.23E-05 IMMP2L 227153_at AI784580 NM 032549 83943 -0.94 1.01 E-03 DACH1 205471_s_at AW772082 NM_004392 1602 -0.94 4.97E-05 AI963605 230269_at AI963605 NM 080759 NM 080760 -0.94 1.40E-03 374 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays R45950 229994_at R45950 — — -0.93 1.97E-03 RGMB 227339_at BE206621 NM_173670 285704 -0.93 3.25E-06 LOC285705 NIN 223981_at AF223937 NM_016350 285705 51199 -0.93 8.04E-03 )KFZp313N062 241666_at BG493222 NM_020921 NM_182944 NM 182945 NM_182946 NM 173826 285343 -0.93 6.42E-03 DKFZP564D17; 212936_at AI927701 NM_032042 83989 -0.93 2.49E-05 CaMKIINalpha 218309 at NM_018584 NM 018584 55450 -0.93 3.41 E-05 MAPK10 237413_at Al568447 NM_002753 5602 -0.93 2.01 E-04 CXXC4 220277_at NM_025212 NM_138980 NM 138981 NM 138982 NM_025212 80319 -0.93 1.90E-04 HEL308 1554341 a at BC011863 NM 133636 113510 -0.93 1.26E-04 SIGIRR 218921_at NM 021805 NM 021805 59307 -0.92 3.82E-03 FBXL17 227203 at AA115629 NM 022824 64839 -0.92 1.44E-03 ATXN1 203231_s_at AW235612 NM_000332 6310 -0.92 5.79E-05 USP46 203869_at AK024318 NM_022832 64854 -0.92 3.21 E-04 CSE-C 224391_s_at AF303378 NM_170601 54414 -0.92 2.82E-03 GGPS1 202321 at AW299507 NM 004837 9453 -0.92 2.16E-03 MUTED 226543_at AI768114 NM 201280 63915 -0.92 3.41 E-03 KIAA0564 212946_at AK025432 NM_00100981 λ 23078 -0.92 4.42E-03 JMY 226352_at BF447037 NM 015058 NM 152405 133746 -0.92 2.68E-04 PALM2-AKAP2 202759_s_at BE879367 NM 007203 445815 -0.92 1.79 E-04 AI631072 228638_at AI631072 NM_147150 -0.92 9.69 E-03 MCAM 209087_x at AF089868 NM 006500 4162 -0.92 2.51 E-03 PSD3 203355_s_at NM_015310 NM 015310 23362 -0.92 4.84 E-03 PTEN 228006 at BG403361 NM 206909 NM_000314 5728 -0.92 3.02 E-03 ABAT 209459_s_at AF237813 NM_000663 18 -0.92 5.61 E-03 AI887898 228423_at AI887898 NM_020686 XM 374094 389237 -0.92 5.43E-04 MGC14595 238562 at BE542779 NM_032334 84294 -0.92 1.59E-05 AA757630 236724_at AA757630 —' ... -0.91 2.99E-04 BF510563 228561_at BF510563 — — -0.91 1.65 E-05 ETS2 201328 at AL575509 NM 005239 2114 -0.91 6.50E-05 TRIM32 236233_at AI768810 NM_012210 22954 -0.91 7.51 E-03 CDC42EP3 209288_s_at AL136842 NM_006449 10602 -0.91 1.33E-04 CNOT6L 227119_at BF103856 NM_144571 246175 -0.91 2.60E-06 AI754871 229075 at AI754871 — — -0.91 2.23E-03 PSD3 218613_at NM_018422 NM_015310 23362 -0.91 2.81 E-05 SLC20A2 229371_at BF940010 NM_206909 NM_006749 6575 -0.91 2.66E-04 SNX10 218404 at NM 013322 NM 013322 29887 -0.90 3.48E-03 KCTD18 226493_at AI627249 NM_152387 130535 -0.90 7.20E-03 MGC31963 1558692_at AW090182 NM_144580 112770 -0.90 9.19E-03 C21orf51 228239_at AA148789 NM_058182 54065 -0.90 3.56E-03 T79639 243466 at T79639 — — -0.90 3.38E-03 BE671727 244177_at BE671727 — — -0.90 7.50E-03 WDR32 219001_s_at NM_024345 NM_024345 79269 -0.90 1.46E-03 AW770320 242523 at AW770320 — — -0.90 5.17E-03 FLJ31265 228341_at AI809108 NM_152395 131870 -0.90 9.74E-03 375 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays TENS1 217853_at NM_022748 NM 022748 64759 -0.90 3.93E-03 AFFX-BioB-3 <\FFX-BioB-3_a AFFX-BioB-3 — — -0.90 4.10E-03 AL359605 227318_at AL359605 — — -0.90 4.75E-04 FIP1L1 1554424_at BC017724 NM 030917 81608 -0.90 2.24E-05 MGC22773 235498_at AI269596 NM_145258 127255 -0.89 3.93E-07 AI765014 224649_x_at AI765014 — — -0.89 3.50E-03 ACSL6 229725_at AV705292 NM_00100918 5 N M 015256 23305 -0.89 6.40E-03 HNRPR 208765_s_at NM_005826 NM_005826 10236 -0.89 9.23E-05 GATM 216733_s_at X86401 NM 001482 2628 -0.89 6.06E-03 SAT 213988_s_at BE971383 NM_002970 6303 -0.89 6.15E-03 MGC16275 1558167 a at BM824870 — 85001 -0.89 3.24E-03 AI743452 237031_at AI743452 — — -0.89 2.69E-03 FLJ11011 222656_at AI625741 NM 00100148 1 NM 00100148 2 NM_018299 55284 -0.89 2.46E-03 BF510762 230262_at BF510762 — — -0.89 7.78E-05 SOCS5 208127_s_at NM_014011 NM_014011 NM_144949 9655 -0.89 2.64E-03 LTBP3 227308_x_at AW515704 NM_021070 4054 -0.89 1.44E-04 AI826437 229975_at AI826437 — — -0.89 3.65E-04 BRAF 236402_at AW184034 NM_004333 673 -0.89 8.26E-03 LNX 227293 at AI264003 NM 032622 84708 -0.88 1.56E-03 F3 204363 at NM_001993 NM 001993 2152 -0.88 2.35E-03 COVA1 204643_s_at NM_006375 NM_006375 NM_182314 10495 -0.88 9.34E-03 TPD52 201691_s_at NM 005079 NM 005079 7163 -0.88 6.44E-04 GRIK2 1560142_at AJ301610 NM_021956 NM_175768 2898 -0.88 5.49E-03 AI025829 235227_at Al025829 — — -0.88 2.45E-03 AI761584 229654_at AI761584 — — -0.88 9.83E-03 MAP3K5 203836_s_at D84476 NM 005923 4217 -0.88 7.19E-03 NOX4 219773_at N M 016931 N M 016931 50507 -0.88 6.53E-03 FBXL17 238174_at AI694129 NM_022824 64839 -0.88 4.28E-04 ERCC6 207347 at NM_000124 NM 000124 2074 -0.88 1.34E-03 TMEM34 219074_at NM_018241 NM_018241 55751 -0.88 2.71 E-03 MGC52110 226039 at AW006441 NM_001008215 493753 -0.87 3.18E-05 SPHAR 206272_at NM_006542 NM_006542 10638 -0.87 3.60E-03 FCMD 205283 at NM_006731 NM 006731 2218 -0.87 3.96E-03 BAI3 205638_at NM_001704 NM_001704 577 -0.87 8.83E-03 N29877 231169_at N29877 — — -0.87 2.33E-03 MBNL1 201153_s_at NM_021038 NM_021038 NM 207292 NM_207293 NM_207294 NM_207295 NM_207296 NM_207297 4154 -0.87 2.24E-05 CLCN3 201734_at AI760629 NM_001829 NM_173872 1182 -0.87 7.31 E-03 MGC13024 221864 at AW517464 NM_152288 93129 -0.87 9.69E-03 XPR1 226615_at BE439489 NM 004736 9213 -0.87 2.22E-04 376 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays CAMK2B 210404_x_at AF078803 NM_001220 NM_172078 NM_172079 NM_172080 NM_172081 NM_172082 NM_172083 NM_172084 816 -0.87 1.66E-03 CHD2 228999_at AW514564 NM 001271 1106 -0.86 2.91 E-03 TMEM1 209412_at U61500 NM_00100172 3 NM_003274 7109 -0.86 2.68E-03 FLJ32130 1554769_at BC040642 NM_152458 146540 -0.86 3.30E-03 MCF2L 212935 at AB002360 NM_024979 23263 -0.86 3.60E-04 PGRMC2 213227_at BE879873 NM_006320 10424 -0.86 1.58E-03 BF434383 235473_at BF434383 — — -0.86 5.25E-03 WARS2 222734_at BF515963 NM_015836 NM_201263 10352 -0.86 9.52E-03 ASB13 218862 at NM_024701 NM 024701 79754 -0.86 5.98E-03 ARSD 225280_x_at N51673 NM 001669 NM_009589 414 -0.86 4.80E-03 HEL308 1554342_s_at BC011863 NM_133636 113510 -0.86 8.97E-03 GLCE 213552 at W87398 NM 015554 26035 -0.86 3.64E-03 ZNF25 235164_at BG433539 NMJ45011 219749 -0.86 8.82E-03 N56912 221944_at N56912 XM 496112 440332 -0.86 2.61 E-03 BMPR2 225144_at AI457436 NM_001204 NM_033346 659 -0.86 9.23E-05 AI796858 236164_at AI796858 — — -0.86 6.19E-05 HPS1 210112_at U96721 NM_000195 NM 182637 NM 182638 NM_182639 3257 -0.86 9.98E-03 SCRN3 219234_x_at NM_024583 NM_024583 79634 -0.86 1.04E-03 EFNB3 205031 at NM 001406 NM 001406 1949 -0.86 4.69E-03 ZNF25 228185_at N32599 NM_145011 219749 -0.85 9.68E-03 AW274846 228108_at AW274846 — — -0.85 3.72E-03 STC1 204595_s_at AI300520 NM_003155 6781 -0.85 1.72E-03 AW044658 229201_at AW044658 — — -0.85 7.58E-05 CA442342 1556097_at CA442342 — — -0.85 6.36E-03 FLJ21159 235550_at AV751613 NM 024826 79884 -0.85 6.98E-04 PKNOX1 54051_at H59033 NM_004571 NM_197976 5316 -0.85 1.84E-03 PDE2A 204134_at NM_002599 NM_002599 5138 -0.85 1.09E-04 DHRSX 225503_at AL547782 NM 145177 207063 -0.85 2.79E-03 SLC19A1 229489_at AI681043 NM 003056 NM_194255 6573 -0.85 2.68E-03 C13orf24 213239_at NM_006346 NM_006346 10464 -0.85 2.61 E-04 SRGAP3 209794_at AB007871 NM 014850 9901 -0.85 7.85E-03 C21orf127 234676_s_at AK021678 NM 013240 NM_182749 29104 -0.85 8.73E-03 PARP11 229138_at AV747166 NM_020367 57097 -0.84 1.23E-03 ELAC1 219325_s_at NM_018696 NM_018696 55520 -0.84 9.17E-03 AV702357 229823_at AV702357 — — -0.84 2.59E-04 FLRT1 210414 at AF169675 NM_013280 23769 -0.84 8.98E-03 C2orf17 222129_at AK026155 NM 024293 79137 -0.84 2.37E-03 PF6 1557593 at AA250798 NM_206996 200162 -0.84 1.52 E-03 BC040191 1568623 a at BC040191 — — -0.84 5.28E-03 H99038 227338 at H99038 XM_498946 440983 -0.84 9.90E-03 377 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., etal., Cells Useful for Immuno-Based BoNT/A Activity Assays MAN BA 203778_at NM_005908 NM_005908 4126 -0.84 4.77E-03 DELGEF 232983_s_at AJ243951 NM 012139 26297 -0.84 7.32E-03 ATP2C1 209934_s_at AF225981 NM_00100148 5 NM_00100148 6 NM_00100148 7 NM_014382 27032 -0.84 5.96E-03 LOC92249 212957_s_at AU154785 XM_499179 92249 -0.83 7.94E-04 SPATA7 234929_s_at AF144488 NM 018418 55812 -0.83 9.12E-03 AW269338 235691_at AW269338 XM_378880 400764 -0.83 1.62E-03 ZNF295 225539_at AP001745 NM_020727 49854 -0.83 1.11E-03 KIAA1223 225731_at BF196876 XM_048747 57182 -0.83 1.79E-06 BF207861 239768 x at BF207861 — — -0.83 3.46E-03 BG236351 217598_at BG236351 — — -0.83 1.23E-03 B3GTL 227083_at N51325 NM 194318 145173 -0.83 2.95E-05 QPCT 205174 s at NM_012413 NM_012413 25797 -0.83 8.28E-03 AL045516 232166 at AL045516 — — -0.83 2.57E-03 ZNF148 230821_at AW594167 NM_021964 7707 -0.83 3.02E-03 GNG2 224964_s_at AK026424 NM 053064 54331 -0.83 6.30E-03 CTPS2 219080_s_at NM_019857 NM_019857 NM 175859 56474 -0.83 3.00E-04 CAMK2D 225019_at BF797381 NM 001221 NM_172115 NM 172127 NM_172128 817 -0.83 8.53E-03 CYLD 213295_at AA555096 NM_015247 1540 -0.83 7.35E-04 TMEM5 204808_s_at NM_014254 NM 014254 10329 -0.83 2.63E-03 FLJ35036 225512 at AI005245 XM_172341 253461 -0.83 6.24E-04 LOC51334 220014 at NM 016644 NM 016644 51334 -0.82 5.21 E-04 MGC34646 224996_at N30209 NM_173519 157807 -0.82 6.97E-05 NDP52 235076_at AA149539 NM_005831 10241 -0.82 2.69E-03 FLJ38991 227442_at BG283902 NM 173827 285521 -0.82 2.38E-03 LOC144363 225469 at AA015609 NM_00100166C 144363 -0.82 6.00E-03 AI627803 236194_at AI627803 — — -0.82 8.90E-03 EIF4E3 238461_at AA228031 — 317649 -0.82 8.67E-03 LOC284262 227478 at BF739885 — 284262 -0.82 1.50E-05 LRCH2 227688_at AK022128 NM_020871 57631 -0.82 4.46E-04 AI635131 1557192_at AI635131 XM_375410 400574 -0.82 2.14E-03 AA935515 242790_at AA935515 — — -0.82 4.73E-04 ZNF423 214761 at AW149417 NM 015069 23090 -0.82 6.45E-03 FBX04 223493_at AF129534 NM_012176 NM_033484 26272 -0.82 2.52E-03 AI417268 225028_at AI417268 — — -0.82 8.20E-03 EIF2C1 228120 at AW136032 NM 012199 26523 -0.81 1.09E-05 FLJ22313 236170_x_at AI377423 NM_022373 64224 -0.81 4.47E-03 LOC401500 233946_at AL512690 XM_379629 401500 -0.81 2.52E-03 AFFX-BioB-M \FFX-BioB-M_a AFFX-BioB-M — — -0.81 3.21 E-03 AI149508 228416 at AI149508 — — -0.81 1.26E-04 ZNF287 220055_at NM_020653 NM_020653 57336 -0.81 1.85E-04 FLJ30851 230435_at BF108666 NM_198553 375190 -0.81 5.13E-03 BC042959 1556194_a_at BC042959 — — -0.81 2.89E-03 CA5BL 238435 at AA521288 XM 291346 340591 -0.81 4.85E-03 WIZ 221784_at AI089655 XM_372716 58525 -0.81 1.35E-03 AW086077 232800_at AW086077 — — -0.81 3.68E-03 FLJ22795 223327 x at AF316855 NM_025084 80154 -0.81 4.57E-03 AI075662 238038 at AI075662 — — -0.81 4.28E-03 378 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays PCDHB14 231726_at NM_018934 NM_018934 56122 -0.81 5.56E-03 LOC130355 227840_at AA738440 XM 496588 130355 -0.81 2.33E-05 FLJ10378 231824_at AK027164 NM 018078 NM_032239 NM 178043 55132 -0.81 7.52E-03 CAMK2B 211483_x_at AF081924 NM_001220 NM 172078 NM_172079 NM_172080 NM 172081 NM 172082 NM_172083 NM_172084 816 -0.81 2.75E-04 RPL4 226556 at BF431260 NM_000968 6124 -0.81 2.30E-07 C21orf108 212996 s at AI803485 — 9875 -0.81 4.93E-03 CYLD 39582_at AL050166 NM 015247 1540 -0.81 8.02E-04 MBNL1 201151_s_at BF512200 NM_021038 NM 207292 NM 207293 NM 207294 NM_207295 NM_207296 NM 207297 4154 -0.80 1.13E-03 HERC4 208055_s_at NM_015601 NM_015601 26091 -0.80 1.46E-03 AI929792 236081_at Al929792 — — -0.80 2.95E-03 SYNJ1 212990_at AB020717 NM 003895 NM_203446 8867 -0.80 1.01 E-03 C9orf123 224860_at AL137489 XM 372075 90871 -0.80 8.84E-04 C21orf66 1556789_a_at AK056384 NM 013329 NM_016631 NM_058191 NM 145328 94104 -0.80 4.85E-03 BMPR2 231873_at AL046696 NM 001204 NM_033346 659 -0.80 1.31 E-04 PCBP3 230486_at BG025371 NM_020528 54039 -0.80 5.61 E-04 JAM2 229127_at BF195118 NM_021219 58494 -0.80 4.44E-03 COG6 225769_at AF116827 NM_020751 57511 -0.80 4.32E-03 FLJ21159 220145 at NM 024826 NM 024826 79884 -0.80 5.05E-03 HSD17B12 217869_at NM_016142 NM_016142 51144 -0.80 5.67E-03 SMAP-5 224953_at AW001618 NM_030799 81555 -0.80 5.29E-03 SAV1 218276 s at NM 021818 NM 021818 60485 -0.80 1.52E-03 PPID 204186_s_at AI014573 NM 005038 5481 -0.80 5.72E-04 AZI2 227905_s_at BF000175 NM_022461 NM_203326 64343 -0.79 9.88E-05 BE219874 236111_at BE219874 — — -0.79 6.26E-03 KPNA1 202057_at BC002374 NM_002264 3836 -0.79 5.21 E-03 LOC339803 227940_at N90774 — 339803 -0.79 1.13E-04 ALKBH 236721_at AI922200 NM_006020 8846 -0.79 2.25E-03 AW237752 229699 at AW237752 — — -0.79 8.75E-03 SLC22A17 218675_at NM_020372 NM_016609 NM_020372 51310 -0.79 1.71 E-04 TOB1 228834_at BF240286 NM_005749 10140 -0.79 7.87E-04 MED28 224416 s at AF358829 NM 025205 80306 -0.79 1.39E-04 ZNF277 1555193_a_at BC020626 NM_021994 11179 -0.79 9.56E-03 WDFY3 212598 at BE348236 NM 014991 NM 178583 NM 178585 23001 -0.79 6.62E-03 379 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays SGNE1 203889_at NM_003020 NM_003020 6447 -0.78 3.31 E-04 ANKRD32 223542_at AL136560 NM 032290 84250 -0.78 2.09E-04 CLCN3 201733_at AA902971 NM 001829 NM_173872 1182 -0.78 1.25E-06 EIF4E3 225939_at AL161983 — 317649 -0.78 2.79E-03 CARF 218929_at NM_017632 NM 017632 55602 -0.78 2.99E-03 DCX 204851_s_at AF040254 NM 000555 NM_178151 NM_178152 NM_178153 1641 -0.78 7.79E-03 C1orf25 220992 s at NM_030934 NM 030934 81627 -0.78 2.30E-03 TNFRSF25 219423_x_at NM_003790 NM_003790 NM_148965 NM 148966 NM_148967 NM_148968 NM_148969 NM 148970 NM 148971 NM_148972 NM_148973 NM 148974 8718 -0.78 8.35E-03 AOF2 212348_s_at AB011173 NM 00100999 9 NM_015013 23028 -0.78 3.47E-03 AW025980 241864_x_at AW025980 XM 371647 389129 -0.78 5.72E-04 ACBD5 225663 at AL047650 NM 145698 91452 -0.78 1.80E-03 FRS2 226045_at AW264515 NM 006654 10818 -0.78 5.02E-03 MYOZ3 213955_at BE673151 NM_133371 91977 -0.78 7.08E-03 DBT 205369 x at J03208 NM_001918 1629 -0.78 5.34E-03 AI061377 235233_s_at Al061377 — — -0.78 2.35E-03 ENOSF1 204142_at NM_017512 NM 017512 55556 -0.78 2.12E-03 CA5BL 239106_at Al801563 XM 291346 340591 -0.77 3.87E-03 GTDC1 219770_at NM_024659 NM 00100663 6 NM_024659 79712 -0.77 5.30 E-04 RAB18 243496_at AW367507 NM_021252 22931 -0.77 5.05E-03 AK025253 227009 at AK025253 — — -0.77 2.24E-03 MRPS6 212944_at AK024896 NM 032476 64968 -0.77 9.32E-03 AFAP 203563_at NM_021638 NM_021638 NM_198595 60312 -0.77 4.32E-04 RGS7 1554500 a at AF493931 NM 002924 6000 -0.77 5.33E-04 QSCN6 201482_at NM_002826 NM_00100412 8 NM 002826 5768 -0.77 5.46E-04 C21orf57 227421_at BF026326 NM_00100611 4 NM_058181 54059 -0.77 2.03E-03 PLEKHA3 227658_s_at BE550332 NM 019091 65977 -0.77 2.93E-04 FLJ10980 225327_at AB037791 NM_019600 56204 -0.77 3.59E-03 PURA 229167 at AM 29941 NM 005859 5813 -0.77 7.80E-03 -X-r2-Ec-bioC-X-r2-Ec-bioC-£!\FFX-r2-Ec-bioC-! t ___ — -0.77 1.36E-03 HSPA12A 214434 at AB007877 XM 048898 259217 -0.77 5.03E-03 ZNF250 213858_at BE350026 NM_021061 58500 -0.77 2.48E-03 CD O 0 LU x: 1 1 -X-r2-Ec-bioB-£i\FFX-r2-Ec-bioB-l — -0.77 4.87E-03 PDXK 222492_at AW262867 NM_003681 8566 -0.77 7.16E-03 H09780 230869 at H09780 — — -0.76 5.31 E-03 LOC283481 230351 at AW070248 — 283481 -0.76 1.35 E-04 380 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 LOC128153 Jacky, B., etal., 1552269_at Cells Useful for Immuno-Based BoNT/A Activity Assays NM_138796 NM_138796 128153 -0.76 8.35E-03 PTP4A2 208617_s_at AF208850 NM_003479 8073 -0.76 8.88E-05 AB029551 201845_s_at AB029551 NM 080391 NM_080392 -0.76 1.96E-04 KIAA1387 226230_at AA541716 NM_020463 57223 -0.76 1.87E-03 C21orf86 226995_at AV705934 NM_153454 257103 -0.76 5.79E-05 ISYNA1 222240 s at AL137749 NM 016368 51477 -0.76 3.08E-03 RNF13 201780_s_at NM_007282 NM_007282 11342 -0.76 6.77E-04 JMJD2C 209984_at AB037901 NM 183381 NM_183382 NM 183383 NM_183384 NM 015061 23081 -0.76 3.62E-03 GTDC1 238585_at AW407668 NM_00100663 79712 -0.76 1.71E-03 6 NM 024659 AI955713 227193_at AI955713 — — -0.76 2.70E-03 FKBP1A 210187_at BC005147 NM_000801 NM_054014 2280 -0.76 7.11E-03 AW117322 239415_at AW117322 XM_374094 389237 -0.76 5.02E-03 BBP 213883_s_at AA012917 NM_032027 83941 -0.76 5.76E-03 LOC284804 1559161_at AI871356 — 284804 -0.75 6.44E-03 DJ159A19.3 205002_at NM_015699 XM_372774 27245 -0.75 8.45E-04 AFFX-BioDn-3 vFFX-BioDn-3_j AFFX-BioDn-3 — — -0.75 2.83E-03 LAMB1 201505_at NM_002291 NM_002291 3912 -0.75 9.18E-03 POLR3A 227872 at AA527570 NM_007055 11128 -0.75 9.27E-04 CDC2L6 212899_at AB028951 NM_015076 23097 -0.75 2.97E-05 GRK4 241989_at AW269179 NM_00100405 6 NM_00100405 7 NM 005307 NM_182982 2868 -0.75 9.15E-03 FEV 207260 at NM_017521 NM_017521 54738 -0.75 5.52E-04 MGC35274 226748_at AI674731 NM_153374 256586 -0.75 6.51 E-03 PRKCB1 209685_s_at M13975 NM_002738 NM_212535 5579 -0.75 4.16E-03 OXR1 222553 x at AL541048 NM_181354 55074 -0.75 3.29E-03 ARP3BETA 218868_at NM_020445 NM 020445 57180 -0.75 9.91 E-03 PFN2 237116_at AI262277 NM_002628 NM_053024 5217 -0.74 8.35E-03 LZTFL1 218437_s_at NM 020347 NM 020347 54585 -0.74 3.96E-03 C6orf96 220329 s at NM 017909 NM_017909 55005 -0.74 1.80E-03 BE890365 222738_at BE890365 — — -0.74 9.64E-03 BG112359 225785_at BG112359 — — -0.74 2.08E-03 ICA1 204002_s_at NM_022307 NM_004968 NM 022307 NM_022308 3382 -0.74 2.94E-03 ENOSF1 213645_at AF305057 NM 017512 55556 -0.74 4.62E-03 CAMK2D 228555_at AA029441 NM_001221 NM_172115 NM 172127 NM_172128 817 -0.74 1 79E-03 AI889373 227414_at AI889373 — — -0.74 1.82E-03 GPR27 227769_at AI703476 NM_018971 2850 -0.74 8.05E-03 AK055769 1558801_at AK055769 — — -0.74 7.07E-03 AFFX-BioB-5 4FFX-BioB-5_a AFFX-BioB-5 — — -0.73 3.91 E-03 381 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays AA928542 226831_at AA928542 — — -0.73 8.48E-04 PAM 202336_s_at NM_000919 NM_000919 NM 138766 NM_138821 NM_138822 5066 -0.73 2.84E-03 THNSL1 222931 s at AI809864 NM_024838 79896 -0.73 3.88E-03 MGC14595 227836 at AI859767 NMJJ32334 84294 -0.73 6.40E-03 PRKCE 226101_at AI093546 NM_005400 5581 -0.73 3.23E-03 LOC92482 213224_s_at AK025724 XM_378250 92482 -0.73 5.89E-03 AKAP14 228493_at T87628 NM_00100853 4 NM_00100853 5 NM_178813 158798 -0.73 8.43E-03 DUSP16 224336 s at AB052156 NM_030640 80824 -0.73 4.69E-04 IRF2BP2 224571 at BF968057 NM_182972 359948 -0.73 6.05E-03 C6orf117 243177_at AI912225 NM 138409 112609 -0.73 7.88E-03 ADD2 205268_s_at NM_017488 NM 001617 NM 017482 NM 017483 NM_017484 NM_017485 NM 017486 NM_017487 NM 017488 119 -0.73 4.20E-07 PCSK6 207414_s_at NM_002570 NM 002570 NM 138319 NM 138320 NM_138321 NM_138322 NM 138323 NM_138324 NM_138325 5046 -0.73 3.49E-03 H62221 243414 at H62221 — — -0.73 2.65E-03 AFFX-BioC-5 ^FFX-BioC-Sa AFFX-BioC-5 — — -0.73 6.02E-04 BF342524 235074_at BF342524 — — -0.73 2.25E-03 LOC96610 226802_s_at W87523 NM_080926 96610 -0.73 9.29E-03 BE645776 227288 at BE645776 XM_068632 133993 -0.73 7.66E-04 KIAA0423 213304_at AI823592 NM_015091 23116 -0.73 2.19E-03 ENOSF1 204143 s at NM 017512 NM 017512 55556 -0.73 2.84E-05 DSCR5 221689_s_at AB035745 NM_016430 NM_153681 NM_153682 51227 -0.73 4.01 E-05 MGC54289 225228 at AI474054 NM_178454 128338 -0.72 2.77E-05 AK026379 232687 at AK026379 — — -0.72 1 93E-04 MGC72075 228600.....x_at BE220330 NM_199136 340277 -0.72 5.28E-04 ASH1L 226447 at BG290742 NM_018489 55870 -0.72 2.78E-03 KIAA0974 213463 s at AW300504 — 317662 -0.72 4.74E-04 C6orf157 227790_at AV692609 NM 198920 90025 -0.72 3.66E-03 CLCN4 214769 at AF052117 NM 001830 1183 -0.72 3.22E-04 LOC440360 236838 at H11609 XM_498641 440360 -0.72 2.56E-03 SYNCRIP 217833 at AL520908 NM_006372 10492 -0.72 4.62E-04 m 0 1 0 LU t 1 X LL "X-r2-Ec-bioB-l\AFFX-r2-Ec-bioB-li — — -0.72 7.96E-03 AKT3 212609_s_at U79271 NM_005465 NM_181690 10000 -0.72 5.74E-03 PP1057 220968 s at NM 031285 — 83441 -0.72 6.75E-03 GM2A 1559776_at H41167 NM_000405 2760 -0.72 1.46E-03 382 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays FLJ37228 1556641_at AK094547 ... 285264 -0.72 6.35E-03 NAV1 227584_at BF339566 NM_020443 89796 -0.71 9.22E-05 MGC10198 225574 at BE613081 NM 152682 201965 -0.71 1.36E-03 PPP2R5C 201877_s_at NM_002719 NM_002719 NM_178586 NM_178587 NM_178588 5527 -0.71 1.25E-03 RAFTLIN 212646_at D42043 NM_015150 23180 -0.71 7.61 E-06 DKFZP564024; 210006_at BC002571 NM_015407 25864 -0.71 5.84E-03 SLC35A5 218519_at NM_017945 NM_017945 55032 -0.71 5.19E-03 BF526978 227125 at BF526978 — — -0.71 2.88E-03 RBM16 227866_at AI743557 NM_014892 22828 -0.71 4.70E-04 gm117 239038 at AW015063 NM_198077 148423 -0.71 2.85E-05 AB058893 223973_at AB058893 — — -0.71 3.00E-03 DUSP16 224832_at AB051487 NM_030640 80824 -0.71 8.84E-04 FFX-r2-Ec-bioCrX-r2-Ec-bioC-C- \FFX-r2-Ec-bioC-: — — -0.71 2.47E-03 AL355532 213845_at AL355532 — — -0.71 1.72E-03 LOC284409 242016_at BE857296 XM 211447 284409 -0.70 7.46E-03 PAK1 226507_at AU154408 NM_002576 5058 -0.70 1.89E-03 BC015852 1560570_a_at BC015852 — — -0.70 5.93E-04 EPM2AIP1 227847_at BF432224 NM_014805 9852 -0.70 6.03E-03 13CDNA73 204072_s_at NM_023037 NM_023037 10129 -0.70 1.50E-04 DECR1 202447 at NM 001359 NM 001359 1666 -0.70 7.20E-03 USP38 223288_at AW977401 NM_032557 84640 -0.70 6.63E-03 RAB4A 203581 at BC002438 NM_004578 5867 -0.70 1.97E-03 PLEKHA3 223370 at AF286162 NM_019091 65977 -0.70 4.19E-03 AFFX-BioC-3 i\FFX-BioC-3_a AFFX-BioC-3 — — -0.70 1.62E-03 PPID 204185_x_at NM_005038 NM_005038 5481 -0.70 5.63E-04 PAM 214620_x_at BF038548 NM_000919 NM 138766 NM 138821 NM_138822 5066 -0.70 2.61 E-04 ARL7 202207_at BG435404 NM 005737 10123 -0.70 1.62E-03 DNAJC6 204720 s at AV729634 NM_014787 9829 -0.70 2.00E-04 SYNCOILIN 225396_at AI928212 NM 030786 81493 -0.70 5.70E-03 ANXA5 200782_at NM_001154 NM_001154 308 -0.70 5.88E-03 MGC14595 238561_s_at BE542779 NM_032334 84294 -0.70 6.39E-05 SELM 226051 at BF973568 NM_080430 140606 -0.70 4.02E-03 AA489100 228390_at AA489100 — — -0.70 5.43E-03 AA740675 244032 at AA740675 — — -0.70 9.18E-04 ALDH5A1 203608_at AL031230 NM_001080 NM_170740 7915 -0.69 3.13E-03 BE646451 235893_at BE646451 — — -0.69 9.91 E-03 DUSP7 213848_at AI655015 NM_001947 1849 -0.69 9.16E-03 MGC42174 242539_at AW665509 NM 152383 129563 -0.69 2.67E-03 FBX025 225591_at AA749085 NM 012173 NM_183420 NM_183421 26260 -0.69 4.48E-03 CNOT6L 226153 s at AW514857 NM 144571 246175 -0.69 4.37E-04 NPR2 204310_s_at NM_003995 NM 000907 NM 003995 4882 -0.69 5.97E-03 DEPDC6 218858 at NM_022783 NM_022783 64798 -0.69 2.62E-03 GARNL4 213280 at AK000478 NM 015085 23108 -0.69 5.49E-03 ANKH 223093_at T99215 NM_054027 56172 -0.69 3.95E-03 NUDT11 219855_at NM_018159 NM 018159 55190 -0.69 1.75E-03 IFNAR2 204785_x_at NM_000874 NM_000874 NM 207584 NM 207585 3455 -0.69 7.44E-05 383 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays ZNF148 235166_at T08836 NMJ321964 7707 -0.68 9.51 E-03 LOC377064 229986_at AW205616 XM_496648 377064 -0.68 3.34E-03 RSL1D1 212019 at AK025446 NM 015659 26156 -0.68 2.80E-03 C10orf22 212500_at AL049319 NM_032804 84890 -0.68 8.22E-03 DAZAP2 214334_x_at N34846 NM 014764 9802 -0.68 2.12E-03 WDFY3 212606_at AL536319 NM_014991 NM_178583 NM_178585 23001 -0.68 8.12E-05 PTPN23 223150_s_at AF290614 NM_015466 25930 -0.68 2.67E-03 SNAP91 204953_at NM_014841 NM_014841 9892 -0.68 1.47E-04 DSU 232682_at BG167210 NM 018000 55686 -0.68 2.28E-04 ZNF490 231988_x_at AB033024 NM_020714 57474 -0.68 8.43E-04 -X-r2-Ec-bioD-X-r2-Ec-bioD-2 ^FFX-r2-Ec-bioD-: — — -0.68 8.66E-03 ZBTB1 242258_at AW168154 NM_014950 22890 -0.68 7.93 E-03 -X-r2-Ec-bioB -X-r2-Ec-bioB-2!VFFX-r2-Ec-bioB-i — — -0.68 4.88E-03 DLG3 212727_at AB033058 NM 021120 1741 -0.68 2.75E-05 P15RS 225953 at AI684281 NM 018170 55197 -0.68 4.56E-03 LRBA 212692_s_at W60686 NM 006726 987 -0.68 1.07E-06 ZBED3 228402 at AI679968 NM 032367 84327 -0.68 2.51 E-03 DNASE1L1 203912_s_at NM_006730 NM_00100993 2 NM_00100993 3 NM_00100993 4 NM 006730 1774 -0.68 4.97E-03 ABR 212895_s_at AL527773 NM 001092 NM_021962 29 -0.68 9.54E-04 AF147335 1557518_a_at AF147335 — . — -0.68 3.85E-03 HNRPD 229129_at Al948456 NM 00100381 0 NM 002138 NM_031369 NM 031370 3184 -0.68 9.99E-03 LOC387895 243905 at AI652676 XM_373553 387895 -0.68 4.51E-03 PLCE1 205111_s_at NM 016341 NM 016341 51196 -0.68 3.83E-04 ANTXR2 228573_at BE673665 NM_058172 118429 -0.68 3.75E-03 MGC48625 1569039 s at BC029855 NM_182609 342926 -0.68 2.30E-04 MGC47869 229888_at AA861435 NM 175874 144608 -0.68 3.57E-03 ZNF197 233070_at AL117657 NM 006991 10168 -0.68 1.50E-04 DYRK2 202969_at AI216690 NM_003583 NM_006482 8445 -0.68 3.24E-03 LOC285513 1556697_at AI819722 NM 198281 285513 -0.67 1.21E-05 CRYZL1 219767_s_at NM 005111 NM 005111 NM_145311 NM_145858 9946 -0.67 6.15E-03 AA935461 242579_at AA935461 — — -0.67 3.50E-04 FLJ30990 1554588_a_at BC033795 NM 152517 150737 -0.67 7.72E-03 RIPK5 229017_s_at N31717 NM 015375 NM_199462 25778 -0.67 5.71 E-03 N63920 226179_at N63920 — — -0.67 9.08E-03 NM_022335 206936_x_at NM 022335 — — -0.67 1.76E-04 SLC25A12 203340_s_at NM_003705 NM 003705 8604 -0.67 6.85E-03 MED28 218438_s_at NM 025205 NM 025205 80306 -0.67 1.38E-03 RAD52 236042_at AI700506 NM 002879 NM 134422 NM 134423 NM 134424 5893 -0.67 1.28E-04 384 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays EPHA8 231796_at AL035703 NM_00100694 3 NM 020526 2046 -0.67 5.79E-03 DSU 219648_at NM_018000 NM_018000 55686 -0.67 3.20E-04 AA843541 229710_at AA843541 — — -0.67 9.95E-04 AA461190 244294_at AA461190 — — -0.67 9.45E-03 JAM2 219213_at NM_021219 NM_021219 58494 -0.66 1.52E-03 CDK6 224847_at AW051349 NM_001259 1021 -0.66 3.40E-03 MCM3APAS 1560542_at BC016306 — 114044 -0.66 9.71 E-03 LOC157657 244569_at N92755 NM_177965 157657 -0.66 1.12E-04 LOC286334 226590 at AA910497 — 286334 -0.66 5.51 E-03 C3orf6 225331_at BF941088 NM_174908 NM_178335 152137 -0.66 4.75E-03 KIAA1579 231851_at AL359613 NM 018211 55225 -0.66 4.44E-03 KIAA0241 212474 at D87682 NM 015060 23080 -0.66 2.52E-03 TFAP2B 214451_at NMJD03221 NM_003221 7021 -0.66 6.69E-04 AI218542 236089_at AI218542 — — -0.66 8.36E-03 EEF2K 225546 at W68180 NM 013302 29904 -0.66 1.99E-03 KIAA0999 204157 s at NM 025164 NM 025164 23387 -0.65 3.68E-05 FXR1 201637_s_at NM 005087 NM 005087 8087 -0.65 8.08E-03 AA406435 230747_s_at AA406435 — — -0.65 6.70E-03 ZNF626 235687_at AA908777 NM_145297 199777 -0.65 5.29E-03 KIAA0582 212675 s at AB011154 NM 015147 23177 -0.65 7.85E-03 DTNA 227084_at AW339310 NM_001390 NM 001391 NM 001392 NM_032975 NM_032978 NM_032979 NM 032980 NM 032981 1837 -0.65 3.98E-03 C9orf109 229059_at AI765785 XM_379665 286333 -0.65 1.91 E-03 TBC1D12 1557609_s_at AW188458 XM 051081 23232 -0.65 4.03E-03 LIN7C 223350_x_at N63709 NM_018362 55327 -0.65 3.22E-03 PIK3R2 1568629_s_at BC033311 NM_005027 5296 -0.65 7.91 E-05 AU151635 232111_at AU151635 — — -0.65 6.09E-04 NM_018678 220494 s at NM_018678 — — -0.65 4.32E-03 FAM8A1 203420 at NM 016255 NM_016255 51439 -0.65 8.87E-03 AL136588 223614_at AL136588 — — -0.65 3.95E-04 KIAA0179 212846 at AA811192 NM_015056 23076 -0.65 7.52E-03 BF509796 229318_at BF509796 — — -0.65 2.51 E-03 SEC31L1 200945_s_at NM_014933 NM 014933 NM_016211 22872 -0.65 8.63E-04 KIAA0711 204301_at NM 014867 NM_014867 9920 -0.65 1.44E-03 AW025141 228400_at AW025141 — — -0.64 6.23E-03 SERP1 235475 at AI580135 NM 014445 27230 -0.64 8.89E-03 C2orf32 226751_at AW193693 NM_015463 25927 -0.64 6.94E-04 KIAA1935 228336_at AW511595 XM_087672 114825 -0.64 2.59E-03 PDE4D 228962 at BF507941 NM 006203 5144 -0.64 2.48E-03 CDC14B 221556_at BF792631 NM 003671 NM_033331 NM_033332 8555 -0.64 2.02 E-03 FANCF 218689 at NM 022725 NM_022725 2188 -0.64 5.25E-03 BCAR3 204032_at NM_003567 NM_003567 8412 -0.64 3.94E-03 385 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays UBE2D3 200667_at BF448062 NM_003340 NM 181886 NM 181887 NM_181888 NM_181889 NM 181890 NM_181891 NM_181892 NM_181893 7323 -0.64 2.05E-03 MGC29463 238115_at T03492 NM_152686 202052 -0.64 4.51 E-03 AFFX-BioDn-5 vFFX-BioDn-5_£ AFFX-BioDn-5 — — -0.64 1.45E-03 TPD52 201690_s_at AA524023 NM_005079 7163 -0.64 8.25E-04 HPSE 222881_at AF155510 NM_006665 10855 -0.64 2.12E-03 MAN1A2 217920 at H97940 NM 006699 10905 -0.64 2.61 E-03 HRMT1L1 221564_at AL570294 NM_001535 NM_206962 3275 -0.64 5.66E-03 C22orf9 227144_at AA476916 NM_00100988 0 NM_015264 23313 -0.63 8.11 E-03 RGS12 1555022_at AF464736 NM_002926 NM_198227 NM_198229 NM_198230 NM_198430 NM_198432 NM_198587 6002 -0.63 3.89E-05 FFX-r2-Ec-bioD-X-r2-Ec-bioD-£\FFX-r2-Ec-bioD-i 1 ___ — -0.63 3.52E-03 AI766065 224647_at AI766065 — — -0.63 4.41 E-04 TDRD3 1569069_s_at BC020604 NM_030794 81550 -0.63 4.16E-03 SOS1 227426_at AV702692 NM 005633 6654 -0.63 3.92E-03 SMAD2 203077_s_at NM_005901 NM 00100365 2 NM 005901 4087 -0.63 7.24E-03 MED28 228992 at BF064162 NM 025205 80306 -0.63 2.06E-05 BICD1 1556051_a_at CA777994 NM_00100339 8 NM 001714 636 -0.63 6.24E-04 GOLPH3L 218361 at NM_018178 NM 018178 55204 -0.63 9.58E-04 MBNL1 201152_s_at N31913 NM_021038 NM 207292 NM_207293 NM_207294 NM_207295 NM_207296 NM 207297 4154 -0.63 4.11E-05 LZTFL1 222632_s_at AA843132 NM_020347 54585 -0.63 4.52E-04 RUFY1 233380 s at AA429145 NM 025158 80230 -0.63 8.27E-04 RBM18 238963_at BG106093 NM 033117 92400 -0.63 1.19E-03 UBXD1 220757_s_at NM 025241 NM 025241 80700 -0.63 9.92E-04 NCAM1 227394_at W94001 NM 000615 NM_181351 4684 -0.63 2.48E-03 C14orf4 223474 at AI932310 NM 024496 64207 -0.63 3.20E-04 PEX11A 205161 s at NM 003847 NM_003847 8800 -0.63 1.24E-04 BF692729 1558044_s_at BF692729 — — -0.62 1.31 E-03 AW290940 226773_at AW290940 — — -0.62 4.57E-04 DDHD1 225970 at AA029818 NM_030637 80821 -0.62 2.27E-03 C9orf10OS 239391 at AA195528 NM_198841 158293 -0.62 7.21 E-03 AI694544 235215 at AI694544 — ... -0.62 3.54E-03 386 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al„ Cells Useful for Immuno-Based BoNT/A Activity Assays TMEM45A 219410 at NM_018004 NM_018004 55076 -0.62 1.39E-03 CXorf38 228700 at AA063608 NM 144970 159013 -0.62 5.45E-03 LOC57149 203897 at BE963444 NM 020424 57149 -0.62 2.10E-03 LOC54499 208715_at BF002031 NM_019026 54499 -0.62 1.19E-03 SCAMP 1 212425_at AL049223 NM_004866 NM_052822 9522 -0.62 8.35E-03 IMPACT 222698_s_at AF208694 NM_018439 55364 -0.62 7.05E-03 TRPM1 243741_at AW665484 NM_002420 4308 -0.62 7.71 E-03 TMAP1 227326_at BE966768 NM 00100852 8 NM 00100852 9 NM_198530 439921 -0.62 4.82E-03 NLK 222589 at AI967933 NM 016231 51701 -0.62 9.48E-03 KIAA0280 36612 at D87470 XM 370635 23201 -0.62 7.88E-03 SYNC RIP 236146_at BF593158 NM 006372 10492 -0.62 2.46E-04 NAV1 224772_at AB032977 NM_020443 89796 -0.61 1.83E-03 AI216347 242087 x at AI216347 — — -0.61 7.98E-03 RTN4R 228550_at NM_023004 NM 023004 65078 -0.61 2.34E-03 TLOC1 225352_at AI763287 NM_003262 7095 -0.61 1.21 E-03 AL137344 232390_at AL137344 — — -0.61 8.75E-06 COMMD2 226910_at AW008502 NM_016094 51122 -0.61 9.68E-03 LOC57228 209679_s_at BC003379 NM_020467 57228 -0.61 9.52E-03 AW873330 225674_at AW873330 — — -0.61 7.46E-03 RAD50 208393_s_at NM_005732 NM_005732 NM_133482 10111 -0.61 2.10E-06 ZFY 230760_at BF592062 NM_003411 7544 -0.61 8.36E-05 C21orf33 202217_at NM_004649 NM_004649 NM 198155 8209 -0.61 9.07E-03 PAM 212958_x_at AI022882 NM_000919 NM_138766 NM_138821 NM 138822 5066 -0.61 1.54E-03 PDCD2 204025_s_at NM_002598 NM 002598 NM_144781 5134 -0.61 4.97E-03 AHI1 221569_at AL136797 NM_017651 54806 -0.61 2.59E-03 TPD52 201689_s at BE974098 NM_005079 7163 -0.61 5.72E-03 AV721564 227620 at AV721564 — — -0.61 9.48E-03 ZNF540 DKFZp761D19 18 GAB1 229328_at T90358 NM_152606 XM_375608 163255 400692 -0.61 8.93E-03 226002_at AK022142 NM 002039 NM 207123 2549 -0.60 4.32E-04 R02709 242149_at R02709 — — -0.60 8.54E-03 DCX 204850_s_at NM_000555 NM_000555 NM_178151 NM_178152 NM 178153 1641 -0.60 4.23E-03 PPARG 208510_s_at NM_015869 NM 005037 NM_015869 NM_138711 NM_138712 5468 -0.60 1.82E-03 PCYOX1 225274_at BF247054 NM 016297 51449 -0.60 6.39E-03 M17S2 201384_s_at NM_005899 NM_005899 NM_031858 NM 031862 4077 -0.60 9.84E-04 KBTBD7 223412 at AL136782 NM_032138 84078 -0.60 3.40E-03 AK094546 1556205_at AK094546 — — -0.60 8.73E-03 387 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al„ Cells Useful for Immuno-Based BoNT/A Activity Assays GAJ 223700 at AY028916 NM 032117 84057 -0.60 2.55E-03 BACE1 222462_s_at AI653425 NM 012104 NM 138971 NM 138972 NM_138973 23621 -0.60 5.62E-04 RAB26 50965 at AI690165 NM 014353 25837 -0.60 2.77E-03 AGPAT4 228667_at AI733330 NM_020133 56895 -0.60 7.61 E-03 LOC134147 227522_at AA209487 NM_138809 134147 -0.60 9.04E-03 MRPS30 222275_at AI039469 NM_016640 10884 -0.60 1.13E-03 AV699883 230782_at AV699883 — — -0.60 1.72E-03 DJ 12208.2 227797 x at AI652464 NM 020466 57226 -0.60 5.64E-03 ULK2 204062_s_at BG526973 N M 014683 9706 -0.60 2.35E-03 AL552727 244080_at AL552727 — — -0.60 4.85E-03 DDEF1 224791 at AW513835 NM 018482 50807 -0.60 1.40E-04 TIAM1 213135 at U90902 NM_003253 7074 -0.60 7.17E-03 HOXC6 206858_s_at NM 004503 NM 004503 NM_153693 3223 -0.60 3.44E-03 POFUT2 209578_s_at BC000626 NM 015227 NM_133634 NM_133635 23275 -0.60 1.08E-03 ZFP36L2 201368_at U07802 NM_006887 678 -0.60 1.13E-03 BC016176 1561529 at BC016176 — — -0.60 5.78E-03 CNOT8 202163_s_at NM_004779 NM_004779 9337 -0.60 7.52E-03 LOC124220 228058_at AI559190 NM 145252 124220 -0.59 4.64E-03 ZC3HDC1 218543_s_at NM 022750 NM_022750 64761 -0.59 7.38E-03 KIAA1126 225598_at AB032952 XM_050325 57210 -0.59 1.48E-03 W26593 213048_s_at W26593 — — -0.59 5.40E-03 FLJ20534 218646_at NM_017867 NM_017867 54969 -0.59 1.34E-04 LOC126167 1560779_a_at AK092139 XM_058997 126167 -0.59 2.41 E-03 AA449838 241411 at AA449838 — — -0.59 3.04E-03 FLJ38451 235052_at AV758821 NM 175872 126375 -0.59 3.59E-03 MAP2 225540_at BF342661 NM 002374 NM 031845 NM 031846 NM 031847 4133 -0.59 2.90E-03 CPD 201941_at BE349147 NM_001304 1362 -0.59 3.19E-04 RP42 218583 s at NM_020640 NM 020640 54165 -0.59 3.27E-06 RBMX 213762 x at AI452524 NM 002139 27316 -0.59 2.27E-04 LRIG2 238653_at BF967997 NM014813 9860 -0.59 4.27E-03 BF431965 213567_at BF431965 — — -0.59 7.58E-03 TRIM23 204732_s_at AI021991 NM 001656 NM_033227 NM 033228 373 -0.59 9.14E-03 C9orf67 224506_s_at BC006362 NM_032728 84814 -0.58 1.45E-03 AB002295 204307 at AB002295 — — -0.58 2.09E-03 KIAA1546 227624_at AB046766 XM_042301 57667 -0.58 4.89E-07 PPM1A 227728_at AA886888 NM_021003 NM 177951 NM 177952 5494 -0.58 7.82E-03 ZNF148 239024_at AI478771 NM_021964 7707 -0.58 2.84E-04 MARCH-I 235385_at AI935334 NM_017923 55016 -0.58 6.65E-03 AB033091 225295 at AB033091 — — -0.58 3.88E-03 IRF2BP2 224570 s at AA166696 NM_182972 359948 -0.58 4.89E-04 D31763 231864_at D31763 — — -0.58 1.86E-03 LOC151146 227604_at BG292251 — 151146 -0.58 8.00E-03 388 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays UBE2D3 229355_at AU150386 NM_003340 NM 181886 NM 181887 NM_181888 NM_181889 NM 181890 NM 181891 NM_181892 NM 181893 7323 -0.58 6.55E-06 CUTL1 214743_at BE046521 NM 001913 NM 181500 NM_181552 1523 -0.58 3.01 E-04 LOC152485 228046_at AA741243 NM_178835 152485 -0.58 8.28E-03 CLPX 223507 at AL136922 NM 006660 10845 -0.58 6.77E-03 MAPKAP1 222426_at BG499947 NM_00100661 7 NM_00100661 8 NM_00100661 9 NM 00100662 0 NM 00100662 1 NM_024117 79109 -0.58 3.51 E-03 BRUNOL4 223654 s at BC004167 NM_020180 56853 -0.58 2.18E-03 ARFIP1 218230_at AL044651 NM_014447 27236 -0.58 3.04E-03 SEC5L1 226270 at AL562686 NM 018303 55770 -0.58 8.15E-06 389 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays

Table 11. Increased Gene Expression in Cell Lines H1 and BB10 vs. SiMa Cell Line in Differentiated State Using Microarray Analysis Representative RefSeq Entrez ene Symbol Probe Set ID Public ID Transcript ID Gene Log2 Ratio pvalue FZp667G211 214030_at BE501352 XM_376254 131544 5.13 6.09E-05 BF476109 1556300_s_at BF476109 — — 5.09 2.02E-05 H99792 225710 at H99792 — — 4.92 2.07E-08 SLITRK5 214930_at AW449813 NM 015567 26050 4.63 3.87E-06 DAZ1 207909_x_at U21663 NM 00100537 1617 4.60 2.31 E-03 DAZ3 5 57054 DAZ2 NM 00100578 57055 DAZ4 5 57135 NM_00100578 6 NM_004081 NM_020363 NM_020364 NM_020420 RGS5 218353_at NM 025226 NM 003617 8490 4.54 1.63E-03 SIM1 206876_at AL121948 NM 005068 6492 4.53 2.11E-04 KCTD12 212192 at AI718937 NM 138444 115207 4.51 4.17E-05 RGS5 1555725 a at AF493929 NM_003617 8490 4.49 3.25E-05 FLJ39639 243547_at BE176531 XM 370932 283876 4.37 2.87E-03 DAZ1 208282_x_at NM 020363 NM 00100537 1617 4.32 3.54E-03 DAZ3 5 57054 DAZ2 NM 00100578 57055 DAZ4 5 57135 NM_00100578 6 NM_004081 NM_020363 NM_020364 NM_020420 PCDH9 219737_s_at AI524125 NM_020403 5101 4.30 1.19E-03 NM_203487 RGS5 209071 s at AF159570 NM 003617 8490 4.10 1.32E-04 RGS5 209070_s_at AM 83997 NM_003617 8490 4.07 1.28E-04 )KFZp761O201 232313_at AL122107 XM_044062 92293 4.01 2.30E-06 MAB21L2 210302_s_at AF262032 NM_006439 10586 3.99 2.81 E-04 ALCAM 240655 at BE502785 NM 001627 214 3.98 3.07E-05 DAZ1 207912_s_at NM_004081 NM_00100537 1617 3.96 1.79E-03 DAZ3 5 57054 DAZ2 NM 00100578 57055 DAZ4 5 57135 NM_00100578 6 NM_004081 NM_020363 NM_020364 NM 020420 GRP 206326_at NM_002091 NM 002091 2922 3.94 1.52E-05 PDZRN3 233442_at AU147500 NM 015009 23024 3.92 2.66E-03 MAB21L1 206163_at NM 005584 NM_005584 4081 3.91 6.73E-06 TIMP3 201149_s_at U67195 NM_000362 7078 3.84 5.07E-03 TIMP3 201147 s at BF347089 NM 000362 7078 3.61 7.18E-03 PDZRN3 212915 at AL569804 NM_015009 23024 3.58 7.05E-03 390 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., etal., Cells Useful for Immuno-Based BoNT/A Activity Assays LOC440738 221697_at AF276659 NM_001004342 440738 3.54 3.13E-03 GNG11 204115 at NM 004126 NM 004126 2791 3.52 6.00E-04 PLK2 201939 at NM 006622 NM 006622 10769 3.49 8.48E-05 CXCR4 217028_at AJ224869 NM_00100854 n 7852 3.49 2.53E-05 u NM_003467 DLL1 224215_s_at AF196571 NM_005618 28514 3.40 1.98E-05 LOC340109 1557765_at BC039509 XM_379322 340109 3.33 4.27E-04 CCDC3 223316_at AL136562 NM 031455 83643 3.32 3.45E-05 P2RY5 218589 at NM_005767 NM 005767 10161 3.27 1.73E-03 QKI 212636_at AL031781 NM_006775 9444 3.23 3.28E-03 NM_206853 NM_206854 NM 206855 DAZ1 208281_x_at NM_020364 NM_00100537 1617 3.19 3.17E-03 DAZ3 5 57054 DAZ2 NM_00100578 57055 DAZ4 5 57135 NM_00100578 a 0 NM 004081 NM 020363 NM_020364 NM 020420 PCDH9 238919_at R49295 NM 020403 5101 3.15 4.07E-03 NM_203487 AI242023 240458_at AI242023 — — 3.11 1.45E-04 SLC4A11 223748_at AF336127 NM_032034 83959 3.10 1.45E-03 RPL10A 242188 at AI743332 NM 007104 4736 3.09 2.35E-03 POLQ 207746_at NM_014125 NM_006596 10721 3.07 7.89E-03 NM_199420 MGC24103 232568_at AU145658 — 158295 3.07 8.38E-03 SPAG6 210033_s_at AF079363 NM 012443 9576 3.06 1.67E-04 NM 172242 RNF182 230720_at AI884906 NM_152737 221687 3.05 5.00E-05 LOC440928 235147_at R56118 XM_498917 440928 3.04 2.36E-03 AL049260 216518_at AL049260 — ... 3.01 8.57E-03 ITGA6 201656 at NM_000210 NM 000210 3655 3.00 2.58E-04 KCTD12 212188_at AA551075 NM 138444 115207 2.98 5.67E-04 CXCR4 211919_s_at AF348491 NM_00100854 n 7852 2.98 7.80E-03 u NM_003467 NEGR1 243357_at AA115106 NM_173808 257194 2.98 6.99E-05 MGC34032 1569112_at AW020413 NM_152697 204962 2.94 4.27E-04 PTPRG 1569323 at BU853579 NM 002841 5793 2.92 3.90E-03 CXCR4 209201_x_at L01639 NM_00100854 π 7852 2.90 6.72E-03 u NM 003467 CBFA2T2 233243_at AU144676 NM 005093 9139 2.88 2.26E-03 NM 175864 391 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays DAZ1 DAZ3 DAZ2 DAZ4 216922_x_at AF271088 NM_00100537 5 NM_00100578 5 NM 00100578 6 NM_004081 NM_020363 NM_020364 NM 020420 1617 57054 57055 57135 2.88 7.32E-03 CGNL1 225817_at AB051536 NM_032866 84952 2.86 3.83E-03 FBXL7 241457_at AI821935 NM_012304 23194 2.84 1.42E-03 TIMP3 201148 s at AW338933 NM_000362 7078 2.79 6.12E-03 BNC2 233036 at AU146418 NM 017637 54796 2.78 9.59E-03 EDG2 204036_at AW269335 NM_001401 NM_057159 1902 2.73 5.34E-03 BE674460 237849 at BE674460 — — 2.73 7.55E-03 MAB21L2 210303 at AF262032 NM 006439 10586 2.69 1.03E-03 PDE5A 227088_at BF221547 NM_001083 NM_033430 NM 033431 NM_033437 8654 2.65 4.68E-03 BC043430 1558714_at BC043430 — — 2.65 4.03E-03 AA699443 241838_at AA699443 — — 2.64 9.15E-04 AL049337 215768 at AL049337 — — 2.62 9.86E-03 RASEF 1553986 at BC023566 NM 152573 158158 2.61 4.66E-04 PTGFRN 224937_at BF311866 NM_020440 5738 2.61 1.34E-06 AK025909 233814_at AK025909 — — 2.60 1.65E-03 CPVL 208146_s_at NM_031311 NM 019029 NM_031311 54504 2.59 5.34E-04 TRIM36 219736 at NM_018700 NM_018700 55521 2.59 6.52E-04 AI377043 230722_at AI377043 — — 2.58 7.06E-03 SLAC2-B 214734 at AB014524 NM_015065 23086 2.58 1.44E-04 AI077566 243994_at AI077566 — — 2.57 2.62E-03 EFNA5 1559360 at AL833045 NM 001962 1946 2.53 7.18E-04 BE464799 214036 at BE464799 — — 2.53 1.16E-03 MSN 200600_at NM 002444 NM 002444 4478 2.52 1.01E-06 RAD23B 214422_at T93562 NM_002874 5887 2.52 2.47E-03 TULP4 232372_at AL157491 NM_00100746 6 NM 020245 56995 2.51 4.65E-03 SCN7A 239984_at AI333640 NM_002976 6332 2.51 8.48E-03 ITGA6 215177 s at AV733308 NM_000210 3655 2.50 6.62E-04 NFIB 211466 at U70862 NM 005596 4781 2.50 1.09E-05 EML1 204797_s_at NM_004434 NM_00100870 7 NM_004434 2009 2.50 1.46E-03 BNC2 220272 at NM 017637 NM_017637 54796 2.49 3.27E-04 BE348318 236167_at BE348318 — — 2.49 5.60E-03 AW963185 241700_at AW963185 — — 2.47 1.92E-04 ENC1 201340 s at AF010314 NM 003633 8507 2.47 8.66E-03 RBMS3 233608 at AU146417 NM_00100379 2 27303 2.44 5.92E-03 NM_00100379 3 NM 014483 392 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays DACH1 1567101_at AF147347 NM_004392 NM 080759 NM_080760 1602 2.42 9.28E-03 AA554772 241391_at AA654772 — — 2.41 7.59E-03 BG400570 1565689_at BG400570 ... — 2.41 6.41 E-03 PIAS1 222371_at Al 732802 NM_016166 8554 2.40 3.91 E-03 EDD 232264_at AK022204 NM_015902 51366 2.40 1.41 E-03 NOL7 242143_at BE674964 NM_016167 51406 2.39 4.55E-03 U80755 243820_at U80755 — — 2.39 2.59E-03 ASCL1 209985_s_at BE797438 NM_004316 429 2.37 8.08E-03 AW052186 239942 at AW052186 — — 2.37 9.33E-03 THRAP2 238883_at AW975051 NM_015335 23389 2.37 9.49E-03 ROB02 226766_at AB046788 XM_031246 6092 2.36 7.82E-03 INA 230859_at BF111276 NM_032727 9118 2.36 2.50E-05 CHC1L 230292 at AA868809 NM 001268 1102 2.36 6.84E-03 CHRNA7 CHRFAM7A 210123_s_at U62436 NM_000746 NM 139320 NM 148911 1139 89832 2.33 2.81 E-03 ARID1B 240008_at Al 955765 NM 017519 NM 020732 NM_175863 57492 2.32 7.87E-03 SSH2 230970_at AA975530 NM_033389 85464 2.29 6.93E-03 BE670307 227955 s at BE670307 — — 2.28 5.03E-04 EB-1 227441_s_at AW005572 NM_020140 NM_152788 NM_181670 56899 2.28 6.31 E-03 GNAI1 209576_at AL049933 NM 002069 2770 2.27 8.26E-06 PIAS1 1559156_at BC036508 NM_016166 8554 2.27 5.54E-03 CUGBP2 202158_s_at NM 006561 NM_006561 10659 2.26 8.77E-03 LOC441157 1558795 at AL833240 XM 499037 441157 2.25 6.17E-05 KIAA0265 238000_at BF195340 NM 014997 23008 2.23 9.27E-03 SOX2 213721_at L07335 NM 003106 6657 2.23 1.49E-03 ENC1 201341_at NM_003633 NM_003633 8507 2.23 8.95E-03 PLXNA2 222159 at AK023058 NM 025179 5362 2.21 5.06E-04 GNAI1 227692_at AU153866 NM_002069 2770 2.21 2.84E-06 NRXN1 209915_s_at AB035356 NM 004801 NM_138735 9378 2.21 3.08E-03 OLFML3 218162 at NM 020190 NM_020190 56944 2.19 8.33E-04 CBLB 233614_at AU145361 NM_170662 868 2.19 8.28E-03 CG012 215318_at AL049782 — 116829 2.19 4.30E-03 SESN3 235150_at AW376955 NM 144665 143686 2.18 1.58E-03 SOX2 228038 at AI669815 NM 003106 6657 2.18 1.19E-03 C1orf43 1555225_at BC008306 NM_015449 NM_138740 25912 2.17 1.21 E-05 SPAG6 210032_s_at AI651156 NM 012443 NM_172242 9576 2.16 1.98E-03 ASCL1 209987_s_at BC002341 NM_004316 429 2.15 4.18E-03 RASEF 235144_at AA826324 NM 152573 158158 2.14 2.84E-04 OSBPL3 209626_s_at AI202969 NM 015550 NM 145320 26031 2.14 4.14E-04 NM_145321 NM_145322 NM_145323 NM 145324 393 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays HGF 210997_at M77227 NM 000601 NM 00101093 1 NM 00101093 2 NM 00101093 3 NM_00101093 4 3082 2.13 3.66E-03 SLC7A2 225516_at AA876372 NM 00100853 6542 2.13 9.92E-04 9 NM 003046 EDG3 228176_at AA534817 NM 005226 1903 2.13 4.95E-04 EFNB2 202668_at BF001670 NM_004093 1948 2.13 5.45E-03 BF513404 239469_at BF513404 — — 2.12 1.51E-03 LRRC16 219573_at NM 017640 NM_017640 55604 2.11 8.45E-04 ARHGAP20 228368_at Al936560 NM_020809 57569 2.11 3.27E-04 ZFHX4 219779_at NM_024721 NM_024721 79776 2.10 3.71 E-04 AW953794 230968_at AW953794 — — 2.09 6.43E-03 LOC23117 238341_at BF677084 XM_290670 23117 2.09 3.42E-03 AK022040 233445 at AK022040 — — 2.08 3.85E-03 TOP1 238988_at Al 863675 NM_003286 7150 2.08 5.99E-03 ALCAM 1569362_at BC041127 NM_001627 214 2.07 5.59E-04 XP01 1560386_at BC041658 NM 003400 7514 2.07 4.79E-04 SPAG9 1554543_at BC007524 NM 003971 NM_172345 9043 2.07 1.57E-04 RAF1 244373_at Al 740571 NM_002880 5894 2.07 9.16E-04 GFRA2 205721_at U97145 NM 001495 2675 2.06 4.42E-03 CXCL12 209687_at U19495 NM_000609 NM_199168 6387 2.04 2.46E-04 MGC34032 235763_at AA001450 NM_152697 204962 2.04 3.86E-03 AI671885 230494 at AI671885 XM 379123 400999 2.01 7.81E-03 GPR125 1569542 at BC020926 NM_145290 166647 1.99 8.83E-03 BF057073 231310_at BF057073 ... — 1.97 9.44E-04 PGAP1 233479_at AU148008 NM_024989 80055 1.95 7.98E-03 LOC440265 1569476 at BC033224 XM 378506 440265 1.95 1.83E-03 TFPI2 209278 s at L27624 NM_006528 7980 1.95 3.05E-03 KIAA1713 233536_at Al202664 XM_290811 80816 1.94 5.70E-05 H37807 241060_x_at H37807 — — 1.94 5.73E-03 AA417878 243463 s at AA417878 — — 1.93 4.35E-04 ZNF537 223392 s at BF510588 NM 020856 57616 1.93 5.36E-04 PTPRG 204944_at NM 002841 NM 002841 5793 1.93 4.06E-07 MAOA 204388_s_at NM_000240 NM_000240 4128 1.92 2.34E-03 TFPI2 209277_at AL574096 NM 006528 7980 1.91 9.47E-03 ASCL1 213768 s at AW950513 NM 004316 429 1.91 9.81 E-03 GFM1 232295_at AK000780 NM_024996 85476 1.90 3.91 E-03 AF131796 231916_at AF131796 — — 1.90 9.65E-06 SLC03A1 219229_at NM 013272 NM 013272 28232 1.89 6.98E-07 FLJ34154 1561130 at AF086006 NM_173813 283450 1.89 4.96E-03 MSI2 239232_at AA521410 NM_138962 NM_170721 124540 1.87 7.62E-03 MAOA 212741 at AA923354 NM 000240 4128 1.87 3.66E-04 PRKCBP1 207130_at NM_018634 NM_012408 NM 183047 NM_183048 23613 1.87 5.52E-03 PPP3R1 1565811 at BC033945 NM 000945 5534 1.86 2.12E-03 CUGBP2 202157_s_at U69546 NM_006561 10659 1.86 4.76E-03 AW024890 229942_at AW024890 — — 1.86 2.32 E-04 394 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al„ Cells Useful for Immuno-Based BoNT/A Activity Assays NOS1 239132_at BE299830 NM_000620 4842 1.85 4.05E-05 AI733341 240911 at AI733341 — — 1.83 2.70E-06 MAOA 204389_at NM 000240 NM_000240 4128 1.83 5.67E-03 AI919519 235092_at AI919519 — — 1.83 1.25E-03 HGF 210755_at U46010 NM_000601 NM 00101093 3082 1.83 4.16E-03 1 NM 00101093 2 NM_00101093 3 NM_00101093 4 EB-1 227439_at AI806510 NM_020140 NM 152788 NM_181670 56899 1.83 4.67E-03 NRG3 229233_at H05240 NM_00101084£ 10718 1.81 5.10E-03 IREB2 1563130_a_at AL109710 NM 004136 3658 1.81 4.45E-05 ASCL1 209988_s_at BC001638 NM_004316 429 1.81 9.72E-03 BF509781 238970_at BF509781 — — 1.81 5.78E-03 AI651786 237945_at AI651786 — — 1.80 9.11E-04 AW206536 243470_at AW206536 — — 1.79 9.87E-03 CAS1 239545 at AI335004 NM 022900 64921 1.78 2.35E-04 FLJ11259 218627_at NM_018370 NM_018370 55332 1.78 3.98E-03 TPBG 203476_at NM_006670 NM 006670 7162 1.78 3.60E-03 IGSF4 244345 at AI627453 NM 014333 23705 1.78 1.19E-03 LOC441157 1558796_a_at AL833240 XM_499037 441157 1.78 6.11E-04 C10orf18 216211_at AL049233 XM_374765 54906 1.78 5.69E-03 TRIM68 219405_at NM 018073 NM_018073 55128 1.77 9.35E-03 NM 018616 220702 at NM_018616 — — 1 76 8.03E-03 SF1 210172_at D26121 NM_004630 NM 201995 NM_201997 NM_201998 7536 1.76 6.92E-03 AM 40305 228849_at AM 40305 — — 1.73 4.71 E-03 BE856929 239349_at BE856929 — — 1.73 8.07E-03 CDC23 223651_x_at BC005258 NM_004661 8697 1.73 3.36E-03 BG542611 1556277 a at BG542611 — — 1.73 3.65E-03 LOC253981 226430_at Al394438 — 253981 1.72 2.43E-04 FNDC5 226096_at Al760132 NM 153756 252995 1.72 6.85E-03 VRK1 241737 x at T89693 NM 003384 7443 1.72 8.45E-04 PDE8B 243590 at AA860184 NM 003719 8622 1.71 3.11 E-03 SESN3 225123_at BE883841 NM_144665 143686 1.71 4.09E-04 MAK3 244341_at AA827728 NM_025146 80218 1.71 1.72E-03 FLJ35740 244297_at Al806762 NMJ47195 253650 1.70 9.74E-03 THOC3 236149 at AA502999 NM 032361 84321 1.69 6.40E-03 INSM1 206502_s_at NM_002196 NM_002196 3642 1.69 4.60E-03 SESN3 242899_at N78412 NM_144665 143686 1.69 1.78E-03 PTGFRN 224950 at BF476250 NM_020440 5738 1.69 3.70E-03 HIC2 1559600 at AL831831 NM_015094 23119 1.69 1.03E-03 AI023295 237600_at AI023295 — — 1.67 3.22E-03 GLMN 236924_at AA814383 NM_007070 NM_053274 11146 1.67 2.06E-03 N50083 229110 at N50083 — — 1.67 1.06E-03 BG542645 242793_at BG542645 — — 1.66 9.11 E-03 FLJ37266 228973_at AA057445 NM_175892 283225 1.65 3.82E-03 AK022258 233286 at AK022258 — — 1.64 4.08E-03 FNDC5 226097_at AI686488 NM_153756 252995 1.64 5.89E-03 395 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays JJAZ1 1566191_at AI907884 NM 015355 23512 1.63 6.56E-03 CNTN1 227202_at AW072790 NM 001843 NM_175038 1272 1.63 3.78E-03 MYLIP 228098_s_at AW292746 NM_013262 29116 1.63 2.87E-04 NM 024972 220898_at NM_024972 — — 1.63 5.35E-03 AL036662 235984_at AL036662 — — 1.62 1.89E-04 TIA1 1558922_at CA776505 NM_022037 NM_022173 7072 1.62 3.98E-03 MY06 203216_s_at NM_004999 NM 004999 4646 1.62 5.80E-04 ZNF537 223393 s at AL136805 NM 020856 57616 1.62 7.69E-04 DNAPTP6 244597_at AA701247 NM_015535 26010 1.61 2.65E-03 PIP5K1A 235646_at BF515595 NM 003557 8394 1.61 1 66E-03 ANAPC7 225521_at AL137586 NM_016238 51434 1.61 5.35E-03 AF5Q31 232865 at N59653 NM_014423 27125 1.60 2.42E-04 C2orf31 221245 s at NM_030804 — 81561 1.60 3.45E-03 FAM55C 243011_at BF317081 NM 145037 91775 1.59 1.18E-03 LHFPL2 212658_at N66633 NM_005779 10184 1.59 1.64E-03 PSCD3 243752 s at Al 870144 NM 004227 9265 1.59 2.84E-03 LOC90701 235676_at BF055352 NM_033280 90701 1.59 6.05E-03 SMAD4 1565703_at AL832789 NM 005359 4089 1.59 3.91 E-03 PITPNB 242074_at AA833902 NM 012399 23760 1.58 1.84E-03 DKFZp761D221 1569603_at BC020900 NM 032291 84251 1.57 3.47E-03 MINA 213189_at BE966695 NM_032778 NM_153182 84864 1.57 9.86E-05 YEATS2 236462_at AA742310 NM 018023 55689 1.57 6.12E-04 ARIH1 242431_at AI656728 NM 005744 25820 1.56 7.68E-03 XP01 235927_at BE350122 NM_003400 7514 1.56 1 83E-05 SPON1 213994_s_at AI885290 NM_006108 10418 1.55 3.33E-03 SIMP 238303_at AW070371 NM 178862 201595 1.55 2.24E-03 KLF12 243089_at AA551114 NM 007249 NM_016285 11278 1.55 7.90E-03 MAK3 231199_at AA701676 NM_025146 80218 1.55 2.30E-03 JARID2 232835_at AA533080 NM_004973 3720 1.55 2.53E-03 H93038 241574_s_at H93038 — ... 1.54 2.24E-03 TGFBR1 236561_at AV700621 NM_004612 7046 1.54 4.78E-03 PRSS12 213802_at AI810767 NM 003619 8492 1.53 6.28E-03 PLCL2 213309_at AL117515 NM 015184 23228 1.52 6.87E-03 PIAS1 1558418 at BC017507 NM 016166 8554 1.52 2.09E-03 USP48 229812_at BE645018 NM 032236 84196 1.51 3.09E-05 SPOCK 202363_at AF231124 NM 004598 6695 1.51 5.55E-05 MLL3 244010_at AI057455 NM 021230 NM 170606 58508 1.50 4.50E-03 STRA6 1569335_a_at BC015881 NM_022369 64220 1.50 2.05E-03 UCHL1 1555834_at AW974143 NM_004181 7345 1.50 5.86E-03 AK025064 215221 at AK025064 — — 1.49 5.96E-03 MINA 213188_s_at AI823896 NM_032778 NMJ53182 84864 1.48 4.75E-05 PSME4 237180_at T97717 NM 014614 23198 1.48 3.52E-03 SLC4A11 233550_s_at AL109976 NM_032034 83959 1.48 5.66E-03 H04482 243287 s at H04482 — ... 1.48 5.28E-03 REPS1 215201_at AW166925 NM 031922 85021 1.48 5.00E-03 OAZIN 240231_at AI742383 NM_015878 NM 148174 51582 1.47 6.87E-03 CBLB 227900 at AV701750 NM_170662 868 1.47 7.93E-03 SLC17A6 220551_at NM_020346 NM 020346 57084 1.47 4.11E-04 CUGBP2 202156_s_at N36839 NM_006561 10659 1.47 2.41E-03 R76828 1558877_at R76828 — — 1.46 4.33E-04 C9orf102 1557164_a_at BM683657 NM_020207 56959 1.46 2.47E-03 396 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al„ Cells Useful for Immuno-Based BoNT/A Activity Assays CLSTN2 219414_at NM_022131 NM 022131 64084 1.46 5.74E-03 FAM19A4 242348_at AA757457 NM_00100552 7 NM_182522 151647 1.45 2.73E-05 HTR2B 206638 at NM 000867 NM_000867 3357 1.44 5.90E-03 AW197616 230787_at AW197616 — ... 1.44 1.22E-03 BC035170 1561079_at BC035170 — ... 1.44 4.66E-03 CUGBP2 1557422_at R49146 NM_006561 10659 1.44 7.71 E-03 LCRISP1 223475_at AF142573 NM_031461 83690 1.44 3.45E-03 SNCAIP 219511 s at NM 005460 NM 005460 9627 1.44 9.60E-03 RNF34 236288_at AW572402 NM_025126 NM_194271 80196 1.44 1.55E-03 ALCAM 201951_at BF242905 NM 001627 214 1.44 1.25E-03 FGD6 1555137 a at BC013319 NM_018351 55785 1.43 8.61 E-03 AI821477 235985_at AI821477 — ... 1.43 8.29E-04 SRPK2 239811_at BF954306 NM_182691 NM 182692 6733 1.43 2.17E-03 CNTN1 227209_at AI091445 NM 001843 NM 175038 1272 1.43 6.48E-03 PDLIM5 213684_s_at BF671400 NM 00101151 3 NM_00101151 4 NM_00101151 5 NM_00101151 6 NM_006457 10611 1.43 4.72E-05 FLJ11710 244646 at AW972881 — 79904 1.43 6.04E-03 MAPRE2 1564733_at BC013931 NM_014268 10982 1.43 4.15E-03 DST 1558019_at BC020911 NM_001723 NM 015548 NM 020388 NM_183380 667 1.42 5.60E-03 SCC-112 241798_at AI339930 NM 015200 23244 1.42 4.68E-03 SPON1 209436_at AB018305 NM 006108 10418 1.41 1.28E-03 PPP3R1 241786 at AI380514 NM 000945 5534 1.41 8.09E-03 ARID1B 1556818_at BE671639 NM_017519 NM 020732 NM 175863 57492 1.40 1.56E-03 ZA20D1 238994 at AW022496 NM 020205 56957 1.40 1.24E-03 HIAT1 242374_at AA747563 NM 033055 64645 1.40 9.78E-04 ZNF503 227195_at AA603467 NM 032772 84858 1.40 1.14E-04 SMARCC2 1561973_at AL833124 NM 003075 NM_139067 6601 1.39 4.39E-03 ZNF215 220214_at NM_013250 NM 013250 7762 1.39 5.26E-03 KIAA0318 238817_at BF063412 NM_015347 23504 1.39 3.46E-03 RAP80 233596 at AF113675 NM 016290 51720 1.38 8.59E-03 ACY1L2 225421 at AI654133 NM 001010853 135293 1.37 9.04E-04 UBE1C 1556338_at BM353142 NM 003968 NM 198195 NM 198197 9039 1.37 4.28E-03 RASEF 1553186 x at NM_152573 NM_152573 158158 1.37 6.41 E-03 MDN1 1569484_s_at AL603301 NM 014611 23195 1.37 1.48E-03 E2-230K 1554814_at BC007822 NM_022066 63893 1.36 5.24 E-03 ZFOC1 1558816 at BC037793 NM 152437 144348 1.35 1.76 E-03 CAPZA2 240146_at A W418562 NM_006136 830 1.35 1.22 E-03 DLEU2 215629_s_at AA905286 NM 006021 8847 1.35 3.10E-03 397 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays CLASP2 1558759_s_at AA310888 NM 015097 23122 1.34 2.92E-03 KIAA1545 1557539 at BC008052 XM 495939 57666 1.34 1 63E-03 FLJ45645 243038 at AW292769 NM 198557 375287 1.34 4.56E-03 MGC34032 1552782_at AK091400 NM_152697 204962 1.34 1.91E-03 ELOVL7 227180_at AW138767 XM_371740 79993 1.33 4.90E-04 FLJ12666 215029 at AL117451 NM_024595 79647 1.32 3.06E-03 AA156721 201952_at AA156721 — — 1.31 9.34E-05 IREB2 1555476_at BC017880 NM_004136 3658 1.31 1.01E-03 SCML1 235652_at Al431345 NM 006746 6322 1.31 1.08E-03 BTBD3 243462_s_at BF590303 NM 014962 NM_181443 22903 1.31 1.87E-03 LRRTM1 243330_at AW304000 NMJ78839 347730 1.30 7.44E-03 RNF159 241956_at Al 521883 NM 032373 84333 1.30 2.94E-03 L3MBTL 242637_at C14069 NM 015478 NM_032107 26013 1.30 2 01E-03 LRRFIP2 232704_s_at AK025207 NM_006309 NM_017724 9209 1.29 1.87E-03 FLJ40773 1563933_a_at AK091691 NM_152666 200150 1.29 6.62E-03 N46436 1556568_a_at N46436 — — 1.29 3.59E-03 TRIM33 239716_at AA908970 NM_015906 NM_033020 51592 1.29 6.38E-03 RIP 1556088_at AK098491 NM_032308 84268 1.29 7.36E-04 AK098258 1564175_at AK098258 — — 1.29 9.36E-03 WWOX 1556595_at BQ025203 NM 016373 NM_018560 NM 130788 NM_130790 NM_130791 NM 130792 NM_130844 51741 1.29 9.57E-03 AW874669 239834_at AW874669 — — 1.29 1.39E-03 SYNCRIP 1555427_s_at AY034482 NM 006372 10492 1.28 1.39E-03 ZNF198 1569091_at BC039458 NM 003453 NM_197968 7750 1.28 9.19E-03 NOL7 244474_at BE549780 NM016167 51406 1.28 9.53E-03 C20orf23 232083_at AB046810 NM 024704 55614 1.28 6.84E-03 THRAP1 236978_at N51961 NM 005121 9969 1.28 5.36E-04 KIAA0217 241965 at BF589232 NM 015155 23185 1.28 7.35E-03 ASXL1 242439_s_at AI819150 NM_015338 171023 1.27 6.77E-03 ELOVL5 1566079_at AL833001 NM 021814 60481 1.27 1.08E-03 XP07 240168 at AA679589 NM 015024 23039 1.26 3.43E-03 IREB2 1563129 at AL109710 NM 004136 3658 1.26 2.34E-03 MMD 244523_at AW104453 NM_012329 23531 1.26 1.24E-06 RASEF 1553185_at NM_152573 NM_152573 158158 1.26 6.94E-03 ZA20D3 238812_at AA741296 NM 019006 54469 1.26 5.79E-03 ARFGEF1 236742_at AA132172 NM_006421 10565 1.25 6.55E-03 CUL3 242362_at AI797788 NM_003590 8452 1.25 5.38E-03 THOC4 226319_s_at AF047002 NM_005782 10189 1.25 5.54E-04 KLHL13 227875_at AB037730 NM 033495 90293 1.25 1.10E-05 TAF15 241885_at BF431050 NM_003487 NM_139215 8148 1.25 3.79E-03 C18965 242853_at C18965 XM 379243 401106 1.24 2.00E-03 EZH2 203358_s_at NM_004456 NM_004456 NM_152998 2146 1.24 4.13E-03 DLEU2 216870_x_at AF264787 NM_006021 8847 1.24 3.31 E-04 CABIN 1 1557581_x_at BC027347 NM_012295 23523 1.23 4.73E-03 HOXD4 205522 at NM 014621 NM_014621 3233 1.23 7.69E-03 AW157450 235716 at AW157450 — — 1.23 1.18E-03 398 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays TPARL 1560622_at AK000203 NM 018475 55858 1.23 3.89E-03 KDELC2 225128 at AL548941 NM_153705 143888 1.23 6.61E-04 PTPRK 203038_at NM_002844 NM_002844 5796 1.23 1.53E-03 SFRS2IP 1570507 at BC020736 NM 004719 9169 1.23 3.26E-03 ZNF326 227680_at Al 057121 NM 181781 NM_182975 NM_182976 284695 1.23 1.88E-03 NM_000575 208200_at NM_000575 — — 1.23 1.37E-03 GPI 232002 at AW843302 NM_000175 2821 1.23 2.05E-03 CAPN1 232012 at AV691296 NM 005186 823 1.22 3.25E-05 XP07 235796_at Al 927957 NM_015024 23039 1.22 8.08E-03 PITPNB 239978_at BF109370 NM 012399 23760 1.22 8.12E-03 DENR 238982 at AW665791 NM_003677 8562 1.22 1.47E-05 PFKFB3 202464 s at NM 004566 NM 004566 5209 1.22 3.62E-04 AA343057 234997_x_at AA343057 XM_496451 388760 1.21 9.45E-03 RB1CC1 237626_at AI801666 NM 014781 9821 1.21 5.81 E-03 NR2C1 210530 s at M21985 NM_003297 7181 1.21 1.06E-06 PLXNA2 213030 s at AI688418 NM_025179 5362 1.21 7.50E-03 AI857788 227126_at AI857788 — — 1.20 3.82E-05 MY06 210480_s_at U90236 NM 004999 4646 1.20 3.13E-03 TH1L 225865_x_at AJ238374 NM 016397 NM_198976 51497 1.20 3.35E-05 AL044078 221860_at AL044078 — — 1.19 1.28E-05 ZGPAT 221848_at AL121845 NM_032527 NM 181484 NM_181485 84619 1.19 7.13E-04 HGF 209960_at X16323 NM_000601 NM 00101093 3082 1.18 7.95E-03 1 NM_00101093 2 NM_00101093 3 NM_00101093 4 MGC47869 243056 at AI301111 NM_175874 144608 1.18 5.95E-03 NKTR 1557737_s_at AI880383 NM_005385 4820 1.18 1.36E-03 TRA2A 229574_at AI268231 NM 013293 29896 1.18 1.72E-03 ITGB5 201125_s_at NM_002213 NM_002213 3693 1.18 5.48E-04 ARIH1 1558710_at BI791845 NM_005744 25820 1.18 7.13E-03 GOLGA4 215203 at AW438464 NM 002078 2803 1.18 3.99E-03 BASP1 202391_at NM_006317 NM_006317 10409 1.18 3.05E-03 TM4SF14 223314_at BF025955 NM_030927 81619 1.18 1.52E-03 SYNCRIP 209025_s_at AF037448 NM 006372 10492 1.17 3.35E-03 TH1L 220607_x_at NM_016397 NM 016397 NM_198976 51497 1.15 2.89E-04 COBRA1 1556434_at BQ777552 NM_015456 25920 1.15 3.42E-03 SPATS2 1570130_at BC032441 NM_023071 65244 1.15 6.79E-03 GATA2 210358 x at BC002557 NM 032638 2624 1.15 2.50E-03 MYST3 242480_at AA868356 NM 006766 7994 1.15 9.06E-03 TH1L 225261_x_at AJ238376 NM_016397 NM 198976 51497 1.15 2.80E-05 PTK2 241387_at AW276701 NM_005607 NM_153831 5747 1.14 7.90E-03 C9orf39 1559005_s_at AK098502 NM 017738 54875 1.14 4.61 E-03 SFRS8 240078_at BG434474 NM_004592 NM_152235 6433 1.14 2.74E-03 TBC1D5 215612_at AU147983 NM 014744 9779 1.14 2.73E-03 399 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays TCTEL1 242109_at Al 038577 NM_006519 6993 1.14 1.48E-06 SMC5L1 1562948 at BC035661 NM 015110 23137 1.14 9.50E-03 PLS3 201215_at NM 005032 NM 005032 5358 1.13 6.23E-03 TM4SF14 221002_s_at NM_030927 NM 030927 81619 1.13 1 20E-03 SSB4 229929 at AL563476 NM_080862 92369 1.13 8.19E-03 THOC4 226320_at AF047002 NM 005782 10189 1.13 6.76E-04 EB-1 227440_at AW005572 NM_020140 56899 1.13 5.86E-03 PCBP2 213517_at AW103422 NM_152788 NM_181670 NM 005016 5094 1.13 2.39E-05 C9orf100 230522_s_at BG028209 NM_031989 NM 032818 84904 1.12 5.16E-03 BNC2 235723_at AA843242 NM 017637 54796 1.12 8.45E-03 UBE1C 1556339_a_at BM353142 NM 003968 9039 1.12 2.60E-03 C20orf58 228017 s at BF593263 NM_198195 NM_198197 NM_152864 128414 1.12 4.82E-03 AW978811 242080 at AW978811 — — 1.12 5.08E-03 EXT1 1564378 a at AK025101 NM_000127 2131 1.12 4.78E-03 KIAA1423 225127_at BF217531 XM_376550 57583 1.11 7.59E-05 CCAR1 236566 at AI291189 NM 018237 55749 1.11 5.91 E-03 SMG1 244766_at BG180003 NM_014006 23049 1.11 2.54E-03 KIAA0220 LOC440345 TMP21 239851 at AW629289 NM_015092 XM_496125 NM_006827 283846 440345 10972 1.11 9.85E-03 NOS1 207309 at NM_000620 NM_000620 4842 1.11 4.13E-03 EIF4ENIF1 242983_at AI806626 NM_019843 56478 1.11 2.41 E-03 ANAPC5 239651_at BE671583 NM_016237 51433 1.11 8.65E-03 FLJ20186 219646_at NM_017702 NM 017702 54849 1.11 7.86 E-03 BF196475 241529_at BF196475 NM_207514 1.11 6.33E-03 FRMD4A 208476_s_at NM_018027 NM_018027 55691 1.11 5.78E-03 SDHA 230077_at W90764 NM_004168 255812 1.10 2.82E-03 SDHAL2 CHCHD3 216170_at AK025271 XM_171032 NM017812 6389 54927 1.10 4.90E-03 SLC30A9 237051_at Al 890591 NM_006345 10463 1.10 3.32E-03 ANP32A 235954 at AA972597 NM_006305 8125 1.10 6.96E-04 AV752058 244574_at AV752058 — — 1.09 1.04E-03 CTGLF1 1565620 at BG621044 NM 133446 119016 1.09 8.36E-03 ZCCHC11 230713 at BF115786 NM_00100988 23318 1.09 6.14E-03 1 NM_00100988 2 KIAA1219 242233_at AI739332 NM_015269 NM 020336 57148 1.09 6.47E-03 PDGFD 219304_s_at NM_025208 NM_025208 80310 1.09 1.44E-03 AA743413 236985 at AA743413 NM_033135 1.08 9.66E-03 RNF10 237062_at BE222109 NM_014868 9921 1.08 5.28E-03 ORC6L 219105_x_at NM_014321 NM_014321 23594 1.08 3.86E-03 TH1L 225006_x_at AJ238379 NM_016397 51497 1.08 3.76E-05 KIAA2024 1566166_at AL833423 NM_198976 NM 172070 130507 1.07 9.88E-03 LOC283871 222622 at BG284709 XM_208887 283871 1.06 3.90E-03 BE856960 242712_x_at BE856960 — — 1.06 1.22E-03 RPUSD3 1566603 s at AK094587 NM_173659 285367 1.05 1.31 E-03 LOC284244 214162 at AF070541 — 284244 1.05 6.69E-03 AI817960 239649_at AI817960 ... — 1.05 8.05E-03 400 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays TRA2A 213593_s_at AW978896 NM 013293 29896 1.05 1.05E-03 SBN01 216161 at AK024128 NM 018183 55206 1.05 2.06E-03 SIRT2 1558331_at BG722779 NM_012237 NM_030593 22933 1.05 4.53E-04 AF090944 233995_at AF090944 — — 1.05 9.19E-03 C20orf58 230668 at AI758937 NM 152864 128414 1.04 8.75E-03 HM13 1560297_at BG928538 NM_030789 NM 178580 NM_178581 NM 178582 81502 1.04 7.20E-03 SLC03A1 227367 at AW976431 NM_013272 28232 1.04 1.11E-03 PAN 3 239393_at AW510927 NM 175854 255967 1.04 2.63E-03 CNTN4 229084_at R42166 NM_175607 NM 175612 NM_175613 152330 1.04 7.84E-03 LOC51760 205613_at NM 016524 NM_016524 51760 1.04 6.90E-03 APC 216933 x at S67788 NM_000038 324 1.04 6.77E-03 H43040 231108_at H43040 — — 1.03 6.01 E-04 C9orf10 241242_at BE503118 NM 014612 23196 1.03 9.13E-03 C13orf25 232291_at AA256157 NM_213723 NM 213724 407975 1.03 4.81 E-03 HAN 11 233782_at AU147133 NM_00100372 5 NM_005828 10238 1.03 2.43E-04 FLJ43654 235376_at BF125564 NM 198562 375341 1.03 1.61 E-03 RTN4 1556049_at CA428769 NM 007008 NM 020532 NM_153828 NM 207520 NM_2 07521 57142 1.02 3.35E-03 CSE1L 210765_at AF053640 NM 001316 NM_177436 1434 1.02 6.67E-05 CBLB 209682 at U26710 NM_170662 868 1.02 1.33E-06 FLJ12750 236889_at AI911084 NM_024667 79720 1.02 9.90E-03 PEG10 212094_at AL582836 XM 496907 XM_499343 23089 1.02 4.05E-03 T40928 241913_at T40928 XM 498972 441028 1.02 9.84E-03 FLJ11783 220546_at NM_024891 NM_024891 79951 1.02 9.99E-04 NM_018627 220410_s_at NM_018627 — — 1.01 5.37E-03 CSPG6 1556925_at AL360194 NM 005445 9126 1.01 1.34E-03 DERA 218102 at NM 015954 NM 015954 51071 1.01 3.80E-03 DLL3 219537_x_at NM_016941 NM_016941 NM_203486 10683 1.01 2.97E-04 CNOT7 233019_at AU 145061 NM 013354 NM 054026 29883 1.01 2.14E-03 HIVEP2 243254_at T08739 NM_006734 3097 1.01 2.67E-03 MGC33926 229302_at AA058832 NM 152390 130733 1.01 3.60E-03 LRRN5 216167_at AK024867 NM 006338 NM 201630 10446 1.01 6.96E-03 API5 214960_at AF229253 NM_006595 8539 1.00 5.16E-04 EAF2 219551_at NM_018456 NM 018456 55840 1.00 5.97E-05 C2orf23 204364 s at BE535746 NM 022912 65055 1.00 9.51 E-04 EVL 227232 at T58044 NM_016337 51466 1.00 6.72E-04 MAP4K3 242448_at AI800895 NM_003618 8491 1.00 4.16E-03 GLS 223080 at AK025021 NM_014905 2744 1.00 5.50E-03 ST8SIA1 210073 at L32867 NM 003034 6489 1.00 2.41 E-03 SNAG1 226683 at AU 146771 NM_052870 112574 0.99 1.15E-03 401 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays TDG 203742_s_at BF674842 NM_00100841 1 NM_003211 6996 0.99 1.56E-03 GALNT7 216756_at AK024995 NM_017423 51809 0.99 7.57E-03 DCP2 244777 at AA504595 NM 152624 167227 0.99 7.31E-03 HIPK2 224016 at AF111850 NM_022740 28996 0.99 3.36E-03 BE467787 243835_at BE467787 — ... 0.99 6.62E-03 C9orf39 239989_at AW170610 NM_017738 54875 0.99 7.75E-05 AI655229 243497 at AI655229 — — 0.99 6.76E-03 WSB1 227501_at AI377135 NM 015626 NM_134264 NM_134265 26118 0.99 6.53E-03 NM_025120 220728 at NM 025120 — — 0.98 1.00E-03 PCBP2 229467_at AA504356 NM_005016 NM_031989 5094 0.98 8.91 E-03 EIF4A1 214805_at U79273 NM_001416 1973 0.98 7.43E-03 MGEA5 214972 at AU144791 NM 012215 10724 0.97 7.74E-03 FLJ10579 230843_at AA482037 NM_018145 55177 0.97 2.54E-03 ZCWPW2 243863_at BF575233 XM 087384 152098 0.97 4.74E-03 RNF111 241413_at W80457 NM_017610 54778 0.97 1.29E-03 PLEKHA6 205093_at NM 014935 NM 014935 22874 0.97 1.50E-04 SEZ6L 207873_x_at NM_021115 NM_021115 23544 0.97 2.35E-04 FLJ10213 219906_at NM_018029 NM 018029 55096 0.97 6.80E-03 WTAP 1558783_at AK024805 NM 004906 NM 152857 NM_152858 9589 0.97 2.62E-04 CTNNB1 242558_at AW362945 NM_001904 1499 0.96 7.55E-03 AA830545 235730_at AA830545 — — 0.96 3.70E-05 MGC33846 231430 at AW205640 NM 175885 220382 0.95 1.36E-03 ZNF238 207164_s_at NM_006352 NM_006352 NM_205768 10472 0.95 2.86E-03 AF5Q31 232864 s at N59653 NM 014423 27125 0.95 4.59E-04 SFRS2 200753 x at BE866585 NM 003016 6427 0.95 2.39E-04 H40696 236122„at H40696 XM 370722 387921 0.95 4.70E-03 AW971254 222369_at AW971254 — — 0.94 4.58E-03 DKFZp547A023 214731 at AB037854 NM_018704 55917 0.94 7.37E-03 AK022388 233017_x_at AK022388 — — 0.94 7.06E-03 PRDX2 215067_x_at AU147942 NM 005809 NM 181737 NM 181738 7001 0.94 2.97E-03 RET 215771_x_at X15786 NM_020630 NM_020975 5979 0.94 8.55E-03 ACTR6 239679_at AI871160 NM 022496 64431 0.94 4.88E-03 HNRPA1 222040_at AI144007 NM 002136 NM_031157 3178 0.93 4.24E-03 TMEM4 209797_at BC001027 NM 014255 10330 0.93 5.35E-04 CIAPIN1 230838_s_at AW771492 NM 020313 57019 0.93 9.30E-04 PRPF4B 202126_at AA156948 NM 003913 NM_176800 8899 0.93 2.94E-03 ETV3 1552423_at NM 005240 NM_005240 2117 0.92 5.12E-03 KCNQ10T1 243435 at AI023707 — 10984 0.92 5.64E-03 HNRPA2B1 205292_s_at NM_002137 NM 002137 NM_031243 3181 0.92 7.56E-04 AW138794 227283_at AW138794 — — 0.92 1.97E-03 HNRPU 236244_at AI458297 NM 004501 NM_031844 3192 0.92 8.40E-04 TUBB6 209191_at BC002654 NM_032525 84617 0.91 2.73E-03 SEZ6L 211894_x_at AB041736 NM_021115 23544 0.91 9.29E-04 402 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., etal., Cells Useful for Immuno-Based BoNT/A Activity Assays C2orf23 204365_s_at NM 022912 NM_022912 65055 0.91 3.53E-04 HNRPM 238610_s_at Al 906424 NM_005968 4670 0.91 6.28E-03 NM_031203 NUP210 220035_at NM_024923 NM_024923 23225 0.91 8.57E-03 RNF130 236292_at AW196696 NM_018434 55819 0.91 5.09E-03 STMN3 222557 at AL353715 NM_015894 50861 0.91 1.21E-04 KIAA0907 230028_at BF508843 NM_014949 22889 0.91 1.57E-04 AI346432 229132 at Al346432 — — 0.91 6.45E-03 DLL3 222898_s_at BE350882 NM_016941 10683 0.90 1.05E-03 NM_203486 CYB561 209164_s_at BC002976 NM_001915 1534 0.90 8.80E-03 CBWD1 226193_x_at AV709992 NM_018491 150472 0.90 5.40E-03 CBWD2 NM 172003 220869 LOC220869 NM_201453 389760 DC36 55871 SFRS2 214882_s at BG254869 NM_003016 6427 0.90 2.75E-04 AK024901 234326_at AK024901 — — 0.90 3.19E-03 RAB12 238714_at AA504249 XM_113967 201475 0.89 3.77E-03 BC001743 209446_s_at BC001743 — — 0.89 2.43E-05 CDK2AP1 201938_at NM_004642 NM_004642 8099 0.89 4.50E-03 AF5Q31 1555436 a at BC025700 NM_014423 27125 0.89 2.72E-03 LOC144997 227289_at AU119437 — 144997 0.88 6.49E-03 C10orf58 224435_at BC005871 NM_032333 84293 0.88 3.29E-03 MAP3K13 211083_s_at Z25428 NM_004721 9175 0.88 1.85E-03 CP110 1569353 at BC030223 NM 014711 9738 0.88 1.17E-03 NDUFS1 1559691_at BC032767 NM 005006 4719 0.88 5.87E-03 NUDT9 241489_at BE671532 NM_024047 53343 0.88 3.25E-03 NM_198038 NM 198039 NFATC2IP 212808_at AI884627 NM_032815 84901 0.88 1.28E-03 AW444985 243690_at AW444985 — — 0.87 3.30E-03 SYT11 232677 at AU146128 NM_152280 23208 0.87 7.93E-03 PTPN1 202716 at NM 002827 NM_002827 5770 0.87 7.56E-03 FLJ45983 240827_at AA846824 NM_207423 399717 0.87 6.25E-03 BM041211 1562062 at BM041211 — — 0.87 8.38E-03 UQCRC2 241755 at Al961429 NM_003366 7385 0.87 1.07E-03 WHSC2 1557300 s at AI741292 NM 005663 7469 0.87 7.80E-03 PDE7A 224046_s_at U67932 NM_002603 5150 0.87 9.76E-03 NM_002604 PHF20 235389 at BG168139 NM_016436 51230 0.87 1.49E-03 AW973410 244310 at AW973410 XM_498613 440283 0.87 4.14E-03 FLJ10120 220220_at NM_018001 — 55073 0.86 4.44E-03 ILF3 208931_s_at AF147209 NM_004516 3609 0.86 4.15E-04 NM_012218 NM_153464 MARCKS 201670_s_at M68956 NM_002356 4082 0.86 1.21E-03 U06715 217200_x at U06715 — — 0.86 6.65E-03 182-FIP 224956 at AI743689 NM_020772 57532 0.85 8.46E-03 FLJ13855 236107_at AA147920 NM_023079 65264 0.85 4.95E-03 BI496583 1557675 at BI496583 — — 0.85 1.81E-03 C10orf58 228155 at BF512388 NM_032333 84293 0.84 4.87E-03 SEZ6L 216047 x at AL050253 NM_021115 23544 0.84 6.17E-04 LOC254057 232370_at AI635756 — 254057 0.84 3.35E-03 TCF7L2 216511_s_at AJ270770 NM__030756 6934 0.84 7.95E-03 1KFZP564K196 223170_at AF132000 NM_015544 26022 0.84 3.64E-03 SFRS2 200754_x_at NM_003016 NM_003016 6427 0.83 7.20E-04 AA447714 244047_at AA447714 — — 0.83 8.79E-03 MARCKS 201668_x_at AW163148 NM_002356 4082 0.83 5.34E-03 403 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., etal., Cells Useful for Immuno-Based BoNT/A Activity Assays AF222691 216187_x_at AF222691 — — 0.83 8.37E-03 DCL-1 232371_at AU155401 NM 014880 9936 0.83 8.82E-04 RPS24 1555878_at AK094613 NM 001026 NM 033022 6229 0.83 7.05E-03 ZNF238 212774_at AJ223321 NM 006352 NM_205768 10472 0.82 1.69E-03 NKTR 202379_s_at Al 361805 NM_005385 4820 0.82 2.20E-03 KIAA0485 242824_at AW191647 — 57235 0.82 2.73E-03 CSE1L 201111_at AF053641 NM 001316 NM_177436 1434 0.82 9.40E-03 NKTR 1557736_at AI880383 NM 005385 4820 0.82 2.47E-03 MBD2 214397_at AI827820 NM_003927 NM 015832 8932 0.82 8.51 E-03 MCCC1 242223 at AA505323 NM 020166 56922 0.82 5.18E-04 CREBBP 237239_at AW183655 NM_004380 1387 0.82 1.36E-03 LOC129285 1554145_a_at BC040721 NM_152994 129285 0.81 7.02E-03 SEZ6L 213609 s at AB023144 NM 021115 23544 0.81 8.59E-03 HNRPM 238611_at Al906424 NM_005968 NM_031203 4670 0.81 5.61E-03 MYLIP 223129 x at T63512 NM_013262 29116 0.81 1.14E-03 AI476542 243032 at AI476542 — — 0.81 4.19E-03 HYPB 241458_at AI868267 NM_012271 NM 014159 29072 0.81 8.29E-03 SNRPB2 1561965_at BE466925 NM_003092 NM_198220 6629 0.81 8.93E-04 SMARCA4 217656 at AW128846 NM_003072 6597 0.80 2.21 E-03 MRPL4 223742_at BC000756 NM 015956 NM 146387 NM 146388 51073 0.80 7.99E-05 HS6ST2 1552767_a_at NMJ47174 NM_147174 NM_147175 90161 0.80 2.64E-03 NEURL 243853_at BF516539 NM 004210 9148 0.80 5.90E-04 SMARCD1 203183_s_at NM_003076 NM 003076 NM_139071 6602 0.80 2.99E-03 HECTD1 242349_at AW275658 NM 015382 25831 0.80 7.69E-04 GGA2 213772_s_at BF196572 NM 015044 NM_138640 23062 0.80 3.58E-03 AA056145 227633_at AA056145 — — 0.79 9.47E-04 MAN2A1 235103_at AA029155 NM_002372 4124 0.79 7.09E-03 SENP3 215114_at AK000923 NM_015670 26168 0.79 2.65E-09 GULP1 223837 at BC001103 NM 016315 51454 0.78 2.45E-03 JARID2 203297_s_at BG029530 NM_004973 3720 0.78 9.88E-04 DNAPTP6 222154_s_at AK002064 NM 015535 26010 0.78 5.12E-03 VPS29 223026_s_at AF201946 NM 016226 NM_057180 51699 0.78 9.91E-03 AF279774 216967_at AF279774 — — 0.78 1.36E-03 COBLL1 203642_s_at NM_014900 NM_014900 22837 0.78 1.12E-03 AI041522 228030 at AI041522 — — 0.78 4.80E-03 FLJ11029 219392_x_at NM 018304 NM 018304 55771 0.78 4.83E-03 RNF34 219035_s_at NM_025126 NM 025126 NM_194271 80196 0.77 2.35E-03 BF056892 229024 at BF056892 — — 0.77 3.47E-06 DKFZP564C18C 1559139 at BC009786 NM 015658 26155 0.77 3.20E-03 SFRS1 227164_at AL521786 NM 006924 6426 0.77 1.00E-03 MR-1 225298_at AA074597 NM 015488 NM_022572 25953 0.76 4.65E-03 ATP6V0A2 217603_at AW444520 NM_012463 23545 0.76 2.94E-03 404 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., etal., Cells Useful for Immuno-Based BoNT/A Activity Assays RECQL 210568_s_at BC001052 NM 002907 NM 032941 5965 0.76 4.23E-03 YWHAB 208743_s_at BC001359 NM_003404 NM_139323 7529 0.76 4.79E-03 ANKHD1 229457_at AU148042 NM 017747 NM 017978 NM_024668 54882 0.76 4.26E-03 STRBP 233251_at AK024960 NM_018387 55342 0.76 3.48E-03 AF147390 1562230 at AF147390 — — 0.76 2.73E-09 HIC2 212966 at AL043112 NM 015094 23119 0.76 4.03E-03 LUC7L2 226758_at AA043552 NM_016019 51631 0.76 5.54E-03 GNG2 224965_at AU118419 NM 053064 54331 0.76 4.33E-03 USP7 230761 at AI972599 NM 003470 7874 0.75 2.83E-03 SH3MD1 213252 at AI739005 NM 014631 9644 0.75 1.10E-03 TLE4 204872_at NM_007005 NM_007005 7091 0.75 4.50E-03 AA167167 243684 at AA167167 — — 0.75 4.31 E-03 SLC25A13 229061 s at AW268880 NM 014251 10165 0.75 6.06E-03 NSD1 235760_at AI421972 NM_022455 NM_172349 64324 0.75 9.51 E-03 BTBD14A 243431_at BF000597 NM_144653 138151 0.75 9.59E-03 AKR1B1 201272_at NM 001628 NM 001628 231 0.74 2.19E-03 SDS3 233841 s at AK026749 NM 022491 64426 0.74 1.60E-04 ANAPC7 225554_s_at AA131793 NM 016238 51434 0.74 4.31 E-03 EPOR 215054_at H16758 NM_000121 2057 0.74 9.06E-04 KHDRBS3 209781 s at AF069681 NM 006558 10656 0.74 6.64E-04 C6orf115 223361_at AF116682 XM_371848 58527 0.73 1.49E-03 LOC157627 214839 at AF052108 — 157627 0.73 8.43E-03 HS6ST2 230030_at Al767756 NM_147174 NM 147175 90161 0.73 3.77E-03 DHX35 218579_s_at NM_021931 NM_021931 60625 0.73 6.34E-06 Al700633 212812_at AI700633 — — 0.73 7.29E-03 ZNF281 222619_at AU150752 NM_012482 23528 0.73 9.28E-04 NARG1 219158_s_at NM 025085 NM 057175 80155 0.73 4.16E-03 C5orf13 201309_x_at U36189 NM_004772 9315 0.73 6.38E-03 PBP 205353_s_at NM_002567 NM_002567 5037 0.73 5.93E-04 KIAA0220 211996_s_at BG256504 — 283846 0.72 1.81 E-03 MYH10 212372 at AK026977 NM_005964 4628 0.72 1.71 E-03 AU147166 215212_at AU147166 — — 0.71 8.93E-03 BTBD3 202946_s_at NM_014962 NM 014962 NM_181443 22903 0.71 8.99E-04 DNAJC9 213088 s at BE551340 NM 015190 23234 0.71 9.31 E-03 MAN1A1 208116_s_at NM_005907 NM_005907 4121 0.71 5.70E-03 ATP5G1 208972_s_at AL080089 NM_00100202 7 NM 005175 516 0.71 3.03E-03 PAICS 201013_s_at AA902652 NM_006452 10606 0.71 2.75E-03 AI378500 229821_at AI378500 — — 0.71 3.49E-03 KLHL5 226001_at AK002174 NM 00100707 5 NM_199039 51088 0.71 2.63E-03 SFRS9 201698_s_at NM_003769 NM_003769 8683 0.71 5.14E-04 PABPN1 213046_at AM30920 NM 004643 8106 0.71 3.81 E-04 GARNL1 234923_at AK022988 NM_014990 NM_194301 253959 0.70 5.70E-03 MAN1A1 221760 at BG287153 NM 005907 4121 0.70 7.22E-03 C5orf13 201310 s at NM 004772 NM_004772 9315 0.70 6.72E-03 NM_031221 208120_x_at NM_031221 — — 0.70 4.42E-04 CYHR1 213681 at AW512817 NM 032687 50626 0.70 4.56E-03 405 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays BF437591 222026_at BF437591 — — 0.70 7.17E-03 SEZ6L 231650_s_at BE672217 NM 021115 23544 0.70 9.10E-03 UFD1L 209103_s_at BC001049 NM_005659 7353 0.70 1.25E-03 H37943 242311_x_at H37943 — — 0.70 2.95E-03 ACY1L2 225431_x_at BE779764 NM_001010853 135293 0.70 3.20E-03 SCC-112 213983_s_at AW991219 NM 015200 23244 0.70 8.02E-04 RPUSD3 1555916_at BM670238 NM 173659 285367 0.70 1.32E-05 CCAR1 224736_at BE617899 NM 018237 55749 0.69 8.03E-03 SNX1 1559154_at AK098001 NM_003099 NM 148955 NM_152826 6642 0.69 5.03E-03 MGC52282 231638_at AA400057 NM_178453 124221 0.69 4.60E-03 MAPKAPK3 202788 at NM_004635 NM_004635 7867 0.69 3.76E-03 HNRPA3 211931_s_at BG505670 NM_194247 220988 0.69 2.94E-04 AK024881 234723_x_at AK024881 — — 0.69 7.45E-03 PCIA1 218260_at NM_024050 NM_024050 79016 0.69 9.77E-03 ANKRD36 238464_at AA463221 XM_371540 375248 0.69 2.40E-03 N4BP2 231996 at AB037834 NM 018177 55728 0.69 1.75E-03 EMID2 229080_at BE741432 NM_133457 136227 0.68 1.65E-03 FLJ22490 242041_at AI933671 NM 024790 79848 0.68 7.80E-03 IDH3B 210418_s_at AF023265 NM_006899 NM_174855 NM_174856 3420 0.68 2.50E-03 MAN2A1 205105_at NM_002372 NM_002372 4124 0.68 1.85E-03 BF055201 228242_at BF055201 — — 0.68 9.05E-03 IDH3B 210014_x_at AF023266 NM 006899 NM_174855 NM_174856 3420 0.68 2.17E-03 GALNT4 231832 at AI890347 NM 003774 8693 0.67 7.13E-03 OCIAD1 232644 x at AK024302 NM 017830 54940 0.67 5.83E-03 GPR51 211679 x_at AF095784 NM 005458 9568 0.67 6.98E-03 SRC 213324_at AK024281 NM_005417 NM 198291 6714 0.67 1.56E-03 PBP 210825_s_at AF130103 NM_002567 5037 0.67 4.20E-03 THRAP4 213043_s_at AI023317 NM 014815 9862 0.67 6.87E-04 ATAD3A ATAD3B 1552641_s_at NM_031921 NM_018188 NM_031921 55210 83858 0.66 7.21E-03 FLJ20364 1559222 at AA781731 NM 017785 54908 0.66 1.64E-03 TA-PP2C 225204_at AA521311 NM_139283 160760 0.66 2.71E-03 EIF5A 201123_s_at NM 001970 NM 001970 1984 0.66 8.31 E-04 RECQL 212917_x_at AI814728 NM 002907 NM_032941 5965 0.66 3.26E-03 ZC3HDC5 1562434_at AL832312 XM 036115 85451 0.66 7.52E-03 BCR 202315_s_at NM_004327 NM_004327 NM_021574 613 0.66 3.87E-03 C14orf2 242858_at BF507638 NM_004894 9556 0.66 1.48E-03 MAP3K13 206249 at NM_004721 NM 004721 9175 0.66 3.65E-03 SULT1A3 222094_at AI580112 NM_003166 NM_177552 6818 0.66 3.16E-04 ZNF207 244153_at AA521438 NM_003457 7756 0.65 8.57E-03 PEX26 219180_s_at AI817074 NM_017929 55670 0.65 4.16E-03 RAN 200750 s at AF054183 NM_006325 5901 0.65 6.43E-03 EIF5A 213753_x_at BF541557 NM 001970 1984 0.65 1.96E-05 C13orf6 235348_at AA404347 NM 032859 84945 0.65 2.02E-03 EWSR1 210012_s_at BC000527 NM 005243 NM 013986 2130 0.65 4.34E-03 SPG7 230885_at BE670386 NM 003119 NM 199367 6687 0.65 7.60E-03 406 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays SCLY 59705_at AA911739 NM 016510 51540 0.65 9.03E-03 KCTD10 223208 at AF113208 NM 031954 83892 0.64 1.07E-04 FLJ13149 219016_at NM_021826 NM_021826 60493 0.64 7.47E-04 ZNF217 203739_at NM_006526 NM 006526 7764 0.64 2.22E-03 GGA2 208913_at AA868560 NM 015044 NM 138640 23062 0.64 4.26E-03 DST 1560296_at AV702787 NM_001723 NM_015548 NM_020388 NM 183380 667 0.64 8.16E-03 UBQLN1 222989_s_at NM_013438 NM_013438 NM_053067 29979 0.64 9.49E-03 TOMM40 202264_s_at NM_006114 NM 006114 10452 0.63 5.40E-03 VTI1A 235034 at AW194969 NM 145206 143187 0.63 9.95E-03 TMEM33 222642_s_at BC000948 NM_018126 55161 0.63 6.62E-03 KIAA1219 221738_at BG236163 NM_020336 57148 0.63 1.93E-03 RPL23 215224_at AK025200 NM 000978 9349 0.63 7.04E-04 ZNF43 222136 x at AK022905 NM_003423 7594 0.63 4.57E-03 BE671123 235798_at BE671123 — ... 0.63 8.79E-03 WDR17 1552430_at NM_170710 NM_170710 NM_181265 116966 0.63 5.45E-04 FUBP1 212847 at AL036840 NM 003902 8880 0.63 6.95E-03 MBTD1 207115_x_at NM_017643 NM 017643 54799 0.63 7.84E-03 PHC2 1557852_at AW418842 NM_004427 NM_198040 1912 0.62 8.02E-03 AP1S2 228415 at AA205444 NM 003916 8905 0.62 8.44E-03 GPR125 210473_s_at M37712 NM_145290 166647 0.62 6.47E-03 SFRS6 208804_s_at AL031681 NM_006275 6431 0.62 3.30E-03 AI216567 236754 at AI216567 — — 0.62 4.60E-03 C15orf25 220071_x_at NM 018097 NM 018097 55142 0.62 9.64E-03 CDH2 203441_s_at NM 001792 NM 001792 1000 0.62 5.11E-03 MRPL35 222775_s_at AK026220 NM_016622 NM_145644 51318 0.62 1.89E-03 CNP 208912 s at BC001362 NM 033133 1267 0.62 3.84E-03 FLJ20331 218577_at NM 017768 NM 017768 55631 0.62 6.26E-03 FLJ21415 218867_s_at NM_024738 NM_024738 79794 0.62 3.36E-03 AF336882 224288_x_at AF336882 — — 0.62 3.59E-03 SSBP3 223635_s_at BC003605 NM_00100995 5 NM 018070 NM 145716 23648 0.62 2.27E-03 ATF7IP 231825_x_at AK025060 NM_018179 55729 0.62 7.81 E-03 TOP1 208901_s_at J03250 NM_003286 7150 0.61 6.28E-04 SYNCRIP 209024_s_at AI472757 NM 006372 10492 0.61 1.15E-03 DHX30 239772_x_at Al368527 NM 014966 NMJ38614 NMJ38615 22907 0.61 1.59E-04 BE878277 212829_at BE878277 — — 0.61 1.63E-03 FBXL10 226215_s_at Al 989996 NM 00100536 6 NM_032590 84678 0.61 7.38E-03 KIAA0251 1555347 at BC033748 NM 015027 23042 0.61 2.52E-03 RBM14 204178 s at NM 006328 NM 006328 10432 0.61 3.59E-05 EXOSC1 1559044_at BC012538 NM 016046 51013 0.61 7.00E-04 KIAA0992 234135_x_at AK021652 NM 016081 23022 0.60 8.94E-03 EIF5A 201122 x at BC000751 NM_001970 1984 0.60 1.14E-03 R26456 243135 x at R26456 — ... 0.60 5.74E-03 TMEM33 218465 at NM 018126 NM_018126 55161 0.60 8.99E-03 407 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B„ et al., Cells Useful for Immuno-Based BoNT/A Activity Assays SFRS1 201741_x_at M69040 NM_006924 6426 0.60 1.36E-03 RAB11FIP3 214999 s at AW243089 NM 014700 9727 0.60 1.50E-04 DDX46 228039_at AI765169 NM_014829 9879 0.60 2.91 E-03 HNRPU 200593_s_at BC003621 NM_004501 NM 031844 3192 0.60 1.26E-05 HNRPU 200594_x_at NM_004501 NM_004501 NM_031844 3192 0.59 1.74E-04 GNG12 212294_at BG111761 NM 018841 55970 0.59 6.29E-03 ARS2 201680_x_at NM_015908 NM_015908 NM_182800 51593 0.59 2.20E-04 FLJ37078 235880 at BF593867 NM_153043 222183 0.59 7.82E-05 GPR51 209990_s_at AF056085 NM 005458 9568 0.59 7.76E-03 MARCKS 201669_s_at NM_002356 NM_002356 4082 0.59 4.74E-05 MAN2A1 226538_at AV700323 NM 002372 4124 0.59 4.65E-03 HCFC1 202474 s at NM_005334 NM_005334 3054 0.59 2.12E-03 FLJ35709 242540_at AI911330 NM 173589 283294 0.58 5.90E-03 MY01B 212365_at BF215996 NM_012223 4430 0.58 6.28E-04 PPP2CA 208652_at BC000400 NM 002715 5515 0.58 3.88E-03 CDC5L 209055_s_at AW268817 NM_001253 988 0.58 2.61 E-04 408 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al„ Cells Useful for Immuno-Based BoNT/A Activity Assays

Gene Symbol Probe Set ID CYTL1 219837_s_at GNAS 217057_s_at CYGB 226632_at TNFRSF10D 227345 at ECEL1 219914_at SYT13 226086_at TMIE 1553601_a_at NNAT 204239_s_at CNGA3 207261_at AU157716 227051_at AF150317 243111 at ASAM 226834_at LOC254128 1557059_at LOC339290 228160_at FUCA2 223120 at STX3A 209238 at CYGB 1553572 a at EDG7 231192_at HTATIP2 207180 s at HTATIP2 209448 at LMCD1 218574 s at BACE2 217867_x_at FLJ45880 228538_at EDG7 220816 at CDC42EP1 204693_at TCEAL2 211276 at MEOX2 206201_s_at FGF13 205110_s_at IGFBP7 201163_s_at BACE2 222446_s_at SLC35F3 229065 at TncRNA 224565_at LGALS3 208949_s_at GALIG HSPA1A 200799_at AW136654 240802 at LOC56901 218484 at MMP14 202827 s at FLJ20701 219093 at CAP2 212554 at BF941609 240218 at SPINT2 210715 s at

Table 12. Decreased Gene Expression in Cell Lines H1 and BB10 vs.Cell Line SIMa in Differentiated State Using Microarray Analysis Representative RefSeq Public ID Transcript ID NM_018659 NM_018659 AF107846 NM_000516 NM_016592 NM 080425 NM 080426 AL513673 NM_134268 Al 738556 NM_003840 NM 004826 NM 004826 AB037848 NM 020826 NMJ47196 NM 147196 NM_005386 NM_005386 NM_181689 NM_001298 NM_001298 AU157716 — AF150317 — BG112263 NM_024769 AK098264 — AI433706 XM_375527 BC003060 NM_032020 BE966922 NM 004177 NM_134268 NM_134268 AW274018 NM_012152 NM 006410 NM 006410 BC002439 NM_006410 NM_014583 NM_014583 NM_012105 NM_012105 NM_138991 NM 138992 BE671164 NM_207404 NM_012152 NM 012152 NM_007061 NM 007061 NM 152243 AF063606 NM_080390 NM_005924 NM 005924 NM_004114 NM 004114 NM 033642 NM 001553 NM 001553 AF178532 NM_012105 NM 138991 NM 138992 BF968270 NM_173508 BE675516 — BC001120 NM_002306 NM_194327 NM 005345 NM_005345 AW136654 — NM 020142 NM 020142 AU149305 NM_004995 NM_017933 NM_017933 N90755 NM_006366 BF941609 — AF027205 NM 021102

Entrez Gene Log2 Ratio pvalue 54360 -6.94 6.41 E-06 2778 -5.47 4.18E-03 114757 -4.81 3.60E-03 8793 -4.68 2.31 E-06 9427 -4.67 3.83E-05 57586 -4.06 1.83E-04 259236 -3.86 6.07E-05 4826 -3.83 5.67E-07 1261 -3.76 4.84E-04 — -3.75 4.31 E-03 — -3.69 9.83E-04 79827 -3.61 5.78E-03 254128 -3.51 1.95E-07 339290 -3.50 6.83E-05 2519 -3.47 8.50E-03 6809 -3.45 8.83E-03 114757 -3.43 4.93E-06 23566 -3.39 1.39E-03 10553 -3.38 4.96E-04 10553 -3.38 3.60E-04 29995 -3.34 6.84E-03 25825 -3.33 5.05E-04 389114 -3.28 4.82E-06 23566 -3.28 2.18E-03 11135 -3.25 9.63E-03 140597 -3.25 3.45E-04 4223 -3.23 2.59E-06 2258 -3.22 4.26E-05 3490 -3.17 3.25E-03 25825 -3.16 1.05E-04 148641 -3.14 1.47E-06 283131 -3.11 3.26E-03 3958 -3.08 1.25E-03 81625 3303 -3.07 6.70E-03 — -3.06 1.56E-03 56901 -3.02 3.26E-03 4323 -3.01 1.34E-05 55022 -2.99 6.11 E-03 10486 -2.95 3.40E-03 — -2.91 1.65E-08 10653 -2.90 6.36E-06 409 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays BG325630 234973_at BG325630 — — -2.90 2.55E-03 )KFZp313N062 1555905_a_at AI147556 NM 173826 285343 -2.87 1.28E-04 NPY 206001_at NM_000905 NM_000905 4852 -2.85 5.26E-03 CYP2E1 1431_at J02843 NM_000773 1571 -2.75 3.27E-03 HHLA3 220387 s at NM 007071 NM 007071 11147 -2.72 6.75E-04 IL13RA2 206172 at NM 000640 NM 000640 3598 -2.66 6.71 E-05 FLJ31295 226509_at AV700302 NM_152320 121274 -2.65 7.10E-04 TncRNA 224566_at Al042152 — 283131 -2.65 1.05E-04 0KFZP564I042: 223588 at AL136607 NM 031435 83591 -2.64 1.28E-05 IGSF4D 1552754_a_at AA640422 NM 153184 253559 -2.64 1.95E-03 PRKACB 235780_at BE622723 NM_002731 NM_182948 NM 207578 5567 -2.63 2.35E-03 GNAS 214157_at AA401492 NM_000516 NM_016592 NM_080425 NM_080426 2778 -2.61 1.23E-04 AW770245 236513_at AW770245 — — -2.60 8.47E-05 LGI1 206349_at NM 005097 NM_005097 9211 -2.60 8.58E-04 AI810266 235456_at Al810266 — ... -2.58 5.24E-03 HIST1H2BD 209911_x_at BC002842 NM 021063 NM_138720 3017 -2.55 2.10E-03 AL353759 215071 s at AL353759 — — -2.51 9.79E-04 LOC339290 215283_at U79248 XM_375527 339290 -2.51 3.84E-04 SLC16A3 202856 s at NM 004207 NM 004207 9123 -2.51 8.97E-03 LGALS1 201105_at NM_002305 NM_002305 3956 -2.49 4.79E-03 N92599 241421_at N92599 — — -2.47 1.03E-04 ECHDC3 219298 at NM_024693 NM 024693 79746 -2.47 7.27E-04 NEBL 203961_at AL157398 NM 006393 NM_213569 10529 -2.43 4.07E-04 RAC2 207419_s_at NM_002872 NM_002872 5880 -2.42 2.93E-03 BF672306 229189 s at BF672306 — — -2.42 1.43E-03 CYP2E1 209975_at AF182276 NM 000773 1571 -2.41 4.83E-03 NEBL 203962_s_at NM_006393 NM 006393 NM_213569 10529 -2.40 9.78E-04 BE045392 243028 x at BE045392 — — -2.40 3.93E-03 LOC339290 217506_at H49382 XM 375527 339290 -2.38 1.30E-05 PPAPDC1 236044_at BF130943 XM_113641 196051 -2.35 1.18E-04 CYP2E1 209976 s at AF182276 NM_000773 1571 -2.34 7.08E-03 ASAM 228082 at BF056275 NM_024769 79827 -2.32 6.80E-04 ICAM2 204683 at NM 000873 NM 000873 3384 -2.32 7.89E-03 MEGF11 1552439_s at NM_032445 NM_032445 84465 -2.31 2.69E-03 CDS1 226185_at AK026697 NM 001263 1040 -2.31 4.59E-05 ADARB1 203865_s_at NM_015833 NM 001112 NM 015833 NM_015834 104 -2.30 2.34E-03 ELM01 204513_s_at NM_014800 NM_014800 NM_130442 9844 -2.30 9.13E-03 BC039553 1559544_s_at BC039553 — — -2.29 2.32E-03 IGFBP5 211959 at AW007532 NM 000599 3488 -2.27 8.27E-03 C6orf198 227834 at AL589605 XM_371849 167838 -2.22 5.80E-03 AI826125 229866 at Al826125 — — -2.20 1.50E-04 NLF1 241031_at BE218239 NM_207322 145741 -2.19 3.17E-03 C6orf154 235935 at Al539370 XM_168060 221424 -2.18 8.19E-04 GAL 214240_at AL556409 NM_015973 51083 -2.17 3.60E-03 CFC1 223753 s at AF312769 NM 032545 55997 -2.17 1.16E-04 LOC344405 237291_at AI695007 XM_293034 344405 -2.16 1.83E-03 PTN 211737_x_at BC005916 NM_002825 5764 -2.13 4.30E-04 410 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 . Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays PTGER2 206631 at NM 000956 NM 000956 5732 -2.12 3.45E-05 )KFZp761O011 207797_s_at NM 018409 NM 018409 55805 -2.12 1.51E-03 C1GALT1C1 238989_at BF749723 NM 00101155 1 NM_152692 29071 -2.11 6.52E-04 AA757630 236724 at AA757630 — — -2.08 7.95E-06 PDLIM3 209621_s_at AF002280 N M 014476 27295 -2.08 9.67E-03 KCNMA1 221584_s_at U11058 NM 002247 3778 -2.08 1.62E-04 TSAP6 218424_s_at NM_018234 NM 00100841 0 NM_018234 NM 182915 55240 -2.07 6.98E-03 ST3GAL3 1555702_a_at AF425866 NM 006279 NM_174963 NM_174964 NM_174965 NM 174966 NM_174967 NM_174968 NM_174969 NM_174970 NM_174971 NM_174972 6487 -2.03 6.54E-03 ZNF346 232753_at AU147613 NM_012279 23567 -2.03 2.80E-04 SYT5 206161 s at AI659957 NM 003180 6861 -2.02 8.93E-03 HEBP2 203430_at NM_014320 NM_014320 23593 -2.02 4.86E-05 C9orf19 225604_s_at AA284532 NM 022343 152007 -2.02 1.60E-03 AKAP12 227529_s_at BF511276 NM_005100 NM_144497 9590 -2.02 6.85E-05 FLJ20152 218532_s_at NM 019000 NM_019000 54463 -2.01 2.04E-03 SYNPR 230303_at H11380 NM 144642 132204 -1.99 7.36E-03 UBE2D3 230171_at AW662789 NM 003340 NM_181886 NM181887 NM_181888 NM 181889 NM_181890 NM181891 NM_181892 NM_181893 7323 -1.97 7.18E-06 STAC2 228888_at AI821472 NM_198993 342667 -1.96 4.27 E-04 BE894882 235681_at BE894882 — — -1.95 5.54E-03 AKAP12 210517_s_at AB003476 NM_005100 NM_144497 9590 -1.94 6.61 E-05 ZNF91 238466_at R43486 NM_003430 7644 -1.93 2.26E-05 HIST1H2BK 209806_at BC000893 NM_080593 85236 -1.92 1.28E-04 BF432875 235782_at BF432875 XM_497668 388620 -1.91 5.20E-03 TMEM4 202857_at NM 014255 NM 014255 10330 -1.91 5.19E-03 FCRH1 243968_x_at AI572979 NM_052938 115350 -1.90 4.72 E-04 AKAP12 227530_at BF511276 NM_005100 NM_144497 9590 -1.89 1.05E-04 COL16A1 204345 at NM 001856 NM_001856 1307 -1.89 4.40E-03 FLJ32752 229631_at AL040892 NM_144666 144132 -1.89 3.14E-03 GPX7 213170_at AA406605 NM_015696 2882 -1.89 3.82E-04 BF000047 235736 at BF000047 — — -1.88 9.64E-03 FLJ25952 243786 at AA454190 NM 153251 253832 -1.87 9.52E-05 ARTS-1 214012_at BE551138 NM_016442 51752 -1.87 5.76E-03 RAC2 213603_s_at BE138888 NM_002872 5880 -1.86 2.55E-03 411 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al„ Cells Useful for Immuno-Based BoNT/A Activity Assays IL7 206693_at NM_000880 NM_000880 3574 -1.86 7.63E-03 B3GNT5 225612 s at BE672260 NM 032047 84002 -1.86 1.01E-03 BCL2 203685_at NM_000633 NM_000633 NM_000657 596 -1.85 3.00E-03 ZAP128 202982_s_at NM_006821 NM_006821 10965 -1.84 2.07E-03 AF085995 1561759 at AF085995 — ... -1.84 4.44E-04 UCN 206072_at NM_003353 NM_003353 7349 -1.84 1.79E-04 CDH10 220115_s_at NM_006727 NM_006727 1008 -1.83 1.73E-03 BF114967 231067_s_at BF114967 — ... -1.83 6.70E-06 ADAMTS1 222162_s_at AK023795 NM 006988 9510 -1.82 1.09E-04 PPFIA4 214978 s at AK023365 NM_015053 8497 -1.82 6.27E-03 BE674309 230913_at BE674309 — ... -1.81 1.25E-03 AL355688 232081_at AL355688 — ... -1.80 1.15E-03 AI698684 1558626 at AI698684 — — - -1.78 3.33E-03 PRPH 213847 at NM_006262 NM 006262 5630 -1.78 3.01 E-03 PTGES 210367_s_at AF010316 NM 004878 NM 198797 9536 -1.78 4.71 E-06 HPCAL1 205462_s_at NM_002149 NM 002149 NM_134421 3241 -1.77 3.68E-03 INSIG1 229370_at BF507344 NM 005542 NM 198336 NM_198337 3638 -1.77 3.55E-04 RAB6B 221792_at AW118072 NM_016577 51560 -1.77 1.12E-04 AI733281 239994_at Al 733281 — — -1.75 1.40E-03 NDFIP2 1568807_a_at Al 301081 NM 019080 54602 -1.75 2.04E-04 KIAA1598 221802_s_at AU157109 NM 018330 57698 -1.74 1.10E-03 CAP2 212551_at NM_006366 NM_006366 10486 -1.74 7.36E-03 TICAM2 228234_at AI423165 NM 021649 353376 -1.73 1.46E-03 DSCAM 237268_at BE503065 NM 001389 NM 206887 1826 -1.73 5.66E-04 MATN3 230390_at AI809899 NM 002381 4148 -1.72 2.82E-04 AL833383 1563776_at AL833383 — ... -1.71 6.57E-06 C21orf109 1553608_a_at NM 138968 — 193629 -1.70 9.95E-03 FLJ35390 1569089 a at BC024303 — 255031 -1.70 2.94E-03 AF052119 214821 at AF052119 — ... -1.69 6.58E-04 M160 223655_at AF264014 NM_174941 283316 -1.69 9.95E-03 AI588962 230477_at AI588962 ... ... -1.69 8.76E-05 )KFZp313N062 1555906 s at AM 47556 NM 173826 285343 -1.69 2.73E-04 DRD1IP 219896_at NM_015722 NM_015722 50632 -1.69 4.68E-03 )KFZp313N062 226688_at AW003508 NM_173826 285343 -1.68 8.18E-03 AW450420 236373 at AW450420 — — -1.66 8.61 E-03 LOC133308 1564746_at BC009732 NM_178833 133308 -1.65 1.14E-04 AL037414 230055_at AL037414 ... ... -1.63 9.73E-05 RGAG4 227823_at BE348679 XM 291322 340526 -1.63 4.87E-05 APOBEC3G 204205 at NM 021822 NM 021822 60489 -1.62 9.31 E-03 BTN3A3 38241_at U90548 NM_006994 NM_197974 10384 -1.62 2.24E-03 LOC133308 229491_at BF433180 NM 178833 133308 -1.61 8.27E-04 C21orf66 239407_at AI793248 NM 013329 NM 016631 NM_058191 NM 145328 94104 -1.61 6.82 E-03 )KFZp761N111· 229254 at BE550027 NM 181644 148808 -1.60 3.14E-03 DSCAM 211484_s_at AF023450 NM 001389 NM_206887 1826 -1.60 1.94E-04 ADAMTS 1 222486_s_at AF060152 NM_006988 9510 -1.59 4.21 E-03 LOC286052 241370 at AA278233 — 286052 -1.59 8.30E-05 MGC40157 239754 at BE671886 NM_152350 125144 -1.59 9.45E-03 412 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays ZNF571 206648 at NM 016536 NM 016536 51276 -1.59 1.41 E-03 LIPT1 242053_at AW665279 NM_015929 NM_145196 NM_145197 NM 145198 NM 145199 51601 -1.59 3.26E-04 FBI4 238081_at AI694300 NM 205857 404201 -1.58 1.29E-03 FLJ11286 53720_at AI862559 NM 018381 55337 -1.58 1.79E-03 FLJ30294 1553301 a_at NM_144632 NM_144632 130827 -1.57 1.18E-04 HUMRGE/M10IIUMRGE/M100S;-HUMRGE/M100 — ... -1.57 8.64E-03 HADHA 232590_at AK025919 NM_000182 3030 -1.57 4.01 E-03 NEDL1 243743_at AI373512 NM_015052 23072 -1.56 9.50E-04 BF114745 235459_at BF114745 — — -1.56 1.20E-03 FLJ13614 226521_s_at AK023676 NM_139076 84142 -1.55 2.64E-03 AI276956 230766_at AI276956 — ... -1.54 4.30E-03 AI765942 243914_at Al 765942 — — -1.54 6.05E-03 TBC1D10 226613 at AI742029 NM 031937 83874 -1.53 5.51 E-03 IL10RB 209575 at BC001903 NM_000628 3588 -1.53 1.40E-05 GLT25D2 209883 at AF288389 NM_015101 23127 -1.52 3.20E-05 AI971535 229626_at Al 971535 XM_370691 387856 -1.52 8.91 E-03 FLJ13614 233543 s at AK021582 NM_139076 84142 -1.51 9.66E-03 BF432855 237364_at BF432855 — ... -1.51 2.88E-05 AI590198 243418_at Al590198 — — -1.50 5.83E-03 B7 206076_at NM_006992 NM 006992 NMJ201650 10233 -1.50 3.23E-03 PDGFRB 202273_at NM_002609 NM_002609 5159 -1.49 1.88E-03 MCTP1 220122_at NM_024717 NM_00100279 6 NM_024717 79772 -1.49 5.73E-04 AA747287 242273_at AA747287 — ... -1.48 9.43E-03 GPR123 239221_at AI884909 NM_032422 84435 -1.48 1.25E-03 C10orf57 222545_s_at AA029276 NM 025125 80195 -1.48 3.36E-03 HPCAL1 212552_at BE617588 NM 002149 NM 134421 3241 -1.48 9.71 E-04 LOC284361 229289_at AL517395 NM_175063 NM 206538 284361 -1.48 2.00E-03 PDE4DIP 213388_at H15535 NM 00100281 0 NM 00100281 1 NM 00100281 2 NM 014644 NM_022359 9659 -1.47 1.48E-03 LOC441422 236453_at AW243154 XR_000264 441422 -1.47 2.36E-05 AA976778 230679_at AA976778 — ... -1.46 1.46E-05 FBI4 241401_at BG496631 NM_205857 404201 -1.46 1.53 E-03 C14orf149 227699_at BF511003 NM 144581 112849 -1.45 1.61 E-03 FBI4 1562953_s_at BC019264 NM_205857 404201 -1.45 5.64E-03 AI758408 227235_at Al 758408 — — -1.45 1.51 E-03 TMEM5 204808_s_at NM 014254 NM_014254 10329 -1.44 3.94E-03 BF111884 230491 at BF111884 — — -1.44 3.82 E-04 COL27A1 225293_at AK021957 NM_032888 85301 -1.44 6.78E-03 AA705933 239866_at AA705933 — ... -1.44 5.37E-03 PTN 209466_x_at M57399 NM 002825 5764 -1.43 9.60E-04 COL6A1 213428 s at AA292373 NM 001848 1291 -1.43 7.05E-03 )KFZp313N062 241666_at BG493222 NM_173826 285343 -1.43 8.80E-04 BF241692 238491_at BF241692 — ... -1.43 8.44E-04 413 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays NR1H3 203920 at NM 005693 NM_005693 10062 -1.42 8.44E-03 DKFZP434I071' 231954 at AL137273 — 54553 -1.42 2.11E-03 AI927692 228528_at AI927692 — — -1.41 9.58E-04 SH3GL2 205751_at NM_003026 NM 003026 6456 -1.41 1.80E-05 SNF1LK 208078 s at NM 030751 NM 173354 150094 -1.40 9.31 E-04 LGALS3BP 200923 at NM_005567 NM_005567 3959 -1.40 1.13E-05 AI796536 229810_at AI796536 — — -1.40 2.02E-03 DUSP22 226440_at BE222746 NM_020185 56940 -1.40 2.32E-03 DUSP16 224336 s at AB052156 NM_030640 80824 -1.39 1.91 E-03 BF591692 231532_at BF591692 — — -1.39 3.15E-04 CAMK2D 228555_at AA029441 NM_001221 NM 172115 NM 172127 NM_172128 817 -1.39 2.14E-04 HRMT1L1 202098_s_at NM_001535 NM 001535 NM_206962 3275 -1.39 4.67E-06 DISP1 228184 at AK023679 NM 032890 84976 -1.39 2.54E-05 MAP3K5 203836_s_at D84476 NM_005923 4217 -1.39 1.24E-03 H46176 237083_at H46176 — — -1.38 8.44E-03 RPL37 224767 at AL044126 NM 000997 6167 -1.37 1.60E-03 TIMP1 201666_at NM 003254 NM 003254 7076 -1.37 7.35E-03 PTGES 207388_s_at NMJ304878 NM_004878 NM_198797 9536 -1.37 6.78E-03 SCRG1 205475_at NM_007281 NM_007281 11341 -1.37 1.72 E-03 LOC153682 232794 at AL137383 — 153682 -1.36 2.78E-04 LOC146174 230721_at BF436957 NM_173501 146174 -1.36 1.19E-04 DUSP22 218845_at NM_020185 NM 020185 56940 -1.36 3.43E-06 PH-4 222125_S_at BC000580 NM 017732 NM 177938 NM_177939 54681 -1.35 5.67E-04 DJ462023.2 225876_at T84558 NM 020448 57185 -1.35 1.26E-03 CDKN2A 209644_x_at U38945 NM 000077 NM_058195 NM_058197 1029 -1.35 1.67E-04 DNER 226281_at BF059512 NM_139072 92737 -1.35 1.29E-04 ANKH 220076_at NM 019847 NM 054027 56172 -1.34 4.18E-03 TBC1D10 233528 s_at AC004997 NM_031937 83874 -1.34 1.10E-03 C1orf21 221272_s_at NM_030806 NM 030806 81563 -1.34 5.15E-04 NMB 205204_at NM_021077 NM_021077 NM_205858 4828 -1.33 1.42E-04 SLC16A1 1560579 s at BC023568 NM_003051 6566 -1.33 8.18E-03 BE672499 230962_at BE672499 — ... -1.32 7.98E-03 C21orf57 227421_at BF026326 NM_00100611 4 NM_058181 54059 -1.31 2.23E-06 C1orf21 223127_s_at AW003850 NM_030806 81563 -1.31 2.69E-03 LOC91526 228471_at AA744636 NM 153697 91526 -1.31 6.93E-03 FHL2 202949_s_at NM_001450 NM 001450 NM_201555 NM_201556 NM_201557 2274 -1.31 1.03E-03 NM 024599 219202 at NM 024599 — — -1.31 6.35E-03 C10orf57 218174_s_at NM 025125 NM 025125 80195 -1.31 7.96E-03 LOC196394 226258_at BG031897 NM 207337 196394 -1.30 8.09E-04 AK001829 232594_at AK001829 XM 498704 440498 -1.30 2.12E-03 BE551142 241091_at BE551142 XM_497668 388620 -1.29 2.90E-03 ZFP28 234300_s_at AF226995 NM_020828 140612 -1.29 6.22E-04 BE046461 215303 at BE046461 — — -1.29 9.65E-03 414 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays PCDHAC2 224539_s_at AF152474 NM 018899 NM_031883 56134 -1.28 4.06E-03 RPL37 224763_at BF724210 NM_000997 6167 -1.28 6.11E-03 AI631072 228638_at AI631072 — — -1.28 1.12E-03 MGC39821 1555363_s_at BC034236 XM 498465 XM_499595 284440 -1.28 1.45E-03 ATP6V1E2 1552286_at NM_080653 NM_080653 90423 -1.28 2.19E-03 DTX3L 225415_at AA577672 NM 138287 151636 -1.26 6.35E-03 ZNF258 213698_at AI805560 NM 007167 NM_145310 9204 -1.26 4.04E-03 RHOU 223168_at AL096776 NM 021205 58480 -1.26 2.56E-04 RFX2 226872_at AK024288 NM 000635 NM_134433 5990 -1.25 5.59E-03 LOC402524 242206_at AW590588 XM_379850 402524 -1.25 2.69E-04 NEFH 33767_at X15306 NM 021076 4744 -1.25 4.29E-03 HRMT1L1 228722_at AI928367 NM 001535 NM_206962 3275 -1.25 1.86E-03 AI963605 230269_at Al963605 — -.-- -1.24 2.72E-03 NDUFV3 226616_s_at NM_021075 NM_00100150 3 NM_021075 4731 -1.24 6.22E-04 NOTCH4 205247_at AI743713 NM_004557 4855 -1.24 2.38E-03 LOC401321 1560371_at BI823265 XM_379483 XM 380099 401321 -1.24 3.08E-03 SMPD1 209420_s_at M59916 NM 000543 6609 -1.24 2.86E-03 NM_00100759 3 RAB6B 225259_at AI805050 NM 016577 51560 -1.24 5.78E-03 BRUNOL6 227775 at BE467313 NM_052840 60677 -1.24 2.38E-04 MCTP1 235740_at BG250585 NM 00100279 6 NM 024717 79772 -1.24 3.07E-04 PHLDB3 1557948_at BC007947 NM_198850 284345 -1.23 5.46E-04 PLRG1 227246 at BF438014 NM_002669 5356 -1.23 4.56E-03 C9orf19 225602_at H92988 NM_022343 152007 -1.23 4.21 E-03 MGC16037 229050 s at AL533103 — 84973 -1.23 9.30E-03 PLP2 201136_at NM_002668 NM_002668 5355 -1.21 2.30E-03 LOC91526 226641_at AU157224 NM 153697 91526 -1.21 9.94E-03 ZNF404 239043_at AA084273 XM_292765 342908 -1.21 8.85E-04 CNN1 203951_at NM 001299 NM_001299 1264 -1.20 5.29E-03 AI862542 235696_at AI862542 — ... -1.19 2.30E-04 FHL3 218818_at NM_004468 NM_004468 2275 -1.19 5.70E-03 LOC90246 233835_at AK023635 — 90246 -1.19 1.62E-04 ARMCX5 1555902 at BC022066 NM 022838 64860 -1.19 1.49E-04 LOC388227 229107_at AW629461 XM_373670 388227 -1.19 5.59E-03 C6orf52 236504_x_at BE670432 XM_371798 347744 -1.19 9.06E-03 ZNF606 219635_at NM_025027 NM_025027 80095 -1.19 2.38E-03 C10orf39 233076_at AL137551 NM 194303 282973 -1.19 6.97E-04 FVT1 1558279_a_at BF666293 NM_002035 2531 -1.19 3.09E-03 TAF12 209463_s_at D50544 NM_005644 6883 -1.18 3.00E-04 AI929792 236081 at AI929792 — — -1.18 2.41 E-05 PDCD2 228420_at AW590850 NM 002598 NM_144781 5134 -1.18 9.07E-03 ETFDH 33494_at S69232 NM_004453 2110 -1.18 6.70E-03 CD302 203799 at NM 014880 NM_014880 9936 -1.17 9.28E-03 N30152 229850 at N30152 — — -1.17 5.16E-03 MGC11332 213403 at BF223370 NM 032718 84804 -1.17 1.04E-03 415 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays SPIN3 1554099_a_at BC032490 NM_001010862 169981 -1.17 1.85E-05 PHKA1 229876_at BE503584 NM 002637 5255 -1.17 2.72E-04 PCNXL2 1554256_a_at BC008300 NM_014801 NM_024938 80003 -1.17 8.67E-05 LOC284409 239995_at AI692774 XM_211447 284409 -1.17 1.43E-04 AV704017 222376 at AV704017 — . ... -1.16 4.90E-03 AI767751 228084_at AI767751 ... ... -1.16 6.90E-05 FLJ30294 238578_at BF574691 NM 144632 130827 -1.16 2.44E-06 BTN3A1 209770_at U90552 NM_007048 NM_194441 11119 -1.16 4.37E-03 ZC3HDC6 241372_at R34135 NM_198581 376940 -1.16 4.27E-05 LOC285550 236321_at AW439843 XM 209656 285550 -1.16 6.99E-03 MGC11332 213393_at Al767210 NM 032718 84804 -1.15 7.85E-03 CYP2U1 226402 at AK026498 NM 183075 113612 -1.15 2.05E-03 OPTN 202074_s_at NM_021980 NM_00100821 1 NM 00100821 2 NM 00100821 3 NM 021980 10133 -1.15 7.05E-03 D4S234E 209569 x_at NM 014392 NM_014392 27065 -1.15 1.26E-03 GUCY1A3 221942_s_at AI719730 NM_000856 2982 -1.15 4.01 E-04 C18orf18 229829_at AA429735 — 147525 -1.14 7.95E-03 DUSP16 224832 at AB051487 NM 030640 80824 -1.14 2.08E-04 C21orf25 212875 s at AP001745 NM 199050 25966 -1.13 2.32E-03 DKFZP434B172 232124_at AL117530 XM_046264 26172 -1.13 1.47E-03 AKT2 236664_at AA448167 NM 001626 208 -1.13 5.51 E-03 FGF7 FLJ30435 1554741_s_at AF523265 NM 002009 NM_174950 2252 387628 -1.13 2.06E-03 SPOCK2 202524_s_at NM_014767 NM 014767 9806 -1.12 8.32E-03 ULK2 204063_s_at NM_014683 NM 014683 9706 -1.12 5.36 E-03 DCTD 201571 s at AI656493 NM 001921 1635 -1.12 9.86E-05 BACE1 217904_s_at NM_012104 NM_012104 NM_138971 NM 138972 NM 138973 23621 -1.12 1.17E-03 BC006438 224519 at BC006438 XR_000264 441422 -1.12 9.10E-04 AW192692 227917_at AW192692 — -1.12 3.83E-06 AGA 216064_s_at W27131 NM_000027 175 -1.12 8.70E-03 AI887898 228423 at AI887898 XM_374094 389237 -1.12 4.40E-03 AV714268 242323_at AV714268 — ... -1.11 2.68E-04 CXorf50 242292_at H12084 NM_152693 203429 -1.11 4.02E-04 BC040287 1558605_at BC040287 — — -1.11 7.41 E-03 RSHL2 223713 at AF353618 NM_031924 83861 -1.11 4.32E-05 Al042344 240121_x_at Al042344 — ... -1.11 1.04E-03 GTDC1 239390_at BE327650 NM 00100663 6 NM_024659 79712 -1.11 5.93E-03 MGC14425 1552665_at NM_032903 — 84989 -1.11 1.79E-03 ERBB2 216836_s_at X03363 NM 00100586 2 NM_004448 2064 -1.11 1.73E-05 C21orf51 228239_at AA148789 NM_058182 54065 -1.11 7.04E-06 FLJ35220 238401_at AI311040 NM_173627 284131 -1.11 2.38E-08 SAMD4 212845_at AB028976 NM 015589 23034 -1.10 5.48E-03 CLCN3 201734_at Al760629 NM_001829 NM 173872 1182 -1.10 9.57E-03 416 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B„ et al., Cells Useful for Immuno-Based BoNT/A Activity Assays FLJ31265 238515_at BF687577 NM 152395 131870 -1.10 7.24E-04 ITGB1BP1 203337_x_at NM_004763 NM 004763 NM_022334 9270 -1.10 2.94E-03 AW467480 236202_at AW467480 — ... -1.09 3.18E-03 LIFR 225575_at AI680541 NM_002310 3977 -1.09 6.39E-03 PCDHB16 232099_at AB046841 NMJ520957 57717 -1.09 5.69E-03 AI304870 236574_at AI304870 — — -1.09 4.77E-03 LOC157378 241342_at BG288115 NM_194291 157378 -1.09 7.42E-03 M19720 214058_at M19720 ... ... -1.09 6.67E-03 LOC90693 228087 at AK026684 NM_138771 90693 -1.08 6.62E-06 C10orf104 229145_at AA541762 NMJ 73473 119504 -1.08 3.73E-03 KIAA1324 221874_at AB037745 NM 020775 57535 -1.07 1.16E-04 FGF19 223761 at AF110400 NM_005117 9965 -1.07 8.40E-03 AI768374 228661_s_at Al 768374 — ... -1.07 9.53E-04 PLRG1 225194_at NM_002669 NM_002669 5356 -1.07 8.76E-05 AI821995 240201_at AI821995 — ... -1.07 5.19E-03 LOC400924 226956 at AW025389 XM 376003 400924 -1.07 6.57E-04 SLC22A5 205074_at NMJD03060 NM 003060 6584 -1.07 4.71 E-03 DALRD3 221934_s_at BF941492 NM 00100999 6 NM_018114 55152 -1.07 8.88E-03 AL122040 232429_at AL122040 — ... -1.07 1.70E-06 FLJ10490 220151_at NM_018111 NM 018111 55150 -1.07 4.45E-04 ABTB1 229164_s_at AI337369 NM 032548 NMJ 72027 NMJ 72028 80325 -1.07 5.29E-03 AI569997 242610_x_at Al 569997 ... ... -1.06 7.58E-03 ZNF285 236328_at AW513227 NM 152354 26974 -1.06 2.76E-04 FSTL1 208782 at BC000055 NM_007085 11167 -1.06 9.38E-03 TAF1B 235673_at AI436217 NM_005680 9014 -1.06 2.05E-03 BF002625 229530_at BF002625 — ... -1.06 6.62E-04 PEX6 204545 at NM 000287 NM 000287 5190 -1.06 4.66E-05 ZNF258 219924_s_at NM_007167 NM_007167 NMJ45310 9204 -1.06 5.59E-03 BE467383 228932_at BE467383 XM 497668 388620 -1.06 3.42E-03 TIGD4 232998_at AK024235 NMJ45720 201798 -1.06 7.64E-04 HCG8 215985 at X92110 — 80869 -1.05 5.10E-03 PTPRD 214043_at BF062299 NMJJ02839 NM 130391 NM 130392 NMJ 30393 5789 -1.05 2.37E-03 MAN2A2 219999_at NM 018621 NM 006122 4122 -1.05 3.41 E-03 CHC1 206499_s_at NM 001269 NM 001269 1104 -1.05 3.22E-03 DUSP16 1558739 at R30807 NM 030640 80824 -1.04 6.86E-04 PLEKHA2 238013_at BF347859 XMJ96973 59339 -1.04 7.63E-03 RODH 37512_at U89281 NM_003725 8630 -1.04 2.71 E-03 TMEM42 226361_at BF056095 NM 144638 131616 -1.04 2.56E-03 MGC4655 226058_at AI651445 NM 033309 84752 -1.04 4.77E-04 LMNA 203411_s_at NM_005572 NM_005572 NMJ 70707 NMJ 70708 4000 -1.04 6.43E-03 AL552727 244080 at AL552727 ... ... -1.04 1.69E-03 ALLC 220365_at NM 018436 NM 018436 NM 199232 55821 -1.04 3.61 E-03 KIAA0543 213444_at AB011115 XM_376720 XMJ379967 23145 -1.04 3.24E-07 TRIM61 238990_x_at AI763262 XM_373038 391712 -1.04 3.91 E-03 417 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays AA156605 226798_at AA156605 — — -1.04 1.65E-03 STX12 212111 at AA628051 NM 177424 23673 -1.03 9.08E-07 PHF17 225816_at AW138134 NM_024900 NM_199320 79960 -1.03 9.73E-03 AL042817 225553_at AL042817 — — -1.03 2.32E-04 HEL308 228736_at AW084661 NM 133636 113510 -1.03 9.31 E-04 LOC440388 228855_at Al 927964 XM_496170 440388 -1.03 2.15E-03 ANKRA2 218769_s_at NM 023039 NM_023039 57763 -1.03 3.79E-04 SH3KBP1 223082_at AF230904 NM 031892 30011 -1.03 5.39E-04 MAP7 202890 at AW242297 NM_003980 9053 -1.03 9.43E-03 AI263044 214376_at AI263044 — ... -1.03 4.37E-03 D4S234E 209570_s_at BC001745 NM_014392 27065 -1.03 5.33E-03 BF510563 228561_at BF510563 — — -1.03 7.28E-03 LOC157378 238045 at BG167675 NM_194291 157378 -1.02 9.58E-03 BF510762 230262_at BF510762 — ... -1.02 3.17E-03 SLC2A11 1558540_s_at AK055523 NM 030807 66035 -1.01 5.49E-03 INPP5A 1554757_a_at AF273055 NM_005539 3632 -1.01 3.78E-03 CARD10 210026 s at AY028896 NM 014550 29775 -1.01 4.13E-03 EFNB3 205031_at NM_001406 NM_001406 1949 -1.01 2.94E-03 SVH 1554480_a_at AY150851 NM_031905 83787 -1.01 4.33E-05 PP1057 220968_s_at NM_031285 — 83441 -1.01 3.02 E-04 LOC401320 238540_at AA933883 XM 379482 XM_380098 401320 -1.00 1.29E-03 GNB5 211871_x_at AF300650 NM_006578 NM_016194 10681 -1.00 2.54E-03 BE549742 230724 s at BE549742 — ... -1.00 3.40E-03 MGC34648 228604_at AI805069 NM_152660 199870 -1.00 2.70E-03 AL390170 213904_at AL390170 — ' — -1.00 4.30E-03 LOC400713 232315_at AU149712 XR 000217 400713 -1.00 1.91E-03 0KFZP434H13i 204494_s_at AW516789 NM 015492 56905 -1.00 2.50E-04 DBT 231919_at AK024946 NM_001918 1629 -1.00 3.13E-04 AI459157 225066_at AI459157 — — -1.00 1.73E-03 WASL 227010_at BF438330 NM 003941 8976 -1.00 3.51 E-04 SH3KBP1 1554168 a at AF542051 NM_031892 30011 -0.99 9.41 E-04 LOC339803 227941_at AW327931 — 339803 -0.99 7.41 E-04 NM 017923 219574_at NM_017923 — — -0.99 1.05 E-04 HMGCLL1 232305_at AF131827 NM_019036 54511 -0.99 7.25E-06 MGC29898 235259 at AA398590 NM 145048 133015 -0.99 2.85E-03 LIN7B 219760_at NM 022165 NM 022165 64130 -0.99 6.61 E-06 AI161338 65472_at AI161338 XM 371506 388969 -0.99 7.88E-03 PIGH 209625 at BC004100 NM 004569 5283 -0.99 6.18E-04 RRN3 216902 s at AF001549 NM_018427 54700 -0.98 1.48E-05 BE646451 235893_at BE646451 — ... -0.98 1.01Ε-Ό3 KIAA1223 225735_at AL110131 XM 048747 57182 -0.98 9.14 E-04 SLC18A2 1553328_a_at NM 003054 NM 003054 6571 -0.98 5.03E-03 C19orf4 219005 at NM 012109 NM 012109 25789 -0.98 2.75E-03 D4S234E 213533_at M98528 NM_014392 27065 -0.98 2.97 E-04 CAPN2 208683_at M23254 NM_001748 824 -0.98 7.76E-03 TMEM23 212989 at AI377497 NM 147156 259230 -0.98 5.42 E-03 NEFH 204412_s_at NM_021076 NM_021076 4744 -0.98 9.35E-03 ANXA5 200782_at NM_001154 NM_001154 308 -0.98 5.17 E-03 AI955713 227193_at Al 955713 — ... -0.97 5.36E-08 LOC284422 231982 at AF161441 XM 209196 284422 -0.97 7.92E-03 KCTD18 226493 at Al627249 NM_152387 130535 -0.97 3.04E-05 LOC90024 228832_at Al884670 XM_028217 90024 -0.97 7.03E-03 CA442342 1556097_at CA442342 — — -0.97 3.17E-03 LOC90639 235533 at AW021673 — 90639 -0.97 4.53E-03 HDAC4 228813 at AW206037 NM_006037 9759 -0.96 3.30E-03 418 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B„ etal., Cells Useful for Immuno-Based BoNT/A Activity Assays BC040901 1559535_s_at BC040901 BBS7 235007_at AI683802 MGC48625 1569039_s_at BC029855 MBNL1 201151 s at BF512200 — — -0.96 6.19E-03 NM_018190 NM_176824 55212 -0.96 1.86E-03 NM 182609 342926 -0.96 7.88E-05 NM 021038 4154 -0.96 4.33E-03 NM_207292 NM_207293 NM_207294 NM_207295 NM_207296 NM 207297 CIB1 201953_at NM_006384 RPP21 218836_at NM 024839 CHC1 215747 s at X06130 ACSL1 201963_at NM_021122 RHOU 223169_s_at AB051826 KIAA0773 205368 at NM_014690 PDPK1 32029_at AC005591 GNG8 234284_at AF188179 C14orf133 233140 s at AF111168 ITR 231871 at AU160685 BC015852 1560570_a_at BC015852 SNF1LK2 223430_at AL136764 CKLFSF1 235286_at BG533580 NM_006384 10519 -0.96 2.33E-04 NM 024839 79897 -0.96 2.49E-03 NM_001269 1104 -0.96 4.49E-03 NM_001995 2180 -0.95 5.71 E-04 NM_021205 58480 -0.95 1.29E-03 NM 014690 9715 -0.95 1.39E-03 NM 002613 NM_031268 5170 -0.95 4.56E-04 NM_033258 94235 -0.95 5.33E-04 NM 022067 63894 -0.95 4.26E-04 NM_180989 160897 -0.95 5.11E-03 — — -0.95 6.20E-03 NM 015191 23235 -0.95 2.99E-03 NM 052999 113540 -0.95 5.78E-03 NM_181268 NM_181269 NM_181270 NM_181271 NM_181272 NM181283 NM_181285 NM_181286 NM_181287 NM_181288 NM_181289 NM_181290 NM_181292 NM_181293 NM_181294 NM_181295 NM_181296 NM_181297 NM_181298 NM_181299 NM_181300 NM 181301 BTN3A3 204821_at NM_006994 PLEKHC1 209210_s_at Z24725 RNF41 201962_s_at NM_005785 NAP1L3 204749_at NM_004538 ZNF251 226754_at W93231 PLEKHA2 217677_at BF542055 SIDT2 56256_at AA150165 STX12 212112 s at AI816243 NM 006994 10384 -0.95 7.79E-05 NM_197974 NM 006832 10979 -0.94 2.90E-03 NM 005785 10193 -0.94 3.16E-03 NM 194358 NM_194359 NM_004538 4675 -0.94 2.43E-03 XM_291262 90987 -0.94 1.04E-03 XM 496973 59339 -0.94 7.55E-03 NM_015996 51092 -0.94 3.96E-04 NM 177424 23673 -0.94 7.35E-05 419 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et at., Cells Useful for Immuno-Based BoNT/A Activity Assays STX17 228091_at Al 800609 NM_017919 55014 -0.94 6.04E-03 C2orf17 221983 at AL040896 NM 024293 79137 -0.94 4.85E-03 ZFP28 234937_x_at AC007228 NM_020828 140612 -0.94 3.30E-03 HLA-G 210514_x_at AF226990 NM_002127 3135 -0.94 1.71E-04 MGC14801 224443_at BC005997 NM_032705 84791 -0.93 9.68E-03 N79601 242981 at N79601 — — -0.93 4.16E-03 LOC284926 1556064_at BQ575161 — 284926 -0.93 5.64E-03 WDR9 225446_at AI638279 NM_00100724 6 NM 018963 NM_033656 54014 -0.93 3.04E-04 AI652546 228853_at AI652546 — — -0.93 4.31 E-03 EIF4E3 238461_at AA228031 — 317649 -0.92 5.07E-03 AU151944 236916_at AU151944 — — -0.92 1.50E-03 ZNF610 235953 at AA776810 NM 173530 162963 -0.92 3.79E-04 RGS14 38290_at AF037195 NM_006480 10636 -0.92 1.22E-03 WDR24 223293_at AL136863 NM_032259 84219 -0.92 5.54E-04 T87730 242500 at T87730 ' — — -0.92 7.27E-03 AW615274 229423 at AW615274 — — -0.92 8.89E-03 SIRT5 219185_at NM 012241 NM_012241 NM_031244 23408 -0.91 1.64E-03 MGC54289 225230_at AI735261 NM 178454 128338 -0.91 9.98E-03 LMNA 212089_at M13452 NM 005572 NM_170707 NM_170708 4000 -0.91 7.00E-03 NINJ1 203045 at NM 004148 NM 004148 4814 -0.91 3.51 E-04 C9orf127 229729_at BF507870 NM_016446 51754 -0.91 1.20E-04 LAF4 227198 at AW085505 NM_002285 3899 -0.91 4.25E-05 ADPRHL2 223097_at AF212236 NM_017825 54936 -0.91 1.91 E-04 N21364 214202 at N21364 — — -0.90 6.59E-06 LOC388727 231233 at Al382195 XM_373881 388727 -0.90 1.97E-03 ALU Sequence,FFX-hum_alu_i AFFX-hum_alu NM_000021 NM 000051 NM_000136 NM_000141 NM_000144 NM_000202 NM 00022 NM_000230 NM_000294 NM 000297 NM 000314 NM_000356 NM_000364 NM 000382 NM 000441 NM_000484 NM_000527 NM 000554 -0.90 2.52E-03 ACYP2 206833_s_at NM_001108 NM_138448 98 -0.90 4.12E-03 EXOC7 212026_s_at BE646386 NM__015219 23265 -0.90 1.03E-03 RPUSD3 225743_at Al 125996 NM_173659 285367 -0.90 3.62E-03 R15431 236440 at R15431 — — -0.90 3.46E-05 AA194266 238728_at AA194266 — — -0.90 8.94E-03 GNB5 207124_s_at NM_006578 NM_006578 NM_016194 10681 -0.90 2.52E-04 TEX264 233350 s at AU158474 NM 015926 51368 -0.89 3.96E-04 TRIM32 1557315_a_at AL134420 NM 012210 22954 -0.89 4.37E-03 420 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al„ Cells Useful for Immuno-Based BoNT/A Activity Assays BF342524 235074_at BF342524 — — -0.89 2.65E-05 HADHA 236120 at AW955973 NM 000182 3030 -0.89 8.56E-03 C21orf119 227424_x_at AI800837 NM_032910 84996 -0.88 6.71 E-03 CLN5 204085_s_at NM_006493 NM_006493 1203 -0.88 6.71 E-03 SAV1 218276_s_at NM_021818 NM 021818 60485 -0.88 4.58E-03 HDHD3 221256 s at NM 031219 NM_031219 81932 -0.88 4.72E-03 EMID1 213779_at AL031186 NM_133455 129080 -0.88 4.61 E-05 GAL3ST3 1553257_at AY026481 NM_033036 89792 -0.88 5.62 E-03 USP44 224048_at AL136825 NM_032147 84101 -0.88 1.11 E-03 ACSL1 207275 s_at NM 001995 NM_001995 2180 -0.87 9.24E-03 AK024681 231972 at AK024681 — — -0.87 6.32 E-03 AL527331 238716_at AL527331 ... — -0.87 3.42E-03 KIAA0711 204301_at NM_014867 NM_014867 9920 -0.87 5.63E-07 NOL3 221566 s at AF043244 NM_003946 8996 -0.87 4.45E-03 AW236954 1557117 at AW236954 — — -0.87 1.02 E-03 MRPS33 218654_s_at N M 016071 NM_016071 NM_053035 51650 -0.87 5.05E-03 SLC19A1 229489_at AI681043 NM 003056 NM_194255 6573 -0.87 4.84E-04 ATP2C1 209935_at AF225981 NM_00100148 5 NM_00100148 6 NM_00100148 7 NM 014382 27032 -0.87 1.03E-03 MBNL1 201153_s_at NM_021038 NM_021038 NM_207292 NM_207293 NM 207294 NM_207295 NM 207296 NM_207297 4154 -0.87 2.49E-04 MGC52110 226039_at AW006441 NM 001008215 493753 -0.86 1.48E-03 OTUB2 219369_s_at NM 023112 NM_023112 78990 -0.86 4.20E-03 ZNF558 227810_at AW 119060 NM_144693 148156 -0.86 1.86E-04 ANKH 229176_at AI672354 NM 054027 56172 -0.86 8.12 E-03 SYNE1 209447_at AF043290 NM 015293 NM_033071 NM_133650 NM_182961 23345 -0.86 3.81 E-03 MGC35097 225755 at AM 60540 NM_173546 200942 -0.86 6.77E-03 AI471969 239278_at AI471969 — — -0.86 2.25E-03 OR6M1 227112_at AW270037 NM 001005325 390261 -0.86 2.99E-04 DSCR3 217309_s_at AJ001867 NM_006052 10311 -0.86 1.52E-04 VGLL4 212399_s_at D50911 NM_014667 9686 -0.86 1.90E-03 RNH 206050_s_at NM_002939 NM 002939 NM 203383 NM_203384 NM_203385 NM_203386 NM 203387 NM 203388 NM_203389 6050 -0.85 1.17E-03 EIF3S2 208756_at U36764 NM_003757 8668 -0.85 3.95E-04 CHCHD5 235825 at AI057238 NM 032309 84269 -0.85 2.48E-03 FLJ25715 231952_at AU157271 NM 182570 284241 -0.85 4.49E-03 H28915 244359 s at H28915 XM 496692 441014 -0.85 2.81 E-03 421 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al„ Cells Useful for Immuno-Based BoNT/A Activity Assays SVH 223328 at BC003586 NM 031905 83787 -0.85 2.28E-03 BRD4 238612_at AW298070 NM_014299 NM_058243 23476 -0.85 4.92E-04 PLEKHC1 209209_s_at AW469573 NM_006832 10979 -0.85 9.05E-03 LOC220930 229090_at AK026657 — 220930 -0.85 5.83E-04 AW665538 244532 x at AW665538 XM_496692 441014 -0.85 3.20E-03 DKFZp727A071 227348_at AW409848 NM_152268 25973 -0.85 4.70E-05 STK19 36019_at L26260 NM_004197 NM 032454 8859 -0.85 1.10E-03 DCTD 210137_s_at BC001286 NM 001921 1635 -0.84 7.33E-03 AMT 204294_at NM 000481 NM_000481 275 -0.84 1.21E-03 ERBB4 206794_at NM_005235 NM_005235 2066 -0.84 7.70E-03 AI003508 244114 x at AI003508 XM 496690 401131 -0.84 2.43E-03 CNOT6L 227119_at BF103856 NM 144571 246175 -0.84 1.58E-04 LRRC14 32062_at D25216 NM_014665 9684 -0.84 1.95E-03 AI796858 236164_at AI796858 — — -0.84 8.09E-03 SUMF2 225002 s at BE349022 NM_015411 25870 -0.84 1.85E-03 CLN8 229958_at W93695 NM 018941 2055 -0.84 1.34E-03 TDRKH 221052_at NM 006862 NM_006862 11022 -0.84 1.92E-03 BF340290 225220_at BF340290 — — -0.84 8.97E-03 LNX 227293_at AI264003 NM 032622 84708 -0.84 2.20E-03 ADCK1 227482_at Al 097656 NM 020421 57143 -0.83 4.63E-03 FLJ31340 235301_at Al 797353 NM 152748 222223 -0.83 9.27E-04 FLJ12716 218179_s_at NM_021942 NM_021942 NM_199053 60684 -0.83 3.97E-04 ACP6 218795_at NM_016361 NM 016361 51205 -0.83 7.19E-04 KIAA0543 226808_at AW771007 XM_376720 XM_379967 23145 -0.83 2.42E-04 PAK6 1555310_a_at BC035596 NM_020168 56924 -0.83 2.78E-03 TXNDC4 208958_at AI827677 NM_015051 23071 -0.83 1.35E-03 PAM 202336_s_at NM_000919 NM_000919 NM 138766 NM 138821 NM_138822 5066 -0.83 4.55E-03 LOC57149 203897 at BE963444 NM 020424 57149 -0.82 1.05E-04 DCP1B 226093_at AW204088 NM 152640 196513 -0.82 6.19E-04 FLJ12716 233558_s_at AK023390 NM_021942 NM_199053 60684 -0.82 8.71 E-04 TP53TG3 220167_s_at NM_015369 NM_015369 NM 016212 24150 -0.82 3.88E-04 OCIAD2 225314_at BG291649 NM_152398 132299 -0.82 8.74E-03 C14orf133 218431_at NM_022067 NM_022067 63894 -0.82 9.75E-04 FLJ38991 227442_at BG283902 NM_173827 285521 -0.82 2.25E-03 FLJ31340 244317 at BF035563 NM 152748 222223 -0.82 5.35E-03 DSCR3 203635_at NM 006052 NM 006052 10311 -0.82 8.42 E-04 PDCD2 204025_s_at NM_002598 NM 002598 NM_144781 5134 -0.81 5.01 E-04 DKFZP564D16f 224952 at BF115054 XM 371074 26115 -0.81 3.50E-04 FLJ13231 219381_at NM_023073 NM 023073 65250 -0.81 9.78E-03 CDC37L1 235787_at T65394 NM017913 55664 -0.81 7.07 E-04 WDTC1 215497_s_at AK023778 NM_015023 23038 -0.81 5.43E-04 LOC94431 216908_x_at AF001549 NM 145237 94431 -0.81 3.74E-06 SEC31L1 215009_s_at U92014 NM_014933 NM_016211 22872 -0.81 2.06E-03 ZNF148 230821_at AW594167 NM_021964 7707 -0.81 5.30E-03 DHRSX 225503_at AL547782 NM 145177 207063 -0.81 8.16E-06 LYPLA3 204458_at AL110209 NM 012320 23659 -0.81 3.93E-03 422 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et aL, Cells Useful for Immuno-Based BoNT/A Activity Assays DCTD 201572_x_at NM_001921 NM_001921 1635 -0.81 5.30E-04 FLJ31265 228341 at AI809108 NM_152395 131870 -0.81 9.80E-04 TBC1D12 221858_at N34407 XM_051081 23232 -0.81 2.80E-03 FLJ22795 223327_x_at AF316855 NM_025084 80154 -0.81 6.81 E-06 ZNF274 204937_s_at NM_016325 NM_016324 NM 016325 NM_133502 10782 -0.81 2.65E-03 CSTB 201201_at NM_000100 NM_000100 1476 -0.80 6.53E-04 LOC151146 227604_at BG292251 — 151146 -0.80 2.89E-03 SLC18A2 205857_at AI269290 NM_003054 6571 -0.80 3.73E-03 MANSC 1 220945 x at NM_018050 NM_018050 54682 -0.80 2.89E-03 R44603 244113_at R44603 — — -0.80 2.19E-03 PAK1 226507 at AU154408 NM 002576 5058 -0.80 4.33E-03 KIRREL3 240402_at H05918 NM_032531 84623 -0.80 2.61 E-03 AW516665 227571_at AW516665 — — -0.80 4.02E-03 FBXL5 209005_at AF157323 NM_012161 NM_033535 26234 -0.80 2.18E-04 TM4SF2 202242 at NM_004615 NM 004615 7102 -0.80 4.39E-03 EHD2 45297_at AI417917 NM 014601 30846 -0.80 2.06E-05 UBE2D3 200667_at BF448062 NM_003340 NM_181886 NM_181887 NM 181888 NM 181889 NM_181890 NM 181891 NM 181892 NM_181893 7323 -0.79 7.56E-06 AA868896 226203_at AA868896 — — -0.79 2.92E-03 DUSP24 233982 x at AF188204 NM_016086 51657 -0.79 9.14E-03 AU157441 226511_at AU157441 — — -0.79 1.27E-03 AK2 205996_s_at NM_013411 NM_001625 NM_013411 NM_172199 204 -0.79 2.76E-03 AF086443 1560982_at AF086443 — — -0.79 4.61 E-03 C9orf9 220050_at NM 018956 NM_018956 11092 -0.79 1.17E-03 ZNF23 213934_s_at AL567808 NM_145911 7571 -0.79 3.42E-03 HLA-G 211529 x at M90684 NM 002127 3135 -0.79 1.15E-03 XPR1 226615_at BE439489 NM_004736 9213 -0.79 8.43E-04 THAP9 230185_at AW301218 NM 024672 79725 -0.79 4.10E-03 CCNDBP1 223084_s_at AF246144 NM 012142 NM_037370 23582 -0.79 1.05E-04 AP3B2 205678_at NM_004644 NM_004644 8120 -0.78 3.03E-03 CTHRC1 225681 at AA584310 NM_138455 115908 -0.78 2.80E-03 LOC93622 225391_at AL562398 NM 138699 93622 -0.78 8.43E-03 JAG2 209784_s_at AF029778 NM_002226 NMJ45159 3714 -0.78 7.94 E-03 ZNF585A 229794_at BE550717 NM_152655 NM_199126 199704 -0.78 4.45E-03 MGC2650 204985_s_at NM 024108 NM 024108 79090 -0.78 4.43E-03 APRT 203219_s_at NM 000485 NM_000485 353 -0.78 5.08E-04 USP36 220370_s_at NM_025090 NM_025090 57602 -0.78 3.64E-03 INPP5A 203006 at NM 005539 NM 005539 3632 -0.78 8.67E-03 ZNF197 205855 at NM 006991 NM 006991 10168 -0.78 6.14E-03 PLEKHA2 225136_at BF968578 XM 496973 59339 -0.78 4.19E-04 ARHGEF4 205109_s_at NM_015320 NM 015320 NM 032995 50649 -0.77 7.05E-03 423 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays NET01 1552736_a_at NM_138966 NM_138966 NM 138999 NM 153181 81832 -0.77 2.29E-04 LRPAP1 201186_at NM_002337 NM 002337 4043 -0.77 7.07E-03 MYST1 221820_s_at AK024102 NM_032188 84148 -0.77 7.03E-03 FLJ12998 244734 at W45568 NM 022764 64779 -0.77 1.04E-04 CLTC 238646_at AA747756 NM 004859 1213 -0.77 8.00E-03 SLC30A5 1555334_s_at AF439324 NM_022902 NM_024055 64924 -0.77 3.91 E-03 PRKAG1 201805_at NM_002733 NM_002733 NM_212461 5571 -0.77 2.24E-03 GPRASP1 204793_at NM014710 NM 014710 9737 -0.77 1.73 E-03 NET01 1562713_a_at AL834354 NM 138966 NM_138999 NM 153181 81832 -0.77 2.38E-03 LOC89894 227172_at BC000282 NM_138341 89894 -0.77 3.71 E-04 STK19 204090_at NM_004197 NM 004197 NM_032454 8859 -0.77 2.21 E-03 LIPT1 205571_at NM_015929 NM_015929 NM 145196 NM_145197 NM_145198 NM_145199 51601 -0.77 1.12E-03 ZCWCC3 213000_at AP000693 NM 015358 23515 -0.77 1.90E-03 CLCN3 201735_s_at NM_001829 NM 001829 NM_173872 1182 -0.77 8.06E-03 FLJ32370 226483_at Al 890761 NM_152417 137695 -0.76 2.24E-03 FYC01 218204 s at NM 024513 NM_024513 79443 -0.76 1.16E-07 NEIL2 226585 at BE466620 NM 145043 252969 -0.76 5.49E-04 KCNH2 205262_at NM 000238 NM_000238 NM_172056 NM_172057 3757 -0.76 9.14E-06 BF966015 226787 at BF966015 — — -0.76 3.80E-06 BBP 213882_at AA012917 NM 032027 83941 -0.76 1.89E-03 GSTZ1 209531_at BC001453 NM_001513 NM_145870 NM 145871 2954 -0.76 3.56E-03 EIF2C1 228120_at AW136032 NM_012199 26523 -0.76 6.17E-03 PCTK2 206474_at NM_002595 NM_002595 5128 -0.76 4.76E-03 C13orf21 243094 at BF509416 NM 001010897 387923 -0.76 5.57E-03 MAPRE3 214270_s_at AI885178 NM_012326 22924 -0.76 3.88E-03 BC017239 1558045_a_at BC017239 — — -0.75 3.87E-03 COL27A1 225288_at AI949136 NM_032888 85301 -0.75 9.38E-04 AI672159 226550 at AI672159 — — -0.75 1.09E-04 MBNL1 201152_s_at N31913 NM_021038 NM_207292 NM_207293 NM 207294 NM_207295 NM_207296 NM 207297 4154 -0.75 1.55E-04 TBN 1556178 x at BU618741 NM 138572 129685 -0.75 9.97E-03 TMAP1 227326_at BE966768 NM_00100852 8 NM 00100852 9 NM 198530 439921 -0.75 4.09E-04 424 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays TNFRSF21 218856_at NM 016629 NM_014452 27242 -0.75 6.87E-03 CHMP1.5 218177 at AA293502 NM 020412 57132 -0.75 5.52E-05 SHFM3 221519 at AF281859 NM_022039 6468 -0.75 1.33E-03 AU151635 232111_at AU151635 — — -0.75 1.40E-07 PTK9L 202009_at NM 007284 NM 007284 11344 -0.75 8.11E-03 PAM 214620_x_at BF038548 NM 000919 NM 138766 NM_138821 NM_138822 5066 -0.75 3.40E-03 WDFY3 212606_at AL536319 NM 014991 NM_178583 NM_178585 23001 -0.75 1.05E-03 KIAA1277 221885_at Al 131051 NM_015689 27147 -Q.75 5.98E-03 DIRAS2 219619 at NM 017594 NM 017594 54769 -0.74 6.42E-03 EXT2 202012_s_at AA196245 NM_000401 NM_207122 2132 -0.74 5.88E-04 C18orf17 238480_at AI871745 NM 153211 125488 -0.74 4.89E-04 SLC9A1 209453_at M81768 NM 003047 6548 -0.74 5.21 E-06 PCBD1 203557_s_at NM_000281 NM_000281 NM_00100193 5092 -0.74 2.72E-04 C6orf83 225850 at BF975327 y NMJ45169 113402 -0.74 6.67E-03 PIGV 219238_at NM_017837 NM_017837 55650 -0.74 4.79E-04 KIAA0276 243691_at AA150455 NM 015115 23142 -0.74 7.85E-03 PAM 212958_x_at Al 022882 NM 000919 NM 138766 NM_138821 NM_138822 5066 -0.74 9.54E-03 NM 152909 1553719 s at NM 152909 — — -0.74 1.13E-03 PKD1 216949_s_at L39891 NM_000296 5310 -0.74 1.43E-03 NM_00100994 4 AI768895 231069 at AI768895 — — -0.74 7.25E-03 MTMR7 228024 at AW028100 NM_004686 9108 -0.74 3.76E-05 BRUNOL4 223653_x_at AW593887 NM 020180 56853 -0.74 9.74E-03 LOH12CR1 227723_at BF439234 NM 058169 118426 -0.74 7.19E-03 PTN 209465 x at AL565812 NM_002825 5764 -0.73 7.19E-03 RPL4 226556 at BF431260 NM_000968 6124 -0.73 4.08E-03 MTRF1 219822_at NM_004294 NM_004294 9617 -0.73 1.42E-04 PCCA 203860_at NM 000282 NM_000282 5095 -0.73 9.56E-03 RPS4Y1 201909_at NM 001008 NM 001008 6192 -0.73 2.03E-03 FLJ11273 222787_s_at AV705186 NM_018374 54664 -0.73 7.27E-04 CSE-C 224391_s_at AF303378 NM_170601 54414 -0.73 3.37E-03 KIAA0323 212356_at AB002321 NM_015299 23351 -0.73 8.63E-03 AI061377 235232_at Al 061377 — — -0.73 9.74E-03 SH3YL1 204019_s_at NM_015677 NM_015677 26751 -0.73 2.48E-03 LOC255458 1556180_at BE646146 — 255458 -0.73 6.08E-05 JAGN1 223104_at AF212230 NM_032492 84522 -0.73 2.17E-05 FLJ10038 205511 at NM_017976 — 55056 -0.73 5.36E-03 FLJ13984 220007_at NM_024770 NM_024770 79828 -0.73 6.13E-03 TMEM34 219074_at NM_018241 NM 018241 55751 -0.73 8.00E-03 ARRDC1 226405 s at AK001822 NM_152285 92714 -0.72 2.87E-03 BF056746 228425_at BF056746 — — -0.72 4.99E-04 P15RS 222559_s_at T79568 NM_018170 55197 -0.72 1.36E-05 FLJ23560 219487 at NM_024685 NM_024685 79738 -0.72 9.23E-03 ANKH 223093 at T99215 NM 054027 56172 -0.72 3.35E-03 VAPA 225198 at AL571942 NM_003574 NM 194434 9218 -0.72 2.38E-03 425 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays CCDC2 219174_at NM 025103 NM_025103 80173 -0.72 2.41 E-03 AA709148 243751_at AA709148 — — -0.72 2.28E-04 GART 217445_s_at AF008655 NM 000819 NM 175085 2618 -0.72 1.27E-03 LOC389906 LOC389910 LOC401625 1558046_x_at BC017239 XM_372273 XM_374343 XM_377076 389906 389910 401625 -0.72 1.71 E-03 SAV1 222573 s at AI679398 NM_021818 60485 -0.72 5.04E-04 BBS2 223227_at AF342736 NM_031885 583 -0.72 2.39E-03 FLJ10726 218314_s_at NM_018195 NM_018195 55216 -0.72 9.03E-04 AK055769 1558801_at AK055769 — — -0.71 5.90E-03 R53065 240430 at R53065 — ... -0.71 6.12E-03 WDFY3 212602_at AI806395 NM_014991 NM 178583 NM 178585 23001 -0.71 1.21 E-03 CSNK2A2 203575_at NM_001896 NM_001896 1459 -0.71 5.96E-03 KIAA0992 200907_s_at AU157932 NM 016081 23022 -0.71 2.15E-03 LMNA 212086_x_at AK026584 NM_005572 NM 170707 NM_170708 4000 -0.71 6.61 E-03 BE502930 235124_at BE502930 — — -0.71 3.16E-04 AI765014 224649_x_at Al 765014 ... ... -0.71 2.78E-03 TTC13 219481 at NM 024525 NM_024525 79573 -0.71 1.48E-03 GAS5 224841_x_at BF316352 — 60674 -0.71 6.06E-03 AI652899 228812_at AI652899 — — -0.71 5.25E-05 PLCB1 213222_at AL049593 NM 015192 NM_182734 23236 -0.71 7.21 E-04 DET1 219641 at NMO17996 NM_017996 55070 -0.71 1.63E-03 ACSL3 201660_at AL525798 NM_004457 NM_203372 2181 -0.71 3.90E-04 MGC2749 200076 s at BC006479 NM 024069 79036 -0.71 6.49E-03 QPCT 205174_s_at NM012413 NM 012413 25797 -0.71 6.07E-03 PML 209640_at M79462 NM 002675 NM 033238 NM_033239 NM 033240 NM_033242 NM_033244 NM_033245 NM_033246 NM_033247 NM 033249 NM_033250 5371 -0.70 3.55E-03 LRRC27 1558483_at AK098652 NM 030626 80313 -0.70 3.75E-03 STK16 209622_at AB020739 NM 00100891 8576 -0.70 2.64E-04 0 NM 003691 CRYZL1 219767_s_at NM_005111 NM_005111 NM 145311 NM_145858 9946 -0.70 2.94 E-03 TMEM43 217795_s_at W74580 NM 024334 79188 -0.70 3.09E-03 DFFA 203277_at NM_004401 NM_004401 NM_213566 1676 -0.70 4.51 E-03 BF062875 230072 at BF062875 — — -0.70 7.79E-04 AW974666 222365_at AW974666 — — -0.70 3.83E-03 AA827878 223577_x_at AA827878 — — -0.70 8.67E-03 TMEM43 222418_s_at AA115485 NM_024334 79188 -0.70 3.97E-03 426 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays C14orf118 219720_s_at NM_017972 NM_017926 NM_017972 55668 -0.70 1.92E-03 LOC285550 227270 at BF593037 XM 209656 285550 -0.70 1.40E-03 LRRC28 227423_at AI655972 NM 144598 123355 -0.70 6.98E-04 PFN2 237116_at Al262277 NM_002628 NM_053024 5217 -0.70 2.39E-03 JMY 226352_at BF447037 NM_152405 133746 -0.70 9.37E-04 TLOC1 225352_at AI763287 NM_003262 7095 -0.69 2.60E-04 PPID 204186_s_at AI014573 NM_005038 5481 -0.69 1.10E-03 FLJ38968 226383_at AI652452 NM 152316 120534 -0.69 1.37E-03 KIAA0992 200897 s at NM 016081 NM 016081 23022 -0.69 1.00E-03 SLC30A5 232432_s_at AK022818 NM 022902 NM_024055 64924 -0.69 2.34E-03 AIG1 230520 at T78402 NM 016108 51390 -0.69 7.09E-05 FKBP9 212169_at AL050187 NM 007270 11328 -0.69 3.13E-03 T1 56829_at H61826 NM 031466 83696 -0.69 4.28E-03 AA813998 235837_at AA813998 — — -0.69 7.10E-03 SNAP91 204953 at NM_014841 NM 014841 9892 -0.69 8.76E-03 PLD3 201050_at NM_012268 NM_012268 23646 -0.69 2.09E-03 CGI-41 218914_at NM_015997 NM_015997 51093 -0.69 6.72E-03 RARA 228037_at AA404273 NM 000964 5914 -0.69 9.78E-04 MY09A 219027_s_at NM 006901 NM 006901 4649 -0.68 3.06E-03 RDH13 I559190_s_at AL833150 NM_138412 112724 -0.68 6.77E-03 RGS14 204280_at NM_006480 NM_006480 10636 -0.68 1.43E-04 FLJ34222 235717_at AA180985 XM_371175 284350 -0.68 3.45E-05 BF434383 235473 at BF434383 — — -0.68 8.03E-04 CDKL3 219831_at NM_016508 NM_016508 51265 -0.68 4.12E-05 FRBZ1 226962_at AW299558 NM 194314 360023 -0.68 3.75E-03 FLJ37953 241825_at AI265967 NM_152382 129450 -0.68 8.57E-04 TRIM4 223384_s_at BE501464 NM 033017 NM_033091 89122 -0.68 2.58E-03 SF3B3 200688 at D13642 NM 012426 23450 -0.68 4.67E-03 PHF10 219126_at NM_018288 NM 018288 NM_133325 55274 -0.68 2.92E-03 IL17RB 235531_at AA928257 NM 018725 NM_172234 55540 -0.68 2.10E-03 BCL2L13 224035 s at AF183411 NM 015367 23786 -0.68 7.08E-04 MAN1A2 217922_at AL157902 NM_006699 10905 -0.68 3.21 E-03 ZNF232 236075_s_at AI693543 NM_014519 7775 -0.68 6.78E-03 BC024246 1556301 at BC024246 — — -0.68 2.06E-04 ZRANB1 225130 at AW003734 NM 017580 54764 -0.67 1.84E-04 PP1665 32502_at AL041124 NM_030792 81544 -0.67 9.49E-04 CAB39 224311_s_at AF151824 NM_016289 51719 -0.67 2.14E-03 KRTAP4-7 225225_at BF791544 NM 033061 85287 -0.67 8.80E-03 SLC30A5 218989_x_at NM_022902 NM_022902 NM_024055 64924 -0.67 6.75E-03 RNF41 201961_s_at AL583171 NM_005785 NM 194358 NM_194359 10193 -0.67 8.95E-03 C6orf168 232067_at BC004869 NM _032511 84553 -0.67 2.42E-03 TNIP2 232160_s_at AL137262 NM_024309 79155 -0.67 1.56E-03 DKFZP564D17i 212936_at Al 927701 NM 032042 83989 -0.67 5.18E-04 LOC439962 1560047_s_at AA127813 XM_498479 439962 -0.67 3.91 E-03 MCM3APAS 220459_at NM_018118 — 114044 -0.67 2.26E-03 SLC35E1 229410_at AI659219 NM 024881 79939 -0.67 5.75E-03 FBXW7 229419_at BF222826 NM 018315 NM 033632 55294 -0.67 9.92E-04 427 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays C10orf22 212500_at AL049319 NM_032804 84890 -0.67 3.49E-04 SURF2 205224_at NM_017503 NM_017503 6835 -0.67 3.01 E-04 MGC12966 224452_s_at BC006110 NM_032706 84792 -0.67 4.02E-04 FLJ20195 223833_at BC002482 NM 017706 54853 -0.67 5.69E-03 FLJ20542 233625_x_at AK021939 NM 017871 NM_032179 54973 -0.67 8.46 E-04 LRCH2 227688_at AK022128 NM 020871 57631 -0.67 2.21 E-04 SLC22A17 218675_at NM_020372 NM_016609 NM_020372 51310 -0.67 3.50E-03 ARNT2 202986_at NM_014862 NM 014862 9915 -0.67 1.18E-03 LOC440118 FX-M27830_MAFFX-M27830_M XM_498554 440118 -0.67 5.77E-03 FLJ23518 223300_s_at AI286012 NM 024725 79780 -0.66 7.90E-04 PROSC 209384_at AA176833 NM 007198 11212 -0.66 1.14E-03 P15RS 222558_at T79568 NM 018170 55197 -0.66 1.67E-04 PPP2R5C 201877_s_at NM_002719 NM_002719 NM_178586 NM 178587 NM 178588 5527 -0.66 3.07E-06 SGNE1 203889_at NM_003020 NM 003020 6447 -0.66 1.31 E-04 CNOT6L 1553267_a_at NM_144571 NM 144571 246175 -0.66 5.11E-03 TTLL1 205652_s_at NM_012263 NM_00100857 2 NM_012263 25809 -0.66 3.38E-04 AD023 223411_at AF225422 NM_020679 57409 -0.66 7.26E-06 KIF3C 203389 at AF035621 NM_002254 3797 -0.66 2.70E-04 AI598222 235679 at AI598222 — ... -0.65 7.93E-03 PPP3CA 202457_s_at AA911231 NM 000944 5530 -0.65 9.97E-03 RPIP8 213439_x_at Al 197870 NM_006695 10900 -0.65 1.89E-03 NSMCE1 224666 at AF161451 NM 145080 197370 -0.65 3.16E-04 BACE1 222462_s_at Al653425 NM_012104 NM 138971 NM 138972 NM 138973 23621 -0.65 3.25E-03 MPI 202472_at NM_002435 NM_002435 4351 -0.65 8.59E-04 FBXW7 222729_at BE551877 NM_018315 NM_033632 55294 -0.65 2.52E-03 NELF 221214 s at NM_015537 NM 015537 26012 -0.65 7.98E-04 HLA-A 215313_x_at AA573862 NM_002116 3105 -0.65 7.23E-03 FGF2 204422_s_at NM_002006 NM_002006 2247 -0.65 4.86E-07 P15RS 225953_at AI684281 NMJD18170 55197 -0.65 3.76E-04 GAS5 224741 x at BG329175 — 60674 -0.65 8.18E-03 IP08 205701_at NM_006390 NM_006390 10526 -0.65 7.25E-04 ECE2 230706_s_at Al084921 NM_014693 9718 -0.65 4.71 E-04 ZCSL3 213853_at AL050199 NM 181706 120526 -0.65 6.76E-03 PSEN1 226577_at N49844 NM 000021 NM_007318 NM 007319 5663 -0.65 3.44E-03 LOC284018 226901_at AI214996 NM 181655 NM_181656 284018 -0.64 5.00E-04 FLJ32384 238547_at AI972367 NM_144608 124790 -0.64 3.77E-03 LOC284106 230727_at BE348515 XM_375449 284106 -0.64 7.65E-03 WDR32 219001 s at NM 024345 NM 024345 79269 -0.64 1.25E-04 RNF13 201779_s_at AF070558 NM_007282 NM_183381 NM_183382 NM 183383 NM 183384 11342 -0.64 1.26E-04 428 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al., Cells Useful for Immuno-Based BoNT/A Activity Assays VPS33B 218415_at NM_018668 NM_018668 26276 -0.64 7.92E-03 SPTBN2 231311 at AA725246 NM 006946 6712 -0.64 1.71 E-03 LOC389906 1569629 x at BC017231 XM 372273 389906 -0.64 4.97E-04 C22orf9 227144_at AA476916 NM 00100988 0 NM 015264 23313 -0.64 3.58E-03 PHKA1 205450_at NM_002637 NM_002637 5255 -0.64 3.01 E-03 COPS7A 209029_at AF193844 NM 016319 50813 -0.64 6.55E-05 EIF2S3 205321_at NM_001415 NM 001415 1968 -0.64 8.39E-03 TM6SF1 1558102 at AK055438 NM 023003 53346 -0.64 2.18E-04 ATCAY 227365 at AL566774 NM_033064 85300 -0.64 8.51 E-03 CGI-119 223892_s_at AF182414 NM_016056 51643 -0.64 1.66E-04 APG7L 224025_s_at BC000091 NM 006395 10533 -0.64 4.74E-03 CIRBP 230142 s at AW088030 NM 001280 1153 -0.64 2.64E-03 C21orf127 220311_at NM_013240 NM_013240 NM_182749 29104 -0.64 2.93 E-03 JKFZP566D134 238597_at BG028770 NM_030816 81573 -0.63 9.05E-03 WNT3 229103 at AA463626 NM 030753 7473 -0.63 1.82E-03 C10orf88 219240 s at NM_024942 NM 024942 80007 -0.63 2.53E-03 KCNMB3 235980_at AA767763 NM 014407 NM 171828 NM 171829 NM_171830 27094 -0.63 9.48E-04 LOC440360 236838_at H11609 XM_498641 440360 -0.63 4.34E-03 AA868380 230569_at AA868380 — — -0.63 7.44E-03 C3orf6 235051_at BF696931 NM 174908 NM_178335 152137 -0.63 9.04E-03 BLP2 1552426_a_at NM_078474 NM_025141 NM_078474 80213 -0.63 9.66 E-03 PPID 204185 x at NM 005038 NM 005038 5481 -0.63 3.34E-03 CXorf12 204340_at NM_003492 NM 003492 8269 -0.63 4.03E-03 PLCB1 211925_s_at AY004175 NM_015192 NM_182734 23236 -0.63 8.12E-05 MY07A 208189 s at NM 000260 NM 000260 4647 -0.63 1.17E-04 UBE2D3 229355_at AU150386 NM 003340 NMJ81886 NM 181887 NM_181888 NM181889 NM 181890 NM_181891 NM_181892 NM_181893 7323 -0.63 6.20E-03 CYP2U1 226393_at AW055161 NM 183075 113612 -0.63 7.35E-03 PFDN5 207132_x_at NM_002624 NM 002624 NM_145896 NM 145897 5204 -0.63 9.53E-04 WSB1 201294_s_at N24643 NM 015626 NM 134264 NM_134265 26118 -0.63 2.39E-03 MGC45386 227008_at AI393309 NM_198527 374659 -0.63 9.40E-03 PROSC 214545_s_at NM 007198 NM 007198 11212 -0.62 3.15E-04 SELM 226051_at BF973568 NM 080430 140606 -0.62 4.03E-03 FLJ21919 202809_s_at NM_023015 NM_023015 65123 -0.62 7.33E-03 MGC5356 220426_at NM_024059 NM_024059 79025 -0.62 6.04E-03 KIAA1671 225525_at AB051458 XM 371461 85379 -0.62 1.04E-03 SNX6 217789_at NM_021249 NM_021249 NM 152233 58533 -0.62 4.75E-03 429 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., etal., Cells Useful for Immuno-Based BoNT/A Activity Assays MPPE1 213727_x_at Al 743654 NM 023075 NM_138608 65258 -0.62 7.16E-04 ST6GALNAC6 222571 at AK023900 NM 013443 30815 -0.62 2.17E-03 MGC5391 226639_at Al 304320 NM 032740 84826 -0.62 3.40E-03 MAP7 215471_s_at AJ242502 NM_003980 9053 -0.62 3.97E-04 FLJ11273 226529 at BF513060 NM 018374 54664 -0.62 7.53E-03 ADCK2 44120_at AI879381 NM_052853 90956 -0.62 3.67E-03 TST 209605_at D87292 NM 003312 7263 -0.62 8.01 E-03 NUDT2 218609_s_at NM_001161 NM_001161 NMJ47172 NM_147173 318 -0.62 7.23E-03 AI632010 244687_at AI632010 — — -0.62 3.57E-04 PHC1 225958_at Al554106 NM_004426 1911 -0.62 8.62E-05 PIK3CB 212688 at BC003393 NM 006219 5291 -0.62 6.77E-04 LOC401466 1555241 at BC032347 XM_376783 401466 -0.61 2.14E-03 KIAA1458 224843_at AB040891 XM 044434 57606 -0.61 4.73E-04 AV756131 224915 x at AV756131 XM_497769 441951 -0.61 3.59E-03 APRT 213892 s at AA927724 NM 000485 353 -0.61 6.05E-04 WDR41 218055_s_at NM_018268 NM_018268 55255 -0.61 5.04E-03 LOC143458 234985_at AW043782 NM_174902 143458 -0.61 1.09E-04 MGC15429 224821_at AL520200 NM_032750 84836 -0.61 1.73E-03 LOC387593 239715_at AI374756 — 387593 -0.61 7.41 E-03 MGC2494 219709_x_at NM_023933 NM_023933 65990 -0.61 7.21 E-03 SBF2 226169_at AW276572 NM_030962 81846 -0.61 2.63E-03 CGI-119 222845_x_at AF161526 NM 016056 51643 -0.61 6.18E-04 UBE2D3 200669_s_at NM_003340 NM 003340 NM_181886 NM_181887 NM_181888 NM_181889 NM_181890 NM_181891 NM 181892 NM 181893 7323 -0.61 7.57E-04 NPC1L1 220106_at NM 013389 NM 013389 29881 -0.61 9.81 E-04 RNF13 201780_s_at NM_007282 NM_007282 NM_183381 NM 183382 NM 183383 NM_183384 11342 -0.61 9.87E-04 ARF1P1 214483_s_at AF124489 NM_014447 27236 -0.60 3.32E-05 AI741365 229757 at AI741365 ... — -0.60 4.00E-03 FAM14A 223626_x_at AF208232 NM_032036 83982 -0.60 4.30E-04 DBT 205369_x_at J03208 NM_001918 1629 -0.60 2.60E-03 MRPL1 223154_at AF212225 NM_020236 65008 -0.60 2.59E-03 KIAA1223 225731_at BF196876 XM_048747 57182 -0.60 4.63E-03 NFATC4 213345_at AI624015 NM_004554 4776 -0.60 1.80E-03 BF185165 226227 x at BF185165 XM 497769 441951 -0.59 3.75E-03 GAL 207466_at NM 015973 NM 015973 51083 -0.59 6.79E-03 LOC92017 225608_at H15273 NM 001009607 92017 -0.59 1.54E-05 WDR9 214820_at AJ002572 NM_00100724 6 NM_018963 NM_033656 54014 -0.59 4.03E-04 PLEKHA3 223370 at AF286162 NM 019091 65977 -0.59 4.77E-03 PPM1K 235061 at AV706522 NM 152542 152926 -0.59 2.94E-03 MTL5 241466 at Al275776 NM 004923 9633 -0.59 5.56E-04 DHX32 218198 at NM 018180 NM 018180 55760 -0.59 7.21 E-03 430 WO 2010/105234 PCT/US2010/027242 2017228675 15 Sep 2017

Patent Application 18495 (BOT)/1957205.00451 Jacky, B., et al.t Cells Useful for Immuno-Based BoNT/A Activity Assays )KFZp451M211 231540_at BF511274 NM 182585 285023 -0.59 1.28E-03 MTM1 36920_at U46024 NM 000252 4534 -0.59 4.62E-03 ALKBH 236721 at Al 922200 NM_006020 8846 -0.59 7.70E-03 BC019017 1558128_at BC019017 — ... -0.59 1.03E-03 CDC42EP3 209288_s_at AL136842 NM_006449 10602 -0.59 8.78E-04 FLJ20277 233638 s at AK026430 NM_017739 55624 -0.59 4.86E-03 AI766065 224647 at Al 766065 ... ... -0.59 1.11E-03 SETDB2 235339_at W65369 NM_031915 83852 -0.59 5.43E-03 BE326214 229287_at BE326214 — — -0.59 8.90E-04 HS2ST1 203285 s at NM_012262 NM 012262 9653 -0.58 4.84E-04 N51708 213930 at N51708 XM_499012 441104 -0.58 1.86E-03 GPR56 212070_at AL554008 NM_005682 NM_201524 NM 201525 9289 -0.58 2.25E-03 LOC119710 228249 at AA535128 NM_138787 119710 -0.58 7.12E-03 FLJ13576 234726 s_at AK025482 NM 022484 64418 -0.58 5.50E-03 PFDN5 210908_s_at AB055804 NM_002624 NM_145896 NM_145897 5204 -0.58 1.71E-03 SIDT2 218765_at NM_015996 NM 015996 51092 -0.58 4.83E-03 FLJ21168 204666_s_at NM_025073 NM_025073 80143 -0.58 9.92E-04 KIAA0241 212475 at Al 797458 NM 015060 23080 -0.58 4.82E-05 CHIC1 228345_at Al745136 XR_000216 53344 -0.58 6.80E-03 BE645776 227288_at BE645776 XM_068632 133993 -0.58 4.35E-04 CTBS 218923_at AW304174 NM 004388 1486 -0.58 8.95E-03 TMF1 235566_at AW591660 NM 007114 7110 -0.58 7.30E-03 PKNOX1 221883_at AA133342 NM_004571 NM_197976 5316 -0.58 1.27E-03 ACTR1B 202135_s_at NM 005735 NM 005735 10120 -0.58 2.50E-03 TNFRSF21 214581 x at BE568134 NM 014452 27242 -0.58 8.02E-03 PEX7 211033_s_at BC006268 NM__000288 5191 -0.58 8.93E-03 EIF4E3 225941 at Al 935522 — 317649 -0.58 5.78E-03 431

Claims (4)

What is claimed:

1. An established clonal cell line comprising cells susceptible to intoxication by BoNT/A, wherein the cells exhibits at least a 1,5-fold difference in gene expression levels of three or more genes as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZACC 164; and wherein the gene expression levels are selected from th group ADAMTS9, ASCL1, BASP1, DOK5, DPYD, GNB4, GNG11, GTSF1, MAOA, MINA, MSN, PEG3, PLK2, PRSS12, RNF182, SLC44A5, SPARC, TFPI2, and TPTE; and wherein the the clonal cell line comprises cells susceptible to BoNT/A intoxication by about 100 pM or less of a BoNT/A.

2. The established clonal cell line of Claim 1, wherein the the cells exhibit at least a 2.0-fold difference in gene expression levels of one or more genes as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164, at least a 3.0-fold difference in gene expression levels of one or more genes as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164, or at least a 4.0-fold difference in gene expression levels of one or more genes as compared to the expression levels of these genes in cells from the parental SiMa cell line DSMZ ACC 164.

3. The established clonal cell line of Claim 1, wherein the gene expression levels are measured before differentiation of the cell or after differentiation of the cell.

4. The established clonal cell line of Claim 1, wherein the cell from an established clonal cell line exhibits about 100 pM or less of a BoNT/A for at least 5 or more cell passages.