US20240002542A1 - Compositions and methods related to il27 receptor binding - Google Patents

Compositions and methods related to il27 receptor binding Download PDF

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US20240002542A1
US20240002542A1 US18/164,386 US202318164386A US2024002542A1 US 20240002542 A1 US20240002542 A1 US 20240002542A1 US 202318164386 A US202318164386 A US 202318164386A US 2024002542 A1 US2024002542 A1 US 2024002542A1
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il27rα
sequence
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Robert KASTELEIN
Patrick Lupardus
Deepti ROKKAM
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Synthekine Inc
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Definitions

  • the interleukin-27 receptor is a type I cytokine receptor for interleukin-27 (IL27). It is a heterodimer composed of the IL27R ⁇ subunit and glycoprotein 130 (gp130). IL27 is expressed by antigen presenting cells and induces differentiation of a diverse populations of T cells in the immune system. When IL27 binds to the IL27R, signaling pathways, such as the JAK-STAT and p38 MAPK pathways, are turned on to induce pro-inflammatory or anti-inflammatory responses, which involve different types of cells, such as macrophages, dendritic cells, T cells, and B cells. The response that is activated can be dependent on the external surrounding of IL27.
  • IL-27 is a heterodimeric cytokine consisting of two non-covalently linked subunits, p28 and EBI3.
  • the p28 subunit belongs to the 4-helix bundle cytokine family, while EBI3 is the shortest form possible of a soluble cytokine receptor, with two typical cytokine binding domains (Roo S, et al., Immunity. 2002 June; 16(6):779-90).
  • the primary binding receptor for IL-27 is the IL-27R1 (also known as TCCR- or WSX-1 receptor).
  • IL-27 and IL-27R1 form a complex of considerable affinity (nM).
  • Gp130 is the second receptor that binds the complex of IL-27/IL-27R to create the active signaling complex. Gp130 binding to the IL-27/IL-27R1 complex is much weaker than the interaction between IL-27 and IL-27R1 (Roo S, et al., J Immunol. 2004 Feb. 15; 172(4):2225-31).
  • the IL-27 extracellular domain has 5 domains.
  • the first two domains form the IL-27 binding domains.
  • the loops between D1 and D2 provide most of the binding energy.
  • the other 3 domains are called Fibronectin type III domains (Fn3).
  • Fn3 Fibronectin type III domains
  • the gp130 receptor has 6 domains.
  • the top domain D1 of gp130 binds p28 of IL-27.
  • D2 and D3 contribute little to binding IL-27.
  • the membrane proximal 3 domains are Fn3 domains. The sequence of each Fn3 domain varies.
  • the structure of the IL-27R is not known but the domain structure is known.
  • the structure of gp130 is known as complexed with IL-6. Based on that structure it is evident that the Fn3 domains do not energetically contribute to IL-27R complex formation. Rather the structure of the gp130 forms a ‘C’ with the domain 4 and 5 at 80% angle of each other. Certain residues in each of the ‘tall’ receptors are conserved similar to D4 and D5 in gp130. This indicates that all tall receptors of the gp130 family, including IL-27R, forms this ‘C’ structure. (Yibin Xu, et al., J Biol Chem. 2010 Jul. 9; 285(28):21214-8).
  • IL-27R has 5 extracellular domains.
  • D1 and D2 are the cytokine binding domains.
  • D3, D4 and D5 are Fn3 domains.
  • the D5 domain of IL-27R and the D6 domain of gp130 will come close together at the membrane because of the ‘C’ shape of each receptor. This is required to be able for the receptor complex to trigger binding of JAKs at the intracellular domains of both receptors.
  • compositions useful in the pairing of cellular receptors to generate desirable effects useful in treatment of disease in mammalian subjects are provided.
  • the natural ligand of the IL-27R, IL-27 causes gp130 and IL-27R ⁇ to come into proximity (i.e., by their simultaneous binding of IL-27).
  • IL-27 when used as a therapeutic in mammalian, particularly human, subjects, it may also trigger a number of adverse and undesirable effects by a variety of mechanisms including the presence of gp130 and IL-27R ⁇ on other cell types and the binding to gp130 and IL-27R ⁇ on the other cell types may result in undesirable effects and/or undesired signaling on cells expressing gp130 and IL-27Ra.
  • the present disclosure is directed to methods and compositions that modulate the multiple effects of gp130 and IL-27R ⁇ binding so that desired therapeutic signaling occurs, particularly in a desired cellular or tissue subtype, while minimizing undesired activity and/or intracellular signaling.
  • the IL-27R binding molecules described herein are partial agonists of the IL-27 receptor. In some embodiments, the binding molecules described herein are designed such that the binding molecules are full agonists. In some embodiments, the binding molecules described herein are designed such that the binding molecules are super agonists.
  • the binding molecules provide the maximal desired IL-27 intracellular signaling from binding to gp130 and IL-27R ⁇ on the desired cell types, while providing significantly less IL-27 signaling on other undesired cell types. This can be achieved, for example, by selection of binding molecules having differing affinities or causing different E max for gp130 and IL-27R ⁇ as compared to the affinity of IL-27 for gp130 and IL-27Ra.
  • the present disclosure provides bivalent binding molecules that are agonists of the IL-27 receptor, the bivalent binding molecule comprising:
  • one sdAb of the bivalent binding molecule is an scFv and the other sdAb is a VHH.
  • the first and second sdAbs are covalently bound via a chemical linkage.
  • the first and second sdAbs are provided as single continuous polypeptide.
  • the first and second sdAbs are provided as single continuous polypeptide optionally comprising an intervening polypeptide linker between the amino acid sequences of the first and second sdAbs.
  • the bivalent binding molecule optionally comprising a linker is optionally expressed as a fusion protein with an additional amino acid sequence.
  • the additional amino acid sequence is a purification handle such as a chelating peptide or an additional protein such as a subunit of an Fc molecule.
  • the disclosure provides an IL27 receptor (IL27R) binding protein that specifically binds to IL27R ⁇ subunit (IL27R ⁇ ) and glycoprotein 130 subunit (gp130), wherein the binding protein causes the multimerization of IL27R ⁇ and gp130 when bound to IL27Ra and gp130 and the multimerization results in the activation of JAK kinases associated with the intracellular domains of IL27R ⁇ and gp130 and intraceullar signaling, and wherein the binding protein comprises a single-domain antibody (sdAb) that specifically binds to IL27R ⁇ (an anti-IL27R ⁇ sdAb) and a sdAb that specifically binds to gp130 (an anti-gp130 sdAb).
  • the multimerization of IL27R ⁇ and gp130 can cause downstream signaling.
  • the anti-IL27R ⁇ sdAb is a V H H antibody (an anti IL27R ⁇ V H H antibody) and/or the anti-gp130 sdAb is a V H H antibody (an anti gp130 V H H antibody).
  • the anti-IL27R ⁇ sdAb and the anti-gp130 sdAb are joined directly or via a peptide linker.
  • the peptide linker comprises between 1 and 50 amino acids.
  • the peptide linker comprises a sequence of GGGS (SEQ ID NO:108).
  • the IL27R binding protein comprises:
  • the IL27R binding protein comprises a sequence at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) identical to any one of the dual VHH dimer sequences shown in Table 1A.
  • the anti IL27R ⁇ V H H antibody comprises a CDR1 having 0, 1, 2, or 3 amino acid changes relative to the sequence of any one of SEQ ID NOS:193-198; a CDR2 having 0, 1, 2, or 3 amino acid changes relative to the sequence of any one of SEQ ID NOS:199-204; and a CDR3 having 0, 1, 2, or 3 amino acid changes relative to the sequence of any one of SEQ ID NOS:205-210.
  • the anti gp130 V H H antibody comprises a CDR1 having 0, 1, 2, or 3 amino acid changes relative to the sequence of any one of SEQ ID NOS:211-217; a CDR2 having 0, 1, 2, or 3 amino acid changes relative to the sequence of any one of SEQ ID NOS:218-224; and a CDR3 having 0, 1, 2, or 3 amino acid changes relative to the sequence of any one of SEQ ID NOS:225-231.
  • the IL27R binding protein comprises a CDR1, a CDR2, and a CDR3 in the anti IL27R ⁇ VHH antibody and a CDR1, a CDR2, and a CDR3 in the anti gp130 VHH antibody as listed in a row of Table 1.
  • the binding protein comprises an anti gp130 VHH antibody linked to the N-terminus of a linker and an anti IL27R ⁇ VHH antibody linked to the C-terminus of the linker.
  • the anti gp130 VHH antibody comprises a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity to a sequence of any one of SEQ ID NOS:232-237.
  • the anti IL27R ⁇ VHH antibody comprises a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity to a sequence of any one of SEQ ID NOS:238-244.
  • each of the anti-gp130 VHH antibody and the anti-IL27Ra VHH antibody comprises a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) identity to a sequence listed in a row of Table 2A.
  • the binding protein comprises a sequence that is substantially identical to a sequence of any one of SEQ ID NOS:1-42. In certain embodiments, the binding protein comprises a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) identity to a sequence of any one of SEQ ID NOS:1-42.
  • the binding protein comprises an anti IL27R ⁇ VHH antibody linked to the N-terminus of a linker and an anti gp130 VHH antibody linked to the C-terminus of the linker.
  • the anti IL27R ⁇ VHH antibody comprises a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity to a sequence of any one of SEQ ID NOS:245-251.
  • the anti gp130 VHH antibody comprises a sequence having at least 90% sequence identity to a sequence of any one of SEQ ID NOS:252-257.
  • each of the anti IL27R ⁇ VHH antibody and the anti gp130 VHH antibody comprises a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) identity to a sequence listed in a row of Table 3A.
  • the binding protein comprises a sequence that is substantially identical to a sequence of any one of SEQ ID NOS:43-84. In certain embodiments, the binding protein comprises a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) identity to a sequence of any one of SEQ ID NOS:43-84.
  • the disclosure provides an isolated nucleic acid encoding the IL27R binding protein described herein.
  • the isolated nucleic acid comprises a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity to a sequence of any one of SEQ ID NOS:109-192 or a sequence from Table 1B.
  • the disclosure also provides an expression vector comprising the nucleic acid.
  • the disclosure also provides an isolated host cell comprising the expression vector.
  • the disclosure provides a pharmaceutical composition
  • a pharmaceutical composition comprising the IL27R binding protein described herein and a pharmaceutically acceptable carrier.
  • the disclosure provides a method of treating an autoimmune or inflammatory disease, disorder, or condition, a neoplastic disease, or a viral infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an IL27R binding protein described herein or a pharmaceutical composition described herein.
  • the method further comprises administering one or more supplementary agents selected from the group consisting of a corticosteroid, a Janus kinase inhibitor, a calcineurin inhibitor, a mTor inhibitor, an IMDH inhibitor, a biologic, a vaccine, and a therapeutic antibody.
  • the therapeutic antibody is an antibody that binds a protein selected from the group consisting of BLyS, CD11a, CD20, CD25, CD3, CD52, IgEIL12/IL23, IL17a, IL1B, IL4Ra, IL5, IL6R, integrin- ⁇ 4 ⁇ 7, RANKL, TNF ⁇ , VEGF-A, and VLA-4.
  • the disease, disorder, or condition is selected from viral infections, heliobacter pylori infection, HTLV, organ rejection, graft versus host disease, autoimmune thyroid disease, multiple sclerosis, allergy, asthma, neurodegenerative diseases including Alzheimer's disease, systemic lupus erythramatosis (SLE), autoinflammatory diseases, inflammatory bowel disease (IBD), Crohn's disease, diabetes, cartilage inflammation, arthritis, rheumatoid arthritis, juvenile arthritis, juvenile rheumatoid arthritis, juvenile rheumatoid arthritis, polyarticular juvenile rheumatoid arthritis, systemic onset juvenile rheumatoid arthritis, juvenile ankylosing spondylitis, juvenile enteropathic arthritis, juvenile reactive arthritis, juvenile Reiter's Syndrome, SEA Syndrome, juvenile dermatomyositis, juvenile psoriatic arthritis, juvenile scleroderma, juvenile systemic lupus erythematosus, juvenile vasculitis,
  • An IL27R binding proteins described herein are useful in the treatment of neoplastic diseases, such as cancer (e.g., a solid tumor cancer; e.g., non-small-cell lung carcinoma (NSCLC), renal cell carcinoma (RCC), or melanoma) and/or infectious diseases (e.g., bacterial infections and viral infections (e.g., viral infections caused by hepatitis C virus (HCV), human papillomavirus (HPV), or human immunodeficiency virus (HIV)) in a subject in need thereof.
  • NSCLC non-small-cell lung carcinoma
  • RRCC renal cell carcinoma
  • infectious diseases e.g., bacterial infections and viral infections (e.g., viral infections caused by hepatitis C virus (HCV), human papillomavirus (HPV), or human immunodeficiency virus (HIV)
  • HCV hepatitis C virus
  • HPV human papillomavirus
  • HIV human immunodeficiency
  • the IL27R binding protein can trigger different levels of downstream signaling in different cell types. For example, by varying the length of the linker between the antiIL27R ⁇ V H H antibody and the antigp130 V H H antibody in the IL27R binding protein, the IL27R binding protein can cause a higher level of downstream signaling in desired cell types compared to undesired cell types. In some embodiments, by varying the linker length, an IL27R binding protein can cause a higher level of downstream signaling in T cells (e.g., CD8 + T cells) compared to the level of downstream signaling in other cells.
  • T cells e.g., CD8 + T cells
  • different antilL27R ⁇ V H H antibodies with different binding affinities and different antigp130 V H H antibodies with different binding affinities can be combined to make different IL27R binding proteins.
  • the orientation of the two antibodies in the binding protein can also be changed to make a different binding protein (i.e., antiIL27R ⁇ V H H antibody-linker-antigp130 V H H antibody, or antigp130 V H H antibody-linker-antiIL27R ⁇ V H H antibody).
  • Different IL27R binding proteins can be screened to find the ideal binding protein that causes a higher level of downstream signaling in desired cell types compared to undesired cell types.
  • the level of downstream signaling in T cells e.g., CD8+ T cells
  • the IL27R binding protein binds to and activates CD8 + T cells.
  • the IL27R binding protein binds to and activates CXCR5 + CD8 + T cells. It is known that IL27 can promote and sustain a rapid division of memory-like CXCR5 + CD8 + T cells during, for example, viral infection. The CXCR5 + CD8 + T cells can sustain T cell responses during persistent infection or cancer and drive the proliferative burst of CD8 + T cells after anti-PD1 treatment. Accordingly, an IL27R binding protein described herein is useful to sustain and augment self-renewing T cells in chronic infections and neoplastic diseases, such as cancer.
  • FIG. 1 of the attached drawings provides a schematic representation of one embodiment of the bivalent binding molecule of the present disclosure comprising a first single domain antibody ( 1 ) and a second single domain antibody ( 3 ) and a linker ( 2 ) depicted as interacting with a cell membrane ( 10 ) associated heterodimeric receptor comprising a first receptor subunit comprising an extracellular domain ( 4 ), and transmembrane domain ( 5 ) and an intracellular domain ( 6 ) interaction of a bivalent binding molecule and a second first receptor subunit comprising an extracellular domain ( 7 ), and transmembrane domain ( 8 ) and an intracellular domain ( 9 ) wherein the intracellular domain of the first receptor ( 6 ) and the intracellular domain of the second receptor ( 9 ) on of a bivalent binding molecule are within a proximal distance ( 11 ).
  • FIGS. 2 A and 2 B of the attached drawings provides a schematic representation of two illustrative configurations of bivalent binding molecules of the present disclosure.
  • FIG. 2 A provides a schematic representation of an illustrative single polypeptide chain bivalent binding molecule comprising, from amino to carboxy, a first single domain antibody ( 1 ) and a second single domain antibody ( 3 ) and a linker ( 2 ).
  • FIG. 1 provides a schematic representation of an illustrative single polypeptide chain bivalent binding molecule comprising, from amino to carboxy, a first single domain antibody ( 1 ) and a second single domain antibody ( 3 ) and a linker ( 2 ).
  • FIG. 1 provides a schematic representation of an illustrative single polypeptide chain bivalent binding molecule comprising, from amino to carboxy, a first single domain antibody ( 1 ) and a second single domain antibody ( 3 ) and a linker ( 2 ).
  • FIG. 1 provides a schematic representation of an illustrative single poly
  • FIG. 2 B provides a schematic representation of a bivalent binding molecule comprising a first single domain antibody ( 1 ) and a second single domain antibody ( 3 ) and a linker ( 2 ) and a knob-into-hole Fc domain, the Fc domain comprising a first subunit which is a Fc knob ( 13 ) and a second subunit which is a Fc hole ( 14 ) wherein the bivalent binding molecule is covalently linked to an Fc domain subunit via a IgG hinge sequence ( 12 ).
  • FIGS. 3 A and 3 B of the attached drawings provides a schematic representations of two illustrative configurations of bivalent binding molecules of the present disclosure.
  • FIG. 3 A provides a schematic representation of an illustrative bivalent binding molecule construct comprising two bivalent binding molecules each attached to a subunit of a knob-into-hole Fe domain, the construct comprising two polypeptide chains, the first polypeptide chain comprising, from amino to carboxy, a first single domain antibody ( 1 ), a linker ( 2 ) and a second single domain antibody ( 3 ), a IgG hinge sequence ( 12 ) and a Fc knob subunit ( 13 ) and a second polypeptide chain comprising, from amino to carboxy, a first single domain antibody ( 1 ), a linker ( 2 ) and a second single domain antibody ( 3 ), a IgG hinge sequence ( 12 ) and a Fc hole subunit ( 14 ) wherein the first and second polypeptides are in stable associate via the interaction of the knob-
  • FIG. 3 B provides schematic representation of a an alternative arrangement of a bivalent binding molecule construct comprising two polypeptides a first polypeptide chain comprising, from amino to carboxy, a first single domain antibody ( 1 ), a linker ( 2 ) and a second single domain antibody ( 3 ), an IgG hinge sequence ( 12 ) and a Fc knob subunit ( 13 ) and a second polypeptide chain comprising, from amino to carboxy, a first second domain antibody ( 3 ), a linker ( 2 ) and a first single domain antibody ( 1 ), a IgG hinge sequence ( 12 ) and a Fc hole subunit ( 14 ), wherein the first and second polypeptides are in stable association via the interaction of the knob-into-hole Fc domain.
  • FIG. 4 A provides alternative schematic representations of configurations of the bivalent binding molecules of the present disclosure where one single domain antibody is attached to each subunit of a knob-into-hole Fc domain comprising two polypeptides, the first polypeptide comprising from amino to carboxy, a first single domain antibody ( 1 ), an IgG hinge sequence ( 12 ) and a Fc knob subunit ( 13 ), the second polypeptide comprising from amino to carboxy, a second single domain antibody ( 3 ), an IgG hinge sequence ( 12 ) and a Fc hole subunit ( 13 ), wherein the first and second single domain antibodies are in stable associate via the interaction of the knob-into-hole Fc domain.
  • FIG. 4 B provides a schematic representation of a binding molecule the binding domains are single domain antibodies associated via transition metal coordinate covalent complex.
  • the binding molecules comprises two polypeptide subunits: the first subunit comprising a first single domain antibody ( 1 ) is attached via a first linker ( 15 ) to a first chelating peptide ( 17 ) and second subunit comprising a second single domain antibody ( 3 ) is attached via a second linker ( 16 ) to a second chelating peptide ( 18 ), wherein the first chelating peptide ( 17 ) and second chelating peptide ( 18 ) form a coordinate covalent complex with a single transition metal ion (“M”).
  • M transition metal ion
  • the transition metal ion may be in a kinetically labile or kinetically inert oxidation state.
  • binding proteins comprise a first domain that binds to IL27R ⁇ and a second domain that binds to gp130, such that upon contacting with a cell expressing IL27R ⁇ and gp130, the binding protein causes the functional association of IL27R ⁇ and gp130, thereby resulting in functional dimerization of the receptors and downstream signaling.
  • IL27R ⁇ and gp130 The natural ligand of IL27R, IL27, causes IL27R ⁇ and gp130 to come into proximity (i.e., by their simultaneous binding of IL27).
  • IL27 when used as a therapeutic in mammalian, particularly human, subjects, it may also trigger a number of adverse and undesirable effects by a variety of mechanisms including the presence of IL27R ⁇ and gp130 on other cell types and the binding to IL27R ⁇ and gp130 on the other cell types may result in undesirable effects and/or undesired signaling on cells expressing IL27R ⁇ and gp130.
  • the present disclosure is directed to methods and compositions that modulate the multiple effects of IL27R ⁇ and gp130 binding so that desired therapeutic signaling occurs, particularly in a desired cellular or tissue subtype, while minimizing undesired activity and/or intracellular signaling.
  • the binding proteins described herein are designed such that the binding proteins provide the maximal desired IL27 intracellular signaling from binding to IL27R ⁇ and gp130 on the desired cell types, while providing significantly less IL27 signaling on other undesired cell types. This can be achieved, for example, by selection of binding proteins having differing affinities or causing different E max for IL27R ⁇ and gp130 as compared to the affinity of IL27 for IL27R ⁇ and gp130.
  • IL27 receptor IL27 receptor
  • downstream signaling activity a number of methods are available. For example, in some embodiments, one can measure JAK/STAT signaling by the presence of phosphorylated receptors and/or phosphorylated STATs. In other embodiments, the expression of one or more downstream genes, whose expression levels can be affected by the level of downstream signalinging caused by the binding protein, can also be measured.
  • Interleukin 27 (IL27) Structure :
  • IL27 is a member of the IL-12 cytokine family.
  • IL27 is a heterodimeric cytokine comprised of two subunits: IL27A (also referred to as IL-27p28) and IL27B (also referred to as Epstein-Barr Virus induced gene 3 or “EBI3”).
  • the human p28 (hIL27A) is expressed as a 243 amino acid pre-protein comprising 28 amino acid signal sequence which is post-translationally removed to render a 215 amino acid mature protein.
  • UniProtKB-Q8NEV9 IL27A_HUMAN.
  • the mature form of p28 (less the signal peptide) possesses the amino acid sequence;
  • hIL27B The human IL27B (hIL27B) is expressed as a 229 amino acid pre-protein comprising 20 amino acid signal sequence which is post-translationally removed to render a 209 amino acid mature protein.
  • UniProtKB-Q14213 IL27B_HUMAN.
  • the mature form of hIL27B (less the signal peptide) possesses the amino acid sequence
  • Interleukin 27 (IL27) Receptor IL27 Receptor
  • IL27 results in intracellular signaling via its interaction with a heterodimeric receptor consisting of: IL-27R ⁇ (or IL27RA) and gp130.
  • IL-27R ⁇ or IL27RA
  • the binding of IL27 to IL27 receptor activates signaling pathways including the JAK/STAT and p38 MAPK pathways.
  • IL27 stimulates both pro-inflammatory and anti-inflammatory response in different cell types such as macrophages, dendritic cells, T cells and B cells. The type of response is dependent on the environment.
  • the human IL27 receptor subunit alpha (hIL27RA) is expressed as a 636 amino acid pre-protein comprising 32 amino acid signal sequence which is post-translationally removed to render a 604 amino acid mature protein.
  • UniProtKB-Q6UWB1 (I27RA_HUMAN)
  • hIL27RA (less the signal peptide) possesses the amino acid sequence:
  • IL27RA-ECD The extracellular domain of hIL27RA (IL27RA-ECD) is a 484 amino acid polypeptide corresponding to amino acids 33-516 of the hIL27RA preprotein and possesses the amino acid sequence:
  • hGP130 The human gp130 receptor subunit (hGP130) is also referred as the IL6 receptor beta subunit.
  • UniProtKB-P40189 IL6RB_HUMAN.
  • hGP130 is expressed as a 918 amino acid pre-protein comprising 22 amino acid signal sequence which is post-translationally removed to render a 896 amino acid mature protein.
  • the mature form of hGP130 possess the amino acid sequence:
  • hGP130-ECD The extracellular domain of hGP130 (hGP130-ECD) is a 597 amino acid polypeptide corresponding to amino acids 23-619 of the hGP130 preprotein and possesses the amino acid sequence:
  • IL27 is expressed by antigen presenting cells.
  • hIL27 induces differentiation of the diverse populations of T cells in the immune system and also upregulates IL10.
  • hIL27 has pro- and anti-inflammatory properties, that can regulate T-helper cell development, suppress T-cell proliferation, stimulate cytotoxic T-cell activity, induce isotype switching in B-cells, and that have diverse effects on innate immune cells.
  • target cells CD4 T-helper cells which can differentiate in type 1 effector cells (TH1), type 2 effector cells (TH2) and IL17 producing helper T-cells (TH17).
  • IL27 plays a significant role in the differentiation through inducing or suppressing of T cell subtypes including Th1, Th2, Th17, Tr1 and Treg cells.
  • IL-27 is greatly involved in differentiation through inducing or suppressing of each T cell subset.
  • Interferon gamma (IFNg) expressing Th1 cells are generated in response IL27 through STAT1 signaling via expression of T-bet and signature Th1 genes.
  • IL4 expressing Th2 cells are inhibited by IL27 through the transcription factor GATA-3.
  • Th17 cells which express IL17, IL22, and GM-CSF, are inhibited by IL27 through STAT1 and expression of transcription factor ROR ⁇ t.
  • Treg cells are inhibited by IL27 through STAT1 and STAT3.
  • IL27 drives rapid clonal expansion of naive but not memory CD4 T-cells.
  • IL27 also strongly synergizes with IL-12 to trigger interferon-gamma/IFN-gamma production of naive CD4 T-cells, binds to the cytokine receptor WSX-1/TCCR.
  • Another important role of IL-27 is its antitumor activity as well as its antiangiogenic activity with activation of production of antiangiogenic chemokines
  • Tr1 cells which express IL-10 are induced by IL-27 through the transcription factor c-Maf providing an anti-inflammatory response.
  • a primary activity of IL-10 is the suppression of inflammatory responses.
  • STAT1 and STAT3 transcription factors that bind specifically to the IL-27 ⁇ . The activation of STAT3 by IL-27 leads to an increase of IL-10 secretion from Treg cells.
  • molecular weight is weight average molecular weight
  • temperature is in degrees Celsius (° C.)
  • pressure is at or near atmospheric.
  • Activate is used in reference to a receptor or receptor complex to reflect a biological effect, directly and/or by participation in a multicomponent signaling cascade, arising from the binding of an agonist ligand to a receptor responsive to the binding of the ligand.
  • Activity is used with respect to a molecule to describe a property of the molecule with respect to a test system (e.g. an assay) or biological or chemical property (e.g. the degree of binding of the molecule to another molecule) or of a physical property of a material or cell (e.g. modification of cell membrane potential).
  • test system e.g. an assay
  • biological or chemical property e.g. the degree of binding of the molecule to another molecule
  • a physical property of a material or cell e.g. modification of cell membrane potential
  • biological functions include but are not limited to catalytic activity of a biological agent, the ability to stimulate intracellular signaling, gene expression, cell proliferation, the ability to modulate immunological activity such as inflammatory response.
  • Activity is typically expressed as a level of a biological activity per unit of agent tested such as [catalytic activity]/[mg protein], [immunological activity]/[mg protein], international units (IU) of activity, [STAT5 phosphorylation]/[mg protein], [T-cell proliferation]/[mg protein], plaque forming units (pfu), etc.
  • proliferative activity referes to an activity that promotes cell proliferation and replication.
  • Administer/Administration refers the act of contacting a subject, including contacting a cell, tissue, organ, or biological fluid of the subject in vitro, in vivo or ex vivo with an agent (e.g. an ortholog, an IL2 ortholog, an engineered cell expressing an orthogonal receptor, an engineered cell expressing an orthogonal IL2 receptor, a CAR-T cell expressing an orthogonal IL2 receptor, a chemotherapeutic agent, an antibody, or a pharmaceutical formulation comprising one or more of the foregoing).
  • an agent e.g. an ortholog, an IL2 ortholog, an engineered cell expressing an orthogonal receptor, an engineered cell expressing an orthogonal IL2 receptor, a CAR-T cell expressing an orthogonal IL2 receptor, a chemotherapeutic agent, an antibody, or a pharmaceutical formulation comprising one or more of the foregoing.
  • Administration of an agent may be achieved through any of a variety of art recognized methods including but not limited to the topical administration, intravascular injection (including intravenous or intraarterial infusion), intradermal injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, inhalation and the like.
  • intravascular injection including intravenous or intraarterial infusion
  • intradermal injection subcutaneous injection
  • intramuscular injection intraperitoneal injection
  • inhalation inhalation and the like.
  • administration includes contact of an agent to the cell, tissue or organ as well as the contact of an agent to a fluid, where the fluid is in contact with the cell, tissue or organ.
  • affinity refers to the degree of specific binding of a first molecule (e.g., a ligand) to a second molecule (e.g., a receptor) and is measured by the equilibrium dissociation constant (KD), a ratio of the dissociation rate constant between the molecule and its target (Koff) and the association rate constant between the molecule and its target (Kon).
  • KD equilibrium dissociation constant
  • Koff ratio of the dissociation rate constant between the molecule and its target
  • Kon association rate constant
  • agonist refers a first agent that specifically binds a second agent (“target”) and interacts with the target to cause or promote an increase in the activation of the target.
  • agonists are activators of receptor proteins that modulate cell activation, enhance activation, sensitize cells to activation by a second agent, or up-regulate the expression of one or more genes, proteins, ligands, receptors, biological pathways, that may result in cell proliferation or pathways that result in cell cycle arrest or cell death such as by apoptosis.
  • an agonist is an agent that binds to a receptor and alters the receptor state, resulting in a biological response.
  • agonist includes partial agonists, full agonists and superagonists.
  • An agonist may be described as a “full agonist” when such agonist which leads to a substantially full biological response (i.e., the response associated with the naturally occurring ligand/receptor binding interaction) induced by receptor under study, or a partial agonist.
  • antagonists may specifically bind to a receptor but do not result the signal cascade typically initiated by the receptor and may to modify the actions of an agonist at that receptor.
  • Inverse agonists are agents that produce a pharmacological response that is opposite in direction to that of an agonist.
  • a “superagonist” is a type of agonist that is capable of producing a maximal response greater than the endogenous agonist for the target receptor, and thus has an activity of more than 100% of the native ligand.
  • a super agonist is typically a synthetic molecule that exhibits greater than 110%, alternatively greater than 120%, alternatively greater than 130%, alternatively greater than 140%, alternatively greater than 150%, alternatively greater than 160%, or alternatively greater than 170% of the response in an evaluable quantitative or qualitative parameter of the naturally occurring form of the molecule when evaluated at similar concentrations in a comparable assay.
  • Antagonist refers a molecule that opposes the action(s) of an agonist.
  • An antagonist prevents, reduces, inhibits, or neutralizes the activity of an agonist, and an antagonist can also prevent, inhibit, or reduce constitutive activity of a target, e.g., a target receptor, even where there is no identified agonist.
  • Inhibitors are molecules that decrease, block, prevent, delay activation, inactivate, desensitize, or down-regulate, e.g., a gene, protein, ligand, receptor, biological pathway, or cell.
  • Antibody refers collectively to: (a) glycosylated and non-glycosylated immunoglobulins (including but not limited to mammalian immunoglobulin classes IgG1, IgG2, IgG3 and IgG4) that specifically binds to target molecule and (b) immunoglobulin derivatives including but not limited to IgG(1-4)deltaC H 2, F(ab′) 2 , Fab, ScFv, V H , V L , tetrabodies, triabodies, diabodies, dsFv, F(ab′) 3 , scFv-Fc and (scFv) 2 that competes with the immunoglobulin from which it was derived for binding to the target molecule.
  • immunoglobulin derivatives including but not limited to IgG(1-4)deltaC H 2, F(ab′) 2 , Fab, ScFv, V H , V L , tetrabodies, triabodies, diabodies, d
  • antibody is not restricted to immunoglobulins derived from any particular mammalian species and includes murine, human, equine, and camelids antibodies (e.g., human antibodies).
  • antibody encompasses antibodies isolatable from natural sources or from animals following immunization with an antigen and as well as engineered antibodies including monoclonal antibodies, bispecific antibodies, trispecific, chimeric antibodies, humanized antibodies, human antibodies, CDR-grafted, veneered, or deimmunized (e.g., to remove T-cell epitopes) antibodies.
  • human antibody includes antibodies obtained from human beings as well as antibodies obtained from transgenic mammals comprising human immunoglobulin genes such that, upon stimulation with an antigen the transgenic animal produces antibodies comprising amino acid sequences characteristic of antibodies produced by human beings.
  • antibody should not be construed as limited to any particular means of synthesis and includes naturally occurring antibodies isolatable from natural sources and as well as engineered antibodies molecules that are prepared by “recombinant” means including antibodies isolated from transgenic animals that are transgenic for human immunoglobulin genes or a hybridoma prepared therefrom, antibodies isolated from a host cell transformed with a nucleic acid construct that results in expression of an antibody, antibodies isolated from a combinatorial antibody library including phage display libraries.
  • binding molecule refers to a bivalent molecule that can bind to the extracellular domain of two cell surface receptors.
  • a binding molecule specifically binds to two different receptors (or domains or subunits thereof) such that the receptors (or domains or subunits) are maintained in proximity to each other such that the receptors (or domains or subunits), including domains thereof (e.g., intracellular domains) interact with each other and result in downstream signaling.
  • CDR complementarity determining region
  • CDRs have been described by Kabat et al., J. Biol. Chem. 252:6609-6616 (1977); Kabat, et al., U.S. Dept. of Health and Human Services publication entitled “Sequences of proteins of immunological interest” (1991) (also referred to herein as “Kabat 1991” or “Kabat”); by Chothia, et al. (1987) J. Mol. Biol.
  • Chothia Numbering is recognized in the arts and refers to a system of numbering amino acid residues based on the location of the structural loop regions (Chothiaet al.
  • CDRs2 and 3 in the variable region of an antibody follows Kabat numbering or simply, “Kabat.”
  • the positioning of CDR1 in the variable region of an antibody follows a hybrid of Kabat and Chothia numbering schemes.
  • Clonotype A clonotype is defined as a collection of binding molecules that originate from the same B-cell progenitor cell.
  • the term “clonotype” is used herein to refer to a collection of antigen binding molecules that belong to the same germline family, have the same CDR3 lengths, and have 70% or greater homology in CDR3 sequence
  • Comparable is used to describe the degree of difference in two measurements of an evaluable quantitative or qualitative parameter. For example, where a first measurement of an evaluable quantitative parameter and a second measurement of the evaluable parameter do not deviate beyond a range that the skilled artisan would recognize as not producing a statistically significant difference in effect between the two results in the circumstances, the two measurements would be considered “comparable.” In some instances, measurements may be considered “comparable” if one measurement deviates from another by less than 30%, alternatively by less than 25%, alternatively by less than 20%, alternatively by less than 15%, alternatively by less than 10%, alternatively by less than 7%, alternatively by less than 5%, alternatively by less than 4%, alternatively by less than 3%, alternatively by less than 2%, or by less than 1%. In particular embodiments, one measurement is comparable to a reference standard if it deviates by less than 15%, alternatively by less than 10%, or alternatively by less than 5% from the
  • downstream signaling refers to the cellular signaling process that is caused by the interaction of two or more cell surface receptors that are brought into proximity of each other.
  • Effective Concentration As used herein, the terms “effective concentration” or its abbreviation “EC” are used interchangeably to refer to the concentration of an agent (e.g., an hIL2 mutein) in an amount sufficient to effect a change in a given parameter in a test system.
  • the abbreviation “E” refers to the magnitude of a given biological effect observed in a test system when that test system is exposed to a test agent. When the magnitude of the response is expressed as a factor of the concentration (“C”) of the test agent, the abbreviation “EC” is used.
  • Emax refers to the maximal magnitude of a given biological effect observed in response to a saturating concentration of an activating test agent.
  • the subscript refers to the percentage of the Emax of the biological observed at that concentration.
  • concentration of a test agent sufficient to result in the induction of a measurable biological parameter in a test system that is 30% of the maximal level of such measurable biological parameter in response to such test agent, this is referred to as the “EC 30 ” of the test agent with respect to such biological parameter.
  • EC 100 is used to denote the effective concentration of an agent that results the maximal (100%) response of a measurable parameter in response to such agent.
  • EC 50 refers to the concentration of an agent sufficient to results in the half-maximal (50%) change in the measurable parameter.
  • concentration refers to the maximum possible quantity of a test agent that can dissolve in a standard volume of a specific solvent (e.g., water) under standard conditions of temperature and pressure.
  • a saturating concentration of a drug is typically used to denote the concentration sufficient of the drug such that all available receptors are occupied by the drug, and EC 50 is the drug concentration to give the half-maximal effect.
  • the EC of a particular effective concentration of a test agent may be abbreviated with respect to the with respect to particular parameter and test system.
  • Extracellular Domain refers to the portion of a cell surface protein (e.g. a cell surface receptor) which is outside of the plasma membrane of a cell.
  • the term “ECD” may include the extra-cytoplasmic portion of a transmembrane protein or the extra-cytoplasmic portion of a cell surface (or membrane associated protein).
  • percent (%) sequence identity refers to a sequence that has at least 50% sequence identity with a reference sequence. Alternatively, percent sequence identity can be any integer from 50% to 100%. In some embodiments, a sequence has at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the reference sequence as determined with BLAST using standard parameters, as described below. For sequence comparison, typically one sequence acts as a reference sequence, to which test sequences are compared.
  • test and reference sequences are entered into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. Default program parameters can be used, or alternative parameters can be designated.
  • sequence comparison algorithm then calculates the percent sequence identities for the test sequences relative to the reference sequence, based on the program parameters.
  • a comparison window includes reference to a segment of any one of the number of contiguous positions, e.g., a segment of at least 10 residues.
  • the comparison window has from 10 to 600 residues, e.g., about 10 to about 30 residues, about 10 to about 20 residues, about 50 to about 200 residues, or about 100 to about 150 residues, in which a sequence may be compared to a reference sequence of the same number of contiguous positions after the two sequences are optimally aligned.
  • Algorithms that are suitable for determining percent sequence identity and sequence similarity are the BLAST and BLAST 2.0 algorithms, which are described in Altschul et al. (1990) J. Mol. Biol. 215: 403-410 and Altschul et al. (1977) Nucleic Acids Res. 25: 3389-3402, respectively.
  • HSPs high scoring sequence pairs
  • T some positive-valued threshold score
  • These initial neighborhood word hits act as seeds for initiating searches to find longer HSPs containing them.
  • the word hits are then extended in both directions along each sequence for as far as the cumulative alignment score can be increased.
  • Cumulative scores are calculated using, for nucleotide sequences, the parameters M (reward score for a pair of matching residues; always >0) and N (penalty score for mismatching residues; always ⁇ 0).
  • M forward score for a pair of matching residues; always >0
  • N penalty score for mismatching residues; always ⁇ 0.
  • a scoring matrix is used to calculate the cumulative score. Extension of the word hits in each direction are halted when: the cumulative alignment score falls off by the quantity X from its maximum achieved value; the cumulative score goes to zero or below, due to the accumulation of one or more negative-scoring residue alignments; or the end of either sequence is reached.
  • the BLAST algorithm parameters W, T, and X determine the sensitivity and speed of the alignment.
  • the BLASTP program uses as defaults a word size (W) of 3, an expectation (E) of 10, and the BLOSUM62 scoring matrix (see Henikoff& Henikoff, Proc. Natl. Acad. Sci. USA 89:10915 (1989)).
  • the BLAST algorithm also performs a statistical analysis of the similarity between two sequences (see, e.g., Karlin & Altschul, Proc. Nat'l. Acad. Sci. USA 90:5873-5787 (1993)).
  • P(N) the smallest sum probability
  • an amino acid sequence is considered similar to a reference sequence if the smallest sum probability in a comparison of the test amino acid sequence to the reference amino acid sequence is less than about 0.01, more preferably less than about 10 ⁇ 5 , and most preferably less than about 10 ⁇ 20 .
  • IL27R interleukin 27 receptor
  • IL27R ⁇ subunits IL27R a
  • gp130 glycoprotein 130
  • the human sequence of IL27R ⁇ is listed as UniProt ID NO. Q6UWB1.
  • the human sequence of gp130 is listed as UniProt ID NO. Q13514.
  • Intracellular signaling As used herein, the terms “intracellular signaling” and “downstream signaling” are used interchangeably to refer to the to the cellular signaling process that is caused by the interaction of the intracellular domains (ICDs) of two or more cell surface receptors that are in proximity of each other.
  • ICDs intracellular domains
  • the association of the ICDS of the receptor subunits brings the JAK domains of the ICDs into proximit which initiates a phosphorylation cascade in which STAT molecules are phosphorylated and translocate to the nucleus associating with particular nucleic acid sequences resulting in the activation and expression of particular genes in the cell.
  • the binding molecules of the present disclosure provide intraceullar signaling characteristic of the IL-27 receptor when activated by its natural cognate IL27.
  • To measure downstream signaling activity a number of methods are available. For example, in some embodiments, one can measure JAK/STAT signaling by the presence of phosphorylated receptors and/or phosphorylated STATs.
  • the expression of one or more downstream genes, whose expression levels can be affected by the level of downstream signalinging caused by the binding molecule can also be measured.
  • Ligand refers to a molecule that exhibits specific binding to a receptor and results in a change in the biological activity of the receptor so as to effect a change in the activity of the receptor to which it binds.
  • the term “ligand” refers to a molecule, or complex thereof, that can act as an agonist or antagonist of a receptor.
  • the term “ligand” encompasses natural and synthetic ligands.
  • Ligand also encompasses small molecules, e.g., peptide mimetics of cytokines and peptide mimetics of antibodies. The complex of a ligand and receptor is termed a “ligand-receptor complex.”
  • linker refers to a linkage between two elements, e.g., protein domains.
  • a linker can be a covalent bond or a peptide linker.
  • bond refers to a chemical bond, e.g., an amide bond or a disulfide bond, or any kind of bond created from a chemical reaction, e.g., chemical conjugation.
  • peptide linker refers to an amino acid or polyeptide that may be employed to link two protein domains to provide space and/or flexibility between the two protein domains.
  • Modulate As used herein, the terms “modulate”, “modulation” and the like refer to the ability of a test agent to affect a response, either positive or negative or directly or indirectly, in a system, including a biological system or biochemical pathway.
  • Multimerization refers to two or more cell surface receptors, or domains or subunits thereof, being brought in close proximity to each other such that the receptors, or domains or subunits thereof, can interact with each other and cause intracellular signaling.
  • N-Terminus As used herein in the context of the structure of a polypeptide, “N-terminus” (or “amino terminus”) and “C-terminus” (or “carboxyl terminus”) refer to the extreme amino and carboxyl ends of the polypeptide, respectively, while the terms “N-terminal” and “C-terminal” refer to relative positions in the amino acid sequence of the polypeptide toward the N-terminus and the C-terminus, respectively, and can include the residues at the N-terminus and C-terminus, respectively.
  • immediateately N-terminal or “immediately C-terminal” are used to refers to a position of a first amino acid residue relative to a second amino acid residue where the first and second amino acid residues are covalently bound to provide a contiguous amino acid sequence.
  • nucleic acid refers to a polymeric form of nucleotides of any length, either deoxyribonucleotides or ribonucleotides, or analogs thereof.
  • polynucleotides include linear and circular nucleic acids, messenger RNA (mRNA), complementary DNA (cDNA), recombinant polynucleotides, vectors, probes, primers and the
  • operably linked is used herein to refer to the relationship between nucleic acid sequences encoding differing functions when combined into a single nucleic acid sequence that, when introduced into a cell, provides a nucleic acid which is capable of effecting the transcription and/or translation of a particular nucleic acid sequence in a cell.
  • DNA for a signal sequence is operably linked to DNA for a polypeptide if it is expressed as a preprotein that participates in the secretion of the polypeptide; a promoter or enhancer is operably linked to a coding sequence if it affects the transcription of the sequence; or a ribosome binding site is operably linked to a coding sequence if it is positioned so as to facilitate translation.
  • operably linked means that the DNA sequences being linked are contiguous, and, in the case of a secretory leader, contiguous and in reading phase. However, certain genetic elements such as enhancers need not be contiguous with respect to the sequence to which they provide their effect.
  • Partial Agonist refers to a molecule that specifically binds that bind to and activate a given receptor but possess only partial activation the receptor relative to a full agonist. Partial agonists may display both agonistic and antagonistic effects. For example, when both a full agonist and partial agonist are present, the partial agonist acts as a competitive antagonist by competing with the full agonist for the receptor binding resulting in net decrease in receptor activation relative to the contact of the receptor with the full agonist in the absence of the partial agonist.
  • partial agonists can be used to activate receptors to give a desired submaximal response when inadequate amounts of the endogenous ligand are present, or they can reduce the overstimulation of receptors when excess amounts of the endogenous ligand are present.
  • the maximum response (Emax) produced by a partial agonist is called its intrinsic activity and may be expressed on a percentage scale where a full agonist produced a 100% response.
  • the IL-27 binding molecule has a reduced E max compared to the E max caused by IL-27.
  • E max reflects the maximum response level in a cell type that can be obtained by a ligand (e.g., a binding molecule described herein or the native cytokine (e.g., IL-27)).
  • the IL-27 binding molecule described herein has at least 1% (e.g., between 1% and 100%, between 10% and 100%, between 20% and 100%, between 30% and 100%, between 40% and 100%, between 50% and 100%, between 60% and 100%, between 70% and 100%, between 80% and 100%, between 90% and 100%, between 1% and 90%, between 1% and 80%, between 1% and 70%, between 1% and 60%, between 1% and 50%, between 1% and 40%, between 10% and 30%, between 10% and 20%, or between 10% and 10%) of the E max caused by IL-27.
  • the E max of the IL-27 binding molecule described herein is greater (e.g., at least 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% greater) than the E max of the natural ligand, IL-27.
  • the E max of the IL-27 binding molecule can be changed.
  • the IL-27 binding molecule can cause E max in the most desired cell types, and a reduced E max in other cell types.
  • Polypeptide As used herein the terms “polypeptide,” “peptide,” and “protein”, used interchangeably herein, refer to a polymeric form of amino acids of any length, which can include genetically coded and non-genetically coded amino acids, chemically or biochemically modified or derivatized amino acids, and polypeptides having modified polypeptide backbones.
  • the terms include fusion proteins, including, but not limited to, fusion proteins with a heterologous amino acid sequence; fusion proteins with heterologous and homologous leader sequences; fusion proteins with or without N-terminus methionine residues; fusion proteins with immunologically tagged proteins; fusion proteins of immunologically active proteins (e.g. antigenic diphtheria or tetanus toxin fragments) and the like.
  • the terms “prevent”, “preventing”, “prevention” and the like refer to a course of action initiated with respect to a subject prior to the onset of a disease, disorder, condition or symptom thereof so as to prevent, suppress, inhibit or reduce, either temporarily or permanently, a subject's risk of developing a disease, disorder, condition or the like (as determined by, for example, the absence of clinical symptoms) or delaying the onset thereof, generally in the context of a subject predisposed due to genetic, experiential or environmental factors to having a particular disease, disorder or condition.
  • the terms “prevent”, “preventing”, “prevention” are also used to refer to the slowing of the progression of a disease, disorder or condition from a present its state to a more deleterious state.
  • proximity refers to the spatial proximity or physical distance between two cell surface receptors, or domains or subunits thereof, after a binding molecule described herein binds to the two cell surface receptors, or domains or subunits thereof.
  • the spatial proximity between the cell surface receptors, or domains or subunits thereof can be, e.g., less than about 500 angstroms, such as e.g., a distance of about 5 angstroms to about 500 angstroms.
  • the spatial proximity amounts to less than about 5 angstroms, less than about 20 angstroms, less than about 50 angstroms, less than about 75 angstroms, less than about 100 angstroms, less than about 150 angstroms, less than about 250 angstroms, less than about 300 angstroms, less than about 350 angstroms, less than about 400 angstroms, less than about 450 angstroms, or less than about 500 angstroms. In some embodiments, the spatial proximity amounts to less than about 100 angstroms. In some embodiments, the spatial proximity amounts to less than about 50 angstroms. In some embodiments, the spatial proximity amounts to less than about 20 angstroms.
  • the spatial proximity amounts to less than about 10 angstroms. In some embodiments, the spatial proximity ranges from about 10 to 100 angstroms, from about 50 to 150 angstroms, from about 100 to 200 angstroms, from about 150 to 250 angstroms, from about 200 to 300 angstroms, from about 250 to 350 angstroms, from about 300 to 400 angstroms, from about 350 to 450 angstroms, or about 400 to 500 angstroms.
  • the spatial proximity amounts to less than about 250 angstroms, alternatively less than about 200 angstroms, alternatively less than about 150 angstroms, alternatively less than about 120 angstroms, alternatively less than about 100 angstroms, alternatively less than about 80 angstroms, alternatively less than about 70 angstroms, or alternatively less than about 50 angstroms.
  • the term “receptor” refers to a polypeptide having a domain that specifically binds a ligand that binding of the ligand results in a change to at least one biological property of the polypeptide.
  • the receptor is a “soluble” receptor that is not associated with a cell surface.
  • the receptor is a cell surface receptor that comprises an extracellular domain (ECD) and a membrane associated domain which serves to anchor the ECD to the cell surface.
  • ECD extracellular domain
  • the receptor is a membrane spanning polypeptide comprising an intracellular domain (ICD) and extracellular domain (ECD) linked by a membrane spanning domain typically referred to as a transmembrane domain (TM).
  • a receptor is a component of a multi-component complex to facilitate intracellular signaling.
  • the ligand may bind a cell surface molecule having not associated with any intracellular signaling alone but upon ligand binding facilitates the formation of a multimeric complex that results in intracellular signaling.
  • Recombinant As used herein, the term “recombinant” is used as an adjective to refer to the method by a polypeptide, nucleic acid, or cell that was modified using recombinant DNA technology.
  • a recombinant protein is a protein produced using recombinant DNA technology and may be designated as such using the abbreviation of a lower case “r” (e.g., rhIL2) to denote the method by which the protein was produced.
  • a cell is referred to as a “recombinant cell” if the cell has been modified by the incorporation (e.g., transfection, transduction, infection) of exogenous nucleic acids (e.g., ssDNA, dsDNA, ssRNA, dsRNA, mRNA, viral or non-viral vectors, plasmids, cosmids and the like) using recombinant DNA technology.
  • exogenous nucleic acids e.g., ssDNA, dsDNA, ssRNA, dsRNA, mRNA, viral or non-viral vectors, plasmids, cosmids and the like.
  • exogenous nucleic acids e.g., ssDNA, dsDNA, ssRNA, dsRNA, mRNA, viral or non-viral vectors, plasmids, cosmids and the like.
  • the techniques and protocols for recombinant DNA technology are well known in
  • response for example, of a cell, tissue, organ, or organism, encompasses a quantitative or qualitative change in a evaluable biochemical or physiological parameter, (e.g., concentration, density, adhesion, proliferation, activation, phosphorylation, migration, enzymatic activity, level of gene expression, rate of gene expression, rate of energy consumption, level of or state of differentiation, where the change is correlated with activation, stimulation, or treatment, or with internal mechanisms such as genetic programming.
  • a biochemical or physiological parameter e.g., concentration, density, adhesion, proliferation, activation, phosphorylation, migration, enzymatic activity, level of gene expression, rate of gene expression, rate of energy consumption, level of or state of differentiation, where the change is correlated with activation, stimulation, or treatment, or with internal mechanisms such as genetic programming.
  • activation “stimulation”, and the like refer to cell activation as regulated by internal mechanisms, as well as by external or environmental factors.
  • the terms “inhibition”, “down-regulation” and the like refer
  • Single Domain Antibody refers to an antibody having a single (only one) monomeric variable antibody domain.
  • a sdAb is able to bind selectively to a specific antigen.
  • a V H H antibody is an example of a sdAb.
  • binding pairs e.g., a binding molecule described herein/receptor, a ligand/receptor, antibody/antigen, antibody/ligand, antibody/receptor binding pairs
  • a first molecule of a binding pair is said to specifically bind to a second molecule of a binding pair when the first molecule of the binding pair does not bind in a significant amount to other components present in the sample.
  • a first molecule of a binding pair is said to specifically bind to a second molecule of a binding pair when the affinity of the first molecule for the second molecule is at least two-fold greater, alternatively at least five times greater, alternatively at least ten times greater, alternatively at least 20-times greater, or alternatively at least 100-times greater than the affinity of the first molecule for other components present in the sample.
  • Stably associated or “in stable association with” are used to refer to the various means by which one molecule (e.g., a polypeptide) may be associated with another molecule over an extended period of time.
  • the stable association of one molecule to another may be effected by a variety of means, including covalent bonding and non-covalent interactions.
  • stable association of two molecules may be effected by covalent bonds such as peptide bonds.
  • stable association of two molecules may be effected b non-covalent interactions.
  • non-covalent interactions which may provide a a stable association between two molecules include electrostatic interactions (e.g., hydrogen bonding, ionic bonding, halogen binding, dipole-dipole interactions, Van der Waals forces and ⁇ -effects including cation- ⁇ interactions, anion- ⁇ interactions and ⁇ - ⁇ interactions) and hydrophobilic/hydrophilic interactions.
  • electrostatic interactions e.g., hydrogen bonding, ionic bonding, halogen binding, dipole-dipole interactions, Van der Waals forces and ⁇ -effects including cation- ⁇ interactions, anion- ⁇ interactions and ⁇ - ⁇ interactions
  • hydrophobilic/hydrophilic interactions e.g., electrostatic interactions (e.g., hydrogen bonding, ionic bonding, halogen binding, dipole-dipole interactions, Van der Waals forces and ⁇ -effects including cation- ⁇ interactions, anion- ⁇ interactions and ⁇ - ⁇ interactions) and hydrophobilic/hydrophilic interactions.
  • An Fe “knob” monomer stably associates non-covalently with an Fe “hole” monomer.
  • Conjugation of a first sdAb which specifically binds to the extracellular domain of a first subunit of a heterodimeric receptor to an “Fc knob” monomer and conjugation of an second sdAb which specifically binds to the extracellular domain of a second subunit of a heterodimeric receptor to an “Fe hole” monomer provides stable association of the first and second sdAbs.
  • the knob-into-hole modification is more fully described in Ridgway, et al. (1996) Protein Engineering 9(7):617-621 and U.S. Pat. No. 5,731,168, issued Mar. 24, 1998, U.S. Pat. No.
  • the knob-into-hole modification refers to a modification at the interface between two immunoglobulin heavy chains in the CH3 domain, wherein: i) in a CH3 domain of a first heavy chain, an amino acid residue is replaced with an amino acid residue having a larger side chain (e.g., tyrosine or tryptophan) creating a projection from the surface (“knob”) and ii) in the CH3 domain of a second heavy chain, an amino acid residue is replaced with an amino acid residue having a smaller side chain (e.g., alanine or threonine), thereby generating a cavity (“hole”) within at interface in the second CH3 domain within which the protruding side chain of the first CH3 domain (“knob”) is received by the cavity in the second CH3 domain.
  • a cavity e.g., alanine or threonine
  • the “knob-into-hole modification” comprises the amino acid substitution T366W and optionally the amino acid substitution S354C in one of the antibody heavy chains, and the amino acid substitutions T366S, L368A, Y407V and optionally Y349C in the other one of the antibody heavy chains.
  • the Fc domains may be modified by the introduction of cysteine residues at positions S354 on one chain and Y349 on the second chain which results in a stabilizing disulfide bridge between the two antibody heavy chains in the Fc region (Carter, et al. (2001) Immunol Methods 248, 7-15).
  • the knob-into-hole format is used to facilitate the expression of a first polypeptide (e.g., an IL27R ⁇ binding sdAb) on a first Fe monomer with a “knob” modification and a second polypeptide on the second Fc monomer possessing a “hole” modification to facilitate the expression of heterodimeric polypeptide conjugates.
  • a first polypeptide e.g., an IL27R ⁇ binding sdAb
  • Subject The terms “recipient”, “individual”, “subject”, and “patient”, are used interchangeably herein and refer to any mammalian subject for whom diagnosis, treatment, or therapy is desired, particularly humans. “Mammal” for purposes of treatment refers to any animal classified as a mammal, including humans, domestic and farm animals, and zoo, sports, or pet animals, such as dogs, horses, cats, cows, sheep, goats, pigs, etc. In some embodiments, the mammal is a human being.
  • the term “substantially” refers to a quantity, level, value, number, frequency, percentage, dimension, size, amount, weight or length that is 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or higher of a reference quantity, level, value, number, frequency, percentage, dimension, size, amount, weight or length.
  • “substantially the same” refers to a quantity, level, value, number, frequency, percentage, dimension, size, amount, weight or length that produces an effect, e.g., a physiological effect, that is approximately the same as a reference quantity, level, value, number, frequency, percentage, dimension, size, amount, weight or length.
  • the term “suffering from” refers to a determination made by a physician with respect to a subject based on the available information accepted in the field for the identification of a disease, disorder or condition including but not limited to X-ray, CT-scans, conventional laboratory diagnostic tests (e.g., blood count), genomic data, protein expression data, immunohistochemistry, that the subject requires or will benefit from treatment.
  • the term suffering from is typically used in conjunction with a particular disease state such as “suffering from a neoplastic disease” refers to a subject which has been diagnosed with the presence of a neoplasm.
  • therapeutically effective amount is used in reference to the administration of an agent to a subject, either alone or as part of a pharmaceutical composition or treatment regimen, in a single dose or as part of a series of doses in an amount capable of having any detectable, positive effect on any symptom, aspect, or characteristic of a disease, disorder or condition when administered to the subject.
  • the therapeutically effective amount can be ascertained by measuring relevant physiological effects, and it may be adjusted in connection with a dosing regimen and in response to diagnostic analysis of the subject's condition, and the like.
  • the parameters for evaluation to determine a therapeutically effective amount of an agent are determined by the physician using art accepted diagnostic criteria including but not limited to indicia such as age, weight, sex, general health, ECOG score, observable physiological parameters, blood levels, blood pressure, electrocardiogram, computerized tomography, X-ray, and the like.
  • a therapeutically effective amount of an agent may be monitored to determine if a therapeutically effective amount of an agent has been administered to the subject such as body temperature, heart rate, normalization of blood chemistry, normalization of blood pressure, normalization of cholesterol levels, or any symptom, aspect, or characteristic of the disease, disorder or condition, modification of biomarker levels, increase in duration of survival, extended duration of progression free survival, extension of the time to progression, increased time to treatment failure, extended duration of event free survival, extension of time to next treatment, improvement objective response rate, improvement in the duration of response, and the like that that are relied upon by clinicians in the field for the assessment of an improvement in the condition of the subject in response to administration of an agent.
  • Treat: The terms “treat”, “treating”, treatment” and the like refer to a course of action (such as administering a binding molecule described herein, or a pharmaceutical composition comprising same) initiated with respect to a subject after a disease, disorder or condition, or a symptom thereof, has been diagnosed, observed, or the like in the subject so as to eliminate, reduce, suppress, mitigate, or ameliorate, either temporarily or permanently, at least one of the underlying causes of such disease, disorder, or condition afflicting a subject, or at least one of the symptoms associated with such disease, disorder, or condition.
  • a course of action such as administering a binding molecule described herein, or a pharmaceutical composition comprising same
  • the treatment includes a course of action taken with respect to a subject suffering from a disease where the course of action results in the inhibition (e.g., arrests the development of the disease, disorder or condition or ameliorates one or more symptoms associated therewith) of the disease in the subject.
  • VHH As used herein, the term “V H H” is a type of sdAb that has a single monomeric heavy chain variable antibody domain. Such antibodies can be found in or produced from Camelid mammals (e.g., camels, llamas) which are naturally devoid of light chainsV H Hs can be obtained from immunization of camelids (including camels, llamas, and alpacas (see, e.g., Hamers-Casterman, et al. (1993) Nature 363:446-448) or by screening libraries (e.g., phage libraries) constructed in V H H frameworks.
  • Camelid mammals e.g., camels, llamas
  • alpacas see, e.g., Hamers-Casterman, et al. (1993) Nature 363:446-448
  • screening libraries e.g., phage libraries
  • Antibodies having a given specificity may also be derived from non-mammalian sources such as V H Hs obtained from immunization of cartilaginous fishes including, but not limited to, sharks.
  • a V H H in a bispecific V H H 2 binding molecule described herein binds to a receptor (e.g., the first receptor or the second receptor of the natural or non-natural receptor pairs) if the equilibrium dissociation constant between the V H H and the receptor is greater than about 10 ⁇ 6 M, alternatively greater than about 10 ⁇ 8 M, alternatively greater than about 10 ⁇ 10 M, alternatively greater than about 10 ⁇ 11 M, alternatively greater than about 10 ⁇ 10 M, greater than about 10 ⁇ 12 M as determined by, e.g., Scatchard analysis (Munsen, et al.
  • V H H described herein can be humanized to contain human framework regions.
  • Examples of human germlines that could be used to create humanized V H Hs include, but are not limited to, VH3-23 (e.g., UniProt ID: P01764), VH3-74 (e.g., UniProt ID: A0A0B4J1X5), VH3-66 (e.g., UniProt ID: A0A0C4DH42), VH3-30 (e.g., UniProt ID: P01768), VH3-11 (e.g., UniProt ID: P01762), and VH3-9 (e.g., UniProt ID: P01782).
  • VH3-23 e.g., UniProt ID: P01764
  • VH3-74 e.g., UniProt ID: A0A0B4J1X5
  • VH3-66 e.g., UniProt ID: A0A0C4DH42
  • VH3-30 e.g., UniProt ID: P01768
  • V H H 2 As used herein, the term “V H H 2 ” and “bispecific V H H 2 ” and “VHH dimer” refers to are used interchangeably to refer to a subtype of the binding molecules of the present disclosure wherein the first and second sdAbs are both VHHs and first V H H binding to a first receptor, or domain or subunit thereof, and a second V H H binding to a second receptor, or domain or subunit thereof.
  • Wild Type As used herein, the term “wild type” or “WT” or “native” is used to refer to an amino acid sequence or a nucleotide sequence that is found in nature and that has not been altered by the hand of man.
  • the IL27 receptor includes IL27R ⁇ subunit (IL27R ⁇ ) and glycoprotein 130 subunit (gp130).
  • IL27R ⁇ subunit
  • gp130 glycoprotein 130 subunit
  • an IL27R binding protein that specifically binds to IL27Ra and gp130.
  • the IL27R binding protein binds to a mammalian cell expressing both IL27R ⁇ and gp130.
  • the IL27R binding protein can be a bispecific V H H 2 as described below.
  • the IL27R binding protein can be a bispecific V H H 2 that has a first V H H binding to IL27R ⁇ (an anti-IL27R ⁇ V H H antibody) and a second V H H binding to gp130 (an anti-gp130 V H H antibody) and causes the dimerization of the two receptor subunits and downstream signaling when bound to a cell expressing IL27R ⁇ and gp130, e.g., a CD8 + T cells, a CD4 + T cells, and/or a T regulatory (Treg) cell.
  • a cell expressing IL27R ⁇ and gp130 e.g., a CD8 + T cells, a CD4 + T cells, and/or a T regulatory (Treg) cell.
  • V H H is a type of single-domain antibody (sdAb) containing a single monomeric variable antibody domain. Like a full-length antibody, it is able to bind selectively to a specific antigen.
  • the complementary determining regions (CDRs) of V H Hs are within a single-domain polypeptide.
  • V H Hs can be engineered from heavy-chain antibodies found in camelids.
  • V H H has a molecular weight of approximately 12-15 kDa which is much smaller than traditional mammalian antibodies (150-160 kDa) composed of two heavy chains and two light chains.
  • V H Hs can be found in or produced from Camelidae mammals (e.g., camels, llamas, dromedary, alpaca, and guanaco) which are naturally devoid of light chains.
  • Descriptions of sdAbs and V H HS can be found in, e.g., De Greve et al., Curr Opin Biotechnol. 61:96-101, 2019; Ciccarese, et al., Front Genet. 10:997, 2019; Chanier and Chames, Antibodies ( Basel ) 8(1), 2019; and De Vlieger et al., Antibodies ( Basel ) 8(1), 2018.
  • the two V H Hs can be synthesized separately, then joined together by a linker.
  • the bispecific V H H 2 can be synthesized as a fusion protein.
  • V H Hs having different binding activities and receptor targets can be paired to make a bispecific V H H 2 .
  • the binding proteins can be screened for signal transduction on cells carrying one or both relevant receptors.
  • a bispecific V H H 2 comprises:
  • a V H H described herein can be humanized to contain human framework regions.
  • human germlines that could be used to create humanized V H Hs include, but are not limited to, VH43-23 (e.g., UniProt ID: P01764), VH43-74 (e.g., UniProtID: A0A0B4JTX5), VH43-66 (e.g., UniProtID: A0A0C4DH42), VH43-30 (e.g., UniProt ID: P01768), VH43-11 (e.g., UniProt ID: P01762), and VH43-9 (e.g., UniProt ID: P01782).
  • VH43-23 e.g., UniProt ID: P01764
  • VH43-74 e.g., UniProtID: A0A0B4JTX5
  • VH43-66 e.g., UniProtID: A0A0C4DH42
  • an IL27R binding protein described herein (e.g., in Table TA) is encoded by an isolated nucleic acid that is substantially identical to a sequence of any one of Table 1B below.
  • an IL27R binding protein described herein (e.g., an IL27R binding protein comprising a sequence of Table TA) is encoded by an isolated nucleic acid comprising a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity to a sequence of Table 1B below.
  • a bispecific V H H 2 comprises:
  • a bispecific V H H 2 described herein comprises an anti-gp130 V H H antibody comprising a CDR1, a CDR2, and a CDR3 and an anti-IL27R ⁇ V H H antibody comprising a CDR1, a CDR2, and a CDR3 as described in each row of Table 1 below.
  • the CDR1, CDR2, and CDR3 in the anti-gp130 V H H antibody and CDR1, CDR2, and CDR3 in the anti-IL27R ⁇ V H H antibody can each, independently, comprise at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity, or have 0, 1, 2, or 3 amino acid changes, optionally conservative amino acid changes, relative to the sequence described in each row of Table 1.
  • the bispecific V H H 2 comprises an anti-gp130 V H H antibody at the N-terminus and an anti-IL27R ⁇ V H H antibody at the C-terminus. In some embodiments, the bispecific V H H 2 comprises an anti-IL27R ⁇ V H H antibody at the N-terminus and an anti-gp130 V H H antibody at the C-terminus.
  • a bispecific V H H 2 can contain, from the N-terminus to the C-terminus, a first V H H binding to gp130 (an anti-gp130 V H H antibody), a linker, and a second V H H binding to IL27R ⁇ (an anti-IL27R ⁇ V H H antibody).
  • the linker joins the C-terminus of the anti-gp130 V H H in the binding protein to the N-terminus of the anti-IL27R ⁇ V H H in the binding protein.
  • a purification peptide e.g., a six-histidine peptide ((His) 6 (SEQ ID NO: 1531) or His-tag) can be included, or not, in the bispecific V H H 2 .
  • a bispecific V H H 2 described herein comprises an anti-gp130 V H H antibody comprising a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity to a sequence of any one of SEQ ID NOS:232-237; and an anti-IL27R ⁇ V H H antibody comprising a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity to a sequence of any one of SEQ ID NOS:238-244.
  • a bispecific V H H 2 described herein comprises an anti-gp130 V H H antibody and an anti-IL27R ⁇ V H H antibody as described in each row of Table 2A below or Table 1A above.
  • the anti-gp130 V H H antibody and the anti-IL27R ⁇ V H H antibody can each, independently, comprise at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity to the sequence described in each row of Table 2A.
  • the bispecific V H H 2 can comprise a linker (e.g., linkers described in Section IV) between the anti-gp130 V H H antibody and the anti-IL27R ⁇ V H H antibody as described in each row of Table 2A below.
  • the linker is GGGS (SEQ ID NO:108) or (GGGS)n (SEQ ID NO: 1532), (GGS)nG (SEQ ID NO: 1533), (GGGGS)n (SEQ ID NO: 1534) as described elwhere herein.
  • the sequence of the anti-gp130 V H H is N-terminus to the linker and the sequence of the anti-IL27R ⁇ V H H is C-terminus to the linker. Examples of linkers are further described in Section IV below. The CDR sequences in each V H H are underlined.
  • the bispecific V H H Z Comprises a sequence that is substantially identical to a sequence of any one of SEQ ID NOS: 1-42.
  • a bispecific V H H 2 can have a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 9900, or 1000%) sequence identity to a sequence of any one of SEQ ID NOS: 1-42, as shown in Table 2B below.
  • the linker GGGS SEQ ID NO: 108 is in bold.
  • the sequence of the anti-gp130 V H H is N-terminus to the linker and the sequence of the anti-IL27R ⁇ V H H is C-terminus to the linker.
  • the CDR sequences in each V H H are underlined.
  • an IL27R binding protein described herein e.g., an IL27R binding protein comprising a sequence of any one of SEQ ID NOS: 1-42
  • an isolated nucleic acid that is substantially identical to a sequence of any one of SEQ ID NOS: 109-150, as listed in Table 2C below.
  • an IL27R binding protein described herein e.g., an IL27R binding protein comprising a sequence of any one of SEQ ID NOS: 1-42
  • an isolated nucleic acid comprising a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity to a sequence of any one of SEQ ID NOS: 109-150, as listed in Table 2C below.
  • a bispecific V H H 2 can contain, from the N-terminus to the C-terminus, a first V H H binding to IL27R ⁇ (an anti-TL27R ⁇ V H H antibody), a linker, and a second V H H binding to gp130 (an anti-gp130 V H H antibody).
  • the linker joins the C-terminus of the anti-IL27R ⁇ V H H in the binding protein to the N-terminus of the anti-gp 130 V H H in the binding protein.
  • a purification peptide e.g., a six-histidine peptide ((His) 6 (SEQ ID NO: 1531) or His-tag) or an Fc tag can be included in the bispecific V H H 2 .
  • a bispecific V H H 2 described herein comprises an anti-IL27R ⁇ V H H antibody comprising a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity to a sequence of any one of SEQ ID NOS:245-251; and an anti-gp130 V H H antibody comprising a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity to a sequence of any one of SEQ ID NOS:252-257.
  • a bispecific V H H 2 described herein comprises an anti-IL27R ⁇ V H H antibody and an anti-gp130 V H H antibody as described in each row of Table 3A below or Table A above.
  • the anti-IL27Ra V H H antibody and the anti-gp130 V H H antibody can each, independently, comprise at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity to the sequence described in each row of Table 3A.
  • the bispecific V H H 2 can comprise a linker (e.g., linkers described in Section IV) between the anti-IL27R ⁇ V H H antibody and the anti-gp130 V H H antibody as described in each row of Table 3A below.
  • the linker is GGGS (SEQ ID NO:108).
  • the sequence of the anti-IL27R ⁇ V H H is N-terminal to the linker and the sequence of the anti-gp130 V H H is C-terminal to the linker. Examples of linkers are further described in Section IV below. The CDR sequences in each V H H are underlined.
  • the bispecific V H H 2 Comprises a sequence that is substantially identical to a sequence of any one of SEQ ID NOS:43-84.
  • a bispecific V H H 2 can have a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity to the sequence of any one of SEQ ID NOS:43-84, as shown in Table 3B below.
  • the linker GGGS SEQ ID NO: 108 is in bold.
  • the sequence of the anti-IL27R ⁇ V H H is N-terminus to the linker and the sequence of the anti-gp130 V H H is C-terminus to the linker.
  • the CDR sequences in each V H H are underlined.
  • an IL27R binding protein described herein e.g., an IL27R binding protein comprising a sequence of any one of SEQ ID NOS:43-84) is encoded by an isolated nucleic acid that is substantially identical to a sequence of any one of SEQ ID NOS: 151-192, as listed in Table 3C below.
  • an IL27R binding protein described herein (e.g., an IL27R binding protein comprising a sequence of any one of SEQ ID NOS:43-84) is encoded by an isolated nucleic acid comprising a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity to a sequence of any one of SEQ ID NOS: 151-192, as listed in Table 3C below.
  • additional IL27R binding proteins can include three CDR sequences as underlined in an anti-IL27R ⁇ V H H antibody listed in Table 4 below, and three CDR sequences as underlined in an anti-gp130 V H H antibody of any one of SEQ ID NOS:232-237.
  • Additional IL27R binding proteins can include an anti-IL27R ⁇ V H H antibody (e.g., any one of the sequences listed in Table 4 below) and an anti-gp130 V H H antibody (e.g., any one of SEQ ID NOS:232-237.
  • the binding protein comprises the anti-IL27R ⁇ V H H antibody at the N-terminus and the anti-gp130 V H H antibody at the C-terminus.
  • the binding protein comprises the anti-gp130 V H H antibody at the N-terminus and the anti-IL27R ⁇ V H H antibody at the C-terminus.
  • the binding protein comprises a linker (e.g., any one of SEQ ID NOS:85-108 (e.g., SEQ ID NO:108)) between the anti-TL27R ⁇ V H H antibody and the anti-gp130 V H H antibody.
  • the binding protein comprises a purification tag, such as as a six-histidine peptide (His) 6 (SEQ ID NO: 1531) (His-tag).
  • An IL27R binding protein can comprise three CDR sequences as underlined in an anti-IL27R ⁇ V H H antibody and three CDR sequences as underlined in an anti-gp130 V H H antibody as described in each row of Table 5 below.
  • an L27R binding protein comprises an anti-IL27R ⁇ V H H antibody and an anti-gp130 V H H antibody as described in each row of Table 5 below.
  • the binding protein comprises the anti-IL27R ⁇ V H H antibody at the N-terminus and the anti-gp130 V H H antibody at the C-terminus.
  • the binding protein comprises the anti-gp130 V H H antibody at the N-terminus and the anti-IL27R ⁇ V H H antibody at the C-terminus.
  • the binding protein comprises a linker (e.g., any one of SEQ ID NOS:85-108 (e.g., SEQ ID NO: 108)) between the anti-IL27R ⁇ V H H antibody and the anti-gp130 V H H antibody.
  • the binding protein comprises a purification tag, such as as a six-histidine peptide (His) 6 (SEQ ID NO: 1531) (His-tag).
  • an IL27R binding protein can comprise a mouse Anti IL27R ⁇ V H H antibody and a mouse Anti gp130 V H H antibody.
  • immunization with an antigen derived from a IL27R ⁇ or gp130 of a first mammalian species may provide antibodies which specifically bind to receptors of one or more additional mammalian species. Such antibodies are termed “cross reactive.”
  • immunization of a camelid with a human derived antigen e.g., the hIL27R ⁇ -ECD
  • a human derived antigen e.g., the hIL27R ⁇ -ECD
  • an IL27R binding protein can comprise three CDR sequences as underlined in a mouse anti-IL27R ⁇ V H H antibody sequence listed below and three CDR sequences as underlined in a mouse anti-gp130 V H H antibody sequence listed below.
  • an IL27R binding protein comprises a mouse anti-IL27R ⁇ V H H antibody listed below and a mouse anti-gp130 V H H antibody listed below.
  • the binding protein comprises the mouse anti-IL27R ⁇ V H H antibody at the N-terminus and the mouse anti-gp130 V H H antibody at the C-terminus.
  • the binding protein comprises the mouse anti-gp130 V H H antibody at the N-terminus and the mouse anti-IL27R ⁇ V H H antibody at the C-terminus.
  • the binding protein comprises a linker (e.g., any one of SEQ ID NOS:85-108 (e.g., SEQ ID NO:108)) between the mouse anti-IL27R ⁇ V H H antibody and the mouse anti-gp130 V H H antibody.
  • the binding protein comprises a purification tag, such as as a six-histidine peptide (His) 6 (SEQ ID NO: 1531) (His-tag).
  • mouse anti-IL27R ⁇ V H H antibody sequences are examples of mouse anti-IL27R ⁇ V H H antibody sequences:
  • mouse anti-gp130 V H H antibody sequences are examples of mouse anti-gp130 V H H antibody sequences:
  • a V H H described herein can be humanized to contain human framework regions.
  • human germlines that could be used to create humanized V H Hs include, but are not limited to, VH3-23 (e.g., UniProt ID: P01764), VH3-74 (e.g., UniProt ID: A0A0B4J1X5), VH3-66 (e.g., UniProt ID: A0A0C4DH42), VH3-30 (e.g., UniProt ID: P01768), VH3-11 (e.g., UniProt ID: P01762), and VH3-9 (e.g., UniProt ID: P01782).
  • VH3-23 e.g., UniProt ID: P01764
  • VH3-74 e.g., UniProt ID: A0A0B4J1X5
  • VH3-66 e.g., UniProt ID: A0A0C4DH42
  • VH3-30
  • the IL27R binding protein has a reduced E max compared to the E max caused by IL27.
  • E max reflects the maximum response level in a cell type that can be obtained by a ligand (e.g., a binding protein described herein or the native cytokine (e.g., IL27)).
  • the IL27R binding protein described herein has at least 1% (e.g., between 1% and 100%, between 10% and 100%, between 20% and 100%, between 30% and 100%, between 40% and 100%, between 50% and 100%, between 60% and 100%, between 70% and 100%, between 80% and 100%, between 90% and 100%, between 1% and 90%, between 1% and 80%, between 1% and 70%, between 1% and 60%, between 1% and 50%, between 10% and 40%, between 10% and 30%, between 10% and 20%, or between 10% and 10%) of the E max caused by IL27.
  • the E max of the IL27R binding protein described herein is greater (e.g., at least 1%, 5%, 10, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% greater) than the E max of the natural ligand, IL27.
  • the E max of the IL27R binding protein can be changed.
  • the IL27R binding protein can cause E max in the most desired cell types, and a reduced E max in other cell types.
  • binding domains of the binding proteins of the present disclosure may be joined contiguously (e.g., the C-terminal amino acid of the first V H H in the binding protein to the N-terminal amino acid of the second V H H in the binding protein) or the binding domains of the binding protein may optionally be joined via a linker.
  • a linker is a linkage between two elements, e.g., protein domains. In a bispecific V H H 2 binding protein described herein, a linker is a linkage between the two V H Hs in the binding protein.
  • a linker can be a covalent bond or a peptide linker.
  • the two V H Hs in a binding protein are joined directly (i.e., via a covalent bond).
  • the length of the linker between two V H Hs in a binding protein can be used to modulate the proximity of the two V H Hs of the binding protein.
  • the overall size and length of the binding protein can be tailored to bind to specific cell receptors or domains or subunits thereof. For example, if the binding protein is designed to bind to two receptors or domains or subunits thereof that are located close to each other on the same cell, then a short linker can be used. In another example, if the binding protein is designed to bind to two receptors or domains or subunits there of that are located on two different cells, then a long linker can be used.
  • the linker is a peptide linker.
  • a peptide linker can include between 1 and 50 amino acids (e.g., between 2 and 50, between 5 and 50, between 10 and 50, between 15 and 50, between 20 and 50, between 25 and 50, between 30 and 50, between 35 and 50, between 40 and 50, between 45 and 50, between 2 and 45, between 2 and 40, between 2 and 35, between 2 and 30, between 2 and 25, between 2 and 20, between 2 and 15, between 2 and 10, between 2 and 5 amino acids).
  • a linker can also be a chemical linker, such as a synthetic polymer, e.g., a polyethylene glycol (PEG) polymer.
  • PEG polyethylene glycol
  • a linker joins the C-terminus of the first V H H in the binding protein to the N-terminus of the second V H H in the binding protein. In other embodiments, a linker joins the C-terminus of the second V H H in the binding protein to the N-terminus of the first V H H in the binding protein.
  • Suitable peptide linkers are known in the art, and include, for example, peptide linkers containing flexible amino acid residues such as glycine and serine.
  • a peptide linker can contain motifs, e.g., multiple or repeating motifs, of GS, GGS, GGGGS (SEQ ID NO:85), GGGGGS (SEQ ID NO:86), GGSG (SEQ ID NO:87), or SGGG (SEQ ID NO:88).
  • a peptide linker can contain 2 to 12 amino acids including motifs of GS, e.g., GS, GSGS (SEQ ID NO:89), GSGSGS (SEQ ID NO:90), GSGSGSGS (SEQ ID NO:91), GSGSGSGSGS (SEQ ID NO:92), or GSGSGSGSGSGSGS (SEQ ID NO:93).
  • a peptide linker can contain 3 to 12 amino acids including motifs of GGS, e.g., GGS, GGSGGS (SEQ ID NO:94), GGSGGSGGS (SEQ ID NO:95), and GGSGGSGGSGGS (SEQ ID NO:96).
  • a peptide linker can contain 4 to 20 amino acids including motifs of GGSG (SEQ ID NO:87), e.g., GGSGGGSG (SEQ ID NO:97), GGSGGGSGGGSG (SEQ ID NO:98), GGSGGGSGGGSGGGSG (SEQ ID NO:99), or GGSGGGSGGGSGGGSG (SEQ ID NO:100).
  • a peptide linker can contain motifs of GGGGS (SEQ ID NO:85), e.g., GGGGSGGGGS (SEQ ID NO:101) or GGGGSGGGGSGGGGS (SEQ ID NO:102).
  • Examples of flexible linkers include glycine polymers (G)n, glycine-alanine polymers, alanine-serine polymers, glycine-serine polymers (for example, (GmSo)n (SEQ ID NO: 1535), (GSGGS)n (SEQ ID NO: 1536), (GmSoGm)n (SEQ ID NO: 1537), (GmSoGmSoGm)n (SEQ ID NO: 1538), (GSGGSm)n (SEQ ID NO: 1539), (GSGSmG)n (SEQ ID NO: 1540), (GGS)nG (SEQ ID NO: 1541) and (GGGSm)n (SEQ ID NO: 1542), and combinations thereof, where m, n, and o are each independently selected from an integer of at least 1 to 20, e.g., 1-18, 216, 3-14, 4-12, 5-10, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10), and other flexible linkers.
  • Glycine and glycine-serine polymers are relatively unstructured, and therefore may serve as a neutral tether between components.
  • Examples of flexible linkers include, but are not limited to GGSG (SEQ ID NO:87), GGSGG (SEQ ID NO:103), GSGSG (SEQ ID NO:104), GSGGG (SEQ ID NO: 105), GGGSG (SEQ ID NO: 106), and GSSSG (SEQ ID NO: 107).
  • G glycine polymers
  • GS glycine-serine polymers
  • Exemplary flexible linkers include, but are not limited to GGGS (SEQ ID NO:108), GGGGS (SEQ ID NO:85), GGSG (SEQ ID NO:87), GGSGG (SEQ ID NO:103), GSGSG (SEQ ID NO:104), GSGGG (SEQ ID NO:105), GGGSG (SEQ ID NO:106), and GSSSG (SEQ ID NO:107).
  • binding proteins described herein can be modified to provide for an extended lifetime in vivo and/or extended duration of action in a subject.
  • the binding protein can be conjugated to carrier molecules to provide desired pharmacological properties such as an extended half-life.
  • the binding protein can be covalently linked to the Fc domain of IgG, albumin, or other molecules to extend its half-life, e.g., by pegylation, glycosylation, and the like as known in the art.
  • the binding protein is conjugated to a functional domain of an Fc-fusion chimeric polypeptide molecule.
  • Fc fusion conjugates have been shown to increase the systemic half-life of biopharmaceuticals, and thus the biopharmaceutical product can require less frequent administration.
  • Fc binds to the neonatal Fc receptor (FcRn) in endothelial cells that line the blood vessels, and, upon binding, the Fc fusion molecule is protected from degradation and re-released into the circulation, keeping the molecule in circulation longer. This Fc binding is believed to be the mechanism by which endogenous IgG retains its long plasma half-life.
  • Fc-fusion technology links a single copy of a biopharmaceutical to the Fc region of an antibody to optimize the pharmacokinetic and pharmacodynamic properties of the biopharmaceutical as compared to traditional Fc-fusion conjugates.
  • the “Fc region” useful in the preparation of Fc fusions can be a naturally occurring or synthetic polypeptide that is homologous to an IgG C-terminal domain produced by digestion of IgG with papain.
  • IgG Fc has a molecular weight of approximately 50 kDa.
  • the binding protein described herein can be conjugated to the entire Fc region, or a smaller portion that retains the ability to extend the circulating half-life of a chimeric polypeptide of which it is a part.
  • full-length or fragmented Fc regions can be variants of the wild-type molecule.
  • each monomer of the dimeric Fc can carry a heterologous polypeptide, the heterologous polypeptides being the same or different.
  • the Fc fusion when the binding protein described herein is to be administered in the format of an Fc fusion, particularly in those situations when the polypeptide chains conjugated to each subunit of the Fe dimer are different, the Fc fusion may be engineered to possess a “knob-into-hole modification.”
  • the knob-into-hole modification is more fully described in Ridgway, et al. (1996) Protein Engineering 9(7):617-621 and U.S. Pat. No. 5,731,168, issued Mar. 24, 1998.
  • the knob-into-hole modification refers to a modification at the interface between two immunoglobulin heavy chains in the CH3 domain, wherein: i) in a CH3 domain of a first heavy chain, an amino acid residue is replaced with an amino acid residue having a larger side chain (e.g., tyrosine or tryptophan) creating a projection from the surface (“knob”), and ii) in the CH3 domain of a second heavy chain, an amino acid residue is replaced with an amino acid residue having a smaller side chain (e.g., alanine or threonine), thereby generating a cavity (“hole”) at interface in the second CH3 domain within which the protruding side chain of the first CH3 domain (“knob”) is received by the cavity in the second CH3 domain.
  • a cavity e.g., alanine or threonine
  • the “knob-into-hole modification” comprises the amino acid substitution T366W and optionally the amino acid substitution S354C in one of the antibody heavy chains, and the amino acid substitutions T366S, L368A, Y407V and optionally Y349C in the other one of the antibody heavy chains.
  • the Fe domains may be modified by the introduction of cysteine residues at positions S354 and Y349 which results in a stabilizing disulfide bridge between the two antibody heavy chains in the Fc region (Carter, et al. (2001) Immunol Methods 248, 7-15).
  • the knob-into-hole format is used to facilitate the expression of a first polypeptide on a first Fc monomer with a “knob” modification and a second polypeptide on the second Fc monomer possessing a “hole” modification to facilitate the expression of heterodimeric polypeptide conjugates.
  • the binding protein can be conjugated to one or more water-soluble polymers.
  • water soluble polymers useful in the practice of the present disclosure include polyethylene glycol (PEG), poly-propylene glycol (PPG), polysaccharides (polyvinylpyrrolidone, copolymers of ethylene glycol and propylene glycol, poly(oxyethylated polyol), polyolefinic alcohol,), polysaccharides), poly-alpha-hydroxy acid), polyvinyl alcohol (PVA), polyphosphazene, polyoxazolines (POZ), poly(N-acryloylmorpholine), or a combination thereof.
  • PEG polyethylene glycol
  • PPG poly-propylene glycol
  • polysaccharides polyvinylpyrrolidone, copolymers of ethylene glycol and propylene glycol
  • PVA polyphosphazene
  • POZ polyoxazolines
  • poly(N-acryloylmorpholine) or a combination thereof.
  • binding protein can be conjugated to one or more polyethylene glycol molecules or “PEGylated.” Although the method or site of PEG attachment to the binding protein may vary, in certain embodiments the PEGylation does not alter, or only minimally alters, the activity of the binding protein.
  • the V H H when employing the V H H sequences describe herein in the preparation of th IL27 binding molecules of the present disclosure, the V H H possesses an N-terminal glutamine (“1Q”) residue. N-terminal glutamine residues have been observed to spontaneously cyclyize to form pyroglutamate (pE) at or near physiological conditions. (See e.g., Liu, et al (2011) J. Biol. Chem. 286(13): 11211-11217). In some embodiments, the formation of pyroglutamate complicates N-terminal PEG conjugation particularly when aldehyde chemistry is used for N-terminal PEGylation.
  • the IL27R ⁇ binding molecules possessing an amino acid at position 1 are substituted at position 1 with an alternative amino acid or are deleted at position 1 (e.g., des-1Q).
  • the IL27R binding molecules of the present disclosure comprise an amino acid substitution selected from the group Q1E and Q1D.
  • selective PEGylation of the binding protein for example, by the incorporation of non-natural amino acids having side chains to facilitate selective PEG conjugation, may be employed.
  • Specific PEGylation sites can be chosen such that PEGylation of the binding protein does not affect its binding to the target receptors.
  • the increase in half-life is greater than any decrease in biological activity.
  • PEGs suitable for conjugation to a polypeptide sequence are generally soluble in water at room temperature, and have the general formula R(O—CH 2 —CH 2 ) n O—R, where R is hydrogen or a protective group such as an alkyl or an alkanol group, and where n is an integer from 1 to 1000.
  • R is a protective group, it generally has from 1 to 8 carbons.
  • the PEG conjugated to the polypeptide sequence can be linear or branched. Branched PEG derivatives, “star-PEGs” and multi-armed PEGs are contemplated by the present disclosure.
  • a molecular weight of the PEG used in the present disclosure is not restricted to any particular range.
  • the PEG component of the binding protein can have a molecular mass greater than about 5 kDa, greater than about 10 kDa, greater than about 15 kDa, greater than about 20 kDa, greater than about 30 kDa, greater than about 40 kDa, or greater than about 50 kDa.
  • the molecular mass is from about 5 kDa to about 10 kDa, from about 5 kDa to about 15 kDa, from about 5 kDa to about 20 kDa, from about 10 kDa to about 15 kDa, from about 10 kDa to about 20 kDa, from about 10 kDa to about 25 kDa, or from about 10 kDa to about 30 kDa.
  • Linear or branched PEG molecules having molecular weights from about 2,000 to about 80,000 daltons, alternatively about 2,000 to about 70,000 daltons, alternatively about 5,000 to about 50,000 daltons, alternatively about 10,000 to about 50,000 daltons, alternatively about 20,000 to about 50,000 daltons, alternatively about 30,000 to about 50,000 daltons, alternatively about 20,000 to about 40,000 daltons, or alternatively about 30,000 to about 40,000 daltons.
  • the PEG is a 40 kD branched PEG comprising two 20 kD arms.
  • Such compositions can be produced by reaction conditions and purification methods known in the art. Chromatography may be used to resolve conjugate fractions, and a fraction is then identified which contains the conjugate having, for example, the desired number of PEGs attached, purified free from unmodified protein sequences and from conjugates having other numbers of PEGs attached.
  • PEGs suitable for conjugation to a polypeptide sequence are generally soluble in water at room temperature, and have the general formula R(O—CH 2 —CH 2 ) n O—R, where R is hydrogen or a protective group such as an alkyl or an alkanol group, and where n is an integer from 1 to 1000.
  • R is a protective group, it generally has from 1 to 8 carbons.
  • mPEGs Two widely used first generation activated monomethoxy PEGs (mPEGs) are succinimdyl carbonate PEG (SC-PEG; see, e.g., Zalipsky, et al. (1992) Biotehnol. Appl. Biochem 15:100-114) and benzotriazole carbonate PEG (BTC-PEG; see, e.g., Dolence, et al. U.S. Pat. No. 5,650,234), which react preferentially with lysine residues to form a carbamate linkage but are also known to react with histidine and tyrosine residues.
  • PEG-aldehyde linker targets a single site on the N-terminus of a polypeptide through reductive amination.
  • Pegylation most frequently occurs at the ⁇ -amino group at the N-terminus of the polypeptide, the epsilon amino group on the side chain of lysine residues, and the imidazole group on the side chain of histidine residues. Since most recombinant polypeptides possess a single alpha and a number of epsilon amino and imidazole groups, numerous positional isomers can be generated depending on the linker chemistry. General PEGylation strategies known in the art can be applied herein.
  • the PEG can be bound to a binding protein of the present disclosure via a terminal reactive group (a “spacer”) which mediates a bond between the free amino or carboxyl groups of one or more of the polypeptide sequences and polyethylene glycol.
  • a terminal reactive group a “spacer” which mediates a bond between the free amino or carboxyl groups of one or more of the polypeptide sequences and polyethylene glycol.
  • the PEG having the spacer which can be bound to the free amino group includes N-hydroxysuccinylimide polyethylene glycol, which can be prepared by activating succinic acid ester of polyethylene glycol with N-hydroxysuccinylimide.
  • the PEGylation of the binding proteins is facilitated by the incorporation of non-natural amino acids bearing unique side chains to facilitate site specific PEGylation.
  • the incorporation of non-natural amino acids into polypeptides to provide functional moieties to achieve site specific PEGylation of such polypeptides is known in the art. See e.g., Ptacin et al., PCT International Application No. PCT/US2018/045257 filed Aug. 3, 2018 and published Feb. 7, 2019 as International Publication Number WO 2019/028419A1.
  • PEG conjugated to the polypeptide sequence can be linear or branched. Branched PEG derivatives, “star-PEGs” and multi-armed PEGs are contemplated by the present disclosure.
  • PEGs useful in the practice of the present disclosure include a 10 kDa linear PEG-aldehyde (e.g., Sunbright® ME-100AL, NOF America Corporation, One North Broadway, White Plains, NY 10601 USA), 10 kDa linear PEG-NHS ester (e.g., Sunbright® ME-100CS, Sunbright® ME-100AS, Sunbright® ME-100GS, Sunbright® ME-100HS, NOF), a 20 kDa linear PEG-aldehyde (e.g., Sunbright® ME-200AL, NOF), a 20 kDa linear PEG-NHS ester (e.g., Sunbright® ME-200CS, Sunbright® ME-200AS, Sunbright® ME-200GS,
  • a linker can be used to join the binding protein and the PEG molecule.
  • Suitable linkers include “flexible linkers” which are generally of sufficient length to permit some movement between the modified polypeptide sequences and the linked components and molecules.
  • the linker molecules are generally about 6-50 atoms long.
  • the linker molecules may also be, for example, aryl acetylene, ethylene glycol oligomers containing 2-10 monomer units, diamines, diacids, amino acids, or combinations thereof.
  • Suitable linkers can be readily selected and can be of any suitable length, such as 1 amino acid (e.g., Gly), 2, 3, 4, 5, 6, 7, 8, 9, 10, 10-20, 20-30, 30-50 or more than 50 amino acids. Examples of flexible linkers are described in Section IV.
  • a multimer e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 10-20, 20-30, or 30-50
  • linker can be a chemical linker, e.g., a PEG-aldehyde linker.
  • the binding protein is acetylated at the N-terminus by enzymatic reaction with N-terminal acetyltransferase and, for example, acetyl CoA.
  • the binding protein can be acetylated at one or more lysine residues, e.g., by enzymatic reaction with a lysine acetyltransferase. See, for example Choudhary et al. (2009) Science 325 (5942):834-840.
  • the binding protein can be modified to include an additional polypeptide sequence that functions as an antigenic tag, such as a FLAG sequence.
  • FLAG sequences are recognized by biotinylated, highly specific, anti-FLAG antibodies, as described herein (see e.g., Blanar et al. (1992) Science 256:1014 and LeClair, et al. (1992) PNAS-USA 89:8145).
  • the binding protein further comprises a C-terminal c-myc epitope tag.
  • the binding protein is expressed as a fusion protein with an albumin molecule (e.g., human serum albumin) which is known in the art to facilitate extended exposure in vivo.
  • an albumin molecule e.g., human serum albumin
  • the binding proteins (including fusion proteins of the binding proteins) of the present disclosure are expressed as a fusion protein with one or more transition metal chelating polypeptide sequences.
  • the incorporation of such a transition metal chelating domain facilitates purification immobilized metal affinity chromatography (IMAC) as described in Smith, et al. U.S. Pat. No. 4,569,794 issued Feb. 11, 1986.
  • IMAC immobilized metal affinity chromatography
  • Examples of transition metal chelating polypeptides useful in the practice of the present disclosure are described in Smith, et al. supra and Dobeli, et al. U.S. Pat. No. 5,320,663 issued May 10, 1995, the entire teachings of which are hereby incorporated by reference.
  • transition metal chelating polypeptides useful in the practice of the present disclosure are peptides comprising 3-6 contiguous histidine residues (SEQ ID NO: 1547) such as a six-histidine peptide (His) 6 (SEQ ID NO: 1531) and are frequently referred to in the art as “His-tags.”
  • fusion proteins may be readily produced by recombinant DNA methodology by techniques known in the art by constructing a recombinant vector comprising a nucleic acid sequence comprising a nucleic acid sequence encoding the binding protein in frame with a nucleic acid sequence encoding the fusion partner either at the N-terminus or C-terminus of the binding protein, the sequence optionally further comprising a nucleic acid sequence in frame encoding a linker or spacer polypeptide.
  • binding proteins of the present disclosure may be administered to a subject in a pharmaceutically acceptable dosage form.
  • the preferred formulation depends on the intended mode of administration and therapeutic application.
  • Pharmaceutical dosage forms of the binding proteins described herein comprise physiologically acceptable carriers that are inherently non-toxic and non-therapeutic.
  • Such carriers include ion exchangers, alumina, aluminum stearate, lecithin, serum proteins, such as human serum albumin, buffer substances such as phosphates, glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salts, or electrolytes such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinyl pyrrolidone, cellulose-based substances, and PEG.
  • buffer substances such as phosphates, glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salts, or electrolytes such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinyl pyrrolidone
  • Carriers for topical or gel-based forms of polypeptides include polysaccharides such as sodium carboxymethylcellulose or methylcellulose, polyvinylpyrrolidone, polyacrylates, polyoxyethylene-polyoxypropylene-block polymers, PEG, polymeric amino acids, amino acid copolymers, and lipid aggregates (such as oil droplets or liposomes).
  • compositions may also comprise pharmaceutically-acceptable, non-toxic carriers, excipients, stabilizers, or diluents, which are defined as vehicles commonly used to formulate pharmaceutical compositions for animal or human administration.
  • diluents are defined as vehicles commonly used to formulate pharmaceutical compositions for animal or human administration.
  • the diluent is selected so as not to affect the biological activity of the combination.
  • Acceptable carriers, excipients, or stabilizers are non-toxic to recipients at the dosages and concentrations employed, and include buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid and methionine; preservatives (such as octadecyidimethylbenzyl ammonium chloride; hexamethonium chloride; benzalkonium chloride, benzethonium chloride; phenol, butyl or benzyl alcohol; alkyl parabens such as methyl or propyl paraben; catechol; resorcinol; cyclohexanol; 3-pentanol; and m-cresol); low molecular weight (less than about 10 residues) polypeptides; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine,
  • Formulations to be used for in vivo administration are typically sterile. Sterilization of the compositions of the present disclosure may readily accomplished by filtration through sterile filtration membranes.
  • compositions are prepared as injectables, either as liquid solutions or suspensions; solid forms suitable for solution in, or suspension in, liquid vehicles prior to injection can also be prepared.
  • the preparation also can be emulsified or encapsulated in liposomes or micro particles such as polylactide, polyglycolide, or copolymer for enhanced adjuvant effect, as discussed above (Langer, Science 249: 1527, 1990 and Hanes, Advanced Drug Delivery Reviews 28: 97-119, 1997).
  • the agents of this disclosure can be administered in the form of a depot injection or implant preparation which can be formulated in such a manner as to permit a sustained or pulsatile release of the active ingredient.
  • the pharmaceutical compositions are generally formulated as sterile, substantially isotonic and in full compliance with all Good Manufacturing Practice (GMP) regulations of the U.S. Food and Drug Administration.
  • GMP Good Manufacturing Practice
  • Administration of a binding protein described herein may be achieved through any of a variety of art recognized methods including but not limited to the topical, intravascular injection (including intravenous or intraarterial infusion), intradermal injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, intracranial injection, intratumoral injection, intranodal injection, transdermal, transmucosal, iontophoretic delivery, intralymphatic injection (Senti and Kundig (2009) Current Opinions in Allergy and Clinical Immunology 9(6):537-543), intragastric infusion, intraprostatic injection, intravesical infusion (e.g., bladder), respiratory inhalers including nebulizers, intraocular injection, intraabdominal injection, intralesional injection, intraovarian injection, intracerebral infusion or injection, intracerebroventricular injection (ICVI), and the like.
  • intravascular injection including intravenous or intraarterial infusion
  • intradermal injection subcutaneous injection
  • intramuscular injection intraperitone
  • administration includes the administration of the binding protein itself (e.g., parenteral), as well as the administration of a recombinant vector (e.g., viral or non-viral vector) to cause the in situ expression of the binding protein in the subject.
  • a recombinant vector e.g., viral or non-viral vector
  • a cell such as a cell isolated from the subject, could also be recombinantly modified to express the binding protein of the present disclosure.
  • the dosage of the pharmaceutical compositions depends on factors including the route of administration, the disease to be treated, and physical characteristics, e.g., age, weight, general health, of the subject.
  • the amount of a binding protein contained within a single dose may be an amount that effectively prevents, delays, or treats the disease without inducing significant toxicity.
  • a pharmaceutical composition of the disclosure may include a dosage of a binding protein described herein ranging from 0.01 to 500 mg/kg (e.g., from 0.01 to 450 mg, from 0.01 to 400 mg, from 0.01 to 350 mg, from 0.01 to 300 mg, from 0.01 to 250 mg, from 0.01 to 200 mg, from 0.01 to 150 mg, from 0.01 to 100 mg, from 0.01 to 50 mg, from 0.01 to 10 mg, from 0.01 to 1 mg, from 0.1 to 500 mg/kg, from 1 to 500 mg/kg, from 5 to 500 mg/kg, from 10 to 500 mg/kg, from 50 to 500 mg/kg, from 100 to 500 mg/kg, from 150 to 500 mg/kg, from 200 to 500 mg/kg, from 250 to 500 mg/kg, from 300 to 500 mg/kg, from 350 to 500 mg/kg, from 400 to 500 mg/kg, or from 450 to 500 mg/kg) and, in a more specific embodiment, about 1 to about 100 mg/kg (e.g., about 1 to about 90 mg/kg, about 1
  • a pharmaceutical composition of the disclosure may include a dosage of a binding protein described herein ranging from 0.01 to 20 mg/kg (e.g., from 0.01 to 15 mg/kg, from 0.01 to 10 mg/kg, from 0.01 to 8 mg/kg, from 0.01 to 6 mg/kg, from 0.01 to 4 mg/kg, from 0.01 to 2 mg/kg, from 0.01 to 1 mg/kg, from 0.01 to 0.1 mg/kg, from 0.01 to 0.05 mg/kg, from 0.05 to 20 mg/kg, from 0.1 to 20 mg/kg, from 1 to 20 mg/kg, from 2 to 20 mg/kg, from 4 to 20 mg/kg, from 6 to 20 mg/kg, from 8 to 20 mg/kg, from 10 to 20 mg/kg, from 15 to 20 mg/kg).
  • the dosage may be adapted by the physician in accordance with conventional factors such as the extent of the disease and different parameters of the subject.
  • a pharmaceutical composition containing a binding protein described herein can be administered to a subject in need thereof, for example, one or more times (e.g., 1-10 times or more) daily, weekly, monthly, biannually, annually, or as medically necessary. Dosages may be provided in either a single or multiple dosage regimens. The timing between administrations may decrease as the medical condition improves or increase as the health of the patient declines.
  • a course of therapy may be a single dose or in multiple doses over a period of time. In some embodiments, a single dose is used. In some embodiments, two or more split doses administered over a period of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 21, 28, 30, 60, 90, 120 or 180 days are used.
  • Each dose administered in such split dosing protocols may be the same in each administration or may be different.
  • Multi-day dosing protocols over time periods may be provided by the skilled artisan (e.g., physician) monitoring the administration, taking into account the response of the subject to the treatment including adverse effects of the treatment and their modulation as discussed above.
  • the present disclosure further provides methods of treating a subject suffering from a disease disorder or condition by the administration of a therapeutically effective amount of an IL27R binding protein (or nucleic acid encoding an IL27R binding protein including recombinant viruses encoding the IL27R binding protein) of the present disclosure.
  • an IL27R binding protein or nucleic acid encoding an IL27R binding protein including recombinant viruses encoding the IL27R binding protein
  • IL27R binding proteins including pharmaceutically acceptable formulations comprising IL27R binding proteins and/or the nucleic acid molecules that encode them including recombinant viruses encoding such IL27R binding proteins
  • inflammatory or autoimmune diseases including but not limited to, viral infections (e.g., AIDS, influenza, chronic HCV, chronic viral hepatitis B, C or D), heliobacter pylori infection, HTLV, organ rejection, graft versus host disease, autoimmune thyroid disease, multiple sclerosis, allergy, asthma, neurodegenerative diseases including Alzheimer's disease, systemic lupus erythramatosis (SLE), autoinflammatory diseases, inflammatory bowel disease (IBD), Crohn's disease, diabetes including Type 1 or type 2 diabetes, inflammation, autoimmune disease, atopic diseases, paraneoplastic autoimmune diseases, cartilage inflammation, arthritis, rheumatoid arthritis, juvenile arthritis, juvenile rheumatoid arthritis, juvenile rhe
  • proliferative and/or differentiative disorders amenable to treatment with IL27R binding proteins include, but are not limited to, skin disorders.
  • the skin disorder may involve the aberrant activity of a cell or a group of cells or layers in the dermal, epidermal, or hypodermal layer, or an abnormality in the dermal-epidermal junction.
  • the skin disorder may involve aberrant activity of keratinocytes (e.g., hyperproliferative basal and immediately suprabasal keratinocytes), melanocytes, Langerhans cells, Merkel cells, immune cell, and other cells found in one or more of the epidermal layers, e.g., the stratum basale (stratum germinativum), stratum spinosum , stratum granulosum , stratum lucidum or stratum corneum.
  • keratinocytes e.g., hyperproliferative basal and immediately suprabasal keratinocytes
  • melanocytes e.g., melanocytes, Langerhans cells, Merkel cells, immune cell, and other cells found in one or more of the epidermal layers, e.g., the stratum basale (stratum germinativum), stratum spinosum , stratum granulosum , stratum lucidum or stratum corneum.
  • the disorder may involve aberrant activity of a dermal cell, for example, a dermal endothelial, fibroblast, immune cell (e.g., mast cell or macrophage) found in a dermal layer, for example, the papillary layer or the reticular layer.
  • a dermal cell for example, a dermal endothelial, fibroblast, immune cell (e.g., mast cell or macrophage) found in a dermal layer, for example, the papillary layer or the reticular layer.
  • Examples of skin disorders include psoriasis, psoriatic arthritis, dermatitis (eczema), for example, exfoliative dermatitis or atopic dermatitis, pityriasis rubra pilaris, pityriasis rosacea, parapsoriasis, pityriasis lichenoiders, lichen planus, lichen nitidus, ichthyosiform dermatosis, keratodermas, dermatosis, alopecia areata, pyoderma gangrenosum, vitiligo, pemphigoid (e.g., ocular cicatricial pemphigoid or bullous pemphigoid), urticaria, prokeratosis, rheumatoid arthritis that involves hyperproliferation and inflammation of epithelial-related cells lining the joint capsule; dermatitises such as seborr
  • compositions of the present disclosure can also be administered to a patient who is suffering from (or may suffer from) psoriasis or psoriatic disorders.
  • psoriasis is intended to have its medical meaning, namely, a disease which afflicts primarily the skin and produces raised, thickened, scaling, nonscarring lesions.
  • the lesions are usually sharply demarcated erythematous papules covered with overlapping shiny scales.
  • the scales are typically silvery or slightly opalescent.
  • Psoriasis is sometimes associated with arthritis, and it may be crippling.
  • Hyperproliferation of keratinocytes is a key feature of psoriatic epidermal hyperplasia along with epidermal inflammation and reduced differentiation of keratinocytes. Multiple mechanisms have been invoked to explain the keratinocyte hyperproliferation that characterizes psoriasis. Disordered cellular immunity has also been implicated in the pathogenesis of psoriasis.
  • psoriatic disorders include chronic stationary psoriasis, plaque psoriasis, moderate to severe plaque psoriasis, psoriasis vulgaris, eruptive psoriasis, psoriatic erythroderma, generalized pustular psoriasis, annular pustular psoriasis, or localized pustular psoriasis.
  • supplementary agents includes agents that can be administered or introduced separately, for example, formulated separately for separate administration (e.g., as may be provided in a kit) and/or therapies that can be administered or introduced in combination with the IL27R binding proteins.
  • the term “in combination with” when used in reference to the administration of multiple agents to a subject refers to the administration of a first agent at least one additional (i.e., second, third, fourth, fifth, etc.) agent to a subject.
  • one agent e.g., IL27R binding protein
  • a second agent e.g. a therapeutic autoimmune antibody such as Humira®
  • the therapeutic antibodies are sometimes administered by IV infusion every two weeks (e.g.
  • the IL27R binding proteins of the present disclosure may be administered more frequently, e.g. daily, BID, or weekly.
  • the administration of the first agent e.g. entaercept
  • the administration of the second agent e.g. an IL27R binding protein
  • the second agent provides its therapeutic effect while the therapeutic effect of the first agent remains ongoing such that the second agent is considered to be administered in combination with the first agent, even though the first agent may have been administered at a point in time significantly distant (e.g. days or weeks) from the time of administration of the second agent.
  • one agent is considered to be administered in combination with a second agent if the first and second agents are administered simultaneously (within 30 minutes of each other), contemporaneously or sequentially.
  • a first agent is deemed to be administered “contemporaneously” with a second agent if first and second agents are administered within about 24 hours of each another, preferably within about 12 hours of each other, preferably within about 6 hours of each other, preferably within about 2 hours of each other, or preferably within about 30 minutes of each other.
  • the term “in combination with” shall also understood to apply to the situation where a first agent and a second agent are co-formulated in single pharmaceutically acceptable formulation and the co-formulation is administered to a subject.
  • the IL27R binding protein and the supplementary agent(s) are administered or applied sequentially, e.g, where one agent is administered prior to one or more other agents.
  • the IL27R binding protein and the supplementary agent(s) are administered simultaneously, e.g., where two or more agents are administered at or about the same time; the two or more agents may be present in two or more separate formulations or combined into a single formulation (i.e., a co-formulation). Regardless of whether the agents are administered sequentially or simultaneously, they are considered to be administered in combination for purposes of the present disclosure.
  • the supplementary agent is one or more agents selected from the group consisting of corticosteroids (including but not limited to prednisone, budesonide, prednilisone), Janus kinase inhibitors (including but not limited to tofacitinib (Xeljanz®), calcineurin inhibitors (including but not limited to cyclosporine and tacrolimus), mTor inhibitors (including but not limited to sirolimus and everolimus), IMDH inhibitors (including but not limited to azathioprine, leflunomide and mycophenolate), biologics such as abatcept (Orencia®) or etanercept (Enbrel®), and therapeutic antibodies.
  • corticosteroids including but not limited to prednisone, budesonide, prednilisone
  • Janus kinase inhibitors including but not limited to tofacitinib (Xeljanz®)
  • calcineurin inhibitors including but not limited to
  • anti-CD25 antibodies e.g. daclizumab and basiliximab
  • anti-VLA-4 antibodies e.g. natalizumab
  • anti-CD52 antibodies e.g. alemtuzumab
  • anti-CD20 antibodies e.g. ritux
  • adalimumab Humira®), golimumab, and infliximab
  • anti-integrin- ⁇ 4 ⁇ 7 antibodies e.g. vedolizumab
  • anti-IL17a antibodies e.g. brodalumab or secukinumab
  • anti-IL4R ⁇ antibodies e.g. dupilumab
  • anti-RANKL antibodies IL6R antibodies
  • anti-IL1ß antibodies e.g. canakinumab
  • anti-CD11a antibodies e.g. efalizumab
  • anti-CD3 antibodies e.g. muramonab
  • anti-IL5 antibodies e.g. mepolizumab, reslizumab
  • anti-BLyS antibodies e.g. belimumab
  • anti-IL12/IL23 antibodies e.g ustekinumab
  • the present disclosure provides methods of use of IL-27R binding molecules in the treatment of subjects suffering from a neoplastic disease disorder or condition by the administration of a therapeutically effective amount of a IL-27R binding molecule (or nucleic acid encoding a IL-27R binding molecule including recombinant vectors encoding IL-27R binding molecules, and eucaryotic and procaryotic cells modified to express a IL-27R binding molecule) as described herein.
  • a IL-27R binding molecule or nucleic acid encoding a IL-27R binding molecule including recombinant vectors encoding IL-27R binding molecules, and eucaryotic and procaryotic cells modified to express a IL-27R binding molecule
  • compositions and methods of the present disclosure are useful in the treatment of subject suffering from a neoplastic disease characterized by the presence neoplasms, including benign and malignant neoplasms, and neoplastic disease.
  • Examples of benign neoplasms amenable to treatment using the compositions and methods of the present disclosure include but are not limited to adenomas, fibromas, hemangiomas, and lipomas.
  • Examples of pre-malignant neoplasms amenable to treatment using the compositions and methods of the present disclosure include but are not limited to hyperplasia, atypia, metaplasia, and dysplasia.
  • malignant neoplasms amenable to treatment using the compositions and methods of the present disclosure include but are not limited to carcinomas (cancers arising from epithelial tissues such as the skin or tissues that line internal organs), leukemias, lymphomas, and sarcomas typically derived from bone fat, muscle, blood vessels or connective tissues). Also included in the term neoplasms are viral induced neoplasms such as warts and EBV induced disease (i.e., infectious mononucleosis), scar formation, hyperproliferative vascular disease including intimal smooth muscle cell hyperplasia, restenosis, and vascular occlusion and the like.
  • carcinomas cancers arising from epithelial tissues such as the skin or tissues that line internal organs
  • leukemias arising from lymphomas
  • sarcomas typically derived from bone fat, muscle, blood vessels or connective tissues.
  • viral induced neoplasms such as warts and EBV induced
  • neoplastic disease includes cancers characterized by solid tumors and non-solid tumors including but not limited to breast cancers; sarcomas (including but not limited to osteosarcomas and angiosarcomas and fibrosarcomas), leukemias, lymphomas, genitourinary cancers (including but not limited to ovarian, urethral, bladder, and prostate cancers); gastrointestinal cancers (including but not limited to colon esophageal and stomach cancers); lung cancers; myelomas; pancreatic cancers; liver cancers; kidney cancers; endocrine cancers; skin cancers; and brain or central and peripheral nervous (CNS) system tumors, malignant or benign, including gliomas and neuroblastomas, astrocytomas, myelodysplastic disorders; cervical carcinoma-in-situ; intestinal polyposes; oral leukoplakias; histiocytoses, hyperprofroliferative scars including keloid scars,
  • neoplastic disease includes carcinomas.
  • carcinoma refers to malignancies of epithelial or endocrine tissues including respiratory system carcinomas, gastrointestinal system carcinomas, genitourinary system carcinomas, testicular carcinomas, breast carcinomas, prostatic carcinomas, endocrine system carcinomas, and melanomas.
  • neoplastic disease includes adenocarcinomas.
  • An “adenocarcinoma” refers to a carcinoma derived from glandular tissue or in which the tumor cells form recognizable glandular structures.
  • hematopoietic neoplastic disorders refers to neoplastic diseases involving hyperplastic/neoplastic cells of hematopoietic origin, e.g., arising from myeloid, lymphoid or erythroid lineages, or precursor cells thereof.
  • Myeloid neoplasms include, but are not limited to, myeloproliferative neoplasms, myeloid and lymphoid disorders with eosinophilia, myeloproliferative/myelodysplastic neoplasms, myelodysplastic syndromes, acute myeloid leukemia and related precursor neoplasms, and acute leukemia of ambiguous lineage.
  • Exemplary myeloid disorders amenable to treatment in accordance with the present disclosure include, but are not limited to, acute promyeloid leukemia (APML), acute myelogenous leukemia (AML) and chronic myelogenous leukemia (CML).
  • APML acute promyeloid leukemia
  • AML acute myelogenous leukemia
  • CML chronic myelogenous leukemia
  • Lymphoid neoplasms include, but are not limited to, precursor lymphoid neoplasms, mature B-cell neoplasms, mature T-cell neoplasms, Hodgkin's Lymphoma, and immunodeficiency-associated lymphoproliferative disorders.
  • Exemplary lymphic disorders amenable to treatment in accordance with the present disclosure include, but are not limited to, acute lymphoblastic leukemia (ALL) which includes B-lineage ALL and T-lineage ALL, chronic lymphocytic leukemia (CLL), prolymphocytic leukemia (PLL), hairy cell leukemia (HLL) and Waldenstrom's macroglobulinemia (WM).
  • ALL acute lymphoblastic leukemia
  • CLL chronic lymphocytic leukemia
  • PLL prolymphocytic leukemia
  • HLL hairy cell leukemia
  • WM Waldenstrom's macroglobulinemia
  • the hematopoietic neoplastic disorder arises from poorly differentiated acute leukemias (e.g., erythroblastic leukemia and acute megakaryoblastic leukemia).
  • the term “hematopoietic neoplastic disorders” refers malignant lymphomas including, but are not limited to, non-Hodgkins lymphoma and variants thereof, peripheral T cell lymphomas, adult T-cell leukemia/lymphoma (ATL), cutaneous T cell lymphoma (CTCL), large granular lymphocytic leukemia (LGF), Hodgkin's disease and Reed-Stemberg disease.
  • the determination of whether a subject is “suffering from a neoplastic disease” refers to a determination made by a physician with respect to a subject based on the available information accepted in the field for the identification of a disease, disorder or condition including but not limited to X-ray, CT-scans, conventional laboratory diagnostic tests (e.g. blood count, etc.), genomic data, protein expression data, immunohistochemistry, that the subject requires or will benefit from treatment.
  • the determination of efficacy of the methods of the present disclosure in the treatment of cancer is generally associated with the achievement of one or more art recognized parameters such as reduction in lesions particularly reduction of metastatic lesion, reduction in metastasis, reduction in tumor volume, improvement in ECOG score, and the like. Determining response to treatment can be assessed through the measurement of biomarker that can provide reproducible information useful in any aspect of IL-27R binding molecule therapy, including the existence and extent of a subject's response to such therapy and the existence and extent of untoward effects caused by such therapy.
  • biomarkers include enhancement of IFN ⁇ , and upregulation of granzyme A, granzyme B, and perforin; increase in CD8+ T-cell number and function; enhancement of IFN ⁇ , an increase in ICOS expression on CD8+ T-cells, enhancement of IL-10 expressing T Reg cells.
  • the response to treatment may be characterized by improvements in conventional measures of clinical efficacy may be employed such as Complete Response (CR), Partial Response (PR), Stable Disease (SD) and with respect to target lesions, Complete Response (CR),” Incomplete Response/Stable Disease (SD) as defined by RECIST as well as immune-related Complete Response (irCR), immune-related Partial Response (irPR), and immune-related Stable Disease (irSD) as defined Immune-Related Response Criteria (irRC) are considered by those of skill in the art as evidencing efficacy in the treatment of neoplastic disease in mammalian (e.g. human) subjects.
  • CR Complete Response
  • PR Partial Response
  • SD Incomplete Response/Stable Disease
  • irCR immune-related Complete Response
  • irPR immune-related Partial Response
  • irSD immune-related Stable Disease
  • the present disclosure provides methods and compositions for the treatment and/or prevention of neoplastic diseases, disorders or conditions by the administration of a therapeutically effective amount of an IL-27R binding molecules the serum concentration of the IL-27R binding molecule is maintained for a majority (i.e., greater than about 50% of the period of time, alternatively greater than about 60%, alternatively greater than about 70%, alternatively greater than about 80%, alternatively greater than about 90%) of a period of time (e.g.
  • supplementary agents include agents that can be administered or introduced separately, for example, formulated separately for separate administration (e.g., as may be provided in a kit) and/or therapies that can be administered or introduced in combination with the IL-27R binding molecules.
  • the supplementary agent is a chemotherapeutic agent.
  • the supplementary agent is a “cocktail” of multiple chemotherapeutic agents.
  • the chemotherapeutic agent or cocktail is administered in combination with one or more physical methods (e.g. radiation therapy).
  • chemotherapeutic agents includes but is not limited to alkylating agents such as thiotepa and cyclosphosphamide; alkyl sulfonates such as busulfan, improsulfan and piposulfan; aziridines such as benzodopa, carboquone, meturedopa, and uredopa; ethylenimines and methylamelamines including altretamine, triethylenemelamine, trietylenephosphoramide, triethylenethiophosphaoramide and trimethyl olomelamime; nitrogen mustards such as chiorambucil, chlomaphazine, cholophosphamide, estramustine, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, melphalan, novembichin, phenesterine, prednimustine, trofosfamide, uracil mustard; nitrosureas such as
  • chemotherapeutic agents also includes anti-hormonal agents that act to regulate or inhibit hormone action on tumors such as anti-estrogens, including for example tamoxifen, raloxifene, aromatase inhibiting 4(5)-imidazoles, 4-hydroxytamoxifen, trioxifene, keoxifene, onapristone, and toremifene; and antiandrogens such as flutamide, nilutamide, bicalutamide, leuprolide, and goserelin; and pharmaceutically acceptable salts, acids or derivatives of any of the above.
  • anti-estrogens including for example tamoxifen, raloxifene, aromatase inhibiting 4(5)-imidazoles, 4-hydroxytamoxifen, trioxifene, keoxifene, onapristone, and toremifene; and antiandrogens such as flutamide, nilutamide, bicalutamide,
  • a supplementary agent isone or more chemical or biological agents identified in the art as useful in the treatment of neoplastic disease, including, but not limited to, a cytokines or cytokine antagonists such as IL-12, INF ⁇ , or anti-epidermal growth factor receptor, irinotecan; tetrahydrofolate antimetabolites such as pemetrexed; antibodies against tumor antigens, a complex of a monoclonal antibody and toxin, a T-cell adjuvant, bone marrow transplant, or antigen presenting cells (e.g., dendritic cell therapy), anti-tumor vaccines, replication competent viruses, signal transduction inhibitors (e.g., Gleevec® or Herceptin®) or an immunomodulator to achieve additive or synergistic suppression of tumor growth, non-steroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 (COX-2) inhibitors, steroids, TNF antagonists (e.g., Rem
  • the IL-27R binding molecule is administered in combination with BRAF/MEK inhibitors, kinase inhibitors such as sunitinib, PARP inhibitors such as olaparib, EGFR inhibitors such as osimertinib (Ahn, et al. (2016) J Thorac Oncol 11 S115), IDO inhibitors such as epacadostat, and oncolytic viruses such as talimogene laherparepvec (T-VEC).
  • BRAF/MEK inhibitors kinase inhibitors such as sunitinib
  • PARP inhibitors such as olaparib
  • EGFR inhibitors such as osimertinib (Ahn, et al. (2016) J Thorac Oncol 11 S115)
  • IDO inhibitors such as epacadostat
  • oncolytic viruses such as talimogene laherparepvec (T-VEC).
  • a “supplementary agent” is a therapeutic antibody (including bi-specific and tri-specific antibodies which bind to one or more tumor associated antigens including but not limited to bispecific T cell engagers (BITEs), dual affinity retargeting (DART) constructs, and trispecific killer engager (TriKE) constructs).
  • BITEs bispecific T cell engagers
  • DART dual affinity retargeting
  • TriKE trispecific killer engager
  • the therapeutic antibody is an antibody that binds to at least one tumor antigen selected from the group consisting of HER2 (e.g. trastuzumab, pertuzumab, ado-trastuzumab emtansine), nectin-4 (e.g. enfortumab), CD79 (e.g. polatuzumab vedotin), CTLA4 (e.g. ipilumumab), CD22 (e.g. moxetumomab pasudotox), CCR4 (e.g. magamuizumab), IL23p19 (e.g. tildrakizumab), PDL1 (e.g.
  • HER2 e.g. trastuzumab, pertuzumab, ado-trastuzumab emtansine
  • nectin-4 e.g. enfortumab
  • CD79 e.g.
  • alemtuzumab EpCam
  • CEA e.g. dinuntuximab
  • GD3, IL6 e.g. silutxumab
  • GM2 e.g. dinuntuximab
  • IL6 e.g. silutxumab
  • VEGF e.g. bevacizumab
  • VEGFR e.g. ramucirumab
  • PDGFR ⁇ e.g. olartumumab
  • EGFR e.g. cetuximab, panitumumab and necitumumab
  • ERBB2 e.g. trastuzumab
  • ERBB3, MET IGF1R, EPHA3, TRAIL R1, TRAIL R2, RANKL RAP, tenascin, integrin ⁇ V ⁇ 3, and integrin ⁇ 4 ⁇ 1.
  • antibody therapeutics which are FDA approved and may be used as supplementary agents for use in the treatment of neoplastic disease include those provided in the Table below.
  • a supplementary agent is one or more non-pharmacological modalities (e.g., localized radiation therapy or total body radiation therapy or surgery).
  • the present disclosure contemplates treatment regimens wherein a radiation phase is preceded or followed by treatment with a treatment regimen comprising a IL-27R binding molecule and one or more supplementary agents.
  • the present disclosure further contemplates the use of a IL-27R binding molecule in combination with surgery (e.g. tumor resection).
  • the present disclosure further contemplates the use of a IL-27R binding molecule in combination with bone marrow transplantation, peripheral blood stem cell transplantation or other types of transplantation therapy.
  • a “supplementary agent” is an immune checkpoint modulator for the treatment and/or prevention neoplastic disease in a subject as well as diseases, disorders or conditions associated with neoplastic disease.
  • the term “immune checkpoint pathway” refers to biological response that is triggered by the binding of a first molecule (e.g. a protein such as PD1) that is expressed on an antigen presenting cell (APC) to a second molecule (e.g. a protein such as PDL1) that is expressed on an immune cell (e.g. a T-cell) which modulates the immune response, either through stimulation (e.g. upregulation of T-cell activity) or inhibition (e.g. downregulation of T-cell activity) of the immune response.
  • a first molecule e.g. a protein such as PD1
  • APC antigen presenting cell
  • PDL1 protein such as PDL1
  • immune checkpoints The molecules that are involved in the formation of the binding pair that modulate the immune response are commonly referred to as “immune checkpoints.”
  • the biological responses modulated by such immune checkpoint pathways are mediated by intracellular signaling pathways that lead to downstream immune effector pathways, such as cell activation, cytokine production, cell migration, cytotoxic factor secretion, and antibody production.
  • Immune checkpoint pathways are commonly triggered by the binding of a first cell surface expressed molecule to a second cell surface molecule associated with the immune checkpoint pathway (e.g. binding of PD1 to PDL1, CTLA4 to CD28, etc.).
  • the activation of immune checkpoint pathways can lead to stimulation or inhibition of the immune response.
  • immune checkpoint pathway modulator refers to a molecule that inhibits or stimulates the activity of an immune checkpoint pathway in a biological system including an immunocompetent mammal.
  • An immune checkpoint pathway modulator may exert its effect by binding to an immune checkpoint protein (such as those immune checkpoint proteins expressed on the surface of an antigen presenting cell (APC) such as a cancer cell and/or immune T effector cell) or may exert its effect on upstream and/or downstream reactions in the immune checkpoint pathway.
  • an immune checkpoint pathway modulator may modulate the activity of SHP2, a tyrosine phosphatase that is involved in PD-1 and CTLA-4 signaling.
  • immune checkpoint pathway modulators encompasses both immune checkpoint pathway modulator(s) capable of down-regulating at least partially the function of an inhibitory immune checkpoint (referred to herein as an “immune checkpoint pathway inhibitor” or “immune checkpoint pathway antagonist”) and immune checkpoint pathway modulator(s) capable of up-regulating at least partially the function of a stimulatory immune checkpoint (referred to herein as an “immune checkpoint pathway effector” or “immune checkpoint pathway agonist.”).
  • Immune checkpoint modulators include but are not limited to immune checkpoint antagonists (e.g. antagonist antibodies) that bind T-cell inhibitory receptors including but not limited to PD1 (also referred to as CD279), TIM3 (T-cell membrane protein 3; also known as HAVcr2), BTLA (B and T lymphocyte attenuator; also known as CD272), the VISTA (B7-H5) receptor, LAG3 (lymphocyte activation gene 3; also known as CD233) and CTLA4 (cytotoxic T-lymphocyte associated antigen 4; also known as CD152).
  • immune checkpoint modulators are agonists that trigger the checkpoint pathway resulting stimulation of the immune response.
  • agonist immune checkpoint modulators include, but is not limited to, agonist that modulate the binding of ICOSL to ICOS(CD278), B7-H6 to NKp30, CD155 to CD96, OX40L to OX40, CD70 to CD27, CD40 to CD40L, and GITRL to GITR.
  • positive immune checkpoint agonists include but are not limited to agonist antibodies that bind T-cell activating receptors such as ICOS (such as JTX-2011, Jounce Therapeutics), OX40 (such as MEDI6383, Medimmune), CD27 (such as varlilumab, Celldex Therapeutics), CD40 (such as dacetuzmumab CP-870,893, Roche, Chi Lob 7/4), HVEM, CD28, CD137 4-1BB, CD226, and GITR (such as MEDI1873, Medimmune; INCAGN1876, Agenus).
  • T-cell activating receptors such as ICOS (such as JTX-2011, Jounce Therapeutics), OX40 (such as MEDI6383, Medimmune), CD27 (such as varlilumab, Celldex Therapeutics), CD40 (such as dacetuzmumab CP-870,893, Roche, Chi Lob 7/4), HVEM, CD28, CD137 4-1BB, CD226,
  • Exemplary negative immune checkpoint pathway inhibitors include but are not limited to programmed death-1 (PD1) pathway inhibitors, programed death ligand-1 (PDL1) pathway inhibitors, TIM3 pathway inhibitors and anti-cytotoxic T-lymphocyte antigen 4 (CTLA4) pathway inhibitors.
  • PD1 programmed death-1
  • PDL1 programed death ligand-1
  • TIM3 TIM3 pathway inhibitors
  • CTLA4 anti-cytotoxic T-lymphocyte antigen 4 pathway inhibitors.
  • the immune checkpoint pathway modulator is an antagonist of a negative immune checkpoint pathway that inhibits the binding of PD1 to PDL1 and/or PDL2 (“PD1 pathway inhibitor”).
  • PD1 pathway inhibitors includes monoclonal antibodies that interfere with the binding of PD1 to PDL1 and/or PDL2.
  • nivolumab Opdivo®, BMS-936558, MDX1106, commercially available from BristolMyers Squibb, Princeton NJ
  • pembrolizumab Keytruda®MK-3475, lambrolizumab, commercially available from Merck and Company, Kenilworth NJ
  • atezolizumab Tecentriq®, Genentech/Roche, South San
  • Additional PD1 pathway inhibitors antibodies are in clinical development including but not limited to durvalumab (MEDI4736, Medimmune/AstraZeneca), pidilizumab (CT-011, CureTech), PDR001 (Novartis), BMS-936559 (MDX1105, BristolMyers Squibb), and avelumab (MSB0010718C, Merck Serono/Pfizer) and SHR-1210 (Incyte). Additional antibody PD1 pathway inhibitors are described in U.S. Pat. No. 8,217,149 (Genentech, Inc) issued Jul. 10, 2012; U.S. Pat. No. 8,168,757 (Merck Sharp and Dohme Corp.) issued May 1, 2012, U.S. Pat. No. 8,008,449 (Medarex) issued Aug. 30, 2011, U.S. Pat. No. 7,943,743 (Medarex, Inc) issued May 17, 2011.
  • Non-antibody biologic PD1 pathway inhibitors are also under clinical development including AMP-224, a PD-L2 IgG2a fusion protein, and AMP-514, a PDL2 fusion protein, are under clinical development by Amplimmune and Glaxo SmithKline), aptamers (Wang, et al. (2016) 145:125-130), peptide PD1 pathway inhibitors (Sasikumar, et al., U.S. Pat. No. 9,422,339 issued Aug. 23, 2016, and Sasilkumar, et al., U.S. Pat. No. 8,907,053 issued Dec.
  • the IL-27R binding molecule is administered in combination with an antagonist of a negative immune checkpoint pathway that inhibits the binding of CTLA4 to CD28 (“CTLA4 pathway inhibitor”).
  • CTLA4 pathway inhibitors are well known in the art (See, e.g., U.S. Pat. No. 6,682,736 (Abgenix) issued Jan. 27, 2004; U.S. Pat. No. 6,984,720 (Medarex, Inc.) issued May 29, 2007; U.S. Pat. No. 7,605,238 (Medarex, Inc.) issued Oct. 20, 2009)
  • the IL-27R binding molecule is administered in combination with an antagonist of a negative immune checkpoint pathway that inhibits the ability TIM3 to binding to TIM3-activating ligands (“TIM3 pathway inhibitor”).
  • TIM3 pathway inhibitors are known in the art and with representative non-limiting examples described in PCT International Patent Publication No. WO 2016/144803 published Sep. 15, 2016; Lifke, et al. United States Patent Publication No. US 20160257749 A1 published Sep. 8, 2016 (F. Hoffman-LaRoche); Karunsky, U.S. Pat. No. 9,631,026 issued Apr. 27, 2017; Karunsky, Sabatos-Peyton, et al. U.S. Pat. No. 8,841,418 issued Sep. 23, 2014; U.S. Pat. No. 9,605,070; Takayanagi, et al., U.S. Pat. No. 8,552,156 issued Oct. 8, 2013.
  • the IL-27R binding molecule is administered in combination with an inhibitor of both LAG3 and PD1 as the blockade of LAG3 and PD1 has been suggested to synergistically reverse anergy among tumor-specific CD8+ T-cells and virus-specific CD8+ T-cells in the setting of chronic infection.
  • IMP321 (ImmuFact) is being evaluated in melanoma, breast cancer, and renal cell carcinoma. See generally Woo et al., (2012) Cancer Res 72:917-27; Goldberg et al., (2011) Curr. Top. Microbiol. Immunol. 344:269-78; Pardoll (2012) Nature Rev. Cancer 12:252-64; Grosso et al., (2007) J. Clin. Invest. 117:3383-392.
  • the IL-27R binding molecule is administered in combination with an A2aR inhibitor.
  • A2aR inhibits T-cell responses by stimulating CD4+ T-cells towards developing into T Reg cells.
  • A2aR is particularly important in tumor immunity because the rate of cell death in tumors from cell turnover is high, and dying cells release adenosine, which is the ligand for A2aR.
  • deletion of A2aR has been associated with enhanced and sometimes pathological inflammatory responses to infection.
  • Inhibition of A2aR can be effected by the administration of molecules such as antibodies that block adenosine binding or by adenosine analogs.
  • Such agents may be used in combination with the IL-27R binding molecules for use in the treatment disorders such as cancer and Parkinson's disease.
  • the IL-27R binding molecule is administered in combination with an inhibitor of IDO (Indoleamine 2,3-dioxygenase).
  • IDO Indoleamine 2,3-dioxygenase
  • IDO down-regulates the immune response mediated through oxidation of tryptophan resulting in in inhibition of T-cell activation and induction of T-cell apoptosis, creating an environment in which tumor-specific cytotoxic T lymphocytes are rendered functionally inactive or are no longer able to attack a subject's cancer cells.
  • Indoximod NewLink Genetics
  • the present invention provides for a method of treatment of neoplastic disease (e.g. cancer) in a mammalian subject by the administration of a IL-27R binding molecule in combination with an agent(s) that modulate at least one immune checkpoint pathway including immune checkpoint pathway modulators that modulate two, three or more immune checkpoint pathways.
  • neoplastic disease e.g. cancer
  • an agent(s) that modulate at least one immune checkpoint pathway including immune checkpoint pathway modulators that modulate two, three or more immune checkpoint pathways.
  • the IL-27R binding molecule is administered in combination with an immune checkpoint modulator that modulates multiple immune checkpoint pathways.
  • Multiple immune checkpoint pathways may be modulated by the administration of multi-functional molecules which act as modulators of multiple immune checkpoint pathways.
  • multiple immune checkpoint pathway modulators include but are not limited to bi-specific or poly-specific antibodies.
  • poly-specific antibodies capable of acting as modulators or multiple immune checkpoint pathways are known in the art.
  • United States Patent Publication No. 2013/0156774 describes bispecific and multispecific agents (e.g., antibodies), and methods of their use, for targeting cells that co-express PD1 and TIM3.
  • BTLA and PD1 dual blockade of BTLA and PD1 has been shown to enhance antitumor immunity (Pardoll, (April 2012) Nature Rev. Cancer 12:252-64).
  • the present disclosure contemplates the use of IL-27R binding molecules in combination with immune checkpoint pathway modulators that target multiple immune checkpoint pathways, including but limited to bi-specific antibodies which bind to both PD1 and LAG3.
  • immune checkpoint pathway modulators that target multiple immune checkpoint pathways, including but limited to bi-specific antibodies which bind to both PD1 and LAG3.
  • antitumor immunity can be enhanced at multiple levels, and combinatorial strategies can be generated in view of various mechanistic considerations.
  • the IL-27R binding molecule may be administered in combination with two, three, four or more checkpoint pathway modulators. Such combinations may be advantageous in that immune checkpoint pathways may have distinct mechanisms of action, which provides the opportunity to attack the underlying disease, disorder or conditions from multiple distinct therapeutic angles.
  • immune checkpoint pathway inhibitors often manifest themselves much later than responses to traditional chemotherapies such as tyrosine kinase inhibitors. In some instance, it can take six months or more after treatment initiation with immune checkpoint pathway inhibitors before objective indicia of a therapeutic response are observed. Therefore, a determination as to whether treatment with an immune checkpoint pathway inhibitors(s) in combination with a IL-27R binding molecule of the present disclosure must be made over a time-to-progression that is frequently longer than with conventional chemotherapies. The desired response can be any result deemed favorable under the circumstances.
  • the desired response is prevention of the progression of the disease, disorder or condition, while in other embodiments the desired response is a regression or stabilization of one or more characteristics of the disease, disorder or conditions (e.g., reduction in tumor size). In still other embodiments, the desired response is reduction or elimination of one or more adverse effects associated with one or more agents of the combination.
  • the methods of the disclosure may include the combination of the administration of a IL-27R binding molecules with supplementary agents in the form of cell therapies for the treatment of neoplastic, autoimmune or inflammatory diseases.
  • cell therapies that are amenable to use in combination with the methods of the present disclosure include but are not limited to engineered T cell products comprising one or more activated CAR-T cells, engineered TCR cells, tumor infiltrating lymphocytes (TILs), engineered Treg cells.
  • engineered T-cell products are commonly activated ex vivo prior to their administration to the subject and therefore provide upregulated levels of CD25
  • cell products comprising such activated engineered T cells types are amenable to further support via the administration of an CD25 biased IL-27R binding molecule as described herein.
  • the supplementary agent is a “chimeric antigen receptor T-cell” and “CAR-T cell” are used interchangeably to refer to a T-cell that has been recombinantly modified to express a chimeric antigen receptor.
  • chimeric antigen receptor and “CAR” are used interchangeably to refer to a chimeric polypeptide comprising multiple functional domains arranged from amino to carboxy terminus in the sequence: (a) an antigen binding domain (ABD), (b) a transmembrane domain (TD); and (c) one or more cytoplasmic signaling domains (CSDs) wherein the foregoing domains may optionally be linked by one or more spacer domains.
  • the CAR may also further comprise a signal peptide sequence which is conventionally removed during post-translational processing and presentation of the CAR on the cell surface of a cell transformed with an expression vector comprising a nucleic acid sequence encoding the CAR.
  • CARs useful in the practice of the present invention are prepared in accordance with principles well known in the art. See e.g., Eshhaar et al. U.S. Pat. No. 7,741,465 B1 issued Jun. 22, 2010; Sadelain, et al (2013) Cancer Discovery 3(4):388-398; Jensen and Riddell (2015) Current Opinions in Immunology 33:9-15; Gross, et al. (1989) PNAS(USA) 86(24):10024-10028; Curran, et al. (2012) J Gene Med 14(6):405-15.
  • CAR-T cell products examples include axicabtagene ciloleucel (marketed as Yescarta® commercially available from Gilead Pharmaceuticals) and tisagenlecleucel (marketed as Kymriah® commercially available from Novartis).
  • axicabtagene ciloleucel marketed as Yescarta® commercially available from Gilead Pharmaceuticals
  • Kymriah® commercially available from Novartis
  • the CAR-T possesses a CAR specifically binds to a cell surface molecule associated with a tumor cell is selected from the group consisting of GD2, BCMA, CD19, CD33, CD38, CD70, GD2, IL3R ⁇ 2, CD19, mesothelin, Her2, EpCam, Muc1, ROR1, CD133, CEA, EGRFRVIII, PSCA, GPC3, Pan-ErbB and FAP
  • the supplementary agent is a anti-neoplastic physical methods including but not limited to radiotherapy, cryotherapy, hyperthermic therapy, surgery, laser ablation, and proton therapy.
  • kits comprising pharmaceutical compositions IL-27R binding molecules and a pharmaceutical composition thereof.
  • the kits are generally in the form of a physical structure housing various components, as described below, and can be utilized, for example, in practicing the methods described above.
  • a kit may comprise a IL-27R binding molecule in the form of a pharmaceutical composition suitable for administration to a subject that is ready for use or in a form or requiring preparation for example, thawing, reconstitution or dilution prior to administration.
  • the kit may also comprise a sterile container providing a reconstitution medium comprising buffers, pharmaceutically acceptable excipients, and the like.
  • a kit of the present disclosure can be designed for conditions necessary to properly maintain the components housed therein (e.g., refrigeration or freezing).
  • a kit may further contain a label or packaging insert including identifying information for the components therein and instructions for their use.
  • Each component of the kit can be enclosed within an individual container, and all of the various containers can be within a single package.
  • Labels or inserts can include manufacturer information such as lot numbers and expiration dates.
  • the label or packaging insert can be, e.g., integrated into the physical structure housing the components, contained separately within the physical structure, or affixed to a component of the kit (e.g., an ampule, syringe or vial). Labels or inserts may be provided in a physical form or a computer readable medium.
  • the actual instructions are not present in the kit, but rather the kit provides a means for obtaining the instructions from a remote source, e.g., via an internet site, including by secure access by providing a password (or scannable code such as a barcode or QR code on the container of the IL-27R binding molecule or kit comprising) in compliance with governmental regulations (e.g., HIPAA) are provided.
  • a password or scannable code such as a barcode or QR code on the container of the IL-27R binding molecule or kit comprising
  • governmental regulations e.g., HIPAA
  • antibodies useful as supplementary agents in the practice of the methods of the present disclosure may be administered alone or in the form of any antibody drug conjugate (ADC) comprising the antibody, linker, and one or more drugs (e.g. 1, 2, 3, 4, 5, 6, 7, or 8 drugs) or in modified form (e.g. PEGylated).
  • ADC antibody drug conjugate
  • drugs e.g. 1, 2, 3, 4, 5, 6, 7, or 8 drugs
  • modified form e.g. PEGylated
  • the supplementary agent is a vaccine.
  • the IL27R binding proteins of the present invention may be administered to a subject in combination with vaccines as an adjuvant to enhance the immune response to the vaccine in accordance with the teaching of Doyle, et al U.S. Pat. No. 5,800,819 issued Sep. 1, 1998.
  • vaccines examples include are HSV vaccines, Bordetella pertussis, Escherichia coli vaccines, pneumococcal vaccines including multivalent pneumococcal vaccines such as Prevnar® 13, diptheria, tetanus and pertussis vaccines (including combination vaccines such as Pediatrix®) and Pentacel®), varicella vaccines, Haemophilus influenzae type B vaccines, human papilloma virus vaccines such as Garasil®, polio vaccines, Leptospirosis vaccines, combination respiratory vaccine, Moraxella vaccines, and attenuated live or killed virus vaccine products such as bovine respiratory disease vaccine (RSV), multivalent human influenza vaccines such as Fluzone® and Quadravlent Fluzone®), feline leukemia vaccine, transmissible gastroenteritis vaccine, COVID-19 vaccine, and rabies vaccine.
  • HSV vaccines Bordetella pertussis
  • Escherichia coli vaccines pneumococcal
  • compositions or medicaments are administered to a patient susceptible to, or otherwise at risk of disease in an amount sufficient to eliminate or reduce the risk, lessen the severity, or delay the outset of the disease, including biochemical, histologic and/or behavioral symptoms of the disease, its complications and intermediate pathological phenotypes presenting during development of the disease.
  • Camels were acclimated at research facility for at least 7 days before immunization. Antigen was diluted with 1 ⁇ PBS (antigen total about 1 mg). The quality of the antigen was assessed by SDS-PAGE to ensure purity (e.g., >80%). For the first time, 10 mL CFA (then followed 6 times using IFA) was added into mortar, then 10 mL antigen in 1 ⁇ PBS was slowly added into the mortar with the pestle grinding. The antigen and CFA/IFA were ground until the component showed milky white color and appeared hard to disperse. Camels were injected with antigen emulsified in CFA subcutaneously at at least six sites on the body, injecting about 2 mL at each site (total of 10 mL per camel).
  • a stronger immune response was generated by injecting more sites and in larger volumes.
  • the immunization was conducted every week (7 days), for 7 times.
  • the needle was inserted into the subcutaneous space for 10 to 15 seconds after each injection to avoid leakage of the emulsion.
  • a light pull on the syringe plunger also prevented leakage.
  • the blood sample was collected three days later after 7 th immunization.
  • the approximately 900 bp reverse transcribed sequences encoding the VH-CH1-hinge-CH2-CH3 constructs were isolated from the approximately desired 700 bp fragments encoding the V H H-hinge-CH2-CH3 species.
  • the purified approximately 700 bp fragments were amplified by nested PCR. The amplified sequences were digested using Pst1 and Not1.
  • the approximately 400 bp PST1/Not1 digested fragments were inserted into a Pst1/Not1 digested pMECS phagemid vector such that the sequence encoding the V H H was in frame with a DNA sequence encoding a HA/His sequence.
  • the PCR generated sequences and the vector of pMECS phagemid were digested with Pst I and Not I, subsequently, ligated to pMECS/Nb recombinant. After ligation, the products were transformed into Escherichia coli ( E. coli ) TG1 cells by electroporation. The transformants were enriched in growth medium, followed by transfer to 2YT+2% glucose agar plates.
  • Bio-panning of the phage library was conducted to identify VHHs that bind IL27R ⁇ .
  • a 96-well plate was coated with IL27R ⁇ and the phage library was incubated in each well to allow phage-expressing IL27R ⁇ reactive VHH to bind to the IL27R ⁇ on the plate. Non-specifically bound phage were washed off and the specifically bound phage isolated. After the selection, the enriched phage library expressing IL27R ⁇ reactive VHH were amplified in TG1 cells. The aforementioned bio-panning process was repeated for 2-3 rounds to enrich the library for VHH selective for IL27R ⁇ .
  • Codon optimized DNA inserts were cloned into modified pcDNA3.4 (Genewiz) for small scale expression in HEK293 cells in 24 well plates.
  • the binding proteins were purified in substantial accordance with the following procedure. Using a Hamilton Star automated system, 96 ⁇ 4 mL of supernatants in 4 ⁇ 24-well blocks were re-arrayed into 4 ⁇ 96-well, 1 mL blocks.
  • PhyNexusTM micropipette tips Biotage, San Jose CA
  • 80 ptL of Ni-Excel IMAC resin (Cytiva) are equilibrated wash buffer: PBS pH 7.4, 30 mM imidazole.
  • PhyNexusTM tips were dipped and cycled through 14 cycles of 1 mL pipetting across all 4 ⁇ 96-well blocks. PhyNexusTM tips were washed in 2 ⁇ 1 mL blocks holding wash buffer. PhyNexusTM tips were eluted in 3 ⁇ 0.36 mL blocks holding elution buffer: PBS pH 7.4, 400 mM imidazole. PhyNexusTM tips were regenerated in 3 ⁇ 1 mL blocks of 0.5 M sodium hydroxide.
  • the purified protein eluates were quantified using a Biacore® T200 as in substantial accordance with the following procedure. 10 uL of the first 96 ⁇ 0.36 mL eluates were transferred to a Biacore® 96-well microplate and diluted to 60 uL in HBS-EP+ buffer (10 mM Hepes pH 7.4, 150 mM NaCl, 1 mM EDTA, 0.05% TweenTM 20). Each of the 96 samples was injected on a CM5 series S chip previously functionalized with anti-histidine capture antibody (Cytiva): injection is performed for 18 seconds at 5 ⁇ L/min. Capture levels were recorded 60 seconds after buffer wash.
  • V H H concentrations 270, 90, 30, 10, 3.3, 1.1 ⁇ g/mL
  • the 96 captures were interpolated against the standard curve using a non-linear model including specific and unspecific, one-site binding.
  • Concentrations in the first elution block varied from 12 to 452 ⁇ g/mL corresponding to a 4-149 ⁇ g.
  • SDS-PAGE analysis of 5 randomly picked samples was performed to ensure molecular weight of eluates corresponded to expected values ( ⁇ 30 kDa).
  • the concentration of the proteins was normalized using the Hamilton Star automated system in substantial accordance with the following procedure. Concentration values are imported in an Excel spreadsheet where pipetting volumes were calculated to perform dilution to 50 ⁇ g/mL in 0.22 mL. The spreadsheet was imported in a Hamilton Star method dedicated to performing dilution pipetting using the first elution block and elution buffer as diluent. The final, normalized plate was sterile filtered using 0.22 ⁇ m filter plates (Corning).
  • VHH binding for all VHH was confirmed by ELISA.
  • One representative VHH from each clonotype was selected for further analysis by surface plasmon resonance using Biacore® T200. See below.

Abstract

Provided herein are IL27R binding proteins that bind to IL27Rα and gp130 and comprise an anti-IL27Rα VHH antibody and an anti-gp130 VHH antibody.

Description

    CROSS-REFERENCES TO RELATED APPLICATIONS
  • This application is a continuation of PCT/US2021/044577, filed Aug. 4, 2021, which claims priority to U.S. Provisional Application No. 63/061,562, filed Aug. 5, 2020, U.S. Provisional Application No. 63/078,745, filed Sep. 15, 2020, and U.S. Provisional Application No. 63/135,884, filed Jan. 11, 2021, the disclosures of which are hereby incorporated by reference in their entirety for all purposes.
    • SEQUENCE LISTING
  • The instant application contains a Sequence Listing which has been submitted electronically in XML format and is hereby incorporated by reference in its entirety. Said XML file, created on Feb. 2, 2023, is named 106249-1361753-006820US_SL.xml, and is 2,426,545 bytes in size.
    • BACKGROUND OF THE DISCLOSURE
  • The interleukin-27 receptor (IL27R) is a type I cytokine receptor for interleukin-27 (IL27). It is a heterodimer composed of the IL27Rα subunit and glycoprotein 130 (gp130). IL27 is expressed by antigen presenting cells and induces differentiation of a diverse populations of T cells in the immune system. When IL27 binds to the IL27R, signaling pathways, such as the JAK-STAT and p38 MAPK pathways, are turned on to induce pro-inflammatory or anti-inflammatory responses, which involve different types of cells, such as macrophages, dendritic cells, T cells, and B cells. The response that is activated can be dependent on the external surrounding of IL27.
  • IL-27 is a heterodimeric cytokine consisting of two non-covalently linked subunits, p28 and EBI3. The p28 subunit belongs to the 4-helix bundle cytokine family, while EBI3 is the shortest form possible of a soluble cytokine receptor, with two typical cytokine binding domains (Pflanz S, et al., Immunity. 2002 June; 16(6):779-90).
  • The primary binding receptor for IL-27 is the IL-27R1 (also known as TCCR- or WSX-1 receptor). IL-27 and IL-27R1 form a complex of considerable affinity (nM). Gp130 is the second receptor that binds the complex of IL-27/IL-27R to create the active signaling complex. Gp130 binding to the IL-27/IL-27R1 complex is much weaker than the interaction between IL-27 and IL-27R1 (Pflanz S, et al., J Immunol. 2004 Feb. 15; 172(4):2225-31).
  • The IL-27 extracellular domain has 5 domains. The first two domains form the IL-27 binding domains. Typically the loops between D1 and D2 provide most of the binding energy.
  • The other 3 domains are called Fibronectin type III domains (Fn3). The sequence of each Fn3 domain varies.
  • The gp130 receptor has 6 domains. The top domain D1 of gp130 binds p28 of IL-27. D2 and D3 contribute little to binding IL-27. The membrane proximal 3 domains are Fn3 domains. The sequence of each Fn3 domain varies.
  • The structure of the IL-27R is not known but the domain structure is known. The structure of gp130 is known as complexed with IL-6. Based on that structure it is evident that the Fn3 domains do not energetically contribute to IL-27R complex formation. Rather the structure of the gp130 forms a ‘C’ with the domain 4 and 5 at 80% angle of each other. Certain residues in each of the ‘tall’ receptors are conserved similar to D4 and D5 in gp130. This indicates that all tall receptors of the gp130 family, including IL-27R, forms this ‘C’ structure. (Yibin Xu, et al., J Biol Chem. 2010 Jul. 9; 285(28):21214-8).
  • IL-27R has 5 extracellular domains. D1 and D2 are the cytokine binding domains. D3, D4 and D5 are Fn3 domains. The D5 domain of IL-27R and the D6 domain of gp130 will come close together at the membrane because of the ‘C’ shape of each receptor. This is required to be able for the receptor complex to trigger binding of JAKs at the intracellular domains of both receptors.
    • SUMMARY OF THE DISCLOSURE
  • The present disclosure provides compositions useful in the pairing of cellular receptors to generate desirable effects useful in treatment of disease in mammalian subjects.
  • Several advantages flow from the binding molecules described herein. The natural ligand of the IL-27R, IL-27, causes gp130 and IL-27Rα to come into proximity (i.e., by their simultaneous binding of IL-27). However, when IL-27 is used as a therapeutic in mammalian, particularly human, subjects, it may also trigger a number of adverse and undesirable effects by a variety of mechanisms including the presence of gp130 and IL-27Rα on other cell types and the binding to gp130 and IL-27Rα on the other cell types may result in undesirable effects and/or undesired signaling on cells expressing gp130 and IL-27Ra. The present disclosure is directed to methods and compositions that modulate the multiple effects of gp130 and IL-27Rα binding so that desired therapeutic signaling occurs, particularly in a desired cellular or tissue subtype, while minimizing undesired activity and/or intracellular signaling.
  • In some embodiments, the IL-27R binding molecules described herein are partial agonists of the IL-27 receptor. In some embodiments, the binding molecules described herein are designed such that the binding molecules are full agonists. In some embodiments, the binding molecules described herein are designed such that the binding molecules are super agonists.
  • In some embodiments, the binding molecules provide the maximal desired IL-27 intracellular signaling from binding to gp130 and IL-27Rα on the desired cell types, while providing significantly less IL-27 signaling on other undesired cell types. This can be achieved, for example, by selection of binding molecules having differing affinities or causing different Emax for gp130 and IL-27Rα as compared to the affinity of IL-27 for gp130 and IL-27Ra. Because different cell types respond to the binding of ligands to its cognate receptor with different sensitivity, by modulating the affinity of the dimeric ligand (or its individual binding moieties) for the IL-27 receptor relative to wild-type IL-27 binding may facilitate the stimulation of desired activities while reducing undesired activities on non-target cells.
  • The present disclosure provides bivalent binding molecules that are agonists of the IL-27 receptor, the bivalent binding molecule comprising:
      • a first single domain antibody (sdAb) that specifically binds to the extracellular domain of gp130 (an “anti-gp130 sdAb”), and
      • a second single domain antibody that specifically binds to extracellular domain IL-27Rα (an “anti-IL-27Rα sdAb”),
        wherein the anti-gp130 sdAb and anti-IL-27Rα sdAb are stably associated and first wherein contacting a cell expressing gp130 and IL-27Rα with an effective amount of the bivalent binding molecule results the dimerization of gp130 and IL-27Rα and results in intracelullar signaling characteristic of the IL-27 receptor when activated by its natural cognate IL-27. In some embodiments, one or both of the sdAbs is an scFv. In some embodiments, one or both of the sdAbs is a VHH.
  • In some embodiments, one sdAb of the bivalent binding molecule is an scFv and the other sdAb is a VHH.
  • In some embodiments, the first and second sdAbs are covalently bound via a chemical linkage.
  • In some some embodiments, the first and second sdAbs are provided as single continuous polypeptide.
  • In some embodiments, the first and second sdAbs are provided as single continuous polypeptide optionally comprising an intervening polypeptide linker between the amino acid sequences of the first and second sdAbs.
  • In some embodiments the bivalent binding molecule optionally comprising a linker, is optionally expressed as a fusion protein with an additional amino acid sequence. In some embodiments, the additional amino acid sequence is a purification handle such as a chelating peptide or an additional protein such as a subunit of an Fc molecule.
  • In one aspect, the disclosure provides an IL27 receptor (IL27R) binding protein that specifically binds to IL27Rα subunit (IL27Rα) and glycoprotein 130 subunit (gp130), wherein the binding protein causes the multimerization of IL27Rα and gp130 when bound to IL27Ra and gp130 and the multimerization results in the activation of JAK kinases associated with the intracellular domains of IL27Rα and gp130 and intraceullar signaling, and wherein the binding protein comprises a single-domain antibody (sdAb) that specifically binds to IL27Rα (an anti-IL27Rα sdAb) and a sdAb that specifically binds to gp130 (an anti-gp130 sdAb). In some embodiments, the multimerization of IL27Rα and gp130 can cause downstream signaling.
  • In some embodiments, the anti-IL27Rα sdAb is a VHH antibody (an anti IL27Rα VHH antibody) and/or the anti-gp130 sdAb is a VHH antibody (an anti gp130 VHH antibody). In some embodiments, the anti-IL27Rα sdAb and the anti-gp130 sdAb are joined directly or via a peptide linker. In some embodiments, the peptide linker comprises between 1 and 50 amino acids. In particular embodiments, the peptide linker comprises a sequence of GGGS (SEQ ID NO:108).
  • In some embodiments, the IL27R binding protein comprises:
      • a first VHH antibody comprising a CDR1 having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity, or having 0, 1, 2, or 3 amino acid changes, optionally conservative amino acid changes relative, to the sequence of a CDR1 from a row of Table 1A; a CDR2 having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity, or having 0, 1, 2, or 3 amino acid changes, optionally conservative amino acid changes relative, to the sequence of a CDR2 from the same row of Table 1A; and a CDR3 having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity, or having 0, 1, 2, or 3 amino acid changes, optionally conservative amino acid changes relative, to the sequence of a CDR3 from the same row of Table 1A; and
      • a second VHH antibody comprising a CDR1 having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity, or having 0, 1, 2, or 3 amino acid changes, optionally conservative amino acid changes relative, to the sequence of a CDR4 from the same row of Table 1A; a CDR2 having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity, or having 0, 1, 2, or 3 amino acid changes, optionally conservative amino acid changes relative, to the sequence of a CDR5 from the same row of Table 1A; and a CDR3 having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity, or having 0, 1, 2, or 3 amino acid changes optionally conservative amino acid changes relative, to the sequence of a CDR6 from the same row of Table 1A.
  • In some embodiments, the IL27R binding protein comprises a sequence at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) identical to any one of the dual VHH dimer sequences shown in Table 1A.
  • In certain embodiments, the anti IL27Rα VHH antibody comprises a CDR1 having 0, 1, 2, or 3 amino acid changes relative to the sequence of any one of SEQ ID NOS:193-198; a CDR2 having 0, 1, 2, or 3 amino acid changes relative to the sequence of any one of SEQ ID NOS:199-204; and a CDR3 having 0, 1, 2, or 3 amino acid changes relative to the sequence of any one of SEQ ID NOS:205-210. In further embodiments, the anti gp130 VHH antibody comprises a CDR1 having 0, 1, 2, or 3 amino acid changes relative to the sequence of any one of SEQ ID NOS:211-217; a CDR2 having 0, 1, 2, or 3 amino acid changes relative to the sequence of any one of SEQ ID NOS:218-224; and a CDR3 having 0, 1, 2, or 3 amino acid changes relative to the sequence of any one of SEQ ID NOS:225-231.
  • In particular embodiments, the IL27R binding protein comprises a CDR1, a CDR2, and a CDR3 in the anti IL27Rα VHH antibody and a CDR1, a CDR2, and a CDR3 in the anti gp130 VHH antibody as listed in a row of Table 1.
  • In some embodiments, the binding protein comprises an anti gp130 VHH antibody linked to the N-terminus of a linker and an anti IL27Rα VHH antibody linked to the C-terminus of the linker. In some embodiments, the anti gp130 VHH antibody comprises a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity to a sequence of any one of SEQ ID NOS:232-237. In some embodiments, the anti IL27Rα VHH antibody comprises a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity to a sequence of any one of SEQ ID NOS:238-244.
  • In particular embodiments, each of the anti-gp130 VHH antibody and the anti-IL27Ra VHH antibody comprises a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) identity to a sequence listed in a row of Table 2A.
  • In certain embodiments, the binding protein comprises a sequence that is substantially identical to a sequence of any one of SEQ ID NOS:1-42. In certain embodiments, the binding protein comprises a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) identity to a sequence of any one of SEQ ID NOS:1-42.
  • In some embodiments, the binding protein comprises an anti IL27Rα VHH antibody linked to the N-terminus of a linker and an anti gp130 VHH antibody linked to the C-terminus of the linker. In some embodiments, the anti IL27Rα VHH antibody comprises a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity to a sequence of any one of SEQ ID NOS:245-251. In certain embodiments, the anti gp130 VHH antibody comprises a sequence having at least 90% sequence identity to a sequence of any one of SEQ ID NOS:252-257.
  • In particular embodiments, each of the anti IL27Rα VHH antibody and the anti gp130 VHH antibody comprises a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) identity to a sequence listed in a row of Table 3A.
  • In certain embodiments, the binding protein comprises a sequence that is substantially identical to a sequence of any one of SEQ ID NOS:43-84. In certain embodiments, the binding protein comprises a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) identity to a sequence of any one of SEQ ID NOS:43-84.
  • In another aspect, the disclosure provides an isolated nucleic acid encoding the IL27R binding protein described herein. In certain embodiments, the isolated nucleic acid comprises a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity to a sequence of any one of SEQ ID NOS:109-192 or a sequence from Table 1B. The disclosure also provides an expression vector comprising the nucleic acid. The disclosure also provides an isolated host cell comprising the expression vector.
  • In another aspect, the disclosure provides a pharmaceutical composition comprising the IL27R binding protein described herein and a pharmaceutically acceptable carrier.
  • In another aspect, the disclosure provides a method of treating an autoimmune or inflammatory disease, disorder, or condition, a neoplastic disease, or a viral infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an IL27R binding protein described herein or a pharmaceutical composition described herein.
  • In some embodiments, the method further comprises administering one or more supplementary agents selected from the group consisting of a corticosteroid, a Janus kinase inhibitor, a calcineurin inhibitor, a mTor inhibitor, an IMDH inhibitor, a biologic, a vaccine, and a therapeutic antibody. In certain embodiments, the therapeutic antibody is an antibody that binds a protein selected from the group consisting of BLyS, CD11a, CD20, CD25, CD3, CD52, IgEIL12/IL23, IL17a, IL1B, IL4Ra, IL5, IL6R, integrin-α4β7, RANKL, TNFα, VEGF-A, and VLA-4.
  • In certain embodiments, the disease, disorder, or condition is selected from viral infections, heliobacter pylori infection, HTLV, organ rejection, graft versus host disease, autoimmune thyroid disease, multiple sclerosis, allergy, asthma, neurodegenerative diseases including Alzheimer's disease, systemic lupus erythramatosis (SLE), autoinflammatory diseases, inflammatory bowel disease (IBD), Crohn's disease, diabetes, cartilage inflammation, arthritis, rheumatoid arthritis, juvenile arthritis, juvenile rheumatoid arthritis, juvenile rheumatoid arthritis, polyarticular juvenile rheumatoid arthritis, systemic onset juvenile rheumatoid arthritis, juvenile ankylosing spondylitis, juvenile enteropathic arthritis, juvenile reactive arthritis, juvenile Reiter's Syndrome, SEA Syndrome, juvenile dermatomyositis, juvenile psoriatic arthritis, juvenile scleroderma, juvenile systemic lupus erythematosus, juvenile vasculitis, pauciarticular rheumatoidarthritis, polyarticular rheumatoidarthritis, systemic onset rheumatoidarthritis, ankylosing spondylitis, enteropathic arthritis, reactive arthritis, Reiter's syndrome, SEA Syndrome, psoriasis, psoriatic arthritis, dermatitis (eczema), exfoliative dermatitis or atopic dermatitis, pityriasis rubra pilaris, pityriasis rosacea, parapsoriasis, pityriasis lichenoiders, lichen planus, lichen nitidus, ichthyosiform dermatosis, keratodermas, dermatosis, alopecia areata, pyoderma gangrenosum, vitiligo, pemphigoid, urticaria, prokeratosis, rheumatoid arthritis; seborrheic dermatitis, solar dermatitis, seborrheic keratosis, senile keratosis, actinic keratosis, photo-induced keratosis, keratosis follicularis; acne vulgaris; keloids; nevi; warts including verruca, condyloma or condyloma acuminatum, and human papilloma viral (HPV) infections.
  • An IL27R binding proteins described herein are useful in the treatment of neoplastic diseases, such as cancer (e.g., a solid tumor cancer; e.g., non-small-cell lung carcinoma (NSCLC), renal cell carcinoma (RCC), or melanoma) and/or infectious diseases (e.g., bacterial infections and viral infections (e.g., viral infections caused by hepatitis C virus (HCV), human papillomavirus (HPV), or human immunodeficiency virus (HIV)) in a subject in need thereof. The IL27R binding protein binds to and activates CD8+ T cells, CD4+ T cells, and/or T regulatory (Treg) cells. The IL27R binding protein can trigger different levels of downstream signaling in different cell types. For example, by varying the length of the linker between the antiIL27Rα VHH antibody and the antigp130 VHH antibody in the IL27R binding protein, the IL27R binding protein can cause a higher level of downstream signaling in desired cell types compared to undesired cell types. In some embodiments, by varying the linker length, an IL27R binding protein can cause a higher level of downstream signaling in T cells (e.g., CD8+ T cells) compared to the level of downstream signaling in other cells. In other embodiments, different antilL27Rα VHH antibodies with different binding affinities and different antigp130 VHH antibodies with different binding affinities can be combined to make different IL27R binding proteins. Further, the orientation of the two antibodies in the binding protein can also be changed to make a different binding protein (i.e., antiIL27Rα VHH antibody-linker-antigp130 VHH antibody, or antigp130 VHH antibody-linker-antiIL27Rα VHH antibody). Different IL27R binding proteins can be screened to find the ideal binding protein that causes a higher level of downstream signaling in desired cell types compared to undesired cell types. In some embodiments, the level of downstream signaling in T cells (e.g., CD8+ T cells) is at least 1.1, 1.5, 2, 3, 5, or 10 times of the level of downstream signaling in other cells.
  • In particular, the IL27R binding protein binds to and activates CD8+ T cells. In some embodiments, the IL27R binding protein binds to and activates CXCR5+ CD8+ T cells. It is known that IL27 can promote and sustain a rapid division of memory-like CXCR5+ CD8+ T cells during, for example, viral infection. The CXCR5+ CD8+ T cells can sustain T cell responses during persistent infection or cancer and drive the proliferative burst of CD8+ T cells after anti-PD1 treatment. Accordingly, an IL27R binding protein described herein is useful to sustain and augment self-renewing T cells in chronic infections and neoplastic diseases, such as cancer.
    • BRIEF DESCRIPTION OF THE FIGURES
  • FIG. 1 of the attached drawings provides a schematic representation of one embodiment of the bivalent binding molecule of the present disclosure comprising a first single domain antibody (1) and a second single domain antibody (3) and a linker (2) depicted as interacting with a cell membrane (10) associated heterodimeric receptor comprising a first receptor subunit comprising an extracellular domain (4), and transmembrane domain (5) and an intracellular domain (6) interaction of a bivalent binding molecule and a second first receptor subunit comprising an extracellular domain (7), and transmembrane domain (8) and an intracellular domain (9) wherein the intracellular domain of the first receptor (6) and the intracellular domain of the second receptor (9) on of a bivalent binding molecule are within a proximal distance (11).
  • FIGS. 2A and 2B of the attached drawings provides a schematic representation of two illustrative configurations of bivalent binding molecules of the present disclosure. FIG. 2A provides a schematic representation of an illustrative single polypeptide chain bivalent binding molecule comprising, from amino to carboxy, a first single domain antibody (1) and a second single domain antibody (3) and a linker (2). FIG. 2B provides a schematic representation of a bivalent binding molecule comprising a first single domain antibody (1) and a second single domain antibody (3) and a linker (2) and a knob-into-hole Fc domain, the Fc domain comprising a first subunit which is a Fc knob (13) and a second subunit which is a Fc hole (14) wherein the bivalent binding molecule is covalently linked to an Fc domain subunit via a IgG hinge sequence (12).
  • FIGS. 3A and 3B of the attached drawings provides a schematic representations of two illustrative configurations of bivalent binding molecules of the present disclosure. FIG. 3A provides a schematic representation of an illustrative bivalent binding molecule construct comprising two bivalent binding molecules each attached to a subunit of a knob-into-hole Fe domain, the construct comprising two polypeptide chains, the first polypeptide chain comprising, from amino to carboxy, a first single domain antibody (1), a linker (2) and a second single domain antibody (3), a IgG hinge sequence (12) and a Fc knob subunit (13) and a second polypeptide chain comprising, from amino to carboxy, a first single domain antibody (1), a linker (2) and a second single domain antibody (3), a IgG hinge sequence (12) and a Fc hole subunit (14) wherein the first and second polypeptides are in stable associate via the interaction of the knob-into-hole Fc domain. FIG. 3B provides schematic representation of a an alternative arrangement of a bivalent binding molecule construct comprising two polypeptides a first polypeptide chain comprising, from amino to carboxy, a first single domain antibody (1), a linker (2) and a second single domain antibody (3), an IgG hinge sequence (12) and a Fc knob subunit (13) and a second polypeptide chain comprising, from amino to carboxy, a first second domain antibody (3), a linker (2) and a first single domain antibody (1), a IgG hinge sequence (12) and a Fc hole subunit (14), wherein the first and second polypeptides are in stable association via the interaction of the knob-into-hole Fc domain.
  • FIG. 4A provides alternative schematic representations of configurations of the bivalent binding molecules of the present disclosure where one single domain antibody is attached to each subunit of a knob-into-hole Fc domain comprising two polypeptides, the first polypeptide comprising from amino to carboxy, a first single domain antibody (1), an IgG hinge sequence (12) and a Fc knob subunit (13), the second polypeptide comprising from amino to carboxy, a second single domain antibody (3), an IgG hinge sequence (12) and a Fc hole subunit (13), wherein the first and second single domain antibodies are in stable associate via the interaction of the knob-into-hole Fc domain.
  • FIG. 4B provides a schematic representation of a binding molecule the binding domains are single domain antibodies associated via transition metal coordinate covalent complex. As illustrated, the binding molecules comprises two polypeptide subunits: the first subunit comprising a first single domain antibody (1) is attached via a first linker (15) to a first chelating peptide (17) and second subunit comprising a second single domain antibody (3) is attached via a second linker (16) to a second chelating peptide (18), wherein the first chelating peptide (17) and second chelating peptide (18) form a coordinate covalent complex with a single transition metal ion (“M”). The transition metal ion may be in a kinetically labile or kinetically inert oxidation state.
    •  DETAILED DESCRIPTION OF THE DISCLOSURE I. Introduction
  • The present disclosure provides compositions useful in the pairing of cellular receptors to generate desirable effects useful in treatment of diseases. In general, binding proteins are provided that comprise a first domain that binds to IL27Rα and a second domain that binds to gp130, such that upon contacting with a cell expressing IL27Rα and gp130, the binding protein causes the functional association of IL27Rα and gp130, thereby resulting in functional dimerization of the receptors and downstream signaling.
  • Several advantages flow from the binding proteins described herein. The natural ligand of IL27R, IL27, causes IL27Rα and gp130 to come into proximity (i.e., by their simultaneous binding of IL27). However, when IL27 is used as a therapeutic in mammalian, particularly human, subjects, it may also trigger a number of adverse and undesirable effects by a variety of mechanisms including the presence of IL27Rα and gp130 on other cell types and the binding to IL27Rα and gp130 on the other cell types may result in undesirable effects and/or undesired signaling on cells expressing IL27Rα and gp130. The present disclosure is directed to methods and compositions that modulate the multiple effects of IL27Rα and gp130 binding so that desired therapeutic signaling occurs, particularly in a desired cellular or tissue subtype, while minimizing undesired activity and/or intracellular signaling.
  • In some embodiments, the binding proteins described herein are designed such that the binding proteins provide the maximal desired IL27 intracellular signaling from binding to IL27Rα and gp130 on the desired cell types, while providing significantly less IL27 signaling on other undesired cell types. This can be achieved, for example, by selection of binding proteins having differing affinities or causing different Emax for IL27Rα and gp130 as compared to the affinity of IL27 for IL27Rα and gp130. Because different cell types respond to the binding of ligands to its cognate receptor with different sensitivity, by modulating the affinity of the dimeric ligand (or its individual binding moieties) for the IL27 receptor relative to wild-type IL27 binding facilitates the stimulation of desired activities while reducing undesired activities on non-target cells. To measure downstream signaling activity, a number of methods are available. For example, in some embodiments, one can measure JAK/STAT signaling by the presence of phosphorylated receptors and/or phosphorylated STATs. In other embodiments, the expression of one or more downstream genes, whose expression levels can be affected by the level of downstream signalinging caused by the binding protein, can also be measured.
    • Interleukin 27 (IL27) Structure:
  • IL27 is a member of the IL-12 cytokine family. IL27 is a heterodimeric cytokine comprised of two subunits: IL27A (also referred to as IL-27p28) and IL27B (also referred to as Epstein-Barr Virus induced gene 3 or “EBI3”). The human p28 (hIL27A) is expressed as a 243 amino acid pre-protein comprising 28 amino acid signal sequence which is post-translationally removed to render a 215 amino acid mature protein. UniProtKB-Q8NEV9 (IL27A_HUMAN). The mature form of p28 (less the signal peptide) possesses the amino acid sequence;
  • (SEQ ID NO: 400)
    FPRPPGRPQLSLQELRREFTVSLHLARKLLSEVRGQAHRF
    AESHLPGVNLYLLPLGEQLPDVSLTFQAWRRLSDPERLCF
    ISTTLQPFHALLGGLGTQGRWTNMERMQLWAMRLDLRDLQ
    RHLRFQVLAAGFNLPEEEEEEEEEEEEERKGLLPGALGSA
    LQGPAQVSWPQLLSTYRLLHSLELVLSRAVRELLLLSKAG
    HSVWPLGFPTLSPQP
  • The human IL27B (hIL27B) is expressed as a 229 amino acid pre-protein comprising 20 amino acid signal sequence which is post-translationally removed to render a 209 amino acid mature protein. UniProtKB-Q14213 (IL27B_HUMAN). The mature form of hIL27B (less the signal peptide) possesses the amino acid sequence
  • (SEQ ID NO: 401)
    RKGPPAALTLPRVQCRASRYPIAVDCSWTLPPAPNSTSPV
    SFIATYRLGMAARGHSWPCLQQTPTSTSCTITDVQLFSMA
    PYVLNVTAVHPWGSSSSFVPFITEHIIKPDPPEGVRLSPL
    AERQLQVQWEPPGSWPFPEIFSLKYWIRYKRQGAARFHRV
    GPIEATSFILRAVRPRARYYVQVAAQDLTDYGELSDWSLP
    ATATMSLGK
    • Interleukin 27 (IL27) Receptor:
  • IL27 results in intracellular signaling via its interaction with a heterodimeric receptor consisting of: IL-27Rα (or IL27RA) and gp130. The binding of IL27 to IL27 receptor activates signaling pathways including the JAK/STAT and p38 MAPK pathways. IL27 stimulates both pro-inflammatory and anti-inflammatory response in different cell types such as macrophages, dendritic cells, T cells and B cells. The type of response is dependent on the environment.
  • The human IL27 receptor subunit alpha (hIL27RA) is expressed as a 636 amino acid pre-protein comprising 32 amino acid signal sequence which is post-translationally removed to render a 604 amino acid mature protein. UniProtKB-Q6UWB1 (I27RA_HUMAN)
  • The mature form of hIL27RA (less the signal peptide) possesses the amino acid sequence:
  • (SEQ ID NO: 402)
    QGSAGPLQCYGVGPLGDLNCSWEPLGDLGAPSELHLQSQK
    YRSNKTQTVAVAAGRSWVAIPREQLTMSDKLLVWGTKAGQ
    PLWPPVFVNLETQMKPNAPRLGPDVDFSEDDPLEATVHWA
    PPTWPSHKVLICQFHYRRCQEAAWTLLEPELKTIPLTPVE
    IQDLELATGYKVYGRCRMEKEEDLWGEWSPILSFQTPPSA
    PKDVWVSGNLCGTPGGEEPLLLWKAPGPCVQVSYKVWFWV
    GGRELSPEGITCCCSLIPSGAEWARVSAVNATSWEPLTNL
    SLVCLDSASAPRSVAVSSIAGSTELLVTWQPGPGEPLEHV
    VDWARDGDPLEKLNWVRLPPGNLSALLPGNFTVGVPYRIT
    VTAVSASGLASASSVWGFREELAPLVGPTLWRLQDAPPGT
    PAIAWGEVPRHQLRGHLTHYTLCAQSGTSPSVCMNVSGNT
    QSVTLPDLPWGPCELWVTASTIAGQGPPGPILRLHLPDNT
    LRWKVLPGILFLWGLFLLGCGLSLATSGRCYHLRHKVLPR
    WVWEKVPDPANSSSGQPHMEQVPEAQPLGDLPILEVEEME
    PPPVMESSQPAQATAPLDSGYEKHFLPTPEELGLLGPPRP
    QVLA
  • The extracellular domain of hIL27RA (IL27RA-ECD) is a 484 amino acid polypeptide corresponding to amino acids 33-516 of the hIL27RA preprotein and possesses the amino acid sequence:
  • (SEQ ID NO: 403)
    QGSAGPLQCYGVGPLGDLNCSWEPLGDLGAPSELHLQSQK
    YRSNKTQTVAVAAGRSWVAIPREQLTMSDKLLVWGTKAGQ
    PLWPPVFVNLETQMKPNAPRLGPDVDFSEDDPLEATVHWA
    PPTWPSHKVLICQFHYRRCQEAAWTLLEPELKTIPLTPVE
    IQDLELATGYKVYGRCRMEKEEDLWGEWSPILSFQTPPSA
    PKDVWVSGNLCGTPGGEEPLLLWKAPGPCVQVSYKVWFWV
    GGRELSPEGITCCCSLIPSGAEWARVSAVNATSWEPLTNL
    SLVCLDSASAPRSVAVSSIAGSTELLVTWQPGPGEPLEHV
    VDWARDGDPLEKLNWVRLPPGNLSALLPGNFTVGVPYRIT
    VTAVSASGLASASSVWGFREELAPLVGPTLWRLQDAPPGT
    PAIAWGEVPRHQLRGHLTHYTLCAQSGTSPSVCMNVSGNT
    QSVTLPDLPWGPCELWVTASTIAGQGPPGPILRLHLPDNT
    LRWK
  • The human gp130 receptor subunit (hGP130) is also referred as the IL6 receptor beta subunit. UniProtKB-P40189 (IL6RB_HUMAN. hGP130 is expressed as a 918 amino acid pre-protein comprising 22 amino acid signal sequence which is post-translationally removed to render a 896 amino acid mature protein. The mature form of hGP130 possess the amino acid sequence:
  • (SEQ ID NO: 404)
    ELLDPCGYISPESPVVQLHSNFTAVCVLKEKCMDYFHVNA
    NYIVWKTNHFTIPKEQYTIINRTASSVTFTDIASLNIQLT
    CNILTFGQLEQNVYGITIISGLPPEKPKNLSCIVNEGKKM
    RCEWDGGRETHLETNFTLKSEWATHKFADCKAKRDTPTSC
    TVDYSTVYFVNIEVWVEAENALGKVTSDHINFDPVYKVKP
    NPPHNLSVINSEELSSILKLTWTNPSIKSVIILKYNIQYR
    TKDASTWSQIPPEDTASTRSSFTVQDLKPFTEYVFRIRCM
    KEDGKGYWSDWSEEASGITYEDRPSKAPSFWYKIDPSHTQ
    GYRTVQLVWKTLPPFEANGKILDYEVTLTRWKSHLQNYTV
    NATKLTVNLTNDRYLATLTVRNLVGKSDAAVLTIPACDFQ
    ATHPVMDLKAFPKDNMLWVEWTTPRESVKKYILEWCVLSD
    KAPCITDWQQEDGTVHRTYLRGNLAESKCYLITVTPVYAD
    GPGSPESIKAYLKQAPPSKGPTVRTKKVGKNEAVLEWDQL
    PVDVQNGFIRNYTIFYRTIIGNETAVNVDSSHTEYTLSSL
    TSDTLYMVRMAAYTDEGGKDGPEFTFTTPKFAQGEIEAIV
    VPVCLAFLLTTLLGVLFCFNKRDLIKKHIWPNVPDPSKSH
    IAQWSPHTPPRHNFNSKDQMYSDGNFTDVSVVEIEANDKK
    PFPEDLKSLDLFKKEKINTEGHSSGIGGSSCMSSSRPSIS
    SSDENESSQNTSSTVQYSTVVHSGYRHQVPSVQVFSRSES
    TQPLLDSEERPEDLQLVDHVDGGDGILPRQQYFKQNCSQH
    ESSPDISHFERSKQVSSVNEEDFVRLKQQISDHISQSCGS
    GQMKMFQEVSAADAFGPGTEGQVERFETVGMEAATDEGMP
    KSYLPQTVRQGGYMPQ
  • The extracellular domain of hGP130 (hGP130-ECD) is a 597 amino acid polypeptide corresponding to amino acids 23-619 of the hGP130 preprotein and possesses the amino acid sequence:
  • (SEQ ID NO: 405)
    ELLDPCGYISPESPVVQLHSNFTAVCVLKEKCMDYFHVNA
    NYIVWKTNHFTIPKEQYTIINRTASSVTFTDIASLNIQLT
    CNILTFGQLEQNVYGITIISGLPPEKPKNLSCIVNEGKKM
    RCEWDGGRETHLETNFTLKSEWATHKFADCKAKRDTPTSC
    TVDYSTVYFVNIEVWVEAENALGKVTSDHINFDPVYKVKP
    NPPHNLSVINSEELSSILKLTWTNPSIKSVIILKYNIQYR
    TKDASTWSQIPPEDTASTRSSFTVQDLKPFTEYVFRIRCM
    KEDGKGYWSDWSEEASGITYEDRPSKAPSFWYKIDPSHTQ
    GYRTVQLVWKTLPPFEANGKILDYEVTLTRWKSHLQNYTV
    NATKLTVNLTNDRYLATLTVRNLVGKSDAAVLTIPACDFQ
    ATHPVMDLKAFPKDNMLWVEWTTPRESVKKYILEWCVLSD
    KAPCITDWQQEDGTVHRTYLRGNLAESKCYLITVTPVYAD
    GPGSPESIKAYLKQAPPSKGPTVRTKKVGKNEAVLEWDQL
    PVDVQNGFIRNYTIFYRTIIGNETAVNVDSSHTEYTLSSL
    TSDTLYMVRMAAYTDEGGKDGPEFTFTTPKFAQGEIE
    • IL27 Activity
  • IL27 is expressed by antigen presenting cells. hIL27 induces differentiation of the diverse populations of T cells in the immune system and also upregulates IL10. hIL27 has pro- and anti-inflammatory properties, that can regulate T-helper cell development, suppress T-cell proliferation, stimulate cytotoxic T-cell activity, induce isotype switching in B-cells, and that have diverse effects on innate immune cells. Among its target cells are CD4 T-helper cells which can differentiate in type 1 effector cells (TH1), type 2 effector cells (TH2) and IL17 producing helper T-cells (TH17).
    • T Cell Differentiation
  • IL27 plays a significant role in the differentiation through inducing or suppressing of T cell subtypes including Th1, Th2, Th17, Tr1 and Treg cells. IL-27 is greatly involved in differentiation through inducing or suppressing of each T cell subset. Interferon gamma (IFNg) expressing Th1 cells are generated in response IL27 through STAT1 signaling via expression of T-bet and signature Th1 genes. IL4 expressing Th2 cells are inhibited by IL27 through the transcription factor GATA-3. Th17 cells, which express IL17, IL22, and GM-CSF, are inhibited by IL27 through STAT1 and expression of transcription factor RORγt. Treg cells are inhibited by IL27 through STAT1 and STAT3.
  • IL27 drives rapid clonal expansion of naive but not memory CD4 T-cells. IL27 also strongly synergizes with IL-12 to trigger interferon-gamma/IFN-gamma production of naive CD4 T-cells, binds to the cytokine receptor WSX-1/TCCR. Another important role of IL-27 is its antitumor activity as well as its antiangiogenic activity with activation of production of antiangiogenic chemokines
    • Induction of IL10
  • Tr1 cells which express IL-10, are induced by IL-27 through the transcription factor c-Maf providing an anti-inflammatory response. A primary activity of IL-10 is the suppression of inflammatory responses. Also involved are the STAT1 and STAT3 transcription factors that bind specifically to the IL-27α. The activation of STAT3 by IL-27 leads to an increase of IL-10 secretion from Treg cells.
    • II. Definitions
  • To facilitate the understanding of present disclosure, certain terms and phrases are defined below as well as throughout the specification. The definitions provided herein are non-limiting and should be read in view of the knowledge of one of skill in the art would know.
  • Before the present methods and compositions are described, it is to be understood that this invention is not limited to a particular method or composition described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing embodiments only and is not intended to be limiting.
  • Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limits of that range is also specifically disclosed. Each smaller range between any stated value or intervening value in a stated range and any other stated or intervening value in that stated range is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included or excluded in the range, and each range where either, neither or both limits are included in the smaller ranges is also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the invention.
  • Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, some potential and preferred methods and materials are now described. All publications mentioned herein are incorporated herein by reference to disclose and describe the methods and/or materials in connection with which the publications are cited.
  • It should be noted that as used herein and in the appended claims, the singular forms “a”, “an”, and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a cell” includes a plurality of such cells and reference to “the peptide” includes reference to one or more peptides and equivalents thereof, e.g. polypeptides, known to those skilled in the art, and so forth.
  • The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. Further, the dates of publication provided may be different from the actual publication dates which may need to be independently confirmed.
  • Unless indicated otherwise, parts are parts by weight, molecular weight is weight average molecular weight, temperature is in degrees Celsius (° C.), and pressure is at or near atmospheric. Standard abbreviations are used, including the following: bp=base pair(s); kb=kilobase(s); p1=picoliter(s); s or sec=second(s); min=minute(s); h or hr=hour(s); AA or aa=amino acid(s); kb=kilobase(s); nt=nucleotide(s); pg=picogram; ng=nanogram; g=microgram; mg=milligram; g=gram; kg=kilogram; dl or dL=deciliter; μl or μL=microliter; ml or mL=milliliter; 1 or L=liter; M=micromolar; mM=millimolar; M=molar; kDa=kilodalton; i.m.=intramuscular(ly); i.p.=intraperitoneal(ly); SC or SQ=subcutaneous(ly); QD=daily; BID=twice daily; QW=once weekly; QM=once monthly; HPLC=high performance liquid chromatography; BW=body weight; U=unit; ns=not statistically significant; PBS=phosphate-buffered saline; PCR=polymerase chain reaction; HSA=human serum albumin; MSA=mouse serum albumin; DMEM=Dulbeco's Modification of Eagle's Medium; EDTA=ethylenediaminetetraacetic acid.
  • It will be appreciated that throughout this disclosure reference is made to amino acids according to the single letter or three letter codes. For the reader's convenience, the single and three letter amino acid codes are provided in the Table below:
  • TABLE
    Amino Acid Abbreviations
    G Glycine Gly
    P Proline Pro
    A Alanine Ala
    V Valine Val
    L Leucine Leu
    I Isoleucine Ile
    M Methionine Met
    C Cysteine Cys
    F Phenylalanine Phe
    Y Tyrosine Tyr
    W Tryptophan Trp
    H Histidine His
    K Lysine Lys
    R Arginine Arg
    Q Glutamine Gln
    N Asparagine Asn
    E Glutamic Acid Glu
    D Aspartic Acid Asp
    S Serine Ser
    T Threonine Thr
  • Standard methods in molecular biology are described in the scientific literature (see, e.g., Sambrook and Russell (2001) Molecular Cloning, 3rd ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.; and Ausubel, et al. (2001) Current Protocols in Molecular Biology, Vols. 1-4, John Wiley and Sons, Inc. New York, N.Y., which describes cloning in bacterial cells and DNA mutagenesis (Vol. 1), cloning in mammalian cells and yeast (Vol. 2), glycoconjugates and protein expression (Vol. 3), and bioinformatics (Vol. 4)). The scientific literature describes methods for protein purification, including immunoprecipitation, chromatography, electrophoresis, centrifugation, and crystallization, as well as chemical analysis, chemical modification, post-translational modification, production of fusion proteins, and glycosylation of proteins (see, e.g., Coligan, et al. (2000) Current Protocols in Protein Science, Vols. 1-2, John Wiley and Sons, Inc., NY).
  • Activate: As used herein the term “activate” is used in reference to a receptor or receptor complex to reflect a biological effect, directly and/or by participation in a multicomponent signaling cascade, arising from the binding of an agonist ligand to a receptor responsive to the binding of the ligand.
  • Activity: As used herein, the term “activity” is used with respect to a molecule to describe a property of the molecule with respect to a test system (e.g. an assay) or biological or chemical property (e.g. the degree of binding of the molecule to another molecule) or of a physical property of a material or cell (e.g. modification of cell membrane potential). Examples of such biological functions include but are not limited to catalytic activity of a biological agent, the ability to stimulate intracellular signaling, gene expression, cell proliferation, the ability to modulate immunological activity such as inflammatory response. “Activity” is typically expressed as a level of a biological activity per unit of agent tested such as [catalytic activity]/[mg protein], [immunological activity]/[mg protein], international units (IU) of activity, [STAT5 phosphorylation]/[mg protein], [T-cell proliferation]/[mg protein], plaque forming units (pfu), etc. As used herein, the term “proliferative activity” referes to an activity that promotes cell proliferation and replication.
  • Administer/Administration: The terms “administration” and “administer” are used interchangeably herein to refer the act of contacting a subject, including contacting a cell, tissue, organ, or biological fluid of the subject in vitro, in vivo or ex vivo with an agent (e.g. an ortholog, an IL2 ortholog, an engineered cell expressing an orthogonal receptor, an engineered cell expressing an orthogonal IL2 receptor, a CAR-T cell expressing an orthogonal IL2 receptor, a chemotherapeutic agent, an antibody, or a pharmaceutical formulation comprising one or more of the foregoing). Administration of an agent may be achieved through any of a variety of art recognized methods including but not limited to the topical administration, intravascular injection (including intravenous or intraarterial infusion), intradermal injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, inhalation and the like. The term “administration” includes contact of an agent to the cell, tissue or organ as well as the contact of an agent to a fluid, where the fluid is in contact with the cell, tissue or organ.
  • Affinity: As used herein the term “affinity” refers to the degree of specific binding of a first molecule (e.g., a ligand) to a second molecule (e.g., a receptor) and is measured by the equilibrium dissociation constant (KD), a ratio of the dissociation rate constant between the molecule and its target (Koff) and the association rate constant between the molecule and its target (Kon).
  • Agonist: As used herein, the term “agonist” refers a first agent that specifically binds a second agent (“target”) and interacts with the target to cause or promote an increase in the activation of the target. In some instances, agonists are activators of receptor proteins that modulate cell activation, enhance activation, sensitize cells to activation by a second agent, or up-regulate the expression of one or more genes, proteins, ligands, receptors, biological pathways, that may result in cell proliferation or pathways that result in cell cycle arrest or cell death such as by apoptosis. In some embodiments, an agonist is an agent that binds to a receptor and alters the receptor state, resulting in a biological response. The response mimics the effect of the endogenous activator of the receptor. The term “agonist” includes partial agonists, full agonists and superagonists. An agonist may be described as a “full agonist” when such agonist which leads to a substantially full biological response (i.e., the response associated with the naturally occurring ligand/receptor binding interaction) induced by receptor under study, or a partial agonist. In contrast to agonists, antagonists may specifically bind to a receptor but do not result the signal cascade typically initiated by the receptor and may to modify the actions of an agonist at that receptor. Inverse agonists are agents that produce a pharmacological response that is opposite in direction to that of an agonist. A “superagonist” is a type of agonist that is capable of producing a maximal response greater than the endogenous agonist for the target receptor, and thus has an activity of more than 100% of the native ligand. A super agonist is typically a synthetic molecule that exhibits greater than 110%, alternatively greater than 120%, alternatively greater than 130%, alternatively greater than 140%, alternatively greater than 150%, alternatively greater than 160%, or alternatively greater than 170% of the response in an evaluable quantitative or qualitative parameter of the naturally occurring form of the molecule when evaluated at similar concentrations in a comparable assay.
  • Antagonist: As used herein, the term “antagonist” or “inhibitor” refers a molecule that opposes the action(s) of an agonist. An antagonist prevents, reduces, inhibits, or neutralizes the activity of an agonist, and an antagonist can also prevent, inhibit, or reduce constitutive activity of a target, e.g., a target receptor, even where there is no identified agonist. Inhibitors are molecules that decrease, block, prevent, delay activation, inactivate, desensitize, or down-regulate, e.g., a gene, protein, ligand, receptor, biological pathway, or cell.
  • Antibody: As used herein, the term “antibody” refers collectively to: (a) glycosylated and non-glycosylated immunoglobulins (including but not limited to mammalian immunoglobulin classes IgG1, IgG2, IgG3 and IgG4) that specifically binds to target molecule and (b) immunoglobulin derivatives including but not limited to IgG(1-4)deltaC H2, F(ab′)2, Fab, ScFv, VH, VL, tetrabodies, triabodies, diabodies, dsFv, F(ab′)3, scFv-Fc and (scFv)2 that competes with the immunoglobulin from which it was derived for binding to the target molecule. The term antibody is not restricted to immunoglobulins derived from any particular mammalian species and includes murine, human, equine, and camelids antibodies (e.g., human antibodies). The term “antibody” encompasses antibodies isolatable from natural sources or from animals following immunization with an antigen and as well as engineered antibodies including monoclonal antibodies, bispecific antibodies, trispecific, chimeric antibodies, humanized antibodies, human antibodies, CDR-grafted, veneered, or deimmunized (e.g., to remove T-cell epitopes) antibodies. The term “human antibody” includes antibodies obtained from human beings as well as antibodies obtained from transgenic mammals comprising human immunoglobulin genes such that, upon stimulation with an antigen the transgenic animal produces antibodies comprising amino acid sequences characteristic of antibodies produced by human beings. The term “antibody” should not be construed as limited to any particular means of synthesis and includes naturally occurring antibodies isolatable from natural sources and as well as engineered antibodies molecules that are prepared by “recombinant” means including antibodies isolated from transgenic animals that are transgenic for human immunoglobulin genes or a hybridoma prepared therefrom, antibodies isolated from a host cell transformed with a nucleic acid construct that results in expression of an antibody, antibodies isolated from a combinatorial antibody library including phage display libraries.
  • Binding molecule: As used herein, the term “binding molecule” refers to a bivalent molecule that can bind to the extracellular domain of two cell surface receptors. In some embodiments, a binding molecule specifically binds to two different receptors (or domains or subunits thereof) such that the receptors (or domains or subunits) are maintained in proximity to each other such that the receptors (or domains or subunits), including domains thereof (e.g., intracellular domains) interact with each other and result in downstream signaling.
  • CDR: As used herein, the term “CDR” or “complementarity determining region” is intended to mean the non-contiguous antigen combining sites found within the variable region of both heavy and light chain immunoglobulin polypeptides. CDRs have been described by Kabat et al., J. Biol. Chem. 252:6609-6616 (1977); Kabat, et al., U.S. Dept. of Health and Human Services publication entitled “Sequences of proteins of immunological interest” (1991) (also referred to herein as “Kabat 1991” or “Kabat”); by Chothia, et al. (1987) J. Mol. Biol. 196:901-917 (also referred to herein as “Chothia”); and MacCallum, et al. (1996) J. Mol. Biol. 262:732-745, where the definitions include overlapping or subsets of amino acid residues when compared against each other. Nevertheless, application of either definition to refer to a CDR of an antibody or grafted antibodies or variants thereof is intended to be within the scope of the term as defined and used herein. The term “Chothia Numbering” as used herein is recognized in the arts and refers to a system of numbering amino acid residues based on the location of the structural loop regions (Chothiaet al. 1986, Science 233:755-758; Chothia & Lesk 1987, JMB 196:901-917; Chothia et al. 1992, JMB 227:799-817). For purposes of the present disclosure, unless otherwise specifically identified, the positioning of CDRs2 and 3 in the variable region of an antibody follows Kabat numbering or simply, “Kabat.” The positioning of CDR1 in the variable region of an antibody follows a hybrid of Kabat and Chothia numbering schemes.
  • Clonotype: A clonotype is defined as a collection of binding molecules that originate from the same B-cell progenitor cell. The term “clonotype” is used herein to refer to a collection of antigen binding molecules that belong to the same germline family, have the same CDR3 lengths, and have 70% or greater homology in CDR3 sequence
  • Comparable: As used herein, the term “comparable” is used to describe the degree of difference in two measurements of an evaluable quantitative or qualitative parameter. For example, where a first measurement of an evaluable quantitative parameter and a second measurement of the evaluable parameter do not deviate beyond a range that the skilled artisan would recognize as not producing a statistically significant difference in effect between the two results in the circumstances, the two measurements would be considered “comparable.” In some instances, measurements may be considered “comparable” if one measurement deviates from another by less than 30%, alternatively by less than 25%, alternatively by less than 20%, alternatively by less than 15%, alternatively by less than 10%, alternatively by less than 7%, alternatively by less than 5%, alternatively by less than 4%, alternatively by less than 3%, alternatively by less than 2%, or by less than 1%. In particular embodiments, one measurement is comparable to a reference standard if it deviates by less than 15%, alternatively by less than 10%, or alternatively by less than 5% from the reference standard.
  • As used herein, the term “downstream signaling” refers to the cellular signaling process that is caused by the interaction of two or more cell surface receptors that are brought into proximity of each other.
  • Effective Concentration (EC): As used herein, the terms “effective concentration” or its abbreviation “EC” are used interchangeably to refer to the concentration of an agent (e.g., an hIL2 mutein) in an amount sufficient to effect a change in a given parameter in a test system. The abbreviation “E” refers to the magnitude of a given biological effect observed in a test system when that test system is exposed to a test agent. When the magnitude of the response is expressed as a factor of the concentration (“C”) of the test agent, the abbreviation “EC” is used. In the context of biological systems, the term Emax refers to the maximal magnitude of a given biological effect observed in response to a saturating concentration of an activating test agent. When the abbreviation EC is provided with a subscript (e.g., EC40, EC50, etc.) the subscript refers to the percentage of the Emax of the biological observed at that concentration. For example, the concentration of a test agent sufficient to result in the induction of a measurable biological parameter in a test system that is 30% of the maximal level of such measurable biological parameter in response to such test agent, this is referred to as the “EC30” of the test agent with respect to such biological parameter. Similarly, the term “EC100” is used to denote the effective concentration of an agent that results the maximal (100%) response of a measurable parameter in response to such agent. Similarly, the term EC50 (which is commonly used in the field of pharmacodynamics) refers to the concentration of an agent sufficient to results in the half-maximal (50%) change in the measurable parameter. The term “saturating concentration” refers to the maximum possible quantity of a test agent that can dissolve in a standard volume of a specific solvent (e.g., water) under standard conditions of temperature and pressure. In pharmacodynamics, a saturating concentration of a drug is typically used to denote the concentration sufficient of the drug such that all available receptors are occupied by the drug, and EC50 is the drug concentration to give the half-maximal effect. The EC of a particular effective concentration of a test agent may be abbreviated with respect to the with respect to particular parameter and test system.
  • Extracellular Domain: As used herein the term “extracellular domain” or its abbreviation “ECD” refers to the portion of a cell surface protein (e.g. a cell surface receptor) which is outside of the plasma membrane of a cell. The term “ECD” may include the extra-cytoplasmic portion of a transmembrane protein or the extra-cytoplasmic portion of a cell surface (or membrane associated protein).
  • Identity: As used herein, the term “percent (%) sequence identity” or “substantially identical” used in the context of nucleic acids or polypeptides, refers to a sequence that has at least 50% sequence identity with a reference sequence. Alternatively, percent sequence identity can be any integer from 50% to 100%. In some embodiments, a sequence has at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the reference sequence as determined with BLAST using standard parameters, as described below. For sequence comparison, typically one sequence acts as a reference sequence, to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are entered into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. Default program parameters can be used, or alternative parameters can be designated. The sequence comparison algorithm then calculates the percent sequence identities for the test sequences relative to the reference sequence, based on the program parameters. A comparison window includes reference to a segment of any one of the number of contiguous positions, e.g., a segment of at least 10 residues. In some embodiments, the comparison window has from 10 to 600 residues, e.g., about 10 to about 30 residues, about 10 to about 20 residues, about 50 to about 200 residues, or about 100 to about 150 residues, in which a sequence may be compared to a reference sequence of the same number of contiguous positions after the two sequences are optimally aligned. Algorithms that are suitable for determining percent sequence identity and sequence similarity are the BLAST and BLAST 2.0 algorithms, which are described in Altschul et al. (1990) J. Mol. Biol. 215: 403-410 and Altschul et al. (1977) Nucleic Acids Res. 25: 3389-3402, respectively. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information (NCBI) web site. The algorithm involves first identifying high scoring sequence pairs (HSPs) by identifying short words of length W in the query sequence, which either match or satisfy some positive-valued threshold score T when aligned with a word of the same length in a database sequence. T is referred to as the neighborhood word score threshold (Altschul et al, supra). These initial neighborhood word hits act as seeds for initiating searches to find longer HSPs containing them. The word hits are then extended in both directions along each sequence for as far as the cumulative alignment score can be increased. Cumulative scores are calculated using, for nucleotide sequences, the parameters M (reward score for a pair of matching residues; always >0) and N (penalty score for mismatching residues; always <0). For amino acid sequences, a scoring matrix is used to calculate the cumulative score. Extension of the word hits in each direction are halted when: the cumulative alignment score falls off by the quantity X from its maximum achieved value; the cumulative score goes to zero or below, due to the accumulation of one or more negative-scoring residue alignments; or the end of either sequence is reached. The BLAST algorithm parameters W, T, and X determine the sensitivity and speed of the alignment. The BLASTN program (for nucleotide sequences) uses as defaults a word size (W) of 28, an expectation (E) of 10, M=1, N=−2, and a comparison of both strands. For amino acid sequences, the BLASTP program uses as defaults a word size (W) of 3, an expectation (E) of 10, and the BLOSUM62 scoring matrix (see Henikoff& Henikoff, Proc. Natl. Acad. Sci. USA 89:10915 (1989)). The BLAST algorithm also performs a statistical analysis of the similarity between two sequences (see, e.g., Karlin & Altschul, Proc. Nat'l. Acad. Sci. USA 90:5873-5787 (1993)). One measure of similarity provided by the BLAST algorithm is the smallest sum probability (P(N)), which provides an indication of the probability by which a match between two nucleotide or amino acid sequences would occur by chance. For example, an amino acid sequence is considered similar to a reference sequence if the smallest sum probability in a comparison of the test amino acid sequence to the reference amino acid sequence is less than about 0.01, more preferably less than about 10−5, and most preferably less than about 10−20.
  • As used herein, the term “interleukin 27 receptor” or “IL27R” refers to a heterodimeric receptor formed by subunits IL27R a (IL27Rα) and glycoprotein 130 (gp130) and bound by the ligand IL27. The human sequence of IL27Rα is listed as UniProt ID NO. Q6UWB1. The human sequence of gp130 is listed as UniProt ID NO. Q13514.
  • Intracellular Signaling: As used herein, the terms “intracellular signaling” and “downstream signaling” are used interchangeably to refer to the to the cellular signaling process that is caused by the interaction of the intracellular domains (ICDs) of two or more cell surface receptors that are in proximity of each other. In rececptor complexes via the JAK/STAT pathway, the association of the ICDS of the receptor subunits brings the JAK domains of the ICDs into proximit which initiates a phosphorylation cascade in which STAT molecules are phosphorylated and translocate to the nucleus associating with particular nucleic acid sequences resulting in the activation and expression of particular genes in the cell. The binding molecules of the present disclosure provide intraceullar signaling characteristic of the IL-27 receptor when activated by its natural cognate IL27. To measure downstream signaling activity, a number of methods are available. For example, in some embodiments, one can measure JAK/STAT signaling by the presence of phosphorylated receptors and/or phosphorylated STATs. In other embodiments, the expression of one or more downstream genes, whose expression levels can be affected by the level of downstream signalinging caused by the binding molecule, can also be measured.
  • Ligand: As used herein, the term “ligand” refers to a molecule that exhibits specific binding to a receptor and results in a change in the biological activity of the receptor so as to effect a change in the activity of the receptor to which it binds. In one embodiment, the term “ligand” refers to a molecule, or complex thereof, that can act as an agonist or antagonist of a receptor. As used herein, the term “ligand” encompasses natural and synthetic ligands. “Ligand” also encompasses small molecules, e.g., peptide mimetics of cytokines and peptide mimetics of antibodies. The complex of a ligand and receptor is termed a “ligand-receptor complex.”
  • As used herein, the term “linker” refers to a linkage between two elements, e.g., protein domains. A linker can be a covalent bond or a peptide linker. The term “bond” refers to a chemical bond, e.g., an amide bond or a disulfide bond, or any kind of bond created from a chemical reaction, e.g., chemical conjugation. The term “peptide linker” refers to an amino acid or polyeptide that may be employed to link two protein domains to provide space and/or flexibility between the two protein domains.
  • Modulate: As used herein, the terms “modulate”, “modulation” and the like refer to the ability of a test agent to affect a response, either positive or negative or directly or indirectly, in a system, including a biological system or biochemical pathway.
  • Multimerization: As used herein, the term “multimerization” refers to two or more cell surface receptors, or domains or subunits thereof, being brought in close proximity to each other such that the receptors, or domains or subunits thereof, can interact with each other and cause intracellular signaling.
  • N-Terminus: As used herein in the context of the structure of a polypeptide, “N-terminus” (or “amino terminus”) and “C-terminus” (or “carboxyl terminus”) refer to the extreme amino and carboxyl ends of the polypeptide, respectively, while the terms “N-terminal” and “C-terminal” refer to relative positions in the amino acid sequence of the polypeptide toward the N-terminus and the C-terminus, respectively, and can include the residues at the N-terminus and C-terminus, respectively. The terms “immediately N-terminal” or “immediately C-terminal” are used to refers to a position of a first amino acid residue relative to a second amino acid residue where the first and second amino acid residues are covalently bound to provide a contiguous amino acid sequence.
  • Nucleic Acid: The terms “nucleic acid”, “nucleic acid molecule”, “polynucleotide” and the like are used interchangeably herein to refer to a polymeric form of nucleotides of any length, either deoxyribonucleotides or ribonucleotides, or analogs thereof. Non-limiting examples of polynucleotides include linear and circular nucleic acids, messenger RNA (mRNA), complementary DNA (cDNA), recombinant polynucleotides, vectors, probes, primers and the
  • Operably Linked: The term “operably linked” is used herein to refer to the relationship between nucleic acid sequences encoding differing functions when combined into a single nucleic acid sequence that, when introduced into a cell, provides a nucleic acid which is capable of effecting the transcription and/or translation of a particular nucleic acid sequence in a cell. For example, DNA for a signal sequence is operably linked to DNA for a polypeptide if it is expressed as a preprotein that participates in the secretion of the polypeptide; a promoter or enhancer is operably linked to a coding sequence if it affects the transcription of the sequence; or a ribosome binding site is operably linked to a coding sequence if it is positioned so as to facilitate translation. Generally, “operably linked” means that the DNA sequences being linked are contiguous, and, in the case of a secretory leader, contiguous and in reading phase. However, certain genetic elements such as enhancers need not be contiguous with respect to the sequence to which they provide their effect.
  • Partial Agonist: As used herein, the term “partial agonist” refers to a molecule that specifically binds that bind to and activate a given receptor but possess only partial activation the receptor relative to a full agonist. Partial agonists may display both agonistic and antagonistic effects. For example, when both a full agonist and partial agonist are present, the partial agonist acts as a competitive antagonist by competing with the full agonist for the receptor binding resulting in net decrease in receptor activation relative to the contact of the receptor with the full agonist in the absence of the partial agonist. Clinically, partial agonists can be used to activate receptors to give a desired submaximal response when inadequate amounts of the endogenous ligand are present, or they can reduce the overstimulation of receptors when excess amounts of the endogenous ligand are present. The maximum response (Emax) produced by a partial agonist is called its intrinsic activity and may be expressed on a percentage scale where a full agonist produced a 100% response. A In some embodiments, the IL-27 binding molecule has a reduced Emax compared to the Emax caused by IL-27. Emax reflects the maximum response level in a cell type that can be obtained by a ligand (e.g., a binding molecule described herein or the native cytokine (e.g., IL-27)). In some embodiments, the IL-27 binding molecule described herein has at least 1% (e.g., between 1% and 100%, between 10% and 100%, between 20% and 100%, between 30% and 100%, between 40% and 100%, between 50% and 100%, between 60% and 100%, between 70% and 100%, between 80% and 100%, between 90% and 100%, between 1% and 90%, between 1% and 80%, between 1% and 70%, between 1% and 60%, between 1% and 50%, between 1% and 40%, between 10% and 30%, between 10% and 20%, or between 10% and 10%) of the Emax caused by IL-27. In other embodiments, the Emax of the IL-27 binding molecule described herein is greater (e.g., at least 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% greater) than the Emax of the natural ligand, IL-27. In some embodiments, by varying the linker length of the IL-27 binding molecule, the Emax of the IL-27 binding molecule can be changed. The IL-27 binding molecule can cause Emax in the most desired cell types, and a reduced Emax in other cell types.
  • Polypeptide: As used herein the terms “polypeptide,” “peptide,” and “protein”, used interchangeably herein, refer to a polymeric form of amino acids of any length, which can include genetically coded and non-genetically coded amino acids, chemically or biochemically modified or derivatized amino acids, and polypeptides having modified polypeptide backbones. The terms include fusion proteins, including, but not limited to, fusion proteins with a heterologous amino acid sequence; fusion proteins with heterologous and homologous leader sequences; fusion proteins with or without N-terminus methionine residues; fusion proteins with immunologically tagged proteins; fusion proteins of immunologically active proteins (e.g. antigenic diphtheria or tetanus toxin fragments) and the like.
  • As used herein the terms “prevent”, “preventing”, “prevention” and the like refer to a course of action initiated with respect to a subject prior to the onset of a disease, disorder, condition or symptom thereof so as to prevent, suppress, inhibit or reduce, either temporarily or permanently, a subject's risk of developing a disease, disorder, condition or the like (as determined by, for example, the absence of clinical symptoms) or delaying the onset thereof, generally in the context of a subject predisposed due to genetic, experiential or environmental factors to having a particular disease, disorder or condition. In certain instances, the terms “prevent”, “preventing”, “prevention” are also used to refer to the slowing of the progression of a disease, disorder or condition from a present its state to a more deleterious state.
  • Proximity: As used herein, the term “proximity” refers to the spatial proximity or physical distance between two cell surface receptors, or domains or subunits thereof, after a binding molecule described herein binds to the two cell surface receptors, or domains or subunits thereof. In some embodiments, after the binding molecule binds to the cell surface receptors, or domains or subunits thereof, the spatial proximity between the cell surface receptors, or domains or subunits thereof, can be, e.g., less than about 500 angstroms, such as e.g., a distance of about 5 angstroms to about 500 angstroms. In some embodiments, the spatial proximity amounts to less than about 5 angstroms, less than about 20 angstroms, less than about 50 angstroms, less than about 75 angstroms, less than about 100 angstroms, less than about 150 angstroms, less than about 250 angstroms, less than about 300 angstroms, less than about 350 angstroms, less than about 400 angstroms, less than about 450 angstroms, or less than about 500 angstroms. In some embodiments, the spatial proximity amounts to less than about 100 angstroms. In some embodiments, the spatial proximity amounts to less than about 50 angstroms. In some embodiments, the spatial proximity amounts to less than about 20 angstroms. In some embodiments, the spatial proximity amounts to less than about 10 angstroms. In some embodiments, the spatial proximity ranges from about 10 to 100 angstroms, from about 50 to 150 angstroms, from about 100 to 200 angstroms, from about 150 to 250 angstroms, from about 200 to 300 angstroms, from about 250 to 350 angstroms, from about 300 to 400 angstroms, from about 350 to 450 angstroms, or about 400 to 500 angstroms. In some embodiments, the spatial proximity amounts to less than about 250 angstroms, alternatively less than about 200 angstroms, alternatively less than about 150 angstroms, alternatively less than about 120 angstroms, alternatively less than about 100 angstroms, alternatively less than about 80 angstroms, alternatively less than about 70 angstroms, or alternatively less than about 50 angstroms.
  • Receptor: As used herein, the term “receptor” refers to a polypeptide having a domain that specifically binds a ligand that binding of the ligand results in a change to at least one biological property of the polypeptide. In some embodiments, the receptor is a “soluble” receptor that is not associated with a cell surface. In some embodiments, the receptor is a cell surface receptor that comprises an extracellular domain (ECD) and a membrane associated domain which serves to anchor the ECD to the cell surface. In some embodiments of cell surface receptors, the receptor is a membrane spanning polypeptide comprising an intracellular domain (ICD) and extracellular domain (ECD) linked by a membrane spanning domain typically referred to as a transmembrane domain (TM). The binding of the ligand to the receptor results in a conformational change in the receptor resulting in a measurable biological effect. In some instances, where the receptor is a membrane spanning polypeptide comprising an ECD, TM and ICD, the binding of the ligand to the ECD results in a measurable intracellular biological effect mediated by one or more domains of the ICD in response to the binding of the ligand to the ECD. In some embodiments, a receptor is a component of a multi-component complex to facilitate intracellular signaling. For example, the ligand may bind a cell surface molecule having not associated with any intracellular signaling alone but upon ligand binding facilitates the formation of a multimeric complex that results in intracellular signaling.
  • Recombinant: As used herein, the term “recombinant” is used as an adjective to refer to the method by a polypeptide, nucleic acid, or cell that was modified using recombinant DNA technology. A recombinant protein is a protein produced using recombinant DNA technology and may be designated as such using the abbreviation of a lower case “r” (e.g., rhIL2) to denote the method by which the protein was produced. Similarly, a cell is referred to as a “recombinant cell” if the cell has been modified by the incorporation (e.g., transfection, transduction, infection) of exogenous nucleic acids (e.g., ssDNA, dsDNA, ssRNA, dsRNA, mRNA, viral or non-viral vectors, plasmids, cosmids and the like) using recombinant DNA technology. The techniques and protocols for recombinant DNA technology are well known in the art such as those can be found in Sambrook, et al. (1989) Molecular Cloning: A Laboratory Manual (2d ed., Cold Spring Harbor Laboratory Press, Plainview, N.Y.) and other standard molecular biology laboratory manuals.
  • Response: The term “response,” for example, of a cell, tissue, organ, or organism, encompasses a quantitative or qualitative change in a evaluable biochemical or physiological parameter, (e.g., concentration, density, adhesion, proliferation, activation, phosphorylation, migration, enzymatic activity, level of gene expression, rate of gene expression, rate of energy consumption, level of or state of differentiation, where the change is correlated with activation, stimulation, or treatment, or with internal mechanisms such as genetic programming. In certain contexts, the terms “activation”, “stimulation”, and the like refer to cell activation as regulated by internal mechanisms, as well as by external or environmental factors. In contrast, the terms “inhibition”, “down-regulation” and the like refer to the opposite effects.
  • Single Domain Antibody (sdAb): The term “single-domain antibody” or “sdAbs,” refers to an antibody having a single (only one) monomeric variable antibody domain. A sdAb is able to bind selectively to a specific antigen. A VHH antibody, further defined below, is an example of a sdAb.
  • Specifically Binds: As used herein, the term “specifically bind” refers to the degree of selectivity or affinity for which one molecule binds to another. In the context of binding pairs (e.g., a binding molecule described herein/receptor, a ligand/receptor, antibody/antigen, antibody/ligand, antibody/receptor binding pairs), a first molecule of a binding pair is said to specifically bind to a second molecule of a binding pair when the first molecule of the binding pair does not bind in a significant amount to other components present in the sample. A first molecule of a binding pair is said to specifically bind to a second molecule of a binding pair when the affinity of the first molecule for the second molecule is at least two-fold greater, alternatively at least five times greater, alternatively at least ten times greater, alternatively at least 20-times greater, or alternatively at least 100-times greater than the affinity of the first molecule for other components present in the sample.
  • Stably Associated: As used herein, the term “stably associated” or “in stable association with” are used to refer to the various means by which one molecule (e.g., a polypeptide) may be associated with another molecule over an extended period of time. The stable association of one molecule to another may be effected by a variety of means, including covalent bonding and non-covalent interactions. In some embodiments, stable association of two molecules may be effected by covalent bonds such as peptide bonds. In other embodiments, stable association of two molecules may be effected b non-covalent interactions. Examples of non-covalent interactions which may provide a a stable association between two molecules include electrostatic interactions (e.g., hydrogen bonding, ionic bonding, halogen binding, dipole-dipole interactions, Van der Waals forces and π-effects including cation-π interactions, anion-π interactions and π-π interactions) and hydrophobilic/hydrophilic interactions. In some embodiments, the stable association of sdAbs of the bivalent binding molecules of the present disclosure may be effected by non-covalent interactions. In one embodiment, the non-covalent stable association of the sdAbs of the bivalent binding molecules may be achieved by conjugation of the sdAbs to “knob-into-hole” modified Fc monomers. An Fe “knob” monomer stably associates non-covalently with an Fe “hole” monomer. Conjugation of a first sdAb which specifically binds to the extracellular domain of a first subunit of a heterodimeric receptor to an “Fc knob” monomer and conjugation of an second sdAb which specifically binds to the extracellular domain of a second subunit of a heterodimeric receptor to an “Fe hole” monomer provides stable association of the first and second sdAbs. The knob-into-hole modification is more fully described in Ridgway, et al. (1996) Protein Engineering 9(7):617-621 and U.S. Pat. No. 5,731,168, issued Mar. 24, 1998, U.S. Pat. No. 7,642,228, issued Jan. 5, 2010, U.S. Pat. No. 7,695,936, issued Apr. 13, 2010, and U.S. Pat. No. 8,216,805, issued Jul. 10, 2012. The knob-into-hole modification refers to a modification at the interface between two immunoglobulin heavy chains in the CH3 domain, wherein: i) in a CH3 domain of a first heavy chain, an amino acid residue is replaced with an amino acid residue having a larger side chain (e.g., tyrosine or tryptophan) creating a projection from the surface (“knob”) and ii) in the CH3 domain of a second heavy chain, an amino acid residue is replaced with an amino acid residue having a smaller side chain (e.g., alanine or threonine), thereby generating a cavity (“hole”) within at interface in the second CH3 domain within which the protruding side chain of the first CH3 domain (“knob”) is received by the cavity in the second CH3 domain. In one embodiment, the “knob-into-hole modification” comprises the amino acid substitution T366W and optionally the amino acid substitution S354C in one of the antibody heavy chains, and the amino acid substitutions T366S, L368A, Y407V and optionally Y349C in the other one of the antibody heavy chains. Furthermore, the Fc domains may be modified by the introduction of cysteine residues at positions S354 on one chain and Y349 on the second chain which results in a stabilizing disulfide bridge between the two antibody heavy chains in the Fc region (Carter, et al. (2001) Immunol Methods 248, 7-15). The knob-into-hole format is used to facilitate the expression of a first polypeptide (e.g., an IL27Rα binding sdAb) on a first Fe monomer with a “knob” modification and a second polypeptide on the second Fc monomer possessing a “hole” modification to facilitate the expression of heterodimeric polypeptide conjugates.
  • Subject: The terms “recipient”, “individual”, “subject”, and “patient”, are used interchangeably herein and refer to any mammalian subject for whom diagnosis, treatment, or therapy is desired, particularly humans. “Mammal” for purposes of treatment refers to any animal classified as a mammal, including humans, domestic and farm animals, and zoo, sports, or pet animals, such as dogs, horses, cats, cows, sheep, goats, pigs, etc. In some embodiments, the mammal is a human being.
  • Substantially: As used herein, the term “substantially” refers to a quantity, level, value, number, frequency, percentage, dimension, size, amount, weight or length that is 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or higher of a reference quantity, level, value, number, frequency, percentage, dimension, size, amount, weight or length. In one embodiment, “substantially the same” refers to a quantity, level, value, number, frequency, percentage, dimension, size, amount, weight or length that produces an effect, e.g., a physiological effect, that is approximately the same as a reference quantity, level, value, number, frequency, percentage, dimension, size, amount, weight or length.
  • Suffering From: As used herein, the term “suffering from” refers to a determination made by a physician with respect to a subject based on the available information accepted in the field for the identification of a disease, disorder or condition including but not limited to X-ray, CT-scans, conventional laboratory diagnostic tests (e.g., blood count), genomic data, protein expression data, immunohistochemistry, that the subject requires or will benefit from treatment. The term suffering from is typically used in conjunction with a particular disease state such as “suffering from a neoplastic disease” refers to a subject which has been diagnosed with the presence of a neoplasm.
  • Therapeutically Effective Amount: As used herein, the term The phrase “therapeutically effective amount” is used in reference to the administration of an agent to a subject, either alone or as part of a pharmaceutical composition or treatment regimen, in a single dose or as part of a series of doses in an amount capable of having any detectable, positive effect on any symptom, aspect, or characteristic of a disease, disorder or condition when administered to the subject. The therapeutically effective amount can be ascertained by measuring relevant physiological effects, and it may be adjusted in connection with a dosing regimen and in response to diagnostic analysis of the subject's condition, and the like. The parameters for evaluation to determine a therapeutically effective amount of an agent are determined by the physician using art accepted diagnostic criteria including but not limited to indicia such as age, weight, sex, general health, ECOG score, observable physiological parameters, blood levels, blood pressure, electrocardiogram, computerized tomography, X-ray, and the like. Alternatively, or in addition, other parameters commonly assessed in the clinical setting may be monitored to determine if a therapeutically effective amount of an agent has been administered to the subject such as body temperature, heart rate, normalization of blood chemistry, normalization of blood pressure, normalization of cholesterol levels, or any symptom, aspect, or characteristic of the disease, disorder or condition, modification of biomarker levels, increase in duration of survival, extended duration of progression free survival, extension of the time to progression, increased time to treatment failure, extended duration of event free survival, extension of time to next treatment, improvement objective response rate, improvement in the duration of response, and the like that that are relied upon by clinicians in the field for the assessment of an improvement in the condition of the subject in response to administration of an agent.
  • Treat: The terms “treat”, “treating”, treatment” and the like refer to a course of action (such as administering a binding molecule described herein, or a pharmaceutical composition comprising same) initiated with respect to a subject after a disease, disorder or condition, or a symptom thereof, has been diagnosed, observed, or the like in the subject so as to eliminate, reduce, suppress, mitigate, or ameliorate, either temporarily or permanently, at least one of the underlying causes of such disease, disorder, or condition afflicting a subject, or at least one of the symptoms associated with such disease, disorder, or condition. The treatment includes a course of action taken with respect to a subject suffering from a disease where the course of action results in the inhibition (e.g., arrests the development of the disease, disorder or condition or ameliorates one or more symptoms associated therewith) of the disease in the subject.
  • VHH: As used herein, the term “VHH” is a type of sdAb that has a single monomeric heavy chain variable antibody domain. Such antibodies can be found in or produced from Camelid mammals (e.g., camels, llamas) which are naturally devoid of light chainsVHHs can be obtained from immunization of camelids (including camels, llamas, and alpacas (see, e.g., Hamers-Casterman, et al. (1993) Nature 363:446-448) or by screening libraries (e.g., phage libraries) constructed in VHH frameworks. Antibodies having a given specificity may also be derived from non-mammalian sources such as VHHs obtained from immunization of cartilaginous fishes including, but not limited to, sharks. In a particular embodiment, a VHH in a bispecific VHH2 binding molecule described herein binds to a receptor (e.g., the first receptor or the second receptor of the natural or non-natural receptor pairs) if the equilibrium dissociation constant between the VHH and the receptor is greater than about 10−6M, alternatively greater than about 10−8 M, alternatively greater than about 10−10 M, alternatively greater than about 10−11 M, alternatively greater than about 10−10 M, greater than about 10−12 M as determined by, e.g., Scatchard analysis (Munsen, et al. 1980 Analyt. Biochem. 107:220-239). Standardized protocols for the generation of single domain antibodies from camelids are well known in the scientific literature. See, e.g., Vincke, et al (2012) Chapter 8 in Methods in Molecular Biology, Walker, J. editor (Humana Press, Totowa NJ). Specific binding may be assessed using techniques known in the art including but not limited to competition ELISA, BIACORE® assays and/or KINEXA® assays. In some embodiments, a VHH described herein can be humanized to contain human framework regions. Examples of human germlines that could be used to create humanized VHHs include, but are not limited to, VH3-23 (e.g., UniProt ID: P01764), VH3-74 (e.g., UniProt ID: A0A0B4J1X5), VH3-66 (e.g., UniProt ID: A0A0C4DH42), VH3-30 (e.g., UniProt ID: P01768), VH3-11 (e.g., UniProt ID: P01762), and VH3-9 (e.g., UniProt ID: P01782).
  • VHH2: As used herein, the term “VHH2” and “bispecific VHH2” and “VHH dimer” refers to are used interchangeably to refer to a subtype of the binding molecules of the present disclosure wherein the first and second sdAbs are both VHHs and first VHH binding to a first receptor, or domain or subunit thereof, and a second VHH binding to a second receptor, or domain or subunit thereof.
  • Wild Type: As used herein, the term “wild type” or “WT” or “native” is used to refer to an amino acid sequence or a nucleotide sequence that is found in nature and that has not been altered by the hand of man.
    • III. IL27 Receptor Binding Proteins
  • The IL27 receptor (IL27R) includes IL27Rα subunit (IL27Rα) and glycoprotein 130 subunit (gp130). Provided herein is an IL27R binding protein that specifically binds to IL27Ra and gp130. In some embodiments, the IL27R binding protein binds to a mammalian cell expressing both IL27Rα and gp130. In some embodiments, the IL27R binding protein can be a bispecific VHH2 as described below.
  • The IL27R binding protein can be a bispecific VHH2 that has a first VHH binding to IL27Rα (an anti-IL27Rα VHH antibody) and a second VHH binding to gp130 (an anti-gp130 VHH antibody) and causes the dimerization of the two receptor subunits and downstream signaling when bound to a cell expressing IL27Rα and gp130, e.g., a CD8+ T cells, a CD4+ T cells, and/or a T regulatory (Treg) cell.
  • A VHH is a type of single-domain antibody (sdAb) containing a single monomeric variable antibody domain. Like a full-length antibody, it is able to bind selectively to a specific antigen. The complementary determining regions (CDRs) of VHHs are within a single-domain polypeptide. VHHs can be engineered from heavy-chain antibodies found in camelids.
  • An exemplary VHH has a molecular weight of approximately 12-15 kDa which is much smaller than traditional mammalian antibodies (150-160 kDa) composed of two heavy chains and two light chains. VHHs can be found in or produced from Camelidae mammals (e.g., camels, llamas, dromedary, alpaca, and guanaco) which are naturally devoid of light chains. Descriptions of sdAbs and VHHS can be found in, e.g., De Greve et al., Curr Opin Biotechnol. 61:96-101, 2019; Ciccarese, et al., Front Genet. 10:997, 2019; Chanier and Chames, Antibodies (Basel) 8(1), 2019; and De Vlieger et al., Antibodies (Basel) 8(1), 2018.
  • To prepare a binding protein that is a bispecific VHH2, in some embodiments, the two VHHs can be synthesized separately, then joined together by a linker. Alternatively, the bispecific VHH2 can be synthesized as a fusion protein. VHHs having different binding activities and receptor targets can be paired to make a bispecific VHH2. The binding proteins can be screened for signal transduction on cells carrying one or both relevant receptors.
  • In some embodiments, a bispecific VHH2 comprises:
      • A first VHH antibody comprising a CDR1 having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity, or having 0, 1, 2, or 3 amino acid changes, optionally conservative amino acid changes relative, to the sequence of a CDR1 from a row of Table 1A; a CDR2 having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity, or having 0, 1, 2, or 3 amino acid changes, optionally conservative amino acid changes relative, to the sequence of a CDR2 from the same row of Table 1A; and a CDR3 having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity, or having 0, 1, 2, or 3 amino acid changes, optionally conservative amino acid changes relative, to the sequence of a CDR3 from the same row of Table 1A; and
      • a second VHH antibody comprising a CDR1 having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity, or having 0, 1, 2, or 3 amino acid changes, optionally conservative amino acid changes relative, to the sequence of a CDR4 from the same row of Table 1A; a CDR2 having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity, or having 0, 1, 2, or 3 amino acid changes, optionally conservative amino acid changes relative, to the sequence of a CDR5 from the same row of Table 1A; and a CDR3 having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity, or having 0, 1, 2, or 3 amino acid changes optionally conservative amino acid changes relative, to the sequence of a CDR6 from the same row of Table TA. In some embodiments, the bispecific VHH2 comprises a sequence at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) identical to any one of the dual VHH dimer sequences shown in Table TA.
  • In some embodiments, a VHH described herein can be humanized to contain human framework regions. Examples of human germlines that could be used to create humanized VHHs include, but are not limited to, VH43-23 (e.g., UniProt ID: P01764), VH43-74 (e.g., UniProtID: A0A0B4JTX5), VH43-66 (e.g., UniProtID: A0A0C4DH42), VH43-30 (e.g., UniProt ID: P01768), VH43-11 (e.g., UniProt ID: P01762), and VH43-9 (e.g., UniProt ID: P01782).
  • Lengthy table referenced here
    US20240002542A1-20240104-T00001
    Please refer to the end of the specification for access instructions.
  • In some embodiments, an IL27R binding protein described herein (e.g., in Table TA) is encoded by an isolated nucleic acid that is substantially identical to a sequence of any one of Table 1B below. In some embodiments, an IL27R binding protein described herein (e.g., an IL27R binding protein comprising a sequence of Table TA) is encoded by an isolated nucleic acid comprising a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity to a sequence of Table 1B below.
  • TABLE 1B
    SEQ
    ID
    Name NO: Sequence
    DR591- 955 CAGGTTCAGCTCCAGGAGAGCGGCGGGGGCTCCGTGCAGGCTGGCGGATCACTG
    hIL27 CGTCTGTCCTGTACTGCGAGCGGCGCTATCGCGAGCGGGTACATTGATAGCAGA
    Ra_VH TGGTGTATGGCTTGGTTCCGTCAGGCACCAGGCAAGGAGCGTGAGGGCGTGGCA
    H1 GCTATCTGGCCTGGAGGGGGTCTCACCGTGTACGCCGACTCCGTGAAGGGCCGT
    TTCACAATTAGTAGAGACCATGCCAAGAATACGCTCTATCTTCAGATGAATAAC
    CTGAAACCCGAGGATACGGCTATGTACTATTGTGCTGCGGGATCACCCCGGATG
    TGCCCGTCTCTGGAGTTTGGATTCGACTATTGGGGACAGGGGACCCAGGTCACC
    GTCAGTTCCGGTGGGGGCTCCCAAGTCCAGCTCCAGGAGTCCGGCGGGGGCTTG
    GTCCAGCCCGGAGGCTCCCTCCGCCTGAGTTGTGCTGCCAGCGGATTCACTTTT
    TCCAGTTACCCTATGTCCTGGGTGAGACAGGCCCCTGGGAAGGGCCTGGAGTGG
    ATCTCTACCATCAGCGCGGGCGGGGATACCACTCTGTATGCCGACTCAGTGAAG
    GGCAGGTTCACGTCTTCCCGCGATAACGCTAAGAATACTCTCTATCTGCAACTC
    AATTCCCTGAAGACAGAGGACGCAGCTATCTACTATTGTGCTAAGCGTATTGAT
    TGCAACAGCGGATACTGCTACCGTAGGAACTATTGGGGCCAGGGCACCCAGGTG
    ACTGTGTCCTCC
    DR591- 956 CAGGTACAGCTCCAGGAGTCTGGTGGAGGCTCTGTGCAAGCAGGGGGTAGCCTG
    hIL27 AGGCTGTCATGCACAGCCTCCGGTGCCATCGCCAGCGGTTACATTGACAGCAGG
    Ra_VH TGGTGTATGGCTTGGTTCAGGCAGGCCCCCGGCAAAGAACGTGAAGGCGTGGCC
    H1 GCTATCTGGCCCGGCGGTGGACTGACTGTCTATGCCGATAGTGTGAAAGGCAGA
    TTCACCATCTCTCGGGATCACGCGAAGAATACACTGTACCTTCAGATGAATAAC
    CTGAAGCCTGAGGACACCGCCATGTACTATTGCGCTGCGGGCTCTCCGAGGATG
    TGCCCCAGCCTGGAGTTCGGGTTCGATTATTGGGGTCAGGGCACCCAAGTGACT
    GTGAGCAGTGGGGGATCTGGCGGGTCCGGTGGCTCTGGTCAGGTGCAGCTGCAA
    GAGTCTGGAGGGGGCCTCGTACAACCTGGAGGTAGTCTGCGCCTCAGTTGTGCT
    GCATCTGGCTTCACCTTCAGCTCCTATCCCATGTCTTGGGTTCGGCAGGCTCCC
    GGCAAGGGGCTGGAGTGGATCTCCACCATCAGCGCGGGCGGGGACACAACTCTG
    TACGCCGATTCTGTGAAGGGGCGTTTCACAAGCTCAAGAGATAACGCAAAAAAC
    ACGCTCTACCTCCAGCTTAATTCATTGAAGACCGAAGACGCAGCTATTTATTAC
    TGCGCTAAGCGCATCGACTGTAACTCCGGCTACTGCTATAGAAGGAATTACTGG
    GGCCAGGGAACACAGGTTACCGTGAGTTCA
    DR591- 957 CAGGTGCAGCTCCAGGAGTCCGGTGGCGGAAGCGTCCAGGCTGGCGGAAGTCTG
    hIL27 AGGCTCTCATGCACCGCCTCTGGTGCCATCGCCAGCGGATACATCGACTCCAGA
    Ra_VH TGGTGTATGGCTTGGTTTAGGCAAGCCCCTGGCAAGGAAAGGGAGGGGGTTGCT
    H2 GCCATCTGGCCCGGCGGAGGCCTGACGGTGTATGCAGACAGCGTCAAAGGGAGA
    TTCACCATTTCTCGCGACCACGCTAAGAACACCCTTTACTTGCAGATGAATAAC
    CTCAAGCCCGAGGACACCGCCATGTATTACTGCGCCGCTGGTTCACCGAGGATG
    TGCCCGAGCCTGGAGTTCGGCTTCGACTACTGGGGCCAAGGTACACAAGTGACT
    GTGTCCAGCGGCGGGGGTAGCCAGGTTCAGCTGCAAGAGAGCGGCGGTGGATTG
    GTGCAGCCAGGCGGTAGCCTGCGCCTGTCTTGCGCGGCCAGCGGATTCACATTC
    TCCCTGAGCGGCATGTCTTGGGTGCGCCAAGCTCCGGGCAAAGGCCTGGAGTGG
    GTCAGCGCCATCTCTAGCGGAGGTGCCTCTACGTATTACACAGATTCCGTTAAG
    GGCCGCTTCACTATCAGCCGCGATAACGCCAAGAACATCCTGTATCTCCAGTTG
    AACAGCCTGAAAACGGAGGACACAGCCATGTACTATTGCGCTAAAGGGGGTTCA
    GGCTATGGTGACGCTTCTCGCATGACCTCACCCGGCTCACAGGGAACCCAGGTG
    ACAGTGTCAAGT
    DR591- 958 CAGGTGCAGCTGCAAGAGTCCGGCGGAGGTAGCGTTCAAGCCGGAGGCTCACTG
    hIL27 AGACTGTCTTGCACCGCCTCTGGTGCAATCGCCTCTGGCTATATTGATTCTCGC
    Ra_VH TGGTGTATGGCGTGGTTTAGGCAAGCGCCTGGGAAAGAGCGTGAAGGAGTTGCA
    H2 GCCATCTGGCCGGGAGGCGGACTGACCGTGTACGCTGACTCTGTGAAGGGCAGA
    TTCACCATCAGTCGTGACCACGCCAAGAACACTCTGTACCTTCAGATGAATAAC
    CTCAAACCAGAGGACACAGCTATGTACTATTGTGCGGCTGGATCTCCGCGCATG
    TGCCCTAGTCTGGAGTTCGGTTTTGATTACTGGGGCCAGGGAACTCAAGTGACC
    GTGTCTAGCGGCGGTTCTGGAGGCAGTGGTGGGTCAGGTCAGGTTCAGCTCCAA
    GAGTCAGGTGGGGGACTCGTGCAACCAGGGGGCTCCCTGCGCCTGTCTTGCGCT
    GCCTCCGGCTTCACTTTCAGCCTGAGCGGTATGTCCTGGGTTCGCCAGGCTCCT
    GGTAAAGGGCTGGAGTGGGTTAGTGCTATCAGCTCCGGCGGAGCTTCTACCTAT
    TACACCGACTCTGTTAAGGGTCGCTTCACTATCAGCCGCGACAACGCCAAAAAT
    ATTTTGTATCTGCAACTCAACTCCTTGAAGACAGAGGACACCGCGATGTATTAC
    TGCGCCAAGGGAGGTAGCGGCTACGGCGATGCTAGTCGTATGACGAGCCCCGGC
    TCTCAGGGTACACAAGTCACCGTAAGCTCC
    DR591- 959 CAGGTTCAGTTGCAGGAGTCTGGCGGAGGGAGCGTTCAGGCTGGCGGTTCCCTG
    hIL27- AGGCTCTCTTGCACAGCCTCTGGCGCTATCGCCTCAGGATATATTGATTCCCGT
    Ra_ TGGTGTATGGCATGGTTCCGTCAGGCCCCTGGCAAGGAACGCGAGGGAGTCGCT
    VH GCCATCTGGCCCGGCGGGGGCCTGACAGTCTACGCTGATTCAGTTAAGGGCCGC
    H3 TTCACTATCAGCCGCGACCACGCTAAAAACACGCTGTACCTGCAAATGAATAAC
    CTCAAACCAGAGGACACTGCAATGTATTACTGCGCCGCAGGCTCTCCCAGAATG
    TGCCCGAGCCTGGAGTTTGGTTTCGATTACTGGGGTCAGGGCACGCAGGTAACC
    GTGAGTTCTGGTGGAGGCTCCCAGGTGCAGCTCCAAGAGTCCGGGGGAGGCTCT
    GTGCAAGCAGGCGGAAGCCTGAGATTGTCCTGCGTGGCCAGCGGTTATGTGTCC
    TGTGATTACTTCCTGCCTTCTTGGTATCGGCAGGCCCCAGGCAAGGAGCGCGAG
    TTCGTCTCCATCATTGATGGCACCGGATCAACAAGCTACGCTGCGTCCGTGAAG
    GGTCGGTTTACAGCAAGCGAGGATAAGGGAAAGAACATCGCGTACCTCCAGATG
    AACAGCCTGAAGCCTGAAGACACTGCTATGTATTACTGTAAGGCTAGTTGTGTG
    CGGGGCCGCGCAGTTTCTGAATATTGGGGTCAGGGAACACAAGTAACCGTGTCT
    TCA
    DR591- 960 CAGGTCCAGCTCCAGGAATCAGGAGGTGGCTCCGTACAGGCCGGAGGGAGTCTC
    hIL27 CGCCTCTCCTGTACTGCCAGTGGTGCCATCGCAAGCGGCTATATCGACAGCCGT
    Ra_ TGGTGCATGGCCTGGTTCAGGCAGGCACCCGGCAAAGAGAGAGAAGGAGTCGCT
    VH GCGATCTGGCCGGGTGGAGGTTTGACCGTCTACGCCGACAGCGTCAAGGGCAGA
    H3 TTTACTATCAGCCGTGACCACGCGAAGAACACCCTCTATCTTCAGATGAATAAC
    CTCAAACCTGAGGATACCGCCATGTATTACTGCGCAGCCGGGAGCCCTCGGATG
    TGCCCTAGCCTGGAGTTCGGCTTCGACTACTGGGGCCAAGGGACACAGGTAACA
    GTTAGTAGCGGTGGCTCCGGTGGCTCCGGGGGTTCTGGTCAGGTCCAGCTCCAG
    GAGTCTGGAGGCGGTTCAGTGCAGGCTGGCGGTTCACTGCGCCTCAGCTGCGTG
    GCCTCCGGCTACGTATCATGCGACTATTTCCTGCCCTCCTGGTATCGCCAGGCC
    CCCGGAAAAGAGAGGGAGTTTGTGTCTATTATCGACGGGACCGGAAGCACCAGC
    TACGCTGCCTCAGTGAAGGGTCGCTTCACCGCCTCCGAGGATAAGGGCAAGAAC
    ATTGCCTACTTGCAGATGAACTCATTGAAACCGGAAGACACTGCGATGTATTAC
    TGTAAGGCTTCTTGCGTTCGCGGACGTGCTGTGAGCGAGTACTGGGGCCAAGGG
    ACCCAAGTGACGGTCTCTTCT
    DR591- 961 CAGGTGCAACTTCAGGAGTCTGGCGGTGGCAGCGTGCAGGCCGGGGGCTCCCTG
    hIL27 CGGCTGTCATGTACGGCCTCCGGCGCTATTGCCAGCGGTTACATTGACTCCAGG
    Ra_ TGGTGCATGGCCTGGTTCCGTCAGGCTCCGGGCAAGGAGAGGGAAGGCGTGGCA
    VH GCCATCTGGCCCGGCGGGGGCCTCACCGTTTATGCCGATTCCGTGAAGGGACGT
    H4 TTTACAATCAGCCGTGACCATGCTAAGAACACCCTGTATTTGCAGATGAATAAC
    CTGAAACCCGAGGACACCGCCATGTATTACTGCGCCGCAGGCAGCCCCCGTATG
    TGCCCGTCCCTGGAGTTTGGCTTCGATTACTGGGGCCAGGGGACCCAGGTGACA
    GTCAGCTCCGGGGGTGGCTCTCAGGTGCAACTTCAGGAATCCGGTGGAGGTCTG
    GTGCAGCCGGGAGAGTCTCTGCGTCTGTCATGCACTGCCTCAGGCTTCACGTTT
    AGTAACTATGCTATGTCCTGGGTGAGGCAAGCTCCTGGAAAGGGCCTCGAATGG
    GTGTCAGGAATCAACGTGGCCTACGGCATTACTTCTTATGCCGATTCTGTTAAG
    GGTCGCTTCACTATCTCAAGAGACAACACTAAAAACACTCTTTACTTGCAGCTG
    AACAGCCTGAAAACAGAGGACACAGCCATTTATTACTGCGTGAAGCACTCTGGC
    ACAACCATCCCACGCGGTTTCATTTCATACACGAAGCGCGGCCAGGGGACCCAG
    GTGACTGTGAGCAGC
    DR591- 962 CAGGTCCAACTTCAGGAATCTGGAGGTGGCTCAGTACAGGCTGGAGGCTCCCTG
    hIL27 AGACTGAGCTGCACCGCCTCAGGAGCAATCGCATCCGGCTATATCGACTCCCGT
    Ra_VH TGGTGTATGGCCTGGTTTCGCCAGGCCCCCGGCAAGGAGCGTGAGGGCGTGGCC
    H4 GCTATCTGGCCAGGCGGGGGCCTGACCGTGTACGCTGACAGTGTTAAAGGAAGG
    TTCACAATTTCCCGCGATCACGCTAAGAATACATTGTATCTTCAGATGAATAAC
    CTCAAGCCAGAGGACACCGCCATGTATTACTGCGCAGCCGGTTCACCCCGCATG
    TGCCCCAGCCTGGAGTTCGGCTTCGACTACTGGGGACAGGGCACCCAGGTTACC
    GTGTCTTCCGGCGGTTCTGGCGGATCTGGTGGCTCCGGGCAGGTGCAGCTCCAG
    GAATCTGGTGGGGGCCTGGTTCAGCCGGGTGAAAGCCTGAGGCTGTCTTGCACC
    GCCTCTGGTTTCACCTTCAGCAACTATGCGATGTCTTGGGTGCGGCAAGCACCG
    GGTAAGGGCCTGGAGTGGGTGAGCGGCATCAACGTGGCCTACGGTATTACAAGC
    TACGCCGATTCCGTTAAAGGTCGTTTCACCATCTCTAGGGACAACACAAAGAAC
    ACACTGTACTTGCAGCTGAACTCTCTGAAGACCGAAGATACCGCCATCTATTAC
    TGTGTGAAGCATTCCGGCACAACCATCCCTCGCGGCTTCATCTCCTATACCAAG
    CGCGGCCAGGGCACCCAGGTCACGGTTTCCTCC
    DR591- 963 CAGGTGCAGCTGCAAGAGTCCGGTGGCGGGTCCGTCCAGGCCGGGGGCTCTCTG
    hIL27 CGTCTTAGCTGCACCGCTTCTGGGGCCATTGCTTCTGGCTACATTGATTCCAGA
    Ra_VH TGGTGTATGGCCTGGTTCCGCCAAGCGCCCGGCAAGGAGCGCGAGGGCGTGGCC
    H5 GCTATCTGGCCCGGTGGAGGCCTTACCGTCTATGCTGACAGCGTGAAAGGACGC
    TTCACCATCTCCCGCGACCACGCCAAAAACACCCTGTACTTGCAGATGAACAAT
    TTGAAGCCCGAGGACACGGCCATGTATTACTGCGCCGCTGGTAGCCCCCGCATG
    TGTCCGTCCCTGGAGTTCGGTTTCGACTACTGGGGGCAGGGCACCCAGGTGACA
    GTCAGCTCTGGAGGGGGCTCCCAGGTGCAGCTCCAGGAGAGCGGCGGAGGCAGC
    GTGCAGGCCGGGGGAAGCCTCAGGCTGAGCTGCACCGCGAGCGGCTACGTTTCC
    TGTGATTATTTTCTCCCATCATGGTATCGCCAAGCGCCAGGAAAGGAGCGTGAG
    TTCGTATCCGTGATTGACGGTACAGGTTCAACATCCTATGCGGCCTCTGTGAAG
    GGGCGCTTCACCGCGAGCCAAGATAAGGGGAAGAACATCGCCTATTTGCAGATG
    AACTCACTGAAGCCTGAGGACACCGCTATGTATTACTGCAAGGCTTCCTGTGTG
    CGTGGCCGCGCCATCTCTGAGTACTGGGGGCAGGGCACCCAGGTGACCGTGTCC
    TCC
    DR591- 964 CAGGTGCAGCTGCAAGAATCTGGAGGCGGTAGCGTACAGGCAGGTGGCAGCCTG
    hIL27 AGGCTGTCTTGTACTGCGTCCGGCGCTATCGCATCAGGATACATTGACTCACGT
    Ra_VH TGGTGCATGGCCTGGTTTCGTCAGGCTCCAGGAAAGGAGCGTGAAGGCGTCGCT
    H5 GCCATTTGGCCTGGTGGAGGCCTGACCGTGTATGCCGATAGCGTCAAGGGACGT
    TTCACCATCAGCCGTGACCACGCTAAGAATACCCTGTACTTGCAAATGAACAAT
    TTGAAGCCAGAGGACACTGCGATGTACTATTGCGCGGCAGGCTCCCCCAGGATG
    TGTCCCAGCCTGGAGTTTGGTTTCGATTACTGGGGGCAGGGCACCCAGGTCACC
    GTTAGCTCCGGGGGTTCTGGAGGTTCCGGCGGTTCAGGACAGGTGCAGCTTCAG
    GAGTCTGGGGGAGGGTCCGTACAAGCCGGGGGCTCCTTGCGCCTGTCTTGCACA
    GCTTCCGGCTATGTTAGTTGTGACTACTTCCTGCCTAGCTGGTATCGCCAAGCC
    CCTGGCAAGGAGAGGGAGTTCGTTTCCGTGATTGATGGCACTGGGTCTACTTCC
    TACGCTGCCAGTGTGAAGGGGCGCTTCACCGCTTCTCAAGACAAGGGCAAGAAC
    ATCGCGTACCTCCAGATGAACAGCCTGAAGCCAGAAGATACCGCAATGTACTAT
    TGTAAGGCCTCCTGCGTTCGCGGGCGGGCCATCTCAGAATACTGGGGCCAGGGG
    ACTCAGGTCACCGTGTCCAGT
    DR591- 965 CAGGTGCAGTTGCAGGAATCTGGCGGAGGCTCCGTCCAGGCTGGTGGCAGTTTG
    hIL27 CGTCTGTCCTGCACAGCTTCAGGCGCGATTGCCTCTGGCTACATTGATAGTAGA
    Ra_VH TGGTGCATGGCTTGGTTCAGACAGGCTCCTGGAAAGGAGAGAGAGGGGGTGGCC
    H6 GCGATCTGGCCCGGAGGCGGGCTGACTGTCTACGCCGATAGCGTTAAGGGTCGC
    TTCACGATTTCTCGGGATCACGCCAAGAACACCCTGTACTTGCAAATGAATAAC
    CTGAAACCCGAAGACACCGCAATGTATTACTGCGCCGCTGGTTCACCAAGGATG
    TGCCCTTCCCTGGAGTTCGGTTTCGACTACTGGGGACAGGGCACCCAGGTAACC
    GTGAGTAGCGGCGGGGGTAGTCAGGTGCAGCTTCAGGAGTCAGGCGGGGGCTTG
    GTCCAACCTGGAGGGAGCCTCAGGCTCTCCTGTGCCGCTTCCGGCTTCAGTTTC
    AGCTCCTATGCCATGAAGTGGGTAAGACAGGCCCCTGGCAAGGGCCTGGAGTGG
    GTTTCCACCATTAGTAGCGGAGGCAGCTCAACCAACTACGCCGATTCCGTTAAG
    GGCCGCTTTACGATCAGCCGTGACAATGCAAAGAACACCTTGTACCTCCAGCTG
    AACTCCCTGAAAATTGAAGACACCGCAATGTATTACTGCGCCAAGGCAATCGTC
    CCTACAGGGGCCACAATGGAGCGCGGTCAGGGAACTCAGGTGACCGTGTCCAGC
    DR591- 966 CAGGTTCAGCTCCAGGAATCTGGAGGGGGAAGTGTGCAGGCTGGAGGTTCCCTC
    hIL27 CGCCTCAGCTGCACTGCCAGCGGAGCTATCGCTTCCGGTTACATTGACAGCCGC
    Ra_VH TGGTGTATGGCTTGGTTTCGCCAAGCGCCCGGCAAGGAACGCGAAGGGGTGGCG
    H6 GCCATCTGGCCTGGGGGAGGCCTGACAGTGTACGCCGACAGCGTCAAGGGTAGG
    TTTACTATCAGCAGAGACCACGCAAAGAACACCCTGTATCTGCAAATGAACAAT
    CTGAAGCCGGAAGACACTGCAATGTATTACTGTGCTGCGGGCTCCCCCAGGATG
    TGTCCCAGCCTGGAGTTCGGGTTTGACTACTGGGGTCAGGGGACGCAGGTGACC
    GTCAGCTCCGGCGGTTCCGGGGGCAGCGGAGGCAGCGGACAGGTCCAGCTTCAG
    GAGTCCGGTGGGGGCCTGGTCCAGCCTGGGGGCTCTCTGCGGCTGAGCTGTGCG
    GCCAGCGGGTTTAGTTTCTCCAGTTACGCTATGAAATGGGTGCGTCAGGCACCG
    GGTAAGGGACTCGAATGGGTCAGCACAATCAGTAGCGGAGGCAGCTCCACGAAC
    TATGCTGATAGCGTGAAGGGAAGATTCACCATTAGCCGCGACAACGCCAAGAAT
    ACATTGTATCTTCAGCTGAACAGCCTGAAGATCGAAGACACCGCGATGTATTAC
    TGTGCTAAGGCCATCGTGCCCACTGGGGCCACAATGGAGAGGGGCCAGGGCACC
    CAGGTCACGGTATCCAGC
    DR591- 967 CAGGTCCAGTTGCAGGAAAGCGGAGGCGGATCTGTGCAGGCAGGTGGCTCCCTT
    hIL27 CGCCTGAGCTGCACCGCAAGCGGGGCCATTGCGTCTGGATACATCGACTCCAGA
    Ra_VH TGGTGCATGGCCTGGTTCCGCCAAGCGCCAGGCAAAGAGCGCGAAGGAGTGGCA
    H7 GCCATCTGGCCTGGAGGGGGCCTCACAGTTTACGCTGACTCCGTTAAGGGCAGA
    TTCACCATCTCCCGCGACCACGCCAAGAACACACTCTACCTCCAGATGAATAAC
    CTGAAGCCCGAGGATACCGCCATGTATTACTGCGCAGCTGGAAGCCCACGTATG
    TGCCCGTCCTTGGAGTTCGGCTTCGACTACTGGGGGCAAGGAACCCAGGTGACC
    GTTTCCAGCGGGGGCGGATCTCAGGTCCAGTTGCAAGAGTCCGGGGGCGGGCTG
    GTGCAGCCTGGGGGCTCTCTGCGCCTGTCCTGCGCAGCGAGCGGCTTCACCTTC
    TCATCCTATCCTATGTCTTGGGTGCGTCAGGCCCCAGGTAAGGGACTGGAGTGG
    ATTTCCACGATCAGTGCCGGTGGCGATACTACCCTCTACGCCGACTCTGTGAAA
    GGACGGTTCACCAGTAGCCGTGACAACGCGAAGAACACATTGTATTTGCAGCTG
    AACAGCCTCAAGACCGAAGATACCGCCATCTATTACTGCGCCAAGAGAATTGAT
    TGTAACTCTGGATACTGCTACCGTCGCAACTACTGGGGACAGGGCACCCAGGTC
    ACCGTCAGTTCC
    DR591- 968 CAGGTGCAGTTGCAGGAATCCGGGGGAGGCAGTGTTCAGGCTGGCGGAAGCCTG
    hIL27 CGCCTTTCCTGCACAGCCAGCGGGGCTATTGCCTCCGGCTACATTGATAGTCGT
    Ra_VH TGGTGCATGGCCTGGTTCCGCCAAGCACCGGGTAAGGAGAGGGAAGGCGTCGCC
    H7 GCAATCTGGCCGGGAGGGGGTCTGACCGTGTATGCTGACAGCGTGAAGGGCAGA
    TTCACCATCTCTAGGGACCACGCCAAGAACACCCTCTATTTGCAGATGAACAAT
    CTCAAACCCGAGGATACCGCGATGTATTACTGCGCTGCGGGTAGCCCACGTATG
    TGTCCATCTCTGGAGTTCGGCTTCGATTATTGGGGTCAGGGCACTCAGGTGACC
    GTCAGCTCCGGGGGCTCCGGCGGTTCTGGTGGGTCAGGCCAGGTGCAGCTCCAG
    GAGTCCGGCGGTGGCCTGGTGCAGCCCGGTGGGTCCCTTCGTCTGAGCTGTGCA
    GCCAGCGGATTTACATTTAGCTCCTACCCCATGTCCTGGGTAAGACAGGCCCCC
    GGAAAGGGCCTGGAATGGATTTCCACCATCTCTGCCGGTGGAGACACCACACTG
    TATGCTGACTCTGTGAAGGGAAGATTCACTTCCTCTCGGGACAACGCCAAGAAC
    ACCCTGTACTTGCAGTTGAACAGCCTGAAGACAGAGGATACCGCCATTTATTAC
    TGTGCCAAGAGGATTGATTGTAACAGCGGATACTGTTATCGCAGGAACTATTGG
    GGACAGGGAACTCAGGTGACCGTCTCTTCA
    DR591- 969 CAGGTCCAGCTTCAGGAGTCCGGCGGAGGCTCTGTGCAGGCAGGCGGTTCACTG
    hIL27 CGCCTGTCATGCACGGCGAGCGGAGCCATCGCCAGCGGTTACATTGATTCCCGT
    Ra_VH TGGTGCATGGCGTGGTTCCGTCAGGCACCCGGCAAGGAACGCGAGGGCGTGGCT
    H8 GCCATCTGGCCTGGGGGCGGGCTTACAGTGTACGCCGATTCCGTGAAAGGTCGC
    TTCACCATCTCCCGCGACCACGCCAAGAATACTCTTTACCTGCAAATGAATAAC
    TTGAAGCCGGAGGACACCGCTATGTATTACTGTGCCGCTGGCAGCCCTCGCATG
    TGTCCCTCTCTGGAGTTCGGCTTTGATTACTGGGGCCAGGGCACCCAGGTGACC
    GTATCTAGCGGTGGAGGCTCCCAAGTGCAGCTGCAAGAATCTGGAGGCGGGAGC
    GTCCAGGTGGGAGGCTCCCTGCGCCTGAGCTGCGCCGCTTCCGGCTTTACCTTT
    AGTAGCTACCCCATGTCCTGGGTCCGCCAGGCACCCGGCAAAGGCCTTGAGTGG
    ATCTCCACGATCAGCGCAGGGGGTGACACCACTCTGTACGCCGACAGCGTTAAA
    GGCAGGTTCACCAGCTCCCGCGACAACGCGAAAAACACCCTGTACTTGCAGCTC
    AACTCACTCAAGACGGAGGACACTGCTATCTATTACTGCGCCAAGCGCATTGAT
    TGTAACAGCGGTTACTGTTACCGGCGTAACTACTGGGGTCAGGGCACTCAGGTC
    ACCGTCTCCTCT
    DR591- 970 CAAGTGCAGCTCCAGGAATCCGGTGGAGGCAGCGTGCAGGCCGGAGGTTCCCTG
    hIL27 CGCCTGTCTTGCACTGCCTCAGGAGCCATTGCCTCCGGTTACATTGATTCCCGT
    Ra_VH TGGTGCATGGCCTGGTTTCGCCAGGCCCCAGGAAAAGAGCGCGAGGGGGTGGCC
    H8 GCTATCTGGCCCGGCGGTGGCCTGACTGTGTACGCTGATTCCGTAAAGGGCCGG
    TTTACCATCTCCAGGGATCATGCAAAAAACACACTCTACCTCCAGATGAATAAC
    CTGAAGCCTGAGGACACCGCCATGTATTACTGCGCCGCTGGCTCACCTCGTATG
    TGTCCCAGCCTCGAATTTGGCTTTGACTATTGGGGCCAGGGCACCCAGGTTACC
    GTCTCTTCCGGTGGCTCAGGAGGTTCCGGGGGCTCTGGTCAGGTGCAGTTGCAG
    GAAAGTGGAGGTGGCAGTGTGCAGGTAGGGGGCAGCCTGCGTCTGAGCTGTGCT
    GCCAGCGGCTTTACATTCAGCTCCTATCCTATGAGCTGGGTGAGACAGGCCCCT
    GGGAAAGGCCTGGAGTGGATCAGCACTATCAGCGCCGGTGGCGATACGACTCTC
    TATGCCGATAGCGTCAAGGGCCGCTTCACGTCCTCAAGGGACAATGCTAAAAAC
    ACCTTGTATCTCCAGTTGAACAGTCTCAAGACGGAGGACACCGCTATCTACTAT
    TGTGCCAAGAGAATTGATTGCAACAGCGGCTACTGTTACAGACGTAATTATTGG
    GGGCAGGGCACCCAGGTAACTGTGTCCTCA
    DR591- 971 CAGGTGCAGTTGCAGGAGTCAGGCGGTGGCTCCGTGCAGGCAGGCGGAAGCCTG
    hIL27 CGCCTGTCTTGCACTGCCTCTGGGGCTATTGCATCAGGGTACATTGATAGCCGC
    Ra_VH TGGTGTATGGCGTGGTTTAGGCAGGCTCCAGGAAAGGAAAGAGAGGGAGTGGCC
    H9 GCGATCTGGCCCGGTGGAGGTCTGACGGTGTATGCTGATTCAGTGAAGGGCCGG
    TTCACTATTTCTCGCGACCATGCCAAGAACACCCTCTACCTTCAGATGAATAAC
    CTGAAACCCGAGGACACCGCTATGTATTACTGCGCTGCGGGTTCTCCCCGCATG
    TGTCCTAGTCTTGAGTTCGGATTTGACTATTGGGGCCAGGGCACCCAAGTGACG
    GTCAGCTCCGGCGGGGGTAGTCAGGTCCAACTGCAAGAATCCGGGGGCGGTAGC
    GTGCAGTCCGGTGGCTCCCTGAGACTCAGCTGCGCCGCTTCCGGGTTTACCTAC
    TCCACTTCCAACTCTTGGATGGCGTGGTTCCGTCAGGCCCCAGGAAAGGAGAGG
    GAGGGCGTGGCCGCTATCTATACGGTGGGTGGCTCCATCTTCTACGCCGATTCT
    GTACGCGGAAGATTCACAATCTCTCAGGACGCAACAAAAAATATGTTTTACTTG
    CAGATGAACACTCTGAAGCCTGAAGACACTGCGATGTACTATTGTGCGGCTGCG
    AGCGGCAGACTGCGCGGTAAGTGGTTCTGGCCCTACGAGTACAACTACTGGGGG
    CAGGGCACTCAGGTCACAGTCTCTAGC
    DR591- 972 CAGGTGCAGTTGCAGGAATCTGGCGGTGGCAGTGTCCAGGCCGGTGGCTCCCTC
    hIL27 AGGCTGTCCTGCACTGCCAGCGGAGCCATCGCTTCAGGCTACATTGACTCTAGG
    Ra_VH TGGTGCATGGCTTGGTTTCGCCAGGCTCCGGGCAAAGAGCGCGAGGGCGTCGCA
    H9 GCCATCTGGCCAGGTGGGGGTTTGACGGTCTATGCTGATTCCGTGAAGGGGCGG
    TTCACTATCTCCCGTGACCACGCCAAGAACACCCTGTACCTCCAGATGAATAAC
    CTGAAGCCTGAGGATACAGCGATGTACTATTGCGCTGCCGGTAGCCCGCGCATG
    TGCCCCAGTCTTGAGTTCGGCTTTGACTATTGGGGCCAGGGCACGCAAGTGACC
    GTGTCCTCTGGGGGCAGTGGCGGTTCTGGTGGCTCAGGTCAGGTCCAGCTCCAG
    GAAAGCGGGGGTGGGTCCGTCCAATCTGGTGGCTCCTTGCGTCTGAGCTGCGCT
    GCCTCTGGCTTCACTTATTCAACGTCCAACTCTTGGATGGCCTGGTTTCGCCAA
    GCGCCAGGCAAGGAGCGTGAAGGCGTCGCTGCCATCTATACCGTTGGTGGCAGC
    ATTTTCTACGCTGACTCAGTGAGGGGCAGATTTACCATTTCTCAGGATGCAACC
    AAGAATATGTTTTACTTGCAGATGAACACACTGAAGCCCGAGGACACAGCTATG
    TACTATTGTGCAGCCGCTTCTGGCCGTCTTCGCGGCAAGTGGTTCTGGCCCTAC
    GAGTACAATTATTGGGGCCAGGGTACGCAGGTGACCGTGTCCAGT
    DR591- 973 CAAGTTCAGTTGCAGGAGTCCGGTGGCGGTAGTGTGCAGGCGGGCGGAAGCCTG
    hIL27 CGCCTGTCTTGTACCGCCTCTGGGGCCATTGCCTCTGGCTACATTGATTCTCGC
    Ra_VH TGGTGTATGGCCTGGTTTAGGCAGGCACCAGGCAAGGAACGCGAAGGCGTGGCC
    H10 GCTATCTGGCCTGGGGGCGGACTGACCGTGTACGCTGACTCAGTCAAAGGCCGC
    TTCACTATCTCACGCGACCACGCCAAGAATACTCTGTACCTCCAGATGAATAAC
    CTGAAGCCTGAGGACACCGCGATGTATTACTGCGCTGCCGGTTCCCCAAGAATG
    TGCCCTTCACTTGAGTTTGGCTTTGACTATTGGGGCCAAGGAACTCAGGTGACC
    GTAAGCTCTGGAGGGGGCAGCCAGGTCCAGCTCCAGGAGTCTGGAGGGGGCTCC
    GTGCAGGCCGGAGGGTCTCTCCGCCTCAGCTGTCGTGCCTCAGGCTCCACGTAC
    TCTAACTACTGCCTGGGGTGGTTCCGCCAGATCACAGGTAAAGAGCGCGAAGGC
    GTAGCTGTCATCAACTGGGTCGGGGGAATGCTGTACTTCGCCGACTCCGTTAAG
    GGTCGGTTCACCGTCTCTCAGGATCAGGCCAAAAATACCCTGTATCTCCAGATG
    AACAGCCTGAAGCCGGAGGACACCGCTATGTATTACTGTGCCGCAGAGAGCGTG
    TCCTCTTTCTCCTGCGGCGGTTGGCTGACCCGCCCGGACAGAGTACCCTACTGG
    GGTCAGGGGACTCAGGTGACAGTGAGCAGC
    DR591- 974 CAGGTGCAACTGCAAGAGTCCGGCGGAGGCTCTGTGCAAGCCGGAGGCTCTCTG
    hIL27 CGCCTGTCCTGTACCGCTAGTGGAGCCATCGCCAGCGGTTACATTGACAGCAGA
    Ra_VH TGGTGTATGGCCTGGTTCCGCCAGGCCCCCGGCAAAGAGCGCGAGGGCGTCGCT
    H10 GCAATCTGGCCTGGCGGGGGCCTTACCGTATATGCCGATTCAGTCAAAGGCCGC
    TTCACAATCTCACGCGACCACGCCAAGAACACCCTGTACTTGCAGATGAATAAC
    CTGAAGCCGGAGGACACCGCAATGTATTACTGCGCAGCCGGGTCTCCGCGCATG
    TGTCCCAGCTTGGAGTTCGGATTCGACTACTGGGGCCAAGGGACCCAGGTGACG
    GTTAGCTCTGGCGGTTCCGGCGGGAGTGGGGGCTCTGGCCAGGTGCAGCTGCAA
    GAGTCTGGGGGAGGTTCTGTCCAGGCGGGAGGCTCCCTGAGGCTGAGTTGTCGT
    GCAAGCGGTTCTACCTACTCCAACTATTGCCTGGGTTGGTTTCGTCAGATTACG
    GGGAAGGAACGCGAGGGGGTCGCCGTCATAAATTGGGTTGGCGGTATGCTTTAT
    TTTGCCGACTCTGTCAAAGGTCGGTTCACCGTGTCTCAAGACCAGGCTAAGAAC
    ACTCTGTACCTCCAGATGAACTCCCTGAAACCAGAGGACACCGCAATGTATTAC
    TGCGCTGCCGAAAGCGTGTCCAGCTTCAGCTGTGGCGGTTGGCTCACCCGCCCT
    GACCGTGTGCCCTATTGGGGTCAGGGGACACAGGTGACCGTCAGCAGC
    DR591- 975 CAGGTGCAGTTGCAGGAAAGCGGAGGGGGCTCCGTGCAAGCCGGAGGGTCTCTG
    hIL27 CGTCTTTCTTGCACTGCCTCTGGGGCCATCGCTTCCGGCTACATTGATAGCCGT
    Ra_VH TGGTGCATGGCCTGGTTCCGTCAAGCGCCTGGAAAGGAGCGCGAGGGCGTGGCC
    H11 GCTATTTGGCCTGGTGGAGGCCTCACTGTGTATGCTGATAGTGTGAAGGGACGT
    TTCACAATCTCCCGTGACCACGCGAAGAACACGCTGTACCTCCAGATGAACAAT
    CTCAAACCCGAGGATACAGCTATGTATTACTGTGCCGCTGGTAGTCCACGCATG
    TGTCCCAGTCTGGAGTTCGGGTTTGATTATTGGGGACAAGGCACGCAGGTTACA
    GTGTCTTCCGGGGGTGGCTCCCAAGTTCAGCTTCAAGAGAGCGGCGGAGGCTCC
    GTGCAGGCGGGTGGCTCACTGAGACTGTCCTGCCGTGCCTCCGGGTCCACTTAT
    AGTAACTATTGTCTGGGTTGGTTCCGTCAAAGTACTGGTAAAGAGCGCGAGGGC
    GTGGCAGTAATCAACTGGGTCGGCGGAATGCTGTACTTCGCGGATTCTGTGAAG
    GGAAGATTCACTGTGTCACAGGACCACGCCAAAAATACCGTGACCCTTCAGATG
    AATAGCCTGAAGCCTGAGGACACGGCAATGTATTACTGTGCCGCTGAATCCGTG
    TCTAGCTTTAGCTGCGGAGGTTGGCTGACACGTCCTGGTAGAGTGCCATATTGG
    GGCCAAGGCACTCAAGTGACTGTATCTTCC
    DR591- 976 CAGGTTCAGCTTCAGGAATCCGGTGGAGGCAGTGTGCAGGCCGGTGGAAGCCTC
    hIL27 CGCCTCTCTTGCACAGCCTCCGGGGCCATCGCATCTGGCTATATTGACAGCCGC
    Ra_ TGGTGTATGGCTTGGTTCCGCCAAGCGCCCGGTAAGGAGCGCGAAGGGGTCGCT
    VH GCCATTTGGCCTGGTGGGGGATTGACTGTGTATGCAGATAGCGTGAAAGGTCGT
    H11 TTCACTATCAGCCGTGACCACGCCAAGAACACCCTGTATCTGCAAATGAACAAT
    CTGAAGCCTGAGGACACCGCCATGTATTACTGTGCGGCAGGCAGCCCTCGCATG
    TGCCCGTCCCTGGAGTTCGGTTTCGACTACTGGGGCCAGGGCACACAGGTGACT
    GTTAGCTCCGGCGGTTCTGGAGGTTCTGGGGGCTCTGGCCAGGTACAGCTCCAG
    GAGAGCGGAGGGGGCTCCGTTCAAGCAGGTGGCTCTTTGCGTTTGAGCTGCCGT
    GCCAGCGGGTCTACCTACTCCAATTACTGTCTGGGATGGTTCCGCCAATCCACC
    GGCAAAGAACGTGAGGGTGTGGCCGTTATCAACTGGGTTGGGGGAATGCTTTAC
    TTTGCGGACAGTGTGAAAGGGCGCTTCACCGTGTCCCAGGATCATGCTAAGAAC
    ACTGTGACCCTCCAGATGAACAGCCTGAAGCCCGAGGATACGGCAATGTATTAC
    TGCGCCGCTGAATCAGTAAGCTCCTTCTCATGTGGCGGATGGCTGACCCGCCCT
    GGCCGCGTGCCCTATTGGGGACAGGGCACCCAGGTGACAGTCAGCAGC
    DR591- 977 CAGGTGCAGTTGCAGGAATCCGGTGGCGGAAGTGTGCAGGCCGGGGGCTCCCTC
    hIL27 CGTCTGTCCTGCACCGCGTCAGGCGCTATCGCCTCCGGGTACATCGACTCCCGC
    Ra_VH TGGTGCATGGCCTGGTTTCGTCAAGCGCCCGGCAAGGAGAGAGAAGGTGTGGCC
    H12 GCGATTTGGCCGGGCGGAGGCCTGACCGTGTACGCTGACTCCGTTAAGGGGCGT
    TTTACTATCTCCCGTGACCACGCCAAGAATACATTGTATCTGCAAATGAATAAC
    CTCAAGCCCGAGGACACTGCTATGTACTATTGTGCTGCCGGTTCCCCGCGCATG
    TGTCCGAGCCTGGAGTTTGGCTTCGACTATTGGGGTCAAGGCACTCAGGTCACC
    GTCTCCTCAGGCGGAGGGAGCCAAGTGCAGCTCCAGGAAAGCGGAGGTGGCTCC
    GTGCAGGCTGGAGAGAGCCTGAGGCTGTCATGCCGCGCCAGCGGGTCTACCTAC
    TCTAACTACTGTCTGGGCTGGTTTAGGCAGATTACCGGCAAAGAGAGAGAGGGG
    GTCGCTGTTATCAACTGGGTGGGAGGGATGTTGTACTTCGCCGACAGCGTCAAG
    GGTAGATTTACCGTCTCTCAGGACCAGGCTAAGAACACAGTATATCTGGAGATG
    AACTCTCTTAAACCCGAGGACACTGCTATGTACTATTGTGCCACCGAGTCCGTG
    TCTTCCTTCTCCTGCGGGGGCTGGCTGACTAGACCTGATCGGGTGCCCTACTGG
    GGTCAGGGTACACAGGTGACAGTCTCTAGC
    DR591- 978 CAAGTTCAGCTTCAGGAAAGTGGCGGTGGCTCCGTACAGGCCGGGGGCAGTCTG
    hIL27 CGCCTGAGCTGCACCGCCAGCGGTGCCATCGCCAGCGGCTACATCGACTCCAGG
    Ra_ TGGTGTATGGCTTGGTTCCGCCAAGCACCGGGCAAGGAGCGCGAAGGAGTTGCC
    VH GCTATCTGGCCCGGCGGGGGCCTGACCGTCTACGCCGACAGCGTGAAAGGTCGC
    H12 TTCACTATCTCTCGCGACCACGCCAAGAACACCTTGTACCTCCAAATGAATAAC
    CTGAAGCCAGAGGACACTGCTATGTATTACTGCGCTGCCGGAAGTCCCCGTATG
    TGTCCCTCTCTGGAGTTTGGGTTTGATTATTGGGGGCAGGGCACACAGGTCACT
    GTGTCAAGCGGGGGTAGTGGCGGTTCCGGCGGTAGCGGCCAGGTGCAGCTTCAA
    GAGAGCGGGGGCGGAAGCGTGCAGGCGGGCGAATCTCTCCGGTTGTCATGTAGA
    GCGTCTGGCTCCACCTACTCTAACTACTGCCTGGGGTGGTTCAGACAGATTACG
    GGGAAAGAGAGGGAAGGCGTGGCCGTTATAAATTGGGTAGGCGGAATGCTCTAC
    TTCGCTGACTCTGTCAAGGGCCGGTTCACAGTGTCTCAGGACCAGGCCAAAAAT
    ACTGTGTATCTGGAGATGAACTCTCTGAAACCCGAGGACACTGCCATGTATTAC
    TGCGCCACGGAGAGCGTCTCCAGCTTCTCATGTGGAGGGTGGCTGACCCGCCCG
    GACCGTGTACCCTACTGGGGTCAGGGAACACAGGTGACAGTGAGCAGC
    DR591- 979 CAGGTGCAGTTGCAGGAGAGCGGAGGCGGGAGCGTCCAGGCCGGAGGCTCCCTT
    hIL27 CGCCTCAGCTGTACCGCGTCTGGAGCAATCGCCAGCGGCTACATTGACTCCCGT
    Ra_ TGGTGCATGGCATGGTTCCGCCAAGCGCCAGGCAAAGAGAGAGAAGGCGTGGCC
    VH GCTATTTGGCCTGGGGGTGGACTCACAGTTTATGCAGACTCTGTGAAGGGCCGC
    H13 TTTACCATCAGTAGAGACCACGCCAAGAACACCCTGTATCTGCAAATGAACAAT
    CTGAAGCCAGAGGACACCGCGATGTACTATTGCGCTGCCGGTTCTCCCAGGATG
    TGTCCCTCATTGGAGTTCGGCTTTGATTACTGGGGCCAGGGAACCCAGGTCACC
    GTATCTTCCGGTGGCGGATCACAGGTTCAGCTCCAGGAATCAGGAGGTGGCTCT
    GTGCAGGCCGGGGGCTCCCTGCGGCTGTCTTGCGTGGCCTCCGGCTACGTCTCT
    TGCGACTACTTTCTGCCTTCTTGGTATCGGCAGGCCCCTGGGAAAGAGCGGGAG
    TTCGTCTCTATCATTGACGGCACCGGCTCCACATCCTACGCTGCGAGCGTGAAG
    GGCCGCTTCACAGCATCCCAGGACAGGGGAAAGAACATCGCTTATTTGCAGATG
    AACAGCCTGAAGCCTGAGGACACAGCTATGTATTACTGTAAGGCCTCTTGTGTG
    CGCGGCAGAACCATCAGCGAGTACTGGGGACAAGGGACCCAGGTGACCGTATCT
    TCA
    DR591- 980 CAGGTGCAGTTGCAGGAGTCCGGCGGGGGCTCTGTCCAAGCTGGAGGCTCCTTG
    hIL27 CGTTTGAGCTGTACCGCTAGTGGAGCCATCGCGAGTGGCTACATCGACAGCAGA
    Ra_ TGGTGCATGGCCTGGTTCCGCCAAGCTCCCGGCAAGGAGAGGGAAGGCGTTGCT
    VH GCAATCTGGCCCGGCGGTGGCCTGACCGTGTACGCGGATTCTGTCAAGGGGCGC
    H13 TTTACTATCAGCCGCGATCATGCTAAAAACACGCTTTATCTGCAAATGAATAAC
    CTCAAACCAGAAGATACCGCGATGTACTATTGCGCAGCTGGTTCTCCCCGGATG
    TGTCCCAGTTTGGAGTTTGGTTTCGATTACTGGGGTCAGGGCACTCAGGTGACC
    GTGAGTTCCGGCGGATCTGGAGGCTCAGGAGGCTCCGGCCAGGTGCAGCTCCAG
    GAGTCCGGCGGTGGCAGCGTACAAGCTGGCGGGTCCCTCCGTCTGAGCTGTGTG
    GCAAGCGGTTATGTTAGCTGTGACTACTTTCTGCCAAGCTGGTATCGCCAAGCG
    CCAGGCAAGGAGCGCGAGTTCGTGAGTATCATTGATGGCACCGGCAGCACCTCC
    TACGCAGCCAGCGTGAAGGGACGGTTTACCGCCTCCCAGGATAGAGGAAAGAAC
    ATCGCATACCTCCAGATGAACAGCCTGAAGCCGGAGGACACAGCCATGTATTAC
    TGCAAGGCCTCTTGCGTGAGGGGCCGCACCATCAGCGAGTACTGGGGGCAGGGC
    ACTCAGGTAACTGTCAGCTCA
    DR591- 981 CAGGTGCAGCTTCAGGAGAGCGGTGGAGGCTCTGTCCAAGCTGGCGGTTCCCTG
    hIL27 AGACTTTCCTGCACCGCCTCCGGGGCCATCGCTTCCGGCTACATTGATAGCAGA
    Ra_VH TGGTGTATGGCATGGTTCAGGCAGGCCCCTGGTAAAGAGCGCGAGGGCGTTGCC
    H14 GCAATCTGGCCTGGCGGAGGCCTGACCGTGTACGCCGACTCCGTGAAGGGCCGT
    TTCACCATCTCTCGTGACCACGCCAAGAATACTCTGTATCTTCAGATGAATAAC
    TTGAAACCTGAAGACACAGCTATGTATTACTGCGCAGCCGGAAGCCCACGCATG
    TGCCCATCCCTGGAGTTTGGCTTCGATTATTGGGGCCAAGGCACCCAAGTGACA
    GTCAGCAGTGGAGGCGGTTCCCAGGTTCAGTTGCAAGAGTCCGGTGGCGGAAGC
    GTGCAGGCAGGCGGTAGCTTGCGCTTGTCCTGTGTGGCCTCCGGCTATGTGAGT
    TGCGACTATTTCCTGCCTTCCTGGTATAGACAGGCCCCCGGCAAGGAACGCGAG
    TTCGTGTCTATTATCGACGGCACCGGGAGCACATCCTACGCTGCGAGCGTCAAG
    GGCCGCTTCACTGCGTCACAGGACAAGGGCAAGAACATCGCTTATCTCCAGATG
    AACTCTCTGAAACCTGAGGATACAGCAATGTATTACTGTAAGGCTTCCTGCGTG
    AGAGGCCGCGCCATTAGCGAGTACTGGGGGCAGGGCACTCAGGTAACCGTAAGC
    AGC
    DR591- 982 CAGGTTCAGCTTCAGGAGTCTGGGGGAGGCAGCGTGCAGGCAGGTGGCTCCCTT
    hIL27 CGCCTCAGCTGTACGGCTTCAGGTGCCATTGCTTCCGGTTACATTGATAGCAGG
    Ra_VH TGGTGTATGGCCTGGTTCCGGCAAGCGCCCGGCAAAGAAAGAGAGGGTGTGGCA
    H14 GCCATCTGGCCAGGCGGTGGGCTTACCGTGTATGCCGATTCTGTTAAGGGCAGG
    TTCACGATCTCCAGGGACCACGCCAAGAATACCCTGTATCTCCAAATGAATAAC
    CTGAAGCCCGAGGACACTGCCATGTATTACTGTGCTGCGGGCTCCCCTCGTATG
    TGTCCCTCTCTGGAGTTCGGGTTTGACTACTGGGGACAAGGAACACAGGTGACC
    GTCTCCAGCGGGGGCAGCGGAGGTAGCGGCGGAAGCGGACAGGTACAGTTGCAG
    GAGTCTGGCGGTGGCTCCGTGCAGGCTGGCGGTTCACTCAGACTGTCCTGTGTG
    GCCAGCGGATACGTGAGCTGCGATTATTTCTTGCCTTCCTGGTATCGCCAGGCC
    CCTGGGAAGGAACGCGAGTTCGTGTCTATCATTGACGGAACCGGCTCCACGTCC
    TATGCCGCTTCTGTCAAGGGTCGCTTTACAGCTTCCCAGGACAAGGGTAAAAAC
    ATCGCTTACCTTCAGATGAACTCCCTGAAGCCTGAAGATACCGCCATGTACTAT
    TGTAAGGCCAGCTGCGTGCGGGGCAGGGCTATCTCAGAGTATTGGGGTCAGGGC
    ACGCAGGTGACAGTGTCCTCT
    DR591- 983 CAGGTGCAGCTCCAGGAAAGCGGGGGAGGCTCCGTGCAGGCGGGCGGTAGCCTC
    hIL27 CGTCTGTCCTGCACTGCCTCAGGAGCCATTGCCTCTGGCTACATTGACTCCCGC
    Ra_ TGGTGTATGGCCTGGTTCCGCCAAGCGCCCGGAAAGGAAAGGGAGGGCGTGGCT
    VH GCAATTTGGCCAGGAGGTGGCCTGACCGTGTATGCGGATTCTGTGAAGGGACGC
    H15 TTCACCATCAGCAGGGACCACGCTAAGAACACCCTGTACCTGCAAATGAATAAC
    CTGAAACCCGAGGACACCGCCATGTACTATTGTGCCGCAGGCTCCCCCAGAATG
    TGCCCTTCTCTGGAGTTCGGGTTCGACTATTGGGGTCAGGGGACCCAGGTGACC
    GTCTCCTCTGGTGGGGGTAGCCAGGTGCAACTCCAGGAATCCGGCGGGGGCTCC
    GTGCAGGCTGGCGGGTCTCTGCGCCTGAGCTGTGTGGCTTCCGGGTATGTGTCC
    TGCGACTACTTCCTGCCTTCTTGGTATCGCCAAGCGCCGGGGAAGGAACGCGAG
    TTCGTAAGCATCATTGATGGCACTGGATCAACAAGCTACGCGGCCTCTGTGAAA
    GGCCGCTTCACAGCGAGCCAGGATAAGGGTAAGAACATCGCGTATTTGCAGATG
    AACACTCTCAAGCCAGAAGACACCGCGATGTATTACTGCAAGGCCAGTTGTGTG
    CGTGGCCGGGCCATCTCCGAGTATTGGGGGCAGGGCACCCAGGTCACCGTGTCC
    TCC
    DR591- 984 CAGGTCCAACTTCAGGAGTCTGGAGGCGGTTCCGTGCAGGCGGGCGGTAGCTTG
    hIL27 CGCCTGAGCTGTACCGCTTCAGGTGCCATCGCGAGCGGATACATCGACTCTCGC
    Ra_VH TGGTGTATGGCCTGGTTCCGCCAGGCCCCTGGCAAGGAACGTGAGGGTGTGGCT
    H15 GCCATTTGGCCCGGCGGGGGACTTACTGTGTACGCCGACTCCGTGAAGGGCCGT
    TTCACCATCTCCCGTGACCACGCGAAGAACACCCTGTACTTGCAGATGAATAAC
    CTCAAACCCGAGGATACCGCGATGTATTACTGTGCCGCTGGCAGCCCACGCATG
    TGTCCCAGTCTGGAGTTCGGTTTTGACTATTGGGGGCAGGGTACACAAGTCACA
    GTGTCTAGCGGAGGCTCTGGTGGCTCCGGGGGTAGCGGACAGGTGCAGTTGCAG
    GAATCTGGCGGTGGCAGTGTGCAGGCGGGTGGCAGCCTGCGCCTGTCCTGCGTT
    GCTAGTGGGTATGTGAGCTGTGATTATTTCCTGCCATCTTGGTATCGCCAGGCC
    CCCGGCAAAGAAAGAGAGTTCGTGTCCATCATTGATGGCACCGGCTCCACCAGT
    TATGCAGCGTCTGTCAAAGGCAGGTTCACTGCCAGCCAGGACAAGGGTAAGAAC
    ATTGCTTATTTGCAGATGAACACCCTGAAGCCCGAGGACACGGCTATGTATTAC
    TGTAAGGCCTCATGTGTGCGTGGCCGGGCGATTTCCGAGTACTGGGGACAAGGC
    ACACAAGTGACCGTGTCCAGC
    DR591- 985 CAAGTGCAACTCCAGGAGTCCGGGGGCGGGTCTGTGCAAGCTGGAGGCTCCCTG
    hIL27 CGCCTGAGTTGTACCGCGTCCGGTGCCATCGCTTCTGGTTATATTGATAGCAGA
    Ra_VH TGGTGTATGGCTTGGTTCCGTCAAGCGCCAGGGAAAGAGAGGGAGGGCGTGGCA
    H16 GCTATTTGGCCAGGAGGCGGACTGACCGTCTACGCAGACTCCGTCAAAGGCCGG
    TTTACAATCTCCAGAGACCACGCGAAAAACACTCTGTATCTCCAGATGAATAAC
    CTGAAGCCAGAGGATACAGCAATGTACTATTGCGCCGCTGGCTCACCCCGTATG
    TGCCCCAGTCTGGAGTTCGGGTTTGACTACTGGGGCCAGGGCACCCAAGTCACT
    GTAAGCTCCGGCGGTGGCTCCCAGGTGCAGTTGCAGGAAAGTGGCGGAGGCAGC
    GTGCAGGCCGGGGGCAGCCTGCGCCTCTCTTGTCGCGCATCCGGCAGTACCTAT
    TCTAACTACTGTTTGGGTTGGTTTAGGCAGATTACCGGCAAGGAGAGGGAGGGG
    GTGGCCGTTATCAACTGGGTCGGGGGCATGTTGTACTTTGCCGACTCTGTGAAG
    GGTAGGTTCACTGTTTCTCAGGATCAGGCTAAGAACACTGTTTATCTTCAGATG
    AACTCTCTGAAGCCAGAGGACACCGCTATGTATTACTGTGCCGCAGAGTCAGCC
    AGCTCCTTTAGTTGTGGGGGCTGGCTGACCCGTCCCGACCGCGTCCCATACTGG
    GGCCAGGGTACACAAGTGACTGTCTCCAGC
    DR591- 986 CAGGTGCAACTTCAGGAGAGTGGGGGAGGCTCTGTTCAGGCAGGCGGGTCCCTG
    hIL27 CGCCTGAGCTGCACCGCCTCAGGTGCCATCGCCTCTGGCTATATTGATAGCCGT
    Ra_VH TGGTGTATGGCCTGGTTCCGGCAGGCACCCGGCAAAGAACGCGAAGGGGTGGCC
    H16 GCTATCTGGCCTGGAGGTGGCCTGACCGTTTACGCTGACAGCGTGAAAGGAAGG
    TTCACCATCTCCAGGGACCACGCTAAGAACACTCTGTACTTGCAGATGAATAAC
    CTGAAACCTGAAGATACCGCCATGTATTACTGCGCCGCTGGCTCTCCACGCATG
    TGTCCATCCCTGGAGTTCGGATTCGATTATTGGGGACAGGGCACCCAGGTCACC
    GTGTCCTCTGGCGGATCTGGTGGCTCAGGGGGCTCTGGCCAGGTCCAGTTGCAG
    GAATCCGGTGGAGGCAGTGTTCAGGCCGGGGGCTCCCTGCGCCTGTCATGTCGG
    GCCTCCGGCAGCACCTACTCCAATTACTGCCTCGGATGGTTCCGCCAGATCACC
    GGCAAAGAGCGTGAAGGCGTGGCCGTCATCAACTGGGTGGGCGGGATGCTTTAC
    TTTGCAGATTCCGTGAAGGGCAGATTTACGGTGTCTCAGGACCAGGCGAAGAAC
    ACAGTGTATCTCCAGATGAACAGCCTCAAGCCTGAAGATACCGCTATGTATTAC
    TGCGCCGCAGAGAGCGCTTCTTCCTTTAGCTGCGGCGGTTGGCTGACCAGGCCC
    GACCGTGTTCCGTACTGGGGTCAGGGCACCCAGGTGACCGTATCCAGT
    DR591- 987 CAAGTCCAGCTCCAGGAATCCGGCGGAGGTAGCGTGCAGGCGGGTGGCAGCCTG
    hIL27 CGCCTGTCCTGTACTGCAAGCGGAGCCATCGCCTCTGGCTACATCGACTCACGC
    Ra_VH TGGTGTATGGCCTGGTTTCGCCAAGCGCCGGGTAAGGAGCGCGAAGGGGTGGCC
    H17 GCGATTTGGCCGGGCGGGGGCCTGACCGTCTACGCTGACAGTGTCAAGGGCCGC
    TTCACCATCTCTCGGGATCACGCCAAGAACACTTTGTATCTGCAAATGAATAAC
    CTGAAACCCGAAGACACCGCAATGTATTACTGCGCCGCTGGTAGTCCGCGTATG
    TGTCCATCACTGGAGTTCGGCTTCGACTACTGGGGTCAGGGAACCCAGGTCACC
    GTGTCCTCTGGTGGCGGTAGCCAGGTCCAGCTGCAAGAATCCGGTGGCGGGCTG
    GTGCAGCCAGGTGGATCTCTGCGCTTGTCCTGTGCCGCAAGCGGTTTTACTTTC
    TCACTGAGCGGCATGTCCTGGGTGAGGCAGGCTCCAGGCAAGGGCCTCGAATGG
    GTCTCAGCCATTAGTAGCGGGGGCGCATCCACCTATTACACAGATTCCGTGAAG
    GGTAGATTCACGATTAGCCGCGACAATGCTAAGAATATGCTGTATCTTCAGTTG
    AATAGCCTGAAGACAGAGGACACCGCTATGTATTACTGCGCGAAGGGCGGATCT
    GGCTACGGCGACGCCTCCAGGATGACAAGTCCGGGTTCCCAGGGCACACAGGTC
    ACGGTCTCTAGC
    DR591- 988 CAGGTGCAGCTCCAGGAGTCCGGCGGAGGCTCAGTCCAGGCTGGGGGCTCCCTC
    hIL27 CGCCTGTCCTGTACGGCAAGTGGCGCTATCGCGAGCGGCTACATTGATTCACGC
    Ra_ TGGTGCATGGCCTGGTTCAGGCAAGCTCCTGGGAAGGAGCGCGAGGGAGTGGCT
    VH GCCATCTGGCCAGGGGGTGGCCTGACTGTGTACGCGGACAGCGTGAAGGGTCGC
    H17 TTCACAATCTCAAGGGACCACGCCAAGAATACCTTGTATCTTCAGATGAATAAC
    CTGAAACCCGAGGACACAGCCATGTACTATTGTGCAGCCGGTTCCCCGAGAATG
    TGCCCTAGTTTGGAGTTCGGCTTCGACTACTGGGGTCAGGGAACCCAGGTGACC
    GTGTCCAGTGGCGGGTCTGGGGGTTCCGGCGGGTCAGGCCAGGTCCAGCTTCAG
    GAATCCGGGGGAGGCCTGGTTCAGCCAGGTGGAAGCCTTCGCCTGTCCTGCGCT
    GCATCCGGGTTCACATTCAGCCTGAGTGGCATGTCCTGGGTGAGACAGGCCCCA
    GGAAAGGGTCTGGAGTGGGTCTCTGCAATCAGCTCCGGCGGTGCTTCTACCTAT
    TACACCGACTCCGTGAAGGGCCGGTTCACTATTAGTCGCGACAACGCTAAGAAC
    ATGCTGTACCTGCAACTGAACTCCTTGAAGACAGAAGACACGGCCATGTATTAC
    TGCGCCAAGGGAGGTTCAGGTTACGGCGACGCCAGCCGCATGACCTCCCCTGGC
    TCTCAGGGGACTCAGGTTACAGTCTCCTCC
    DR591- 989 CAGGTCCAGCTCCAGGAAAGCGGAGGCGGGTCCGTCCAGGCTGGCGGTAGTTTG
    hIL27 CGCCTCTCATGTACCGCCAGCGGCGCAATCGCTTCTGGATATATCGACTCTCGC
    Ra_VH TGGTGTATGGCCTGGTTCCGGCAGGCCCCCGGCAAGGAGAGGGAGGGAGTGGCA
    H18 GCCATCTGGCCGGGTGGCGGGTTGACCGTGTATGCCGACTCTGTCAAGGGCCGC
    TTCACAATCAGCAGAGACCATGCCAAGAACACCCTGTACCTTCAGATGAATAAC
    CTGAAGCCCGAAGACACCGCCATGTATTACTGCGCCGCAGGCTCCCCAAGAATG
    TGCCCTAGTCTGGAGTTCGGCTTCGACTACTGGGGCCAGGGGACCCAGGTGACC
    GTCAGCTCTGGTGGAGGTAGCCAGGTGCAACTCCAGGAGAGCGGAGGCGGTAGC
    GTGCAGGCTGGCGGTTCCCTGCGCCTGAGCTGCGTGGCCTCTGGTTACGTTAGT
    TGCGACTATTTTCTGCCCAGCTGGTATCGTCAGGCTCCGGGCAAGGAAAGAGAA
    TTTGTCTCCATCATTGACGGAACTGGCTCTACAAGTTACGCCGCAAGTGTCAAG
    GGTCGCTTCACCGCCAGCCAGGACAAGGGTAAGAACATCGCCTACCTGCAAATG
    AACTCCCTCAAGCCAGAAGACACCGCGATGTACTATTGCAAGGCCAGCTGTGTA
    AGGGGCAGGGGCATTAGCGAGTACTGGGGCCAGGGAACCCAGGTGACCGTGTCC
    TCC
    DR591- 990 CAGGTCCAGCTCCAGGAGTCAGGCGGTGGATCTGTGCAGGCGGGCGGGAGCCTC
    hIL27 AGGCTGAGCTGTACTGCCAGCGGCGCTATTGCCTCCGGTTACATTGACAGCCGC
    Ra_VH TGGTGTATGGCTTGGTTTCGCCAAGCCCCTGGAAAGGAGAGGGAGGGCGTTGCT
    H18 GCCATCTGGCCTGGTGGGGGACTGACCGTCTATGCTGATTCAGTGAAGGGGCGT
    TTTACCATCTCCCGCGATCACGCTAAGAACACACTGTACCTCCAGATGAACAAT
    TTGAAGCCCGAAGACACAGCCATGTACTATTGCGCCGCTGGGAGTCCCCGCATG
    TGCCCTAGCCTGGAGTTTGGCTTCGACTATTGGGGCCAGGGCACTCAGGTCACT
    GTTAGTTCCGGTGGCTCTGGTGGCAGCGGTGGCAGTGGCCAAGTGCAGCTCCAG
    GAGTCCGGCGGAGGCTCAGTACAGGCCGGTGGCTCCCTTCGCCTGTCCTGCGTC
    GCCTCCGGTTACGTTAGTTGCGACTATTTCCTGCCCAGCTGGTATCGCCAGGCA
    CCAGGGAAGGAGCGCGAGTTCGTGTCCATTATCGACGGAACAGGGTCTACATCT
    TATGCTGCCAGCGTGAAAGGAAGGTTCACCGCCTCCCAGGATAAGGGAAAAAAC
    ATCGCCTACCTCCAGATGAACAGCCTGAAGCCAGAGGACACGGCTATGTACTAT
    TGCAAGGCCTCCTGCGTGCGCGGCAGAGGTATCTCCGAATATTGGGGCCAGGGA
    ACACAGGTGACCGTGAGCAGC
    DR591- 991 CAGGTCCAGCTCCAGGAATCTGGTGGCGGAAGCGTGCAGGCCGGTGGGTCCCTG
    hIL27 AGACTGAGCTGTACCGCGAGCGGAGCTATCGCTTCTGGGTACATTGACTCCCGG
    Ra_VH TGGTGCATGGCGTGGTTCCGTCAGGCTCCAGGTAAGGAGCGGGAGGGCGTTGCT
    H19 GCGATCTGGCCAGGAGGGGGATTGACTGTGTACGCTGACTCTGTCAAGGGTCGC
    TTTACTATCTCCCGCGACCACGCAAAGAATACCTTGTACTTGCAAATGAACAAT
    CTGAAGCCTGAGGACACCGCCATGTATTACTGTGCCGCTGGTAGCCCACGCATG
    TGTCCCAGTCTGGAGTTCGGGTTCGATTATTGGGGCCAGGGCACGCAGGTGACT
    GTGTCCTCTGGTGGAGGCAGCCAAGTGCAGTTGCAGGAGTCAGGCGGAGGGAGC
    GTGCAGGCGGGAGGTTCCCTGCGGCTGTCCTGTCGCGCGTCCGGTTCCACCTAC
    TCTAACTATTGCCTCGGTTGGTTCCGCCAGATCACCGGCAAGGAGCGCGAGGGA
    GTGGCGGTTATCAACTGGGTCGGCGGTATGCTGTACTTTGCAGACTCTGTTAAA
    GGACGCTTCACTGTGAGCCAGGACCAGGCAAAGAATACTGTGTACTTGCAGATG
    AACTCCCTGAAGCCAGAAGACACCGCCATGTATTACTGTGCTGCGGAATCTGTG
    AGTTCCTTCAGTTGCGGTGGGTGGCTCACTAGACCCGATAGAGTCCCATATTGG
    GGACAGGGTACTCAGGTGACTGTTAGCTCC
    DR591- 992 CAGGTGCAGTTGCAGGAGAGTGGCGGTGGCAGCGTGCAGGCGGGCGGGAGCCTG
    hIL27 AGGCTGTCCTGTACTGCCTCTGGTGCAATCGCTTCAGGTTACATTGACTCACGC
    Ra_VH TGGTGCATGGCTTGGTTTCGCCAGGCTCCAGGCAAGGAGCGCGAGGGTGTGGCC
    H19 GCTATCTGGCCGGGTGGAGGCCTCACCGTGTACGCCGATAGTGTCAAGGGACGC
    TTTACAATCTCCCGTGACCATGCGAAGAACACATTGTATCTTCAGATGAATAAC
    CTCAAACCCGAGGACACCGCTATGTATTACTGTGCAGCCGGAAGCCCTCGTATG
    TGTCCAAGCCTGGAGTTCGGCTTTGATTACTGGGGACAAGGCACCCAGGTGACA
    GTTTCTAGTGGAGGCTCTGGCGGTTCAGGAGGCTCCGGGCAAGTGCAGTTGCAG
    GAATCCGGGGGTGGCTCCGTGCAGGCTGGGGGCTCTCTGCGGCTGTCTTGTCGT
    GCATCTGGTTCCACATATAGCAACTACTGCCTGGGCTGGTTCCGCCAGATTACG
    GGCAAGGAAAGAGAAGGTGTTGCAGTGATAAATTGGGTAGGTGGAATGCTGTAC
    TTTGCCGACTCAGTGAAAGGGCGCTTTACAGTGAGCCAGGACCAGGCCAAGAAC
    ACAGTCTACTTGCAGATGAACAGCCTCAAGCCTGAAGACACCGCAATGTACTAT
    TGTGCTGCCGAGAGCGTCTCATCCTTTTCCTGCGGAGGCTGGCTGACCCGTCCA
    GACCGCGTCCCCTACTGGGGCCAGGGCACCCAGGTGACTGTGTCCTCT
    DR591- 993 CAAGTGCAGCTGCAAGAGTCCGGTGGAGGCAGCGTACAAGCGGGTGGCTCACTG
    hIL27 CGCCTGAGTTGTACCGCTTCTGGTGCAATCGCAAGCGGCTACATTGATTCCAGA
    Ra_VH TGGTGCATGGCATGGTTTCGCCAAGCCCCAGGCAAGGAAAGGGAGGGCGTGGCC
    H20 GCAATCTGGCCTGGGGGTGGACTGACCGTGTATGCCGACAGCGTGAAGGGGCGC
    TTTACCATCTCCCGTGACCACGCTAAGAACACACTGTACTTGCAGATGAATAAC
    CTCAAGCCTGAAGACACTGCTATGTACTATTGCGCTGCCGGAAGTCCCCGCATG
    TGTCCTAGTCTGGAGTTTGGTTTTGATTACTGGGGCCAGGGCACCCAGGTGACC
    GTTTCAAGCGGAGGGGGCAGTCAGGTTCAGCTCCAGGAATCTGGAGGTGGGCTT
    GTCCAGCCAGGGGGCAGCCTCCGCCTGTCCTGTGCAGCGTCTGGCTTTACTTTC
    AGCTCCTATCCCATGTCTTGGGTTAGACAGGCACCAGGCAAGGGCCTGGAGTGG
    GTGTCCACAATCTCAAGCGGGGGCGATACAACCCTCTATGCCGATTCCGTGAAG
    GGCAGATTCACAAGCTCTAGGGACAACGCCAAGAATACCTTGTACCTCCAGCTG
    AACTCCCTGAAGACCGAGGACACTGCGATGTATTACTGCGCTAAGCGCATTGAT
    TGTAACTCTGGGTATTGTTACAAGCGCTCTTATTGGGGACAGGGCACGCAGGTG
    ACTGTCAGTTCC
    DR591- 994 CAGGTGCAGTTGCAAGAGAGCGGCGGAGGCTCCGTTCAGGCAGGGGGCTCCTTG
    hIL27 CGCTTGTCTTGCACCGCATCCGGGGCCATTGCCTCAGGCTATATCGACTCCCGC
    Ra_VH TGGTGTATGGCTTGGTTCCGGCAAGCGCCGGGTAAGGAGCGTGAGGGGGTGGCA
    H20 GCCATCTGGCCCGGAGGCGGTTTGACCGTGTATGCCGACTCTGTGAAGGGCCGG
    TTCACCATCTCTAGGGACCATGCGAAGAACACACTGTATCTCCAGATGAATAAC
    CTGAAGCCCGAAGACACCGCGATGTATTACTGTGCCGCTGGCTCCCCCAGGATG
    TGCCCCTCATTGGAGTTCGGTTTCGACTATTGGGGGCAGGGAACTCAAGTGACC
    GTAAGCTCCGGCGGGTCCGGCGGTAGTGGAGGCTCTGGGCAGGTGCAGTTGCAG
    GAGTCAGGCGGGGGCTTGGTGCAGCCCGGCGGTAGCCTGAGGCTGAGTTGCGCT
    GCCTCAGGCTTTACCTTTTCCAGCTACCCTATGTCTTGGGTGCGCCAGGCTCCG
    GGCAAGGGCTTGGAGTGGGTGTCCACCATCTCCAGCGGAGGCGATACGACCCTC
    TATGCGGATTCCGTCAAAGGGCGCTTTACCTCCAGCCGCGATAACGCCAAGAAC
    ACCTTGTACCTCCAGCTGAACTCCCTGAAGACCGAGGATACCGCAATGTACTAT
    TGTGCAAAGCGGATTGATTGTAACAGCGGCTATTGCTACAAGAGGTCTTACTGG
    GGCCAGGGCACCCAGGTGACAGTCTCCAGT
    DR591- 995 CAGGTCCAGCTCCAGGAGAGCGGTGGCGGTTCCGTGCAGGCTGGTGGCAGTCTT
    hIL27 CGTCTCTCCTGTACCGCGTCCGGTGCCATCGCCAGTGGCTACATTGATTCTCGC
    Ra_VH TGGTGCATGGCATGGTTCCGCCAAGCTCCCGGCAAGGAGCGCGAGGGCGTCGCT
    H21 GCCATTTGGCCAGGTGGCGGGCTGACCGTGTACGCGGACTCTGTGAAGGGTCGG
    TTTACGATCAGCCGGGACCATGCTAAGAATACGCTCTACCTGCAAATGAACAAT
    CTGAAACCCGAGGACACAGCAATGTACTATTGCGCAGCCGGAAGTCCTCGCATG
    TGCCCATCTTTGGAGTTTGGCTTCGATTATTGGGGCCAGGGCACCCAGGTCACT
    GTGTCCAGTGGGGGCGGTTCTCAGGTGCAGTTGCAGGAAAGTGGAGGTGGCCTT
    GTCCAACCTGGAGGGAGTCTGCGTCTCTCCTGCGCTGCCTCCGGGTTCACCTTT
    AGTCTGTCCAGTATGTCTTGGGTCCGCCAAGCGCCCGGAAAGGGTCTGGAGTGG
    GTCAGCGCGATTAGCTCCGGTGGAGCCAGTACTTATTACACCGACAGCGTGAAA
    GGACGGTTTACCATCTCCCGCGATAATGCTAAGAATATGCTCTACTTGCAGCTG
    AACAGCCTGAAGACCGAGGACACAGCGATGTATTACTGTGCCAAGGGAGGTTCT
    GGCTATGGTGATGCCAGCCGCATGACCTCCCCTGGCTCCCAGGGAACTCAGGTT
    ACTGTGTCCTCC
    DR591- 996 CAAGTGCAGTTGCAGGAGAGCGGTGGCGGTAGCGTCCAAGCTGGGGGCAGTTTG
    hIL27 CGCCTGAGCTGTACTGCGTCTGGCGCTATTGCGAGCGGTTACATTGATTCCAGG
    Ra_VH TGGTGTATGGCCTGGTTCAGGCAGGCACCGGGTAAAGAGCGTGAGGGGGTGGCA
    H21 GCCATTTGGCCTGGCGGTGGACTGACCGTCTACGCGGACTCTGTCAAGGGACGT
    TTCACGATCAGCCGCGATCACGCTAAAAACACCCTCTACCTCCAGATGAATAAC
    CTGAAGCCTGAGGACACAGCTATGTATTACTGTGCTGCGGGCAGTCCCAGAATG
    TGTCCCAGCCTGGAGTTCGGCTTCGACTACTGGGGGCAAGGCACCCAGGTGACA
    GTGTCCAGCGGGGGCTCCGGCGGGTCTGGGGGCAGCGGCCAGGTGCAACTGCAA
    GAGTCTGGCGGTGGACTTGTTCAGCCAGGGGGATCTCTGAGGCTCTCCTGCGCC
    GCTTCCGGTTTTACCTTCTCCCTCAGCAGTATGTCCTGGGTCCGTCAGGCTCCA
    GGCAAAGGCCTGGAATGGGTTTCCGCTATTAGCTCTGGCGGTGCCTCCACCTAC
    TATACGGACTCAGTCAAAGGCCGTTTCACGATCTCCAGGGACAATGCTAAGAAT
    ATGCTCTACCTCCAGTTGAACTCTCTGAAAACGGAGGACACCGCTATGTACTAT
    TGCGCCAAAGGGGGTTCCGGCTACGGCGACGCCTCCCGGATGACATCCCCTGGG
    TCCCAGGGAACCCAGGTGACCGTGTCCAGC
    DR591- 997 CAGGTGCAGTTGCAGGAGTCCGGCGGAGGCTCCGTGCAAGCTGGCGGTAGCTTG
    hIL27 CGGCTGAGTTGCACTGCCAGCGGTGCCATCGCGAGCGGGTACATCGACAGCAGG
    Ra_VH TGGTGCATGGCCTGGTTCCGTCAAGCGCCAGGAAAGGAGAGGGAGGGCGTCGCA
    H22 GCCATCTGGCCGGGCGGAGGCCTGACCGTGTACGCAGATTCCGTCAAAGGCCGT
    TTCACCATCTCCCGCGACCACGCCAAGAACACCCTGTATCTTCAGATGAATAAC
    CTGAAACCCGAGGACACCGCCATGTACTATTGTGCTGCGGGCTCACCCCGGATG
    TGTCCCTCTCTGGAGTTCGGCTTCGATTATTGGGGCCAGGGCACCCAGGTCACC
    GTGTCAAGTGGTGGCGGTTCCCAGGTGCAGCTGCAAGAGAGCGGCGGTGGCAGC
    GTGCAGGCGGGCGGTAGCTTGCGCCTGAGCTGTCGCGCCTCCGGCAGCACTTAC
    AGCAACTACTGCCTGGGCTGGTTCCGTCAGACTACAGGTAAGGAGCGTGAGGGC
    GTAGCGGTAATCAACTGGGTCGGGGGAATGCTTTACTTTGCGGACAGTGTGAAA
    GGCCGTTTCACCGTGTCTCAGGACCAGGCTAAGAACACTGTGTACCTCCAGATG
    AACTCTCTGAAGCCTGAGGACACGGCCATGTATTACTGTGCAGCGGAGTCCGTT
    AGCTCCTTCTCTTGTGGCGGATGGCTGACCCGGCCAGACCGCGTGCCATATTGG
    GGCCAAGGGACCCAAGTGACCGTGTCATCC
    DR591- 998 CAGGTGCAGCTCCAGGAGTCCGGCGGTGGGTCCGTGCAGGCTGGTGGATCTCTT
    hIL27 AGACTGTCCTGTACCGCTTCTGGAGCGATTGCCTCAGGTTACATTGACAGTAGG
    Ra_VH TGGTGTATGGCTTGGTTCCGTCAGGCTCCAGGCAAGGAACGCGAGGGCGTTGCT
    H22 GCCATTTGGCCAGGAGGCGGTCTGACTGTCTACGCTGACAGCGTAAAGGGCCGC
    TTTACCATCTCTCGGGATCACGCGAAAAATACACTGTACCTCCAGATGAATAAC
    CTGAAGCCGGAGGACACCGCCATGTATTACTGCGCTGCCGGGAGCCCCCGTATG
    TGCCCTTCCCTGGAGTTCGGATTTGACTATTGGGGCCAGGGCACCCAAGTGACC
    GTCAGCTCCGGTGGCTCTGGCGGTTCCGGGGGCTCTGGCCAAGTGCAGCTTCAG
    GAGTCAGGGGGTGGCTCTGTGCAGGCCGGTGGCAGCCTGCGTCTGAGCTGCCGT
    GCCAGCGGCTCTACCTATTCCAACTACTGCCTGGGGTGGTTTCGGCAGACCACA
    GGAAAGGAAAGAGAGGGTGTGGCAGTTATCAACTGGGTGGGAGGGATGTTGTAC
    TTCGCCGACTCCGTCAAGGGGCGCTTCACCGTCAGTCAGGACCAGGCAAAGAAC
    ACCGTGTACCTCCAGATGAACTCCCTGAAGCCTGAGGATACCGCCATGTATTAC
    TGCGCCGCTGAGTCTGTGTCATCTTTCTCATGCGGTGGCTGGCTCACCCGCCCA
    GACCGCGTGCCTTATTGGGGCCAGGGCACACAGGTCACCGTCAGCTCA
    DR591- 999 CAGGTTCAACTCCAGGAAAGCGGCGGGGGCTCTGTGCAAGCTGGCGGAAGTTTG
    hIL27 CGTCTGTCCTGCACCGCCTCTGGAGCCATCGCCAGCGGCTACATCGACTCAAGA
    Ra_VH TGGTGTATGGCCTGGTTCAGACAGGCTCCAGGAAAAGAACGCGAAGGCGTGGCC
    H23 GCTATCTGGCCCGGAGGTGGCCTGACCGTGTACGCTGACTCCGTCAAGGGCCGC
    TTCACCATCTCCCGTGACCACGCAAAGAACACACTGTACCTCCAGATGAATAAC
    CTGAAGCCCGAGGATACCGCCATGTACTATTGCGCTGCGGGCTCCCCTCGGATG
    TGTCCCAGCCTGGAGTTCGGCTTCGACTATTGGGGACAGGGAACTCAGGTCACA
    GTCAGCTCCGGCGGAGGCTCTCAGGTCCAGCTCCAGGAATCAGGTGGAGGCTCT
    GTTCAGGCGGGCGGATCTCTTCGCCTGTCATGCCGTGCATCCAGATCCCCGTAT
    GGCAACTATTGCCTGGGGTGGTTCCGCCAGAGTACAGGTAAGGAGCGCGAGGGC
    GTGGCTGTTATCAACTGGGTCGGCGGAATGCTGTATTTTGCCGATTCCGTGAAG
    GGTCGTTTCACAGTGAGCCAGGATCACGCCAAGAACACCGTGACCTTGCAGATG
    AACTCCCTGAAGCCTGAAGATACCGCCATGTATTACTGTGCTGCGGAGAGCGTG
    TCCTCTTTCTCTTGCGGCGGTTGGCTGACCAGGCCTGATCGTGTCCCCTACTGG
    GGGCAGGGCACCCAGGTGACCGTCTCTAGC
    DR591- 1000 CAAGTGCAGTTGCAGGAGTCAGGCGGAGGCTCTGTCCAGGCTGGAGGCTCTCTG
    hIL27 AGACTCTCCTGCACCGCATCCGGGGCCATCGCCAGCGGATATATCGACTCCAGA
    Ra_ TGGTGTATGGCGTGGTTTCGCCAAGCTCCGGGGAAGGAGCGTGAGGGTGTCGCT
    VH GCGATCTGGCCTGGCGGGGGACTGACCGTGTATGCTGATTCCGTAAAGGGCCGT
    H23 TTCACCATCAGCCGCGACCATGCCAAGAACACACTCTACCTCCAGATGAACAAT
    CTTAAACCCGAGGACACTGCAATGTACTATTGTGCGGCTGGTTCTCCCCGCATG
    TGTCCTTCCCTGGAGTTCGGCTTCGACTACTGGGGGCAGGGCACCCAGGTCACC
    GTGAGTAGCGGCGGGAGCGGCGGGAGCGGTGGCTCCGGCCAGGTGCAGCTTCAA
    GAGTCCGGGGGTGGCTCCGTGCAAGCTGGTGGAAGTCTTCGCCTGAGTTGCCGC
    GCGTCCCGCTCCCCTTACGGCAATTATTGCCTGGGATGGTTTCGCCAATCCACC
    GGGAAGGAGCGCGAGGGCGTGGCAGTAATCAACTGGGTGGGCGGTATGCTGTAC
    TTTGCCGATTCTGTGAAGGGCAGATTTACCGTGTCTCAAGACCACGCCAAGAAC
    ACTGTCACCTTGCAGATGAACTCACTGAAGCCAGAGGATACCGCTATGTATTAC
    TGCGCTGCCGAATCAGTCAGCTCCTTCTCTTGCGGTGGCTGGCTGACCCGCCCT
    GATAGGGTCCCCTATTGGGGCCAGGGCACCCAGGTCACCGTGTCCAGT
    DR591- 1001 CAGGTCCAGCTCCAGGAGTCCGGCGGAGGTTCTGTCCAGGCCGGTGGATCACTG
    hIL27 CGTCTGTCTTGCACCGCCAGCGGCGCAATCGCGTCTGGCTATATCGACAGCCGT
    Ra_VH TGGTGCATGGCTTGGTTTCGCCAGGCTCCCGGCAAGGAAAGGGAAGGGGTGGCC
    H24 GCGATTTGGCCTGGGGGCGGTCTGACCGTCTACGCCGACAGCGTGAAGGGCCGC
    TTTACCATCTCCCGCGACCACGCCAAGAACACATTGTACCTGCAAATGAATAAC
    CTCAAGCCTGAGGACACAGCGATGTATTACTGTGCCGCTGGCTCACCCCGCATG
    TGTCCGTCCCTGGAGTTTGGGTTTGATTATTGGGGCCAGGGCACACAGGTGACT
    GTGTCATCTGGAGGCGGTTCCCAGGTCCAGTTGCAGGAGTCTGGCGGAGGTCTG
    GTGCAGCCAGGAGGCAGCCTGCGGCTGTCTTGTGCTGCGTCTGGTTTCACCTTC
    TCTCACAGCGGCATGTCTTGGGTGCGCCAAGCACCGGGCAAGGGCCTGGAGTGG
    GTCTCCACAATTAACTCCGGCGGGGCCTCCACCTATTACACCGACTCTGTAAAG
    GGTCGGTTTACCATTAGCCGCGATAACGCCAAAAATATGTTGTATTTGCAGCTT
    AACTCCCTGAAGACCGAAGATACCGCTATGTATTACTGCGCAAAGGGTGGGAGC
    GGTTACGGCGACGCCTCCCGCATGACCTCTCCGGGATCTCAGGGAACCCAAGTT
    ACCGTGAGTAGT
    DR591- 1002 CAGGTGCAGCTCCAGGAATCTGGAGGCGGTTCCGTGCAGGCAGGCGGTTCCCTG
    hIL27 AGGCTTAGTTGTACCGCCTCTGGGGCTATCGCCTCCGGCTACATTGACTCTCGC
    Ra_ TGGTGTATGGCCTGGTTCAGGCAGGCTCCAGGTAAGGAGCGCGAGGGTGTCGCG
    VH GCTATTTGGCCTGGTGGCGGACTGACTGTGTACGCCGATTCTGTGAAGGGCCGG
    H24 TTTACTATTAGCAGGGATCATGCGAAAAATACCCTTTACTTGCAGATGAACAAT
    CTGAAGCCGGAGGACACGGCCATGTACTATTGCGCCGCTGGCTCACCTAGAATG
    TGTCCTAGCTTGGAGTTCGGGTTTGATTACTGGGGCCAGGGAACCCAGGTGACC
    GTCTCTAGCGGTGGGAGCGGCGGGAGCGGGGGAAGCGGGCAGGTTCAGTTGCAG
    GAATCAGGAGGCGGACTGGTGCAACCGGGAGGCTCCCTGCGCCTGTCTTGTGCT
    GCCTCTGGTTTTACTTTTAGCCATAGCGGGATGTCCTGGGTTCGCCAGGCTCCA
    GGCAAGGGCCTGGAGTGGGTATCTACCATCAACTCTGGAGGTGCCAGCACCTAT
    TACACCGACAGCGTGAAGGGGAGGTTCACCATCTCCCGCGACAACGCTAAGAAC
    ATGCTGTACCTCCAGCTCAACTCTCTGAAGACCGAGGACACCGCTATGTATTAC
    TGCGCGAAGGGCGGTTCCGGTTACGGAGACGCCTCCCGCATGACCAGTCCGGGT
    TCCCAAGGTACACAGGTGACCGTGTCTAGC
    DR592- 1003 CAGGTTCAACTCCAGGAGTCCGGGGGCGGTTCCGTGCAAGCTGGAGGTTCACTG
    hIL27 CGCCTGAGCTGCACTGCGCCAGGCTTCACATCAAATTCTTGTGGTATGGATTGG
    Ra_ TATCGGCAAGCCCCCGGAAAAGAGCGGGAGTTCGTGTCCAGTATTAGCACAGAC
    VH GGTACGACCGGATATGCGGACTCTGTGAAAGGACGCTTCACGATTTCCAAAGAC
    H1 AAGGCCAAGGACACCGTGTACCTTCAGATGAACTCACTGAAACCAGAGGACACG
    GGCATGTACTCCTGTAAGACGAAGGACGGAACAATCGCCACTATGGAATTGTGC
    GATTTCGGCTATTGGGGCCAGGGGACGCAGGTTACCGTTTCTTCAGGGGGAGGG
    AGTCAGGTTCAGTTGCAGGAGTCCGGCGGTGGCTTGGTGCAACCTGGGGGAAGC
    CTGCGTCTTTCTTGTGCAGCCAGCGGCTTCACCTTCAGTTCATACCCCATGAGC
    TGGGTCCGTCAGGCCCCCGGTAAAGGGCTGGAGTGGATCTCAACCATCTCTGCC
    GGTGGCGACACCACGCTTTACGCTGACTCCGTCAAAGGCAGATTCACCAGTAGC
    AGAGACAACGCGAAGAACACCCTCTATTTGCAGCTTAACTCCCTCAAGACCGAG
    GACGCAGCTATCTACTATTGTGCTAAGAGGATTGACTGTAACAGCGGCTACTGT
    TATCGTCGCAACTATTGGGGCCAGGGCACTCAGGTCACAGTGTCTTCC
    DR592- 1004 CAGGTCCAGCTCCAGGAGAGCGGCGGAGGGTCTGTGCAGGCGGGCGGTAGTTTG
    hIL27 CGCTTGAGCTGTACCGCACCCGGATTCACCTCCAACAGCTGCGGTATGGACTGG
    Ra_ TATCGCCAGGCTCCTGGTAAAGAGCGTGAGTTCGTGTCTTCAATCAGCACCGAC
    VH GGTACAACTGGGTATGCCGATTCCGTGAAAGGAAGATTCACCATCTCCAAGGAC
    H1 AAGGCCAAAGACACAGTTTATCTTCAGATGAACAGTCTGAAGCCCGAGGACACC
    GGCATGTATTCTTGTAAGACTAAGGACGGGACGATTGCGACAATGGAACTGTGC
    GACTTCGGTTACTGGGGCCAGGGGACTCAGGTAACTGTGTCAAGCGGAGGCTCT
    GGCGGAAGTGGAGGCTCAGGACAGGTGCAGCTCCAGGAGTCAGGAGGGGGCCTG
    GTCCAGCCGGGCGGGTCTCTGCGCCTCTCTTGCGCTGCCTCTGGGTTCACATTC
    AGCAGTTACCCTATGTCCTGGGTACGCCAGGCTCCAGGCAAAGGTCTGGAGTGG
    ATCTCCACCATCAGTGCCGGAGGCGATACCACTCTGTATGCCGACAGCGTGAAG
    GGACGCTTTACCTCCTCACGCGATAATGCCAAGAACACTCTGTACCTGCAACTC
    AATAGTCTGAAGACTGAGGACGCGGCCATCTATTACTGCGCCAAGCGCATTGAT
    TGCAATAGTGGCTACTGTTACCGGCGCAACTATTGGGGACAGGGTACTCAGGTA
    ACAGTCAGCTCC
    DR592- 1005 CAGGTCCAACTGCAAGAGTCTGGAGGGGGCTCTGTGCAGGCCGGAGGCTCCCTT
    hIL27 CGCCTGTCTTGTACCGCCCCAGGTTTTACCTCAAACTCCTGCGGCATGGATTGG
    Ra_VH TATAGACAGGCTCCTGGGAAAGAGAGGGAGTTCGTGTCTTCCATCAGCACCGAC
    H2 GGTACAACCGGCTACGCGGATTCCGTGAAAGGTCGCTTTACCATTTCAAAGGAC
    AAAGCTAAAGATACCGTGTACCTCCAGATGAACTCACTGAAGCCCGAGGACACT
    GGCATGTACTCTTGTAAGACCAAGGATGGCACCATCGCCACTATGGAGTTGTGT
    GATTTCGGGTACTGGGGCCAGGGCACACAAGTGACCGTCTCCAGCGGTGGAGGC
    AGCCAGGTGCAGCTTCAAGAGTCCGGCGGTGGGCTGGTCCAGCCAGGAGGCTCA
    CTCCGCCTGTCCTGTGCGGCTTCCGGGTTTACCTTCTCACTGTCCGGCATGTCC
    TGGGTCCGCCAGGCCCCCGGCAAAGGCCTTGAGTGGGTGTCCGCTATTAGCTCC
    GGTGGAGCCAGCACTTACTATACTGACTCTGTTAAAGGCCGGTTTACAATCTCC
    CGTGACAATGCCAAGAACATCCTGTATCTTCAGCTGAACAGTCTCAAGACAGAG
    GATACTGCCATGTACTATTGTGCTAAAGGTGGCTCCGGCTACGGCGACGCGAGC
    CGTATGACTTCTCCTGGCTCCCAGGGCACTCAGGTGACTGTTTCCAGC
    DR592- 1006 CAGGTCCAGCTTCAGGAGAGCGGGGGTGGGAGCGTGCAGGCCGGGGGCTCTCTG
    hIL27 CGCCTGTCCTGCACAGCGCCCGGTTTTACGTCCAACTCTTGCGGCATGGATTGG
    Ra_VH TATCGCCAAGCGCCTGGCAAGGAAAGAGAGTTTGTCAGCTCCATCAGCACCGAT
    H2 GGCACTACCGGCTACGCGGATTCTGTAAAGGGTCGTTTCACCATCAGTAAGGAT
    AAGGCTAAGGACACGGTGTACCTCCAGATGAACTCCCTCAAGCCCGAGGATACC
    GGGATGTACTCTTGCAAGACCAAGGACGGCACCATCGCCACTATGGAGCTTTGC
    GACTTCGGCTATTGGGGCCAGGGAACTCAGGTGACTGTGTCAAGTGGTGGGTCA
    GGAGGTAGCGGAGGTTCTGGCCAGGTGCAGCTTCAGGAATCTGGCGGTGGGCTC
    GTCCAGCCGGGAGGCTCTCTGCGCCTGAGCTGCGCAGCCTCTGGCTTTACCTTT
    TCTCTGTCTGGCATGTCTTGGGTCCGCCAGGCACCTGGAAAGGGGCTGGAGTGG
    GTTTCCGCCATCTCCTCTGGTGGCGCATCCACATATTACACCGACTCTGTCAAG
    GGCCGCTTCACCATTTCACGCGATAATGCCAAGAACATCCTGTACCTTCAGCTG
    AACTCCCTGAAGACCGAGGACACAGCTATGTATTACTGCGCTAAGGGAGGGTCC
    GGCTACGGGGATGCGAGCAGAATGACCAGCCCTGGTTCACAAGGCACCCAGGTA
    ACTGTTAGCAGT
    DR592- 1007 CAAGTCCAACTTCAGGAGTCCGGCGGGGGCTCTGTGCAGGCTGGAGGGTCTCTG
    hIL27 CGCCTGTCCTGCACTGCACCTGGGTTCACTTCAAACTCTTGCGGCATGGACTGG
    Ra_VH TATCGCCAGGCCCCAGGCAAGGAACGTGAGTTTGTGTCCAGCATTTCAACTGAC
    H3 GGCACAACCGGGTATGCTGATAGCGTGAAGGGTAGGTTTACCATCTCCAAGGAT
    AAGGCCAAGGATACCGTGTACTTGCAGATGAACTCCCTCAAACCTGAGGATACC
    GGAATGTATAGCTGCAAGACCAAAGATGGAACCATCGCTACTATGGAGCTGTGT
    GACTTTGGCTACTGGGGGCAGGGCACCCAGGTGACCGTGTCCAGCGGCGGTGGA
    TCTCAGGTCCAGCTCCAGGAGAGCGGGGGCGGGTCTGTGCAGGCAGGCGGGTCC
    CTGCGTCTGTCATGCGTCGCGTCAGGCTACGTCTCCTGCGATTACTTCCTGCCT
    TCCTGGTATCGCCAGGCCCCTGGCAAGGAAAGGGAGTTCGTCAGTATCATTGAC
    GGAACCGGCTCCACCAGCTACGCTGCCTCCGTCAAGGGCCGCTTCACCGCCTCT
    GAGGACAAAGGGAAGAACATCGCCTACCTCCAGATGAACAGTCTGAAACCAGAG
    GATACTGCAATGTACTATTGCAAGGCCTCCTGTGTCCGTGGCCGTGCCGTTTCT
    GAGTACTGGGGCCAAGGGACTCAGGTGACTGTCTCCTCC
    DR592- 1008 CAGGTTCAGTTGCAGGAGAGTGGAGGGGGCTCCGTGCAGGCCGGTGGCTCCCTG
    hIL27 AGGCTGTCCTGCACAGCTCCCGGCTTCACCAGTAATTCCTGTGGCATGGACTGG
    Ra_VH TATCGCCAGGCCCCCGGTAAGGAAAGAGAGTTTGTGTCCAGTATCTCAACCGAC
    H3 GGCACCACTGGCTATGCGGACTCCGTCAAGGGCAGGTTCACTATCTCCAAGGAT
    AAGGCCAAAGACACAGTGTACCTCCAAATGAACTCTCTCAAGCCCGAGGACACG
    GGCATGTATTCCTGTAAAACCAAGGACGGCACCATCGCTACTATGGAGCTGTGT
    GATTTCGGATACTGGGGCCAGGGAACCCAGGTGACCGTGTCAAGCGGAGGTAGT
    GGTGGCTCAGGCGGGTCCGGGCAGGTCCAACTCCAGGAGTCTGGAGGCGGGAGT
    GTGCAGGCTGGTGGCTCCCTGCGGCTGAGCTGCGTGGCTTCCGGGTATGTTTCT
    TGCGATTACTTCCTGCCGAGCTGGTACAGGCAGGCTCCCGGTAAGGAGCGTGAG
    TTCGTTTCCATCATTGACGGCACCGGGAGCACAAGCTACGCCGCTAGTGTGAAG
    GGACGCTTCACGGCAAGCGAAGACAAGGGCAAAAACATCGCGTACTTGCAGATG
    AACTCCTTGAAGCCCGAGGACACCGCTATGTATTACTGTAAAGCCTCATGCGTC
    AGAGGCAGGGCTGTCTCAGAGTACTGGGGTCAGGGCACGCAAGTGACAGTCTCT
    TCC
    DR592- 1009 CAAGTGCAACTCCAGGAGTCCGGCGGTGGGTCTGTGCAGGCTGGGGGCTCACTG
    - CGTCTGAGCTGCACCGCTCCCGGTTTTACCAGTAACTCTTGTGGTATGGACTGG
    hIL27 TATCGCCAGGCCCCCGGCAAGGAGAGGGAATTTGTCAGTTCCATCTCTACAGAC
    Ra_VH GGCACTACAGGATACGCCGACTCCGTCAAGGGGCGGTTCACCATCTCAAAAGAT
    H4 AAAGCAAAGGACACAGTCTACCTTCAGATGAACAGCCTGAAACCTGAGGACACT
    GGAATGTATAGCTGCAAGACAAAGGATGGAACAATCGCCACGATGGAGCTGTGT
    GACTTCGGATACTGGGGCCAGGGGACACAGGTCACTGTGTCCTCTGGAGGCGGG
    TCCCAGGTGCAGCTCCAGGAGAGCGGCGGAGGCCTGGTGCAGCCCGGCGAGTCC
    CTTAGGCTGAGCTGTACGGCGAGCGGCTTTACTTTCAGCAACTACGCCATGAGC
    TGGGTCCGTCAAGCGCCGGGGAAGGGGCTGGAGTGGGTTTCTGGCATCAACGTG
    GCATACGGCATCACCTCCTATGCTGATAGCGTCAAGGGCCGCTTCACCATTTCC
    AGAGATAATACCAAGAATACCCTCTACCTCCAGCTCAATTCCCTGAAGACCGAG
    GACACTGCTATTTATTACTGTGTGAAGCACTCTGGCACCACAATTCCTCGCGGC
    TTTATCAGCTATACAAAGAGAGGCCAGGGAACTCAGGTCACCGTCAGCTCT
    DR592- 1010 CAGGTCCAGTTGCAGGAATCTGGCGGGGGATCAGTGCAGGCCGGGGGCTCCCTG
    hIL27 CGTCTTTCTTGCACAGCCCCTGGCTTTACCTCCAATTCCTGTGGCATGGATTGG
    Ra_VH TATCGGCAGGCCCCCGGCAAGGAGCGCGAGTTTGTCTCTAGCATTAGCACCGAC
    H4 GGCACCACTGGTTACGCTGACTCAGTGAAGGGACGGTTCACCATTTCCAAGGAC
    AAGGCTAAAGACACAGTCTACCTTCAGATGAACAGTCTGAAGCCTGAGGATACA
    GGGATGTACTCCTGTAAGACCAAGGACGGCACCATCGCAACGATGGAGCTGTGC
    GACTTCGGCTATTGGGGGCAAGGGACCCAGGTGACTGTGTCCTCTGGGGGCTCC
    GGGGGCAGCGGAGGCTCCGGCCAAGTGCAACTCCAGGAGAGCGGCGGTGGACTG
    GTGCAGCCAGGCGAGAGCCTCCGGCTTTCCTGCACCGCAAGCGGCTTCACTTTT
    AGCAACTACGCTATGTCCTGGGTAAGGCAGGCTCCAGGTAAGGGCCTGGAGTGG
    GTGAGCGGTATTAACGTGGCATACGGCATCACTTCCTACGCGGACAGCGTCAAG
    GGCCGTTTTACTATCAGCAGGGATAATACTAAGAATACTCTGTACTTGCAGCTG
    AACAGCCTGAAGACTGAAGATACTGCCATCTATTACTGCGTGAAGCACTCTGGA
    ACAACCATTCCACGGGGCTTCATCAGTTACACCAAGCGGGGCCAGGGCACTCAG
    GTCACCGTGTCTTCC
    DR592- 1011 CAAGTGCAGCTCCAGGAGTCCGGCGGTGGAAGCGTGCAGGCCGGAGGCTCTCTG
    hIL27 CGCTTGAGTTGCACCGCCCCTGGATTCACATCTAACTCCTGTGGTATGGATTGG
    Ra_VH TACAGGCAGGCACCAGGCAAGGAACGTGAGTTCGTGTCTTCCATCAGTACCGAC
    H5 GGTACTACCGGCTACGCGGACTCCGTCAAAGGTAGATTTACGATCAGCAAAGAT
    AAGGCTAAGGATACCGTGTATCTCCAGATGAACTCCCTGAAACCTGAGGATACA
    GGTATGTATAGCTGCAAGACCAAGGACGGCACTATCGCGACTATGGAATTGTGT
    GACTTTGGTTACTGGGGCCAAGGAACCCAGGTGACCGTCAGTAGCGGTGGCGGT
    TCCCAAGTACAGCTGCAAGAGTCTGGAGGTGGATCTGTGCAGGCTGGGGGTAGT
    CTTCGCCTGTCTTGTACCGCCAGCGGTTACGTGTCCTGTGACTACTTTCTGCCC
    TCCTGGTACAGACAGGCTCCTGGTAAGGAGCGCGAGTTCGTGAGCGTCATCGAC
    GGCACAGGGTCCACCAGTTACGCGGCATCCGTAAAGGGACGTTTCACCGCTTCC
    CAAGATAAGGGCAAAAACATCGCTTATCTCCAGATGAACAGTTTGAAGCCTGAG
    GACACAGCGATGTATTACTGTAAGGCTTCCTGCGTGAGAGGCCGCGCTATCTCT
    GAATATTGGGGACAGGGCACTCAGGTGACTGTGTCTTCA
    DR592- 1012 CAGGTGCAGCTCCAGGAGTCTGGGGGTGGCTCCGTCCAGGCTGGCGGAAGCCTG
    - CGCCTGTCCTGTACCGCTCCGGGTTTCACAAGTAACAGTTGTGGAATGGATTGG
    hIL27 TATCGCCAGGCCCCCGGAAAGGAACGGGAGTTCGTCTCTAGCATCTCAACTGAC
    Ra_VH GGCACTACCGGCTACGCCGACTCCGTGAAGGGCCGTTTCACCATTAGCAAGGAC
    H5 AAGGCCAAAGACACGGTGTACCTCCAGATGAACTCCCTGAAGCCCGAGGATACC
    GGGATGTATAGCTGTAAGACCAAGGACGGTACTATCGCTACGATGGAGCTGTGT
    GACTTCGGATACTGGGGCCAGGGGACCCAGGTGACTGTTTCCAGCGGTGGCTCC
    GGTGGGTCCGGCGGTTCTGGCCAGGTGCAGCTTCAGGAGTCCGGCGGTGGGAGC
    GTCCAAGCTGGCGGTTCCCTGCGCTTGAGTTGCACAGCATCTGGCTATGTGTCC
    TGTGACTATTTCTTGCCATCCTGGTACAGACAAGCGCCTGGTAAGGAGAGAGAG
    TTCGTGTCCGTGATTGATGGGACGGGCTCAACAAGCTATGCCGCTTCCGTTAAA
    GGAAGGTTTACCGCTTCTCAAGATAAAGGGAAGAACATCGCTTATCTCCAGATG
    AATAGCCTCAAACCAGAGGATACTGCTATGTATTACTGCAAGGCATCTTGTGTG
    CGTGGACGTGCAATCTCCGAGTATTGGGGACAAGGCACCCAGGTTACAGTGTCT
    TCA
    DR592- 1013 CAGGTGCAGCTCCAGGAGTCTGGAGGTGGCTCCGTTCAGGCTGGCGGAAGCCTG
    - CGGTTGAGCTGTACTGCCCCTGGATTTACCTCCAATTCTTGTGGCATGGATTGG
    hIL27 TATAGACAGGCTCCAGGGAAAGAGCGCGAGTTTGTCTCCAGCATTTCCACCGAT
    Ra_VH GGTACGACTGGTTATGCCGACAGCGTTAAGGGTAGATTTACAATCAGTAAGGAC
    H6 AAAGCTAAGGACACAGTGTATTTGCAGATGAACTCTCTGAAACCGGAGGATACA
    GGTATGTATAGTTGTAAGACAAAAGATGGCACCATTGCTACTATGGAACTTTGT
    GACTTCGGCTACTGGGGACAGGGCACTCAGGTAACAGTCTCTAGCGGTGGAGGC
    TCTCAAGTGCAGCTTCAGGAGTCTGGCGGAGGCCTCGTCCAGCCGGGAGGCTCC
    TTGCGCCTGAGCTGTGCCGCTTCTGGTTTTTCATTTAGCTCCTATGCTATGAAA
    TGGGTGCGCCAGGCTCCCGGCAAGGGCCTGGAGTGGGTCTCCACGATTTCCTCT
    GGGGGCTCAAGCACCAACTACGCCGACAGCGTAAAGGGCCGTTTTACCATCTCT
    CGGGACAACGCCAAAAACACCCTGTACCTTCAGTTGAACTCACTGAAAATCGAG
    GATACTGCAATGTATTACTGTGCCAAGGCCATCGTCCCAACCGGAGCTACAATG
    GAAAGGGGCCAGGGGACCCAGGTCACCGTGAGTAGC
    DR592- 1014 CAGGTGCAGTTGCAGGAATCTGGTGGAGGCAGCGTGCAAGCTGGAGGCTCTCTG
    hIL27 AGGTTGAGCTGCACCGCCCCTGGGTTTACAAGCAACTCATGTGGCATGGACTGG
    Ra_VH TATCGGCAAGCGCCTGGGAAAGAGCGCGAATTTGTAAGCTCTATCTCTACTGAC
    H6 GGCACAACCGGCTACGCAGATAGCGTGAAGGGCAGGTTCACCATCTCAAAGGAT
    AAAGCCAAGGATACCGTGTACCTGCAAATGAACTCCCTTAAACCCGAGGATACC
    GGCATGTATAGCTGCAAGACCAAGGACGGCACCATCGCAACGATGGAGCTGTGC
    GACTTCGGTTATTGGGGACAGGGAACCCAGGTGACCGTTAGTTCCGGTGGCTCA
    GGCGGTAGCGGAGGCAGTGGCCAGGTGCAGTTGCAAGAGAGCGGAGGTGGGCTG
    GTGCAGCCAGGGGGCTCCCTGCGTCTGTCCTGCGCAGCCAGCGGCTTTAGCTTT
    TCCAGCTATGCCATGAAATGGGTTCGGCAAGCGCCTGGGAAGGGTCTGGAATGG
    GTGTCCACTATCTCCTCAGGGGGCTCCTCTACAAACTACGCAGATTCAGTGAAG
    GGTCGGTTTACTATTTCTAGGGACAACGCGAAGAACACCCTGTACCTTCAGTTG
    AACTCCCTCAAGATTGAGGATACTGCCATGTACTATTGCGCGAAGGCCATCGTA
    CCCACCGGCGCTACAATGGAGAGGGGCCAGGGCACCCAAGTAACTGTCTCCTCA
    DR592- 1015 CAAGTGCAGTTGCAGGAGAGCGGTGGGGGATCTGTCCAGGCCGGAGGCAGTCTC
    hIL27 CGCCTGTCCTGCACTGCCCCTGGCTTCACCTCTAACAGTTGTGGCATGGACTGG
    Ra_VH TATCGCCAGGCCCCTGGTAAAGAGCGCGAATTTGTCAGCTCAATCAGTACAGAT
    H7 GGCACAACTGGTTATGCTGACAGCGTTAAGGGCCGCTTTACGATCAGCAAAGAC
    AAGGCTAAAGATACTGTGTACCTCCAGATGAACAGCCTCAAGCCTGAAGACACC
    GGAATGTATAGCTGTAAGACCAAGGACGGCACCATTGCGACAATGGAACTGTGC
    GACTTTGGCTATTGGGGCCAAGGGACCCAGGTCACAGTCAGCAGTGGAGGGGGC
    AGCCAGGTGCAGTTGCAGGAATCAGGGGGTGGCCTTGTGCAGCCTGGCGGGAGT
    CTGCGCCTGTCATGTGCGGCCTCCGGGTTCACCTTCAGCTCCTACCCAATGTCT
    TGGGTGAGGCAGGCACCTGGCAAGGGCCTGGAGTGGATCAGCACTATCAGCGCA
    GGCGGTGACACCACTCTGTACGCAGACAGCGTGAAGGGAAGATTCACCAGTAGC
    CGCGATAACGCGAAGAACACACTGTATCTCCAGCTCAATTCACTCAAGACCGAG
    GACACTGCCATCTACTATTGTGCCAAACGCATTGATTGTAATTCTGGCTACTGC
    TATCGGCGTAACTACTGGGGACAGGGCACCCAGGTTACCGTCAGTTCC
    DR592- 1016 CAGGTTCAGCTTCAAGAGAGTGGAGGTGGGTCCGTCCAGGCCGGAGGCTCACTG
    hIL27 CGGCTGTCTTGCACCGCTCCTGGTTTCACTAGCAACTCCTGCGGCATGGATTGG
    Ra_VH TATAGGCAAGCCCCTGGTAAGGAACGTGAGTTTGTTTCTTCCATCTCCACAGAT
    H7 GGTACTACCGGGTATGCTGACAGTGTGAAAGGCCGTTTTACCATCTCCAAGGAC
    AAGGCAAAGGACACCGTGTACCTCCAGATGAACAGTCTTAAACCCGAGGACACC
    GGCATGTACTCTTGTAAGACAAAGGATGGCACAATCGCCACTATGGAGCTGTGT
    GATTTCGGGTACTGGGGCCAGGGCACACAGGTGACTGTGTCAAGCGGGGGAAGC
    GGAGGCAGCGGTGGCTCAGGCCAGGTCCAGCTCCAGGAGTCCGGCGGTGGACTG
    GTTCAACCGGGTGGCAGCCTCCGTCTGTCCTGCGCCGCGAGTGGATTCACGTTC
    AGTAGCTACCCCATGTCTTGGGTCAGACAGGCTCCCGGCAAAGGTCTCGAATGG
    ATCTCTACAATCTCTGCCGGTGGGGACACAACCCTGTATGCGGATAGCGTGAAA
    GGGAGATTCACCAGCAGTAGGGACAACGCTAAGAACACCCTGTATCTTCAGCTG
    AACAGCCTGAAAACCGAAGACACAGCGATCTATTACTGTGCAAAGAGAATTGAT
    TGCAACAGCGGGTATTGCTACCGTCGCAACTATTGGGGGCAGGGAACCCAAGTC
    ACTGTGTCCTCC
    DR592- 1017 CAGGTGCAGCTCCAGGAATCCGGTGGAGGTTCTGTGCAGGCCGGTGGCAGCCTC
    hIL27 CGTCTTAGCTGCACCGCTCCGGGGTTTACCTCCAACAGCTGTGGTATGGATTGG
    Ra_VH TATCGTCAGGCCCCTGGTAAGGAGCGGGAGTTTGTGTCTTCCATTTCAACTGAT
    H8 GGCACCACTGGTTACGCCGACAGCGTAAAGGGTCGTTTCACAATCAGTAAGGAT
    AAGGCAAAGGACACCGTCTATTTGCAGATGAACAGCCTGAAGCCGGAAGACACA
    GGGATGTACTCTTGCAAGACAAAGGACGGCACGATTGCTACGATGGAGCTGTGT
    GACTTCGGCTACTGGGGCCAGGGTACACAGGTGACCGTGTCCAGCGGCGGGGGC
    AGTCAGGTTCAGTTGCAGGAGTCCGGCGGTGGCAGCGTCCAGGTGGGCGGTAGC
    CTGCGCCTGTCCTGTGCTGCATCCGGCTTTACCTTCTCTAGTTATCCAATGAGT
    TGGGTCCGCCAGGCTCCAGGGAAAGGTCTGGAATGGATCTCCACCATTTCCGCA
    GGTGGGGACACCACACTGTACGCCGATAGCGTGAAGGGCAGATTCACCAGCTCC
    AGAGACAATGCCAAAAACACTTTGTACCTCCAGCTGAATAGCCTGAAGACCGAG
    GATACCGCCATCTACTATTGTGCCAAGCGTATTGATTGTAATTCCGGCTATTGT
    TATCGCAGAAACTACTGGGGCCAGGGCACACAGGTCACTGTATCTAGC
    DR592- 1018 CAGGTGCAGCTCCAGGAGAGCGGCGGTGGCTCTGTCCAGGCTGGGGGAAGTCTG
    hIL27 CGTTTGTCTTGCACTGCACCCGGATTCACCTCAAATTCCTGCGGTATGGATTGG
    Ra_VH TACAGACAAGCGCCTGGCAAGGAGCGTGAATTTGTAAGCTCCATTAGCACCGAC
    H8 GGGACCACTGGCTATGCTGATAGCGTGAAGGGCCGCTTCACCATTTCTAAGGAT
    AAGGCTAAAGACACCGTGTACCTCCAGATGAACTCCTTGAAGCCAGAGGATACC
    GGGATGTATTCTTGTAAGACCAAGGACGGCACCATCGCAACTATGGAACTCTGT
    GACTTCGGTTACTGGGGGCAGGGAACCCAAGTGACAGTCTCTTCCGGGGGCTCC
    GGCGGTTCTGGCGGATCTGGGCAGGTGCAACTTCAGGAATCCGGTGGAGGTAGC
    GTCCAGGTGGGAGGCTCCCTGCGCCTGAGTTGTGCCGCAAGTGGCTTCACCTTC
    TCATCCTACCCCATGTCTTGGGTACGCCAGGCTCCCGGCAAGGGCCTGGAGTGG
    ATCTCCACCATCTCCGCCGGAGGTGACACTACCCTGTACGCCGACTCCGTGAAG
    GGCCGCTTTACAAGCTCCCGTGACAACGCTAAGAATACACTGTACCTCCAGCTT
    AATTCACTGAAGACCGAAGACACGGCTATCTACTATTGCGCCAAGCGCATTGAT
    TGTAACAGCGGGTACTGTTACAGGAGAAACTATTGGGGACAGGGCACACAGGTG
    ACTGTGTCCTCC
    DR592- 1019 CAGGTTCAGCTCCAGGAGAGCGGCGGAGGCAGCGTGCAGGCTGGTGGCAGTCTG
    hIL27 CGCCTGAGCTGCACAGCCCCCGGCTTCACCAGTAACAGCTGTGGAATGGACTGG
    Ra_VH TATCGTCAAGCGCCTGGCAAGGAAAGGGAGTTCGTGTCTAGTATCAGCACCGAT
    H9 GGCACCACAGGATACGCCGACTCCGTGAAGGGACGCTTCACTATCTCAAAGGAT
    AAGGCAAAAGATACAGTGTATCTCCAGATGAACTCCCTCAAGCCTGAAGACACA
    GGCATGTACTCTTGTAAGACCAAGGACGGCACTATCGCTACTATGGAGTTGTGC
    GACTTCGGATACTGGGGACAAGGAACCCAGGTCACCGTATCCTCAGGGGGAGGT
    TCACAGGTGCAGCTTCAGGAGTCCGGTGGCGGTTCTGTGCAGAGTGGAGGCTCC
    CTGCGTTTGAGTTGCGCAGCCAGTGGCTTCACCTACTCTACTAGCAACAGCTGG
    ATGGCGTGGTTCCGCCAGGCCCCCGGCAAAGAACGCGAGGGCGTTGCCGCTATT
    TACACCGTGGGCGGTTCCATTTTCTACGCCGATTCCGTGCGTGGCAGGTTTACT
    ATCTCTCAGGATGCCACTAAAAATATGTTCTACCTGCAAATGAACACACTGAAG
    CCCGAGGACACCGCTATGTATTACTGCGCAGCCGCTTCTGGCCGCCTGAGAGGC
    AAGTGGTTTTGGCCCTACGAGTACAATTACTGGGGTCAGGGCACCCAGGTGACG
    GTGTCTAGC
    DR592- 1020 CAGGTGCAACTCCAGGAGTCTGGAGGGGGCTCTGTCCAGGCCGGAGGCTCTCTC
    hIL27 CGTCTGAGCTGCACCGCTCCCGGCTTCACCAGTAATAGCTGCGGTATGGACTGG
    Ra_VH TACAGACAGGCTCCAGGCAAGGAGAGAGAATTTGTCAGCTCCATTTCTACTGAT
    H9 GGGACTACGGGCTACGCCGACTCCGTGAAGGGCCGCTTTACCATCTCTAAGGAT
    AAGGCTAAGGACACCGTATATTTGCAGATGAACTCCCTGAAGCCAGAAGATACT
    GGCATGTATAGCTGCAAGACGAAGGATGGAACCATCGCCACTATGGAATTGTGC
    GATTTCGGTTACTGGGGCCAGGGAACACAGGTGACTGTGAGTTCCGGGGGCTCA
    GGCGGGTCTGGAGGCTCTGGACAGGTGCAACTCCAGGAGAGCGGAGGCGGTTCA
    GTCCAGTCTGGGGGCTCCCTTCGCCTGAGTTGCGCTGCCAGTGGCTTTACCTAC
    AGTACCAGCAACTCCTGGATGGCGTGGTTCAGACAGGCACCCGGAAAGGAACGC
    GAAGGCGTGGCTGCCATCTACACAGTCGGGGGCTCCATCTTCTACGCTGACTCC
    GTTAGAGGCCGCTTCACCATTTCTCAGGATGCCACCAAAAATATGTTCTATCTG
    CAAATGAACACCTTGAAGCCCGAGGACACCGCCATGTATTACTGCGCAGCTGCC
    AGCGGACGGCTTCGCGGTAAGTGGTTCTGGCCGTATGAGTATAACTACTGGGGA
    CAGGGCACCCAGGTCACGGTGAGTTCT
    DR592- 1021 CAAGTGCAGTTGCAGGAAAGTGGAGGCGGTTCCGTGCAGGCAGGAGGCAGTCTG
    hIL27 AGGCTGAGTTGTACCGCGCCTGGCTTTACCTCAAACAGTTGCGGCATGGACTGG
    Ra_VH TATAGGCAGGCCCCAGGCAAGGAGCGCGAGTTTGTCTCAAGCATCTCCACCGAT
    H10 GGAACCACTGGCTACGCCGACTCCGTCAAGGGAAGGTTCACTATCTCCAAGGAT
    AAGGCCAAGGACACCGTGTATCTCCAGATGAACTCATTGAAGCCAGAAGACACC
    GGGATGTACTCCTGTAAAACCAAGGACGGCACGATTGCGACAATGGAACTGTGT
    GATTTCGGTTACTGGGGTCAGGGAACGCAGGTGACCGTGTCTAGCGGGGGCGGT
    TCCCAGGTTCAGCTCCAGGAGAGCGGTGGGGGCTCTGTGCAGGCCGGTGGAAGT
    CTGCGTCTGAGCTGTCGCGCCTCTGGCTCCACATACTCCAACTATTGCCTGGGA
    TGGTTTCGGCAAATCACGGGTAAAGAAAGAGAGGGCGTGGCTGTCATCAACTGG
    GTGGGCGGAATGCTGTACTTCGCCGATAGTGTGAAGGGGCGCTTCACCGTTTCC
    CAGGATCAAGCTAAAAACACACTTTACCTTCAGATGAACAGTCTGAAACCCGAA
    GACACCGCAATGTATTACTGTGCCGCTGAGAGTGTCAGTTCCTTCTCATGCGGA
    GGTTGGCTTACGAGGCCTGATCGCGTGCCGTATTGGGGCCAGGGGACCCAGGTG
    ACCGTGAGTTCT
    DR592- 1022 CAGGTGCAGTTGCAGGAATCCGGCGGAGGCTCCGTGCAGGCTGGGGGAAGCCTG
    hIL27 AGACTTAGCTGCACTGCTCCGGGATTTACGAGCAACAGCTGTGGCATGGACTGG
    Ra_VH TACAGACAGGCCCCTGGGAAGGAGCGCGAGTTCGTGTCAAGCATCAGCACTGAC
    H10 GGCACAACTGGGTACGCTGATAGCGTGAAGGGCCGTTTTACCATCTCCAAGGAT
    AAGGCCAAAGACACTGTCTACCTGCAAATGAACTCCCTCAAGCCTGAGGACACC
    GGAATGTACTCCTGTAAGACTAAGGACGGGACCATTGCCACGATGGAGCTTTGT
    GACTTCGGCTATTGGGGACAGGGAACCCAGGTCACCGTCTCTAGTGGAGGCAGC
    GGCGGTAGTGGCGGGTCCGGCCAGGTTCAGCTCCAGGAGTCCGGTGGCGGATCT
    GTGCAAGCAGGAGGCAGCCTGCGCCTTAGCTGCCGTGCGAGCGGCAGCACTTAC
    AGCAATTATTGTCTGGGTTGGTTTCGTCAGATCACTGGTAAAGAACGGGAGGGC
    GTGGCCGTCATCAACTGGGTCGGCGGTATGCTGTACTTCGCGGACAGCGTCAAA
    GGCCGGTTTACCGTGTCTCAGGACCAGGCGAAGAACACATTGTACCTCCAGATG
    AATAGCCTGAAGCCTGAGGATACAGCTATGTATTACTGTGCAGCGGAGTCCGTC
    TCTTCATTCAGCTGTGGTGGATGGCTCACGAGACCGGATAGAGTGCCTTACTGG
    GGCCAGGGCACCCAGGTGACCGTGTCCAGC
    DR592- 1023 CAGGTGCAGTTGCAGGAGTCTGGTGGCGGTTCCGTTCAGGCAGGCGGTTCCCTG
    hIL27 AGACTGTCCTGCACCGCCCCTGGTTTTACCTCCAACTCCTGTGGCATGGATTGG
    Ra_VH TATCGCCAGGCACCAGGCAAGGAACGCGAGTTCGTATCTTCCATTAGCACTGAC
    H11 GGCACAACTGGTTACGCCGATTCAGTCAAGGGGCGCTTTACAATCAGTAAGGAC
    AAGGCTAAGGATACCGTTTACTTGCAGATGAATAGCCTGAAACCAGAGGACACC
    GGAATGTACTCTTGCAAAACTAAAGACGGCACCATTGCAACTATGGAACTCTGT
    GACTTTGGGTATTGGGGTCAAGGCACTCAAGTGACCGTCTCCTCTGGCGGGGGC
    TCTCAGGTCCAGTTGCAGGAAAGCGGCGGAGGGAGCGTGCAGGCTGGAGGTAGT
    CTCAGGCTGTCTTGCCGCGCCAGCGGAAGCACCTACTCAAACTACTGCCTTGGC
    TGGTTTAGACAGAGCACTGGTAAGGAGCGGGAGGGAGTGGCCGTCATCAACTGG
    GTCGGTGGGATGCTGTATTTCGCTGATAGCGTAAAGGGAAGATTTACGGTAAGC
    CAGGATCACGCAAAGAACACCGTGACCCTCCAGATGAACTCTCTGAAGCCCGAG
    GACACTGCCATGTACTATTGCGCAGCCGAATCCGTCAGTTCCTTCTCCTGCGGC
    GGATGGCTGACCCGCCCCGGAAGAGTTCCATATTGGGGTCAGGGGACCCAGGTG
    ACAGTTTCTTCT
    DR592- 1024 CAGGTGCAACTCCAGGAGAGCGGTGGAGGTAGCGTGCAGGCTGGCGGTTCCCTG
    hIL27 CGGCTGTCCTGCACCGCTCCGGGTTTTACCTCCAACTCCTGCGGGATGGATTGG
    Ra_VH TACAGACAGGCCCCCGGAAAGGAGCGCGAGTTTGTGTCTTCCATTAGCACCGAC
    H11 GGCACAACCGGCTATGCAGACAGTGTCAAGGGACGGTTCACAATCTCCAAGGAC
    AAAGCTAAAGACACGGTGTATCTTCAGATGAACAGCTTGAAGCCTGAAGATACT
    GGTATGTATTCCTGCAAAACCAAGGATGGTACTATCGCCACTATGGAACTCTGC
    GATTTCGGATATTGGGGACAGGGGACCCAGGTGACGGTGTCTAGCGGGGGCTCT
    GGTGGGTCTGGAGGCTCTGGTCAGGTGCAACTCCAGGAGAGCGGGGGCGGAAGC
    GTTCAGGCCGGGGGCAGCCTGCGGCTGTCCTGCCGGGCTAGTGGATCTACGTAC
    TCCAACTACTGCCTGGGATGGTTTCGCCAATCTACTGGAAAGGAGCGTGAGGGG
    GTGGCCGTCATCAACTGGGTGGGCGGAATGTTGTATTTTGCCGATTCTGTCAAA
    GGAAGGTTCACTGTGTCTCAGGACCATGCCAAGAACACCGTCACCCTCCAGATG
    AACTCTTTGAAGCCGGAAGATACCGCTATGTATTACTGCGCGGCAGAAAGCGTG
    AGTAGCTTCTCTTGCGGTGGGTGGCTGACACGTCCGGGTAGGGTGCCGTACTGG
    GGCCAGGGAACTCAGGTAACCGTCTCATCC
    DR592- 1025 CAGGTCCAACTCCAGGAATCCGGCGGGGGCTCCGTACAGGCAGGTGGCAGTCTG
    hIL27 AGGCTTTCCTGCACTGCCCCTGGTTTCACCAGCAACAGCTGTGGGATGGACTGG
    Ra_VH TATCGCCAGGCTCCCGGCAAAGAGCGGGAGTTCGTCAGCTCTATCTCAACCGAC
    H12 GGCACAACCGGGTATGCCGACTCCGTTAAAGGCCGGTTCACCATCAGCAAAGAC
    AAGGCCAAGGATACAGTCTACCTCCAGATGAACAGCCTGAAGCCTGAGGATACC
    GGAATGTATAGTTGCAAAACTAAGGATGGCACTATCGCCACTATGGAGTTGTGC
    GATTTCGGATACTGGGGACAGGGCACCCAGGTTACCGTCTCATCTGGAGGGGGC
    TCCCAGGTGCAGCTGCAAGAATCCGGCGGAGGCAGTGTCCAGGCTGGCGAATCC
    CTCCGCTTGAGCTGTCGTGCCAGCGGTAGTACCTACTCCAATTACTGCCTGGGT
    TGGTTTCGCCAGATCACCGGCAAGGAACGTGAAGGCGTGGCCGTCATCAACTGG
    GTAGGGGGTATGCTCTACTTCGCTGACTCCGTGAAGGGACGCTTCACGGTGAGT
    CAGGACCAGGCTAAAAACACCGTGTACCTTGAAATGAACTCCTTGAAGCCCGAG
    GACACCGCTATGTATTACTGCGCCACAGAGTCTGTTTCTTCCTTCTCATGCGGA
    GGCTGGCTGACTCGTCCAGACCGCGTGCCCTACTGGGGCCAGGGGACCCAGGTG
    ACCGTGTCCTCA
    DR592- 1026 CAAGTTCAGTTGCAGGAGAGTGGAGGCGGTTCTGTCCAGGCTGGGGGTAGTTTG
    hIL27 CGGTTGAGTTGCACCGCGCCTGGGTTCACCTCCAACAGCTGTGGTATGGATTGG
    Ra_VH TATCGCCAGGCCCCCGGCAAGGAGCGCGAGTTCGTGAGTTCCATCAGCACCGAC
    H12 GGCACCACTGGTTACGCAGACTCAGTGAAGGGAAGATTCACCATCAGCAAGGAC
    AAAGCCAAGGACACTGTGTATCTTCAGATGAATAGCCTCAAGCCGGAGGATACT
    GGCATGTATTCCTGCAAGACCAAGGACGGCACCATCGCTACGATGGAGTTGTGT
    GATTTCGGGTACTGGGGACAGGGAACCCAGGTAACTGTGAGTAGCGGAGGTAGC
    GGGGGAAGCGGCGGGTCAGGGCAGGTACAGCTTCAGGAGTCCGGCGGTGGGTCC
    GTTCAGGCCGGTGAGTCCTTGCGCCTGAGCTGCCGCGCCAGCGGTTCCACCTAC
    AGTAACTATTGTCTGGGCTGGTTTCGTCAGATCACAGGCAAGGAGCGCGAGGGC
    GTTGCTGTCATTAACTGGGTTGGCGGAATGCTGTATTTTGCCGACAGCGTGAAG
    GGTCGTTTCACGGTATCCCAAGACCAAGCAAAGAACACTGTCTATCTTGAAATG
    AACAGTCTGAAACCAGAAGACACCGCCATGTACTATTGTGCCACCGAGTCCGTA
    TCCAGTTTCTCCTGCGGCGGATGGCTGACCAGACCTGACCGTGTGCCATACTGG
    GGACAGGGGACACAGGTGACTGTGTCCAGC
    DR592- 1027 CAGGTGCAGCTCCAGGAGTCCGGGGGAGGCTCTGTGCAGGCCGGGGGTTCCCTG
    hIL27 AGACTTTCATGTACTGCACCAGGCTTTACCTCAAATTCTTGCGGGATGGACTGG
    Ra_VH TACAGGCAGGCCCCCGGTAAGGAGCGGGAGTTTGTGTCTTCCATTTCCACCGAT
    H13 GGTACAACCGGCTACGCGGACTCTGTGAAGGGCCGCTTTACCATTTCTAAGGAC
    AAGGCTAAAGACACCGTCTATCTCCAGATGAACTCTTTGAAGCCTGAAGACACA
    GGCATGTATAGCTGCAAGACAAAGGATGGCACCATTGCCACGATGGAGTTGTGC
    GACTTTGGCTATTGGGGTCAGGGCACCCAGGTCACTGTGTCTTCCGGCGGGGGC
    TCTCAGGTCCAACTCCAGGAGAGCGGGGGAGGGTCTGTTCAGGCTGGTGGCTCA
    CTGCGCCTCAGTTGCGTGGCCTCTGGATACGTGTCCTGTGACTACTTTCTGCCC
    TCTTGGTACAGACAGGCCCCAGGCAAAGAGCGCGAGTTCGTGAGCATCATTGAC
    GGTACTGGCTCTACAAGCTACGCGGCCTCCGTCAAGGGCCGTTTCACTGCCTCC
    CAAGACAGAGGTAAAAACATCGCTTATCTCCAGATGAACAGCCTGAAGCCCGAG
    GATACGGCTATGTACTATTGCAAGGCCAGCTGTGTACGTGGACGCACTATCTCT
    GAGTACTGGGGCCAGGGGACACAAGTGACGGTGTCCTCC
    DR592- 1028 CAGGTGCAGCTTCAAGAGAGCGGAGGCGGGTCTGTGCAGGCTGGTGGGTCCCTC
    hIL27 CGCCTGTCATGCACTGCCCCCGGCTTCACTTCTAACAGCTGCGGCATGGACTGG
    Ra_VH TATCGCCAGGCCCCAGGCAAAGAGCGCGAGTTTGTATCATCCATCTCCACCGAC
    H13 GGCACGACTGGCTACGCCGACTCCGTGAAGGGCCGGTTCACCATCAGCAAGGAC
    AAAGCCAAGGATACCGTGTACCTCCAGATGAACTCCCTCAAACCTGAAGACACT
    GGGATGTACTCATGCAAGACAAAAGACGGTACGATTGCCACTATGGAGCTGTGT
    GATTTCGGATACTGGGGACAGGGAACTCAGGTGACCGTTTCCTCTGGAGGCAGT
    GGAGGGAGCGGAGGCTCCGGCCAGGTGCAGCTGCAAGAGAGCGGTGGCGGTAGC
    GTGCAAGCCGGAGGCTCCCTCCGTCTTTCTTGTGTCGCGAGCGGCTACGTGAGC
    TGTGATTACTTTCTGCCCAGCTGGTATCGTCAAGCGCCAGGCAAAGAGCGCGAA
    TTTGTGTCTATTATCGACGGCACCGGCAGCACGAGCTACGCAGCCTCCGTGAAG
    GGACGTTTCACTGCTTCACAGGATCGCGGCAAAAACATTGCTTACCTCCAGATG
    AACTCCCTGAAGCCTGAGGACACAGCAATGTATTACTGTAAGGCCTCCTGTGTG
    CGTGGACGCACCATCTCAGAGTACTGGGGACAGGGAACCCAGGTGACCGTATCT
    TCC
    DR592- 1029 CAGGTTCAGCTTCAGGAGTCCGGGGGTGGCTCCGTCCAAGCTGGTGGCTCACTG
    hIL27 CGCCTGTCCTGCACCGCCCCTGGCTTCACCTCCAATTCCTGCGGAATGGACTGG
    Ra_VH TATCGCCAGGCCCCAGGCAAAGAACGCGAGTTCGTCAGTAGCATCTCTACTGAT
    H14 GGAACCACAGGCTACGCGGACAGCGTGAAGGGGCGTTTCACTATCTCCAAGGAC
    AAGGCCAAGGACACCGTGTACCTTCAAATGAACTCCCTGAAGCCCGAGGATACT
    GGAATGTACTCCTGTAAGACCAAGGACGGGACTATCGCCACTATGGAGCTGTGT
    GACTTCGGATATTGGGGCCAGGGCACGCAGGTGACCGTCAGCTCTGGGGGCGGG
    TCCCAGGTCCAGCTTCAGGAAAGTGGAGGCGGGTCCGTGCAGGCCGGAGGTTCC
    CTCCGCCTGTCATGTGTCGCAAGCGGCTACGTGTCTTGCGACTACTTCCTGCCC
    TCCTGGTATCGCCAGGCTCCGGGCAAGGAGAGAGAGTTCGTAAGCATCATTGAT
    GGCACCGGCTCTACTTCTTACGCCGCTAGTGTGAAGGGCCGCTTCACAGCGTCC
    CAGGATAAGGGTAAAAACATCGCTTACTTGCAGATGAATAGCCTGAAGCCTGAG
    GACACGGCAATGTATTACTGTAAGGCCTCCTGTGTTAGAGGCCGCGCTATTTCT
    GAATACTGGGGACAGGGCACTCAGGTGACAGTCTCCTCC
    DR592- 1030 CAGGTGCAGCTTCAGGAGTCCGGTGGGGGCTCTGTGCAGGCTGGAGGTTCCCTT
    hIL27 CGCCTGTCATGTACTGCCCCTGGGTTCACTTCTAACTCCTGTGGTATGGACTGG
    Ra_VH TATCGTCAGGCCCCTGGGAAGGAGCGTGAGTTCGTCAGCTCCATCTCTACTGAT
    H14 GGCACTACCGGCTATGCCGATTCTGTGAAGGGGCGTTTTACCATCAGCAAGGAC
    AAGGCCAAGGATACCGTGTACCTGCAAATGAACAGCTTGAAGCCTGAGGACACT
    GGCATGTATTCTTGTAAAACCAAAGACGGCACCATCGCCACAATGGAGCTGTGT
    GACTTTGGCTACTGGGGCCAGGGCACTCAAGTGACCGTGTCCTCAGGCGGGTCT
    GGCGGATCTGGGGGAAGCGGACAGGTGCAGCTTCAGGAGAGCGGAGGTGGCTCT
    GTCCAGGCCGGTGGGTCCCTGAGACTGTCTTGCGTGGCCAGTGGGTACGTGAGC
    TGCGATTACTTCCTCCCCAGTTGGTATAGGCAGGCCCCTGGAAAGGAACGTGAG
    TTCGTAAGCATCATTGACGGCACCGGCTCTACTTCTTATGCGGCCTCCGTAAAG
    GGCCGCTTCACTGCTTCCCAGGACAAGGGTAAGAATATCGCCTACCTTCAGATG
    AACAGCCTGAAACCCGAAGACACGGCTATGTATTACTGCAAGGCTTCCTGCGTA
    AGAGGGAGAGCAATCTCCGAGTATTGGGGCCAGGGCACCCAGGTGACTGTGTCT
    TCA
    DR592- 1031 CAGGTGCAGCTCCAGGAGAGCGGCGGGGGCTCCGTACAAGCGGGCGGTTCCCTC
    hIL27 CGTCTGTCTTGTACCGCCCCAGGCTTCACCAGTAACTCCTGTGGCATGGACTGG
    Ra_VH TACAGACAGGCTCCTGGCAAAGAAAGAGAGTTCGTATCCAGCATCTCCACCGAC
    H15 GGCACCACAGGCTACGCGGATTCAGTTAAGGGCAGATTTACGATCTCCAAGGAT
    AAGGCTAAAGATACTGTGTACCTCCAGATGAATAGCCTGAAGCCGGAAGACACC
    GGCATGTATAGCTGTAAGACTAAGGATGGCACCATTGCCACAATGGAGCTGTGC
    GACTTCGGCTACTGGGGTCAGGGAACACAGGTGACGGTGTCCTCTGGTGGCGGT
    AGCCAGGTTCAGTTGCAGGAATCTGGAGGTGGCTCTGTGCAGGCCGGTGGATCT
    CTGCGTCTGTCTTGCGTGGCCTCCGGCTACGTGAGTTGCGACTATTTCCTTCCC
    AGCTGGTATCGCCAGGCTCCAGGCAAGGAACGCGAGTTTGTGTCCATTATCGAC
    GGAACAGGCAGCACATCCTACGCAGCTAGTGTTAAGGGTAGATTCACTGCGAGC
    CAGGACAAGGGCAAAAACATCGCTTATCTTCAGATGAATACCCTCAAACCTGAG
    GACACCGCCATGTATTACTGCAAGGCCAGCTGTGTGCGTGGCCGCGCTATCTCT
    GAATATTGGGGCCAGGGCACCCAGGTGACAGTTTCCTCT
    DR592- 1032 CAGGTGCAGCTCCAGGAGAGCGGCGGAGGCTCAGTGCAGGCCGGGGGTTCATTG
    hIL27 AGGCTGTCCTGCACCGCCCCAGGGTTTACTAGCAACTCTTGTGGGATGGATTGG
    Ra_VH TATCGTCAGGCCCCTGGGAAGGAACGTGAGTTCGTTTCTAGTATCTCAACCGAT
    H15 GGTACAACCGGCTATGCAGACTCCGTAAAGGGCCGGTTCACGATCTCCAAAGAT
    AAGGCTAAGGACACTGTTTATCTGCAAATGAACTCCCTGAAGCCTGAGGACACC
    GGCATGTACTCCTGTAAGACTAAGGACGGCACCATCGCTACGATGGAGTTGTGC
    GACTTCGGATATTGGGGTCAGGGAACCCAGGTTACTGTGTCTAGCGGGGGCAGC
    GGTGGCAGCGGGGGATCTGGCCAGGTGCAGTTGCAGGAATCCGGGGGCGGTTCA
    GTGCAGGCAGGAGGCTCTCTTCGGTTGTCCTGCGTCGCGAGTGGCTATGTGTCT
    TGTGATTACTTCCTGCCATCCTGGTATCGTCAGGCCCCAGGGAAGGAACGTGAG
    TTCGTGTCCATCATTGATGGCACTGGCAGTACTTCCTACGCCGCTTCCGTGAAG
    GGTAGGTTTACAGCGAGTCAGGATAAGGGTAAGAACATCGCCTATCTCCAGATG
    AACACCCTGAAACCGGAGGACACAGCCATGTACTATTGCAAGGCCTCTTGTGTG
    CGTGGCCGCGCAATTAGCGAGTACTGGGGACAGGGTACACAGGTTACCGTCTCC
    TCC
    DR592- 1033 CAGGTCCAGCTCCAGGAGAGTGGTGGGGGCAGCGTGCAGGCCGGAGGCTCTCTT
    hIL27 AGACTCTCTTGCACCGCCCCCGGCTTCACATCCAACTCCTGTGGCATGGACTGG
    Ra_VH TATCGCCAGGCTCCCGGCAAGGAGAGGGAATTTGTGTCCAGCATTTCTACCGAC
    H16 GGAACCACAGGCTACGCTGACAGCGTTAAGGGACGTTTCACTATCAGCAAGGAT
    AAGGCCAAGGACACCGTATACCTCCAGATGAACTCCCTCAAACCCGAGGACACC
    GGCATGTATAGCTGTAAAACCAAGGATGGAACCATCGCGACTATGGAGCTGTGC
    GATTTCGGCTACTGGGGCCAGGGCACTCAAGTGACTGTTTCTAGCGGCGGGGGC
    AGCCAGGTGCAGCTTCAGGAGTCTGGCGGAGGCAGCGTCCAAGCTGGAGGTAGC
    CTGCGGCTCTCCTGTCGCGCTTCTGGCTCTACGTACAGTAATTATTGCCTGGGT
    TGGTTCAGACAGATCACCGGCAAAGAACGCGAGGGTGTTGCAGTCATCAACTGG
    GTTGGGGGAATGCTGTATTTTGCCGACAGTGTGAAGGGCAGGTTCACGGTCAGC
    CAAGACCAGGCCAAGAATACCGTCTACCTCCAGATGAACTCTTTGAAACCCGAA
    GACACCGCCATGTACTATTGTGCTGCGGAGTCAGCTTCATCTTTCTCTTGCGGA
    GGCTGGCTGACCCGTCCAGACCGCGTACCTTACTGGGGCCAGGGGACCCAGGTG
    ACCGTCTCCTCC
    DR592- 1034 CAAGTCCAGCTGCAAGAGAGTGGAGGGGGCAGCGTTCAGGCCGGAGGCTCTCTG
    hIL27 CGTCTTTCATGCACCGCGCCCGGTTTCACTTCCAACTCCTGCGGCATGGACTGG
    Ra_VH TATCGGCAGGCCCCAGGCAAGGAAAGGGAGTTCGTAAGCTCCATCTCCACTGAT
    H16 GGAACAACCGGCTATGCCGATTCCGTCAAGGGCCGCTTCACCATCAGCAAGGAT
    AAGGCAAAAGACACTGTCTATCTGCAAATGAACTCTCTGAAGCCCGAAGACACC
    GGAATGTACTCTTGTAAAACTAAGGACGGCACCATTGCCACTATGGAGCTGTGT
    GATTTCGGGTACTGGGGCCAGGGCACCCAGGTGACGGTCTCTAGCGGGGGCTCA
    GGGGGCTCTGGTGGCTCTGGTCAGGTGCAGCTCCAGGAGTCCGGTGGCGGAAGC
    GTGCAGGCTGGAGGTAGTCTGCGCCTGTCTTGTCGTGCCAGCGGCAGCACATAT
    AGCAATTACTGCCTTGGCTGGTTTAGACAGATTACTGGTAAGGAGCGGGAGGGC
    GTGGCCGTAATAAATTGGGTTGGCGGGATGCTCTATTTTGCAGACTCAGTCAAG
    GGCCGCTTCACAGTGTCCCAGGATCAGGCCAAGAACACCGTGTATCTCCAGATG
    AACTCCCTGAAGCCGGAAGACACCGCCATGTACTATTGTGCCGCAGAGTCCGCT
    TCCTCTTTCTCTTGCGGCGGATGGCTGACACGTCCTGATCGTGTGCCCTATTGG
    GGACAGGGCACACAGGTCACCGTGTCCTCC
    DR592- 1035 CAGGTTCAGCTGCAAGAGAGCGGCGGTGGCTCTGTGCAGGCTGGTGGCAGCTTG
    hIL27 AGACTGTCCTGTACTGCGCCTGGCTTCACTTCCAATTCTTGCGGCATGGACTGG
    Ra_VH TATAGACAAGCTCCGGGAAAAGAACGCGAATTTGTGTCTTCCATTAGCACCGAC
    H17 GGAACTACAGGCTATGCTGACAGCGTGAAGGGACGCTTTACCATCTCCAAGGAC
    AAGGCGAAGGATACCGTCTATTTGCAGATGAACAGTCTGAAACCAGAAGACACC
    GGCATGTATTCCTGCAAAACCAAAGATGGCACAATCGCCACTATGGAACTCTGT
    GATTTTGGCTACTGGGGCCAAGGGACCCAAGTTACCGTGTCTTCCGGCGGAGGC
    AGCCAAGTCCAGTTGCAAGAGTCAGGTGGCGGTCTGGTCCAGCCCGGAGGCTCT
    CTGAGGCTGAGTTGTGCCGCTTCCGGTTTCACATTCTCCCTGAGCGGTATGTCC
    TGGGTACGCCAGGCTCCCGGCAAGGGCCTCGAATGGGTGTCCGCGATCAGCTCT
    GGCGGGGCCTCCACTTATTACACAGACAGCGTTAAGGGGCGCTTCACAATCAGC
    CGCGATAACGCAAAGAATATGTTGTACTTGCAACTCAATTCTCTCAAGACAGAA
    GACACCGCGATGTATTACTGTGCTAAAGGGGGTTCCGGCTATGGCGATGCCTCT
    CGTATGACTTCACCCGGTAGCCAGGGAACCCAGGTGACCGTCTCTAGC
    DR592- 1036 CAGGTGCAGCTCCAAGAGTCTGGGGGCGGTTCTGTGCAGGCAGGCGGGTCCTTG
    hIL27 AGACTCTCTTGCACCGCCCCAGGCTTTACCAGCAATTCCTGTGGAATGGATTGG
    Ra_VH TACAGGCAAGCGCCCGGTAAAGAACGCGAGTTCGTCAGCTCTATTAGCACAGAC
    H17 GGAACCACTGGCTATGCTGACTCAGTTAAGGGCCGGTTCACCATCAGTAAGGAT
    AAAGCCAAGGACACCGTGTACCTTCAGATGAACTCTCTGAAGCCCGAGGACACT
    GGCATGTATAGCTGTAAGACAAAAGACGGAACAATCGCGACTATGGAGTTGTGT
    GACTTCGGATACTGGGGTCAGGGAACGCAGGTGACCGTGTCCAGCGGCGGTTCT
    GGGGGTAGCGGGGGCAGCGGACAAGTTCAGCTCCAGGAAAGCGGAGGCGGGCTC
    GTGCAGCCTGGGGGCTCCCTCCGCCTGTCCTGTGCAGCCTCAGGCTTCACGTTT
    TCACTGTCTGGCATGAGCTGGGTTCGCCAGGCTCCCGGCAAAGGACTCGAATGG
    GTGTCCGCCATCTCTTCCGGCGGAGCCTCCACCTATTACACAGATTCCGTCAAA
    GGACGCTTCACTATCTCACGTGATAACGCGAAGAATATGTTGTACCTTCAGTTG
    AACTCCCTGAAAACCGAGGATACAGCCATGTATTACTGCGCTAAGGGCGGAAGC
    GGATACGGAGACGCCTCCCGCATGACATCCCCTGGTTCCCAGGGGACACAGGTG
    ACCGTGTCCTCA
    DR592- 1037 CAGGTCCAGCTCCAGGAATCCGGGGGCGGGTCCGTGCAGGCGGGTGGCTCCCTT
    hIL27 AGGCTCTCCTGTACCGCCCCCGGCTTCACCAGCAACTCCTGTGGGATGGATTGG
    Ra_VH TATCGGCAAGCACCGGGCAAGGAGCGCGAGTTTGTGTCCTCTATCAGCACCGAC
    H18 GGCACTACCGGCTACGCAGACAGCGTAAAGGGTCGTTTCACAATCTCCAAGGAT
    AAGGCAAAGGACACAGTGTATCTTCAGATGAACAGCCTGAAGCCCGAGGATACT
    GGCATGTATTCCTGCAAGACCAAAGACGGAACCATCGCCACTATGGAACTCTGT
    GATTTCGGCTACTGGGGGCAAGGCACCCAGGTGACGGTGTCTAGCGGCGGTGGC
    AGCCAGGTGCAGTTGCAGGAGTCTGGAGGGGGCTCCGTGCAGGCTGGAGGCAGC
    CTGCGCCTGTCTTGCGTTGCTTCCGGGTATGTCTCTTGCGATTACTTCCTGCCT
    AGCTGGTACAGACAGGCCCCTGGGAAGGAGCGCGAGTTCGTTTCAATCATTGAT
    GGGACGGGCTCCACCTCCTATGCTGCATCCGTTAAGGGGCGCTTTACAGCCTCT
    CAGGATAAGGGAAAAAATATCGCCTACCTCCAGATGAACTCTCTGAAGCCTGAG
    GACACTGCCATGTACTATTGCAAGGCCTCATGTGTTCGCGGGCGCGGTATTAGT
    GAGTACTGGGGGCAGGGCACCCAGGTGACTGTCTCCAGC
    DR592- 1038 CAAGTTCAGCTCCAGGAGAGCGGAGGTGGGTCAGTCCAGGCTGGTGGCAGTCTG
    hIL27 CGTCTGTCCTGCACTGCCCCCGGTTTCACCTCCAACAGCTGCGGCATGGATTGG
    Ra_VH TACAGGCAGGCACCTGGCAAAGAAAGGGAGTTCGTGTCCTCTATTTCCACTGAC
    H18 GGAACGACCGGCTACGCCGACAGTGTGAAGGGAAGGTTCACAATCTCCAAGGAC
    AAGGCCAAGGACACCGTGTATCTTCAGATGAACTCACTGAAGCCCGAAGACACC
    GGGATGTATAGCTGCAAGACAAAGGACGGGACTATCGCTACTATGGAGCTGTGT
    GATTTCGGTTACTGGGGGCAAGGCACTCAGGTGACCGTTAGCTCCGGCGGTAGC
    GGCGGATCAGGAGGCTCTGGGCAAGTGCAGCTTCAAGAGTCTGGCGGTGGCTCC
    GTACAAGCGGGCGGAAGCCTGAGACTGAGTTGCGTGGCTTCCGGCTACGTTAGC
    TGCGACTACTTTCTGCCAAGCTGGTATCGCCAAGCTCCCGGCAAGGAGCGGGAG
    TTCGTGTCAATTATCGACGGCACTGGTTCTACCTCTTACGCCGCTTCTGTAAAG
    GGACGCTTTACCGCCAGCCAGGATAAGGGCAAAAACATCGCATACCTTCAGATG
    AACTCTCTGAAGCCAGAGGACACAGCAATGTATTACTGTAAGGCTTCCTGCGTT
    CGCGGTCGCGGTATCTCTGAATATTGGGGCCAGGGGACCCAGGTAACTGTGTCT
    TCT
    DR592- 1039 CAGGTGCAACTTCAGGAATCTGGAGGGGGATCAGTCCAGGCCGGGGGTAGTCTG
    hIL27 AGATTGTCTTGCACCGCTCCCGGATTTACGTCAAACTCTTGCGGTATGGACTGG
    Ra_VH TATCGCCAGGCTCCCGGCAAGGAACGTGAGTTCGTGTCCAGCATTAGTACCGAT
    H19 GGCACCACGGGCTATGCTGACAGTGTGAAGGGTCGGTTTACCATCTCCAAGGAC
    AAGGCCAAGGACACCGTGTATCTTCAGATGAACAGCCTGAAGCCCGAAGACACC
    GGCATGTATTCCTGCAAGACCAAGGATGGCACCATCGCTACGATGGAACTGTGC
    GATTTCGGTTACTGGGGTCAGGGAACCCAGGTCACCGTGTCTAGCGGAGGCGGT
    TCTCAAGTGCAGCTCCAGGAATCTGGCGGGGGCTCCGTGCAGGCTGGCGGGTCT
    CTGCGCCTGTCCTGTCGGGCGAGCGGTTCCACCTACTCCAATTATTGTCTGGGC
    TGGTTTAGACAGATCACAGGCAAGGAAAGAGAGGGCGTGGCCGTTATCAACTGG
    GTCGGAGGTATGCTTTACTTCGCCGACAGCGTCAAGGGCAGGTTCACCGTCTCT
    CAGGACCAAGCTAAGAATACCGTGTACCTTCAGATGAACTCCCTGAAGCCTGAG
    GATACCGCGATGTATTACTGTGCAGCTGAGTCCGTCAGCTCTTTCTCTTGTGGA
    GGTTGGTTGACTAGGCCTGATCGGGTGCCATACTGGGGCCAGGGGACACAGGTC
    ACCGTATCTAGC
    DR592- 1040 CAGGTACAGTTGCAGGAAAGCGGCGGTGGATCTGTCCAGGCCGGGGGTAGCCTC
    hIL27 CGCCTGTCCTGCACAGCCCCTGGGTTCACCAGCAACTCATGTGGCATGGACTGG
    Ra_VH TATCGCCAGGCTCCGGGTAAAGAGCGTGAGTTCGTGTCCTCTATCTCCACAGAT
    H19 GGAACGACAGGCTATGCAGACAGCGTCAAAGGGAGGTTTACAATCTCCAAGGAC
    AAGGCCAAGGATACGGTTTACCTTCAGATGAACTCTCTGAAGCCCGAGGACACC
    GGCATGTACTCCTGTAAGACTAAGGACGGAACCATCGCCACTATGGAACTCTGC
    GATTTCGGCTATTGGGGACAGGGAACCCAGGTGACGGTGTCCAGCGGAGGCTCA
    GGAGGGTCCGGTGGCAGCGGACAGGTCCAACTCCAGGAGTCTGGTGGAGGCTCC
    GTCCAGGCCGGAGGTTCTCTGAGACTGTCTTGTCGGGCATCTGGATCTACTTAC
    AGCAACTACTGCCTGGGATGGTTCAGACAAATCACAGGAAAGGAGCGCGAAGGT
    GTGGCCGTGATTAACTGGGTGGGCGGTATGCTGTATTTCGCAGACTCCGTCAAG
    GGCCGCTTCACCGTGTCTCAGGATCAGGCTAAAAACACTGTTTATCTCCAGATG
    AACTCCCTCAAGCCTGAGGATACTGCCATGTATTACTGTGCCGCAGAGTCCGTA
    AGCTCCTTCTCTTGCGGGGGCTGGCTGACTCGCCCCGACCGTGTACCGTACTGG
    GGCCAGGGAACACAGGTCACAGTGTCCTCT
    DR592- 1041 CAGGTGCAGCTCCAGGAATCTGGCGGTGGCTCCGTGCAGGCCGGTGGCTCCCTC
    - AGACTGTCCTGCACAGCGCCAGGCTTCACGTCCAACTCTTGCGGCATGGATTGG
    hIL27 TATCGGCAAGCACCGGGCAAGGAAAGAGAGTTCGTTTCTTCCATCTCCACGGAC
    Ra_VH GGCACGACAGGCTATGCGGACTCAGTCAAAGGCCGTTTCACTATTTCTAAGGAT
    H20 AAAGCCAAGGATACAGTCTACCTTCAGATGAACTCCTTGAAACCAGAGGACACC
    GGAATGTATAGTTGCAAGACTAAGGACGGCACAATCGCCACTATGGAACTGTGC
    GACTTCGGGTACTGGGGCCAGGGCACACAGGTCACTGTTAGCTCCGGTGGCGGT
    TCACAGGTCCAGCTCCAGGAGAGCGGCGGTGGGCTGGTTCAGCCGGGAGGGAGC
    CTGCGCCTGTCCTGTGCCGCTTCCGGGTTCACGTTTTCTTCCTACCCTATGTCT
    TGGGTTCGCCAGGCCCCTGGTAAGGGTCTTGAATGGGTCTCTACAATTTCTAGT
    GGTGGCGACACAACGCTGTATGCCGACTCCGTCAAGGGTCGCTTTACCTCAAGC
    AGGGATAATGCTAAGAACACCCTCTATTTGCAGTTGAACTCTCTTAAAACTGAG
    GATACCGCAATGTATTACTGTGCAAAACGTATCGACTGTAATAGCGGTTATTGC
    TATAAGCGTAGCTACTGGGGTCAGGGCACCCAGGTGACGGTGTCTAGT
    DR592- 1042 CAGGTGCAACTCCAGGAATCCGGCGGGGGCAGCGTTCAGGCGGGAGGCTCTCTC
    hIL27 CGTCTGTCCTGCACCGCCCCCGGCTTCACAAGTAATTCCTGCGGCATGGACTGG
    Ra_VH TATCGTCAGGCCCCTGGCAAAGAACGGGAGTTCGTAAGCTCCATCTCAACCGAT
    H20 GGCACAACCGGCTATGCAGACTCCGTGAAGGGGCGCTTCACCATCTCAAAGGAC
    AAGGCCAAAGATACAGTGTACCTTCAGATGAACAGCCTTAAACCGGAGGATACA
    GGCATGTATTCTTGCAAGACCAAGGACGGCACCATCGCAACAATGGAGCTGTGC
    GACTTCGGATACTGGGGTCAAGGCACCCAGGTGACTGTCTCATCTGGGGGTAGC
    GGAGGGAGCGGAGGCAGTGGTCAGGTGCAGCTTCAGGAGAGCGGTGGAGGGCTC
    GTGCAACCCGGCGGTAGCCTGCGCCTGTCCTGCGCAGCTTCTGGGTTTACGTTT
    TCTTCCTACCCTATGAGCTGGGTGAGGCAGGCCCCTGGCAAGGGGCTGGAGTGG
    GTCTCAACCATTTCCAGCGGTGGGGATACCACACTCTACGCCGATTCCGTCAAG
    GGACGCTTCACCAGTTCCCGCGATAATGCCAAGAACACCCTGTACCTTCAGCTG
    AACAGCCTGAAGACTGAGGACACTGCCATGTACTATTGTGCGAAGCGGATTGAC
    TGCAATTCTGGGTACTGTTATAAGCGTTCTTACTGGGGGCAAGGAACCCAGGTG
    ACCGTGTCCAGT
    DR592- 1043 CAAGTGCAGCTTCAAGAAAGCGGGGGCGGTTCCGTGCAGGCAGGCGGGAGCCTG
    CGCTTGAGTTGCACCGCTCCGGGCTTTACAAGTAACAGCTGCGGGATGGATTGG
    hIL27 TATCGCCAGGCACCTGGAAAGGAGCGCGAGTTCGTGTCCTCTATTTCCACGGAC
    Ra_VH GGGACTACCGGGTATGCCGATTCCGTGAAGGGCCGGTTTACTATCTCCAAGGAC
    H21 AAAGCCAAGGACACCGTTTACCTTCAGATGAACAGCCTCAAGCCTGAAGATACC
    GGAATGTATAGTTGTAAGACCAAGGACGGCACCATCGCCACGATGGAGCTGTGT
    GATTTCGGATACTGGGGTCAGGGCACACAGGTTACTGTGTCCAGTGGAGGCGGT
    AGCCAGGTGCAGTTGCAGGAATCTGGCGGGGGCTTGGTCCAGCCTGGGGGCTCT
    CTGCGCCTCAGCTGCGCGGCCTCCGGCTTCACGTTTAGCCTGAGTAGCATGTCT
    TGGGTTCGGCAAGCACCGGGTAAGGGCCTGGAGTGGGTCTCCGCTATTTCCAGC
    GGCGGTGCTAGTACCTATTACACCGACTCTGTGAAAGGCCGCTTCACGATTTCC
    CGCGACAACGCAAAGAACATGCTTTATCTCCAGCTGAACTCACTGAAGACAGAG
    GACACAGCAATGTATTACTGTGCCAAGGGAGGTTCCGGCTACGGGGATGCGTCA
    CGTATGACATCCCCTGGTTCACAGGGCACCCAGGTGACGGTGAGCAGC
    DR592- 1044 CAAGTCCAGCTCCAGGAGTCCGGCGGGGGTTCCGTCCAGGCTGGCGGTAGCCTG
    hIL27 AGGCTGTCCTGTACCGCCCCCGGTTTCACATCTAACTCCTGCGGCATGGACTGG
    Ra_VH TATCGCCAGGCTCCCGGAAAAGAACGCGAGTTCGTGAGTTCCATCTCCACAGAC
    H21 GGCACCACTGGCTATGCAGACAGTGTGAAGGGAAGGTTCACCATCTCTAAGGAT
    AAAGCTAAGGACACCGTTTACTTGCAGATGAACTCTCTCAAGCCAGAGGACACC
    GGAATGTACTCCTGTAAGACCAAAGATGGGACCATCGCGACAATGGAGCTGTGT
    GACTTTGGATACTGGGGACAAGGGACCCAGGTGACTGTTTCATCCGGCGGTTCT
    GGCGGGTCTGGTGGGTCCGGTCAGGTGCAGCTCCAGGAGTCCGGCGGGGGACTG
    GTGCAGCCTGGGGGATCACTGCGCCTCAGCTGCGCTGCCTCAGGTTTCACATTT
    AGTCTTAGCTCTATGAGCTGGGTGCGCCAGGCACCCGGAAAGGGGCTGGAATGG
    GTCAGCGCAATCAGCTCAGGCGGGGCTTCTACGTATTACACGGATAGCGTGAAA
    GGGCGCTTCACCATCAGCCGTGACAACGCCAAGAACATGCTGTACCTTCAGCTG
    AACTCACTGAAGACGGAAGATACTGCCATGTACTATTGTGCCAAGGGTGGATCT
    GGGTATGGTGATGCCTCCCGTATGACCTCACCTGGAAGCCAGGGTACACAGGTC
    ACCGTCTCCTCC
    DR592- 1045 CAGGTGCAGTTGCAGGAGAGCGGCGGGGGCAGCGTGCAAGCCGGTGGCAGCCTG
    hIL27 CGGCTGTCTTGTACCGCCCCCGGTTTTACTAGCAATTCTTGCGGCATGGATTGG
    Ra_VH TATCGCCAGGCCCCAGGCAAGGAAAGAGAGTTCGTGTCCTCTATCAGCACTGAC
    H22 GGCACAACCGGCTACGCCGATTCAGTGAAGGGCCGCTTCACCATCTCAAAGGAT
    AAGGCCAAGGACACCGTGTACCTTCAGATGAACTCTCTTAAACCGGAGGACACT
    GGTATGTACTCTTGCAAGACCAAAGACGGGACCATCGCGACTATGGAGCTGTGC
    GATTTCGGGTACTGGGGCCAGGGAACACAGGTCACTGTCTCTTCCGGCGGAGGT
    TCTCAGGTTCAGTTGCAGGAGAGCGGTGGGGGTAGCGTTCAGGCTGGCGGAAGC
    CTGCGGTTGAGTTGTCGCGCATCTGGCTCTACCTATAGCAACTATTGCCTGGGA
    TGGTTCAGACAGACAACCGGCAAGGAGCGCGAGGGTGTGGCCGTCATCAACTGG
    GTCGGGGGTATGCTGTATTTTGCTGATTCCGTGAAGGGCCGTTTCACCGTGAGC
    CAGGACCAGGCTAAGAACACAGTTTATCTCCAGATGAACAGCCTGAAACCCGAG
    GATACTGCCATGTACTATTGTGCGGCAGAATCCGTGTCCTCTTTTAGCTGTGGT
    GGCTGGCTCACACGCCCTGACCGCGTCCCGTACTGGGGTCAGGGAACCCAAGTG
    ACCGTGAGTTCA
    DR592- 1046 CAAGTGCAGCTTCAGGAGTCTGGCGGGGGCTCCGTACAGGCTGGGGGCAGCCTT
    hIL27 AGATTGTCATGCACTGCCCCTGGATTCACAAGCAACAGCTGTGGCATGGATTGG
    Ra_VH TATCGCCAAGCACCTGGGAAGGAGCGGGAGTTCGTCTCCAGCATTTCTACTGAT
    H22 GGTACGACCGGCTACGCTGACAGTGTGAAGGGACGCTTCACTATCTCCAAGGAC
    AAGGCCAAAGATACCGTGTATTTGCAGATGAACAGTCTCAAGCCGGAGGACACC
    GGAATGTATTCCTGCAAGACTAAGGACGGGACTATCGCCACTATGGAACTTTGC
    GACTTTGGCTATTGGGGCCAGGGCACCCAGGTGACCGTAAGTTCCGGGGGTTCC
    GGCGGAAGCGGCGGTAGCGGCCAGGTTCAACTTCAGGAGTCCGGGGGAGGCTCT
    GTGCAGGCCGGGGGCTCTCTGAGACTGTCCTGCCGGGCCTCCGGCTCCACATAC
    TCTAACTACTGCCTGGGATGGTTCCGTCAGACTACAGGCAAGGAGCGCGAGGGT
    GTTGCAGTCATCAACTGGGTAGGGGGAATGCTGTATTTCGCCGATTCAGTCAAA
    GGACGCTTCACTGTGTCCCAAGACCAGGCCAAGAACACAGTCTATCTTCAGATG
    AACAGCCTCAAGCCCGAGGATACCGCTATGTACTATTGCGCAGCTGAGAGCGTG
    TCCAGCTTCTCTTGCGGAGGCTGGCTGACCAGGCCGGATCGGGTGCCCTATTGG
    GGTCAAGGCACACAGGTGACAGTTTCAAGT
    DR592- 1047 CAGGTGCAGCTCCAGGAGAGTGGAGGTGGGTCCGTGCAGGCGGGAGGTAGCCTG
    hIL27 CGGCTGTCCTGTACTGCGCCCGGCTTTACCAGTAACAGCTGCGGCATGGACTGG
    Ra_VH TATAGACAGGCCCCCGGAAAGGAACGCGAGTTTGTCAGCAGTATCTCTACTGAT
    H23 GGCACCACTGGATATGCGGACTCCGTGAAGGGTCGGTTCACCATTAGCAAGGAC
    AAGGCAAAGGATACCGTGTATTTGCAGATGAACAGTCTCAAACCAGAGGACACA
    GGCATGTATAGTTGCAAAACCAAGGACGGGACCATCGCCACTATGGAACTCTGT
    GATTTTGGGTATTGGGGCCAGGGGACTCAGGTGACCGTCAGCTCCGGGGGCGGT
    TCCCAAGTTCAGTTGCAAGAGTCTGGAGGCGGATCAGTGCAGGCCGGGGGCTCT
    CTGCGGCTTAGCTGCCGTGCTTCTCGCAGCCCTTATGGGAACTACTGTCTTGGC
    TGGTTCAGGCAGAGTACAGGTAAGGAACGCGAAGGGGTGGCCGTCATCAACTGG
    GTGGGCGGAATGCTCTATTTCGCTGACTCTGTGAAGGGCCGTTTCACAGTGTCC
    CAGGACCATGCTAAGAACACTGTCACCCTCCAGATGAACAGCCTGAAGCCAGAG
    GACACCGCTATGTATTACTGCGCAGCCGAGTCTGTGTCCAGTTTCTCATGCGGT
    GGGTGGCTGACCAGACCTGATCGCGTTCCATACTGGGGACAAGGGACTCAGGTC
    ACAGTGTCCTCT
    DR592- 1048 CAGGTGCAGCTCCAGGAGTCCGGGGGTGGCTCCGTTCAGGCGGGAGGCTCTTTG
    hIL27 CGTTTGTCCTGCACCGCACCCGGTTTCACAAGTAACTCCTGCGGCATGGACTGG
    Ra_VH TATCGTCAGGCTCCAGGCAAGGAGCGCGAGTTCGTGAGTTCTATCTCCACAGAC
    H23 GGCACCACGGGCTACGCCGACAGTGTTAAGGGTCGCTTTACTATCTCAAAGGAT
    AAGGCGAAGGACACCGTATACCTTCAGATGAACTCCCTCAAGCCTGAAGACACC
    GGAATGTATAGCTGTAAGACCAAGGACGGCACCATCGCCACAATGGAGCTGTGC
    GACTTTGGATACTGGGGGCAGGGAACACAGGTGACAGTATCCAGCGGGGGCTCT
    GGCGGTTCCGGCGGTTCCGGCCAGGTCCAGTTGCAGGAGTCTGGTGGCGGTAGC
    GTCCAGGCTGGGGGCAGCCTGCGGCTGTCCTGTCGCGCATCAAGAAGCCCTTAC
    GGCAATTATTGTTTGGGCTGGTTCCGCCAATCAACTGGTAAGGAGAGAGAAGGA
    GTCGCTGTCATTAACTGGGTGGGCGGTATGCTTTATTTTGCCGATAGCGTGAAG
    GGGCGCTTCACGGTGTCTCAGGACCATGCCAAGAATACCGTTACGTTGCAGATG
    AACAGCCTGAAACCCGAAGACACCGCAATGTATTACTGTGCCGCTGAGTCCGTA
    TCCTCTTTCTCCTGTGGAGGCTGGCTGACACGCCCCGACCGCGTGCCTTATTGG
    GGCCAAGGGACCCAGGTTACCGTGTCCTCC
    DR592- 1049 CAGGTGCAGTTGCAGGAAAGTGGTGGAGGCAGCGTGCAGGCAGGAGGCTCTCTG
    hIL27 CGCCTGAGCTGCACAGCGCCTGGCTTTACCTCCAACAGCTGTGGAATGGACTGG
    Ra_VH TATCGCCAGGCTCCCGGTAAGGAGCGGGAATTTGTCAGCTCCATTTCCACCGAC
    H24 GGCACCACTGGCTACGCCGATTCCGTCAAGGGCAGGTTCACAATCTCAAAGGAC
    AAAGCCAAGGACACAGTGTATCTCCAGATGAACTCCCTGAAGCCTGAGGACACA
    GGTATGTATAGCTGCAAGACTAAGGACGGCACAATCGCCACGATGGAATTGTGC
    GACTTCGGATATTGGGGACAAGGTACTCAGGTGACCGTCTCCTCTGGAGGGGGC
    TCCCAGGTGCAGCTCCAGGAGTCTGGCGGTGGCCTGGTGCAGCCCGGTGGGTCT
    CTGCGGCTGAGTTGTGCTGCGTCTGGATTCACCTTTTCCCACAGCGGGATGTCA
    TGGGTGAGGCAGGCACCCGGCAAGGGCCTGGAGTGGGTGAGCACAATTAACTCC
    GGGGGTGCTTCCACGTACTATACCGATAGCGTGAAGGGCAGGTTTACCATCTCA
    CGCGACAACGCGAAGAACATGCTGTATCTTCAGCTGAATAGTTTGAAGACCGAG
    GACACCGCTATGTATTACTGCGCCAAAGGCGGTTCTGGCTACGGGGACGCCTCC
    CGCATGACAAGCCCTGGGTCTCAGGGCACACAGGTGACCGTGTCTTCT
    DR592- 1050 CAAGTTCAGCTTCAGGAATCAGGTGGCGGTAGCGTGCAGGCTGGGGGCTCCTTG
    hIL27 AGATTGTCCTGCACGGCCCCAGGATTCACCAGCAACTCTTGCGGGATGGATTGG
    Ra_VH TATCGCCAGGCTCCGGGGAAGGAGAGGGAGTTCGTAAGCTCCATTTCAACCGAT
    H24 GGGACCACTGGATACGCTGACTCCGTTAAGGGTAGGTTCACGATCAGTAAGGAC
    AAGGCCAAGGATACAGTGTATCTTCAAATGAACTCACTGAAGCCCGAGGACACC
    GGGATGTACTCCTGTAAGACCAAAGATGGCACTATCGCAACGATGGAGCTGTGC
    GACTTCGGCTATTGGGGCCAGGGAACCCAGGTTACTGTGTCCAGCGGAGGCAGC
    GGCGGTTCTGGAGGCTCTGGACAGGTCCAACTCCAGGAATCTGGGGGCGGTCTC
    GTGCAGCCAGGTGGGTCACTGCGCTTGTCATGTGCGGCCTCCGGTTTCACCTTC
    AGCCATTCTGGAATGAGCTGGGTGCGTCAAGCACCGGGCAAAGGCCTCGAATGG
    GTCTCTACTATTAACAGCGGAGGTGCATCTACCTACTATACAGACAGCGTTAAG
    GGGAGGTTCACCATCTCTCGCGATAATGCTAAAAACATGCTGTATTTGCAGCTT
    AATTCACTGAAGACGGAGGACACGGCCATGTACTATTGTGCCAAGGGTGGGTCC
    GGGTACGGTGACGCCTCTCGCATGACCTCCCCAGGAAGTCAGGGCACCCAGGTG
    ACCGTGTCATCC
    DR593- 1051 CAGGTGCAGCTCCAGGAATCTGGCGGTGGCAGCGTGCAGGCCGGTGGCTCCCTG
    hIL27 AGGCTGTCCTGTGCTGCCTCTGGATACCCATACTCCAACGGGTACATGGGCTGG
    Ra_VH TTCCGTCAGGCCCCTGGAAAGGAACGTGAGGGCGTGGCCACTATTTACACCGGC
    H1 GACGGTCGTACTTATTACGCCGACTCCGTGAAAGGCCGCTTCACCATTTCTAGG
    GATAACGCTAAGAACACAGTTGACCTCCAGATGTCTAGCCTGAAACCTGAGGAT
    ACCGCCATGTATTACTGCGCTGCCAGGGCTGCCCCACTCTACAGCTCTGGTTCT
    CCCCTGACACGCGCCAGGTATAACGTGTGGGGACAGGGGACCCAGGTCACAGTG
    AGTTCTGGCGGGGGTTCTCAGGTGCAACTCCAGGAATCTGGCGGAGGCCTGGTC
    CAGCCTGGTGGCTCCCTTCGCCTGAGCTGTGCAGCCTCTGGCTTCACATTCAGC
    TCCTATCCTATGTCCTGGGTGCGCCAGGCCCCTGGGAAGGGCCTGGAGTGGATC
    TCCACCATCTCTGCGGGTGGCGACACTACACTCTACGCCGACAGCGTGAAGGGC
    CGCTTTACCTCCAGTCGCGATAACGCTAAGAATACACTGTACCTCCAGCTTAAC
    AGCCTGAAGACAGAGGACGCTGCAATCTATTACTGTGCCAAGAGGATCGACTGC
    AACAGCGGATATTGCTACCGTAGGAATTATTGGGGCCAGGGAACCCAGGTTACC
    GTATCATCC
    DR593- 1052 CAAGTTCAGTTGCAGGAATCCGGTGGCGGTAGCGTGCAGGCTGGTGGCAGCCTG
    hIL27 CGTCTGAGCTGCGCTGCATCCGGGTATCCGTACAGCAACGGTTACATGGGATGG
    Ra_VH TTCCGCCAAGCTCCTGGGAAGGAGCGCGAAGGCGTGGCGACCATTTACACCGGA
    H1 GACGGACGCACTTATTACGCCGACTCAGTGAAGGGCCGCTTTACGATCTCTCGG
    GACAACGCTAAGAATACCGTGGACTTGCAGATGAGTTCCCTGAAGCCTGAGGAC
    ACCGCAATGTATTACTGTGCCGCACGCGCTGCGCCCCTCTACAGCTCTGGTTCT
    CCCCTGACCCGTGCCCGTTACAATGTATGGGGACAAGGCACCCAGGTGACCGTG
    AGTAGCGGGGGAAGCGGAGGCAGCGGGGGATCTGGCCAGGTGCAGCTCCAGGAA
    AGCGGCGGGGGCCTGGTCCAGCCCGGTGGCAGCCTGCGCCTGTCCTGTGCTGCC
    AGTGGATTCACCTTTTCTTCCTATCCTATGTCATGGGTCCGCCAGGCACCTGGC
    AAGGGCCTGGAGTGGATTTCCACTATCTCAGCTGGCGGAGACACAACTCTCTAC
    GCGGACTCTGTAAAGGGTCGGTTTACGTCTTCCCGCGACAACGCCAAGAATACC
    CTGTACCTTCAGTTGAACTCCCTTAAAACCGAAGATGCAGCTATCTACTATTGT
    GCGAAGCGTATTGATTGCAACTCCGGTTACTGCTACCGGCGTAACTACTGGGGT
    CAAGGCACACAGGTCACAGTCTCCTCC
    DR593- 1053 CAAGTCCAGCTCCAAGAGAGTGGGGGCGGTTCCGTGCAGGCTGGAGGCTCCCTC
    hIL27 AGATTGAGTTGTGCGGCTAGTGGCTATCCCTATAGCAACGGCTACATGGGCTGG
    Ra_VH TTCCGCCAGGCCCCCGGCAAGGAAAGGGAGGGTGTTGCAACCATCTACACAGGA
    H2 GATGGCCGCACTTACTATGCAGACTCCGTTAAGGGTCGTTTCACCATTTCCCGC
    GATAACGCTAAGAATACAGTGGATCTTCAGATGTCCAGCCTCAAACCAGAGGAT
    ACTGCAATGTATTACTGCGCAGCGCGGGCCGCGCCCCTGTACTCTTCCGGCTCT
    CCACTGACCCGCGCTCGCTACAACGTGTGGGGCCAAGGCACGCAGGTCACAGTT
    TCTTCCGGCGGGGGCAGCCAGGTCCAGCTCCAGGAAAGTGGCGGGGGCCTGGTT
    CAGCCCGGCGGTTCCCTGCGCCTCAGCTGTGCTGCCTCTGGGTTTACCTTCAGC
    CTGTCAGGCATGAGCTGGGTGCGGCAGGCTCCTGGCAAGGGTCTGGAATGGGTT
    TCCGCCATTTCAAGCGGCGGGGCCTCTACCTATTACACAGACTCCGTGAAGGGC
    CGTTTCACGATCAGTCGCGACAACGCGAAAAACATTCTCTATCTCCAGCTGAAC
    AGCTTGAAGACCGAGGACACTGCGATGTATTACTGTGCCAAAGGGGGATCAGGA
    TACGGCGATGCGTCTCGCATGACTTCCCCAGGTTCACAGGGCACTCAGGTTACC
    GTCTCTTCC
    DR593- 1054 CAGGTACAGCTTCAAGAAAGCGGCGGGGGAAGCGTGCAAGCTGGCGGGAGCCTT
    hIL27 AGGCTGAGTTGCGCGGCCTCAGGTTACCCCTATAGCAACGGATATATGGGATGG
    Ra_VH TTCCGGCAGGCACCGGGGAAGGAACGCGAGGGAGTGGCCACCATTTACACCGGG
    H2 GACGGGAGGACCTACTATGCCGACTCTGTGAAGGGCCGTTTCACTATCTCTAGG
    GATAACGCGAAGAACACAGTGGACTTGCAGATGTCATCTCTCAAGCCGGAGGAC
    ACTGCCATGTATTACTGTGCGGCTCGTGCCGCTCCTCTCTACAGCTCCGGGAGT
    CCACTGACCCGCGCAAGGTACAACGTGTGGGGTCAGGGAACTCAGGTGACCGTT
    TCATCCGGGGGCAGCGGTGGCTCCGGTGGCTCTGGTCAGGTTCAGCTCCAGGAA
    AGCGGGGGCGGGCTGGTGCAGCCCGGAGGCTCCCTGCGTCTTTCTTGCGCTGCC
    AGTGGCTTTACCTTTTCCCTGAGTGGAATGAGCTGGGTGAGGCAAGCGCCAGGC
    AAGGGACTGGAATGGGTGAGCGCAATCAGTTCAGGCGGGGCCAGTACTTATTAC
    ACTGACTCCGTCAAGGGTCGGTTTACCATCTCTCGGGATAACGCTAAGAACATC
    CTTTATTTGCAGCTCAACTCCTTGAAGACGGAAGACACCGCTATGTATTACTGC
    GCTAAAGGAGGGAGTGGATACGGAGACGCATCTCGCATGACCAGTCCAGGTTCC
    CAGGGAACCCAGGTGACTGTGTCAAGC
    DR593- 1055 CAGGTCCAGCTTCAGGAAAGCGGCGGTGGGTCTGTCCAGGCAGGTGGCTCTCTG
    hIL27 AGACTGTCCTGTGCTGCCAGCGGGTATCCGTACTCAAATGGCTACATGGGCTGG
    Ra_VH TTCCGCCAGGCCCCTGGAAAGGAGCGCGAGGGCGTGGCCACGATCTATACCGGG
    H3 GACGGACGCACCTATTACGCTGACAGTGTCAAAGGTAGATTCACTATCAGCCGG
    GACAACGCGAAGAACACCGTTGACCTTCAGATGTCAAGCCTGAAGCCTGAGGAC
    ACTGCCATGTATTACTGCGCTGCAAGGGCTGCCCCTCTTTACAGCTCCGGCTCT
    CCCCTTACAAGAGCCCGGTACAACGTCTGGGGCCAGGGAACTCAGGTGACCGTT
    AGCTCCGGCGGGGGCTCCCAGGTGCAGCTCCAGGAGTCCGGTGGCGGAAGTGTT
    CAGGCGGGCGGAAGTCTGCGCCTGTCTTGCGTGGCCTCTGGATACGTCTCCTGT
    GACTATTTCTTGCCCAGCTGGTATCGCCAGGCTCCGGGAAAAGAGAGAGAGTTC
    GTGAGCATCATTGACGGCACTGGCTCCACCAGCTACGCAGCCTCCGTTAAGGGT
    CGCTTTACCGCCTCAGAGGATAAGGGTAAGAACATCGCATACTTGCAGATGAAC
    AGTCTCAAGCCCGAGGATACCGCTATGTATTACTGCAAGGCCAGCTGCGTCCGG
    GGTCGCGCTGTCTCCGAATACTGGGGACAGGGCACCCAGGTGACCGTATCTAGT
    DR593- 1056 CAGGTTCAGCTCCAGGAGAGTGGCGGAGGGAGTGTGCAAGCTGGCGGTTCTTTG
    hIL27 CGCCTCTCTTGTGCTGCCTCCGGTTATCCCTACAGTAACGGCTATATGGGCTGG
    Ra_VH TTTCGCCAAGCACCAGGGAAGGAACGGGGGGGGTCGCCACCATTTATACTGGC
    H3 GATGGCCGCACCTATTACGCCGACTCCGTGAAAGGTCGCTTCACCATCAGTCGG
    GACAATGCAAAGAACACTGTAGACTTGCAAATGTCTTCCCTCAAGCCTGAGGAT
    ACTGCTATGTACTATTGCGCTGCAAGGGCAGCTCCCCTGTACTCTAGTGGCTCT
    CCTCTGACCCGCGCTCGGTACAACGTCTGGGGTCAGGGAACCCAGGTTACCGTC
    TCTAGCGGGGGCTCAGGTGGCAGCGGCGGTTCCGGCCAGGTCCAACTCCAGGAG
    TCCGGCGGTGGCTCCGTTCAAGCCGGAGGCAGTCTGAGACTGAGCTGCGTGGCG
    TCCGGTTACGTCTCCTGTGACTACTTCCTGCCTAGCTGGTATCGGCAAGCGCCT
    GGTAAGGAAAGAGAGTTCGTGAGTATCATTGATGGGACCGGCTCCACCTCCTAC
    GCCGCATCTGTTAAGGGGCGCTTCACAGCTTCCGAAGACAAGGGAAAGAACATC
    GCTTATCTTCAGATGAACTCTCTCAAACCTGAAGACACGGCTATGTACTATTGC
    AAGGCCTCCTGTGTACGGGGTCGCGCCGTGTCCGAGTACTGGGGGCAGGGGACA
    CAGGTTACCGTATCCAGC
    DR593- 1057 CAGGTGCAGCTGCAAGAGAGCGGCGGAGGCAGCGTGCAAGCTGGAGGCTCTCTC
    hIL27 CGGCTTTCATGCGCTGCCAGCGGCTATCCTTATAGCAACGGCTACATGGGCTGG
    Ra_VH TTCCGCCAAGCGCCCGGCAAGGAGCGCGAGGGGGTGGCGACGATTTATACGGGG
    H4 GACGGCAGGACTTATTACGCAGACTCCGTCAAAGGGCGCTTCACCATCTCCCGC
    GACAACGCCAAAAATACCGTCGATCTTCAGATGTCAAGCCTCAAGCCCGAGGAT
    ACAGCCATGTACTATTGCGCAGCCCGCGCCGCACCCCTCTATTCCTCAGGATCT
    CCACTCACACGCGCCCGGTACAATGTGTGGGGTCAAGGAACCCAGGTGACCGTA
    TCCAGCGGGGGCGGTTCTCAAGTCCAGCTTCAGGAGTCCGGCGGAGGCCTTGTG
    CAGCCCGGAGAATCTCTGAGACTGTCCTGTACTGCCAGCGGGTTCACCTTTTCT
    AACTACGCGATGAGCTGGGTACGGCAAGCGCCCGGAAAGGGTCTGGAATGGGTC
    AGCGGAATCAATGTTGCCTACGGCATCACTTCTTACGCCGACAGTGTTAAGGGC
    CGCTTCACTATTAGTCGTGACAACACCAAAAACACTCTGTATCTCCAGCTCAAC
    AGCCTGAAAACAGAGGATACTGCGATTTACTATTGTGTCAAACACTCTGGCACC
    ACTATCCCAAGGGGGTTCATCTCCTACACTAAGCGCGGTCAGGGAACCCAGGTG
    ACCGTGTCATCC
    DR593- 1058 CAGGTGCAGTTGCAGGAGAGTGGTGGCGGAAGCGTGCAAGCTGGCGGAAGCCTG
    hIL27 AGACTGAGCTGCGCTGCGAGCGGCTACCCTTACTCAAATGGCTACATGGGGTGG
    Ra_VH TTCCGTCAGGCCCCCGGCAAGGAGCGTGAGGGGGTGGCCACGATCTACACTGGA
    H4 GATGGCCGCACTTATTACGCCGATTCTGTTAAGGGGAGATTCACAATCAGCCGC
    GACAATGCTAAGAACACCGTGGACCTTCAGATGTCCAGCCTCAAACCGGAAGAC
    ACTGCAATGTATTACTGTGCGGCCCGTGCCGCGCCGCTTTACTCTTCAGGGTCA
    CCTCTGACCCGCGCTCGGTACAATGTATGGGGCCAGGGTACACAGGTGACCGTG
    TCTAGCGGAGGCAGCGGTGGCTCAGGAGGTTCTGGGCAAGTCCAGCTCCAAGAG
    TCAGGTGGCGGTCTGGTGCAGCCAGGTGAAAGCCTGCGTCTTTCCTGCACTGCC
    AGCGGCTTTACCTTCTCCAACTATGCCATGTCCTGGGTGCGCCAAGCTCCGGGG
    AAGGGCCTGGAATGGGTATCCGGCATTAACGTGGCCTATGGGATCACAAGTTAC
    GCTGACTCTGTGAAGGGCAGATTTACTATTAGCAGAGACAACACCAAGAATACC
    TTGTACTTGCAACTGAACTCCCTCAAGACCGAGGATACAGCCATCTACTATTGC
    GTGAAACACAGCGGCACTACAATCCCGCGCGGCTTTATTAGTTATACGAAGAGG
    GGACAAGGTACGCAGGTGACCGTGTCCAGC
    DR593- 1059 CAGGTGCAGTTGCAGGAGTCCGGCGGGGGCAGCGTTCAGGCTGGGGGCTCTCTC
    hIL27 AGACTGTCCTGTGCCGCGAGCGGCTATCCATACAGTAACGGATACATGGGCTGG
    Ra_VH TTCCGCCAAGCGCCCGGCAAGGAGAGGGAGGGTGTCGCCACTATCTACACGGGG
    H5 GATGGCCGGACTTATTACGCGGATAGCGTGAAAGGTCGTTTTACCATCTCCCGC
    GACAACGCGAAGAACACCGTGGATTTGCAGATGTCTAGCCTCAAACCCGAGGAC
    ACGGCTATGTACTATTGCGCAGCCCGTGCCGCACCTTTGTATTCCTCTGGTTCA
    CCCCTCACTAGGGCCAGATATAACGTGTGGGGACAGGGGACCCAGGTGACTGTG
    AGTTCTGGGGGTGGCTCCCAGGTGCAGCTCCAGGAGAGCGGAGGTGGCTCCGTT
    CAGGCGGGAGGCTCCCTGAGGCTGTCTTGCACCGCCTCTGGATACGTTTCCTGC
    GACTATTTCCTCCCCTCCTGGTACAGACAGGCACCCGGAAAGGAACGCGAGTTT
    GTGAGCGTCATCGACGGAACAGGGAGCACCTCCTATGCGGCCTCAGTGAAGGGC
    AGATTCACAGCTTCCCAAGACAAGGGTAAGAACATCGCATACCTTCAGATGAAC
    TCCCTGAAACCCGAAGATACCGCCATGTATTACTGCAAAGCATCTTGCGTTCGG
    GGAAGGGCAATCAGCGAATACTGGGGCCAGGGCACGCAGGTGACCGTGTCCTCT
    DR593- 1060 CAGGTGCAGCTTCAAGAGAGTGGTGGAGGGTCCGTCCAGGCCGGGGGTTCTCTG
    hIL27 AGGTTGTCCTGCGCAGCCAGCGGTTACCCCTACTCCAACGGCTATATGGGGTGG
    Ra_VH TTCCGTCAGGCCCCAGGCAAGGAACGCGAAGGGGTCGCAACAATCTACACAGGT
    H5 GATGGCCGCACTTATTACGCTGATAGCGTGAAAGGTCGGTTCACCATTTCTCGG
    GACAACGCCAAGAACACCGTAGATTTGCAGATGTCTTCCTTGAAACCCGAGGAC
    ACTGCCATGTATTACTGCGCTGCACGGGCTGCCCCACTCTATAGTTCCGGCTCC
    CCACTCACACGCGCCAGATACAACGTGTGGGGGCAAGGGACACAGGTCACTGTG
    TCTAGTGGGGGCTCCGGTGGCAGCGGAGGTAGCGGCCAGGTTCAGCTTCAGGAA
    TCTGGCGGAGGCTCCGTGCAAGCCGGTGGGAGCCTCAGACTGTCTTGTACTGCC
    AGCGGGTACGTAAGCTGCGACTACTTCCTGCCTTCCTGGTATCGCCAAGCTCCA
    GGGAAGGAACGTGAGTTCGTATCTGTGATCGACGGAACAGGCTCTACATCTTAT
    GCAGCTTCAGTGAAGGGGAGATTCACAGCCAGCCAGGACAAGGGTAAAAACATT
    GCTTATCTCCAGATGAACTCACTCAAGCCGGAGGACACCGCTATGTATTACTGT
    AAAGCATCCTGCGTGAGAGGACGGGCTATCAGCGAATACTGGGGGCAGGGAACC
    CAGGTGACCGTGAGCAGC
    DR593- 1061 CAGGTGCAGTTGCAGGAGTCCGGGGGAGGTTCCGTCCAGGCCGGGGGAAGTCTG
    hIL27 CGCTTGTCATGCGCTGCCAGCGGCTATCCCTACTCCAACGGCTATATGGGCTGG
    Ra_VH TTTAGGCAGGCCCCTGGGAAGGAACGCGAAGGCGTCGCGACGATCTACACGGGC
    H6 GATGGGAGGACCTATTACGCAGATTCCGTAAAGGGCAGATTTACCATCTCCCGT
    GATAACGCCAAGAATACCGTTGACCTCCAGATGTCCTCTCTGAAACCCGAGGAT
    ACCGCCATGTACTATTGCGCCGCTCGCGCCGCTCCCCTCTACAGCTCTGGATCA
    CCACTGACCCGCGCTAGGTATAACGTGTGGGGTCAGGGGACACAGGTGACCGTC
    AGCTCTGGGGGAGGCTCCCAGGTTCAGCTCCAGGAGTCTGGAGGGGGCCTTGTG
    CAGCCCGGCGGGTCCCTCCGTCTGAGTTGTGCTGCCTCAGGCTTTAGTTTCTCT
    TCCTACGCTATGAAATGGGTCCGTCAAGCGCCCGGCAAAGGCCTGGAGTGGGTC
    TCTACCATTAGCTCCGGGGGTTCCAGCACGAATTATGCTGACTCCGTCAAAGGC
    AGGTTCACTATCAGCCGCGACAACGCCAAGAATACCCTGTACTTGCAGCTCAAC
    AGCCTGAAGATCGAGGACACCGCGATGTATTACTGCGCTAAAGCCATCGTGCCT
    ACTGGAGCGACGATGGAACGCGGACAGGGCACTCAGGTCACCGTGTCCAGC
    DR593- 1062 CAAGTGCAGCTGCAAGAATCAGGCGGAGGCAGTGTCCAAGCTGGCGGTAGTCTG
    hIL27 CGCCTGAGCTGCGCCGCATCAGGCTACCCATACTCTAACGGCTATATGGGGTGG
    Ra_VH TTTAGGCAAGCCCCCGGCAAGGAGCGCGAAGGCGTGGCGACCATCTACACTGGT
    H6 GATGGCCGCACTTACTATGCGGACTCTGTGAAAGGACGCTTCACAATTTCTCGT
    GACAATGCTAAGAACACTGTGGATCTTCAGATGAGTTCCCTGAAGCCCGAAGAC
    ACGGCGATGTATTACTGTGCTGCCAGAGCCGCTCCGCTGTACTCCAGCGGCAGC
    CCCCTCACCCGCGCCCGTTATAACGTCTGGGGGCAGGGCACCCAGGTCACTGTT
    TCTTCCGGTGGCAGTGGAGGCTCTGGGGGCAGCGGACAAGTACAACTCCAGGAG
    TCAGGCGGGGGCCTGGTTCAGCCAGGGGGTTCCCTGCGCCTGAGCTGTGCCGCT
    TCTGGCTTTTCATTCTCTTCCTATGCCATGAAGTGGGTGCGCCAGGCCCCTGGG
    AAGGGACTGGAGTGGGTGAGCACCATTTCAAGTGGAGGTAGCTCCACCAACTAC
    GCGGATTCCGTCAAAGGCCGCTTCACCATTTCCAGGGACAACGCTAAAAACACC
    CTGTATCTTCAGCTCAACTCCCTGAAGATCGAAGACACTGCTATGTACTATTGC
    GCCAAGGCCATCGTCCCCACAGGTGCCACAATGGAGAGGGGCCAGGGCACGCAG
    GTGACAGTCAGCAGT
    DR593- 1063 CAGGTGCAGCTCCAGGAATCCGGCGGAGGCTCCGTGCAGGCTGGCGGGTCCCTT
    hIL27 AGGTTGTCTTGCGCTGCCAGCGGATACCCTTACAGCAATGGATATATGGGTTGG
    Ra_VH TTCCGCCAGGCCCCTGGCAAGGAGAGAGAGGGAGTGGCCACCATCTACACGGGT
    H7 GACGGGCGTACCTACTATGCCGATTCCGTTAAGGGCAGGTTCACAATCTCCCGC
    GACAACGCCAAGAACACCGTGGACCTGCAAATGTCTTCCCTTAAACCCGAAGAC
    ACTGCCATGTATTACTGCGCTGCCCGCGCGGCCCCACTCTACAGCTCTGGGAGC
    CCTTTGACCCGTGCTCGCTATAACGTGTGGGGCCAGGGTACTCAGGTGACCGTC
    TCAAGCGGCGGAGGCTCTCAGGTGCAGCTCCAGGAGTCAGGTGGAGGTTTGGTG
    CAGCCAGGAGGCTCACTGAGACTGAGCTGCGCTGCCAGCGGGTTCACTTTCTCC
    TCTTATCCTATGTCCTGGGTTCGCCAGGCACCCGGCAAAGGCTTGGAGTGGATC
    AGCACCATCAGTGCGGGTGGCGACACAACTTTGTACGCCGACTCTGTGAAGGGT
    CGTTTTACCTCCAGTCGCGACAATGCTAAAAACACACTGTATCTGCAACTGAAC
    TCTCTGAAGACCGAGGACACCGCCATCTATTACTGTGCCAAAAGAATTGACTGT
    AACAGCGGATATTGCTATAGACGCAACTATTGGGGTCAGGGCACACAGGTTACC
    GTGTCCTCA
    DR593- 1064 CAAGTCCAGCTCCAGGAATCCGGCGGTGGCAGCGTTCAAGCCGGTGGCTCCCTG
    hIL27 CGCCTGAGTTGTGCAGCTTCAGGTTATCCCTACAGCAACGGATACATGGGATGG
    Ra_VH TTCCGTCAGGCTCCCGGTAAGGAGCGTGAGGGTGTGGCAACTATCTATACGGGA
    H7 GATGGCAGGACCTACTATGCGGACTCTGTGAAGGGCAGGTTCACGATCTCTCGT
    GATAACGCTAAGAACACCGTCGATCTCCAGATGTCTTCCTTGAAGCCTGAGGAT
    ACGGCTATGTATTACTGCGCCGCGAGAGCTGCCCCGCTCTATTCCTCTGGCAGT
    CCTCTGACTCGGGCACGGTACAACGTGTGGGGCCAAGGCACCCAGGTCACTGTG
    TCCTCTGGCGGTAGCGGTGGCTCTGGCGGTTCAGGTCAGGTGCAGCTGCAAGAA
    TCCGGTGGAGGCCTGGTGCAGCCCGGCGGTTCCCTCCGTCTGTCCTGTGCTGCA
    TCTGGATTCACTTTTTCTAGCTACCCAATGTCATGGGTGCGCCAGGCCCCAGGC
    AAAGGGCTGGAGTGGATCTCAACTATCTCCGCAGGTGGCGATACTACCCTCTAC
    GCTGACTCCGTGAAGGGGCGGTTTACCAGTTCCCGTGACAACGCCAAGAACACT
    TTGTATCTTCAGCTGAACTCATTGAAGACTGAGGACACCGCCATCTATTACTGC
    GCTAAGAGAATCGACTGCAACTCAGGGTACTGCTATAGACGCAACTATTGGGGC
    CAGGGGACTCAGGTGACCGTGTCAAGC
    DR593- 1065 CAGGTGCAGTTGCAGGAAAGCGGCGGTGGCTCCGTGCAGGCTGGGGGCTCTCTG
    hIL27 CGTTTGTCATGTGCCGCAAGTGGATACCCCTACAGCAACGGCTACATGGGCTGG
    Ra_VH TTCAGGCAGGCTCCCGGAAAGGAGCGCGAAGGGGTGGCCACCATCTACACTGGG
    H8 GATGGAAGGACTTACTATGCGGATAGCGTAAAGGGGCGTTTTACTATCTCCAGA
    GACAATGCCAAAAACACAGTTGACCTCCAGATGTCTAGCTTGAAGCCTGAAGAC
    ACTGCCATGTACTATTGTGCAGCGCGGGCAGCCCCGCTGTATAGCTCCGGCTCC
    CCTCTGACACGCGCCCGCTACAACGTGTGGGGACAGGGCACCCAGGTTACCGTG
    AGTTCCGGCGGTGGGTCCCAGGTCCAGCTTCAGGAGTCCGGGGGCGGTTCCGTC
    CAAGTTGGTGGCAGCCTGCGCCTGTCCTGCGCTGCCTCCGGGTTTACTTTCAGT
    TCCTACCCAATGTCATGGGTGCGCCAGGCTCCTGGTAAGGGGCTGGAATGGATT
    TCTACTATCAGTGCAGGCGGAGATACGACCCTCTACGCCGATAGCGTGAAGGGG
    CGGTTCACTTCATCTCGTGATAACGCCAAGAACACCCTGTACCTTCAGCTGAAC
    TCCCTGAAGACGGAAGACACCGCCATTTATTACTGCGCGAAGAGGATCGACTGC
    AACTCCGGCTACTGCTATCGTCGCAACTATTGGGGCCAGGGTACGCAGGTGACG
    GTCAGTTCC
    DR593- 1066 CAGGTGCAGCTCCAGGAGTCAGGCGGTGGCTCTGTGCAGGCCGGAGGGTCTCTC
    hIL27 CGGTTGAGTTGTGCAGCTTCAGGCTACCCTTATAGCAACGGCTACATGGGATGG
    Ra_VH TTCAGACAGGCACCCGGTAAGGAACGCGAGGGCGTAGCCACGATCTACACTGGT
    H8 GATGGGAGGACCTATTACGCTGACTCTGTGAAAGGTCGCTTCACAATTAGTCGC
    GATAACGCTAAGAACACCGTGGATCTCCAGATGAGCAGTTTGAAGCCTGAGGAC
    ACCGCAATGTACTATTGTGCTGCACGCGCGGCCCCTCTCTACAGTTCCGGCAGC
    CCACTGACTAGAGCCCGGTACAACGTCTGGGGCCAAGGCACCCAGGTCACCGTC
    AGTAGCGGCGGGAGCGGAGGCTCCGGTGGCTCCGGCCAGGTGCAGCTCCAGGAG
    TCTGGAGGCGGATCTGTCCAGGTTGGAGGGAGCCTGCGCTTGAGTTGCGCTGCC
    AGCGGATTCACCTTTTCTTCATACCCCATGAGCTGGGTGCGCCAAGCGCCCGGA
    AAGGGGCTGGAGTGGATCTCAACGATCAGCGCCGGAGGTGATACAACCCTCTAC
    GCAGACAGCGTCAAAGGCAGGTTTACATCTAGCCGCGACAACGCAAAGAACACC
    CTGTATTTGCAGCTGAACAGCCTGAAAACGGAAGACACCGCCATCTATTACTGC
    GCCAAAAGAATTGATTGCAATTCTGGTTATTGTTACAGACGCAATTACTGGGGA
    CAGGGGACCCAGGTTACAGTCTCCAGT
    DR593- 1067 CAGGTCCAGCTTCAGGAAAGCGGCGGGGGTAGCGTCCAGGCAGGTGGCAGCCTG
    hIL27 CGTCTGAGCTGTGCGGCCAGCGGTTATCCTTACTCCAACGGTTACATGGGCTGG
    Ra_VH TTCCGCCAGGCCCCTGGCAAGGAGCGTGAGGGAGTGGCCACCATCTACACTGGA
    H9 GATGGAAGAACCTACTATGCAGATTCAGTTAAGGGCAGGTTTACAATCAGCCGC
    GATAATGCCAAGAACACAGTCGATCTCCAGATGTCCTCTCTGAAGCCCGAAGAC
    ACTGCCATGTATTACTGTGCTGCACGCGCTGCCCCGCTGTATTCTTCAGGTAGT
    CCCCTCACACGCGCCCGCTACAACGTGTGGGGGCAGGGTACACAGGTAACTGTG
    TCTAGCGGCGGTGGGAGCCAGGTCCAGCTCCAGGAGTCTGGTGGCGGATCTGTG
    CAGAGCGGGGGTTCCCTGCGCCTGTCCTGTGCTGCCTCTGGGTTCACGTATAGC
    ACTTCCAACAGCTGGATGGCCTGGTTCCGTCAAGCGCCTGGAAAGGAGCGTGAG
    GGGGTGGCTGCCATCTATACAGTGGGAGGTTCTATCTTTTACGCAGACAGCGTG
    CGTGGACGTTTCACAATCTCTCAAGACGCTACTAAGAATATGTTTTACCTTCAG
    ATGAACACTCTCAAGCCCGAGGACACCGCAATGTATTACTGCGCTGCGGCATCT
    GGCCGCCTGAGAGGCAAGTGGTTTTGGCCCTACGAGTATAATTACTGGGGCCAG
    GGCACGCAGGTGACGGTCTCTAGT
    DR593- 1068 CAAGTTCAACTTCAGGAGAGTGGGGGTGGCTCTGTGCAGGCCGGTGGCTCTCTG
    hIL27 AGACTCAGTTGTGCTGCCTCCGGTTACCCTTATTCCAACGGCTACATGGGCTGG
    Ra_VH TTCCGTCAGGCCCCAGGCAAGGAGCGCGAAGGCGTCGCCACCATTTACACAGGC
    H9 GACGGACGCACATACTATGCTGATTCTGTGAAGGGCAGATTTACCATCAGCCGG
    GATAACGCCAAAAATACCGTGGACCTTCAAATGAGTTCTCTGAAGCCTGAGGAT
    ACCGCCATGTATTACTGCGCCGCGCGGGCAGCTCCCCTCTACAGCAGTGGTTCC
    CCGCTGACCCGCGCCCGCTATAACGTGTGGGGCCAAGGCACACAGGTGACCGTG
    TCCAGCGGGGGCTCCGGGGGCTCTGGGGGCTCAGGACAGGTCCAGTTGCAGGAA
    TCTGGCGGTGGCAGCGTTCAGAGTGGAGGTTCCCTGCGGCTCTCTTGTGCCGCT
    TCCGGCTTCACCTACTCAACCTCTAATAGCTGGATGGCCTGGTTCCGTCAAGCC
    CCCGGCAAGGAGCGCGAAGGCGTGGCTGCAATCTACACCGTAGGCGGATCTATC
    TTCTACGCCGATTCAGTGCGCGGCAGGTTTACCATCTCACAGGACGCCACTAAG
    AATATGTTTTATTTGCAGATGAATACTCTGAAGCCTGAGGACACCGCTATGTAT
    TACTGCGCTGCGGCCAGTGGCCGCCTGAGGGGCAAGTGGTTCTGGCCATACGAA
    TACAACTACTGGGGACAGGGGACCCAGGTTACAGTTAGTAGC
    DR593- 1069 CAGGTGCAGTTGCAGGAATCTGGGGGTGGCAGTGTGCAGGCTGGAGGCTCCCTG
    hIL27 CGCCTGTCCTGTGCGGCCTCTGGCTATCCATATAGTAATGGTTACATGGGATGG
    Ra_VH TTTAGGCAGGCTCCGGGCAAGGAGCGCGAGGGCGTGGCCACTATCTACACTGGT
    H10 GATGGTCGGACCTACTATGCTGACTCTGTGAAGGGGCGCTTCACAATTTCTCGG
    GATAACGCCAAAAATACCGTGGACTTGCAGATGAGTTCCCTCAAACCGGAAGAC
    ACCGCCATGTATTACTGTGCAGCTAGGGCGGCACCGCTGTATAGTTCTGGCAGC
    CCTCTGACTCGGGCTCGCTATAATGTCTGGGGCCAGGGAACCCAGGTTACAGTC
    TCCAGCGGGGGTGGGTCCCAAGTGCAGTTGCAGGAATCCGGTGGGGGTTCCGTT
    CAGGCCGGAGGCTCACTGCGGCTGTCTTGCAGAGCGTCCGGCTCCACTTACTCT
    AACTATTGCCTGGGCTGGTTCCGTCAGATTACTGGCAAGGAGAGGGAGGGCGTG
    GCCGTCATAAATTGGGTGGGAGGTATGCTGTACTTTGCCGATTCAGTTAAAGGA
    CGTTTTACGGTGAGCCAGGACCAGGCTAAGAACACCCTTTACCTTCAGATGAAC
    AGCCTGAAGCCCGAAGACACAGCCATGTACTATTGTGCTGCGGAGTCCGTGTCT
    AGCTTTTCTTGCGGAGGCTGGCTCACGAGACCGGATAGAGTGCCATACTGGGGC
    CAGGGCACCCAGGTGACCGTCTCCAGC
    DR593- 1070 CAGGTGCAGCTCCAGGAAAGCGGAGGCGGGTCTGTCCAGGCAGGGGGCTCCCTG
    hIL27 AGACTCTCTTGTGCTGCGAGCGGTTATCCTTATAGCAACGGGTATATGGGATGG
    Ra_VH TTTCGCCAGGCTCCGGGGAAGGAGCGCGAGGGTGTGGCTACCATCTATACGGGT
    H10 GATGGTCGGACTTACTATGCAGACAGTGTCAAGGGCCGCTTCACCATCAGCAGA
    GACAACGCAAAAAATACCGTGGACTTGCAGATGTCATCCCTCAAGCCAGAGGAC
    ACAGCAATGTATTACTGCGCCGCGAGAGCTGCGCCCCTGTACTCCTCTGGATCT
    CCCTTGACCAGAGCCCGCTATAATGTCTGGGGACAGGGAACCCAGGTAACAGTG
    TCCAGCGGAGGTTCCGGGGGTTCTGGAGGTTCTGGACAGGTTCAACTCCAGGAG
    TCTGGCGGGGGCTCAGTCCAGGCTGGCGGGTCTTTGCGCCTGTCCTGTCGGGCC
    AGCGGCTCCACCTACTCCAACTACTGCCTCGGTTGGTTCCGCCAGATTACTGGC
    AAAGAGCGTGAGGGCGTGGCTGTTATCAACTGGGTGGGCGGAATGCTGTACTTC
    GCCGATTCTGTTAAGGGACGCTTCACCGTCTCTCAGGACCAGGCCAAGAACACG
    CTGTATTTGCAGATGAACAGTCTGAAGCCAGAGGATACAGCAATGTATTACTGT
    GCTGCGGAGTCTGTTAGCTCTTTTTCCTGTGGTGGCTGGCTGACCAGGCCGGAT
    CGCGTGCCTTACTGGGGGCAGGGAACCCAGGTGACTGTCAGCAGT
    DR593- 1071 CAGGTGCAGCTTCAGGAGTCCGGCGGAGGCAGTGTCCAGGCAGGGGGCTCCCTG
    hIL27 CGCCTCTCTTGTGCGGCCTCTGGATATCCCTACTCTAACGGATACATGGGCTGG
    Ra_VH TTTCGTCAGGCCCCAGGAAAAGAGCGGGAGGGGGTGGCGACAATCTACACTGGC
    H11 GATGGCCGCACCTACTATGCTGATTCCGTTAAGGGGCGCTTCACCATCAGCAGA
    GACAACGCAAAGAACACTGTCGATCTTCAGATGAGTTCCCTCAAACCTGAAGAC
    ACAGCCATGTATTACTGTGCAGCCCGCGCGGCCCCTCTTTACAGCTCTGGGAGC
    CCCCTGACACGCGCTCGCTACAATGTTTGGGGTCAGGGCACACAGGTGACAGTC
    TCCTCTGGCGGAGGCTCCCAAGTCCAGCTTCAGGAATCCGGCGGTGGGAGTGTG
    CAAGCTGGTGGATCTCTGCGCCTGAGCTGTAGGGCCTCCGGCAGCACATACTCT
    AACTACTGCCTGGGCTGGTTTAGGCAGTCCACAGGAAAAGAACGCGAAGGAGTC
    GCGGTAATAAATTGGGTCGGGGGTATGCTCTACTTCGCCGACTCCGTGAAAGGC
    CGCTTCACAGTGTCTCAGGATCACGCCAAAAATACCGTAACCCTTCAGATGAAC
    TCCTTGAAGCCAGAGGACACCGCGATGTATTACTGCGCTGCGGAGTCCGTATCC
    AGCTTCAGCTGTGGTGGCTGGCTGACCCGCCCAGGACGGGTTCCATACTGGGGC
    CAGGGTACACAGGTCACAGTGTCTAGC
    DR593- 1072 CAGGTGCAGCTCCAGGAGTCCGGCGGAGGGTCCGTCCAGGCCGGAGGTTCCCTC
    hIL27 CGTCTGTCTTGCGCCGCGTCCGGTTATCCTTACAGCAACGGCTATATGGGTTGG
    Ra_VH TTCCGTCAGGCCCCCGGAAAGGAAAGAGAAGGCGTCGCCACGATCTACACCGGG
    H11 GATGGCAGGACCTACTATGCTGACTCCGTGAAGGGCCGCTTCACAATTAGTCGC
    GACAATGCCAAGAACACGGTGGACCTCCAGATGTCTTCACTTAAACCCGAGGAC
    ACCGCTATGTATTACTGTGCAGCCAGAGCAGCTCCTCTGTACTCCTCAGGCTCT
    CCCCTCACCCGTGCTCGCTACAACGTGTGGGGACAGGGCACACAGGTCACAGTG
    TCATCCGGGGGTTCCGGTGGCAGTGGAGGCAGCGGACAGGTACAGCTTCAGGAG
    TCCGGCGGGGGTTCTGTGCAGGCTGGAGGCTCTTTGCGCCTTAGCTGTCGCGCG
    AGCGGTTCCACCTACTCCAATTACTGCCTGGGTTGGTTCAGGCAGAGCACCGGC
    AAGGAGCGCGAAGGAGTGGCCGTCATCAACTGGGTCGGTGGGATGCTCTATTTT
    GCTGACTCTGTGAAGGGCAGGTTTACTGTGAGCCAGGACCATGCCAAGAACACT
    GTGACTCTCCAGATGAATAGTCTTAAACCAGAGGACACGGCTATGTATTACTGT
    GCAGCCGAATCAGTCTCCTCTTTCTCTTGTGGTGGGTGGTTGACGAGGCCGGGT
    CGTGTTCCCTATTGGGGCCAGGGGACCCAGGTGACTGTATCCTCT
    DR593- 1073 CAGGTGCAGCTCCAAGAGTCCGGTGGCGGGAGCGTGCAGGCGGGCGGTTCCCTT
    hIL27 CGCCTGTCTTGTGCTGCCTCCGGCTACCCCTACTCTAATGGCTACATGGGCTGG
    Ra_VH TTCCGCCAAGCTCCAGGGAAGGAAAGGGAAGGCGTGGCCACTATTTACACGGGC
    H12 GACGGTCGCACATATTACGCTGACTCTGTTAAAGGCCGCTTCACTATCTCCAGA
    GACAACGCAAAGAACACGGTGGACCTCCAGATGTCCTCTCTGAAGCCCGAAGAC
    ACCGCTATGTATTACTGCGCTGCAAGGGCTGCCCCTCTGTACTCCAGCGGTTCC
    CCTCTGACCAGAGCCCGCTATAACGTCTGGGGCCAAGGAACACAGGTCACTGTC
    AGCTCCGGTGGCGGGTCACAGGTGCAGCTTCAGGAGAGCGGCGGGGGCAGTGTC
    CAAGCTGGTGAGAGCCTCAGACTGAGTTGCAGAGCCAGCGGTTCCACCTACTCC
    AACTACTGCTTGGGTTGGTTCAGGCAGATCACAGGCAAGGAGCGTGAGGGCGTC
    GCTGTCATCAACTGGGTGGGCGGGATGCTCTACTTTGCTGACAGCGTTAAGGGC
    CGGTTCACCGTGAGCCAGGATCAGGCGAAGAACACGGTTTATCTGGAGATGAAC
    TCACTGAAGCCCGAGGATACAGCTATGTATTACTGTGCAACTGAGTCAGTTTCC
    TCTTTCTCCTGCGGCGGGTGGCTGACCAGGCCGGATAGGGTGCCGTATTGGGGC
    CAAGGGACTCAGGTTACCGTCTCCTCT
    DR593- 1074 CAAGTGCAGCTCCAAGAATCAGGAGGCGGTTCCGTGCAGGCCGGGGGCTCCCTG
    hIL27 CGCTTGTCTTGCGCGGCCAGCGGGTATCCCTACTCTAATGGTTACATGGGCTGG
    Ra_VH TTCCGTCAGGCTCCTGGCAAGGAACGGGAGGGAGTGGCCACTATCTATACTGGC
    H12 GACGGGAGGACCTACTATGCCGACTCCGTGAAGGGCCGGTTCACCATCAGCCGC
    GACAACGCAAAAAATACCGTGGACTTGCAAATGAGTTCCCTGAAGCCCGAGGAC
    ACCGCGATGTACTATTGTGCGGCCCGCGCCGCGCCTCTGTACTCCAGTGGGAGC
    CCTCTCACCCGCGCCAGATACAACGTGTGGGGCCAGGGCACCCAGGTCACGGTG
    TCTAGCGGAGGCAGCGGTGGATCTGGTGGCTCTGGACAAGTGCAACTCCAGGAG
    TCAGGCGGTGGCTCCGTGCAGGCTGGCGAGAGCTTGCGGCTGTCCTGCCGCGCG
    TCTGGCAGCACGTACAGCAATTACTGCCTGGGATGGTTCCGGCAGATCACCGGG
    AAAGAGCGTGAGGGAGTCGCCGTGATTAACTGGGTCGGGGGCATGTTGTATTTT
    GCTGATTCCGTGAAAGGGCGCTTTACCGTCAGCCAGGACCAGGCCAAGAACACG
    GTGTATCTTGAGATGAACTCACTCAAGCCTGAGGACACAGCTATGTATTACTGT
    GCGACCGAGTCCGTGTCATCTTTTTCCTGTGGCGGTTGGCTTACAAGGCCTGAT
    CGCGTTCCTTACTGGGGCCAGGGCACTCAGGTGACCGTGTCTAGC
    DR593- 1075 CAGGTACAGTTGCAGGAAAGTGGCGGAGGCAGCGTGCAGGCCGGGGGCAGTCTC
    hIL27 CGTCTGTCTTGTGCCGCTAGTGGCTATCCCTATTCTAACGGCTATATGGGATGG
    Ra_VH TTCCGCCAGGCACCCGGCAAAGAGAGGGAAGGCGTCGCCACCATCTACACAGGT
    H13 GATGGAAGGACATACTATGCAGACAGCGTGAAGGGCCGCTTCACGATTAGCCGC
    GACAACGCGAAGAACACTGTGGATCTCCAAATGAGTTCCCTCAAGCCTGAGGAC
    ACTGCGATGTATTACTGCGCAGCCAGAGCAGCTCCCCTTTACAGCAGTGGAAGC
    CCGCTGACTCGGGCAAGATACAACGTCTGGGGCCAGGGAACTCAGGTTACGGTA
    TCTTCCGGCGGTGGATCTCAGGTTCAGCTTCAGGAATCAGGCGGTGGATCAGTG
    CAGGCGGGCGGAAGTTTGCGCCTGTCCTGTGTAGCCTCCGGGTACGTCTCCTGT
    GACTATTTCCTGCCCAGCTGGTATAGGCAGGCCCCCGGCAAGGAGCGCGAGTTC
    GTGTCCATCATTGATGGCACCGGGTCCACGTCCTACGCCGCTTCTGTGAAGGGG
    AGATTCACGGCGAGCCAAGATCGCGGCAAAAACATCGCATACTTGCAGATGAAC
    TCACTCAAGCCCGAGGATACCGCCATGTATTACTGTAAGGCCAGCTGCGTTCGC
    GGTCGCACTATCTCTGAATATTGGGGCCAGGGAACCCAGGTGACAGTAAGCAGT
    DR593- 1076 CAAGTGCAGCTCCAGGAGAGTGGTGGGGGCTCCGTACAGGCGGGCGGTTCTCTG
    hIL27 CGCCTTAGTTGCGCGGCCAGCGGCTACCCTTATTCCAACGGTTACATGGGCTGG
    Ra_VH TTCCGCCAGGCACCAGGCAAAGAGAGAGAGGGGGTTGCAACCATCTACACTGGC
    H13 GATGGTAGAACTTATTACGCCGACTCTGTAAAGGGGCGCTTCACAATTTCCCGT
    GATAATGCCAAGAACACCGTTGACCTCCAGATGAGCAGTCTGAAGCCAGAGGAT
    ACAGCCATGTATTACTGCGCCGCTCGGGCAGCCCCACTCTACAGCTCCGGTAGC
    CCCCTGACCCGTGCCCGCTACAACGTGTGGGGACAGGGCACACAGGTCACCGTG
    TCCTCTGGTGGCTCCGGGGGCAGCGGCGGATCAGGCCAGGTGCAGCTCCAGGAA
    AGCGGAGGCGGATCTGTGCAAGCCGGAGGCTCTCTGAGACTCTCCTGTGTTGCC
    AGCGGCTACGTGTCCTGTGACTACTTCTTGCCTTCTTGGTATCGTCAGGCACCT
    GGAAAGGAGCGTGAGTTCGTGTCCATCATTGACGGCACAGGCTCTACCTCCTAC
    GCCGCGAGCGTGAAGGGTCGTTTCACCGCTTCACAGGATCGCGGTAAGAACATC
    GCGTATCTCCAGATGAACTCCCTGAAACCCGAAGACACCGCCATGTATTACTGC
    AAAGCCTCCTGTGTGCGCGGGCGCACGATCAGCGAATACTGGGGGCAGGGTACA
    CAGGTCACCGTGTCCTCC
    DR593- 1077 CAGGTGCAGTTGCAGGAGAGCGGTGGAGGCTCCGTTCAGGCAGGTGGCAGCCTG
    hIL27 CGGCTCTCCTGCGCCGCATCCGGTTACCCATACAGCAATGGCTACATGGGATGG
    Ra_VH TTCCGCCAAGCGCCTGGAAAAGAAAGGGAAGGTGTGGCCACTATCTACACTGGT
    H14 GATGGCCGGACGTACTATGCCGACTCAGTGAAGGGCCGGTTCACAATCAGCCGG
    GATAACGCTAAGAACACAGTGGATCTTCAGATGAGTTCCCTGAAACCCGAGGAC
    ACTGCCATGTATTACTGTGCGGCCAGGGCGGCTCCCCTGTACTCTTCCGGCTCC
    CCCTTGACCCGTGCCCGTTATAATGTGTGGGGTCAAGGCACACAGGTCACTGTG
    TCTTCCGGGGGAGGCTCCCAGGTCCAACTCCAGGAAAGTGGTGGAGGCTCTGTG
    CAGGCAGGCGGTTCCCTCCGCCTGAGCTGTGTGGCCTCCGGCTACGTGTCATGT
    GATTACTTTCTGCCAAGCTGGTATCGTCAGGCTCCCGGTAAGGAGCGCGAGTTC
    GTTAGCATTATCGACGGCACCGGCTCCACCAGCTATGCGGCCAGCGTCAAGGGG
    CGCTTCACCGCCTCTCAGGACAAAGGTAAGAACATCGCCTACCTGCAAATGAAC
    TCCCTGAAGCCCGAGGACACAGCCATGTATTACTGCAAGGCCTCCTGTGTCAGA
    GGTAGGGCGATCTCAGAGTACTGGGGTCAGGGAACCCAGGTGACCGTGTCCTCC
    DR593- 1078 CAAGTGCAGTTGCAGGAGAGCGGCGGAGGCTCTGTGCAGGCGGGAGGCAGTCTG
    hIL27 AGACTGTCCTGTGCCGCTTCCGGCTACCCCTATAGCAACGGTTATATGGGTTGG
    Ra_VH TTCCGCCAGGCCCCAGGAAAAGAGCGCGAGGGCGTAGCGACTATTTACACGGGT
    H14 GATGGTAGAACTTACTATGCAGATTCAGTAAAGGGCCGTTTCACCATTTCCCGT
    GACAACGCTAAGAATACCGTAGATTTGCAGATGTCTTCCCTGAAGCCGGAAGAC
    ACTGCCATGTATTACTGCGCTGCACGCGCGGCTCCCCTTTATTCTTCCGGGTCA
    CCACTCACCCGTGCCCGCTACAACGTGTGGGGCCAGGGCACGCAGGTCACTGTA
    TCCAGCGGAGGCAGCGGCGGAAGCGGGGGCTCTGGCCAAGTCCAGCTCCAGGAG
    TCAGGCGGTGGCTCAGTCCAGGCTGGGGGCTCACTGCGCCTGAGCTGCGTGGCC
    TCTGGCTATGTCAGTTGTGATTACTTCCTTCCGAGCTGGTATCGCCAAGCGCCT
    GGGAAGGAGAGGGAGTTCGTGTCTATTATCGACGGGACCGGCAGCACCAGCTAT
    GCGGCTAGTGTGAAGGGCCGTTTCACCGCTTCCCAGGATAAGGGCAAGAACATC
    GCCTATTTGCAAATGAACAGTCTTAAACCGGAGGATACTGCTATGTACTATTGC
    AAGGCCTCCTGCGTGCGGGGAAGAGCCATCAGTGAGTACTGGGGGCAGGGCACC
    CAGGTCACGGTATCCTCC
    DR593- 1079 CAGGTTCAGCTTCAGGAGAGTGGAGGCGGTAGCGTGCAGGCCGGGGGCAGCTTG
    hIL27 CGCCTGTCTTGCGCTGCCTCCGGTTACCCTTATAGTAACGGATACATGGGTTGG
    Ra_VH TTCAGGCAGGCCCCCGGCAAAGAGAGAGAGGGCGTTGCTACCATTTACACCGGC
    H15 GATGGCCGCACCTACTATGCTGACTCTGTGAAGGGTCGCTTCACAATCTCCCGT
    GATAACGCTAAAAATACCGTCGATCTCCAGATGTCTTCCCTGAAACCCGAGGAT
    ACTGCAATGTATTACTGTGCTGCCCGCGCCGCTCCTCTGTACTCTTCAGGTTCT
    CCTCTGACCCGCGCCAGGTACAACGTCTGGGGTCAGGGCACCCAGGTTACCGTA
    AGCTCCGGTGGAGGCTCTCAAGTGCAGTTGCAGGAATCAGGAGGTGGCTCCGTC
    CAGGCAGGTGGGAGCCTCCGCCTCTCATGCGTCGCAAGCGGCTACGTGAGCTGC
    GACTACTTCTTGCCCTCATGGTATCGCCAGGCTCCTGGGAAGGAGCGTGAGTTC
    GTGAGCATCATTGACGGCACCGGCTCCACCAGCTATGCCGCTTCCGTGAAGGGC
    CGGTTCACTGCGTCCCAGGATAAGGGCAAGAACATCGCGTACCTTCAGATGAAC
    ACCCTGAAGCCGGAGGATACAGCTATGTACTATTGCAAGGCATCTTGCGTGAGG
    GGTAGAGCCATCAGCGAGTATTGGGGCCAAGGAACCCAGGTGACTGTTTCCTCT
    DR593- 1080 CAGGTGCAGTTGCAGGAGTCCGGTGGGGGATCTGTGCAGGCGGGAGGGAGCCTG
    hIL27 CGTCTTAGCTGCGCCGCAAGCGGATACCCCTACTCCAACGGATACATGGGTTGG
    Ra_VH TTTCGCCAAGCCCCTGGGAAGGAAAGGGAGGGCGTGGCCACCATCTATACCGGA
    H15 GATGGCCGCACCTATTACGCTGATTCCGTGAAGGGACGTTTCACAATCAGCAGA
    GATAACGCTAAGAACACTGTGGACCTCCAGATGTCTAGCCTGAAACCCGAAGAC
    ACTGCCATGTATTACTGCGCGGCCAGAGCAGCCCCTCTGTATTCCTCTGGAAGC
    CCGTTGACCAGAGCCCGCTACAATGTGTGGGGACAGGGCACCCAGGTCACTGTG
    TCATCCGGCGGAAGCGGCGGTAGTGGGGGCTCTGGCCAAGTTCAGCTCCAGGAA
    AGCGGCGGAGGCAGCGTGCAGGCTGGCGGATCACTGAGATTGAGCTGTGTTGCT
    TCCGGCTATGTGAGCTGTGATTATTTCCTCCCCAGCTGGTACAGACAGGCTCCC
    GGCAAGGAACGCGAGTTTGTCAGTATCATTGATGGCACCGGCTCTACCAGTTAC
    GCTGCGTCAGTTAAAGGACGCTTCACCGCGTCCCAAGACAAAGGCAAGAACATC
    GCCTATTTGCAGATGAACACCCTGAAGCCAGAAGACACTGCCATGTATTACTGC
    AAGGCTTCTTGCGTGCGCGGTCGCGCCATTTCTGAATACTGGGGCCAGGGCACT
    CAAGTCACCGTGTCTTCC
    DR593- 1081 CAGGTGCAGCTCCAGGAGTCTGGAGGCGGAAGTGTCCAGGCTGGCGGTAGCCTG
    hIL27 CGGCTTTCATGTGCCGCTTCCGGCTACCCGTACTCAAACGGCTACATGGGCTGG
    Ra_VH TTCAGACAAGCGCCTGGAAAAGAGAGAGAAGGCGTGGCCACCATCTATACAGGT
    H16 GATGGCCGTACTTATTACGCTGACTCCGTCAAGGGCCGCTTCACCATCAGCCGG
    GATAACGCTAAGAATACCGTCGATCTTCAAATGAGTTCCTTGAAGCCGGAAGAC
    ACCGCTATGTATTACTGTGCCGCGCGGGCTGCCCCGCTGTATAGTAGCGGCTCT
    CCCCTCACCCGCGCTCGCTACAACGTGTGGGGACAGGGGACTCAAGTAACCGTG
    AGTTCCGGCGGTGGCTCTCAGGTGCAGCTGCAAGAAAGCGGCGGGGGCTCCGTG
    CAGGCAGGCGGAAGCCTGCGCCTGTCTTGCAGAGCCTCCGGCAGTACCTACAGT
    AACTATTGTCTGGGCTGGTTTCGCCAGATCACAGGTAAAGAGAGAGAAGGTGTT
    GCCGTTATCAACTGGGTAGGTGGAATGCTGTACTTTGCCGATTCCGTGAAGGGT
    CGCTTCACCGTGTCCCAAGACCAAGCCAAGAATACTGTATATTTGCAGATGAAC
    TCCCTGAAGCCCGAGGACACAGCTATGTACTATTGTGCCGCTGAGTCTGCTAGT
    AGCTTTTCCTGCGGGGGTTGGCTGACCCGCCCGGACCGCGTCCCCTACTGGGGA
    CAGGGCACCCAGGTAACCGTGAGTTCT
    DR593- 1082 CAGGTGCAGTTGCAGGAGTCTGGGGGTGGAAGCGTGCAAGCCGGGGGATCTCTG
    hIL27 CGGCTGAGCTGCGCTGCCAGTGGATATCCATATTCCAACGGCTATATGGGCTGG
    Ra_VH TTTCGCCAAGCGCCCGGCAAGGAGCGCGAAGGCGTCGCCACAATCTACACAGGC
    H16 GATGGCCGCACCTATTACGCTGATTCCGTTAAAGGACGGTTCACGATCAGCCGC
    GACAACGCCAAGAACACAGTTGACCTCCAGATGTCCAGCCTGAAGCCCGAGGAT
    ACTGCGATGTATTACTGTGCCGCGAGAGCTGCCCCACTCTACAGTTCCGGGAGC
    CCCCTTACTCGCGCCCGTTACAATGTTTGGGGACAGGGCACTCAAGTGACAGTG
    TCCAGCGGAGGTTCCGGTGGCTCCGGCGGGTCTGGACAGGTGCAGTTGCAGGAG
    TCCGGCGGAGGGAGCGTACAGGCCGGGGGCTCTTTGCGTCTGTCTTGCAGAGCT
    TCCGGGTCTACCTATTCCAATTATTGTCTGGGTTGGTTCCGCCAGATTACTGGC
    AAGGAGCGTGAAGGGGTCGCCGTCATCAACTGGGTGGGTGGGATGCTCTATTTC
    GCGGATAGTGTGAAGGGCCGCTTTACAGTCTCTCAGGACCAGGCTAAGAATACT
    GTCTATCTTCAGATGAACTCTTTGAAGCCCGAGGATACGGCCATGTACTATTGC
    GCTGCGGAAAGTGCCTCTAGCTTCAGCTGTGGCGGTTGGCTCACCCGCCCAGAC
    CGCGTCCCCTACTGGGGCCAGGGAACCCAGGTGACAGTGTCCAGT
    DR593- 1083 CAGGTTCAGCTGCAAGAATCCGGCGGAGGGTCCGTCCAAGCGGGAGGCAGTCTC
    hIL27 AGACTTTCCTGCGCAGCTTCTGGATACCCTTACTCTAACGGATATATGGGTTGG
    Ra_VH TTTAGACAGGCACCCGGCAAGGAGAGGGAAGGCGTGGCCACGATCTACACTGGG
    H17 GATGGCAGGACCTATTACGCAGACAGCGTGAAGGGCCGCTTCACCATTTCCAGA
    GATAATGCTAAGAACACCGTTGATCTCCAGATGAGTTCCCTGAAGCCAGAAGAT
    ACCGCCATGTATTACTGCGCTGCCCGCGCCGCGCCTCTTTACAGCTCTGGGAGC
    CCGCTGACTCGTGCTAGGTATAACGTCTGGGGCCAGGGAACCCAGGTGACTGTC
    AGCTCTGGGGGCGGGAGCCAGGTGCAGCTCCAGGAGAGTGGCGGTGGCCTTGTT
    CAGCCCGGTGGCTCCTTGCGGCTGTCATGTGCTGCCTCCGGCTTCACATTTTCT
    CTGAGCGGGATGTCCTGGGTGCGGCAGGCCCCCGGCAAGGGCCTTGAGTGGGTC
    TCCGCTATCTCCAGCGGCGGTGCAAGCACTTACTATACCGACAGCGTCAAGGGC
    CGTTTCACTATCTCACGCGATAACGCCAAAAACATGCTGTATCTCCAGCTGAAC
    TCCCTCAAGACCGAGGATACCGCTATGTACTATTGTGCCAAAGGCGGTTCCGGC
    TATGGCGATGCGTCCCGCATGACTTCTCCCGGCTCCCAGGGCACTCAGGTTACC
    GTGTCTAGC
    DR593- 1084 CAAGTTCAGCTTCAGGAGAGTGGAGGCGGATCTGTCCAGGCAGGTGGCTCACTT
    hIL27 AGGCTGTCTTGTGCTGCCAGTGGCTACCCCTACTCCAACGGATATATGGGTTGG
    Ra_VH TTTCGCCAGGCACCAGGGAAGGAGCGCGAGGGCGTCGCTACCATCTACACTGGC
    H17 GACGGACGCACCTACTATGCGGACAGCGTGAAGGGCCGGTTCACCATCAGCCGC
    GACAACGCCAAAAACACCGTCGATTTGCAGATGTCTTCCCTGAAGCCTGAAGAC
    ACAGCCATGTATTACTGTGCCGCGCGTGCTGCCCCACTCTACTCCTCTGGGAGC
    CCCCTCACCCGTGCCCGCTACAACGTGTGGGGCCAGGGCACACAGGTGACCGTT
    TCCAGTGGTGGCAGCGGTGGCAGCGGGGGTTCCGGCCAGGTCCAGCTCCAGGAG
    TCAGGGGGTGGGCTGGTGCAGCCCGGCGGTAGCCTGCGCTTGTCCTGCGCTGCC
    AGCGGGTTCACCTTCAGTCTGTCAGGTATGTCCTGGGTAAGGCAGGCTCCCGGT
    AAGGGCCTGGAGTGGGTATCCGCCATCTCTAGCGGTGGAGCCAGCACCTATTAC
    ACTGATTCAGTAAAAGGACGCTTCACCATTAGCAGGGACAACGCCAAAAACATG
    CTGTATCTTCAACTGAACTCCCTCAAGACTGAGGACACAGCCATGTACTATTGC
    GCCAAGGGAGGGTCTGGCTACGGCGATGCCTCCAGGATGACCTCCCCCGGTAGC
    CAGGGCACTCAGGTGACAGTGTCAAGC
    DR593- 1085 CAGGTGCAGCTCCAGGAGAGCGGTGGGGGAAGCGTGCAGGCTGGCGGAAGCCTC
    hIL27 CGCCTGTCCTGTGCGGCATCTGGCTACCCATATTCTAACGGTTATATGGGCTGG
    Ra_VH TTTCGGCAAGCGCCTGGGAAGGAGCGCGAGGGGGTCGCCACCATTTATACTGGC
    H18 GATGGCCGCACCTATTACGCCGATTCTGTGAAGGGCCGCTTCACGATTTCTAGG
    GATAACGCTAAAAACACCGTGGATCTGCAAATGTCCAGCCTGAAGCCAGAAGAC
    ACAGCCATGTACTATTGCGCCGCTCGGGCCGCTCCTTTGTACTCATCCGGCTCA
    CCTCTCACTAGAGCCCGTTACAACGTCTGGGGACAGGGTACTCAGGTTACCGTA
    AGCTCTGGGGGTGGCTCACAAGTGCAGTTGCAGGAGAGCGGTGGAGGTTCCGTT
    CAGGCTGGAGGCTCCCTGCGGCTTTCCTGCGTGGCTTCCGGCTACGTGTCATGC
    GACTACTTCCTGCCTAGCTGGTATCGCCAGGCTCCTGGGAAGGAGCGTGAATTT
    GTTAGCATCATTGATGGCACAGGCAGCACTAGCTACGCGGCTTCTGTTAAGGGA
    CGTTTTACAGCGTCTCAGGACAAAGGGAAGAACATCGCCTACCTCCAGATGAAC
    TCCCTGAAACCGGAGGATACCGCCATGTACTATTGCAAGGCCTCCTGCGTGCGC
    GGTCGCGGTATTAGCGAATACTGGGGACAGGGCACCCAGGTCACTGTGTCTTCA
    DR593- 1086 CAGGTCCAGCTCCAGGAATCCGGTGGAGGCTCCGTGCAGGCCGGAGGGTCTCTC
    hIL27 AGACTCAGCTGCGCTGCCAGTGGTTATCCGTACTCTAATGGGTACATGGGTTGG
    Ra_VH TTCCGCCAGGCCCCCGGCAAGGAGAGGGAAGGCGTGGCCACAATCTATACCGGC
    H18 GACGGGCGTACATATTACGCGGATAGTGTGAAGGGACGCTTCACCATCAGCCGT
    GACAACGCCAAGAACACCGTGGACCTTCAGATGTCTTCCTTGAAGCCAGAAGAC
    ACCGCGATGTATTACTGCGCGGCTCGCGCAGCTCCCCTCTATTCCTCTGGCTCC
    CCACTGACCCGCGCCAGATACAATGTTTGGGGCCAGGGCACTCAGGTCACTGTG
    TCCAGTGGCGGTAGCGGCGGTAGTGGTGGCTCCGGTCAGGTGCAGCTCCAGGAG
    TCAGGGGGTGGCTCCGTACAGGCTGGTGGCTCACTCCGTCTGAGTTGTGTAGCC
    AGCGGTTACGTCTCCTGCGATTATTTCCTTCCTTCCTGGTATCGCCAGGCTCCC
    GGCAAAGAGCGGGAGTTCGTTTCCATTATCGACGGAACTGGATCAACATCCTAT
    GCCGCTTCTGTCAAGGGGCGCTTCACCGCCTCACAGGATAAGGGCAAGAATATC
    GCTTACCTCCAGATGAACAGCCTGAAACCAGAAGACACCGCGATGTATTACTGT
    AAGGCGAGCTGTGTTCGCGGGCGGGGGATCTCAGAGTATTGGGGCCAGGGCACA
    CAGGTGACCGTATCCTCC
    DR593- 1087 CAAGTGCAGCTCCAGGAGTCAGGCGGTGGCAGCGTACAGGCCGGAGGCTCCCTG
    hIL27 AGACTGAGCTGTGCAGCCTCTGGCTACCCATACAGCAATGGCTATATGGGATGG
    Ra_VH TTCCGCCAGGCTCCGGGTAAAGAGCGCGAGGGCGTGGCCACTATTTATACCGGG
    H19 GACGGAAGAACCTATTACGCGGATTCCGTGAAAGGCCGCTTCACAATTTCCCGT
    GACAACGCGAAGAACACCGTCGATCTCCAGATGTCTTCCCTGAAGCCAGAGGAC
    ACCGCTATGTATTACTGCGCCGCTAGGGCAGCTCCGCTTTACAGTAGCGGATCT
    CCCCTCACCCGCGCCCGCTACAACGTGTGGGGACAGGGAACACAAGTGACAGTT
    TCCTCAGGCGGTGGCTCTCAGGTGCAGCTCCAGGAATCTGGGGGAGGGTCCGTA
    CAGGCCGGAGGCTCCCTGAGATTGAGCTGCCGCGCAAGTGGGTCCACCTACAGC
    AACTATTGTCTGGGGTGGTTTCGCCAGATTACTGGTAAGGAGAGGGAGGGCGTG
    GCCGTCATCAACTGGGTGGGCGGAATGCTCTACTTCGCCGACTCCGTGAAGGGT
    CGGTTCACCGTTTCACAGGACCAAGCAAAGAACACCGTGTACCTCCAGATGAAC
    AGTCTGAAGCCCGAGGATACCGCCATGTATTACTGTGCGGCTGAATCCGTCAGC
    TCCTTCTCCTGCGGCGGGTGGCTGACACGGCCAGATCGGGTCCCTTACTGGGGA
    CAGGGCACACAGGTGACTGTGTCCTCC
    DR593- 1088 CAGGTGCAGTTGCAGGAGAGTGGAGGTGGCAGCGTGCAGGCCGGAGGCAGCCTT
    hIL27 CGCCTCTCTTGCGCTGCGAGTGGCTACCCCTACAGCAATGGGTACATGGGCTGG
    Ra_VH TTCCGTCAGGCACCCGGTAAAGAAAGAGAGGGCGTGGCTACTATCTACACTGGG
    H19 GATGGCAGGACCTATTACGCCGATAGCGTCAAGGGCCGGTTCACGATTAGCCGT
    GACAACGCCAAAAATACTGTGGACCTCCAGATGTCTTCACTGAAACCTGAGGAC
    ACAGCAATGTATTACTGCGCTGCCCGTGCCGCTCCTCTCTACAGCTCCGGCTCT
    CCATTGACCCGCGCCCGTTACAATGTTTGGGGGCAGGGCACCCAAGTCACCGTG
    TCATCCGGCGGTTCCGGCGGAAGCGGTGGCAGCGGCCAGGTGCAGCTTCAGGAG
    TCTGGTGGCGGTAGCGTTCAGGCAGGTGGCAGTCTGCGTCTGAGCTGCCGGGCG
    AGCGGCAGCACATACTCCAACTATTGCCTGGGCTGGTTTCGGCAGATCACTGGT
    AAGGAGCGCGAGGGCGTGGCTGTCATAAATTGGGTCGGAGGTATGCTGTACTTC
    GCCGACTCAGTTAAAGGACGCTTCACCGTGTCCCAGGACCAGGCTAAGAATACT
    GTGTATCTCCAGATGAACAGTCTGAAACCAGAGGACACAGCAATGTATTACTGT
    GCTGCCGAAAGCGTCTCATCTTTCTCCTGTGGGGGCTGGCTCACACGCCCGGAC
    CGTGTTCCGTATTGGGGTCAGGGAACCCAGGTGACCGTAAGCTCC
    DR593- 1089 CAAGTGCAGCTCCAGGAGTCCGGGGGCGGGTCTGTGCAAGCTGGCGGTTCTCTG
    hIL27 AGGCTGTCCTGCGCTGCATCCGGCTACCCTTACTCCAATGGCTACATGGGTTGG
    Ra_VH TTCAGACAAGCTCCCGGAAAGGAGAGGGAGGGTGTGGCTACCATCTACACCGGC
    H20 GACGGACGCACTTATTACGCAGACTCCGTGAAGGGCCGCTTCACCATTTCTCGG
    GATAACGCTAAGAACACCGTGGACCTTCAGATGTCTTCCCTTAAACCTGAGGAC
    ACTGCCATGTATTACTGTGCCGCTCGGGCCGCGCCACTGTACTCTTCCGGGTCC
    CCACTTACACGTGCTCGTTACAATGTGTGGGGTCAAGGAACCCAGGTGACTGTG
    TCCAGCGGAGGCGGTTCACAAGTGCAGCTTCAGGAAAGCGGAGGCGGGTTGGTG
    CAGCCTGGGGGCTCACTCCGTCTGAGCTGTGCCGCTTCTGGTTTCACCTTCTCT
    TCATATCCTATGAGTTGGGTGAGACAAGCGCCGGGCAAAGGACTGGAGTGGGTC
    TCCACTATTTCTTCCGGCGGTGATACTACCTTGTATGCTGACTCCGTGAAGGGT
    CGTTTCACCTCCAGTCGCGACAATGCGAAGAATACCCTGTACCTCCAGCTCAAC
    TCCCTGAAGACCGAGGACACAGCGATGTATTACTGCGCTAAGCGTATCGACTGC
    AATTCCGGGTACTGCTACAAGAGAAGCTACTGGGGGCAAGGGACTCAGGTGACA
    GTGTCTAGC
    DR593- 1090 CAGGTCCAACTTCAGGAGTCTGGTGGAGGCTCCGTTCAGGCGGGCGGGTCCCTG
    hIL27 CGCTTGTCTTGTGCAGCCAGCGGTTACCCATACAGCAACGGATATATGGGCTGG
    Ra_VH TTCCGGCAGGCCCCTGGGAAAGAACGTGAGGGCGTCGCGACTATCTATACTGGA
    H20 GATGGACGCACTTATTACGCCGATAGCGTCAAGGGACGGTTTACCATCAGCAGG
    GACAACGCCAAAAACACCGTGGACCTTCAGATGTCTTCCCTGAAACCCGAGGAC
    ACGGCTATGTACTATTGCGCGGCCCGCGCTGCCCCTCTCTATAGTTCTGGGAGT
    CCCTTGACAAGGGCCAGATACAACGTGTGGGGGCAGGGGACTCAGGTTACTGTC
    TCCTCTGGTGGCTCCGGTGGCAGCGGAGGCTCTGGCCAGGTGCAGTTGCAGGAG
    AGTGGGGGTGGCCTGGTGCAGCCTGGTGGCAGCCTGCGCCTGTCTTGCGCAGCC
    TCTGGGTTTACCTTTAGCTCTTACCCCATGTCCTGGGTCCGCCAGGCTCCCGGC
    AAAGGACTGGAGTGGGTGTCCACCATTTCTAGCGGAGGCGATACTACCCTGTAC
    GCCGACTCTGTGAAGGGGCGCTTCACTAGCTCACGGGACAATGCTAAGAACACA
    CTGTACCTTCAGCTGAACTCACTGAAAACCGAAGACACTGCTATGTATTACTGC
    GCTAAACGCATTGATTGCAACAGCGGCTATTGTTATAAAAGATCCTACTGGGGC
    CAGGGCACCCAGGTCACGGTCTCCAGC
    DR593- 1091 CAAGTTCAGCTCCAGGAGAGTGGAGGGGGCAGTGTTCAGGCCGGAGGTAGCCTG
    hIL27 CGCCTCAGCTGTGCAGCCAGTGGCTACCCCTACTCTAATGGCTACATGGGCTGG
    Ra_VH TTCAGGCAGGCCCCCGGAAAAGAGCGTGAGGGTGTGGCTACAATTTATACCGGA
    H21 GACGGCAGAACCTACTATGCCGACTCCGTGAAGGGCCGCTTCACAATCTCTCGG
    GACAACGCTAAGAACACAGTGGATCTTCAGATGAGCAGTCTCAAGCCAGAGGAT
    ACCGCCATGTATTACTGTGCCGCGCGGGCTGCCCCTTTGTACTCATCTGGGAGC
    CCTCTGACCCGCGCCCGCTATAATGTGTGGGGCCAGGGGACCCAAGTGACGGTA
    TCCTCTGGGGGCGGTAGCCAGGTGCAGCTCCAGGAAAGCGGAGGGGGACTGGTG
    CAGCCCGGCGGGAGCCTGCGGCTTAGCTGCGCAGCCTCCGGCTTCACCTTCTCC
    CTCAGTTCCATGAGTTGGGTTCGCCAGGCTCCAGGGAAGGGACTGGAATGGGTG
    TCAGCCATCTCCTCTGGCGGGGCGTCCACTTATTACACAGACTCCGTGAAGGGT
    AGGTTCACCATTTCTAGGGATAATGCCAAGAACATGCTGTACCTCCAGCTGAAC
    AGTCTGAAAACAGAAGACACAGCTATGTACTATTGCGCCAAAGGTGGGTCCGGT
    TATGGCGATGCGTCCAGGATGACTTCCCCTGGGTCCCAGGGCACACAGGTCACC
    GTGAGTAGC
    DR593- 1092 CAGGTGCAACTCCAGGAGAGCGGCGGAGGCTCTGTCCAAGCAGGCGGGTCTCTC
    hIL27 CGTCTGTCTTGCGCCGCAAGCGGATACCCCTACAGCAACGGTTATATGGGTTGG
    Ra_VH TTCCGCCAGGCCCCCGGAAAGGAGCGTGAGGGTGTGGCCACCATCTACACTGGC
    H21 GATGGAAGAACCTATTACGCAGACAGCGTGAAGGGCCGGTTTACCATCAGCCGC
    GACAACGCCAAGAACACCGTTGACTTGCAGATGTCCAGCCTGAAACCTGAGGAC
    ACAGCTATGTACTATTGTGCTGCCAGAGCGGCTCCTCTCTACAGTTCTGGATCT
    CCCCTTACACGGGCTAGGTACAATGTTTGGGGGCAGGGCACCCAGGTCACCGTG
    TCCTCTGGCGGATCAGGAGGCAGCGGGGGCTCTGGTCAAGTGCAGCTCCAGGAG
    TCCGGCGGGGGACTGGTTCAGCCTGGAGGTTCCCTGCGCCTTTCTTGTGCTGCC
    AGCGGCTTCACGTTCTCCCTGAGTTCCATGAGCTGGGTCCGGCAGGCCCCCGGC
    AAAGGCCTGGAGTGGGTTTCCGCTATCTCCAGCGGCGGGGCCTCCACCTACTAT
    ACCGACTCCGTGAAGGGACGGTTCACAATCTCCAGGGACAATGCTAAGAATATG
    TTGTACCTTCAGTTGAACTCCCTGAAAACCGAAGACACGGCCATGTATTACTGC
    GCCAAGGGAGGCTCCGGTTACGGCGATGCCAGCAGAATGACCTCCCCTGGTAGC
    CAGGGGACACAGGTGACTGTATCCAGC
    DR593- 1093 CAGGTGCAGTTGCAGGAGTCCGGCGGAGGCTCCGTTCAGGCCGGTGGCAGCCTC
    hIL27 AGACTGTCATGTGCAGCCTCCGGTTATCCCTATTCCAATGGTTACATGGGATGG
    Ra_VH TTCCGTCAGGCCCCTGGGAAAGAGAGGGAGGGCGTCGCCACGATCTACACCGGC
    H22 GATGGACGCACATATTACGCCGACAGTGTTAAGGGCCGTTTCACCATCTCTCGC
    GACAACGCCAAAAACACAGTTGATTTGCAGATGAGTTCCCTCAAGCCCGAAGAC
    ACCGCTATGTACTATTGTGCAGCCCGCGCCGCTCCTCTCTACAGCTCTGGCTCC
    CCACTGACGAGGGCGCGGTACAACGTGTGGGGCCAGGGCACCCAGGTTACCGTT
    TCTAGTGGCGGTGGCTCCCAGGTCCAGCTCCAGGAGAGTGGCGGAGGCAGCGTG
    CAGGCAGGCGGTAGCCTTCGCCTGAGCTGCCGGGCCTCCGGGAGCACGTACTCT
    AACTACTGTCTTGGATGGTTCCGGCAGACAACTGGGAAGGAGCGCGAGGGAGTC
    GCCGTTATCAACTGGGTAGGGGGAATGCTGTACTTTGCCGATTCCGTCAAGGGA
    CGCTTTACCGTCTCTCAGGATCAGGCCAAGAACACCGTCTACCTCCAGATGAAC
    AGTCTGAAGCCCGAGGACACCGCTATGTACTATTGCGCTGCGGAGAGCGTTTCC
    TCTTTCTCCTGCGGCGGTTGGCTTACCCGCCCCGACCGGGTGCCTTACTGGGGT
    CAGGGCACACAGGTGACCGTCTCCTCC
    DR593- 1094 CAGGTTCAGCTTCAGGAAAGTGGAGGGGGCTCCGTTCAAGCCGGGGGTTCCCTT
    hIL27 AGGCTGTCCTGCGCCGCTTCTGGTTATCCGTATTCAAATGGGTACATGGGATGG
    Ra_VH TTCCGCCAGGCTCCCGGCAAGGAGCGCGAGGGTGTCGCAACAATCTATACGGGC
    H22 GACGGTCGGACCTACTATGCAGACTCTGTCAAGGGCCGGTTCACAATCTCCCGC
    GATAACGCCAAGAACACAGTGGACCTCCAGATGTCATCCCTGAAGCCAGAGGAT
    ACAGCAATGTATTACTGTGCTGCACGTGCCGCTCCCCTGTACTCTAGTGGGAGC
    CCCCTCACCAGAGCGCGGTATAACGTGTGGGGTCAGGGGACTCAGGTAACCGTG
    TCCAGCGGCGGTTCCGGCGGTAGCGGAGGCTCCGGCCAGGTACAGCTCCAGGAG
    AGCGGAGGGGGCTCCGTCCAGGCTGGCGGGTCCCTGCGCCTGTCCTGCCGGGCC
    TCCGGTAGCACATACTCTAACTACTGCCTGGGCTGGTTCAGGCAGACCACTGGA
    AAGGAACGCGAGGGCGTCGCTGTAATCAACTGGGTCGGAGGTATGCTTTACTTC
    GCAGACTCCGTGAAGGGTCGCTTCACAGTGAGCCAGGACCAAGCTAAGAACACT
    GTGTACCTCCAGATGAACTCTCTCAAGCCGGAGGATACCGCCATGTATTACTGT
    GCAGCCGAGAGTGTGTCTAGCTTCTCCTGCGGAGGCTGGCTGACGAGACCCGAT
    AGGGTCCCGTACTGGGGGCAGGGCACTCAAGTCACTGTGAGCAGC
    DR593- 1095 CAGGTACAACTTCAGGAAAGCGGGGGAGGCTCCGTACAGGCGGGAGGCAGCTTG
    hIL27 CGCCTGAGCTGTGCCGCAAGTGGTTACCCGTACAGCAACGGCTACATGGGCTGG
    Ra_VH TTTCGTCAGGCTCCTGGGAAAGAGAGAGAGGGCGTGGCTACGATCTACACGGGT
    H23 GACGGACGCACCTATTACGCCGACTCCGTGAAAGGAAGATTCACCATCAGCCGC
    GATAACGCTAAGAACACAGTTGACCTGCAAATGTCTAGCCTGAAACCGGAGGAC
    ACTGCTATGTACTATTGTGCCGCACGCGCTGCCCCTCTCTATTCTTCCGGCAGC
    CCCCTCACCAGGGCTCGCTACAACGTCTGGGGCCAAGGGACCCAGGTGACTGTG
    TCCAGCGGTGGAGGGAGCCAGGTGCAGCTCCAGGAGAGCGGCGGGGGCTCTGTC
    CAGGCCGGTGGCAGTCTGCGCCTGTCCTGCCGGGCCTCCCGTTCCCCTTACGGG
    AATTATTGCCTGGGCTGGTTCAGACAGTCTACGGGTAAGGAGCGGGAAGGCGTG
    GCAGTTATCAACTGGGTCGGCGGAATGCTGTACTTTGCCGACTCCGTCAAAGGC
    CGCTTCACTGTGTCTCAGGACCATGCAAAGAACACCGTAACCTTGCAGATGAAC
    TCTCTGAAACCCGAAGACACGGCGATGTATTACTGCGCTGCCGAGTCCGTTTCT
    AGCTTCAGCTGTGGCGGTTGGTTGACAAGGCCAGATCGCGTCCCGTACTGGGGC
    CAAGGAACCCAGGTAACCGTAAGCAGT
    DR593- 1096 CAAGTCCAGCTGCAAGAGAGCGGAGGCGGGAGCGTTCAGGCTGGTGGCAGCCTG
    hIL27 CGGCTGAGTTGTGCTGCCAGCGGATACCCCTATTCCAATGGTTATATGGGTTGG
    Ra_VH TTTAGACAGGCACCTGGAAAGGAACGCGAGGGCGTAGCTACTATTTACACTGGA
    H23 GACGGCAGGACTTATTACGCGGATAGCGTGAAGGGCCGTTTCACAATTTCACGC
    GACAATGCCAAAAACACCGTGGATCTGCAAATGTCCAGCCTGAAGCCCGAGGAC
    ACCGCCATGTACTATTGCGCCGCACGCGCGGCTCCCCTGTACTCCTCAGGTAGC
    CCTTTGACTCGCGCACGCTATAATGTGTGGGGCCAGGGCACCCAGGTGACGGTT
    TCTAGCGGAGGGAGCGGGGGTTCTGGTGGCTCAGGTCAGGTGCAGCTTCAGGAA
    TCTGGAGGTGGCTCCGTACAGGCTGGGGGCTCCCTGCGTCTGAGCTGCCGGGCG
    AGCAGGTCCCCTTATGGTAACTACTGTCTCGGTTGGTTCCGCCAATCCACCGGC
    AAGGAGCGCGAGGGAGTGGCCGTTATAAATTGGGTGGGCGGTATGCTGTACTTT
    GCTGACAGTGTTAAGGGACGTTTCACCGTATCTCAGGACCACGCCAAGAACACC
    GTGACATTGCAGATGAACTCTCTCAAGCCAGAGGACACCGCTATGTATTACTGT
    GCCGCTGAGTCAGTGTCCTCTTTCAGCTGCGGCGGGTGGCTCACTCGCCCTGAC
    AGAGTACCCTATTGGGGGCAGGGGACACAGGTCACGGTTTCCAGC
    DR593- 1097 CAAGTACAGTTGCAGGAGTCCGGCGGTGGCAGTGTTCAGGCGGGCGGGTCCCTG
    hIL27 CGCCTCAGCTGCGCAGCCAGCGGATACCCATACTCTAACGGTTACATGGGTTGG
    Ra_VH TTCCGCCAGGCCCCAGGTAAGGAAAGAGAGGGAGTGGCGACTATTTATACCGGG
    H24 GATGGCCGCACCTACTATGCCGATTCTGTAAAAGGTAGGTTCACGATCTCTCGC
    GATAACGCCAAAAACACAGTCGATCTCCAGATGTCTTCCCTGAAGCCCGAGGAC
    ACCGCCATGTATTACTGTGCGGCACGGGCAGCTCCCCTTTACAGCTCCGGTTCC
    CCGCTGACTCGTGCCCGTTACAACGTCTGGGGGCAGGGCACACAGGTAACCGTG
    TCCAGCGGCGGAGGTTCACAGGTGCAGCTCCAGGAGTCTGGTGGCGGACTGGTG
    CAGCCCGGAGGCTCCCTGCGTCTCAGCTGTGCAGCCAGCGGCTTTACATTTAGC
    CACTCCGGTATGAGCTGGGTACGGCAGGCACCTGGAAAGGGTCTGGAGTGGGTG
    TCCACAATCAACTCAGGCGGAGCCTCTACATACTATACTGACTCAGTCAAGGGA
    CGTTTCACCATCTCCCGCGACAACGCTAAAAACATGCTGTACCTTCAGTTGAAC
    AGTCTGAAGACTGAGGATACAGCCATGTATTACTGTGCCAAAGGGGGCTCTGGC
    TACGGGGATGCCTCCAGAATGACTAGCCCTGGCTCCCAGGGCACCCAGGTGACC
    GTGTCTTCC
    DR593- 1098 CAGGTGCAGTTGCAAGAGTCTGGCGGAGGCTCCGTCCAAGCAGGCGGGAGTCTT
    hIL27 CGGCTGTCTTGTGCAGCCTCCGGGTATCCGTACTCTAATGGTTACATGGGCTGG
    Ra_VH TTCAGGCAGGCCCCAGGTAAAGAACGGGAGGGCGTGGCCACCATTTACACCGGC
    H24 GATGGCCGCACATACTATGCCGACTCCGTGAAGGGTAGGTTCACCATTTCACGT
    GACAATGCCAAGAATACCGTGGATCTCCAGATGTCTAGCCTGAAGCCGGAGGAC
    ACAGCCATGTATTACTGTGCTGCCCGCGCTGCCCCTCTGTACTCCAGCGGTTCT
    CCTCTGACTAGAGCCCGGTACAACGTGTGGGGCCAGGGCACCCAAGTCACTGTG
    TCTAGTGGCGGGTCCGGCGGAAGCGGTGGCTCAGGCCAAGTTCAGCTCCAGGAA
    TCAGGTGGGGGCCTGGTCCAGCCCGGTGGATCTCTGCGGCTGTCCTGTGCTGCC
    AGCGGATTCACGTTTAGCCACAGCGGCATGAGCTGGGTACGCCAGGCTCCAGGC
    AAAGGATTGGAATGGGTGTCCACAATTAACTCTGGCGGGGCCAGCACCTATTAC
    ACTGACAGCGTTAAAGGGCGCTTTACAATCTCTCGCGACAACGCCAAGAATATG
    TTGTACCTCCAGCTGAACTCACTCAAGACCGAGGATACTGCCATGTATTACTGT
    GCTAAAGGCGGAAGCGGCTACGGCGACGCTTCCAGGATGACCAGTCCTGGCTCC
    CAGGGCACACAGGTGACCGTGTCCTCC
    DR594- 1099 CAGGTCCAGCTTCAGGAGTCCGGCGGAGGCAGCGTACAGGCGGGCGGGTCCTTG
    hIL27 CGCCTGTCCTGTGTGGCCTCCGCATCTACGTATTGCACCTATGATATGCACTGG
    Ra_VH TATCGTCAGGCCCCTGGCAAAGGTCGGGAGTTCGTGAGCGCCATTGATTCTGAT
    H1 GGCACTACCCGCTACGCCGACAGTGTGAAGGGACGGTTTACCATTTCCCAGGGA
    ACCGCGAAGAATACCGTGTACCTCCAGATGAACAGCCTGCAACCCGAGGACACA
    GCTATGTACTATTGTAAGACCGTGTGTGTCGTGGGTTCCCGCTGGAGCGACTAT
    TGGGGACAGGGCACCCAAGTGACCGTCAGCTCCGGCGGGGGCTCTCAGGTGCAG
    TTGCAGGAGAGCGGGGGTGGATTGGTGCAGCCCGGCGGATCTCTGCGCCTGAGC
    TGCGCCGCTTCCGGGTTCACTTTTTCATCTTACCCAATGTCCTGGGTGCGCCAA
    GCGCCGGGCAAGGGACTGGAGTGGATCTCCACGATCAGCGCTGGCGGTGATACA
    ACCCTTTACGCCGACTCCGTGAAGGGCCGCTTTACCAGCTCAAGAGACAACGCA
    AAAAACACTCTGTACTTGCAGCTGAACTCTCTCAAGACCGAGGATGCGGCCATT
    TATTACTGCGCCAAGCGCATTGATTGTAACTCTGGGTACTGTTATAGACGCAAC
    TATTGGGGTCAGGGCACGCAGGTGACCGTGTCTTCC
    DR594- 1100 CAGGTTCAGCTCCAGGAAAGCGGCGGAGGCAGTGTGCAGGCAGGCGGAAGCCTG
    hIL27 AGACTGTCCTGTGTAGCGTCAGCCAGTACCTACTGCACATACGATATGCACTGG
    Ra_VH TATCGCCAAGCTCCTGGGAAAGGAAGAGAGTTCGTTTCCGCCATCGACTCTGAC
    H1 GGCACTACAAGATATGCCGATAGCGTTAAAGGCCGCTTTACAATTTCCCAGGGC
    ACCGCGAAGAACACCGTCTACCTGCAAATGAATAGTTTGCAGCCAGAAGACACT
    GCTATGTACTATTGCAAGACCGTGTGCGTGGTCGGGTCAAGGTGGAGCGATTAC
    TGGGGCCAAGGTACTCAGGTCACCGTCAGCTCCGGTGGAAGCGGGGGCTCCGGG
    GGCTCTGGACAGGTCCAGCTCCAGGAGTCTGGCGGAGGCCTCGTTCAGCCAGGG
    GGCTCATTGAGGCTTTCCTGTGCGGCCTCCGGCTTCACATTTTCTAGCTACCCG
    ATGAGTTGGGTACGCCAGGCTCCTGGAAAAGGCCTGGAATGGATCAGCACAATC
    AGCGCAGGTGGGGACACAACCCTGTACGCTGATAGCGTGAAGGGTAGGTTTACA
    TCTTCCCGCGACAACGCTAAGAACACCCTTTACTTGCAGCTCAATTCCCTCAAG
    ACCGAGGACGCGGCCATCTATTACTGCGCCAAACGTATTGACTGCAACTCTGGT
    TATTGTTACAGAAGGAATTACTGGGGCCAGGGGACCCAGGTGACCGTATCTTCC
    DR594- 1101 CAGGTGCAGCTCCAAGAATCCGGGGGTGGCAGTGTGCAGGCCGGTGGCTCTCTG
    hIL27 AGGTTGAGCTGCGTCGCCTCAGCCAGCACTTACTGCACCTATGACATGCACTGG
    Ra_VH TACAGACAGGCACCCGGTAAGGGACGTGAGTTCGTGTCTGCTATTGATTCCGAT
    H2 GGCACTACCAGATATGCCGATTCCGTGAAAGGCAGATTCACGATTTCCCAAGGA
    ACCGCTAAGAACACCGTGTATCTCCAAATGAACTCCCTTCAGCCCGAAGACACC
    GCTATGTATTACTGTAAGACCGTGTGCGTAGTGGGCAGTCGTTGGTCAGACTAT
    TGGGGCCAGGGCACCCAGGTCACCGTCAGTTCCGGCGGAGGCTCTCAGGTCCAA
    CTTCAGGAATCTGGGGGAGGTTTGGTGCAGCCGGGTGGCTCCCTGCGGCTGTCC
    TGTGCGGCAAGTGGCTTCACCTTCAGCCTCTCCGGCATGTCCTGGGTGCGCCAA
    GCGCCCGGTAAGGGGCTGGAGTGGGTGTCCGCCATTAGCTCTGGCGGTGCTTCT
    ACCTATTACACCGACTCCGTCAAGGGTCGGTTTACCATCTCTCGCGACAACGCT
    AAGAACATCTTGTACCTTCAGCTCAATTCTCTGAAGACTGAGGACACTGCCATG
    TATTACTGTGCGAAAGGTGGCTCCGGCTACGGAGATGCCTCTCGCATGACCTCC
    CCTGGGTCCCAGGGCACACAGGTTACCGTGTCCTCC
    DR594- 1102 CAGGTCCAGCTCCAGGAGTCTGGCGGAGGGAGCGTTCAGGCCGGGGGCTCTCTG
    hIL27 AGGCTCTCCTGTGTGGCGAGCGCCTCTACTTACTGTACTTACGACATGCACTGG
    Ra_VH TATCGCCAAGCCCCAGGCAAGGGCAGGGAGTTCGTCAGTGCCATCGACTCCGAC
    H2 GGCACAACTCGCTACGCCGACTCCGTCAAGGGACGTTTCACAATCTCTCAGGGC
    ACGGCTAAGAACACTGTGTATCTCCAAATGAACAGTCTCCAGCCTGAAGATACA
    GCCATGTACTATTGCAAAACTGTGTGTGTGGTCGGCTCACGGTGGTCTGACTAC
    TGGGGTCAGGGGACCCAGGTCACAGTAAGCTCAGGAGGTTCCGGCGGTTCTGGC
    GGTTCAGGACAGGTGCAACTTCAGGAAAGCGGTGGCGGACTCGTCCAGCCCGGA
    GGTTCACTGCGTCTCAGCTGTGCTGCCAGCGGTTTTACCTTCAGCCTCAGTGGA
    ATGAGCTGGGTCAGACAGGCCCCTGGCAAAGGGCTGGAGTGGGTGAGTGCCATT
    TCCTCAGGAGGTGCCTCTACCTATTACACCGACTCTGTCAAAGGCAGGTTTACC
    ATCAGCCGCGATAACGCCAAGAACATCCTGTATCTCCAGCTTAATTCCCTCAAG
    ACAGAAGACACAGCTATGTATTACTGTGCGAAAGGGGGCTCCGGTTACGGGGAC
    GCTTCCAGAATGACATCCCCTGGTTCTCAGGGCACACAGGTGACCGTGTCCTCA
    DR594- 1103 CAAGTTCAGCTCCAGGAATCTGGCGGTGGGTCTGTTCAAGCCGGTGGCTCCCTG
    hIL27 CGCCTTTCATGTGTCGCCTCTGCTTCTACATACTGCACCTACGACATGCACTGG
    Ra_VH TATCGTCAGGCTCCCGGCAAGGGCCGCGAATTTGTTAGTGCTATCGACTCCGAC
    H3 GGCACTACACGCTATGCCGACAGTGTTAAAGGCCGCTTCACCATCTCTCAGGGC
    ACGGCGAAAAACACCGTGTACCTCCAGATGAACTCCCTGCAACCCGAGGATACA
    GCCATGTATTACTGCAAGACAGTCTGTGTCGTGGGATCTCGCTGGTCTGACTAC
    TGGGGACAGGGGACCCAGGTTACTGTCTCCTCTGGCGGAGGCAGCCAGGTGCAG
    CTTCAGGAGTCCGGTGGGGGCTCCGTGCAGGCTGGCGGAAGCCTGCGCCTGTCC
    TGCGTTGCATCCGGTTATGTTAGCTGCGATTACTTCCTGCCCTCCTGGTATCGT
    CAAGCTCCCGGCAAGGAGCGCGAGTTTGTTTCCATTATCGACGGCACCGGCAGC
    ACGTCATACGCTGCGAGCGTTAAGGGCCGCTTCACCGCTTCCGAAGACAAGGGC
    AAGAACATCGCCTACTTGCAGATGAACTCCCTGAAGCCTGAGGATACCGCCATG
    TATTACTGCAAGGCCAGCTGCGTCCGGGGCCGGGCCGTGTCCGAGTATTGGGGG
    CAGGGCACCCAGGTGACAGTGAGTAGC
    DR594- 1104 CAAGTCCAACTCCAGGAAAGTGGCGGTGGGTCCGTACAGGCCGGGGGCAGTCTG
    hIL27 CGGCTTTCCTGTGTGGCCTCTGCATCTACTTACTGTACTTACGACATGCACTGG
    Ra_VH TATCGCCAGGCCCCAGGTAAGGGTCGGGAGTTTGTTAGCGCAATCGACTCAGAC
    H3 GGGACTACCCGCTACGCGGATAGCGTCAAGGGCCGGTTCACCATCTCTCAGGGC
    ACCGCCAAGAACACCGTTTATTTGCAGATGAATAGCCTCCAACCTGAAGATACT
    GCAATGTATTACTGCAAGACAGTGTGCGTGGTTGGCAGCCGCTGGTCAGACTAT
    TGGGGTCAGGGCACCCAGGTCACCGTTAGCTCTGGAGGCAGCGGCGGTAGCGGT
    GGCAGCGGACAGGTCCAGCTCCAGGAGTCAGGAGGGGGCTCTGTCCAGGCCGGG
    GGCTCTCTCCGTCTTTCTTGCGTCGCCTCAGGCTACGTCAGCTGCGATTACTTC
    CTCCCTAGCTGGTATCGTCAAGCGCCGGGGAAGGAACGGGAGTTTGTGTCAATC
    ATTGACGGCACCGGCTCTACTTCCTATGCTGCCAGCGTGAAGGGCCGCTTTACA
    GCCTCCGAAGACAAGGGCAAGAACATCGCTTACCTCCAGATGAACTCTCTGAAG
    CCCGAAGACACCGCTATGTACTATTGCAAGGCCAGCTGCGTCAGAGGTAGGGCT
    GTGTCCGAATATTGGGGTCAGGGCACGCAGGTTACCGTGTCTTCT
    DR594- 1105 CAGGTCCAACTCCAGGAGAGCGGAGGCGGTTCCGTGCAAGCAGGTGGCTCCCTG
    hIL27 CGCTTGAGCTGTGTGGCCTCCGCTAGTACTTACTGCACTTACGATATGCACTGG
    Ra_VH TATAGGCAAGCCCCAGGGAAGGGGCGCGAGTTCGTGTCCGCCATTGACAGCGAC
    H4 GGTACAACCCGGTATGCCGACTCTGTGAAAGGCCGTTTCACAATCTCCCAGGGA
    ACAGCCAAGAACACCGTATACCTCCAGATGAACTCCTTGCAGCCTGAGGATACA
    GCCATGTACTATTGTAAAACCGTGTGCGTGGTCGGCTCACGCTGGAGTGATTAC
    TGGGGCCAAGGAACCCAGGTCACTGTCTCCTCAGGGGGAGGTAGCCAGGTCCAG
    CTTCAGGAGTCCGGCGGTGGCCTGGTTCAGCCTGGGGAATCACTGCGTCTCTCT
    TGCACTGCCAGTGGATTCACATTTTCAAACTATGCTATGTCTTGGGTGCGGCAG
    GCCCCTGGGAAGGGGCTCGAATGGGTATCCGGTATTAACGTGGCATACGGCATC
    ACCTCCTACGCTGATTCCGTGAAGGGCAGGTTCACCATCTCTCGCGACAACACC
    AAGAACACACTGTACTTGCAACTTAACAGTCTTAAAACTGAAGACACTGCTATC
    TACTATTGCGTCAAGCACAGCGGTACGACTATCCCGCGTGGATTCATCAGCTAT
    ACAAAGAGGGGCCAAGGCACCCAAGTCACTGTGAGCAGC
    DR594- 1106 CAGGTCCAACTTCAGGAATCTGGCGGAGGCTCTGTGCAGGCTGGAGGGAGTCTT
    hIL27 AGACTGTCCTGTGTCGCAAGCGCAAGCACGTACTGCACCTACGACATGCACTGG
    Ra_VH TATCGCCAGGCTCCGGGTAAGGGACGCGAATTTGTGAGCGCAATCGACTCCGAC
    H4 GGGACCACAAGGTACGCCGATAGCGTTAAGGGACGTTTCACCATCAGTCAGGGT
    ACTGCCAAGAACACGGTCTACCTCCAGATGAATAGCCTCCAGCCGGAAGATACC
    GCTATGTATTACTGCAAGACAGTGTGCGTAGTGGGCAGCCGTTGGTCCGATTAT
    TGGGGCCAGGGTACACAGGTGACAGTCTCCAGTGGAGGCTCCGGCGGATCTGGG
    GGCAGCGGTCAGGTGCAGTTGCAGGAGAGCGGCGGTGGCTTGGTGCAACCCGGT
    GAATCTTTGCGTCTGAGCTGCACAGCGAGCGGATTCACATTTAGCAACTACGCC
    ATGTCCTGGGTGCGCCAGGCTCCCGGTAAGGGTCTGGAGTGGGTGAGTGGTATC
    AATGTGGCCTATGGGATCACCAGTTATGCGGATAGCGTGAAGGGCCGGTTTACC
    ATCAGCCGGGACAACACCAAGAACACCCTGTACCTTCAGCTTAACTCTCTGAAG
    ACCGAAGATACAGCCATCTATTACTGTGTGAAGCACTCAGGGACTACCATCCCT
    CGTGGTTTTATTAGCTACACTAAGCGTGGGCAAGGAACACAAGTGACGGTGTCT
    TCC
    DR594- 1107 CAGGTGCAGCTCCAGGAATCCGGCGGGGGCAGCGTGCAGGCCGGAGGCTCCTTG
    hIL27 CGTCTGTCTTGCGTCGCATCCGCCAGCACGTACTGCACCTACGATATGCACTGG
    Ra_VH TATCGTCAGGCTCCCGGTAAGGGGAGGGAGTTTGTCAGTGCTATCGACAGCGAT
    H5 GGGACCACTCGCTACGCTGACTCCGTGAAGGGTCGTTTTACCATCAGCCAGGGC
    ACAGCTAAGAACACGGTGTACTTGCAGATGAACTCTCTCCAGCCGGAAGACACC
    GCGATGTATTACTGCAAGACTGTTTGCGTCGTGGGCTCTCGTTGGTCTGACTAT
    TGGGGTCAGGGCACCCAAGTCACGGTGAGTAGCGGCGGGGGTAGCCAAGTGCAG
    CTTCAGGAGTCCGGTGGCGGAAGCGTGCAGGCTGGGGGCAGCCTTCGGCTGTCA
    TGTACCGCCTCCGGTTACGTGTCTTGTGACTACTTCTTGCCAAGCTGGTATCGT
    CAGGCCCCTGGTAAAGAGCGGGAGTTCGTCAGCGTGATTGATGGCACTGGGTCC
    ACCAGCTACGCTGCCAGCGTTAAGGGCCGCTTCACCGCCAGCCAGGACAAGGGA
    AAGAATATTGCATATCTCCAGATGAACTCCCTGAAGCCTGAAGATACCGCTATG
    TATTACTGCAAGGCCTCATGCGTCCGTGGACGCGCTATTTCCGAGTATTGGGGA
    CAGGGTACTCAGGTCACCGTGAGTTCT
    DR594- 1108 CAGGTGCAGCTGCAAGAAAGCGGTGGGGGCTCCGTCCAGGCGGGCGGTAGCCTG
    hIL27 AGGCTGAGTTGCGTCGCCAGCGCTAGTACATACTGTACCTACGACATGCACTGG
    Ra_VH TATCGCCAGGCCCCCGGCAAAGGCAGGGAGTTCGTGTCAGCCATCGACTCTGAC
    H5 GGGACTACCAGATACGCCGACTCCGTGAAAGGGCGGTTTACCATCAGTCAGGGT
    ACAGCTAAGAATACCGTGTACCTCCAGATGAACTCCTTGCAGCCTGAGGACACT
    GCAATGTATTACTGCAAGACCGTGTGTGTTGTCGGCAGCCGTTGGTCCGACTAC
    TGGGGACAGGGAACCCAGGTCACAGTCTCTAGCGGCGGAAGCGGGGGCTCAGGA
    GGCTCTGGGCAAGTGCAGTTGCAGGAGAGTGGCGGAGGCAGTGTGCAGGCCGGG
    GGCTCCCTCCGCCTGAGCTGTACTGCGAGCGGCTACGTCAGCTGTGACTACTTT
    CTGCCATCTTGGTATCGTCAGGCTCCCGGAAAGGAACGCGAGTTTGTGTCTGTG
    ATCGACGGGACCGGCTCTACCTCTTACGCCGCTTCCGTCAAGGGCCGCTTTACC
    GCTTCCCAAGATAAGGGGAAGAATATCGCTTACTTGCAGATGAACTCCCTGAAG
    CCAGAAGACACCGCCATGTACTATTGCAAGGCTTCCTGTGTTCGTGGCCGCGCC
    ATTAGCGAGTACTGGGGCCAGGGCACCCAGGTCACCGTGTCCAGT
    DR594- 1109 CAGGTACAACTCCAGGAGAGTGGTGGCGGGAGCGTGCAAGCAGGGGGCTCCCTG
    hIL27 CGCCTGTCCTGCGTCGCGTCCGCCAGCACATATTGCACCTACGATATGCACTGG
    Ra_VH TATCGCCAGGCCCCTGGGAAGGGTCGCGAGTTCGTGTCCGCCATCGACTCAGAC
    H6 GGCACTACCCGCTACGCGGATTCTGTGAAGGGCAGATTCACAATTTCCCAGGGG
    ACCGCCAAGAACACGGTGTATCTCCAGATGAACTCTTTGCAGCCCGAGGACACT
    GCCATGTATTACTGCAAGACCGTGTGTGTCGTGGGCTCCAGGTGGAGCGACTAT
    TGGGGCCAGGGGACACAGGTTACCGTGTCCAGCGGTGGCGGTTCCCAGGTACAG
    CTCCAGGAGTCTGGCGGTGGCCTGGTACAGCCCGGTGGAAGCCTGCGCCTCAGC
    TGTGCCGCTTCCGGCTTTAGCTTCAGTTCTTATGCCATGAAGTGGGTCCGCCAG
    GCCCCCGGCAAGGGCCTGGAATGGGTCTCCACCATCTCCAGTGGGGGTAGCTCC
    ACCAACTATGCTGATAGCGTGAAGGGACGCTTTACCATCAGTCGTGATAACGCG
    AAGAACACCCTTTACCTTCAGCTGAACTCTCTGAAGATCGAAGACACCGCCATG
    TACTATTGTGCCAAGGCTATCGTGCCTACCGGGGCCACTATGGAAAGAGGACAG
    GGCACCCAGGTGACAGTGTCCTCC
    DR594- 1110 CAGGTGCAGTTGCAGGAGTCTGGTGGCGGGTCAGTGCAGGCTGGAGGCTCCCTC
    - AGGCTGAGTTGTGTCGCAAGCGCAAGCACATACTGCACCTATGATATGCACTGG
    hIL27 TATCGCCAAGCTCCTGGCAAAGGTCGGGAGTTTGTGTCTGCTATTGATAGCGAC
    Ra_VH GGCACCACGCGCTACGCGGACTCCGTGAAGGGCAGATTTACAATCTCACAAGGG
    H6 ACGGCGAAAAATACCGTGTACCTCCAGATGAACTCTCTCCAGCCCGAGGATACC
    GCTATGTATTACTGCAAGACCGTCTGCGTCGTGGGTAGCAGGTGGTCCGACTAC
    TGGGGTCAGGGCACTCAGGTGACGGTGTCTTCAGGAGGCTCCGGGGGCTCTGGC
    GGTAGCGGACAGGTGCAGTTGCAGGAGAGCGGCGGGGGTCTGGTGCAGCCTGGG
    GGTTCCCTGAGACTGAGCTGCGCCGCTTCTGGTTTCAGTTTTAGTTCTTACGCT
    ATGAAGTGGGTACGCCAAGCCCCTGGTAAGGGTCTGGAGTGGGTTTCTACGATT
    TCTAGCGGGGGCAGCTCTACAAACTACGCGGATAGCGTGAAAGGACGCTTTACC
    ATCTCCCGCGACAATGCAAAGAACACTTTGTACCTCCAGCTTAATTCACTGAAG
    ATCGAGGACACGGCTATGTACTATTGCGCTAAGGCCATCGTGCCGACCGGAGCC
    ACTATGGAAAGAGGTCAAGGCACCCAGGTGACTGTGTCCTCA
    DR594- 1111 CAGGTCCAGCTCCAGGAGTCCGGCGGAGGCTCTGTGCAGGCAGGGGGCTCTCTG
    hIL27 AGGCTGAGCTGCGTCGCCTCAGCCTCTACCTACTGCACCTATGACATGCACTGG
    Ra_VH TATCGTCAGGCTCCTGGCAAGGGTCGCGAGTTCGTTTCTGCCATTGATTCCGAC
    H7 GGCACCACTAGATACGCTGACTCCGTCAAGGGCCGCTTCACCATCTCCCAGGGG
    ACTGCTAAGAACACCGTGTACCTTCAGATGAACTCTCTTCAGCCTGAAGATACT
    GCGATGTATTACTGCAAGACTGTTTGCGTTGTGGGAAGTCGTTGGTCCGATTAC
    TGGGGCCAGGGTACTCAAGTGACTGTAAGCTCAGGTGGCGGATCTCAGGTCCAG
    CTCCAGGAGTCAGGCGGTGGCCTCGTTCAGCCAGGCGGGTCTCTGAGACTGAGC
    TGCGCTGCCTCTGGATTCACCTTCTCATCTTACCCCATGTCTTGGGTGCGTCAA
    GCGCCTGGGAAAGGTCTGGAGTGGATCAGCACAATTTCAGCTGGTGGAGATACC
    ACTCTCTACGCTGACAGCGTGAAAGGCCGGTTCACCTCCAGCCGCGACAACGCC
    AAGAATACCCTGTACCTCCAGCTTAACTCCCTCAAGACAGAGGACACTGCAATT
    TACTATTGCGCTAAGCGGATTGATTGTAACTCCGGCTACTGCTACAGGCGTAAC
    TATTGGGGCCAGGGGACGCAGGTGACAGTGTCATCC
    DR594- 1112 CAGGTCCAGCTCCAGGAGAGTGGAGGCGGATCTGTGCAGGCCGGGGGCTCCCTG
    hIL27 CGTCTCTCATGCGTCGCCAGCGCATCTACTTACTGCACATACGACATGCACTGG
    Ra_VH TATCGTCAGGCACCGGGCAAGGGCCGTGAGTTCGTCTCTGCGATTGACTCTGAC
    H7 GGAACTACCCGCTACGCCGATTCTGTGAAAGGGCGGTTCACCATCTCTCAGGGC
    ACTGCCAAGAATACCGTCTACCTGCAAATGAACAGCCTCCAGCCAGAGGATACC
    GCCATGTACTATTGCAAGACGGTCTGCGTCGTGGGCTCCAGATGGTCCGATTAC
    TGGGGCCAGGGAACACAAGTGACAGTTAGTTCCGGTGGCTCAGGAGGTTCCGGG
    GGCAGCGGTCAAGTGCAGTTGCAGGAGAGCGGAGGCGGTCTGGTTCAGCCTGGC
    GGTTCTCTTCGCCTGAGCTGCGCTGCCTCAGGCTTTACGTTCTCCTCTTACCCC
    ATGTCCTGGGTGCGGCAAGCTCCGGGGAAGGGCCTGGAGTGGATCTCCACCATT
    AGTGCAGGTGGCGACACCACTCTGTACGCTGACAGTGTAAAGGGCCGCTTCACA
    TCCTCTCGGGACAACGCCAAAAATACACTCTATTTGCAGCTGAATAGCCTGAAA
    ACCGAGGACACGGCCATTTACTATTGTGCAAAGAGAATTGATTGCAACAGCGGA
    TACTGTTATCGCAGGAACTACTGGGGCCAGGGCACCCAGGTGACAGTGTCCTCT
    DR594- 1113 CAGGTGCAGCTCCAGGAGTCCGGCGGGGGCTCAGTGCAGGCCGGAGGCAGCTTG
    hIL27 AGGCTGAGTTGTGTGGCCAGTGCCTCCACATATTGCACCTACGACATGCACTGG
    Ra_VH TATCGGCAAGCCCCTGGTAAGGGACGGGAATTTGTAAGTGCTATTGATTCTGAT
    H8 GGCACTACCCGTTACGCCGACAGCGTGAAAGGCCGCTTCACTATTTCACAGGGG
    ACTGCCAAAAATACCGTGTACCTTCAGATGAACTCTCTTCAGCCCGAGGACACG
    GCGATGTACTATTGCAAGACCGTTTGTGTTGTGGGTAGTCGCTGGTCCGACTAT
    TGGGGCCAGGGTACTCAGGTGACTGTATCCAGCGGCGGAGGCAGCCAGGTGCAG
    TTGCAGGAGTCCGGCGGTGGAAGCGTCCAGGTGGGTGGCAGTCTGCGCCTCTCA
    TGTGCCGCATCCGGCTTCACCTTCTCTAGTTACCCTATGTCCTGGGTCCGTCAG
    GCCCCTGGAAAGGGTCTTGAGTGGATTTCCACAATCTCTGCTGGGGGCGACACA
    ACCCTGTATGCCGACTCCGTGAAAGGCCGCTTCACCTCCAGTCGCGACAATGCG
    AAGAACACCCTTTATTTGCAGCTGAACTCACTGAAGACCGAGGACACCGCAATT
    TACTATTGTGCTAAGCGCATTGATTGCAATAGCGGCTACTGTTACCGGCGCAAT
    TATTGGGGCCAGGGTACTCAGGTGACTGTGTCCTCT
    DR594- 1114 CAGGTGCAACTGCAAGAGAGCGGCGGTGGCAGCGTACAGGCCGGTGGCTCTCTC
    hIL27 CGCCTTAGCTGCGTCGCCAGCGCTTCCACTTACTGTACTTACGACATGCACTGG
    Ra_VH TACAGGCAAGCGCCCGGCAAGGGACGCGAGTTCGTCTCCGCCATCGACAGCGAC
    H8 GGCACCACTCGCTACGCCGATAGCGTTAAGGGTCGCTTCACCATTTCACAGGGC
    ACCGCCAAGAACACCGTCTATCTTCAGATGAACAGCCTCCAGCCAGAGGATACA
    GCCATGTACTATTGCAAGACCGTCTGCGTCGTGGGCTCTCGTTGGAGTGACTAT
    TGGGGCCAGGGCACTCAAGTGACCGTGTCCTCTGGAGGCTCCGGGGGCAGCGGC
    GGGTCCGGTCAGGTGCAACTCCAGGAGTCCGGCGGAGGCTCTGTGCAGGTTGGT
    GGAAGCCTGCGTCTCTCCTGCGCGGCCTCCGGCTTCACTTTCTCCTCTTACCCT
    ATGAGCTGGGTCAGGCAGGCCCCCGGCAAGGGGCTGGAGTGGATCTCTACCATT
    TCTGCCGGAGGGGACACTACCCTGTACGCAGATTCTGTGAAAGGCCGCTTCACC
    AGCTCTAGGGACAACGCCAAGAATACCTTGTATCTCCAGCTCAACTCCCTCAAG
    ACCGAGGACACAGCTATCTATTACTGTGCTAAGAGGATCGACTGTAACTCTGGT
    TATTGTTATCGCAGGAACTATTGGGGACAGGGGACCCAAGTGACCGTCAGCTCT
    DR594- 1115 CAGGTGCAGCTTCAGGAGTCTGGCGGTGGCAGCGTCCAAGCTGGCGGGAGCCTG
    hIL27 CGGCTGTCTTGTGTGGCCTCCGCCTCAACATACTGTACCTATGATATGCACTGG
    Ra_VH TATAGACAAGCGCCCGGCAAGGGCAGGGAGTTCGTCTCCGCTATTGATAGCGAT
    H9 GGAACCACTCGTTACGCGGACTCCGTGAAGGGCCGCTTTACGATCAGCCAGGGC
    ACCGCGAAGAACACCGTGTATCTTCAGATGAACTCTTTGCAGCCCGAGGACACT
    GCCATGTATTACTGCAAGACTGTTTGTGTAGTGGGCAGCAGGTGGAGCGACTAC
    TGGGGCCAGGGAACACAGGTCACAGTAAGCTCTGGTGGAGGGTCTCAGGTGCAG
    CTTCAAGAATCTGGTGGAGGCTCCGTGCAATCCGGTGGCAGCCTGAGGCTGTCC
    TGCGCTGCCTCAGGATTCACTTACAGCACCTCTAACTCCTGGATGGCCTGGTTT
    CGCCAAGCGCCCGGAAAAGAGAGGGAAGGCGTGGCCGCTATTTACACTGTCGGT
    GGCTCCATCTTCTACGCGGATAGTGTAAGGGGCCGCTTCACCATCTCTCAGGAC
    GCCACAAAAAATATGTTCTACCTCCAGATGAATACCCTTAAACCGGAGGACACC
    GCTATGTATTACTGTGCAGCGGCAAGTGGAAGGCTTCGCGGGAAGTGGTTCTGG
    CCTTACGAATACAACTACTGGGGTCAGGGAACTCAGGTCACAGTTTCCTCC
    DR594- 1116 CAGGTCCAGTTGCAGGAATCTGGTGGCGGTTCCGTCCAGGCGGGAGGTTCCCTG
    hIL27 CGCCTCTCCTGCGTGGCCTCTGCCTCTACGTATTGTACCTACGACATGCACTGG
    Ra_VH TATCGCCAGGCCCCAGGTAAGGGCCGCGAGTTCGTTTCCGCCATTGATTCCGAT
    H9 GGGACCACACGCTATGCTGATTCCGTGAAGGGCCGGTTCACCATCAGTCAAGGC
    ACCGCCAAGAACACAGTGTACCTCCAGATGAACTCCCTCCAGCCTGAGGACACA
    GCCATGTACTATTGTAAGACAGTGTGTGTAGTCGGTTCCCGCTGGAGCGACTAT
    TGGGGACAGGGAACCCAGGTGACGGTTTCATCCGGTGGCAGCGGAGGTAGCGGC
    GGTAGCGGACAGGTGCAGTTGCAAGAATCCGGCGGTGGCTCCGTGCAGAGCGGA
    GGCTCTCTGCGGCTCTCTTGTGCGGCCAGTGGCTTCACCTACTCCACCAGCAAC
    TCTTGGATGGCTTGGTTCCGCCAAGCCCCTGGCAAAGAACGCGAAGGCGTCGCT
    GCCATCTACACTGTTGGGGGAAGTATTTTTTACGCTGACTCCGTCCGTGGCCGT
    TTTACCATCTCCCAGGATGCCACAAAAAATATGTTCTACCTCCAGATGAACACC
    CTGAAGCCCGAGGATACCGCAATGTACTATTGTGCTGCCGCATCTGGTCGTCTG
    CGCGGCAAGTGGTTCTGGCCCTACGAATACAACTACTGGGGTCAAGGTACACAG
    GTGACGGTGTCTTCC
    DR594- 1117 CAGGTGCAGCTTCAGGAATCCGGCGGAGGCTCTGTGCAGGCGGGCGGAAGCCTT
    hIL27 CGGCTGTCTTGTGTTGCCTCCGCGAGCACCTACTGCACCTACGATATGCACTGG
    Ra_VH TATCGCCAGGCTCCTGGCAAGGGCCGTGAGTTTGTGAGCGCCATTGATTCCGAC
    H10 GGAACTACGAGATATGCCGACAGTGTGAAAGGTCGTTTCACTATTTCACAGGGC
    ACCGCCAAGAATACCGTCTATCTCCAAATGAACAGTCTCCAGCCGGAGGACACC
    GCCATGTATTACTGTAAGACGGTATGTGTTGTGGGGTCTCGCTGGTCAGACTAC
    TGGGGCCAGGGGACACAGGTGACTGTCAGCTCCGGCGGGGGCTCACAGGTGCAG
    CTGCAAGAGAGCGGCGGTGGCAGTGTTCAGGCGGGCGGTTCTCTCCGCCTGTCT
    TGCAGGGCCTCCGGGAGCACTTACAGCAATTATTGTTTGGGGTGGTTTAGACAA
    ATCACCGGCAAGGAGCGCGAGGGGGTGGCCGTGATAAATTGGGTGGGCGGTATG
    CTCTACTTCGCTGACTCTGTGAAGGGCCGTTTCACAGTGTCCCAGGACCAGGCG
    AAAAACACCCTTTACCTCCAGATGAACTCTCTCAAGCCCGAGGACACCGCCATG
    TATTACTGTGCTGCCGAGTCCGTGTCCTCTTTCAGCTGCGGTGGCTGGCTGACC
    CGCCCTGATAGGGTGCCGTATTGGGGTCAAGGAACTCAGGTCACAGTGTCCAGC
    DR594- 1118 CAAGTGCAGCTCCAGGAGTCCGGCGGAGGTTCTGTCCAGGCCGGAGGCTCACTG
    hIL27 CGCCTGTCCTGTGTCGCTTCTGCGTCTACTTACTGTACTTATGATATGCACTGG
    Ra_VH TATCGCCAGGCTCCAGGTAAGGGCAGGGAGTTCGTGTCTGCTATTGATTCCGAT
    H10 GGCACGACCCGCTATGCCGATTCAGTGAAAGGCCGTTTCACAATCTCTCAGGGA
    ACAGCCAAGAACACGGTGTACTTGCAGATGAACTCTCTGCAACCCGAGGACACC
    GCCATGTATTACTGTAAGACTGTCTGCGTGGTCGGCTCACGCTGGTCCGACTAT
    TGGGGCCAGGGGACCCAAGTTACTGTTTCCAGCGGAGGCAGCGGTGGATCTGGG
    GGCTCCGGCCAGGTGCAGCTCCAGGAATCTGGGGGCGGGTCCGTGCAGGCTGGG
    GGATCTCTGCGCCTGAGTTGTCGCGCAAGTGGGAGTACCTACAGTAATTATTGC
    CTGGGATGGTTCCGCCAGATCACAGGTAAGGAGCGCGAGGGCGTGGCCGTGATT
    AACTGGGTGGGTGGCATGTTGTACTTCGCTGATTCCGTCAAGGGACGTTTCACT
    GTCTCTCAGGACCAGGCTAAGAATACCTTGTATCTTCAGATGAACTCCCTGAAG
    CCTGAAGATACTGCTATGTATTACTGTGCGGCTGAGAGCGTCAGTTCCTTCTCC
    TGTGGGGGCTGGCTGACTCGCCCGGACCGTGTGCCCTACTGGGGCCAGGGCACT
    CAGGTGACCGTGAGCAGC
    DR594- 1119 CAGGTGCAGCTTCAGGAGAGCGGAGGCGGGTCCGTGCAGGCTGGTGGGTCACTG
    hIL27 AGACTGTCATGTGTGGCTTCAGCTTCAACGTACTGTACCTATGACATGCACTGG
    Ra_VH TACAGGCAAGCTCCTGGGAAAGGCCGCGAGTTCGTGTCCGCTATTGACAGCGAC
    H11 GGTACTACCCGTTATGCCGACAGCGTCAAGGGCAGATTTACCATCTCCCAAGGC
    ACGGCCAAAAACACCGTGTATCTCCAGATGAACAGCCTTCAGCCCGAGGACACC
    GCAATGTATTACTGCAAGACCGTGTGTGTTGTGGGGAGCCGTTGGTCCGACTAC
    TGGGGCCAGGGCACCCAAGTGACCGTCTCCTCTGGGGGTGGCTCCCAGGTCCAG
    CTTCAGGAGTCCGGCGGAGGCAGTGTTCAGGCCGGAGGGAGCCTGAGACTGAGC
    TGCCGTGCTTCTGGTAGTACTTACTCTAACTACTGTTTGGGCTGGTTTCGCCAA
    TCCACCGGCAAAGAGCGTGAGGGGGTCGCGGTCATCAACTGGGTCGGAGGTATG
    CTGTACTTTGCCGATAGCGTCAAGGGAAGATTTACCGTCTCCCAAGACCACGCC
    AAGAACACCGTGACCCTGCAAATGAACAGCCTGAAGCCAGAGGATACCGCCATG
    TACTATTGCGCGGCAGAATCCGTCTCCAGCTTTTCTTGCGGAGGCTGGCTCACA
    AGACCAGGGCGCGTGCCTTACTGGGGACAAGGCACCCAGGTGACAGTCAGCTCA
    DR594- 1120 CAGGTGCAGTTGCAGGAGTCTGGGGGCGGAAGTGTCCAGGCTGGAGGCTCCCTG
    hIL27 CGCCTGAGTTGTGTGGCCAGCGCCAGCACTTACTGCACTTATGACATGCACTGG
    Ra_VH TACAGACAAGCCCCTGGCAAGGGTAGGGAGTTCGTGTCTGCTATTGACTCCGAC
    H11 GGGACCACACGTTATGCCGACTCTGTCAAGGGCCGTTTCACTATCTCCCAGGGA
    ACGGCCAAGAACACAGTGTACTTGCAGATGAACTCTTTGCAACCCGAAGACACC
    GCTATGTATTACTGTAAGACTGTGTGCGTCGTGGGTTCCAGGTGGTCAGACTAC
    TGGGGTCAGGGTACTCAGGTCACTGTTAGCTCAGGGGGTTCTGGGGGCTCCGGG
    GGTTCCGGCCAGGTGCAGCTTCAGGAGTCTGGAGGCGGTTCCGTCCAGGCGGGA
    GGCTCTCTTAGACTGTCCTGCCGCGCCAGCGGCAGCACCTACTCCAACTACTGC
    CTCGGATGGTTTCGTCAGTCCACAGGTAAGGAGCGCGAAGGCGTGGCTGTTATC
    AACTGGGTGGGCGGAATGCTGTACTTTGCTGACTCCGTGAAAGGCCGCTTCACT
    GTGTCACAAGACCATGCAAAGAACACCGTCACATTGCAGATGAACTCTCTGAAA
    CCAGAGGATACTGCCATGTATTACTGCGCAGCTGAATCTGTGTCCTCTTTCTCT
    TGCGGTGGCTGGCTGACCCGCCCTGGGAGAGTGCCGTACTGGGGCCAGGGCACC
    CAAGTGACAGTCAGTTCT
    DR594- 1121 CAAGTACAGCTCCAGGAATCTGGAGGCGGTAGCGTGCAGGCCGGGGGCTCCTTG
    hIL27 CGCTTGTCCTGCGTTGCCTCAGCCAGCACCTACTGCACCTACGACATGCACTGG
    Ra_VH TATCGCCAAGCACCAGGGAAGGGCAGAGAGTTCGTGTCTGCCATCGACAGTGAT
    H12 GGCACTACCCGCTACGCCGACTCCGTTAAGGGGCGCTTTACCATTTCCCAGGGA
    ACAGCCAAGAACACCGTGTACTTGCAGATGAACAGCTTGCAGCCTGAAGACACC
    GCCATGTATTACTGCAAGACCGTGTGTGTAGTGGGTTCAAGGTGGTCCGACTAT
    TGGGGACAGGGCACTCAGGTGACTGTGTCTTCCGGCGGAGGCAGCCAGGTACAG
    CTCCAGGAATCCGGTGGGGGCTCCGTTCAGGCTGGCGAGTCCCTGCGCCTGTCC
    TGTAGGGCCTCCGGCTCCACGTATAGTAACTACTGTCTGGGCTGGTTCCGCCAG
    ATCACCGGCAAGGAACGCGAGGGAGTGGCGGTAATAAATTGGGTTGGGGGAATG
    CTGTATTTCGCCGACAGCGTGAAAGGCAGATTCACCGTGTCCCAGGACCAGGCG
    AAGAACACCGTGTATTTGGAAATGAACTCTCTGAAGCCCGAGGATACCGCTATG
    TATTACTGCGCTACCGAAAGCGTAAGCTCCTTCAGCTGTGGGGGTTGGCTGACA
    CGCCCTGATCGGGTTCCCTACTGGGGCCAGGGTACGCAGGTCACCGTTTCCTCC
    DR594- 1122 CAGGTCCAGCTGCAAGAGTCCGGTGGAGGCAGTGTGCAGGCAGGCGGTAGCCTG
    hIL27 CGTTTGTCCTGTGTGGCATCCGCCAGTACCTACTGCACTTACGATATGCACTGG
    Ra_VH TACAGACAAGCCCCCGGCAAAGGCCGGGAGTTCGTTTCAGCTATCGACTCTGAC
    H12 GGGACCACTAGGTATGCGGACTCTGTCAAGGGCCGCTTTACAATTAGCCAGGGC
    ACGGCCAAAAACACCGTATATCTCCAGATGAACAGCCTCCAACCAGAAGACACA
    GCCATGTATTACTGCAAGACTGTATGCGTGGTCGGCTCCCGTTGGTCTGACTAT
    TGGGGCCAGGGAACTCAGGTCACCGTCTCATCCGGTGGCTCTGGTGGGAGCGGG
    GGTTCCGGCCAGGTGCAGCTCCAGGAGTCAGGTGGCGGGAGCGTGCAGGCGGGG
    GAGTCCCTCCGGCTGAGTTGTAGGGCTTCCGGTAGCACTTACTCCAACTACTGC
    CTCGGCTGGTTTCGCCAGATCACGGGCAAGGAGCGCGAGGGCGTGGCCGTAATT
    AACTGGGTCGGAGGGATGCTGTATTTCGCGGACAGCGTTAAGGGACGCTTCACC
    GTGTCCCAGGATCAGGCCAAGAACACCGTCTATCTGGAGATGAACTCCCTGAAG
    CCGGAGGACACAGCCATGTATTACTGCGCAACGGAATCCGTGTCTAGCTTCAGC
    TGCGGTGGGTGGCTCACCCGTCCCGACCGCGTGCCGTATTGGGGGCAGGGGACC
    CAGGTGACTGTGTCCTCC
    DR594- 1123 CAGGTGCAACTCCAGGAGTCAGGCGGTGGCTCCGTCCAGGCGGGAGGTTCCCTG
    hIL27 CGCCTTTCTTGCGTTGCATCTGCGTCCACCTACTGTACCTATGACATGCACTGG
    Ra_VH TATCGTCAGGCACCAGGCAAGGGGAGGGAGTTCGTGTCTGCGATTGATTCTGAT
    H13 GGCACAACTAGGTATGCTGACTCCGTCAAGGGACGGTTCACAATCTCTCAAGGG
    ACCGCCAAGAATACCGTGTATCTCCAGATGAACTCCCTTCAGCCCGAGGACACG
    GCCATGTATTACTGCAAGACCGTTTGCGTCGTGGGTTCCAGGTGGTCTGACTAC
    TGGGGGCAAGGCACGCAGGTGACCGTTAGCTCTGGCGGGGGTAGCCAGGTGCAG
    TTGCAGGAATCTGGTGGAGGTTCTGTGCAAGCAGGAGGGTCTCTGCGCTTGAGT
    TGCGTAGCAAGTGGGTACGTGAGTTGTGATTACTTCCTGCCTTCTTGGTACAGG
    CAGGCTCCGGGCAAGGAACGCGAGTTCGTGTCCATTATCGACGGGACCGGCTCC
    ACCAGCTATGCCGCGAGCGTCAAGGGGCGCTTCACAGCCAGCCAGGATCGCGGG
    AAGAACATCGCCTACTTGCAGATGAACAGCCTGAAACCGGAAGATACAGCTATG
    TATTACTGTAAGGCCTCCTGCGTCCGTGGCCGTACTATTAGTGAATACTGGGGC
    CAAGGCACGCAGGTGACCGTATCTTCC
    DR594- 1124 CAGGTTCAGCTCCAGGAGAGCGGAGGTGGCAGCGTTCAAGCCGGTGGCTCCCTG
    hIL27 CGCCTGTCTTGTGTCGCGTCTGCTTCCACGTACTGCACCTACGACATGCACTGG
    Ra_VH TATCGGCAGGCTCCTGGAAAGGGCCGCGAGTTCGTCTCCGCTATCGACTCTGAC
    H13 GGAACCACTCGCTATGCCGATAGCGTGAAGGGCCGCTTCACCATTAGCCAAGGC
    ACAGCCAAGAACACAGTGTACTTGCAGATGAACAGCCTCCAGCCGGAAGACACT
    GCTATGTACTATTGCAAGACTGTGTGTGTTGTGGGGTCCCGTTGGTCTGATTAT
    TGGGGCCAGGGCACCCAGGTGACCGTCAGTAGCGGGGGCAGTGGCGGGTCAGGA
    GGCTCCGGTCAGGTGCAGTTGCAGGAGAGCGGAGGGGGCAGTGTTCAGGCCGGG
    GGCAGCCTGAGACTGTCTTGTGTCGCCTCCGGCTATGTGTCTTGTGACTACTTT
    CTGCCATCCTGGTATCGGCAGGCCCCTGGGAAAGAAAGAGAGTTCGTGTCCATT
    ATCGACGGCACTGGAAGCACCTCTTATGCTGCCTCTGTGAAGGGTAGGTTTACT
    GCCTCCCAAGACAGGGGGAAGAACATTGCTTATCTCCAGATGAACAGTCTGAAG
    CCCGAGGACACTGCGATGTATTACTGTAAGGCCTCTTGCGTTCGCGGTCGCACA
    ATTTCCGAGTACTGGGGCCAGGGAACACAGGTGACGGTGAGTAGC
    DR594- 1125 CAGGTACAGCTCCAGGAGTCTGGCGGAGGTTCAGTGCAGGCTGGCGGTTCTTTG
    hIL27 CGCCTGTCCTGTGTAGCCTCCGCCAGCACATATTGCACTTACGACATGCACTGG
    Ra_VH TATCGCCAGGCTCCGGGTAAGGGCCGCGAGTTTGTTAGCGCCATCGACTCCGAT
    H14 GGAACAACCCGTTATGCTGACTCTGTGAAGGGCCGCTTTACAATTAGTCAGGGA
    ACCGCAAAGAATACTGTTTATTTGCAGATGAATAGCCTGCAACCCGAGGACACC
    GCTATGTATTACTGTAAGACAGTGTGCGTTGTGGGCTCCCGCTGGAGCGACTAT
    TGGGGTCAGGGCACACAGGTTACCGTGTCCAGCGGAGGCGGGAGCCAGGTGCAG
    CTCCAGGAGTCAGGTGGCGGATCTGTCCAAGCTGGAGGTTCCCTGCGGTTGTCT
    TGTGTGGCCTCTGGTTATGTGTCATGCGATTATTTCTTGCCCAGCTGGTATCGC
    CAGGCTCCGGGCAAGGAGCGCGAATTTGTGTCTATCATTGACGGCACCGGCTCC
    ACCTCCTACGCAGCCAGTGTCAAGGGGCGCTTCACGGCAAGCCAAGACAAGGGA
    AAGAACATCGCCTATTTGCAGATGAACTCTTTGAAGCCAGAGGACACCGCCATG
    TATTACTGTAAGGCATCTTGTGTGAGGGGCCGCGCGATCAGCGAGTACTGGGGC
    CAGGGCACCCAGGTGACCGTGAGCAGC
    DR594- 1126 CAGGTGCAGCTTCAGGAGTCCGGCGGGGGCAGCGTGCAAGCCGGGGGATCTCTG
    hIL27 CGCCTCTCCTGTGTCGCGAGCGCAAGCACATACTGCACCTACGATATGCACTGG
    Ra_VH TATCGCCAGGCCCCCGGCAAGGGCAGAGAGTTCGTGAGCGCGATTGATTCCGAT
    H14 GGCACTACCCGCTACGCTGATAGTGTGAAAGGACGGTTCACTATCTCCCAGGGC
    ACTGCCAAAAACACAGTGTACCTCCAGATGAACTCCCTTCAGCCCGAGGACACC
    GCCATGTATTACTGCAAAACTGTGTGCGTGGTAGGGTCTCGCTGGAGCGATTAT
    TGGGGGCAGGGAACCCAGGTGACAGTTTCCTCTGGGGGCAGCGGAGGTTCTGGC
    GGTTCCGGCCAGGTGCAGCTTCAGGAAAGCGGAGGTGGGAGCGTGCAGGCCGGA
    GGCAGCCTCAGGCTGAGCTGCGTGGCCTCCGGTTACGTATCATGCGATTACTTC
    CTCCCCTCCTGGTATCGGCAGGCTCCGGGCAAGGAGCGCGAGTTCGTGAGCATT
    ATCGACGGTACAGGCTCCACCAGCTATGCCGCATCTGTGAAGGGACGTTTCACA
    GCTTCCCAGGACAAGGGTAAAAACATTGCCTACTTGCAGATGAACAGCTTGAAG
    CCGGAAGATACCGCAATGTATTACTGCAAAGCCAGTTGTGTCCGTGGCCGCGCT
    ATCTCCGAGTATTGGGGACAGGGCACACAGGTGACGGTGTCCTCC
    DR594- 1127 CAGGTCCAGCTCCAGGAGAGCGGCGGTGGAAGCGTCCAGGCTGGGGGCTCTCTG
    hIL27 CGTCTGTCTTGTGTAGCCTCTGCCTCCACTTACTGTACTTACGACATGCACTGG
    Ra_VH TATCGCCAGGCCCCTGGCAAGGGCCGCGAGTTCGTTTCCGCCATTGATTCTGAC
    H15 GGTACTACCAGATACGCCGACTCCGTGAAAGGTAGGTTCACGATCAGCCAGGGC
    ACTGCCAAAAACACAGTTTATCTCCAGATGAACTCCCTCCAGCCTGAGGACACT
    GCCATGTATTACTGTAAAACCGTTTGTGTGGTCGGATCTCGGTGGTCTGACTAT
    TGGGGGCAGGGCACCCAGGTGACCGTATCTTCCGGCGGAGGGTCCCAGGTCCAG
    TTGCAGGAGTCTGGCGGAGGCTCCGTACAGGCAGGGGGCTCCCTGCGCCTCTCT
    TGCGTGGCCTCCGGCTACGTGTCTTGCGACTATTTCCTGCCATCTTGGTATAGA
    CAGGCTCCCGGCAAGGAGCGCGAGTTTGTGTCTATTATCGACGGCACCGGCTCA
    ACTTCCTACGCTGCCTCTGTGAAGGGCCGCTTTACCGCCAGCCAGGACAAAGGC
    AAGAACATCGCGTACCTCCAGATGAACACCCTGAAGCCCGAGGACACCGCCATG
    TATTACTGTAAGGCCTCCTGTGTGCGTGGACGTGCCATCTCCGAATACTGGGGC
    CAGGGCACCCAGGTGACCGTAAGCTCA
    DR594- 1128 CAGGTGCAGCTGCAAGAGAGCGGTGGGGGCAGCGTGCAAGCTGGGGGCAGCCTG
    hIL27 CGCCTCTCCTGCGTCGCGTCTGCTTCCACTTACTGTACTTACGACATGCACTGG
    Ra_VH TATCGCCAGGCCCCTGGCAAGGGCCGCGAGTTCGTGTCTGCCATTGACAGCGAT
    H15 GGAACGACCCGCTACGCGGACAGCGTTAAGGGTCGCTTCACTATCTCTCAGGGC
    ACTGCTAAAAACACTGTGTACCTCCAGATGAACTCTTTGCAGCCCGAGGATACT
    GCCATGTATTACTGTAAGACCGTTTGCGTTGTGGGTTCCCGTTGGTCCGATTAT
    TGGGGCCAGGGCACCCAGGTGACCGTATCAAGCGGCGGGTCCGGGGGCAGCGGA
    GGTTCAGGTCAGGTGCAGTTGCAGGAAAGCGGAGGTGGCAGCGTACAGGCCGGG
    GGCTCCCTGAGGCTGAGCTGCGTGGCGAGTGGCTACGTCAGTTGCGACTACTTC
    TTGCCTTCTTGGTATCGGCAAGCCCCCGGTAAGGAGCGCGAGTTCGTGAGTATT
    ATCGACGGCACTGGTAGCACCTCCTATGCTGCCAGCGTGAAAGGTCGTTTTACC
    GCCTCCCAGGACAAGGGTAAAAACATTGCCTATTTGCAAATGAACACCCTTAAA
    CCTGAGGACACTGCCATGTATTACTGTAAGGCTTCATGTGTGAGAGGTCGTGCT
    ATCTCAGAATACTGGGGCCAGGGCACCCAAGTCACTGTTTCTTCT
    DR594- 1129 CAGGTTCAGCTCCAGGAATCCGGCGGTGGCTCCGTTCAGGCAGGGGGCAGCCTG
    hIL27 CGTCTGTCCTGTGTCGCATCCGCCTCTACCTACTGCACTTACGATATGCACTGG
    Ra_VH TATCGGCAGGCTCCTGGTAAGGGCCGCGAGTTCGTCAGTGCTATTGACTCCGAC
    H16 GGTACAACCCGGTATGCGGATTCTGTGAAAGGAAGATTTACGATCTCCCAAGGG
    ACCGCAAAAAACACCGTGTACCTTCAGATGAACTCTCTCCAGCCCGAAGATACA
    GCGATGTATTACTGCAAGACTGTATGCGTGGTAGGTTCTCGTTGGAGCGACTAC
    TGGGGCCAGGGTACACAAGTCACCGTCTCCAGCGGCGGGGGCAGCCAGGTCCAG
    CTCCAGGAATCTGGCGGAGGTTCCGTGCAGGCCGGAGGTAGCCTTCGCCTCTCT
    TGCCGCGCATCCGGCAGCACCTACTCCAACTACTGTCTGGGCTGGTTCAGGCAG
    ATCACCGGCAAGGAGCGCGAGGGCGTAGCCGTAATAAATTGGGTAGGCGGTATG
    CTGTACTTTGCTGACAGCGTTAAGGGTCGGTTTACGGTGTCCCAGGATCAGGCC
    AAGAACACCGTGTATCTCCAGATGAACTCCCTGAAGCCGGAGGATACCGCTATG
    TACTATTGCGCAGCCGAGTCAGCTAGTTCCTTCAGCTGCGGTGGCTGGCTCACG
    AGACCAGATCGCGTCCCCTACTGGGGACAAGGCACACAGGTTACCGTGTCCTCC
    DR594- 1130 CAGGTCCAGCTTCAGGAGAGCGGGGGAGGCTCCGTGCAAGCTGGAGGTTCCCTC
    hIL27 CGCTTGTCCTGCGTTGCGTCCGCAAGCACCTACTGCACTTATGACATGCACTGG
    Ra_VH TATCGCCAGGCTCCTGGCAAAGGGAGAGAGTTCGTCTCCGCCATTGATAGCGAT
    H16 GGTACAACTAGGTACGCAGATTCCGTTAAAGGTAGGTTTACTATCAGCCAGGGC
    ACGGCCAAAAACACCGTCTATCTGCAAATGAACTCTCTCCAGCCCGAGGATACC
    GCGATGTACTATTGCAAGACCGTCTGTGTAGTGGGCAGCCGCTGGTCAGACTAT
    TGGGGCCAGGGAACGCAGGTGACAGTGTCTAGCGGCGGGTCCGGCGGTTCCGGT
    GGCTCCGGCCAGGTACAGCTCCAGGAGTCAGGCGGAGGCTCCGTGCAAGCCGGG
    GGTTCTCTGCGGCTCTCCTGTCGCGCTTCTGGGTCCACCTATTCCAATTACTGC
    CTGGGCTGGTTCCGTCAAATTACGGGCAAGGAGCGCGAAGGCGTGGCCGTGATA
    AATTGGGTGGGCGGGATGTTGTACTTTGCTGACAGCGTTAAGGGACGTTTTACT
    GTGTCCCAGGACCAGGCCAAGAACACCGTGTACTTGCAGATGAACTCCTTGAAG
    CCAGAGGACACAGCAATGTATTACTGTGCCGCTGAAAGCGCCAGCTCTTTCAGT
    TGTGGGGGCTGGCTGACTAGACCAGACCGTGTCCCTTACTGGGGTCAGGGCACC
    CAGGTTACCGTGTCCTCC
    DR594- 1131 CAAGTCCAGCTCCAGGAGTCCGGCGGTGGCTCCGTCCAGGCGGGCGGATCTCTG
    - CGCCTGTCCTGTGTCGCCTCCGCTTCCACATACTGCACCTATGACATGCACTGG
    hIL27 TATCGGCAGGCTCCTGGTAAGGGCCGCGAGTTCGTCAGCGCCATCGACTCCGAC
    Ra_VH GGAACGACCCGGTACGCTGATAGCGTGAAAGGTAGGTTTACCATCTCACAGGGC
    H17 ACCGCCAAAAATACCGTCTACTTGCAGATGAACAGTTTGCAGCCTGAGGACACC
    GCCATGTATTACTGCAAGACTGTGTGTGTAGTGGGGTCACGCTGGTCTGATTAT
    TGGGGCCAGGGTACTCAGGTGACTGTGTCTAGTGGCGGTGGCAGCCAGGTGCAG
    TTGCAGGAGAGTGGAGGCGGTCTCGTCCAGCCAGGAGGCAGTCTGCGCCTGTCA
    TGCGCTGCCTCCGGCTTTACTTTTTCCCTGTCTGGTATGTCATGGGTGCGGCAG
    GCCCCCGGCAAGGGTCTGGAGTGGGTCAGTGCAATCAGCAGTGGAGGGGCCTCT
    ACTTATTACACCGACAGCGTCAAAGGCAGATTCACCATCAGTAGGGATAATGCC
    AAGAACATGCTGTACCTCCAGCTGAACTCTCTGAAGACAGAGGACACGGCTATG
    TACTATTGTGCTAAAGGGGGCAGCGGTTACGGGGATGCTTCCAGAATGACTTCT
    CCGGGATCTCAGGGTACTCAAGTCACCGTTAGTTCT
    DR594- 1132 CAAGTCCAGCTCCAGGAGAGCGGAGGGGGTTCCGTGCAGGCAGGGGGTTCACTT
    hIL27 CGCCTGTCCTGTGTGGCTTCTGCTTCCACCTATTGCACGTATGATATGCACTGG
    Ra_VH TATCGCCAGGCTCCCGGCAAGGGCCGCGAGTTCGTCTCAGCGATTGATTCTGAC
    H17 GGCACCACTCGCTACGCTGACTCTGTGAAGGGCCGCTTTACCATCAGTCAAGGT
    ACTGCGAAGAACACCGTGTACCTTCAGATGAACTCACTGCAACCGGAGGACACC
    GCGATGTACTATTGCAAGACTGTTTGTGTGGTCGGTTCCCGCTGGTCCGATTAC
    TGGGGGCAGGGCACTCAGGTGACGGTCAGTTCCGGCGGGAGTGGCGGGTCCGGG
    GGCTCTGGCCAAGTGCAGTTGCAGGAGAGCGGGGGAGGCCTCGTGCAGCCAGGT
    GGATCTCTGCGGCTGTCTTGTGCCGCTTCCGGCTTCACTTTTTCCCTGTCCGGC
    ATGAGTTGGGTCCGCCAGGCCCCAGGGAAAGGCCTGGAGTGGGTGTCCGCCATC
    TCTAGCGGCGGTGCCTCCACATATTACACTGACAGCGTCAAGGGTCGCTTTACG
    ATTTCCCGCGATAACGCTAAGAACATGCTCTACCTCCAGCTGAACAGCCTGAAG
    ACCGAGGATACTGCCATGTATTACTGTGCCAAAGGGGGTAGCGGCTATGGGGAC
    GCCAGCAGGATGACCAGTCCCGGAAGTCAGGGAACTCAGGTCACCGTTTCTTCC
    DR594- 1133 CAGGTACAGCTTCAGGAGAGCGGGGGAGGCTCTGTGCAGGCCGGAGGCTCTCTG
    hIL27 CGCCTCTCTTGTGTCGCCTCCGCGTCTACCTATTGCACCTACGACATGCACTGG
    Ra_VH TATCGCCAGGCCCCCGGAAAAGGTCGCGAGTTCGTGTCTGCTATCGACTCCGAC
    H18 GGGACCACTCGCTACGCTGACTCCGTAAAAGGACGTTTTACAATTAGTCAGGGT
    ACAGCCAAGAATACAGTATACCTGCAAATGAACTCCTTGCAGCCAGAGGACACC
    GCCATGTATTACTGCAAGACCGTGTGCGTGGTCGGCAGTCGCTGGTCCGACTAC
    TGGGGCCAGGGAACCCAGGTCACGGTCTCAAGCGGAGGGGGATCACAGGTCCAG
    CTGCAAGAATCAGGAGGTGGAAGCGTGCAGGCAGGCGGAAGCCTGAGGCTGTCC
    TGCGTGGCCAGCGGCTACGTGTCCTGCGATTACTTTCTCCCTAGCTGGTATCGC
    CAGGCACCCGGAAAAGAGAGGGAGTTCGTCTCAATTATCGACGGAACTGGAAGC
    ACCTCTTACGCCGCTTCCGTGAAGGGCCGCTTTACTGCATCACAGGATAAGGGC
    AAGAATATCGCCTACCTCCAGATGAACTCACTGAAGCCTGAGGACACTGCTATG
    TATTACTGCAAGGCTTCCTGTGTGCGGGGTCGCGGAATCTCTGAGTACTGGGGT
    CAGGGTACTCAGGTCACCGTCTCTTCT
    DR594- 1134 CAGGTGCAGTTGCAGGAGAGCGGAGGTGGGAGTGTCCAGGCTGGTGGCTCCTTG
    hIL27 CGCCTGAGCTGCGTGGCCTCCGCCTCCACTTATTGCACCTACGACATGCACTGG
    Ra_VH TACAGGCAAGCCCCTGGTAAGGGTAGGGAGTTCGTCAGCGCCATTGATAGCGAT
    H18 GGCACAACCCGTTACGCGGATAGCGTGAAGGGCCGTTTCACAATCTCACAGGGC
    ACCGCCAAGAACACCGTTTATTTGCAGATGAACAGCCTCCAGCCCGAAGATACA
    GCTATGTATTACTGTAAGACCGTGTGTGTGGTTGGTAGCAGATGGTCCGACTAC
    TGGGGTCAAGGCACTCAAGTCACCGTATCCAGCGGCGGATCAGGAGGCAGCGGG
    GGTTCCGGGCAGGTGCAGCTCCAGGAATCAGGCGGTGGCAGCGTGCAGGCAGGG
    GGTTCCTTGCGTCTGAGTTGTGTGGCAAGTGGCTATGTAAGCTGTGACTACTTC
    CTCCCCAGTTGGTATCGCCAGGCTCCCGGCAAGGAGCGGGAGTTCGTGAGTATC
    ATTGATGGCACTGGTAGCACCTCCTACGCAGCGAGCGTCAAGGGTCGTTTTACC
    GCGTCTCAGGACAAGGGAAAAAACATCGCGTACCTCCAGATGAACAGCCTGAAG
    CCTGAGGACACAGCCATGTATTACTGCAAGGCCTCCTGCGTGCGCGGTCGCGGA
    ATTTCCGAGTATTGGGGCCAGGGCACCCAAGTAACAGTAAGCTCT
    DR594- 1135 CAGGTCCAACTTCAAGAGTCTGGCGGTGGGTCCGTCCAGGCCGGGGGTTCCCTC
    hIL27 AGACTGTCATGCGTGGCCTCCGCTTCCACCTATTGTACCTACGACATGCACTGG
    Ra_VH TATCGCCAGGCTCCTGGCAAGGGCCGCGAGTTCGTGTCTGCCATTGATTCAGAC
    H19 GGGACAACCCGCTACGCAGACTCCGTGAAAGGTCGTTTTACCATCTCACAGGGC
    ACTGCAAAAAACACTGTCTATCTGCAAATGAACTCCTTGCAGCCAGAAGACACC
    GCCATGTATTACTGCAAGACCGTATGTGTCGTGGGAAGCCGTTGGTCAGACTAC
    TGGGGGCAGGGCACCCAAGTTACGGTGTCCTCTGGCGGGGGCAGTCAGGTGCAG
    TTGCAGGAGAGCGGGGGCGGTTCTGTGCAAGCTGGCGGTTCCCTGCGCCTGAGC
    TGTCGCGCCTCTGGATCTACGTATAGCAACTACTGCCTGGGCTGGTTCCGCCAG
    ATCACCGGAAAGGAACGTGAGGGAGTGGCCGTCATCAACTGGGTGGGCGGAATG
    CTGTACTTCGCCGATTCTGTCAAGGGCCGGTTTACTGTCTCCCAGGATCAGGCG
    AAGAACACGGTATACCTTCAGATGAACAGCCTGAAACCAGAAGATACCGCTATG
    TATTACTGTGCCGCAGAGAGCGTCTCCAGCTTTTCCTGCGGAGGCTGGCTCACC
    CGCCCAGATCGTGTGCCTTACTGGGGGCAGGGGACCCAGGTGACTGTTTCCTCC
    DR594- 1136 CAAGTCCAGCTCCAGGAGTCCGGCGGGGGTTCCGTCCAGGCTGGGGGCTCTTTG
    hIL27 CGGTTGTCTTGTGTCGCATCAGCCTCCACTTATTGTACCTATGATATGCACTGG
    Ra_VH TATCGCCAGGCTCCGGGGAAGGGCAGGGAATTTGTGTCAGCTATTGATTCCGAC
    H19 GGAACCACACGGTATGCAGATTCTGTGAAAGGCCGCTTCACTATCTCACAGGGT
    ACTGCCAAGAACACCGTCTACTTGCAGATGAACTCCCTCCAGCCAGAGGACACT
    GCCATGTATTACTGCAAGACCGTCTGTGTGGTTGGGAGTAGGTGGAGTGACTAC
    TGGGGCCAGGGCACACAGGTCACGGTATCTTCCGGCGGAAGCGGCGGAAGTGGT
    GGCTCTGGACAAGTGCAGTTGCAGGAGAGCGGCGGGGGTTCCGTGCAGGCAGGC
    GGAAGCCTGAGGCTGAGCTGTCGTGCTTCTGGCTCCACCTATTCCAACTATTGC
    TTGGGTTGGTTTCGCCAAATTACCGGCAAGGAGCGTGAAGGCGTTGCTGTCATC
    AACTGGGTTGGGGGTATGCTCTACTTTGCTGACTCCGTGAAGGGTCGCTTCACA
    GTCAGCCAAGACCAGGCTAAGAACACAGTGTATCTCCAGATGAACTCTCTTAAA
    CCGGAAGACACTGCTATGTATTACTGCGCCGCAGAAAGCGTCAGCTCCTTCAGT
    TGCGGTGGCTGGCTGACCAGGCCAGATCGCGTACCATATTGGGGACAGGGAACC
    CAGGTCACCGTGTCCTCC
    DR594- 1137 CAAGTGCAGCTGCAAGAGAGCGGCGGTGGCTCCGTGCAGGCCGGGGGCTCCCTG
    hIL27 CGCCTGAGCTGTGTGGCAAGCGCCTCAACATACTGCACCTATGACATGCACTGG
    Ra_VH TATCGTCAGGCTCCCGGAAAGGGCAGAGAGTTCGTGTCCGCCATCGACAGCGAT
    H20 GGGACAACCCGCTACGCAGACAGCGTGAAGGGCCGCTTCACTATCTCTCAGGGC
    ACAGCTAAGAACACCGTGTACCTTCAGATGAACTCCTTGCAGCCTGAGGATACT
    GCCATGTACTATTGCAAGACCGTGTGTGTAGTGGGCTCCAGATGGTCTGACTAC
    TGGGGGCAGGGAACACAGGTTACCGTCTCTAGCGGGGGCGGAAGCCAAGTGCAG
    TTGCAGGAAAGCGGGGGCGGGCTGGTCCAGCCAGGGGGATCTCTGAGGCTGTCT
    TGCGCCGCATCAGGTTTTACTTTCTCAAGCTACCCCATGTCCTGGGTCAGACAA
    GCGCCGGGGAAGGGCTTGGAATGGGTGAGCACCATCTCCAGCGGTGGAGACACG
    ACCCTGTACGCCGACAGCGTCAAAGGGCGCTTCACATCTAGCCGCGACAATGCA
    AAAAACACCCTGTACCTCCAGCTTAATTCCCTGAAGACAGAGGACACCGCAATG
    TACTATTGCGCGAAACGGATTGACTGCAACTCCGGTTATTGTTACAAGCGCAGT
    TACTGGGGCCAGGGGACCCAGGTGACCGTGTCTAGC
    DR594- 1138 CAGGTTCAGCTTCAGGAATCTGGAGGGGGATCTGTGCAGGCTGGTGGAAGCCTG
    hIL27 CGTCTCAGCTGCGTGGCCTCTGCCTCCACGTATTGTACCTACGACATGCACTGG
    Ra_VH TACAGGCAGGCTCCAGGGAAGGGCCGGGAGTTTGTGAGCGCTATTGATTCAGAC
    H20 GGCACTACACGGTACGCTGACAGTGTCAAGGGGAGGTTCACCATCAGCCAGGGG
    ACAGCTAAGAATACCGTCTACCTCCAGATGAACTCCCTTCAGCCGGAGGATACC
    GCTATGTATTACTGCAAGACGGTGTGCGTGGTCGGCTCCCGTTGGAGCGACTAC
    TGGGGGCAGGGCACCCAAGTTACCGTGTCCAGCGGAGGTTCAGGCGGTTCTGGT
    GGCTCTGGCCAGGTGCAGCTCCAGGAGAGCGGAGGCGGTCTGGTGCAGCCGGGT
    GGCTCCCTGAGACTTTCCTGCGCAGCTTCCGGCTTTACCTTCTCTAGCTATCCA
    ATGTCTTGGGTGAGACAGGCCCCTGGAAAGGGTCTGGAGTGGGTGTCTACTATT
    TCCTCTGGTGGCGATACAACCCTGTACGCGGATTCTGTCAAAGGTCGTTTCACC
    AGCTCACGCGACAACGCTAAGAACACCTTGTATCTTCAGTTGAACAGCCTGAAG
    ACAGAGGACACTGCGATGTATTACTGTGCAAAGCGCATTGATTGTAATAGCGGC
    TACTGTTACAAGCGTAGCTACTGGGGCCAAGGCACCCAGGTCACGGTCAGCAGC
    DR594- 1139 CAGGTGCAGCTTCAGGAGTCTGGTGGCGGTTCCGTCCAGGCTGGCGGTTCTCTG
    hIL27 AGGCTGTCATGCGTGGCATCTGCGAGCACCTACTGTACTTACGACATGCACTGG
    Ra_VH TATCGTCAGGCCCCCGGTAAGGGTCGGGAGTTCGTGTCCGCCATTGATAGCGAT
    H21 GGGACAACCCGGTACGCCGACTCCGTGAAGGGTCGCTTCACTATCTCACAGGGA
    ACCGCTAAGAACACAGTCTACCTTCAGATGAACTCTTTGCAGCCAGAGGACACC
    GCCATGTATTACTGTAAGACAGTGTGTGTAGTTGGAAGCCGCTGGAGCGACTAC
    TGGGGCCAAGGCACTCAGGTCACCGTCAGCTCTGGCGGAGGCAGCCAGGTGCAG
    TTGCAGGAGAGCGGCGGAGGCTTGGTACAGCCCGGAGGCTCCCTCAGGCTCAGC
    TGTGCTGCCTCCGGTTTCACCTTTTCCCTGTCTTCCATGTCCTGGGTGCGTCAG
    GCACCAGGCAAGGGTCTGGAGTGGGTGTCTGCTATCAGCTCCGGCGGAGCTTCC
    ACGTACTATACAGATTCCGTTAAGGGACGGTTCACTATCTCCCGTGACAACGCG
    AAGAATATGCTGTACCTTCAGCTCAACTCACTGAAGACTGAGGACACCGCCATG
    TATTACTGCGCCAAAGGGGGCTCCGGCTATGGCGACGCGAGCCGTATGACTAGC
    CCTGGAAGCCAAGGCACACAGGTCACCGTTAGCTCC
    DR594- 1140 CAGGTTCAGCTTCAGGAGAGCGGGGGAGGCAGCGTCCAGGCCGGAGGCTCACTG
    hIL27 CGCCTGTCTTGTGTCGCCTCTGCATCTACCTACTGCACTTATGACATGCACTGG
    Ra_VH TATCGCCAAGCGCCGGGTAAAGGACGCGAGTTCGTCTCTGCCATCGACTCCGAC
    H21 GGCACAACTCGCTACGCCGACTCTGTGAAGGGCAGGTTTACCATCAGCCAGGGA
    ACCGCTAAGAACACCGTTTACCTCCAGATGAACTCCCTCCAGCCTGAGGACACC
    GCCATGTATTACTGTAAGACCGTTTGTGTCGTGGGCTCCAGGTGGTCCGACTAC
    TGGGGACAGGGCACCCAGGTGACAGTCTCCAGCGGTGGAAGTGGTGGCTCCGGC
    GGTTCAGGCCAGGTCCAGTTGCAGGAGTCTGGCGGTGGACTCGTGCAACCTGGG
    GGCTCTCTGAGACTGAGCTGTGCGGCTTCTGGGTTCACCTTCAGTCTGAGCAGT
    ATGAGCTGGGTCCGCCAAGCCCCAGGAAAGGGACTGGAATGGGTGTCCGCCATC
    TCCTCTGGCGGAGCGAGCACATACTATACAGATAGCGTGAAAGGGAGGTTTACT
    ATCTCTAGGGATAACGCGAAGAACATGCTTTATCTCCAGCTTAATTCCTTGAAG
    ACTGAGGACACTGCCATGTACTATTGCGCCAAAGGTGGCAGCGGTTATGGAGAC
    GCCAGTAGAATGACCAGCCCAGGTTCCCAGGGGACTCAAGTGACCGTCAGTTCT
    DR594- 1141 CAGGTGCAGCTTCAGGAAAGCGGAGGCGGTAGCGTACAGGCCGGGGGTAGCCTG
    hIL27 CGTTTGTCCTGCGTGGCGAGCGCTTCCACGTACTGTACCTACGACATGCACTGG
    Ra_VH TATCGCCAAGCGCCGGGAAAGGGACGCGAGTTCGTTTCCGCTATTGATTCCGAT
    H22 GGGACCACACGCTACGCAGATTCCGTGAAGGGCCGCTTCACAATTTCCCAGGGC
    ACAGCCAAGAACACCGTGTACCTCCAGATGAACTCCTTGCAGCCTGAGGATACC
    GCCATGTATTACTGCAAAACAGTCTGCGTCGTGGGTTCTCGTTGGTCTGACTAT
    TGGGGCCAGGGAACTCAGGTTACCGTTTCCTCTGGGGGCGGGTCCCAGGTCCAG
    CTCCAGGAGTCAGGTGGCGGGTCCGTCCAAGCAGGTGGCTCCCTGCGCCTGTCT
    TGTCGGGCGAGCGGCAGTACTTATAGCAATTACTGTCTGGGCTGGTTCCGGCAG
    ACAACCGGCAAAGAGAGAGAGGGCGTTGCCGTTATTAACTGGGTGGGTGGAATG
    CTGTACTTCGCCGACTCCGTAAAGGGACGCTTCACCGTTAGCCAGGATCAGGCT
    AAAAATACAGTATACCTGCAAATGAACAGTTTGAAGCCTGAAGACACAGCCATG
    TACTATTGCGCCGCTGAGTCTGTCAGCTCTTTTTCTTGCGGGGGATGGCTGACT
    CGCCCGGATCGCGTACCTTATTGGGGCCAGGGAACCCAAGTCACGGTCTCTAGT
    DR594- 1142 CAAGTGCAGCTTCAGGAAAGCGGAGGTGGAAGTGTGCAGGCTGGGGGTAGCCTG
    hIL27 AGGCTGTCCTGCGTGGCGAGCGCGTCCACTTACTGTACCTACGACATGCACTGG
    Ra_VH TATCGCCAAGCACCAGGCAAGGGTCGCGAGTTCGTTTCCGCCATTGATAGCGAT
    H22 GGCACCACTCGTTACGCTGACAGTGTGAAGGGTCGCTTTACCATTTCCCAGGGC
    ACAGCGAAGAACACCGTTTACCTCCAGATGAACAGCCTTCAGCCAGAGGATACA
    GCCATGTACTATTGCAAAACCGTGTGCGTTGTGGGCAGCCGTTGGTCTGACTAT
    TGGGGACAAGGCACTCAGGTTACTGTCAGCTCCGGTGGGTCCGGGGGATCTGGG
    GGCAGCGGCCAGGTCCAGCTGCAAGAGTCTGGTGGCGGTTCCGTCCAGGCGGGC
    GGGAGTTTGCGGCTCAGCTGCCGCGCCTCAGGCTCAACTTACAGTAACTATTGC
    CTGGGCTGGTTCAGGCAGACCACAGGCAAGGAGAGAGAGGGTGTCGCCGTCATC
    AACTGGGTAGGCGGTATGCTGTACTTCGCCGACTCCGTTAAAGGGCGTTTCACG
    GTTTCCCAAGACCAGGCAAAGAACACTGTGTATCTCCAGATGAACAGCCTCAAA
    CCCGAAGATACCGCGATGTATTACTGTGCTGCCGAGAGCGTGTCTTCCTTCAGC
    TGTGGCGGTTGGCTTACACGCCCGGATCGGGTTCCTTACTGGGGCCAGGGCACA
    CAGGTGACAGTCTCCAGC
    DR594- 1143 CAGGTGCAGCTCCAGGAGAGCGGTGGAGGCTCTGTGCAGGCCGGTGGCTCACTT
    hIL27 CGCCTGTCCTGCGTGGCTTCAGCCAGCACTTACTGTACCTATGATATGCACTGG
    Ra_VH TATCGCCAGGCCCCTGGCAAAGGACGCGAGTTCGTGTCTGCCATTGATAGTGAT
    H23 GGCACCACACGCTACGCCGACTCAGTTAAGGGTAGGTTTACCATTTCCCAAGGC
    ACGGCCAAGAACACCGTGTACCTGCAAATGAACTCCCTCCAGCCCGAGGACACA
    GCGATGTATTACTGCAAGACCGTGTGTGTTGTGGGTTCCCGCTGGTCCGACTAT
    TGGGGTCAGGGCACGCAGGTGACCGTTAGTTCCGGTGGAGGCAGCCAGGTCCAG
    CTTCAGGAGTCAGGCGGGGGCTCAGTCCAGGCTGGCGGATCTCTCCGCTTGTCC
    TGTAGGGCCTCCCGTAGCCCCTACGGCAACTATTGTTTGGGTTGGTTCCGCCAG
    TCCACTGGCAAGGAGCGGGAGGGAGTTGCGGTCATCAACTGGGTGGGCGGGATG
    CTCTACTTTGCGGACTCCGTGAAAGGCCGCTTCACCGTTAGCCAGGATCACGCT
    AAGAACACTGTGACACTCCAGATGAACAGCCTGAAGCCTGAGGATACTGCCATG
    TACTATTGCGCCGCAGAGAGCGTGTCTAGCTTCTCCTGCGGCGGTTGGCTGACC
    AGACCCGACAGGGTTCCGTATTGGGGTCAAGGCACCCAGGTGACTGTCTCTAGT
    DR594- 1144 CAGGTTCAGCTTCAGGAGAGCGGGGGCGGTTCTGTTCAGGCAGGTGGGTCCCTG
    hIL27 AGACTGTCTTGCGTTGCCAGCGCCTCCACGTATTGCACCTATGACATGCACTGG
    Ra_VH TATCGCCAGGCCCCTGGCAAGGGCAGAGAGTTCGTTTCTGCCATTGATTCTGAT
    H23 GGCACAACCCGCTACGCCGATTCTGTCAAGGGACGCTTCACGATTTCCCAGGGG
    ACCGCCAAGAACACGGTATATCTGCAAATGAACTCTCTCCAGCCTGAAGACACA
    GCGATGTACTATTGTAAAACCGTGTGCGTCGTAGGCAGTCGTTGGTCCGATTAC
    TGGGGCCAGGGCACTCAAGTGACTGTCAGCTCCGGGGGCTCTGGAGGGAGCGGT
    GGCTCTGGTCAGGTCCAACTGCAAGAGTCAGGCGGGGGCTCCGTGCAGGCCGGA
    GGCTCCCTGCGCCTTTCCTGTCGCGCAAGCCGTTCTCCATACGGGAACTATTGT
    CTGGGCTGGTTCAGACAGAGTACTGGGAAGGAGAGGGAGGGCGTGGCCGTCATC
    AACTGGGTCGGTGGAATGCTGTACTTCGCTGACAGTGTGAAGGGCCGTTTCACT
    GTGTCCCAGGATCACGCCAAAAACACTGTTACACTCCAGATGAACAGCCTGAAG
    CCAGAAGATACAGCAATGTATTACTGTGCGGCTGAATCTGTTTCCAGCTTTTCT
    TGCGGCGGTTGGCTGACGCGCCCTGATCGCGTCCCCTATTGGGGCCAGGGTACT
    CAGGTTACTGTGTCATCT
    DR594- 1145 CAGGTTCAGCTGCAAGAGTCTGGCGGAGGCTCTGTGCAGGCAGGAGGCTCTCTC
    hIL27 CGGCTGAGCTGCGTGGCCTCCGCCTCCACTTACTGTACTTACGATATGCACTGG
    Ra_VH TATCGCCAAGCGCCGGGGAAGGGCCGTGAGTTTGTTAGCGCCATCGACTCCGAC
    H24 GGTACGACTCGCTACGCCGATTCTGTGAAAGGGCGCTTCACTATTTCCCAAGGC
    ACCGCCAAAAACACCGTGTACCTTCAGATGAACTCTCTTCAGCCAGAGGACACC
    GCCATGTATTACTGCAAGACAGTCTGTGTTGTGGGCAGTCGTTGGAGCGATTAC
    TGGGGTCAGGGTACTCAGGTTACTGTCAGCTCCGGCGGGGGAAGCCAGGTCCAG
    CTCCAGGAGAGCGGCGGGGGCCTGGTGCAACCTGGCGGTTCTCTGCGCCTTTCC
    TGCGCTGCGTCTGGCTTCACATTCTCCCACTCCGGCATGAGCTGGGTCCGTCAG
    GCTCCGGGGAAGGGCCTTGAGTGGGTGTCCACGATCAATAGTGGCGGAGCCAGC
    ACCTATTACACCGACTCTGTCAAGGGCCGGTTCACTATCAGCCGGGATAACGCC
    AAGAACATGCTGTATTTGCAGCTGAACTCTCTGAAGACGGAGGACACCGCGATG
    TATTACTGTGCCAAGGGAGGCTCCGGCTATGGGGATGCCTCCAGGATGACTTCT
    CCGGGTAGCCAGGGAACACAGGTGACAGTCTCAAGC
    DR594- 1146 CAGGTCCAACTGCAAGAGTCTGGAGGCGGTAGCGTCCAGGCCGGGGGTTCCCTG
    hIL27 CGGCTGTCCTGTGTCGCCTCTGCGAGCACATACTGTACCTATGATATGCACTGG
    Ra_VH TATCGCCAAGCGCCGGGGAAGGGACGCGAGTTCGTCAGCGCCATTGATTCAGAC
    H24 GGAACGACTCGGTACGCGGACTCTGTCAAGGGACGGTTCACCATCTCACAGGGT
    ACAGCCAAGAATACAGTCTACTTGCAGATGAACTCCTTGCAGCCCGAGGACACA
    GCCATGTATTACTGTAAAACCGTTTGCGTAGTGGGCTCCAGGTGGAGCGATTAC
    TGGGGCCAGGGCACTCAGGTCACCGTCAGCTCCGGCGGTTCCGGCGGGAGCGGA
    GGCAGCGGTCAGGTACAGCTGCAAGAAAGCGGAGGTGGGCTGGTTCAGCCGGGA
    GGCAGCCTGCGCCTGTCCTGCGCCGCGTCAGGTTTCACGTTCTCTCACTCTGGG
    ATGAGCTGGGTGCGGCAAGCGCCGGGCAAGGGCCTCGAATGGGTCTCTACCATC
    AATTCTGGCGGGGCCTCCACCTATTACACCGATAGCGTTAAAGGCAGATTCACT
    ATCTCACGTGACAATGCCAAGAATATGCTGTACTTGCAGCTCAACAGTCTGAAG
    ACCGAAGATACTGCTATGTATTACTGTGCCAAGGGCGGGAGCGGATATGGTGAC
    GCATCCCGTATGACCAGCCCTGGCTCCCAGGGCACCCAGGTGACCGTCTCTAGC
    DR595- 1147 CAAGTCCAGCTCCAGGAGAGCGGGGGAGGCTCTGTTCAGGCTGGGGGCAGTCTG
    hIL27 ACATTGTCCTGCGCTGCCAGCGAGTACGCCTATTCCACCTGTAACATGGGATGG
    Ra_VH TATCGGCAAGCCCCAGGTAAGGAACGCGAACTCGTCTCAGCTTTCATCAGCGAT
    H1 GGCAGCACTTATTACGCCGACTCTGTGAAGGGCCGCTTTACCATCACAAGGGAT
    AATGCAAAGAATACAGTGTATCTGCAAATGAACTCCCTCAAGCCGGAGGACACA
    GCTATCTATTACTGTTCCGCGAACTGCTACAGGCGTCTGAGGAACTACTGGGGG
    CAGGGCACTCAGGTTACCGTTAGCTCCGGCGGTGGAAGCCAGGTGCAGCTCCAG
    GAGTCTGGAGGCGGGCTGGTGCAGCCTGGGGGCAGCCTTCGCCTGTCTTGCGCG
    GCCAGCGGATTCACCTTCTCTAGCTACCCAATGTCTTGGGTGAGGCAGGCTCCT
    GGCAAAGGCCTTGAGTGGATCTCCACAATCAGCGCCGGAGGTGATACCACTCTG
    TACGCAGACAGTGTGAAGGGCCGCTTCACATCTTCCCGCGACAATGCCAAGAAC
    ACCCTGTACCTCCAGCTGAACTCACTGAAGACCGAGGACGCAGCGATCTACTAT
    TGTGCTAAACGTATTGACTGCAACAGTGGGTATTGCTACCGCCGTAACTACTGG
    GGGCAAGGGACGCAGGTCACCGTCTCTTCC
    DR595- 1148 CAGGTGCAGCTCCAGGAGTCTGGTGGCGGTTCTGTGCAGGCAGGGGGCTCCCTT
    hIL27 ACACTGAGCTGCGCCGCGTCAGAGTATGCGTACAGCACCTGCAACATGGGCTGG
    Ra_VH TATCGCCAAGCCCCAGGTAAGGAGCGTGAGCTGGTGTCCGCGTTCATCTCCGAT
    H1 GGCTCTACTTATTACGCTGACTCCGTCAAGGGACGCTTCACAATCACACGTGAC
    AACGCGAAGAACACCGTGTACCTTCAGATGAACTCTCTGAAACCAGAAGACACA
    GCGATCTACTATTGCTCTGCTAACTGCTACCGCAGGCTGCGCAACTACTGGGGT
    CAAGGCACCCAGGTCACCGTCAGCTCCGGTGGGAGTGGTGGCAGCGGTGGCTCC
    GGCCAGGTGCAGCTCCAGGAGTCTGGGGGCGGGCTGGTGCAGCCAGGTGGCTCC
    CTTAGATTGTCTTGCGCAGCTAGTGGATTTACCTTTTCTTCCTACCCAATGTCC
    TGGGTTCGCCAAGCTCCCGGCAAGGGGCTGGAATGGATTAGTACCATCTCTGCG
    GGAGGCGATACTACACTGTATGCCGATTCCGTCAAAGGCCGGTTCACCTCTTCC
    AGAGACAACGCCAAGAACACCCTGTATTTGCAGCTGAACAGCCTGAAGACCGAG
    GATGCTGCCATCTACTATTGCGCTAAGCGTATTGATTGCAACAGCGGCTACTGT
    TATCGGCGCAACTACTGGGGCCAGGGCACCCAGGTTACTGTTAGCAGT
    DR595- 1149 CAGGTTCAGCTCCAGGAAAGCGGTGGCGGGAGCGTGCAGGCCGGAGGCTCTCTG
    hIL27 ACTCTGTCCTGTGCTGCGAGCGAATACGCCTACTCAACTTGCAACATGGGCTGG
    Ra_VH TATCGCCAGGCACCCGGCAAAGAGCGCGAGTTGGTGAGTGCCTTCATCTCCGAT
    H2 GGCAGCACCTATTACGCAGATTCCGTTAAGGGGCGCTTCACAATCACCCGCGAC
    AACGCGAAGAACACCGTGTACCTCCAGATGAACTCTCTGAAGCCCGAGGATACC
    GCCATTTATTACTGTTCTGCTAACTGTTACAGACGCCTTCGTAATTATTGGGGC
    CAGGGCACCCAGGTAACCGTTAGCTCTGGCGGGGGCAGCCAGGTGCAGTTGCAG
    GAGTCCGGCGGGGGACTGGTGCAGCCTGGAGGGTCTCTTAGGCTGTCTTGTGCC
    GCGTCCGGGTTCACCTTTTCCCTCTCCGGCATGTCATGGGTTAGACAGGCACCA
    GGCAAGGGCCTTGAGTGGGTATCTGCCATCTCATCCGGCGGGGCCTCTACCTAC
    TATACCGATTCCGTTAAAGGCCGCTTCACCATTTCTAGGGACAATGCAAAGAAT
    ATCCTGTACCTCCAGTTGAACAGTCTGAAGACCGAGGATACAGCCATGTACTAT
    TGTGCAAAAGGGGGCTCCGGCTACGGCGACGCCAGCCGCATGACATCTCCAGGG
    TCTCAAGGCACCCAAGTGACCGTATCTAGC
    DR595- 1150 CAGGTCCAGCTGCAAGAAAGCGGTGGGGGCAGCGTACAGGCTGGGGGATCTCTG
    hIL27 ACCCTGAGCTGTGCTGCCTCAGAGTACGCATATTCAACCTGCAATATGGGCTGG
    Ra_VH TATCGCCAAGCCCCCGGAAAGGAGCGCGAACTCGTGTCCGCTTTCATCAGTGAC
    H2 GGGTCCACGTACTATGCCGATTCCGTCAAAGGCCGTTTTACTATCACACGCGAC
    AACGCCAAGAATACCGTCTACCTCCAGATGAACAGCCTGAAGCCAGAAGATACA
    GCCATCTATTACTGTAGTGCGAACTGCTACAGACGCCTGCGCAACTACTGGGGA
    CAGGGCACCCAAGTGACTGTGTCCTCTGGAGGCAGCGGCGGATCTGGAGGGAGT
    GGACAGGTTCAGCTTCAGGAGAGCGGGGGCGGACTGGTGCAGCCAGGAGGCTCC
    CTGAGGTTGTCATGCGCGGCCAGCGGTTTCACCTTCAGTTTGTCCGGCATGTCA
    TGGGTACGCCAAGCGCCCGGTAAGGGTCTGGAATGGGTGTCCGCTATTTCTAGC
    GGAGGCGCGAGTACCTATTACACCGACAGCGTGAAGGGGCGCTTTACTATCTCT
    CGTGATAACGCCAAGAACATTCTCTATCTCCAACTTAATTCTCTGAAGACCGAG
    GACACCGCGATGTATTACTGCGCCAAGGGCGGTTCTGGTTATGGCGACGCTTCC
    CGCATGACATCTCCGGGTAGTCAGGGCACACAGGTGACTGTGTCTAGC
    DR595- 1151 CAGGTGCAGCTCCAGGAGTCCGGCGGAGGCAGCGTGCAAGCCGGTGGCTCCCTC
    hIL27 ACCCTGTCATGCGCGGCCAGCGAGTACGCCTATAGCACCTGTAACATGGGCTGG
    Ra_VH TACAGGCAAGCGCCGGGTAAGGAGCGTGAACTCGTCTCTGCCTTTATCTCCGAT
    H3 GGGTCCACCTATTACGCAGACAGCGTGAAGGGCCGGTTTACGATCACCCGCGAC
    AACGCCAAAAACACAGTCTATCTCCAGATGAACAGTCTGAAACCCGAGGATACG
    GCAATTTACTATTGTAGCGCTAACTGCTACCGTAGACTCAGAAACTACTGGGGC
    CAGGGCACACAGGTGACCGTGAGTTCCGGGGGTGGGTCTCAGGTGCAACTCCAA
    GAGTCCGGCGGGGGCTCCGTCCAGGCTGGCGGTAGCCTGCGCTTGTCTTGTGTG
    GCATCTGGATACGTATCTTGCGACTATTTCCTCCCCTCCTGGTATCGTCAAGCT
    CCGGGAAAAGAGCGGGAGTTCGTGTCCATTATCGACGGGACCGGCTCCACGAGC
    TATGCTGCCTCTGTGAAGGGAAGATTTACTGCCAGTGAGGACAAGGGTAAGAAT
    ATCGCTTATCTGCAAATGAATAGTCTGAAGCCGGAAGACACTGCGATGTATTAC
    TGCAAGGCGAGTTGCGTCAGAGGACGCGCCGTATCCGAATACTGGGGGCAGGGT
    ACGCAGGTGACGGTCTCATCT
    DR595- 1152 CAAGTCCAGCTTCAAGAGAGTGGCGGAGGCTCCGTTCAGGCCGGTGGCTCTCTG
    hIL27 ACTTTGTCCTGCGCCGCAAGCGAGTACGCATACTCTACCTGCAATATGGGCTGG
    Ra_VH TATAGACAAGCGCCTGGCAAGGAGCGCGAGCTGGTATCAGCCTTCATCAGCGAC
    H3 GGATCTACCTACTATGCGGATTCAGTGAAGGGGAGGTTCACCATCACACGCGAC
    AACGCGAAGAATACTGTGTACCTTCAGATGAACAGCCTGAAACCCGAGGACACC
    GCAATCTATTACTGCTCTGCCAACTGTTACAGGCGGCTGCGCAATTACTGGGGC
    CAAGGAACGCAAGTGACAGTATCCAGCGGCGGGAGTGGCGGTAGTGGCGGATCT
    GGCCAGGTGCAGCTCCAGGAGAGCGGCGGAGGCTCCGTACAGGCGGGTGGCAGT
    TTGCGCCTGTCCTGTGTCGCTAGTGGTTACGTGTCCTGCGACTATTTTTTGCCC
    TCTTGGTATCGGCAGGCTCCTGGGAAGGAACGTGAGTTCGTAAGCATCATTGAT
    GGGACCGGCTCCACCTCCTACGCTGCCAGCGTCAAGGGGAGATTTACTGCATCC
    GAAGATAAAGGCAAAAACATTGCTTACCTCCAGATGAACTCCCTCAAACCAGAG
    GATACCGCCATGTATTACTGCAAGGCCTCCTGTGTGAGGGGCCGCGCCGTGTCT
    GAGTACTGGGGTCAGGGCACTCAGGTGACTGTCTCCTCC
    DR595- 1153 CAGGTGCAGCTTCAGGAATCCGGCGGAGGCAGCGTCCAAGCGGGAGGCAGCCTG
    hIL27 ACCCTGTCTTGCGCTGCCAGTGAGTATGCTTACTCCACTTGTAACATGGGCTGG
    Ra_VH TATCGTCAAGCGCCAGGGAAGGAGCGTGAGCTGGTCTCTGCCTTCATCTCAGAT
    H4 GGTTCCACCTATTACGCTGACAGTGTCAAGGGCAGGTTCACCATCACTCGGGAT
    AATGCCAAGAACACCGTGTACCTCCAGATGAACTCCCTGAAGCCTGAAGACACT
    GCCATCTATTACTGCTCCGCCAACTGCTACCGTCGCCTGAGAAATTACTGGGGT
    CAGGGAACCCAGGTCACCGTGTCTTCCGGCGGAGGCTCCCAGGTCCAGCTGCAA
    GAGTCTGGTGGCGGTTTGGTGCAGCCTGGCGAGTCCCTGCGCCTGTCTTGCACC
    GCGAGCGGCTTCACCTTCAGCAATTACGCTATGAGCTGGGTCCGTCAGGCTCCT
    GGGAAGGGCCTGGAGTGGGTAAGTGGAATCAACGTGGCCTACGGTATCACGTCC
    TATGCTGATAGCGTGAAGGGCAGATTTACCATCTCTCGGGACAACACCAAGAAC
    ACACTGTACCTCCAACTCAACAGCCTGAAGACCGAAGACACGGCTATCTATTAC
    TGTGTCAAGCACAGTGGCACCACGATCCCCAGAGGCTTTATTAGTTATACTAAA
    CGGGGTCAGGGGACCCAGGTGACCGTCAGCTCC
    DR595- 1154 CAAGTTCAGCTTCAGGAAAGCGGCGGAGGCAGCGTCCAGGCCGGTGGAAGTTTG
    hIL27 ACGCTGAGCTGTGCGGCTAGTGAATACGCATATTCCACCTGCAATATGGGGTGG
    Ra_VH TACAGGCAGGCCCCCGGCAAGGAACGCGAACTGGTGAGTGCTTTTATCAGCGAC
    H4 GGCTCCACGTATTACGCAGATTCCGTGAAAGGAAGGTTTACCATTACCCGCGAT
    AACGCCAAGAACACTGTGTACCTTCAGATGAACTCTCTCAAACCCGAGGACACT
    GCCATCTACTATTGCTCAGCCAACTGTTACCGCAGGTTGCGTAACTACTGGGGC
    CAGGGCACCCAGGTCACAGTCAGCTCCGGCGGGAGTGGTGGATCTGGCGGTTCC
    GGGCAAGTGCAACTTCAGGAATCCGGCGGGGGCCTGGTGCAGCCTGGGGAGTCC
    CTGCGCCTTAGCTGTACTGCTTCCGGCTTCACCTTTTCCAACTACGCCATGAGT
    TGGGTGCGCCAGGCTCCTGGCAAGGGCTTGGAGTGGGTGTCTGGGATTAACGTG
    GCTTACGGGATTACCTCTTATGCCGACTCAGTCAAGGGTCGTTTCACAATCAGT
    CGCGACAACACCAAAAACACTCTGTATCTGCAACTGAATAGTCTGAAGACCGAG
    GATACCGCTATCTATTACTGCGTCAAGCACTCCGGTACTACCATCCCCAGGGGC
    TTTATTAGTTACACGAAACGGGGTCAGGGGACTCAGGTGACAGTGTCCTCC
    DR595- 1155 CAGGTGCAGCTGCAAGAATCCGGCGGAGGCTCCGTGCAGGCAGGTGGCAGTCTG
    hIL27 ACACTGAGCTGCGCCGCTTCCGAGTATGCCTATTCCACCTGCAACATGGGTTGG
    Ra_VH TACAGGCAGGCTCCTGGTAAGGAACGCGAATTGGTGTCCGCCTTCATTTCCGAT
    H5 GGTAGCACCTACTATGCCGACAGTGTAAAGGGGCGGTTCACCATCACTCGGGAC
    AACGCAAAAAATACCGTGTACCTGCAAATGAACTCCTTGAAGCCAGAGGACACC
    GCTATCTATTACTGCTCCGCAAACTGCTATCGCAGGCTGAGGAACTATTGGGGC
    CAGGGCACCCAGGTGACGGTCTCCTCTGGGGGTGGCTCCCAAGTCCAGCTCCAG
    GAGTCAGGAGGTGGGAGTGTGCAAGCCGGGGGAAGCCTGCGTCTCTCCTGTACC
    GCCAGCGGCTACGTGAGCTGTGACTATTTCCTCCCCTCATGGTATAGACAGGCC
    CCTGGGAAGGAGAGAGAATTTGTTAGCGTGATCGACGGCACCGGGTCCACCAGT
    TACGCTGCCAGCGTCAAAGGGCGCTTTACCGCTTCTCAGGACAAGGGGAAGAAC
    ATTGCCTACCTGCAAATGAACAGCCTGAAACCCGAGGACACTGCAATGTATTAC
    TGTAAGGCCAGTTGTGTGCGTGGCCGTGCCATTAGCGAATATTGGGGCCAGGGC
    ACCCAGGTGACCGTGTCTAGT
    DR595- 1156 CAGGTCCAGCTCCAGGAGAGCGGAGGTGGCAGTGTGCAGGCTGGTGGCTCCCTG
    hIL27 ACCCTTAGTTGTGCAGCCAGCGAATATGCTTACTCCACCTGTAACATGGGATGG
    Ra_VH TATCGTCAGGCTCCGGGCAAGGAGCGGGAGCTTGTGAGCGCATTTATCAGCGAC
    H5 GGGTCAACCTATTACGCAGATTCCGTGAAAGGGCGCTTCACCATCACCCGTGAC
    AACGCTAAGAACACCGTCTACCTCCAGATGAACTCACTGAAGCCCGAGGACACT
    GCTATCTATTACTGTTCTGCCAACTGCTACAGACGCCTCAGGAATTACTGGGGA
    CAGGGCACGCAGGTCACTGTTAGCTCCGGTGGCAGTGGTGGCAGCGGGGGCAGT
    GGACAGGTGCAGTTGCAGGAATCCGGTGGCGGGAGTGTTCAGGCAGGCGGATCT
    CTGCGCCTGAGCTGCACCGCCTCTGGATATGTGAGCTGTGATTACTTCCTGCCT
    AGCTGGTATCGGCAGGCCCCCGGCAAGGAACGTGAGTTCGTGAGCGTCATCGAC
    GGCACCGGCTCCACCTCTTACGCAGCCTCTGTGAAGGGCCGCTTCACAGCCAGC
    CAAGACAAGGGGAAGAATATCGCCTATCTCCAGATGAACAGCCTGAAACCCGAG
    GATACAGCCATGTATTACTGTAAAGCCAGCTGTGTGCGCGGCAGAGCTATCTCC
    GAGTACTGGGGCCAGGGCACCCAGGTTACCGTCTCCTCC
    DR595- 1157 CAGGTCCAACTCCAGGAGAGCGGAGGGGGCTCTGTTCAGGCCGGAGGCTCCCTG
    hIL27 ACCCTCTCCTGCGCAGCCAGTGAATATGCTTACTCCACTTGTAACATGGGATGG
    Ra_VH TATCGTCAAGCCCCTGGTAAAGAACGTGAGCTGGTCTCCGCCTTTATCTCCGAC
    H6 GGTTCCACTTATTACGCCGATAGTGTCAAGGGCCGCTTTACCATCACGAGGGAC
    AATGCCAAGAATACCGTCTACCTCCAGATGAACTCTCTGAAGCCTGAGGATACT
    GCCATCTACTATTGTAGTGCAAACTGCTACCGGAGATTGAGAAATTATTGGGGT
    CAGGGCACCCAGGTGACAGTGTCCAGCGGTGGCGGGAGTCAAGTGCAGTTGCAG
    GAGTCTGGTGGCGGACTGGTGCAGCCGGGCGGAAGTCTGCGTTTGTCTTGCGCC
    GCGAGCGGTTTCAGTTTTAGCAGTTACGCCATGAAATGGGTGCGTCAGGCCCCT
    GGGAAGGGCCTGGAGTGGGTGAGTACCATCTCCAGCGGTGGCAGCAGTACTAAC
    TACGCCGACTCTGTGAAAGGCCGCTTCACAATCTCACGTGATAACGCCAAAAAT
    ACCCTCTACCTTCAGCTCAACTCCCTGAAAATCGAGGACACTGCCATGTACTAT
    TGTGCTAAGGCCATTGTGCCGACTGGTGCCACTATGGAACGTGGGCAGGGCACT
    CAGGTGACCGTTTCTTCC
    DR595- 1158 CAGGTGCAGCTCCAGGAAAGCGGTGGAGGCTCCGTGCAGGCTGGCGGTTCCCTG
    hIL27 ACGCTGTCTTGTGCAGCCTCCGAGTACGCCTATAGCACCTGCAACATGGGCTGG
    Ra_VH TATCGCCAGGCCCCCGGCAAGGAACGTGAACTGGTATCCGCGTTCATCTCTGAT
    H6 GGCAGTACCTACTATGCGGATTCTGTGAAGGGCCGCTTCACCATCACAAGAGAC
    AACGCTAAGAACACCGTGTATCTCCAAATGAACTCCCTCAAGCCCGAGGATACA
    GCAATCTACTATTGCAGCGCTAACTGCTACAGACGCCTGAGGAACTATTGGGGA
    CAGGGGACCCAGGTGACAGTTTCTAGTGGAGGCAGCGGAGGCAGCGGAGGGTCT
    GGCCAGGTTCAGTTGCAGGAGAGTGGGGGCGGTTTGGTGCAGCCAGGGGGCTCC
    CTGAGGCTCAGTTGCGCTGCCTCTGGATTCTCCTTCTCCTCTTATGCCATGAAG
    TGGGTGCGCCAAGCGCCCGGCAAGGGCCTGGAGTGGGTATCTACCATCAGCTCT
    GGGGGCTCCAGCACGAATTACGCAGACAGCGTGAAGGGACGCTTTACTATTTCA
    AGAGATAATGCCAAGAACACTCTGTATCTTCAGCTCAACTCCCTGAAGATCGAG
    GATACCGCTATGTACTATTGCGCCAAAGCCATCGTCCCCACTGGGGCAACAATG
    GAACGCGGCCAAGGAACACAGGTCACCGTCAGTTCT
    DR595- 1159 CAGGTGCAGTTGCAGGAGAGCGGCGGTGGCTCCGTACAGGCAGGGGGCTCACTG
    hIL27 ACCCTGAGCTGTGCAGCTAGTGAGTATGCCTATAGCACTTGCAACATGGGGTGG
    Ra_VH TATCGTCAGGCCCCTGGCAAGGAGCGCGAGCTTGTGAGCGCGTTCATTAGCGAT
    H7 GGCTCCACCTACTATGCAGACAGCGTTAAGGGCCGCTTTACCATCACCCGCGAT
    AACGCTAAAAACACCGTTTACCTCCAGATGAACTCCCTGAAGCCTGAGGATACG
    GCTATCTATTACTGCTCCGCTAATTGTTATCGCAGGCTGCGTAACTACTGGGGT
    CAAGGCACCCAGGTGACCGTGTCTTCCGGCGGTGGCTCCCAGGTCCAGCTGCAA
    GAGTCCGGCGGTGGCCTTGTGCAACCTGGAGGCTCCCTGAGACTTTCCTGCGCT
    GCCTCCGGCTTCACGTTCAGCTCTTATCCCATGAGCTGGGTGAGACAGGCTCCT
    GGTAAGGGCCTGGAATGGATTTCCACCATCTCTGCGGGCGGTGACACGACACTC
    TACGCTGATAGTGTTAAGGGACGTTTCACCTCCTCTCGCGATAACGCGAAGAAC
    ACCCTGTACCTTCAGCTTAATTCCCTGAAAACCGAAGACACCGCTATCTACTAT
    TGCGCCAAGAGAATTGACTGCAACTCCGGTTACTGTTATCGTCGCAACTACTGG
    GGCCAGGGCACCCAGGTGACAGTCTCTTCT
    DR595- 1160 CAGGTCCAGTTGCAGGAGTCTGGCGGGGGCTCAGTGCAAGCCGGGGGCTCCCTG
    hIL27 ACTCTGAGCTGCGCTGCCTCTGAGTATGCTTACTCCACGTGCAACATGGGGTGG
    Ra_VH TATCGCCAGGCCCCCGGAAAGGAACGCGAGCTGGTGTCTGCCTTCATCTCTGAC
    H7 GGCAGCACATATTACGCTGACTCCGTAAAAGGTAGATTTACCATCACCCGCGAC
    AATGCGAAAAACACAGTTTATCTCCAGATGAACTCCCTGAAACCGGAGGACACC
    GCGATCTACTATTGCAGCGCGAATTGTTACCGCCGTCTTCGTAATTACTGGGGG
    CAGGGAACCCAGGTGACAGTCTCCAGCGGGGGCTCCGGTGGCTCCGGTGGCTCC
    GGCCAGGTGCAGCTCCAGGAGTCTGGTGGCGGGTTGGTGCAGCCCGGAGGTAGC
    CTGAGGCTGTCCTGTGCTGCATCTGGTTTTACCTTCAGCAGTTATCCAATGTCT
    TGGGTACGCCAAGCGCCCGGTAAGGGCTTGGAGTGGATTTCTACAATTAGCGCC
    GGAGGCGATACTACCCTGTACGCTGACTCTGTGAAGGGTCGTTTCACATCCTCT
    AGGGATAACGCGAAAAATACACTGTACCTTCAGCTCAATAGTCTGAAGACCGAG
    GACACCGCAATCTATTACTGTGCAAAACGCATCGACTGTAATAGCGGATACTGC
    TACAGGCGTAACTACTGGGGCCAGGGAACCCAGGTGACCGTCAGTAGC
    DR595- 1161 CAGGTACAGTTGCAGGAAAGTGGGGGCGGGTCTGTGCAGGCTGGCGGGTCCTTG
    hIL27 ACCCTGTCATGTGCCGCTTCTGAGTACGCCTACTCCACCTGTAACATGGGCTGG
    Ra_VH TATCGTCAGGCTCCCGGCAAGGAGCGCGAGCTGGTATCCGCCTTCATCTCTGAT
    H8 GGCAGCACCTATTACGCCGATAGCGTGAAGGGTCGTTTCACTATCACACGGGAC
    AACGCGAAGAACACAGTGTATTTGCAAATGAACAGCTTGAAGCCCGAAGATACC
    GCTATCTATTACTGCTCTGCTAACTGTTATCGTCGCCTGCGGAACTACTGGGGG
    CAGGGGACTCAGGTAACTGTTTCCAGCGGAGGCGGTAGCCAGGTCCAGCTTCAG
    GAGAGCGGCGGAGGCTCCGTGCAGGTCGGTGGCTCTCTCCGCCTCTCATGTGCT
    GCCAGCGGATTTACTTTCAGCTCCTACCCCATGTCATGGGTGCGGCAGGCTCCC
    GGAAAGGGCCTTGAATGGATTAGCACGATTAGCGCCGGTGGCGACACAACCCTG
    TACGCCGACTCTGTCAAGGGTCGTTTCACGTCCTCAAGAGACAACGCGAAGAAC
    ACTCTGTACTTGCAGCTCAATTCTCTGAAGACAGAGGACACCGCCATCTATTAC
    TGTGCAAAGAGGATTGACTGCAACAGCGGCTATTGCTACAGACGTAACTATTGG
    GGTCAGGGCACTCAGGTGACTGTGTCCAGT
    DR595- 1162 CAGGTGCAGCTGCAAGAGTCTGGGGGCGGGTCCGTGCAGGCCGGAGGTAGTCTG
    hIL27 ACTCTTTCCTGCGCTGCGTCTGAGTACGCCTACTCCACCTGTAACATGGGATGG
    Ra_VH TACAGACAGGCCCCTGGCAAAGAGAGAGAACTGGTGTCCGCTTTTATCAGCGAC
    H8 GGCAGCACTTACTATGCTGACAGTGTGAAGGGCAGGTTCACCATCACCCGTGAT
    AACGCCAAGAACACTGTCTACCTTCAGATGAACTCTTTGAAACCAGAGGACACA
    GCTATCTACTATTGCAGCGCTAACTGCTACAGACGCCTCAGGAACTATTGGGGG
    CAGGGCACCCAGGTGACCGTTTCTAGTGGAGGTAGCGGAGGCAGCGGTGGAAGC
    GGCCAGGTGCAGCTCCAGGAGTCCGGTGGCGGGTCCGTCCAGGTCGGCGGGTCT
    CTCCGCCTGTCCTGCGCTGCCAGCGGGTTCACCTTCTCCAGCTACCCCATGAGC
    TGGGTCAGGCAGGCCCCTGGCAAGGGCCTCGAATGGATCAGCACTATTTCCGCC
    GGTGGCGACACAACCCTCTACGCCGACAGCGTCAAGGGACGGTTCACCAGCAGT
    CGTGACAACGCTAAAAATACCCTGTACCTCCAGCTTAATAGCCTGAAGACCGAA
    GATACAGCAATCTATTACTGCGCCAAGAGGATCGACTGCAACTCAGGGTACTGT
    TACCGTCGCAACTACTGGGGACAGGGAACTCAAGTGACTGTGTCTTCC
    DR595- 1163 CAGGTCCAGTTGCAGGAGTCCGGCGGTGGAAGTGTGCAGGCTGGTGGCAGCCTG
    hIL27 ACCTTGTCTTGTGCCGCTAGTGAGTACGCTTATTCAACCTGCAACATGGGCTGG
    Ra_VH TACAGACAGGCTCCGGGAAAGGAGCGCGAGCTGGTGTCTGCCTTCATCTCCGAT
    H9 GGTTCAACATACTATGCTGACTCCGTGAAGGGGCGCTTCACCATCACGCGCGAT
    AATGCAAAGAATACCGTGTACCTTCAAATGAATAGTCTGAAACCCGAGGATACC
    GCTATCTATTACTGCTCCGCCAACTGCTATCGTCGCCTGCGTAATTACTGGGGC
    CAGGGCACCCAGGTCACTGTTAGTTCAGGAGGCGGAAGCCAGGTCCAGTTGCAG
    GAGTCCGGGGGTGGCTCCGTCCAGAGCGGCGGTAGCCTGAGATTGAGTTGCGCG
    GCCTCAGGCTTCACCTACAGCACCAGCAATAGCTGGATGGCCTGGTTCCGTCAG
    GCTCCGGGCAAAGAGAGGGAGGGCGTGGCGGCCATCTACACTGTGGGCGGTAGC
    ATCTTCTACGCGGACAGCGTTCGGGGTCGCTTCACTATCAGCCAAGACGCTACC
    AAGAATATGTTCTACCTCCAGATGAACACTCTGAAGCCCGAGGACACCGCCATG
    TACTATTGCGCTGCCGCTTCTGGCCGCCTGCGCGGTAAGTGGTTTTGGCCCTAT
    GAGTACAACTATTGGGGTCAAGGAACCCAGGTGACCGTGTCTTCC
    DR595- 1164 CAGGTCCAGTTGCAGGAGAGCGGTGGCGGATCTGTCCAAGCCGGAGGTAGTCTC
    hIL27 ACGCTCAGCTGTGCCGCGAGCGAATACGCCTACTCCACCTGTAATATGGGGTGG
    Ra_VH TATCGTCAGGCACCAGGCAAAGAGCGCGAACTGGTGTCCGCGTTCATCTCCGAC
    H9 GGCTCAACGTATTACGCCGATAGCGTAAAGGGCCGGTTTACAATCACCCGCGAC
    AACGCCAAGAATACCGTCTACCTTCAGATGAACTCCCTGAAGCCAGAGGACACT
    GCAATTTACTATTGCAGCGCTAACTGTTACCGCCGTCTGCGCAACTACTGGGGA
    CAAGGAACCCAAGTTACCGTGAGTTCTGGTGGCTCTGGTGGCAGCGGAGGCAGC
    GGACAAGTTCAGCTTCAGGAGTCTGGAGGTGGCTCAGTACAGTCTGGTGGCTCC
    CTCCGCCTCAGCTGTGCAGCTTCAGGTTTCACCTACTCCACGTCCAACAGTTGG
    ATGGCCTGGTTTCGGCAAGCTCCGGGAAAAGAGCGTGAGGGAGTGGCTGCGATC
    TATACAGTCGGGGGATCTATCTTCTACGCGGACTCCGTCAGAGGCAGGTTCACC
    ATTTCTCAGGATGCTACTAAAAATATGTTCTATCTTCAGATGAACACGCTGAAG
    CCAGAGGACACAGCCATGTACTATTGCGCCGCAGCCTCAGGCAGGCTGCGCGGT
    AAATGGTTTTGGCCTTACGAGTACAACTATTGGGGTCAGGGCACCCAGGTGACC
    GTGAGTTCT
    DR595- 1165 CAGGTGCAGTTGCAGGAGTCCGGCGGGGGCTCCGTGCAGGCGGGCGGTAGCCTG
    hIL27 ACTCTGTCATGTGCCGCGTCCGAGTACGCTTACTCTACCTGCAACATGGGCTGG
    Ra_VH TATCGCCAGGCTCCTGGAAAAGAACGCGAACTGGTGAGTGCCTTTATCTCTGAC
    H10 GGTTCCACTTATTACGCCGATTCCGTGAAGGGGCGCTTTACAATCACTCGCGAT
    AATGCCAAGAACACAGTGTACCTCCAGATGAACAGCCTGAAACCAGAGGACACC
    GCTATTTACTATTGCAGCGCGAACTGCTACAGACGCCTCAGGAACTATTGGGGA
    CAGGGCACCCAGGTGACAGTTTCCAGTGGAGGTGGCTCCCAGGTCCAGTTGCAG
    GAAAGTGGGGGAGGGTCCGTCCAAGCTGGCGGTTCTCTGCGGCTCTCATGCAGG
    GCCTCCGGTTCCACTTATAGTAACTATTGCTTGGGCTGGTTCAGGCAGATCACC
    GGCAAGGAGCGCGAGGGAGTGGCTGTCATCAACTGGGTGGGCGGTATGCTTTAT
    TTCGCCGACTCCGTGAAGGGCCGTTTTACAGTGTCACAAGACCAGGCCAAAAAT
    ACTCTGTACCTGCAAATGAACAGTTTGAAGCCTGAGGATACCGCGATGTACTAT
    TGTGCCGCTGAGTCCGTAAGTAGCTTTAGCTGCGGCGGTTGGTTGACCAGACCT
    GACCGCGTGCCATATTGGGGTCAGGGCACACAGGTGACAGTGAGCAGC
    DR595- 1166 CAAGTGCAGTTGCAGGAAAGCGGAGGCGGGTCTGTTCAGGCCGGAGGCAGCCTT
    hIL27 ACGCTGTCCTGCGCTGCCTCAGAATACGCATACAGTACCTGTAACATGGGCTGG
    Ra_VH TATCGCCAGGCCCCTGGGAAGGAGAGAGAGCTGGTGAGTGCCTTCATTTCTGAC
    H10 GGCTCTACCTACTATGCTGATAGCGTGAAGGGTAGGTTTACAATCACCCGCGAC
    AACGCCAAAAATACCGTTTACCTTCAGATGAACAGCCTGAAGCCGGAAGACACC
    GCCATCTATTACTGCTCTGCCAACTGCTATCGCCGTCTGCGCAATTACTGGGGC
    CAGGGCACCCAGGTCACCGTGTCCAGCGGCGGTTCTGGTGGGTCTGGAGGGTCC
    GGGCAGGTGCAGCTGCAAGAGTCTGGAGGTGGCTCCGTCCAGGCCGGGGGCAGT
    CTGCGCTTGTCATGTCGGGCCTCTGGTTCCACTTACTCCAACTACTGCTTGGGA
    TGGTTCCGGCAGATTACAGGCAAGGAACGCGAGGGAGTCGCAGTCATCAACTGG
    GTGGGCGGAATGCTTTACTTTGCCGATTCCGTCAAGGGCAGGTTCACTGTGAGC
    CAGGATCAGGCTAAGAACACACTGTACCTTCAGATGAATAGCCTGAAGCCCGAG
    GACACTGCTATGTATTACTGTGCTGCCGAAAGCGTGTCCTCATTCTCCTGCGGA
    GGCTGGCTGACCCGCCCTGATCGGGTGCCGTACTGGGGTCAAGGCACTCAAGTG
    ACTGTCTCATCT
    DR595- 1167 CAAGTACAGTTGCAGGAGAGCGGTGGCGGTTCAGTGCAGGCCGGGGGAAGTCTG
    hIL27 ACCCTGAGTTGCGCGGCCAGCGAGTATGCCTACAGTACCTGTAACATGGGCTGG
    Ra_VH TATCGCCAAGCACCTGGCAAGGAACGTGAGCTGGTTTCAGCCTTCATCTCCGAC
    H11 GGCTCCACCTATTACGCTGACAGCGTGAAGGGTAGGTTCACTATTACTCGGGAC
    AACGCGAAGAATACCGTATACTTGCAGATGAACTCACTGAAGCCTGAGGACACC
    GCCATCTATTACTGCTCCGCCAACTGCTACCGTCGCCTTCGTAATTATTGGGGG
    CAGGGAACCCAGGTCACTGTCAGCTCTGGAGGCGGTTCACAAGTACAGTTGCAG
    GAGTCTGGTGGGGGTAGCGTCCAGGCCGGGGGAAGCCTTCGCCTTTCTTGCCGC
    GCCAGCGGCTCCACCTACTCAAATTACTGCCTCGGATGGTTTCGCCAGTCTACC
    GGAAAGGAACGCGAGGGTGTCGCAGTGATAAATTGGGTCGGCGGTATGCTGTAC
    TTCGCGGATTCTGTGAAGGGCAGGTTCACAGTTTCCCAGGATCACGCCAAGAAC
    ACCGTGACCCTCCAGATGAACTCCCTGAAGCCGGAAGATACCGCAATGTATTAC
    TGTGCCGCTGAGTCTGTGTCATCTTTTTCTTGCGGTGGATGGTTGACTCGCCCC
    GGTCGCGTGCCTTATTGGGGCCAAGGCACACAAGTGACAGTGTCTAGC
    DR595- 1168 CAGGTGCAGTTGCAGGAAAGCGGTGGAGGGTCCGTGCAGGCCGGGGGCTCTCTG
    hIL27 ACACTGTCTTGTGCCGCTAGTGAGTACGCATACAGCACATGCAACATGGGCTGG
    Ra_VH TATCGTCAAGCTCCGGGTAAGGAGCGTGAGCTTGTCTCCGCATTCATCAGTGAC
    H11 GGCTCAACCTATTACGCGGACAGCGTGAAGGGAAGATTTACCATCACCCGCGAT
    AACGCCAAGAACACTGTCTACCTCCAGATGAACAGCCTGAAACCTGAGGATACT
    GCTATTTACTATTGCAGTGCAAACTGTTACCGTCGCCTTCGCAACTATTGGGGC
    CAGGGCACACAAGTGACTGTGAGTTCAGGTGGCTCCGGTGGCTCAGGTGGCTCC
    GGTCAGGTCCAGCTCCAGGAGTCCGGCGGAGGCTCCGTGCAGGCAGGGGGCTCT
    CTGAGGCTGTCCTGTAGGGCATCCGGTTCCACCTATAGTAACTACTGCCTGGGC
    TGGTTCCGCCAGAGCACCGGAAAGGAACGCGAGGGCGTGGCCGTCATCAACTGG
    GTCGGGGGCATGTTGTACTTCGCGGACTCTGTGAAGGGCCGCTTCACCGTGTCC
    CAAGATCACGCCAAAAACACTGTGACTCTCCAGATGAATAGCCTCAAGCCCGAA
    GATACGGCGATGTACTATTGCGCAGCCGAGTCCGTGAGTTCCTTCTCATGCGGT
    GGCTGGCTGACCCGCCCCGGTCGCGTGCCTTACTGGGGCCAGGGTACTCAGGTG
    ACCGTCTCCTCC
    DR595- 1169 CAGGTGCAGTTGCAGGAGTCCGGCGGTGGGAGCGTACAGGCTGGCGGTTCTCTG
    hIL27 ACACTTTCCTGCGCAGCCAGCGAGTACGCCTACTCCACCTGCAACATGGGGTGG
    Ra_VH TATCGCCAAGCGCCTGGAAAGGAGCGCGAGCTGGTTAGCGCCTTCATCAGTGAT
    H12 GGCTCCACATATTACGCGGACAGCGTGAAGGGACGCTTCACCATCACCCGTGAC
    AACGCGAAAAACACAGTCTACTTGCAGATGAACTCCCTCAAGCCTGAGGATACA
    GCCATCTACTATTGCTCCGCCAACTGCTATAGGAGATTGCGCAACTACTGGGGG
    CAAGGAACGCAGGTCACCGTCTCCTCTGGGGGAGGCAGCCAAGTGCAACTCCAG
    GAGAGCGGGGGTGGCAGCGTGCAGGCGGGTGAGTCTCTCAGACTGTCTTGCCGC
    GCGTCTGGCTCTACATATTCTAACTATTGCCTGGGTTGGTTCCGGCAGATTACT
    GGCAAGGAGCGCGAGGGTGTTGCTGTGATTAACTGGGTGGGCGGTATGCTGTAC
    TTCGCCGATTCCGTCAAGGGACGTTTCACCGTTAGCCAGGACCAGGCCAAAAAC
    ACCGTCTACCTGGAGATGAATAGCTTGAAGCCCGAAGATACCGCGATGTATTAC
    TGCGCCACCGAGAGTGTCTCATCTTTTTCCTGTGGGGGTTGGCTTACTCGCCCA
    GACAGGGTGCCATACTGGGGACAGGGCACTCAGGTGACTGTAAGCAGC
    DR595- 1170 CAGGTTCAGTTGCAGGAGAGTGGCGGAGGCAGCGTTCAGGCCGGAGGCTCTCTG
    hIL27 ACCCTGTCATGCGCGGCCAGCGAGTACGCCTACAGCACCTGCAACATGGGATGG
    Ra_VH TATCGCCAGGCACCCGGTAAGGAGAGAGAACTGGTGTCCGCCTTCATCTCTGAC
    H12 GGCTCCACTTACTATGCTGATAGCGTGAAGGGTCGCTTTACCATCACGCGCGAT
    AACGCAAAAAATACCGTGTATTTGCAGATGAACTCTCTCAAGCCCGAGGATACC
    GCCATTTATTACTGTAGCGCTAACTGTTACCGTCGCCTGCGCAACTATTGGGGC
    CAGGGCACCCAGGTTACTGTCAGCTCCGGTGGCTCCGGCGGTTCTGGGGGCTCC
    GGCCAGGTGCAGCTCCAGGAGTCTGGTGGAGGCTCCGTGCAGGCAGGTGAGTCC
    TTGCGTCTGTCCTGCCGGGCCAGCGGTTCAACATATTCTAACTACTGCCTGGGG
    TGGTTCCGCCAGATTACCGGCAAAGAGCGCGAGGGTGTCGCAGTCATCAACTGG
    GTCGGAGGTATGCTGTACTTCGCCGATTCTGTGAAGGGACGTTTCACCGTGTCC
    CAGGACCAGGCCAAGAACACAGTATATCTGGAGATGAACTCCCTGAAGCCTGAA
    GATACAGCCATGTATTACTGCGCCACGGAGTCCGTCAGCTCCTTCTCCTGTGGC
    GGATGGTTGACCAGGCCCGACAGGGTGCCTTATTGGGGTCAGGGCACCCAAGTC
    ACCGTGAGCAGC
    DR595- 1171 CAGGTGCAGCTCCAGGAGTCCGGCGGTGGCTCTGTGCAGGCGGGCGGTAGCCTT
    hIL27 ACTCTCAGCTGTGCTGCGTCTGAATACGCTTATTCTACCTGTAATATGGGCTGG
    Ra_VH TATCGGCAGGCCCCTGGCAAGGAGAGAGAACTCGTGAGCGCCTTCATCTCCGAC
    H13 GGCTCTACCTACTATGCCGACAGTGTGAAGGGCCGCTTCACTATTACTCGCGAT
    AACGCTAAGAACACGGTGTACCTCCAGATGAACTCTCTGAAGCCGGAGGACACG
    GCCATTTATTACTGCTCCGCTAACTGCTACAGACGGCTGCGTAACTACTGGGGC
    CAGGGCACCCAGGTAACCGTCAGCTCCGGCGGAGGTTCTCAGGTTCAGCTCCAA
    GAGTCTGGGGGCGGGAGCGTCCAGGCCGGAGGGTCCCTCAGGTTGTCCTGCGTG
    GCCAGCGGATATGTGTCTTGTGACTACTTCCTGCCCAGCTGGTATCGCCAGGCT
    CCAGGGAAGGAACGTGAGTTTGTTTCCATCATTGATGGTACAGGCAGCACATCC
    TACGCCGCATCTGTGAAGGGCCGGTTCACTGCCAGCCAGGACCGTGGCAAAAAC
    ATCGCTTACTTGCAGATGAACTCCCTGAAGCCCGAGGATACCGCAATGTACTAT
    TGCAAGGCGAGCTGTGTGCGTGGCAGAACCATTAGCGAATACTGGGGACAGGGC
    ACGCAGGTGACCGTCTCCTCC
    DR595- 1172 CAGGTCCAACTCCAGGAGTCTGGCGGAGGTTCCGTTCAGGCCGGTGGGTCCCTT
    hIL27 ACCCTGAGTTGCGCCGCTTCAGAATACGCCTACTCAACCTGTAACATGGGCTGG
    Ra_VH TATCGCCAAGCTCCTGGTAAGGAAAGAGAGTTGGTGTCCGCTTTCATCTCTGAT
    H13 GGTTCTACCTATTACGCGGACTCTGTGAAGGGCAGATTTACCATCACAAGAGAC
    AACGCCAAGAATACCGTGTACCTCCAGATGAACTCTCTGAAGCCTGAGGATACT
    GCCATCTATTACTGTTCAGCAAACTGCTACCGTCGCCTGCGCAATTACTGGGGG
    CAGGGCACCCAGGTGACAGTATCCAGCGGTGGCAGTGGAGGCTCCGGTGGCTCT
    GGCCAAGTGCAGCTCCAGGAGTCCGGGGGCGGTTCAGTGCAGGCCGGGGGCTCC
    CTGCGGCTGTCCTGTGTCGCGTCTGGATACGTGAGTTGCGACTACTTTCTCCCC
    TCCTGGTATCGCCAGGCTCCAGGAAAGGAGCGCGAGTTTGTCAGCATCATTGAT
    GGCACCGGGAGTACCAGTTATGCGGCTTCTGTTAAGGGCCGTTTCACCGCTTCT
    CAGGATCGCGGAAAGAACATCGCCTATTTGCAGATGAACTCTCTGAAGCCGGAA
    GACACAGCCATGTATTACTGCAAAGCCAGTTGTGTCAGGGGACGGACCATCTCT
    GAGTATTGGGGACAGGGTACGCAGGTCACTGTGAGTTCC
    DR595- 1173 CAGGTGCAGCTTCAGGAGTCTGGAGGCGGATCTGTCCAGGCCGGGGGCAGTCTG
    hIL27 ACCCTGTCCTGCGCCGCTTCTGAGTATGCCTATAGTACTTGCAACATGGGTTGG
    Ra_VH TATCGGCAGGCTCCGGGCAAGGAGCGCGAACTGGTTTCAGCGTTCATCTCTGAC
    H14 GGTAGCACCTACTATGCCGACAGCGTGAAGGGCCGCTTTACTATCACCAGGGAT
    AACGCAAAGAACACCGTTTACCTCCAGATGAATAGCCTCAAGCCTGAGGATACC
    GCTATCTATTACTGCTCAGCTAACTGTTATCGTCGGCTGCGTAACTACTGGGGC
    CAGGGAACTCAAGTTACCGTCAGCAGTGGGGGAGGCAGTCAGGTGCAGTTGCAG
    GAAAGCGGCGGGGGCAGCGTCCAGGCTGGTGGAAGCCTTCGTCTCTCTTGTGTC
    GCCAGTGGCTATGTCTCCTGTGATTATTTTCTGCCGTCCTGGTATCGTCAAGCG
    CCTGGCAAGGAAAGGGAGTTCGTATCCATTATCGACGGAACTGGTAGTACCAGC
    TACGCTGCCTCCGTGAAGGGAAGGTTCACAGCCTCCCAGGATAAGGGTAAGAAC
    ATTGCCTACCTCCAGATGAACTCCCTGAAGCCTGAAGATACGGCCATGTACTAT
    TGCAAAGCCTCTTGTGTCAGGGGCAGAGCCATCAGCGAATACTGGGGCCAAGGC
    ACTCAGGTCACCGTGAGCAGC
    DR595- 1174 CAGGTTCAGCTCCAGGAGTCTGGGGGCGGTTCTGTCCAGGCCGGAGGCAGCCTT
    hIL27 ACACTGTCTTGCGCTGCCAGCGAGTATGCTTACTCTACCTGCAACATGGGTTGG
    Ra_VH TATCGGCAAGCGCCGGGCAAGGAACGGGAACTCGTCTCTGCTTTCATCTCCGAT
    H14 GGCAGCACATATTACGCTGATAGCGTAAAGGGCCGGTTCACCATCACAAGAGAC
    AACGCAAAGAACACAGTTTACCTCCAGATGAACTCCCTCAAACCTGAGGATACC
    GCCATCTATTACTGCTCCGCTAACTGCTACCGCCGTCTGCGCAACTACTGGGGT
    CAAGGCACCCAGGTTACCGTGTCTAGCGGGGGCTCTGGTGGCAGTGGTGGGTCA
    GGGCAGGTCCAGCTCCAGGAGAGCGGCGGAGGTAGCGTACAGGCCGGGGGTTCA
    CTGAGACTGTCTTGTGTGGCCTCTGGATACGTCTCTTGCGATTACTTCCTTCCC
    AGTTGGTATAGGCAAGCGCCCGGTAAGGAGAGAGAGTTCGTTAGCATCATTGAT
    GGCACAGGTTCAACAAGTTATGCGGCTTCCGTAAAGGGACGCTTTACTGCGTCT
    CAGGACAAGGGCAAAAACATCGCCTATCTTCAAATGAACAGTCTGAAGCCTGAA
    GATACCGCTATGTATTACTGCAAAGCCTCCTGCGTGCGCGGTCGCGCTATCAGC
    GAATACTGGGGCCAGGGTACGCAAGTGACTGTCAGTTCT
    DR595- 1175 CAGGTTCAACTCCAGGAATCAGGAGGCGGTTCAGTGCAGGCTGGCGGTAGCCTG
    hIL27 ACCCTCAGCTGCGCTGCGAGTGAGTATGCTTATTCCACCTGCAACATGGGGTGG
    Ra_VH TATCGCCAAGCGCCTGGCAAGGAGAGAGAGCTGGTCAGTGCATTTATTTCCGAT
    H15 GGCTCCACCTACTATGCTGACTCAGTGAAGGGGCGCTTCACCATCACTCGCGAC
    AACGCCAAGAATACTGTCTATCTCCAGATGAACAGCCTCAAACCAGAGGATACA
    GCCATCTACTATTGCAGTGCGAATTGTTATCGTAGGCTGCGCAACTACTGGGGC
    CAAGGCACACAGGTGACCGTGTCTAGTGGAGGTGGCTCTCAGGTCCAGCTCCAG
    GAATCTGGTGGAGGCTCCGTCCAGGCTGGCGGTTCCCTTCGTCTGTCCTGCGTG
    GCCAGCGGCTACGTGAGCTGTGATTATTTCCTCCCTAGCTGGTATCGGCAGGCT
    CCCGGCAAGGAACGCGAGTTCGTTTCTATCATTGATGGAACGGGTTCTACTAGC
    TACGCGGCCTCCGTGAAGGGGCGCTTCACAGCAAGCCAGGACAAAGGGAAGAAC
    ATCGCTTACCTGCAAATGAATACCTTGAAGCCTGAGGACACCGCAATGTATTAC
    TGCAAGGCTTCCTGCGTGAGGGGCCGCGCCATCTCCGAATACTGGGGGCAGGGT
    ACTCAGGTGACCGTTAGCAGT
    DR595- 1176 CAGGTCCAGCTCCAGGAGTCCGGGGGCGGATCAGTCCAGGCTGGCGGGAGTCTG
    hIL27 ACACTGTCCTGTGCTGCCTCTGAGTATGCTTACAGCACCTGTAACATGGGCTGG
    Ra_VH TACAGACAAGCCCCTGGGAAGGAGCGCGAACTCGTGTCCGCGTTTATTAGTGAC
    H15 GGTTCCACCTACTATGCTGACTCCGTGAAGGGTCGCTTCACGATCACCCGCGAC
    AACGCCAAAAATACCGTGTACTTGCAGATGAACTCCCTGAAGCCGGAGGACACA
    GCCATCTATTACTGTAGCGCAAATTGCTACCGTCGCCTGCGTAACTATTGGGGT
    CAGGGCACTCAGGTCACAGTCAGTAGCGGCGGTAGCGGTGGCTCCGGCGGTAGT
    GGACAGGTGCAGTTGCAGGAATCCGGCGGTGGAAGTGTTCAAGCAGGGGGCTCT
    CTGCGCCTGTCATGTGTTGCATCAGGCTATGTCTCTTGCGACTACTTCCTGCCA
    TCTTGGTATCGTCAGGCCCCAGGGAAGGAAAGGGAGTTCGTCTCCATCATTGAT
    GGCACCGGCTCAACCTCTTACGCTGCCAGCGTAAAGGGGCGCTTCACCGCCTCC
    CAGGATAAGGGCAAGAACATCGCTTACCTCCAGATGAACACACTCAAGCCTGAG
    GATACCGCGATGTATTACTGTAAGGCGAGTTGCGTTCGTGGCCGTGCGATCAGC
    GAGTATTGGGGGCAGGGAACCCAGGTAACAGTCAGCTCC
    DR595- 1177 CAAGTGCAGCTCCAGGAGTCCGGGGGCGGTAGCGTGCAGGCCGGTGGCTCCCTC
    hIL27 ACTCTGTCCTGCGCTGCCAGCGAGTATGCGTACTCCACCTGCAACATGGGATGG
    Ra_VH TACAGGCAAGCGCCTGGCAAGGAAAGAGAGCTTGTGAGCGCCTTCATCTCCGAT
    H16 GGTTCTACCTACTATGCTGACTCCGTTAAGGGCCGGTTCACCATTACTCGCGAT
    AACGCCAAGAACACCGTGTATCTCCAGATGAACTCCCTCAAGCCAGAGGACACA
    GCTATCTACTATTGCTCAGCTAACTGTTACCGTCGCCTCCGCAACTATTGGGGC
    CAGGGCACTCAGGTGACTGTCTCTTCCGGGGGTGGCTCCCAAGTGCAGCTCCAG
    GAGTCAGGAGGCGGGTCTGTCCAGGCGGGTGGCTCCCTGCGCCTCAGCTGCCGT
    GCGTCTGGCAGCACCTACAGCAACTACTGTTTGGGCTGGTTCAGACAGATTACT
    GGAAAAGAACGCGAGGGCGTTGCGGTCATCAACTGGGTGGGCGGGATGCTTTAC
    TTTGCAGACAGTGTGAAGGGTCGCTTTACCGTCAGCCAGGACCAGGCCAAGAAC
    ACAGTGTATTTGCAGATGAATAGCCTGAAGCCAGAGGACACTGCCATGTATTAC
    TGCGCGGCTGAGTCAGCCAGCTCTTTCAGTTGCGGTGGCTGGTTGACGCGCCCT
    GACCGCGTTCCTTACTGGGGGCAGGGGACTCAGGTTACCGTGAGCAGC
    DR595- 1178 CAGGTGCAGCTTCAGGAATCAGGGGGTGGAAGCGTGCAGGCAGGAGGCTCTCTG
    hIL27 ACTTTGTCATGTGCCGCTAGTGAGTATGCGTATTCTACGTGCAACATGGGCTGG
    Ra_VH TATCGTCAAGCCCCCGGAAAAGAGCGTGAACTCGTGTCAGCTTTCATTTCCGAC
    H16 GGTAGCACATATTACGCCGACAGCGTGAAGGGGCGCTTTACTATCACTCGCGAT
    AATGCCAAGAATACAGTTTACCTCCAGATGAACTCACTGAAGCCCGAAGACACC
    GCCATCTACTATTGTAGCGCCAACTGTTATAGGAGACTGCGGAACTACTGGGGT
    CAAGGCACCCAGGTGACCGTGTCCTCTGGAGGCTCTGGAGGCTCCGGCGGTAGC
    GGACAGGTGCAGTTGCAGGAGTCCGGTGGCGGGTCAGTGCAGGCCGGGGGCTCA
    CTCAGGCTTTCCTGCCGCGCCAGTGGTTCCACTTATTCCAACTATTGCCTGGGC
    TGGTTCAGGCAGATCACAGGTAAGGAACGTGAGGGGGTGGCTGTGATTAACTGG
    GTCGGCGGGATGCTGTATTTTGCCGACAGTGTGAAAGGGAGATTCACCGTCAGC
    CAGGATCAGGCCAAAAACACCGTGTACCTGCAAATGAACAGTCTGAAGCCAGAG
    GATACCGCCATGTATTACTGTGCAGCGGAGAGCGCCTCCAGCTTTTCCTGCGGA
    GGTTGGCTCACTCGGCCTGACCGCGTTCCCTACTGGGGTCAAGGGACCCAGGTG
    ACAGTCTCCTCC
    DR595- 1179 CAGGTCCAACTCCAAGAAAGCGGTGGCGGTTCCGTCCAGGCCGGAGGCTCCCTG
    hIL27 ACCCTGTCCTGTGCTGCAAGTGAGTACGCCTATTCCACCTGTAATATGGGTTGG
    Ra_VH TATAGGCAGGCACCAGGAAAAGAGCGCGAACTGGTGTCCGCGTTCATCTCCGAC
    H17 GGCTCCACTTACTATGCTGATAGTGTTAAAGGCCGCTTCACCATCACCCGTGAT
    AACGCGAAGAACACTGTGTACTTGCAGATGAACAGCCTGAAGCCCGAGGATACA
    GCCATCTACTATTGCTCTGCCAACTGCTATAGAAGGCTGCGGAACTACTGGGGT
    CAGGGAACCCAGGTGACCGTGAGTTCCGGCGGGGGTTCCCAGGTCCAGCTCCAG
    GAATCTGGCGGGGGTCTGGTGCAGCCTGGAGGTTCACTCAGATTGTCTTGCGCC
    GCGTCTGGCTTCACATTCTCCCTCTCCGGGATGAGTTGGGTCCGCCAAGCCCCC
    GGCAAGGGTCTGGAGTGGGTATCCGCCATCAGTTCCGGCGGAGCCTCAACCTAC
    TATACGGACTCCGTGAAGGGACGTTTTACCATCAGCCGGGACAACGCTAAGAAC
    ATGCTGTACCTCCAGCTGAACTCTCTGAAGACTGAAGACACCGCCATGTATTAC
    TGTGCCAAGGGTGGCTCCGGGTACGGGGATGCCAGCCGCATGACCTCTCCTGGT
    AGCCAGGGCACGCAGGTCACAGTGTCTTCT
    DR595- 1180 CAGGTACAGCTTCAGGAATCTGGAGGCGGAAGCGTGCAGGCTGGTGGCTCTCTG
    hIL27 ACACTGTCTTGCGCCGCGAGCGAATACGCATACAGTACGTGTAATATGGGTTGG
    Ra_VH TACAGGCAAGCTCCGGGCAAGGAAAGAGAACTCGTAAGCGCCTTCATCAGCGAT
    H17 GGCTCCACTTATTACGCAGACAGCGTGAAGGGCCGCTTCACTATCACGAGGGAT
    AACGCCAAGAACACTGTCTATCTCCAGATGAACTCCCTCAAACCTGAAGACACC
    GCCATTTATTACTGCTCCGCTAATTGTTACCGCCGTCTGCGCAATTATTGGGGA
    CAGGGCACCCAGGTAACAGTGTCCTCTGGAGGGAGCGGTGGATCTGGAGGCTCC
    GGCCAAGTCCAGTTGCAGGAAAGCGGAGGCGGGTTGGTGCAGCCTGGTGGCAGC
    CTGCGCCTGTCTTGCGCGGCCTCTGGCTTCACATTCTCCCTGTCTGGAATGTCT
    TGGGTCCGGCAGGCCCCAGGTAAGGGCCTGGAGTGGGTGAGCGCAATTTCCTCT
    GGCGGGGCATCCACCTATTACACCGACTCCGTGAAGGGCAGGTTCACTATTAGC
    CGGGATAATGCGAAGAACATGCTGTACCTTCAGCTGAACTCCTTGAAGACTGAG
    GACACCGCTATGTATTACTGTGCCAAGGGCGGTAGCGGCTACGGTGACGCTTCC
    CGCATGACCTCTCCGGGTTCCCAGGGCACCCAGGTGACCGTGTCTTCC
    DR595- 1181 CAGGTCCAGTTGCAGGAATCCGGCGGGGGTTCCGTCCAAGCAGGCGGTTCCCTT
    hIL27 ACACTCAGCTGCGCTGCCAGCGAGTACGCCTATTCTACGTGTAACATGGGCTGG
    Ra_VH TATCGCCAGGCTCCTGGGAAGGAACGCGAGCTGGTGAGCGCATTTATCTCAGAT
    H18 GGGTCCACATACTATGCTGACTCTGTTAAGGGTCGTTTCACTATCACCAGGGAC
    AACGCTAAGAACACTGTCTATCTGCAAATGAACTCCCTGAAACCAGAGGACACC
    GCTATCTATTACTGCTCTGCCAACTGTTATCGTCGGTTGCGCAATTATTGGGGG
    CAGGGGACACAGGTGACCGTGTCCTCAGGTGGAGGCTCCCAGGTGCAGTTGCAG
    GAATCTGGGGGAGGCTCCGTGCAGGCTGGCGGTTCACTGAGGCTGAGTTGTGTT
    GCATCTGGCTATGTAAGTTGTGATTACTTCTTGCCAAGCTGGTATCGTCAGGCC
    CCAGGGAAGGAACGCGAGTTCGTCTCTATTATCGACGGCACGGGTTCTACCAGC
    TACGCTGCCAGCGTTAAGGGGCGGTTTACGGCATCCCAGGACAAGGGAAAGAAC
    ATCGCTTATTTGCAGATGAACTCCCTGAAACCCGAGGATACTGCGATGTATTAC
    TGCAAGGCCAGCTGTGTAAGGGGGCGCGGCATCAGCGAATATTGGGGCCAGGGA
    ACTCAGGTGACCGTGTCCTCT
    DR595- 1182 CAGGTGCAGCTCCAGGAAAGCGGCGGGGGCTCCGTGCAGGCTGGGGGCAGCTTG
    hIL27 ACACTGTCCTGTGCAGCTTCCGAGTACGCCTACTCAACCTGCAACATGGGCTGG
    Ra_VH TACAGGCAGGCTCCCGGTAAGGAGCGCGAACTGGTGTCCGCCTTCATTTCTGAC
    H18 GGCTCCACCTATTACGCCGACTCAGTGAAAGGTAGGTTCACCATTACAAGGGAC
    AACGCCAAGAACACTGTCTACTTGCAGATGAACAGTTTGAAGCCCGAAGACACT
    GCTATCTACTATTGCAGCGCCAACTGTTACAGGCGTCTGCGCAACTATTGGGGT
    CAGGGCACCCAAGTGACTGTGTCTTCCGGTGGGTCCGGTGGCTCCGGGGGCTCC
    GGCCAGGTGCAGCTGCAAGAGTCCGGCGGTGGCTCCGTACAGGCCGGGGGCAGC
    CTCAGACTGTCTTGCGTAGCCTCCGGCTACGTTTCTTGCGACTACTTTCTTCCT
    TCTTGGTACAGACAAGCTCCAGGGAAGGAACGGGAGTTCGTGAGCATTATCGAC
    GGCACCGGGTCAACCTCTTACGCGGCCTCCGTGAAGGGCCGTTTTACCGCCAGC
    CAAGACAAGGGCAAAAACATCGCGTATCTTCAGATGAACTCCCTTAAACCTGAG
    GACACCGCGATGTACTATTGCAAGGCTTCTTGCGTTCGCGGGCGCGGGATCAGC
    GAGTATTGGGGCCAGGGCACCCAGGTGACCGTGTCTTCT
    DR595- 1183 CAGGTGCAGTTGCAGGAGTCTGGCGGGGGCTCCGTTCAAGCGGGCGGATCTCTC
    hIL27 ACCCTGTCATGTGCCGCTTCTGAGTATGCCTATTCCACTTGCAACATGGGGTGG
    Ra_VH TATCGCCAGGCACCGGGCAAGGAACGCGAACTCGTGTCTGCCTTCATCTCTGAT
    H19 GGCTCCACCTATTACGCAGATTCCGTCAAGGGCAGATTTACCATTACCAGAGAC
    AACGCTAAGAACACCGTTTACCTCCAGATGAACTCCCTGAAACCTGAGGATACA
    GCCATTTATTACTGTTCCGCCAACTGCTATAGACGCCTGCGGAACTATTGGGGA
    CAAGGCACGCAGGTTACTGTGTCCTCTGGGGGCGGATCTCAGGTGCAGCTTCAG
    GAGAGCGGTGGCGGGTCTGTCCAGGCTGGAGGGAGCTTGAGACTGTCCTGTCGT
    GCGTCCGGGTCAACCTATTCCAACTATTGCCTGGGTTGGTTTCGCCAGATCACT
    GGTAAGGAGCGTGAGGGGGTCGCTGTTATCAACTGGGTGGGTGGGATGCTGTAT
    TTCGCTGATTCAGTAAAGGGCCGCTTCACCGTCTCCCAGGACCAGGCGAAGAAC
    ACCGTGTATCTTCAGATGAACAGCCTCAAGCCTGAGGACACCGCAATGTATTAC
    TGCGCAGCTGAGTCTGTTTCCAGCTTCAGTTGCGGTGGATGGCTTACACGCCCA
    GATCGCGTGCCATACTGGGGTCAGGGTACGCAAGTTACCGTCTCCTCC
    DR595- 1184 CAGGTGCAGCTCCAGGAGTCCGGTGGCGGTTCCGTCCAGGCTGGTGGCTCTCTG
    hIL27 ACGTTGAGTTGCGCGGCCAGCGAGTACGCTTACTCAACGTGCAACATGGGGTGG
    Ra_VH TATCGCCAAGCGCCAGGGAAAGAGCGCGAACTCGTAAGTGCCTTTATTTCCGAT
    H19 GGAAGCACCTATTACGCAGACAGTGTGAAGGGGCGCTTTACTATTACCCGTGAC
    AACGCCAAAAACACCGTCTACCTGCAAATGAACTCCCTGAAACCGGAGGACACC
    GCCATTTATTACTGTTCCGCCAACTGCTATCGCCGTCTGCGCAATTATTGGGGC
    CAGGGGACCCAGGTGACAGTGAGTTCTGGCGGGAGCGGCGGGAGCGGAGGGAGC
    GGGCAGGTCCAGCTTCAGGAGAGCGGGGGAGGCAGCGTGCAGGCTGGGGGTAGC
    CTGCGCTTGTCTTGCAGAGCCTCCGGTTCCACATACAGTAACTATTGCCTGGGA
    TGGTTCCGCCAGATTACCGGCAAGGAACGGGAAGGAGTCGCGGTCATCAACTGG
    GTCGGTGGAATGCTGTATTTTGCTGACTCTGTCAAAGGCCGCTTTACAGTGTCC
    CAGGATCAGGCTAAGAATACTGTCTATCTCCAGATGAACAGCCTGAAGCCTGAA
    GACACAGCCATGTATTACTGTGCCGCAGAGTCCGTCAGCTCCTTCTCCTGCGGT
    GGGTGGCTTACCAGGCCTGATCGCGTTCCTTACTGGGGTCAGGGTACACAGGTG
    ACGGTGTCCAGT
    DR595- 1185 CAGGTACAGCTCCAGGAGAGCGGCGGAGGTTCCGTGCAGGCCGGTGGCAGTCTC
    hIL27 ACCCTGTCCTGCGCTGCCTCTGAGTATGCGTATTCTACCTGTAATATGGGCTGG
    Ra_VH TACAGGCAGGCTCCAGGCAAAGAGAGAGAACTCGTGTCTGCTTTCATCTCTGAC
    H20 GGTAGTACCTATTACGCGGACAGCGTTAAAGGCAGGTTCACCATCACCAGAGAC
    AACGCCAAAAACACAGTTTACCTCCAGATGAACTCCCTCAAGCCCGAGGACACC
    GCAATTTACTATTGTTCCGCTAACTGCTATCGCAGACTGCGTAACTATTGGGGT
    CAGGGTACTCAGGTTACCGTGTCTAGCGGCGGGGGCAGTCAGGTTCAGCTTCAG
    GAAAGTGGCGGTGGACTTGTGCAGCCCGGAGGGTCTCTTCGCCTTTCATGTGCT
    GCCAGCGGCTTCACCTTTTCCAGTTACCCAATGTCCTGGGTCAGACAGGCCCCT
    GGCAAGGGGCTGGAGTGGGTCAGCACCATCTCTTCCGGCGGTGATACAACCTTG
    TACGCAGACTCTGTTAAGGGCAGGTTCACATCCAGCCGGGACAATGCTAAGAAT
    ACCCTCTATCTGCAACTCAACAGCCTGAAGACCGAGGACACCGCAATGTACTAT
    TGCGCCAAACGCATTGATTGCAACAGCGGCTACTGTTACAAACGCTCTTACTGG
    GGCCAGGGCACCCAGGTGACAGTCTCCTCC
    DR595- 1186 CAGGTCCAGTTGCAGGAATCTGGCGGTGGCTCCGTACAGGCGGGCGGGTCCCTC
    hIL27 ACGCTGTCTTGTGCCGCATCCGAATATGCTTATTCCACCTGCAACATGGGCTGG
    Ra_VH TATCGCCAGGCCCCTGGAAAGGAACGCGAACTTGTGAGCGCCTTTATTAGCGAT
    H20 GGTTCTACTTATTACGCTGATAGCGTGAAAGGAAGATTTACTATCACACGCGAT
    AATGCTAAAAATACTGTGTACTTGCAGATGAACTCTTTGAAGCCTGAGGATACG
    GCCATCTATTACTGCTCTGCAAATTGCTACCGCCGTCTGCGTAATTACTGGGGC
    CAGGGCACTCAGGTCACAGTGTCAAGCGGCGGGTCAGGAGGCTCCGGCGGAAGC
    GGCCAGGTCCAGCTCCAGGAGTCTGGAGGTGGCTTGGTGCAGCCTGGTGGCTCT
    CTTCGTCTGTCTTGCGCTGCCTCCGGTTTCACCTTTAGTTCTTACCCTATGTCC
    TGGGTGCGTCAGGCCCCCGGAAAAGGGCTGGAATGGGTGTCCACCATTTCCTCT
    GGCGGTGACACTACACTGTATGCAGACAGTGTGAAGGGGAGATTCACCTCTTCC
    CGTGACAACGCCAAGAACACCCTGTATCTCCAGCTCAATAGCCTGAAGACTGAG
    GATACCGCAATGTACTATTGCGCCAAACGGATCGACTGTAACAGTGGATATTGT
    TACAAGCGTTCCTATTGGGGCCAGGGGACCCAGGTGACTGTGAGTTCT
    DR595- 1187 CAGGTGCAGCTTCAGGAGTCCGGTGGCGGTTCCGTACAGGCAGGAGGGTCCTTG
    hIL27 ACCCTGAGTTGTGCGGCTTCCGAATACGCCTATAGTACATGCAACATGGGTTGG
    Ra_VH TATCGCCAGGCCCCCGGTAAGGAACGCGAGTTGGTAAGCGCCTTCATCTCCGAT
    H21 GGAAGTACCTACTATGCCGATTCAGTCAAGGGTCGCTTTACGATCACACGTGAC
    AACGCTAAGAACACAGTCTATCTCCAGATGAATAGTCTGAAGCCCGAAGATACA
    GCAATCTATTACTGTTCAGCCAACTGTTATCGGCGTTTGCGTAACTACTGGGGA
    CAGGGCACCCAAGTCACCGTCTCCAGTGGTGGCGGTTCCCAGGTCCAGCTTCAG
    GAATCCGGCGGTGGCTTGGTTCAGCCTGGGGGCTCCCTGCGCCTGAGCTGCGCT
    GCCTCTGGATTTACCTTCTCATTGTCCAGCATGTCATGGGTCCGTCAGGCTCCC
    GGCAAGGGCCTGGAGTGGGTCAGTGCCATCTCTTCCGGTGGGGCCTCAACGTAC
    TATACCGATAGCGTGAAGGGACGCTTTACCATCAGCCGGGACAACGCAAAAAAT
    ATGCTGTATCTCCAGTTGAACAGCCTGAAGACGGAGGACACTGCAATGTACTAT
    TGCGCAAAGGGAGGGTCCGGGTACGGTGACGCCTCCAGGATGACCTCTCCTGGC
    TCCCAGGGGACCCAGGTGACTGTCTCCAGC
    DR595- 1188 CAGGTACAGCTTCAGGAGTCAGGGGGGGGTAGCGTCCAGGCGGGCGGTTCTTTG
    hIL27 ACACTCTCCTGCGCCGCGAGCGAGTACGCATACTCTACATGCAACATGGGCTGG
    Ra_VH TACAGGCAGGCCCCAGGCAAGGAAAGGGAGCTGGTGTCCGCCTTCATTAGCGAC
    H21 GGAAGCACCTACTATGCTGATTCCGTGAAGGGCCGGTTCACCATCACACGCGAT
    AACGCTAAGAACACGGTGTACTTGCAGATGAACTCTCTGAAGCCCGAAGACACC
    GCCATCTATTACTGCTCCGCTAACTGCTATCGCAGACTGCGCAATTATTGGGGG
    CAGGGCACCCAGGTGACCGTTAGCTCCGGCGGTAGCGGTGGCAGTGGCGGTTCC
    GGTCAGGTGCAGCTGCAAGAGTCAGGCGGGGGTCTGGTGCAGCCGGGAGGTTCC
    CTGCGCCTCTCCTGCGCCGCTTCTGGGTTTACCTTCAGCCTCTCTTCCATGTCC
    TGGGTGCGCCAAGCGCCGGGCAAGGGTCTTGAGTGGGTTTCTGCGATCTCTTCC
    GGTGGAGCCTCTACATACTATACAGATTCTGTGAAGGGGAGGTTCACTATCAGC
    CGCGACAACGCCAAAAACATGCTGTACCTTCAGCTCAATTCCCTCAAGACTGAG
    GACACAGCTATGTATTACTGTGCAAAGGGTGGCAGCGGATATGGGGACGCCTCT
    CGCATGACTAGCCCTGGTTCCCAGGGGACCCAGGTGACCGTGTCCAGC
    DR595- 1189 CAGGTGCAGCTGCAAGAGAGCGGCGGGGGTTCCGTACAGGCTGGTGGCTCTCTG
    hIL27 ACCTTGTCTTGCGCGGCTTCAGAGTATGCCTATAGTACCTGTAATATGGGTTGG
    Ra_VH TATCGCCAGGCACCGGGAAAGGAGCGGGAGCTGGTGTCTGCTTTCATCTCCGAC
    H22 GGTTCTACCTACTATGCCGATTCTGTAAAGGGGAGGTTTACTATCACTCGGGAT
    AACGCGAAGAACACCGTCTACCTCCAGATGAACAGCCTGAAACCCGAGGATACT
    GCGATTTACTATTGCAGCGCCAACTGTTACCGGCGCTTGCGCAACTACTGGGGC
    CAGGGAACTCAAGTCACTGTCAGTTCTGGCGGAGGCAGCCAGGTCCAGCTCCAG
    GAGAGCGGGGGCGGATCTGTCCAAGCTGGCGGTTCCCTCCGCCTCAGCTGTCGC
    GCATCTGGTAGCACTTACTCTAACTACTGTCTCGGCTGGTTTCGTCAGACAACC
    GGAAAAGAGCGCGAGGGCGTGGCTGTCATCAACTGGGTGGGCGGGATGCTGTAC
    TTTGCGGATAGCGTCAAGGGCCGCTTTACTGTCTCCCAGGACCAGGCAAAAAAC
    ACCGTCTACCTCCAGATGAACTCTCTGAAGCCGGAGGACACCGCGATGTACTAT
    TGTGCTGCCGAGAGCGTCTCCTCATTCTCTTGCGGCGGATGGCTGACCCGCCCA
    GACCGGGTTCCATACTGGGGCCAGGGCACCCAGGTGACCGTTTCTTCC
    DR595- 1190 CAGGTGCAGCTCCAGGAGTCTGGAGGGGGTAGCGTGCAGGCCGGAGGCTCCCTT
    hIL27 ACCCTGTCCTGTGCGGCCTCCGAGTACGCTTACTCTACCTGTAACATGGGCTGG
    Ra_VH TATCGGCAAGCGCCCGGCAAAGAACGCGAACTCGTGTCCGCTTTCATCAGTGAC
    H22 GGTTCCACTTATTACGCTGATTCCGTTAAAGGCCGGTTTACTATCACAAGGGAT
    AACGCGAAGAACACGGTGTATTTGCAGATGAACTCTTTGAAGCCAGAAGATACA
    GCTATCTACTATTGCTCCGCCAACTGTTACAGGCGTCTGCGTAACTATTGGGGT
    CAGGGCACCCAGGTAACAGTGTCATCTGGTGGGAGCGGCGGTTCTGGCGGGTCT
    GGTCAGGTCCAGTTGCAAGAGAGCGGTGGAGGTAGCGTCCAGGCTGGTGGCTCT
    CTGCGCCTGTCTTGCCGTGCCTCCGGCAGCACCTACTCCAACTATTGCTTGGGT
    TGGTTCCGGCAGACAACCGGCAAAGAACGCGAGGGTGTGGCTGTTATCAACTGG
    GTGGGCGGAATGCTGTACTTTGCAGATAGCGTAAAAGGCCGGTTTACCGTGAGC
    CAAGACCAGGCTAAGAACACCGTGTACCTCCAGATGAATAGCTTGAAGCCCGAG
    GACACGGCGATGTATTACTGTGCTGCCGAATCTGTGTCATCTTTCAGCTGCGGA
    GGGTGGCTGACCAGACCAGACCGCGTCCCTTATTGGGGACAGGGCACCCAGGTC
    ACCGTCTCATCT
    DR595- 1191 CAGGTGCAGTTGCAGGAGAGCGGCGGGGGAAGTGTTCAGGCTGGCGGGTCCCTT
    hIL27 ACACTTAGCTGCGCAGCCAGCGAGTACGCATATTCTACCTGCAACATGGGTTGG
    Ra_VH TATCGCCAGGCCCCTGGAAAAGAGCGCGAACTGGTGTCCGCATTCATCTCTGAT
    H23 GGCTCCACCTATTACGCTGACTCCGTGAAGGGCAGGTTCACTATCACTCGGGAT
    AACGCAAAAAATACAGTGTACCTCCAAATGAACTCCTTGAAACCCGAGGATACT
    GCGATTTATTACTGTAGCGCCAACTGTTACCGCAGACTGAGAAACTACTGGGGG
    CAGGGCACACAGGTGACCGTAAGCTCCGGCGGGGGCAGTCAGGTGCAGCTCCAG
    GAGAGTGGCGGAGGTTCCGTGCAGGCTGGAGGCTCACTGAGGTTGTCTTGCCGT
    GCCTCCCGCAGTCCCTACGGTAATTACTGCCTCGGGTGGTTCCGCCAGTCCACG
    GGTAAGGAGAGAGAGGGTGTGGCCGTTATCAACTGGGTCGGCGGTATGCTGTAT
    TTTGCCGACAGCGTCAAGGGACGCTTCACCGTAAGCCAGGACCACGCTAAGAAT
    ACCGTCACTCTGCAAATGAACTCCCTGAAGCCTGAGGATACGGCTATGTACTAT
    TGTGCAGCGGAGAGCGTGAGTTCCTTCTCTTGTGGCGGGTGGCTGACCAGACCA
    GACCGGGTGCCCTACTGGGGCCAGGGCACTCAAGTTACCGTCTCATCC
    DR595- 1192 CAGGTGCAACTTCAGGAATCCGGCGGTGGCAGCGTTCAGGCCGGTGGCTCCCTG
    hIL27 ACCCTGTCCTGTGCAGCGAGCGAATATGCGTACTCTACGTGCAATATGGGCTGG
    Ra_VH TATCGTCAGGCTCCAGGCAAGGAGCGCGAATTGGTGAGTGCGTTCATCTCCGAT
    H23 GGGTCAACATACTATGCGGACTCTGTGAAGGGCCGCTTTACCATCACCAGAGAC
    AACGCCAAGAACACGGTCTACCTGCAAATGAACAGCCTGAAGCCCGAGGACACC
    GCAATCTACTATTGTAGTGCTAATTGTTACCGCAGGCTGAGGAATTACTGGGGT
    CAAGGCACCCAAGTCACCGTGTCCAGCGGGGGTTCCGGCGGTAGCGGAGGCTCC
    GGCCAGGTGCAGCTCCAGGAGAGTGGGGGAGGGAGCGTGCAAGCGGGAGGGAGT
    CTCAGGCTTTCATGCCGTGCTTCTCGCAGCCCTTATGGCAACTATTGTCTGGGC
    TGGTTCAGGCAGAGTACAGGCAAGGAACGCGAGGGCGTGGCAGTCATCAACTGG
    GTCGGCGGGATGTTGTACTTCGCTGACTCCGTGAAGGGCCGCTTTACAGTCTCC
    CAAGACCACGCCAAGAACACCGTCACGCTCCAGATGAACAGTCTCAAGCCCGAA
    GATACTGCCATGTATTACTGCGCTGCGGAGTCAGTGTCCTCTTTCAGCTGTGGG
    GGTTGGCTGACTCGCCCAGACCGGGTGCCATATTGGGGCCAGGGTACACAAGTC
    ACCGTCAGCAGC
    DR595- 1193 CAAGTCCAGTTGCAGGAGAGCGGGGGCGGAAGCGTGCAGGCTGGAGGGAGCCTC
    hIL27 ACCCTGTCCTGCGCCGCTTCCGAGTACGCCTACTCTACTTGTAACATGGGGTGG
    Ra_VH TATAGGCAGGCTCCCGGCAAAGAACGCGAGCTGGTCTCCGCGTTTATTTCTGAC
    H24 GGATCTACCTATTACGCGGACAGTGTGAAGGGCAGATTTACAATCACTAGGGAT
    AACGCAAAAAACACTGTCTATCTCCAGATGAACTCTTTGAAGCCTGAGGACACA
    GCTATCTATTACTGTTCCGCGAACTGCTACAGACGCCTCCGTAACTATTGGGGT
    CAGGGTACTCAGGTGACTGTTAGTTCAGGTGGGGGCTCCCAGGTCCAGCTTCAA
    GAATCTGGGGGTGGATTGGTCCAGCCTGGCGGTTCTCTGCGCCTGTCTTGTGCT
    GCCAGTGGCTTCACTTTTTCCCACAGCGGCATGTCCTGGGTGCGCCAGGCTCCA
    GGCAAGGGCCTCGAATGGGTTAGTACCATCAACAGCGGAGGTGCCAGCACCTAC
    TATACAGATTCTGTGAAGGGCAGATTCACTATTAGTCGCGACAATGCGAAGAAC
    ATGCTTTACTTGCAGCTGAACTCCCTGAAGACCGAAGACACTGCAATGTATTAC
    TGCGCCAAGGGCGGTTCTGGCTACGGTGATGCGTCTCGCATGACATCCCCAGGG
    AGTCAGGGAACCCAGGTGACCGTGAGTTCA
    DR595- 1194 CAGGTCCAGCTCCAGGAATCTGGAGGCGGTAGCGTACAAGCTGGCGGTTCTCTG
    hIL27 ACTCTGAGCTGCGCTGCCTCCGAGTACGCCTACTCAACTTGCAATATGGGCTGG
    Ra_VH TATAGGCAAGCACCAGGGAAGGAAAGAGAATTGGTTTCCGCCTTCATCTCCGAC
    H24 GGAAGTACTTATTACGCCGATTCCGTGAAGGGACGCTTCACGATTACACGGGAC
    AACGCAAAGAACACCGTGTATCTCCAGATGAACAGCCTGAAGCCTGAGGACACC
    GCAATTTATTACTGTTCCGCCAACTGCTACAGACGCTTGCGCAACTACTGGGGT
    CAAGGCACCCAGGTGACCGTCTCTAGTGGAGGCTCCGGTGGCTCCGGGGGCTCT
    GGACAGGTGCAGCTTCAGGAGAGTGGTGGCGGGCTGGTGCAGCCTGGCGGTTCC
    CTTCGTCTCTCTTGTGCAGCCAGCGGATTCACATTTAGTCACAGCGGCATGAGT
    TGGGTTCGGCAAGCACCTGGGAAGGGGCTGGAGTGGGTATCCACAATCAACAGC
    GGAGGTGCCAGCACGTACTATACCGACTCAGTTAAAGGGCGCTTCACCATTAGT
    CGCGACAACGCGAAGAATATGCTGTACTTGCAGCTGAACAGCCTGAAGACCGAG
    GACACTGCCATGTACTATTGCGCCAAAGGGGGCAGCGGCTACGGAGATGCGAGC
    CGTATGACTTCACCTGGGAGCCAGGGCACCCAGGTGACCGTCTCCTCT
    DR596- 1195 CAGGTGCAGCTTCAGGAGTCTGGGGGAGGCCTGGTACAACCCGGTGGCAGTCTC
    hIL27 AGGCTCAGCTGCACAGCCTCCGGCCTGACCTTCGACGATTCCGTGATGGGCTGG
    Ra_VH TTTAGGCAGGCCCCAGGTAAAGGCCGGGAGGCTGTAAGCTGCATTAGCTCCTCT
    H1 GGAGCCAACGCCTTCTACGCTGATTCTGTGAAGGGGCGTTTTACCATTTCTCGC
    GACAACGCCAAGAACACCTTGTATTTGCAGATGAACTCCCTGAAACCCGAGGAC
    ACCGCCACCTACTATTGTAAGCGTGGCCACGCTTGTGCGGGTTATTACCCCATT
    CCCTACGATGACTATTGGGGTCAGGGTACGCAAGTCACCGTATCTTCCGGCGGA
    GGCTCCCAGGTGCAGCTCCAGGAGTCAGGGGGCGGACTGGTGCAGCCCGGAGGT
    TCCCTGCGGCTGTCTTGTGCGGCATCCGGCTTTACTTTCTCTTCCTACCCCATG
    AGCTGGGTCCGCCAAGCGCCAGGGAAGGGTCTGGAGTGGATTTCTACAATCTCA
    GCTGGAGGCGACACTACCCTCTACGCTGACTCTGTTAAAGGCCGCTTCACTAGC
    AGTCGGGATAACGCCAAGAACACGCTGTACCTCCAGCTTAATAGCTTGAAAACC
    GAGGACGCGGCCATCTATTACTGCGCCAAGCGTATTGACTGTAACTCTGGATAC
    TGCTATCGTCGCAACTATTGGGGTCAGGGGACCCAAGTTACAGTGAGTTCT
    DR596- 1196 CAGGTTCAGCTTCAGGAGAGTGGCGGGGGCCTGGTTCAGCCCGGCGGTTCCCTT
    hIL27 CGCCTGAGCTGTACGGCAAGCGGTCTGACATTTGACGATTCCGTGATGGGCTGG
    Ra_VH TTTCGTCAGGCTCCTGGCAAGGGTAGGGAGGCGGTGAGTTGCATCAGCTCCAGC
    H1 GGAGCCAACGCCTTTTACGCGGATAGCGTCAAGGGAAGGTTTACCATCAGCCGG
    GACAATGCTAAGAACACCCTGTACTTGCAGATGAACAGTCTGAAACCAGAGGAC
    ACCGCAACTTATTACTGCAAGCGCGGCCACGCTTGCGCGGGCTATTACCCGATT
    CCCTATGACGATTACTGGGGCCAGGGCACTCAGGTGACAGTCAGCTCTGGCGGA
    AGTGGCGGAAGCGGCGGTTCTGGCCAGGTTCAGTTGCAGGAGAGCGGAGGTGGC
    CTGGTCCAGCCCGGTGGCTCTCTGCGCCTGAGCTGCGCCGCTTCCGGTTTCACT
    TTCTCTAGCTATCCCATGAGTTGGGTGCGTCAGGCTCCAGGCAAGGGACTGGAG
    TGGATCAGTACCATCTCAGCTGGGGGCGACACCACATTGTACGCCGATTCTGTG
    AAGGGCAGATTTACCTCCTCTCGCGATAATGCCAAGAACACCCTGTATCTCCAG
    TTGAACTCTCTGAAGACCGAGGACGCTGCCATCTACTATTGCGCCAAGCGTATC
    GACTGTAATTCCGGCTACTGTTACCGTCGGAACTACTGGGGACAAGGCACCCAG
    GTTACCGTTAGCTCC
    DR596- 1197 CAGGTCCAACTGCAAGAATCCGGTGGGGGTCTGGTTCAGCCCGGTGGCTCACTG
    hIL27 CGCCTGTCATGTACCGCCAGCGGCCTGACTTTCGATGACAGTGTCATGGGATGG
    Ra_VH TTTCGCCAGGCCCCTGGAAAGGGAAGGGAAGCGGTCAGCTGTATTTCTTCCAGC
    H2 GGGGCTAATGCCTTCTACGCTGACTCCGTGAAAGGTCGGTTTACCATCAGTAGG
    GATAATGCCAAGAACACCTTGTACTTGCAGATGAACTCCCTGAAACCTGAGGAC
    ACCGCCACCTATTACTGTAAGCGTGGCCACGCCTGCGCTGGCTACTATCCCATC
    CCATACGATGACTACTGGGGCCAGGGTACTCAGGTAACTGTTAGCTCTGGAGGG
    GGCTCCCAGGTGCAGCTTCAGGAATCTGGTGGCGGACTGGTCCAGCCTGGGGGT
    TCCCTTCGTCTGAGCTGCGCAGCCTCTGGTTTCACTTTTAGCCTGAGCGGTATG
    AGCTGGGTGAGGCAGGCCCCTGGCAAGGGTCTGGAGTGGGTCAGCGCGATCTCC
    AGCGGCGGTGCCTCTACCTACTATACAGATTCCGTGAAGGGCAGATTCACTATC
    TCCAGAGATAACGCTAAAAACATCCTCTACCTGCAACTGAACTCCCTCAAGACC
    GAGGATACTGCCATGTATTACTGTGCAAAGGGAGGCTCTGGTTATGGTGATGCC
    AGTCGGATGACCTCCCCTGGCTCCCAGGGAACACAGGTTACGGTCTCATCC
    DR596- 1198 CAGGTCCAGCTTCAGGAGAGTGGCGGGGGACTGGTACAGCCCGGAGGCTCCCTG
    hIL27 AGACTGAGTTGCACCGCCAGTGGTCTGACATTCGATGACAGCGTGATGGGCTGG
    Ra_VH TTCAGACAGGCCCCCGGCAAAGGCCGCGAGGCCGTTAGCTGTATCTCTAGTAGC
    H2 GGGGCCAACGCTTTTTACGCTGACTCTGTTAAGGGCAGGTTCACCATTTCCCGC
    GACAATGCGAAGAACACCCTGTACTTGCAGATGAACAGTCTGAAACCCGAAGAC
    ACGGCTACTTACTATTGTAAGAGGGGTCACGCCTGCGCCGGTTATTACCCCATT
    CCCTACGATGACTATTGGGGGCAAGGGACCCAGGTCACAGTCTCCAGCGGCGGG
    TCCGGCGGTAGCGGGGGCTCCGGCCAGGTGCAGCTGCAAGAGTCCGGGGGCGGT
    CTTGTTCAGCCAGGTGGCTCTCTGCGGCTGTCCTGCGCGGCCTCTGGATTCACA
    TTCTCTCTCAGTGGCATGTCTTGGGTGCGCCAGGCTCCGGGCAAGGGCCTCGAA
    TGGGTGTCCGCCATCTCCAGCGGTGGCGCTTCCACTTATTACACCGATTCTGTG
    AAGGGACGCTTCACCATCTCTAGGGACAACGCGAAGAACATTTTGTATCTCCAA
    CTGAACAGTCTTAAAACCGAGGACACTGCCATGTATTACTGTGCTAAGGGTGGG
    TCTGGCTACGGAGATGCGTCCAGGATGACGAGCCCAGGCTCCCAGGGCACCCAG
    GTGACCGTGTCCTCT
    DR596- 1199 CAGGTCCAGCTCCAGGAGTCCGGTGGGGGCCTCGTTCAGCCCGGCGGATCTCTG
    hIL27 AGGCTGAGCTGTACCGCCTCTGGCCTGACCTTCGACGATTCCGTGATGGGCTGG
    Ra_VH TTCAGACAGGCTCCCGGCAAGGGCCGCGAAGCTGTCTCCTGCATCTCCTCTTCC
    H3 GGCGCAAATGCGTTCTACGCCGACTCAGTGAAGGGCCGTTTTACCATTTCTCGG
    GATAACGCTAAAAACACGCTGTATCTGCAAATGAACTCCTTGAAACCGGAGGAT
    ACCGCCACCTATTACTGCAAACGCGGTCATGCCTGTGCTGGGTATTACCCAATC
    CCTTACGATGACTATTGGGGCCAAGGCACCCAGGTCACCGTCAGTAGCGGCGGT
    GGCTCCCAGGTTCAGTTGCAGGAATCAGGCGGGGGCTCCGTCCAAGCCGGAGGC
    TCTCTGCGTCTGTCATGTGTAGCCAGTGGCTACGTGTCATGCGATTACTTCCTG
    CCTTCCTGGTATAGACAGGCTCCCGGCAAGGAGCGCGAGTTCGTGAGCATTATC
    GACGGCACGGGTTCCACGTCCTACGCTGCCTCCGTTAAGGGTCGCTTTACAGCT
    AGTGAGGACAAGGGCAAGAACATTGCGTACCTCCAGATGAACTCCCTGAAGCCT
    GAAGATACAGCCATGTACTATTGCAAGGCCAGCTGTGTGAGGGGCCGCGCTGTT
    TCAGAATACTGGGGCCAGGGCACCCAGGTCACTGTTTCTTCT
    DR596- 1200 CAGGTTCAGTTGCAGGAATCCGGGGGCGGATTGGTCCAGCCAGGAGGCTCCCTT
    CGCCTGAGCTGCACTGCCTCTGGACTGACATTTGACGATTCTGTTATGGGCTGG
    hIL27 TTCCGCCAAGCACCAGGAAAGGGCAGAGAGGCAGTGTCTTGTATCTCTTCCAGC
    Ra_VH GGAGCCAATGCGTTTTATGCTGACAGCGTGAAGGGCAGGTTCACCATCTCACGC
    H3 GACAACGCTAAGAACACCCTCTATCTTCAGATGAACTCTCTCAAACCTGAGGAT
    ACCGCCACCTATTACTGTAAACGCGGACATGCTTGCGCCGGTTACTATCCTATC
    CCCTATGATGACTACTGGGGGCAGGGCACCCAGGTGACCGTGTCAAGCGGGGGA
    TCAGGAGGCAGCGGAGGCAGCGGCCAGGTCCAACTTCAGGAGTCAGGAGGCGGT
    TCTGTGCAGGCCGGAGGCTCACTGCGGCTGTCCTGTGTGGCGAGTGGCTACGTA
    AGCTGCGACTACTTCCTGCCTTCTTGGTACAGGCAGGCCCCTGGCAAAGAGAGG
    GAATTTGTGTCCATCATTGATGGTACAGGCAGCACCTCCTATGCGGCCTCCGTT
    AAGGGCAGATTTACTGCCTCCGAGGACAAGGGCAAGAATATCGCCTATCTCCAG
    ATGAACTCCCTGAAGCCGGAAGATACCGCAATGTACTATTGCAAAGCCAGTTGT
    GTGAGAGGGAGAGCGGTAAGTGAGTATTGGGGTCAGGGCACTCAGGTGACGGTT
    TCCAGC
    DR596- 1201 CAGGTGCAACTTCAGGAGTCTGGAGGCGGACTGGTCCAGCCTGGGGGCTCTCTG
    hIL27 CGTCTGTCTTGCACCGCCTCCGGCCTGACGTTTGATGACTCAGTCATGGGGTGG
    Ra_VH TTCCGCCAAGCCCCTGGGAAGGGCAGGGAGGCCGTCAGCTGCATCTCTAGCTCC
    H4 GGGGCCAACGCTTTCTACGCGGATAGCGTCAAGGGCCGCTTCACCATCAGTAGA
    GATAACGCAAAAAACACTTTGTATCTCCAGATGAACAGCCTGAAACCCGAGGAT
    ACCGCAACGTATTACTGTAAGCGCGGACACGCTTGTGCGGGCTATTACCCTATT
    CCCTATGATGACTACTGGGGTCAGGGCACTCAAGTCACCGTCAGTTCTGGCGGA
    GGTTCTCAGGTACAGCTCCAGGAGTCTGGCGGGGGCCTGGTGCAGCCCGGCGAA
    TCTCTGAGACTGTCATGCACCGCATCCGGCTTTACCTTCTCTAATTACGCCATG
    AGCTGGGTCAGACAGGCCCCTGGTAAGGGGCTGGAGTGGGTCAGTGGAATCAAC
    GTGGCCTATGGGATCACCTCCTACGCGGACTCCGTCAAGGGTAGATTTACAATC
    TCTCGCGACAACACCAAGAACACCCTGTACCTTCAGCTGAACTCACTCAAAACC
    GAAGACACCGCGATCTATTACTGTGTGAAACACTCAGGTACAACCATCCCCAGA
    GGATTCATCTCATACACAAAACGCGGCCAGGGTACTCAGGTAACCGTGTCCTCA
    DR596- 1202 CAGGTCCAGCTCCAGGAGAGCGGCGGGGGCCTGGTGCAGCCTGGCGGTTCCCTG
    hIL27 CGGCTCAGCTGTACCGCCTCCGGGCTGACGTTCGACGATTCTGTGATGGGCTGG
    Ra_VH TTTCGCCAGGCCCCCGGCAAGGGACGCGAAGCTGTAAGCTGCATTAGTTCCTCT
    H4 GGAGCGAATGCCTTCTACGCCGACTCTGTGAAGGGCCGCTTCACAATCTCCCGC
    GACAACGCTAAGAACACGCTGTACCTTCAGATGAACTCTCTGAAACCCGAGGAT
    ACTGCCACCTACTATTGCAAGCGCGGCCATGCCTGTGCTGGGTACTATCCAATC
    CCGTATGACGATTACTGGGGCCAAGGGACCCAGGTCACCGTAAGTTCAGGAGGT
    AGCGGTGGCTCTGGGGGCTCTGGTCAAGTACAGTTGCAGGAAAGTGGCGGGGGT
    CTGGTTCAGCCAGGCGAGTCATTGAGATTGTCTTGTACGGCTAGTGGATTCACA
    TTTAGTAACTACGCCATGAGCTGGGTCCGTCAAGCACCTGGCAAGGGCCTGGAG
    TGGGTATCCGGTATTAACGTGGCCTACGGAATTACAAGTTATGCAGACTCTGTG
    AAGGGCAGGTTCACAATCTCTCGGGACAACACCAAGAACACGCTGTACCTTCAG
    CTGAACTCTCTGAAAACCGAAGATACTGCTATCTATTACTGCGTGAAGCACAGC
    GGCACAACCATCCCACGCGGTTTCATCTCTTATACCAAGAGAGGCCAGGGCACC
    CAAGTCACCGTGTCATCC
    DR596- 1203 CAGGTGCAACTCCAGGAGTCCGGCGGTGGCCTCGTGCAACCGGGTGGCTCCTTG
    hIL27 AGACTGTCTTGTACCGCCAGCGGACTTACCTTCGACGATTCTGTGATGGGCTGG
    Ra_VH TTCCGGCAAGCGCCGGGCAAGGGCAGAGAGGCCGTGAGCTGCATCTCTAGTTCT
    H5 GGTGCTAACGCTTTTTACGCCGACTCCGTGAAAGGCCGTTTCACGATTTCAAGA
    GATAACGCCAAAAACACTCTCTACCTCCAGATGAACTCCCTCAAGCCTGAGGAC
    ACTGCCACCTATTACTGTAAGCGGGGCCACGCTTGCGCAGGCTATTACCCTATT
    CCCTATGACGATTACTGGGGCCAGGGTACACAGGTGACGGTGTCCAGTGGCGGA
    GGGTCACAAGTTCAACTTCAGGAGAGCGGCGGAGGGTCTGTCCAGGCTGGTGGC
    TCCCTGCGTCTCTCCTGTACCGCCTCCGGCTACGTGTCATGTGATTACTTTCTG
    CCTTCCTGGTACAGGCAAGCACCCGGTAAGGAGCGCGAATTTGTCAGCGTTATT
    GACGGCACGGGTAGTACGTCCTATGCTGCCTCCGTGAAGGGCCGCTTCACGGCA
    TCCCAGGACAAGGGGAAAAATATCGCATACCTCCAAATGAACAGTCTGAAGCCG
    GAGGATACAGCTATGTATTACTGCAAGGCTTCATGTGTGCGCGGAAGAGCTATT
    AGTGAGTATTGGGGCCAGGGTACACAGGTAACGGTCAGCTCC
    DR596- 1204 CAGGTCCAGTTGCAGGAGAGCGGCGGTGGCTTGGTGCAGCCCGGTGGGTCACTG
    hIL27 AGACTGTCCTGCACTGCAAGCGGCCTTACGTTCGATGACAGCGTGATGGGGTGG
    Ra_VH TTCCGCCAGGCACCCGGCAAGGGACGTGAGGCCGTGTCCTGCATTAGCTCATCC
    H5 GGCGCTAATGCCTTTTATGCCGACAGCGTCAAGGGCAGATTTACCATCTCTCGC
    GACAATGCCAAAAATACCCTGTATCTTCAAATGAATAGCCTGAAGCCAGAGGAT
    ACCGCTACTTACTATTGTAAGCGCGGCCACGCCTGCGCGGGCTATTACCCTATC
    CCCTACGATGACTATTGGGGCCAGGGTACTCAAGTGACTGTGAGTTCCGGTGGC
    TCCGGCGGGTCTGGAGGCTCAGGTCAAGTCCAGTTGCAGGAGTCCGGGGGCGGT
    AGCGTGCAGGCGGGCGGTTCCCTGCGCCTGTCTTGTACCGCATCTGGGTACGTC
    TCCTGCGATTACTTCCTGCCTTCCTGGTACAGGCAGGCCCCTGGCAAGGAGCGT
    GAGTTTGTGTCCGTGATCGACGGGACAGGTTCCACCTCCTACGCTGCATCCGTT
    AAGGGTCGCTTTACAGCCAGCCAGGACAAAGGAAAGAACATCGCTTACCTGCAA
    ATGAACTCCCTGAAACCTGAGGATACCGCTATGTATTACTGCAAGGCCTCCTGC
    GTCCGTGGCCGTGCGATCTCCGAATACTGGGGCCAGGGCACCCAGGTGACTGTT
    AGCAGC
    DR596- 1205 CAGGTGCAGTTGCAGGAGTCTGGGGGAGGTCTCGTGCAGCCAGGAGGGTCACTC
    hIL27 CGCCTGAGTTGTACTGCCAGCGGTTTGACATTCGACGATTCTGTCATGGGCTGG
    Ra_VH TTTCGCCAAGCTCCAGGGAAGGGCCGCGAGGCTGTGTCCTGCATCTCATCCTCT
    H6 GGGGCCAACGCTTTTTACGCTGATTCTGTCAAAGGCCGCTTCACAATCAGCCGG
    GACAACGCCAAGAACACTTTGTATCTCCAAATGAACAGCCTGAAGCCTGAGGAC
    ACTGCAACCTATTACTGTAAGCGCGGACACGCCTGCGCTGGCTATTACCCCATC
    CCTTACGACGATTATTGGGGTCAAGGAACTCAGGTTACTGTTAGCTCCGGCGGG
    GGCAGCCAGGTGCAGCTTCAGGAGTCAGGTGGAGGTCTGGTGCAACCTGGAGGC
    TCCCTGCGCCTGTCCTGTGCCGCATCCGGCTTTAGTTTCTCTAGCTACGCAATG
    AAATGGGTGCGTCAAGCCCCAGGCAAAGGTCTGGAGTGGGTGTCCACCATCAGT
    AGCGGTGGCTCCAGCACGAACTACGCCGACTCCGTGAAAGGCCGGTTCACCATC
    AGCCGTGATAACGCTAAGAACACGCTGTACCTCCAGCTGAACTCTCTGAAGATC
    GAGGACACGGCAATGTATTACTGTGCAAAGGCAATCGTTCCAACTGGTGCCACT
    ATGGAGAGGGGGCAGGGAACCCAAGTCACCGTTAGCTCC
    DR596- 1206 CAAGTGCAGCTCCAAGAAAGCGGCGGAGGCCTGGTGCAGCCTGGCGGTTCTCTG
    hIL27 AGACTGAGCTGTACTGCCTCAGGTCTGACTTTTGACGATTCTGTCATGGGATGG
    Ra_VH TTTAGACAAGCTCCAGGCAAGGGTCGTGAGGCGGTGAGCTGTATTAGCTCCTCT
    H6 GGCGCGAACGCATTTTATGCCGATTCCGTTAAGGGTCGCTTCACAATCTCACGG
    GACAACGCGAAGAATACACTGTACCTGCAAATGAACTCCCTGAAGCCCGAGGAC
    ACAGCTACCTATTACTGCAAGCGCGGCCACGCCTGTGCAGGTTATTACCCTATT
    CCCTATGATGACTACTGGGGACAAGGGACTCAGGTTACCGTCAGCTCCGGTGGC
    AGCGGCGGATCTGGTGGCTCCGGCCAGGTGCAGCTTCAGGAGTCCGGGGGAGGC
    CTGGTGCAGCCGGGCGGTTCATTGCGCCTTTCTTGCGCCGCGAGTGGCTTCTCC
    TTTTCCAGCTATGCCATGAAGTGGGTCCGCCAGGCTCCTGGGAAGGGCCTGGAG
    TGGGTGTCCACCATCTCCTCTGGGGGCTCCAGTACCAACTACGCCGACAGCGTG
    AAGGGTCGCTTCACTATCAGCAGAGATAACGCTAAGAACACACTGTACCTCCAG
    CTGAATAGCCTGAAGATCGAGGATACGGCTATGTATTACTGTGCCAAGGCGATT
    GTGCCTACAGGAGCCACTATGGAACGCGGCCAAGGCACCCAGGTGACGGTGTCA
    AGC
    DR596- 1207 CAGGTGCAACTTCAAGAATCTGGAGGTGGACTGGTCCAGCCTGGCGGTTCTCTG
    hIL27 CGCCTCTCTTGTACTGCTTCCGGCCTCACATTTGACGATTCTGTTATGGGATGG
    Ra_VH TTCAGACAGGCCCCAGGTAAGGGTCGCGAGGCCGTGAGTTGTATCAGCTCCAGC
    H7 GGCGCTAACGCATTCTATGCCGACAGTGTCAAGGGACGCTTTACAATCTCCAGG
    GACAACGCCAAAAACACGCTCTACCTTCAGATGAACTCACTGAAGCCCGAGGAT
    ACTGCTACCTATTACTGCAAACGCGGTCATGCTTGTGCCGGTTATTACCCCATC
    CCATACGATGACTACTGGGGCCAGGGGACCCAGGTAACCGTCAGCTCCGGCGGT
    GGATCACAGGTGCAGCTTCAGGAGAGTGGTGGAGGTCTCGTGCAACCTGGAGGT
    AGTCTCCGCTTGTCTTGTGCTGCCTCCGGTTTCACCTTTTCCAGCTACCCCATG
    AGTTGGGTGCGCCAAGCGCCGGGGAAGGGCCTGGAGTGGATTTCAACTATCAGC
    GCTGGAGGCGATACCACACTGTACGCCGATAGTGTTAAGGGAAGGTTCACTTCC
    TCTAGGGATAACGCCAAGAACACCCTGTATCTTCAGCTGAACAGTCTGAAGACG
    GAGGACACTGCTATCTATTACTGCGCAAAACGCATTGATTGCAACTCCGGCTAT
    TGCTACCGCCGGAACTACTGGGGCCAGGGGACCCAGGTGACAGTCAGTTCC
    DR596- 1208 CAGGTACAGCTCCAGGAGAGCGGCGGTGGCCTGGTACAGCCAGGGGGTTCATTG
    hIL27 CGTCTGAGCTGCACTGCTTCTGGTCTGACGTTTGATGACTCTGTTATGGGCTGG
    Ra_VH TTCCGCCAAGCGCCCGGCAAGGGACGGGAAGCTGTTAGCTGTATCTCCAGTTCT
    H7 GGGGCCAACGCCTTCTACGCCGATTCTGTGAAGGGTCGCTTCACTATCTCACGC
    GACAACGCCAAGAACACCCTGTACCTTCAGATGAACAGTCTGAAGCCTGAGGAT
    ACCGCCACCTACTATTGCAAGCGCGGCCATGCGTGCGCGGGCTATTACCCTATC
    CCTTACGATGACTATTGGGGGCAGGGCACCCAGGTGACTGTGTCCAGTGGAGGC
    TCCGGTGGCAGTGGAGGGTCCGGCCAGGTCCAACTCCAGGAGTCTGGTGGGGGC
    TTGGTCCAGCCTGGGGGTAGCTTGCGCCTGTCTTGCGCTGCCTCCGGGTTCACC
    TTCTCTAGTTATCCTATGTCTTGGGTGCGGCAAGCGCCGGGTAAGGGCCTGGAG
    TGGATTTCTACTATCTCTGCTGGCGGTGACACCACGTTGTACGCAGATTCCGTG
    AAGGGGCGTTTCACCTCCTCAAGAGACAATGCGAAGAACACCTTGTACCTCCAG
    CTGAACAGCCTGAAGACCGAGGACACCGCTATTTACTATTGTGCCAAGCGTATT
    GATTGTAATAGCGGTTATTGCTACCGCAGGAACTACTGGGGCCAGGGCACACAG
    GTCACCGTGAGCAGT
    DR596- 1209 CAGGTGCAACTCCAGGAAAGCGGTGGCGGGCTTGTGCAGCCCGGCGGTAGCCTG
    hIL27 CGGCTGAGTTGTACTGCAAGCGGTCTCACCTTCGACGATAGTGTAATGGGTTGG
    Ra_VH TTTCGTCAAGCACCCGGAAAGGGAAGGGAGGCGGTGTCTTGCATCTCCAGCAGT
    H8 GGCGCGAATGCGTTTTATGCCGATTCCGTCAAGGGGCGGTTTACGATCTCCAGG
    GATAACGCCAAGAACACGCTGTACCTCCAGATGAACAGTCTGAAGCCCGAGGAT
    ACGGCCACATATTACTGTAAGCGCGGGCACGCCTGTGCCGGATACTATCCCATC
    CCTTATGACGATTATTGGGGTCAAGGTACGCAGGTCACAGTTAGCTCTGGCGGA
    GGTTCCCAGGTCCAACTTCAGGAGTCCGGTGGAGGGTCCGTTCAGGTGGGCGGA
    TCTCTTCGCCTGAGCTGCGCGGCCAGCGGATTTACCTTCAGCTCCTACCCAATG
    AGTTGGGTGCGTCAGGCTCCGGGTAAGGGCCTGGAGTGGATCTCTACCATTAGT
    GCTGGCGGAGACACCACGCTGTACGCCGACAGCGTGAAGGGGCGCTTCACCTCC
    TCTCGCGATAACGCAAAGAATACCCTGTACCTCCAGCTCAATTCCTTGAAGACC
    GAAGATACGGCCATTTATTACTGCGCCAAGCGCATTGATTGCAATAGCGGCTAT
    TGCTATCGGAGGAACTACTGGGGACAGGGAACCCAAGTCACTGTTTCATCC
    DR596- 1210 CAGGTCCAGCTCCAAGAGTCAGGAGGCGGACTCGTGCAACCGGGTGGCTCCCTG
    hIL27 AGGCTGTCTTGTACCGCAAGCGGCCTGACCTTCGATGACAGTGTCATGGGCTGG
    Ra_VH TTCAGGCAGGCCCCCGGCAAAGGCCGTGAGGCCGTCAGCTGTATCAGTTCTAGT
    H8 GGAGCCAACGCCTTTTACGCCGATTCCGTAAAGGGCCGTTTCACCATTTCAAGG
    GACAATGCCAAGAATACCCTGTATCTGCAAATGAACTCCCTCAAGCCCGAAGAT
    ACCGCCACCTACTATTGCAAGCGCGGACATGCCTGTGCCGGTTATTACCCCATT
    CCCTATGACGATTATTGGGGTCAGGGAACCCAGGTGACCGTGTCCAGTGGAGGG
    TCCGGGGGCTCTGGCGGGTCCGGCCAGGTGCAGTTGCAGGAGTCAGGGGGTGGG
    AGCGTCCAGGTTGGGGGTAGTCTGCGCCTGTCTTGTGCAGCCTCTGGGTTCACC
    TTCAGCTCCTACCCCATGAGCTGGGTGCGCCAGGCTCCGGGAAAAGGTCTTGAG
    TGGATCTCTACAATCTCCGCCGGTGGCGACACTACCCTGTACGCTGACAGCGTG
    AAGGGCCGGTTTACAAGTTCTCGCGACAACGCCAAGAACACCTTGTACCTCCAG
    CTCAACTCCCTGAAGACCGAGGATACCGCCATTTATTACTGTGCAAAAAGGATT
    GATTGTAACTCCGGCTACTGTTATCGCAGAAATTACTGGGGCCAGGGGACCCAG
    GTTACAGTGTCTAGC
    DR596- 1211 CAGGTTCAGCTGCAAGAGAGCGGAGGGGGTCTCGTGCAGCCGGGTGGGAGCCTG
    hIL27 CGCCTTTCCTGTACTGCTTCTGGACTGACCTTCGATGACTCCGTGATGGGTTGG
    Ra_VH TTCCGGCAGGCCCCTGGAAAGGGCCGTGAAGCTGTGTCCTGTATCAGCTCTTCC
    H9 GGGGCGAATGCTTTCTACGCCGATAGCGTTAAGGGCCGCTTTACCATCTCCCGC
    GACAACGCAAAGAATACTCTGTACTTGCAGATGAACAGCCTCAAGCCCGAAGAC
    ACCGCCACTTATTACTGTAAGCGCGGCCACGCTTGCGCGGGTTACTATCCCATC
    CCTTACGATGACTACTGGGGACAGGGAACCCAGGTAACCGTGTCATCTGGCGGG
    GGCAGTCAGGTCCAGTTGCAGGAAAGCGGAGGTGGCAGCGTTCAGAGTGGCGGT
    TCCCTGCGTCTTAGCTGTGCAGCCTCCGGCTTTACATACAGCACTTCTAATTCC
    TGGATGGCCTGGTTCAGACAGGCCCCAGGCAAGGAACGCGAAGGCGTGGCTGCC
    ATTTACACGGTCGGAGGGTCCATCTTTTACGCCGATTCCGTGCGTGGCCGCTTT
    ACCATCTCCCAGGACGCTACTAAGAATATGTTCTACCTGCAAATGAATACCCTG
    AAACCGGAGGACACCGCCATGTACTATTGTGCCGCAGCGTCCGGTCGCCTGAGG
    GGGAAGTGGTTCTGGCCCTATGAATACAATTACTGGGGACAGGGCACCCAGGTT
    ACCGTGTCTTCA
    DR596- 1212 CAGGTACAGCTGCAAGAGAGCGGAGGCGGATTGGTGCAGCCCGGAGGCAGTTTG
    hIL27 AGGTTGAGCTGTACCGCTTCCGGCCTCACTTTCGATGACTCCGTCATGGGCTGG
    Ra_VH TTCCGCCAAGCACCTGGAAAGGGACGGGAAGCTGTCTCCTGCATCAGCAGTAGC
    H9 GGAGCCAACGCATTCTACGCTGACAGCGTCAAAGGCAGGTTCACAATTAGCCGT
    GATAATGCAAAGAACACTCTGTACCTGCAAATGAACTCTTTGAAGCCCGAGGAC
    ACCGCGACGTATTACTGCAAGAGAGGACATGCCTGTGCCGGTTATTACCCCATC
    CCCTACGATGACTATTGGGGACAGGGTACTCAGGTGACGGTGAGTTCCGGCGGT
    AGCGGTGGCAGTGGAGGGAGCGGTCAGGTGCAGTTGCAGGAGAGCGGGGGCGGA
    AGCGTGCAGTCCGGCGGGTCCCTGCGCCTTAGTTGCGCCGCTTCCGGCTTCACT
    TATAGCACCTCTAACTCTTGGATGGCTTGGTTTCGCCAGGCCCCCGGCAAGGAG
    AGAGAGGGCGTGGCTGCCATCTACACAGTGGGCGGAAGCATCTTTTACGCGGAT
    AGCGTGAGAGGCCGTTTCACAATCAGCCAGGATGCAACAAAGAATATGTTCTAT
    CTCCAGATGAACACACTGAAGCCCGAAGACACCGCTATGTATTACTGTGCTGCC
    GCTTCAGGACGCTTGAGGGGCAAATGGTTTTGGCCCTATGAATACAACTACTGG
    GGACAGGGCACCCAGGTGACTGTAAGCAGC
    DR596- 1213 CAGGTGCAGTTGCAGGAAAGCGGCGGAGGCCTGGTGCAGCCTGGCGGTTCCCTG
    hIL27 CGTCTTTCCTGTACTGCCTCAGGACTTACCTTCGATGACAGTGTGATGGGTTGG
    Ra_VH TTCCGTCAGGCCCCTGGTAAAGGGCGGGAAGCAGTCAGTTGTATCTCCAGCTCT
    H10 GGTGCAAACGCATTCTACGCCGACTCTGTCAAGGGACGTTTCACTATCAGTCGC
    GATAACGCTAAGAATACCCTGTACCTCCAGATGAACAGCCTGAAGCCTGAGGAT
    ACGGCTACCTATTACTGTAAACGGGGACACGCCTGTGCTGGCTACTATCCCATT
    CCATACGACGATTATTGGGGCCAGGGAACTCAGGTGACAGTGTCAAGCGGCGGT
    GGCTCACAGGTTCAGCTCCAGGAATCTGGCGGGGGCTCTGTCCAGGCAGGAGGC
    AGCTTGCGCCTGTCCTGTAGGGCAAGTGGAAGCACTTACTCCAACTACTGCCTG
    GGCTGGTTCCGCCAAATTACTGGTAAAGAGCGGGAAGGTGTCGCGGTCATTAAC
    TGGGTCGGCGGTATGCTGTATTTTGCTGATTCTGTGAAGGGTCGGTTCACTGTG
    TCCCAGGACCAGGCTAAGAACACCTTGTATCTGCAAATGAACAGCCTGAAGCCA
    GAGGATACCGCGATGTATTACTGCGCAGCCGAGAGCGTCTCTAGCTTTAGCTGC
    GGCGGTTGGCTGACCAGGCCGGATCGCGTGCCTTACTGGGGTCAAGGAACCCAG
    GTGACCGTCTCTTCA
    DR596- 1214 CAAGTCCAACTCCAGGAGTCCGGGGGTGGCCTCGTCCAGCCTGGTGGCTCCCTT
    hIL27 AGGCTGAGCTGCACTGCATCTGGCCTGACTTTCGATGACTCCGTCATGGGCTGG
    Ra_VH TTCCGCCAGGCTCCGGGAAAGGGACGCGAGGCCGTGTCTTGTATCAGCTCCAGT
    H10 GGTGCCAACGCTTTTTACGCTGACTCTGTAAAAGGCCGGTTCACTATCAGCCGC
    GACAACGCCAAAAACACCCTCTACTTGCAGATGAATAGCCTGAAGCCTGAGGAC
    ACCGCCACATACTATTGTAAACGTGGCCACGCTTGCGCCGGTTATTACCCTATC
    CCCTACGATGACTACTGGGGCCAGGGCACCCAGGTGACCGTGAGTTCCGGTGGC
    AGCGGCGGTTCTGGCGGATCAGGCCAGGTCCAACTTCAGGAAAGCGGAGGGGGC
    AGTGTTCAGGCTGGTGGCTCCCTGCGTCTGTCCTGCCGTGCTAGTGGCTCTACC
    TATTCTAACTACTGCCTCGGCTGGTTCCGCCAAATCACGGGTAAGGAGCGTGAG
    GGGGTTGCCGTCATAAATTGGGTGGGCGGGATGCTTTACTTCGCCGATAGTGTG
    AAGGGGCGTTTTACTGTGTCCCAGGACCAGGCAAAGAATACCCTGTACCTCCAA
    ATGAACTCTCTGAAGCCCGAAGACACAGCCATGTACTATTGTGCCGCAGAGAGC
    GTGTCATCCTTCTCTTGTGGCGGATGGCTGACCCGCCCTGATCGCGTGCCCTAC
    TGGGGTCAGGGCACCCAGGTGACCGTCTCATCC
    DR596- 1215 CAGGTGCAGCTCCAGGAATCAGGCGGGGGCCTCGTGCAGCCAGGGGGCAGCCTG
    hIL27 AGACTCTCTTGCACAGCCAGCGGACTCACCTTTGATGACAGCGTCATGGGCTGG
    Ra_VH TTCAGGCAGGCTCCCGGCAAAGGAAGGGAGGCCGTCTCCTGCATCTCTTCCTCT
    H11 GGTGCTAATGCCTTCTACGCTGACTCCGTCAAGGGCCGCTTTACTATCTCCCGC
    GACAACGCAAAGAACACTCTGTACCTCCAGATGAACTCCCTGAAGCCTGAGGAC
    ACCGCGACATATTACTGTAAGAGAGGCCACGCCTGTGCGGGCTATTACCCCATC
    CCCTACGATGACTATTGGGGTCAGGGCACGCAAGTTACAGTCTCCAGCGGGGGA
    GGTTCCCAGGTCCAGCTCCAGGAATCTGGCGGGGGCAGTGTCCAGGCCGGAGGC
    TCCCTGAGACTGAGCTGCCGGGCCTCCGGTTCCACATACTCCAACTACTGCCTG
    GGCTGGTTCCGCCAGTCCACAGGTAAAGAGAGAGAGGGCGTCGCAGTGATTAAC
    TGGGTTGGCGGAATGCTGTACTTTGCTGACTCCGTTAAGGGCCGCTTCACCGTC
    TCCCAGGATCACGCTAAGAACACTGTCACCTTGCAGATGAACTCATTGAAGCCC
    GAAGATACCGCCATGTACTATTGTGCTGCCGAGAGCGTTAGTTCATTTTCTTGC
    GGCGGTTGGCTGACGCGCCCAGGCCGCGTGCCCTACTGGGGCCAGGGAACGCAA
    GTGACCGTGTCATCC
    DR596- 1216 CAGGTACAGTTGCAGGAGTCCGGTGGGGGACTGGTCCAGCCCGGCGGATCACTG
    hIL27 CGCCTGAGCTGCACCGCATCCGGGCTGACCTTCGACGATAGCGTTATGGGTTGG
    Ra_VH TTCCGCCAGGCCCCAGGTAAGGGACGCGAAGCTGTCAGCTGCATTTCTTCCTCT
    H11 GGGGCCAATGCCTTCTATGCCGATTCTGTGAAAGGAAGATTCACCATCAGCCGC
    GACAATGCTAAGAATACTCTGTACCTCCAGATGAACAGCCTCAAGCCGGAGGAC
    ACTGCCACATATTACTGCAAGAGAGGTCATGCTTGCGCAGGTTATTACCCGATT
    CCCTACGACGATTATTGGGGCCAGGGGACCCAGGTTACGGTTTCTAGCGGAGGG
    AGCGGAGGGTCCGGTGGCAGTGGACAAGTTCAGCTCCAGGAAAGTGGCGGGGGC
    TCTGTCCAAGCCGGGGGCTCCCTGCGGCTCTCCTGCCGGGCTTCTGGCTCTACT
    TATTCTAACTATTGCTTGGGTTGGTTCCGTCAATCCACTGGGAAGGAGAGAGAG
    GGCGTGGCCGTTATAAATTGGGTTGGCGGGATGCTCTACTTCGCTGATTCCGTC
    AAAGGAAGGTTCACAGTGTCCCAGGACCACGCTAAGAACACTGTGACTCTGCAA
    ATGAACTCCCTGAAGCCAGAGGACACTGCTATGTATTACTGTGCCGCTGAGAGC
    GTCTCATCCTTCTCCTGCGGCGGGTGGCTGACCCGTCCTGGCCGTGTGCCTTAC
    TGGGGGCAGGGCACCCAGGTGACCGTCTCTAGT
    DR596- 1217 CAGGTGCAACTCCAGGAGAGCGGAGGTGGACTTGTTCAGCCCGGCGGAAGCCTT
    hIL27 CGCCTTTCATGCACTGCCAGCGGACTGACGTTCGATGACTCAGTCATGGGCTGG
    Ra_VH TTCAGGCAGGCCCCCGGTAAGGGCCGCGAAGCCGTGTCTTGTATCTCTAGCTCT
    H12 GGAGCAAACGCTTTCTACGCGGATTCCGTGAAGGGCCGTTTTACAATTAGCAGA
    GACAACGCCAAGAATACTCTGTACTTGCAGATGAACTCTCTGAAGCCTGAAGAT
    ACCGCTACCTATTACTGTAAGAGAGGCCATGCGTGTGCAGGGTATTACCCTATT
    CCTTACGACGATTACTGGGGTCAAGGAACCCAGGTAACCGTGTCTTCAGGCGGG
    GGTTCCCAGGTGCAGCTCCAGGAGTCCGGGGGAGGCAGTGTGCAAGCAGGCGAG
    AGCTTGCGTCTGAGTTGCCGCGCTTCCGGTTCAACTTACTCTAACTACTGTCTT
    GGATGGTTCCGCCAGATCACCGGCAAGGAGCGGGAGGGTGTGGCTGTCATCAAC
    TGGGTTGGGGGTATGCTTTACTTCGCAGACTCTGTGAAGGGCCGCTTTACCGTA
    TCACAGGACCAAGCAAAGAACACCGTGTACCTGGAGATGAACAGTCTGAAGCCC
    GAAGACACCGCTATGTACTATTGTGCCACCGAATCCGTCTCTTCCTTCTCCTGT
    GGAGGCTGGCTGACACGCCCCGACCGGGTGCCCTATTGGGGCCAGGGAACTCAG
    GTCACAGTCTCTAGT
    DR596- 1218 CAGGTCCAGCTCCAGGAGTCTGGCGGTGGGCTCGTGCAGCCCGGAGGCTCTTTG
    hIL27 AGGCTGAGCTGCACCGCGAGCGGCCTGACTTTCGACGATAGTGTGATGGGCTGG
    Ra_VH TTCCGTCAAGCCCCTGGCAAAGGCCGCGAGGCGGTTAGCTGTATCTCCTCTTCC
    H12 GGGGCCAATGCCTTCTATGCTGACAGCGTGAAGGGCCGCTTTACCATCAGCCGT
    GACAACGCCAAGAACACTCTTTACCTTCAGATGAACTCCTTGAAGCCGGAGGAC
    ACCGCGACATACTATTGTAAGCGCGGCCACGCTTGTGCAGGCTATTACCCCATC
    CCCTATGACGATTATTGGGGACAGGGCACCCAGGTGACCGTCTCCTCTGGGGGC
    AGCGGAGGCTCTGGTGGCTCCGGGCAGGTGCAGCTCCAGGAGTCCGGCGGTGGC
    TCCGTGCAGGCTGGCGAAAGCCTGCGCCTGTCCTGTCGTGCGTCCGGCAGTACA
    TATAGCAACTACTGTCTCGGATGGTTCCGTCAAATTACCGGGAAGGAACGCGAG
    GGAGTGGCCGTTATCAACTGGGTGGGAGGCATGTTGTATTTTGCCGACAGTGTG
    AAAGGCAGGTTTACAGTGAGCCAGGACCAGGCCAAGAACACGGTGTATCTCGAA
    ATGAACAGCCTGAAGCCCGAAGACACTGCAATGTATTACTGCGCCACCGAGTCT
    GTTAGCTCCTTTTCATGTGGTGGGTGGCTGACACGCCCAGACCGCGTGCCATAC
    TGGGGTCAGGGAACCCAGGTTACCGTGAGTAGT
    DR596- 1219 CAGGTGCAGTTGCAGGAGTCCGGTGGCGGACTCGTACAGCCAGGAGGTAGCCTT
    hIL27 CGCCTGAGTTGCACTGCCTCCGGTCTGACCTTCGATGACTCCGTTATGGGTTGG
    Ra_VH TTCCGCCAAGCCCCAGGGAAGGGCAGAGAAGCTGTCTCTTGTATCAGCTCTAGC
    H13 GGGGCCAACGCCTTCTACGCAGACTCCGTGAAGGGCCGCTTTACCATCAGTCGT
    GACAACGCCAAGAATACACTCTATTTGCAAATGAACTCTCTCAAGCCTGAGGAT
    ACCGCTACGTACTATTGCAAACGTGGACACGCTTGTGCCGGTTATTACCCTATC
    CCTTACGATGACTACTGGGGCCAGGGCACCCAGGTGACCGTGAGTAGCGGCGGA
    GGCTCTCAGGTGCAGCTCCAGGAGTCTGGTGGCGGGAGCGTCCAGGCCGGGGGC
    TCTCTGCGCCTGTCCTGCGTGGCTTCCGGGTATGTTTCCTGCGATTACTTTCTG
    CCCTCCTGGTATCGTCAGGCCCCTGGTAAGGAGCGCGAGTTCGTGAGCATCATT
    GATGGCACTGGATCTACTTCTTACGCAGCGAGTGTGAAGGGCCGCTTCACCGCC
    AGCCAGGATAGGGGAAAAAATATCGCATACCTCCAGATGAACAGCCTGAAGCCT
    GAGGACACTGCCATGTATTACTGCAAGGCGTCCTGTGTGAGGGGAAGGACTATC
    AGCGAGTATTGGGGCCAAGGTACGCAGGTGACAGTAAGCTCC
    DR596- 1220 CAAGTTCAACTTCAGGAGAGTGGTGGAGGCCTGGTGCAGCCAGGGGGTTCCCTC
    hIL27 AGGCTCAGCTGTACCGCAAGCGGTCTGACATTTGATGACTCCGTGATGGGATGG
    Ra_VH TTTCGCCAGGCACCCGGTAAGGGGCGTGAAGCCGTTAGTTGTATTAGTTCCAGC
    H13 GGAGCCAATGCTTTCTATGCCGACTCCGTGAAGGGTAGATTCACCATCTCCCGT
    GACAACGCCAAAAACACGCTGTATCTTCAGATGAACTCTCTGAAGCCGGAGGAC
    ACGGCCACCTATTACTGTAAGCGTGGTCATGCCTGCGCGGGGTATTACCCCATC
    CCCTACGATGACTACTGGGGGCAGGGAACCCAGGTCACTGTTTCCAGCGGTGGC
    TCCGGTGGCTCAGGAGGCAGTGGCCAGGTACAGTTGCAAGAGTCTGGCGGAGGC
    AGCGTTCAGGCTGGCGGGTCCCTCAGACTGTCATGCGTGGCATCTGGGTATGTT
    TCCTGCGACTACTTCCTTCCCAGTTGGTATCGTCAAGCGCCGGGTAAGGAACGC
    GAATTTGTGAGTATCATTGATGGGACCGGGTCTACCTCTTACGCCGCGAGCGTG
    AAGGGCCGCTTCACCGCGTCTCAGGATCGCGGTAAGAACATTGCCTACCTCCAG
    ATGAACAGTCTGAAACCAGAAGACACCGCTATGTATTACTGCAAGGCGAGCTGC
    GTGAGAGGCAGAACCATTTCTGAGTATTGGGGACAGGGAACTCAGGTGACCGTG
    TCTTCA
    DR596- 1221 CAGGTGCAGCTCCAGGAGTCAGGTGGCGGATTGGTGCAGCCCGGTGGCAGCTTG
    hIL27 CGCCTGTCCTGCACAGCGAGTGGCTTGACTTTCGACGATTCCGTCATGGGGTGG
    Ra_VH TTTAGACAGGCTCCTGGCAAGGGCCGTGAGGCAGTCTCCTGTATCTCTTCCAGT
    H14 GGTGCTAACGCTTTTTACGCCGATAGTGTTAAGGGGAGATTCACGATCTCTCGC
    GACAACGCCAAGAATACGCTCTACTTGCAGATGAACTCTCTCAAGCCTGAAGAT
    ACCGCCACCTATTACTGCAAGCGTGGTCACGCTTGCGCAGGCTATTACCCCATC
    CCCTACGACGATTACTGGGGCCAGGGCACCCAGGTGACCGTCAGTTCCGGTGGG
    GGAAGCCAGGTCCAGCTTCAGGAGTCCGGCGGTGGCTCCGTCCAGGCAGGTGGC
    TCCCTGCGCCTGTCTTGCGTGGCTTCTGGGTACGTGAGCTGCGACTACTTTCTC
    CCCTCTTGGTATCGCCAGGCCCCCGGAAAGGAGCGCGAGTTCGTTTCTATCATT
    GACGGCACTGGCTCCACCAGCTATGCTGCCAGCGTGAAAGGCCGCTTTACCGCC
    AGCCAGGACAAAGGCAAGAACATCGCTTACCTCCAGATGAACTCCCTGAAGCCC
    GAAGATACCGCGATGTATTACTGTAAGGCTTCATGCGTGCGCGGCAGAGCCATC
    TCCGAGTACTGGGGCCAAGGCACTCAAGTTACAGTCTCTTCA
    DR596- 1222 CAGGTGCAGTTGCAGGAGAGCGGTGGGGGCCTGGTGCAGCCCGGTGGCTCCCTG
    - CGTCTTTCTTGCACTGCGTCCGGCTTGACTTTTGACGATAGCGTCATGGGCTGG
    hIL27 TTCCGCCAGGCCCCTGGCAAAGGACGTGAGGCCGTGAGCTGCATCTCTTCAAGT
    Ra_VH GGAGCCAACGCATTCTATGCTGACTCCGTGAAAGGCCGCTTCACCATCAGTCGG
    H14 GACAACGCCAAGAACACCCTCTACTTGCAGATGAACTCCCTGAAGCCCGAGGAC
    ACCGCCACCTATTACTGTAAGCGCGGCCACGCTTGCGCTGGCTATTACCCGATC
    CCATACGATGACTACTGGGGACAAGGCACCCAGGTTACCGTGTCTTCCGGGGGC
    TCTGGTGGCTCAGGGGGCTCTGGCCAGGTCCAACTCCAAGAGTCTGGGGGAGGC
    TCTGTGCAGGCGGGTGGCTCCCTGCGTCTGAGCTGCGTAGCTTCCGGTTACGTC
    TCCTGCGATTACTTCCTGCCCTCCTGGTATAGGCAGGCTCCCGGCAAGGAGCGC
    GAGTTTGTCTCTATTATCGACGGTACAGGCTCTACCTCTTACGCCGCAAGCGTG
    AAGGGCCGGTTCACAGCCTCTCAGGATAAGGGTAAAAACATCGCCTACTTGCAG
    ATGAACAGCCTTAAACCAGAGGACACCGCCATGTACTATTGTAAGGCAAGCTGC
    GTGAGGGGCCGCGCCATCAGCGAGTACTGGGGCCAGGGAACGCAGGTGACCGTC
    AGCAGC
    DR596- 1223 CAGGTCCAGCTCCAGGAGTCCGGGGGTGGCCTGGTCCAGCCCGGCGGGTCTCTG
    hIL27 AGACTGTCCTGTACGGCAAGCGGGCTGACCTTCGATGACTCCGTCATGGGCTGG
    Ra_VH TTTCGTCAAGCCCCTGGTAAGGGCCGCGAGGCGGTTTCTTGCATCAGCTCTTCA
    H15 GGCGCGAATGCGTTCTACGCCGACTCTGTGAAGGGTCGGTTTACTATCAGCCGC
    GATAATGCGAAGAACACACTGTACTTGCAAATGAACTCCCTGAAGCCTGAGGAC
    ACAGCCACTTATTACTGCAAACGTGGACACGCCTGCGCTGGCTATTACCCAATC
    CCTTACGACGATTACTGGGGCCAGGGCACCCAAGTGACCGTGAGTTCCGGCGGT
    GGCTCCCAAGTCCAGCTCCAGGAAAGTGGTGGCGGGTCCGTGCAGGCGGGAGGC
    AGCCTTAGGCTCTCTTGCGTCGCCTCTGGGTACGTCTCTTGCGACTATTTCCTC
    CCTTCCTGGTATCGCCAAGCGCCGGGCAAGGAGCGCGAGTTCGTCTCCATCATT
    GATGGCACCGGCTCCACCTCCTACGCTGCCTCCGTGAAAGGCCGCTTCACTGCC
    TCCCAGGACAAGGGGAAAAACATCGCCTACTTGCAGATGAACACCCTTAAACCC
    GAAGACACGGCCATGTATTACTGTAAAGCGTCCTGCGTGAGGGGAAGAGCAATC
    TCCGAGTACTGGGGCCAGGGGACCCAGGTGACAGTGTCCTCA
    DR596- 1224 CAGGTGCAGTTGCAGGAGTCCGGTGGCGGACTGGTACAGCCCGGCGGTTCCTTG
    hIL27 AGGCTGAGTTGTACCGCTTCCGGCTTGACTTTCGATGACTCAGTGATGGGATGG
    Ra_VH TTCAGACAAGCGCCCGGTAAGGGTCGCGAGGCGGTCAGTTGCATCAGCTCCAGT
    H15 GGAGCCAATGCGTTCTACGCTGATTCTGTGAAAGGACGTTTCACCATCTCCAGG
    GACAATGCTAAGAATACACTGTACCTTCAGATGAACAGCCTGAAGCCTGAAGAT
    ACAGCTACGTATTACTGCAAGCGCGGACACGCTTGTGCAGGATATTACCCAATT
    CCTTATGATGACTACTGGGGTCAGGGGACCCAGGTGACTGTATCCAGCGGGGGC
    TCCGGCGGAAGCGGAGGCAGTGGGCAGGTGCAGCTCCAGGAGTCCGGCGGAGGC
    TCAGTTCAGGCCGGAGGTTCACTCAGACTGTCATGTGTGGCCTCTGGCTACGTG
    TCCTGTGACTACTTCCTGCCAAGTTGGTATCGGCAGGCCCCTGGCAAGGAGCGG
    GAGTTCGTTAGCATTATCGACGGCACGGGCAGCACCAGTTACGCTGCCTCCGTG
    AAAGGCAGATTCACAGCATCTCAGGATAAGGGGAAAAATATCGCCTACCTCCAG
    ATGAACACTCTGAAGCCCGAGGACACCGCCATGTACTATTGTAAGGCTTCATGC
    GTGAGAGGCCGCGCCATTAGCGAGTACTGGGGCCAGGGAACCCAGGTTACTGTC
    AGTTCT
    DR596- 1225 CAGGTGCAGTTGCAGGAATCTGGCGGTGGACTGGTGCAGCCCGGAGGCTCACTG
    hIL27 CGCCTCTCTTGTACGGCCAGCGGACTCACTTTCGATGACAGCGTGATGGGGTGG
    Ra_VH TTCCGCCAGGCCCCTGGCAAAGGCCGCGAGGCTGTCTCCTGTATCTCCAGCAGT
    H16 GGTGCGAACGCCTTCTACGCTGACTCCGTGAAAGGCCGTTTCACCATCAGCCGT
    GATAACGCTAAGAACACACTCTACTTGCAGATGAACAGCCTGAAGCCGGAGGAC
    ACTGCCACCTATTACTGTAAGCGCGGTCACGCATGTGCTGGCTATTACCCTATT
    CCTTACGACGATTACTGGGGCCAGGGCACCCAGGTTACGGTGTCCTCTGGCGGG
    GGTAGCCAGGTGCAGCTTCAGGAGTCCGGTGGAGGTTCCGTGCAGGCAGGGGGA
    AGCCTTAGGCTGAGCTGCCGCGCTTCCGGTTCTACCTACAGCAATTACTGCCTG
    GGGTGGTTCCGGCAGATTACAGGTAAAGAGCGCGAGGGTGTCGCCGTGATTAAC
    TGGGTGGGCGGGATGCTTTACTTCGCTGATTCAGTGAAGGGCCGCTTCACTGTG
    AGTCAGGACCAGGCCAAGAACACAGTGTACCTCCAGATGAACTCCCTTAAACCC
    GAGGACACTGCAATGTACTATTGCGCTGCCGAGTCAGCGTCCTCTTTCAGTTGC
    GGCGGATGGCTCACTCGTCCTGACCGTGTCCCTTACTGGGGCCAGGGCACGCAG
    GTGACCGTCTCCTCC
    DR596- 1226 CAGGTGCAGTTGCAGGAGAGCGGCGGAGGCCTGGTCCAGCCCGGAGGCAGCCTG
    hIL27 AGACTTTCTTGCACAGCTTCCGGGCTTACCTTCGATGACTCCGTCATGGGCTGG
    Ra_VH TTTCGGCAGGCTCCAGGTAAGGGTAGGGAGGCTGTTAGCTGTATCAGTTCCAGC
    H16 GGCGCTAATGCCTTCTACGCCGACTCTGTGAAGGGCCGGTTTACCATCAGCAGA
    GACAACGCAAAAAATACGCTCTACTTGCAGATGAACTCTCTGAAGCCCGAAGAT
    ACCGCCACCTACTATTGCAAGAGGGGCCACGCCTGCGCCGGTTACTATCCAATC
    CCATACGATGACTACTGGGGCCAGGGTACTCAGGTGACTGTGTCTTCCGGTGGA
    AGCGGCGGAAGCGGCGGTAGCGGGCAGGTCCAGCTGCAAGAAAGCGGAGGCGGG
    TCTGTGCAAGCTGGCGGTTCCCTGAGGCTGAGCTGTCGTGCATCAGGCTCAACC
    TACTCTAACTACTGCTTGGGGTGGTTCCGCCAGATTACCGGCAAGGAGCGCGAG
    GGCGTGGCCGTCATCAACTGGGTAGGCGGGATGCTGTATTTCGCTGATTCCGTG
    AAGGGCCGCTTTACCGTCTCACAGGACCAGGCCAAGAACACCGTCTACCTTCAG
    ATGAACTCCCTGAAACCTGAAGATACTGCCATGTATTACTGTGCAGCGGAGAGC
    GCCAGCTCCTTCTCCTGTGGAGGGTGGCTGACCCGCCCGGATCGTGTTCCGTAC
    TGGGGCCAGGGGACTCAAGTGACCGTGTCCTCC
    DR596- 1227 CAGGTGCAGCTCCAGGAATCAGGGGGCGGACTGGTTCAGCCCGGAGGTTCTCTC
    hIL27 AGGCTCAGCTGCACTGCCTCCGGGCTTACTTTTGACGATAGCGTTATGGGCTGG
    Ra_VH TTCCGCCAGGCTCCCGGCAAAGGCCGCGAGGCCGTGTCTTGTATCTCCAGCTCC
    H17 GGTGCCAACGCCTTCTACGCTGACTCCGTGAAGGGACGCTTTACCATCTCACGC
    GACAACGCGAAGAACACACTTTACCTGCAAATGAACAGCTTGAAACCTGAGGAT
    ACAGCAACCTACTATTGCAAGCGCGGTCACGCTTGCGCCGGTTATTACCCTATC
    CCTTACGATGACTACTGGGGTCAGGGTACTCAGGTAACGGTGTCAAGTGGGGGC
    GGGTCCCAGGTCCAGCTTCAAGAGTCCGGCGGGGGACTGGTGCAGCCCGGTGGC
    TCTCTGAGGCTCTCTTGTGCTGCGAGCGGATTCACTTTCTCTCTGTCAGGGATG
    TCTTGGGTGCGTCAAGCACCTGGGAAGGGCCTGGAATGGGTCTCAGCAATCTCC
    AGCGGCGGTGCTTCCACCTATTACACTGACAGCGTGAAGGGCAGGTTTACCATC
    TCCAGAGACAACGCCAAGAACATGCTGTATCTCCAGTTGAACTCACTGAAAACC
    GAGGATACAGCCATGTATTACTGTGCCAAAGGAGGGAGCGGCTACGGTGATGCC
    TCTCGTATGACCAGCCCCGGCTCCCAGGGAACCCAGGTGACGGTGTCTTCC
    DR596- 1228 CAGGTCCAGCTCCAGGAGTCTGGCGGGGGCCTGGTCCAGCCTGGGGGTAGCCTG
    hIL27 AGACTGTCCTGCACTGCTTCTGGTCTTACCTTTGATGACAGCGTGATGGGCTGG
    Ra_VH TTTAGACAAGCGCCCGGCAAAGGCCGCGAAGCCGTGAGTTGTATCTCCTCTAGC
    H17 GGCGCGAACGCATTCTACGCTGACTCTGTCAAGGGCCGGTTCACCATTTCCAGG
    GATAACGCCAAGAACACCCTGTACCTTCAGATGAACAGCCTGAAACCCGAAGAC
    ACCGCCACTTATTACTGCAAGCGGGGCCACGCCTGTGCTGGCTATTACCCTATT
    CCTTACGACGATTACTGGGGGCAGGGCACCCAGGTAACTGTCTCTTCAGGCGGA
    AGCGGCGGTTCCGGCGGGTCTGGGCAGGTGCAGTTGCAAGAGTCCGGCGGTGGG
    CTGGTCCAGCCGGGTGGCTCACTCCGCTTGTCCTGCGCGGCTTCAGGATTTACT
    TTCAGTCTGAGTGGTATGAGCTGGGTACGCCAGGCACCCGGCAAGGGCCTGGAG
    TGGGTGTCCGCCATTTCCTCTGGCGGAGCGAGCACATACTATACCGATTCAGTG
    AAAGGGCGTTTTACTATCTCTCGCGATAATGCCAAGAACATGCTGTACCTCCAG
    CTCAACTCTCTGAAGACTGAGGACACCGCCATGTACTATTGCGCCAAAGGCGGA
    AGTGGATACGGTGACGCCTCAAGGATGACTTCCCCTGGTTCCCAGGGCACGCAG
    GTGACCGTGAGTAGC
    DR596- 1229 CAGGTGCAGCTCCAGGAATCCGGTGGGGGACTCGTCCAGCCAGGCGGGTCACTG
    hIL27 CGTCTCTCCTGTACCGCGAGTGGACTGACATTCGATGACTCCGTGATGGGGTGG
    Ra_VH TTCCGCCAGGCCCCCGGCAAGGGCCGCGAGGCGGTGTCTTGCATTTCTAGCTCT
    H18 GGGGCCAATGCGTTTTACGCTGACTCTGTGAAGGGCAGATTCACTATCAGCAGA
    GACAACGCGAAGAACACGCTGTATCTGCAAATGAACTCTCTGAAACCCGAGGAT
    ACTGCCACATACTATTGTAAGCGCGGCCACGCCTGCGCAGGCTACTATCCTATT
    CCTTACGATGACTACTGGGGCCAGGGAACACAGGTCACCGTTAGCTCAGGGGGA
    GGCTCCCAGGTGCAGCTCCAGGAGAGCGGAGGTGGCAGCGTCCAGGCTGGCGGA
    TCTCTGCGCCTGTCTTGTGTCGCCAGCGGATACGTGAGCTGTGACTACTTCCTG
    CCTAGCTGGTATCGTCAAGCGCCGGGGAAGGAAAGGGAGTTCGTGTCCATTATC
    GACGGTACTGGGTCTACCTCATACGCGGCCTCCGTCAAGGGCCGTTTCACGGCC
    TCCCAGGACAAGGGGAAAAACATCGCATATCTGCAAATGAACTCTCTGAAGCCT
    GAGGACACCGCAATGTATTACTGCAAGGCCTCCTGTGTACGCGGACGTGGAATC
    TCTGAGTATTGGGGCCAGGGGACCCAGGTGACCGTGTCTTCC
    DR596- 1230 CAGGTGCAGCTCCAGGAATCCGGGGGCGGTCTGGTTCAGCCAGGTGGCTCTCTC
    hIL27 CGTCTGAGCTGCACCGCTTCCGGTCTCACATTCGACGATTCCGTAATGGGGTGG
    Ra_VH TTCCGCCAGGCCCCTGGAAAAGGTCGCGAGGCCGTGTCTTGCATTTCTTCCAGC
    H18 GGGGCGAACGCATTCTACGCAGACTCTGTGAAGGGTCGTTTTACAATCTCCCGC
    GACAACGCGAAGAACACCCTTTACTTGCAAATGAACTCCCTCAAGCCCGAGGAC
    ACCGCGACCTACTATTGCAAGCGTGGCCATGCTTGCGCCGGGTATTACCCCATC
    CCCTATGATGACTACTGGGGACAGGGAACCCAAGTGACAGTTTCTAGCGGAGGC
    AGTGGTGGCAGCGGTGGGTCCGGCCAGGTGCAGTTGCAAGAGAGTGGCGGAGGC
    TCTGTCCAAGCTGGCGGTTCCCTCCGCCTGTCCTGCGTGGCCTCTGGCTACGTT
    AGCTGCGACTATTTCCTGCCTTCATGGTATCGTCAGGCCCCAGGGAAAGAAAGG
    GAGTTCGTTAGCATCATTGATGGAACTGGCTCCACCTCCTATGCTGCAAGCGTG
    AAGGGTCGGTTCACCGCCTCCCAGGATAAGGGCAAGAATATCGCTTATTTGCAG
    ATGAACTCTCTGAAGCCAGAGGATACCGCCATGTACTATTGCAAGGCATCCTGC
    GTGCGGGGACGCGGGATCAGCGAATATTGGGGCCAGGGAACTCAGGTGACCGTC
    AGTTCT
    DR596- 1231 CAGGTTCAGCTCCAGGAAAGCGGAGGCGGTCTCGTACAGCCTGGCGGTTCCCTG
    hIL27 AGGCTGTCCTGCACCGCCAGCGGACTCACGTTTGACGATAGTGTAATGGGATGG
    Ra_VH TTCAGGCAGGCTCCCGGCAAGGGCCGCGAGGCCGTAAGTTGCATCTCCAGCTCA
    H19 GGTGCCAATGCGTTCTATGCCGACTCCGTGAAGGGTAGATTCACCATCAGCCGT
    GATAACGCGAAAAACACGCTCTACCTCCAGATGAACTCACTGAAGCCTGAGGAC
    ACGGCCACATATTACTGCAAGAGGGGCCACGCCTGTGCTGGGTATTACCCCATC
    CCCTATGATGACTACTGGGGCCAGGGGACACAAGTGACCGTCTCCAGCGGGGGC
    GGAAGCCAGGTGCAGTTGCAGGAATCCGGGGGTGGCAGCGTGCAGGCTGGTGGG
    TCTCTCAGGCTCAGTTGTAGGGCCTCTGGTTCCACCTACAGCAACTACTGTCTG
    GGCTGGTTCCGTCAGATCACTGGTAAAGAGAGGGAGGGCGTGGCAGTCATCAAC
    TGGGTTGGCGGAATGTTGTATTTCGCTGACTCTGTCAAGGGCAGATTCACCGTC
    TCCCAGGATCAGGCTAAGAACACAGTATACTTGCAGATGAACTCCCTGAAGCCC
    GAGGATACTGCTATGTATTACTGTGCCGCAGAAAGCGTGTCCTCTTTCTCTTGC
    GGTGGCTGGCTGACACGCCCTGACAGAGTCCCTTATTGGGGTCAGGGGACCCAG
    GTAACGGTATCTTCC
    DR596- 1232 CAGGTCCAGCTGCAAGAAAGCGGCGGAGGCCTGGTGCAGCCTGGCGGTTCTCTC
    hIL27 CGTCTGAGCTGTACCGCCTCTGGCCTGACATTCGATGACTCCGTTATGGGTTGG
    Ra_VH TTCCGCCAAGCGCCTGGGAAAGGAAGGGAGGCAGTGAGCTGTATTTCTAGCTCT
    H19 GGAGCCAATGCTTTCTATGCTGATAGCGTGAAGGGGCGGTTCACTATCTCAAGG
    GACAACGCCAAGAATACACTGTATCTTCAGATGAACAGCCTGAAGCCAGAGGAT
    ACAGCCACCTATTACTGTAAGCGCGGACATGCCTGTGCTGGCTATTACCCGATT
    CCCTACGACGATTACTGGGGGCAAGGAACTCAGGTTACTGTGAGTTCCGGGGGC
    TCTGGGGGCTCAGGCGGTTCCGGCCAGGTACAACTCCAGGAGAGCGGCGGAGGC
    TCCGTACAGGCCGGGGGCAGCCTGAGACTGAGCTGTCGCGCGAGCGGCAGTACC
    TACAGCAATTACTGCCTGGGGTGGTTCCGCCAGATTACTGGGAAGGAGCGGGAA
    GGCGTCGCAGTGATAAATTGGGTCGGTGGAATGCTCTACTTCGCCGATAGCGTC
    AAGGGACGCTTCACCGTGAGTCAGGATCAGGCCAAAAACACCGTTTATCTTCAG
    ATGAACTCCTTGAAGCCGGAAGACACAGCAATGTACTATTGCGCCGCTGAAAGT
    GTCTCCAGCTTCAGCTGCGGAGGGTGGCTCACCCGCCCGGATCGCGTGCCTTAC
    TGGGGGCAGGGCACCCAGGTCACTGTGTCCTCT
    DR596- 1233 CAGGTGCAGTTGCAGGAGTCCGGGGGAGGCCTCGTGCAGCCTGGGGGCTCCCTG
    hIL27 CGCCTCTCTTGTACTGCGTCAGGTCTGACTTTTGACGATTCTGTTATGGGATGG
    Ra_VH TTCCGGCAAGCGCCCGGCAAGGGCCGCGAGGCGGTGAGTTGCATCTCCAGCTCT
    H20 GGCGCAAACGCTTTCTATGCTGACAGTGTGAAGGGCCGTTTTACAATTTCCAGG
    GACAATGCCAAGAATACACTGTACCTCCAGATGAACAGTCTGAAACCCGAAGAT
    ACCGCAACCTATTACTGCAAGCGCGGCCACGCTTGCGCCGGATACTATCCAATC
    CCCTATGATGACTACTGGGGCCAGGGCACGCAGGTCACCGTGAGTAGCGGGGGT
    GGCTCCCAGGTTCAGCTTCAGGAGTCAGGTGGAGGCCTGGTTCAGCCAGGTGGC
    AGCCTGCGCTTGAGCTGCGCGGCCAGCGGTTTCACCTTTAGCTCTTACCCGATG
    TCTTGGGTCAGACAGGCTCCCGGCAAGGGCCTGGAGTGGGTGTCTACCATCTCT
    TCCGGGGGCGATACCACTCTGTACGCGGATTCCGTGAAAGGTCGCTTTACCTCC
    TCTAGGGATAATGCTAAAAATACGCTGTACCTCCAGCTTAATTCCCTGAAGACA
    GAAGATACCGCCATGTATTACTGCGCGAAGCGCATCGACTGCAACTCCGGGTAC
    TGTTACAAACGCAGCTATTGGGGCCAGGGAACACAGGTGACCGTGTCCTCC
    DR596- 1234 CAGGTGCAACTTCAGGAATCCGGCGGGGGCTTGGTGCAGCCAGGCGGGTCTCTC
    hIL27 CGCCTGTCCTGCACGGCCTCTGGCCTGACCTTTGACGATTCCGTGATGGGCTGG
    Ra_VH TTTCGCCAAGCGCCAGGCAAGGGGCGGGAGGCCGTTAGTTGCATCAGTTCCTCT
    H20 GGAGCCAACGCTTTCTACGCCGACTCCGTCAAGGGCCGTTTCACCATCAGCAGA
    GACAACGCCAAGAATACACTGTATCTCCAGATGAACAGCCTCAAACCGGAGGAC
    ACGGCCACCTACTATTGTAAGCGCGGTCACGCATGTGCGGGGTATTACCCAATC
    CCGTATGATGACTACTGGGGTCAGGGCACCCAGGTCACCGTTAGCTCCGGTGGA
    TCTGGCGGAAGCGGGGGCAGCGGACAGGTCCAGCTCCAGGAGAGCGGCGGGGGA
    CTGGTTCAGCCTGGCGGGTCTCTGCGTCTGTCCTGCGCCGCTTCAGGCTTCACC
    TTTTCATCTTATCCGATGTCCTGGGTCAGACAAGCCCCAGGTAAGGGGCTGGAG
    TGGGTTTCTACGATTAGCTCTGGTGGCGATACCACACTGTACGCGGACAGCGTG
    AAGGGGCGGTTCACCAGCTCAAGAGACAACGCCAAAAACACCTTGTACCTCCAG
    CTGAACTCCCTGAAGACCGAGGACACCGCCATGTATTACTGCGCCAAGAGAATT
    GACTGTAACAGCGGTTATTGTTATAAAAGATCCTACTGGGGCCAGGGAACCCAG
    GTGACAGTCAGTTCT
    DR596- 1235 CAGGTGCAGTTGCAGGAGAGCGGTGGAGGCCTGGTCCAGCCAGGTGGCTCTCTG
    hIL27 CGGCTGAGCTGCACCGCTTCTGGTCTGACCTTTGATGACAGCGTGATGGGGTGG
    Ra_VH TTCCGCCAGGCTCCCGGAAAGGGGCGCGAAGCTGTGTCCTGCATCAGCTCCTCT
    H21 GGTGCCAACGCCTTTTACGCTGATTCCGTGAAGGGTCGCTTCACCATTAGCCGC
    GACAACGCAAAGAATACCCTCTACTTGCAGATGAACAGCTTGAAGCCCGAGGAC
    ACAGCGACCTATTACTGTAAGCGCGGCCATGCGTGCGCAGGCTACTATCCGATC
    CCCTATGATGACTACTGGGGCCAGGGAACCCAGGTGACTGTCTCTTCCGGTGGC
    GGTTCCCAGGTCCAGCTTCAGGAGAGCGGTGGCGGACTGGTTCAGCCCGGCGGG
    AGCCTCAGGTTGAGCTGTGCCGCTAGTGGCTTCACCTTCTCCCTCTCTAGCATG
    AGCTGGGTTCGTCAGGCCCCAGGCAAAGGGCTCGAATGGGTCAGCGCAATCTCC
    AGCGGGGGTGCCTCCACCTATTACACAGACTCTGTGAAAGGAAGATTCACTATC
    TCACGTGACAATGCTAAAAACATGCTGTACCTTCAGCTGAACAGCCTGAAGACC
    GAGGATACCGCTATGTACTATTGTGCCAAGGGTGGCTCCGGCTATGGCGACGCA
    TCACGCATGACCTCTCCGGGCTCCCAAGGAACCCAAGTTACCGTATCTTCA
    DR596- 1236 CAGGTGCAGCTCCAGGAGTCCGGTGGAGGCCTGGTACAACCCGGCGGTTCCCTG
    - CGCCTGTCCTGCACAGCAAGCGGGCTTACTTTTGATGACAGTGTCATGGGATGG
    hIL27 TTCCGCCAAGCGCCCGGTAAGGGCAGGGAGGCTGTCAGCTGTATCAGTTCCAGC
    Ra_VH GGGGCTAATGCGTTTTATGCCGATAGTGTCAAGGGCCGGTTTACCATCAGCCGC
    H21 GACAACGCCAAAAACACCCTGTATTTGCAGATGAATAGCCTCAAACCAGAGGAC
    ACAGCGACCTATTACTGTAAGCGCGGTCATGCGTGCGCGGGCTATTACCCGATT
    CCTTACGACGATTATTGGGGACAGGGCACCCAGGTGACCGTCAGCTCCGGTGGC
    AGTGGCGGTTCCGGTGGCTCCGGCCAGGTGCAGCTTCAGGAGAGCGGTGGCGGG
    CTGGTGCAGCCCGGAGGTTCCCTCCGCCTGTCCTGTGCTGCCAGCGGCTTCACA
    TTTTCCCTGTCATCCATGAGCTGGGTGCGCCAGGCACCCGGTAAGGGACTGGAA
    TGGGTTTCTGCGATTTCTTCCGGCGGTGCCTCCACCTACTATACCGATAGCGTC
    AAGGGGCGGTTTACGATTTCCAGAGACAACGCCAAGAATATGCTGTACCTTCAG
    CTCAATTCTCTTAAAACCGAGGACACCGCCATGTATTACTGTGCTAAAGGGGGC
    TCTGGATATGGTGATGCCTCACGCATGACATCCCCTGGATCTCAGGGCACCCAG
    GTAACCGTGTCCTCA
    DR596- 1237 CAGGTCCAACTCCAGGAGAGCGGTGGAGGCTTGGTGCAGCCCGGCGGGTCCCTG
    hIL27 CGGCTGTCTTGCACTGCTAGTGGACTGACCTTCGACGATTCCGTGATGGGGTGG
    Ra_VH TTCCGCCAAGCTCCGGGAAAGGGCCGCGAGGCCGTGAGTTGCATTTCTTCCAGT
    H22 GGTGCAAACGCCTTTTATGCGGACAGCGTTAAAGGACGGTTCACCATCTCACGC
    GATAACGCGAAGAATACACTGTATCTTCAGATGAACTCCCTGAAGCCCGAGGAT
    ACCGCTACCTACTATTGTAAGAGGGGTCATGCGTGTGCGGGATACTATCCAATC
    CCGTATGACGATTATTGGGGTCAAGGCACTCAGGTTACTGTGTCTTCCGGTGGA
    GGGTCCCAGGTGCAGTTGCAGGAGTCAGGAGGCGGTAGCGTGCAGGCCGGAGGG
    AGCCTGCGCCTGTCTTGTCGCGCATCCGGGAGCACATATTCAAATTATTGTCTC
    GGGTGGTTCCGCCAAACCACAGGCAAGGAACGGGAGGGCGTGGCTGTAATCAAC
    TGGGTCGGTGGAATGCTCTACTTTGCTGACTCTGTGAAAGGCCGCTTCACTGTC
    TCCCAGGACCAGGCCAAGAACACCGTTTATCTTCAGATGAACTCCCTGAAGCCC
    GAAGACACCGCCATGTATTACTGCGCTGCCGAGAGCGTCTCCAGCTTCTCCTGC
    GGCGGATGGCTGACCCGTCCTGATAGAGTGCCCTATTGGGGCCAAGGCACCCAG
    GTTACCGTGTCCAGC
    DR596- 1238 CAGGTGCAGCTCCAGGAGAGTGGCGGGGGCTTGGTGCAGCCAGGCGGATCTCTG
    hIL27 AGGCTGTCTTGCACAGCGAGCGGCCTGACATTCGATGACTCCGTGATGGGCTGG
    Ra_VH TTTCGCCAGGCCCCCGGCAAGGGCCGCGAGGCCGTCTCCTGTATCAGTTCATCT
    H22 GGAGCAAACGCCTTTTACGCTGATTCCGTGAAGGGACGCTTTACCATTAGCCGG
    GACAACGCCAAGAACACCCTCTACCTCCAGATGAACAGCCTGAAGCCTGAAGAT
    ACCGCAACGTATTACTGTAAGAGAGGCCATGCTTGTGCGGGTTACTATCCAATC
    CCCTATGACGATTACTGGGGTCAGGGCACCCAAGTCACCGTGTCTAGCGGAGGG
    TCTGGAGGCTCCGGCGGTAGCGGTCAGGTGCAGCTCCAGGAATCTGGTGGCGGA
    AGCGTGCAGGCGGGCGGTAGCCTGCGCCTGAGCTGTCGCGCCAGCGGTAGCACC
    TACAGCAATTATTGTCTCGGCTGGTTTCGTCAGACCACTGGCAAGGAACGGGAA
    GGCGTTGCCGTTATCAACTGGGTGGGCGGTATGCTGTACTTCGCCGATAGTGTG
    AAGGGTCGCTTCACCGTGTCCCAGGACCAGGCTAAGAACACTGTGTATCTCCAG
    ATGAACTCCTTGAAGCCCGAGGACACCGCGATGTACTATTGCGCCGCTGAGTCT
    GTCAGCTCTTTTTCCTGCGGCGGGTGGCTGACGCGGCCCGACCGGGTGCCATAT
    TGGGGCCAAGGTACTCAGGTGACCGTTAGCAGT
    DR596- 1239 CAGGTGCAGCTTCAGGAATCCGGCGGAGGCCTGGTGCAACCTGGAGGTAGCTTG
    hIL27 CGTCTGTCATGCACAGCCAGTGGACTTACTTTCGACGATAGCGTGATGGGTTGG
    Ra_VH TTCCGGCAGGCTCCTGGCAAGGGCCGTGAGGCCGTGAGCTGCATCTCCAGCTCC
    H23 GGTGCCAATGCCTTTTACGCTGATTCCGTCAAAGGACGGTTCACTATCTCCCGC
    GATAACGCCAAAAACACATTGTATCTCCAGATGAATAGTCTGAAGCCGGAGGAT
    ACCGCAACCTATTACTGCAAGCGCGGCCACGCTTGCGCAGGATACTATCCTATC
    CCTTATGACGATTATTGGGGACAGGGAACACAAGTGACGGTGTCCTCTGGCGGA
    GGTTCCCAGGTGCAGTTGCAGGAGTCTGGGGGCGGGTCCGTCCAGGCCGGAGGC
    AGCCTGCGCCTTTCCTGTCGCGCCAGCCGCTCCCCCTACGGGAACTATTGTCTG
    GGCTGGTTTCGCCAGTCCACTGGTAAGGAAAGAGAGGGCGTAGCCGTGATAAAT
    TGGGTCGGGGGTATGTTGTACTTCGCTGACAGCGTTAAGGGAAGATTCACCGTG
    AGCCAGGATCACGCGAAGAACACCGTCACCCTCCAGATGAACTCTCTCAAGCCT
    GAGGATACAGCTATGTATTACTGTGCCGCTGAGTCCGTTAGCTCCTTTTCATGC
    GGCGGATGGCTGACCCGCCCCGACCGTGTCCCCTATTGGGGCCAGGGCACCCAA
    GTTACTGTGAGTTCT
    DR596- 1240 CAAGTGCAGCTCCAGGAGTCTGGGGGCGGTCTTGTTCAGCCAGGAGGCTCTTTG
    hIL27 CGGCTGTCCTGTACCGCTTCCGGCCTGACATTCGATGACTCTGTCATGGGGTGG
    Ra_VH TTCAGACAAGCCCCTGGGAAGGGACGCGAAGCCGTGAGCTGCATCTCTAGCTCT
    H23 GGGGCTAACGCCTTTTACGCGGACTCCGTGAAAGGAAGATTCACCATCTCCAGA
    GACAACGCCAAGAACACACTCTACCTCCAGATGAACTCCCTGAAACCCGAGGAC
    ACCGCCACCTATTACTGCAAGCGCGGCCATGCGTGCGCGGGCTATTACCCTATT
    CCTTATGATGACTACTGGGGGCAGGGGACACAGGTGACCGTTTCTAGCGGCGGT
    TCCGGTGGCTCCGGCGGTTCTGGGCAGGTCCAGCTCCAGGAGAGCGGTGGAGGC
    TCAGTGCAGGCTGGGGGCTCACTGAGACTGTCCTGCCGCGCCTCCCGCTCTCCG
    TATGGCAACTACTGCCTTGGCTGGTTTCGCCAGAGCACTGGTAAGGAACGTGAG
    GGAGTCGCCGTCATCAACTGGGTGGGAGGGATGCTGTATTTCGCTGACAGCGTG
    AAGGGCCGCTTCACTGTGTCCCAGGACCACGCGAAGAACACAGTGACCCTGCAA
    ATGAATAGTCTCAAACCAGAAGACACTGCTATGTATTACTGTGCTGCCGAATCC
    GTCAGCTCTTTCAGCTGCGGTGGATGGCTGACAAGGCCAGATCGGGTGCCTTAC
    TGGGGTCAGGGCACCCAGGTGACCGTTAGCAGC
    DR596- 1241 CAGGTGCAGTTGCAGGAATCCGGGGGGGGATTGGTGCAACCTGGGGGCTCCCTG
    hIL27 CGCTTGTCCTGTACTGCAAGCGGACTGACCTTCGATGACTCTGTTATGGGCTGG
    Ra_VH TTTCGCCAAGCTCCGGGTAAAGGGAGGGAAGCAGTGTCCTGTATCAGCTCCAGC
    H24 GGGGCCAATGCTTTCTACGCGGATAGCGTGAAGGGTCGTTTTACTATTAGCCGC
    GACAATGCAAAGAACACCCTGTACTTGCAGATGAACTCACTCAAGCCCGAAGAT
    ACAGCCACTTACTATTGTAAGCGCGGCCACGCCTGCGCCGGATATTACCCAATC
    CCTTACGATGACTACTGGGGCCAGGGCACACAGGTTACCGTGAGTTCTGGCGGT
    GGCAGTCAGGTGCAGCTCCAGGAGAGCGGGGGTGGCTTGGTGCAGCCGGGAGGC
    TCTCTGAGGCTGTCCTGTGCTGCCTCAGGTTTCACCTTTTCCCACTCCGGCATG
    TCCTGGGTGCGCCAGGCCCCCGGCAAGGGTCTGGAATGGGTGAGTACCATCAAC
    AGTGGGGGCGCAAGTACCTACTATACCGACTCTGTTAAGGGACGCTTCACTATC
    AGCCGCGACAACGCTAAGAACATGCTGTACCTCCAGTTGAACAGCCTTAAAACC
    GAAGACACGGCCATGTATTACTGCGCGAAAGGGGGCTCTGGCTACGGCGACGCG
    AGCAGGATGACCAGTCCCGGTTCCCAGGGCACACAGGTGACTGTTAGCAGC
    DR596- 1242 CAGGTGCAGTTGCAGGAATCTGGGGGTGGCCTGGTGCAACCTGGGGGCAGCCTG
    hIL27 CGCCTGAGCTGCACCGCCAGCGGTCTGACCTTCGACGATTCCGTGATGGGATGG
    Ra_VH TTCCGCCAGGCTCCTGGAAAGGGAAGGGAAGCTGTGAGCTGCATCAGCTCATCC
    H24 GGCGCGAACGCCTTCTACGCCGATTCTGTGAAGGGCCGTTTTACCATCAGCAGA
    GACAACGCCAAGAACACTCTTTATTTGCAGATGAACTCCCTGAAACCAGAGGAT
    ACAGCAACCTATTACTGTAAGAGGGGTCACGCCTGCGCCGGTTATTACCCCATT
    CCGTATGACGATTACTGGGGACAGGGCACCCAGGTAACCGTGTCCTCAGGTGGC
    AGTGGTGGCTCCGGCGGGAGCGGTCAGGTGCAACTCCAGGAGAGCGGCGGGGGC
    CTGGTCCAGCCCGGTGGCTCCCTGCGTCTGTCCTGCGCGGCCTCTGGGTTCACT
    TTCAGCCATTCCGGCATGAGCTGGGTCCGCCAGGCCCCTGGCAAGGGTCTGGAG
    TGGGTTAGCACGATCAACTCAGGCGGGGCCAGCACTTATTACACCGACTCCGTG
    AAGGGACGCTTCACCATCTCTCGTGACAATGCTAAGAACATGCTGTATTTGCAG
    CTGAACTCCCTGAAGACTGAGGACACTGCCATGTACTATTGCGCCAAAGGTGGG
    TCCGGTTACGGTGACGCGAGCAGAATGACCTCACCTGGGAGCCAGGGCACGCAG
    GTGACCGTGTCCTCT
    hIL27 1243 CAGGTGCAGCTGCAAGAGTCTGGCGGGGGCCTGGTGCAGCCTGGAGGCAGCCTG
    Ra_VH CGCCTGAGCTGTGCGGCATCAGGATTCACGTTTAGCTCCTACCCTATGTCTTGG
    H1- GTCAGACAGGCACCGGGAAAGGGTTTGGAGTGGATCTCCACAATTTCCGCTGGT
    DR591 GGCGACACCACTCTCTACGCTGATTCTGTGAAGGGCCGCTTCACCTCATCTCGC
    GACAACGCTAAGAACACCTTGTACCTGCAACTGAACTCTCTCAAGACCGAGGAC
    GCCGCAATTTACTATTGCGCCAAGCGTATTGATTGCAATTCCGGTTACTGCTAC
    CGTAGGAACTACTGGGGCCAGGGTACTCAGGTCACAGTGTCTAGTGGTGGCGGT
    TCCCAAGTGCAGCTCCAGGAATCTGGAGGTGGGTCTGTGCAGGCTGGAGGCAGC
    CTGAGGCTGAGCTGTACCGCATCCGGGGCAATCGCCTCTGGCTACATCGACTCC
    CGCTGGTGCATGGCCTGGTTTCGCCAGGCTCCCGGCAAAGAGCGCGAGGGCGTG
    GCCGCAATCTGGCCTGGCGGGGGCCTGACCGTTTATGCCGACAGCGTCAAGGGA
    CGCTTCACTATTAGCCGGGACCACGCTAAAAACACACTGTACCTTCAGATGAAT
    AACCTCAAACCGGAGGACACTGCGATGTACTATTGCGCGGCAGGATCACCCCGC
    ATGTGTCCCTCCCTGGAGTTCGGTTTCGATTACTGGGGGCAGGGCACCCAGGTT
    ACCGTAAGTTCC
    hIL27 1244 CAAGTCCAGCTCCAAGAGAGCGGCGGTGGCCTGGTGCAACCTGGGGGCTCCCTG
    Ra_VH CGCCTGTCTTGCGCTGCATCCGGGTTCACCTTCTCTAGCTACCCGATGTCTTGG
    H1- GTGCGTCAGGCTCCGGGTAAGGGCCTGGAATGGATCAGTACCATCTCAGCCGGA
    DR591 GGCGATACCACTCTGTATGCCGATTCTGTGAAAGGCCGCTTTACCTCCAGCCGT
    GATAACGCAAAGAACACTTTGTACCTCCAGCTGAACTCATTGAAGACTGAGGAT
    GCGGCCATTTATTACTGTGCAAAACGCATTGATTGTAATTCCGGCTACTGCTAC
    CGCCGTAACTATTGGGGTCAAGGTACACAGGTAACCGTGTCCAGTGGTGGCTCT
    GGCGGTAGTGGTGGGTCTGGCCAGGTGCAGCTTCAGGAAAGTGGTGGAGGTAGC
    GTGCAAGCTGGAGGCTCCCTGAGGCTCAGCTGTACCGCCTCTGGAGCAATCGCC
    TCCGGCTACATCGACAGCCGCTGGTGCATGGCTTGGTTCCGCCAGGCTCCAGGG
    AAGGAGAGGGAAGGTGTGGCTGCAATTTGGCCTGGAGGGGGCTTGACGGTGTAT
    GCTGATAGCGTCAAGGGACGCTTCACCATTTCCAGGGATCACGCGAAAAACACC
    CTGTACCTGCAAATGAATAACCTGAAACCCGAGGACACCGCAATGTATTACTGC
    GCTGCGGGTTCCCCGCGCATGTGTCCTTCTCTGGAGTTCGGGTTCGATTACTGG
    GGGCAGGGTACACAAGTGACTGTGTCCTCT
    hIL27 1245 CAGGTGCAGCTCCAGGAATCAGGCGGTGGACTGGTCCAACCCGGAGGGTCCCTG
    Ra_VH CGGCTTTCCTGCGCCGCAAGCGGATTTACTTTCTCCTCTTACCCAATGAGCTGG
    H1- GTGCGCCAAGCGCCAGGGAAGGGTCTGGAGTGGATCTCTACAATTAGTGCGGGC
    DR592 GGTGACACCACACTCTACGCTGACAGCGTCAAGGGTCGGTTTACCTCCTCTCGC
    GACAACGCCAAGAACACTCTGTATCTTCAGCTGAACTCCCTGAAAACCGAAGAC
    GCGGCAATTTACTATTGCGCTAAGCGGATCGACTGCAACTCCGGCTACTGTTAC
    CGTCGGAACTACTGGGGCCAGGGCACACAAGTTACCGTCAGCTCCGGTGGCGGT
    TCACAAGTACAGCTCCAGGAGTCCGGCGGGGGCAGTGTGCAGGCTGGTGGCTCC
    CTGCGCCTGTCCTGCACGGCTCCCGGCTTCACGTCCAACTCATGCGGTATGGAT
    TGGTATCGGCAGGCTCCTGGAAAGGAACGCGAATTTGTGAGTTCAATTTCTACT
    GACGGCACCACGGGCTACGCTGACAGCGTCAAGGGCAGATTTACTATTTCCAAA
    GATAAGGCCAAGGATACCGTGTATCTCCAAATGAATAGCTTGAAGCCTGAGGAT
    ACGGGGATGTACTCTTGCAAGACCAAGGACGGCACCATCGCAACTATGGAACTC
    TGTGATTTCGGCTATTGGGGGCAAGGGACACAGGTGACCGTCAGCTCT
    hIL27 1246 CAAGTACAGCTTCAGGAGTCTGGCGGGGGCCTCGTCCAGCCCGGAGGCAGCCTG
    Ra_VH CGGTTGTCCTGTGCCGCATCCGGGTTCACCTTCTCCTCTTACCCAATGTCTTGG
    H1- GTGCGCCAGGCCCCAGGTAAGGGATTGGAGTGGATCTCCACCATCTCTGCGGGC
    DR592 GGAGACACGACTCTTTACGCCGACAGCGTTAAGGGCCGGTTTACCTCTTCCCGC
    GATAACGCCAAAAACACTCTGTATCTTCAGCTGAACAGTCTGAAGACCGAGGAT
    GCCGCTATTTATTACTGTGCTAAGCGCATCGACTGCAACAGCGGATATTGCTAC
    CGGAGGAACTACTGGGGGCAGGGCACCCAGGTTACTGTCAGCTCAGGCGGTTCC
    GGGGGCTCTGGGGGCTCCGGGCAGGTGCAGCTCCAGGAGTCCGGCGGAGGCAGT
    GTCCAAGCAGGAGGTTCACTGCGTCTGTCCTGTACCGCCCCCGGTTTTACATCA
    AACTCATGTGGCATGGACTGGTATCGCCAGGCCCCCGGTAAGGAACGCGAATTT
    GTCTCAAGCATTTCCACTGACGGCACCACTGGTTACGCTGACTCCGTGAAGGGC
    CGTTTCACAATCTCCAAGGACAAGGCCAAGGACACCGTGTACCTTCAGATGAAC
    AGCTTGAAGCCAGAAGACACGGGTATGTACTCTTGCAAGACCAAGGACGGGACC
    ATCGCTACAATGGAGTTGTGTGACTTCGGTTACTGGGGGCAGGGCACGCAAGTC
    ACCGTTTCCTCC
    hIL27 1247 CAGGTTCAGCTCCAGGAAAGTGGAGGCGGTCTCGTGCAGCCGGGCGGATCTCTT
    Ra_VH AGACTGAGCTGTGCGGCCAGCGGCTTCACTTTCTCTAGCTACCCCATGTCCTGG
    H1- GTGCGGCAGGCTCCGGGTAAGGGCCTGGAGTGGATCTCCACCATTTCCGCAGGA
    DR593 GGCGATACTACCCTGTATGCCGACTCTGTCAAAGGCCGGTTCACCTCATCCCGC
    GACAACGCCAAGAACACTCTGTACCTCCAGCTCAACTCCCTGAAGACCGAAGAC
    GCCGCTATCTACTATTGTGCCAAGCGCATCGACTGTAATTCCGGCTACTGTTAT
    AGACGTAACTACTGGGGTCAGGGAACACAGGTTACTGTGTCCTCTGGCGGAGGT
    TCTCAGGTTCAGCTTCAGGAGTCAGGTGGAGGTTCTGTGCAGGCAGGCGGGAGC
    TTGAGACTCTCCTGTGCGGCCAGCGGATACCCTTACTCAAATGGCTATATGGGA
    TGGTTCAGGCAGGCTCCCGGAAAGGAGAGGGAGGGCGTGGCGACTATCTACACA
    GGGGACGGTAGGACTTATTACGCAGACAGCGTCAAAGGGAGGTTTACTATCTCA
    CGTGACAATGCGAAGAACACAGTGGACCTCCAAATGTCCAGCCTGAAGCCAGAG
    GATACTGCCATGTATTACTGTGCAGCTAGGGCGGCACCCCTCTACTCTAGTGGC
    TCTCCCTTGACACGGGCGAGGTACAATGTTTGGGGTCAGGGGACCCAGGTGACT
    GTGTCCTCA
    hIL27 1248 CAGGTCCAGTTGCAGGAAAGTGGAGGCGGACTCGTGCAACCCGGAGGCAGCCTC
    Ra_VH CGTTTGTCCTGTGCGGCTTCCGGCTTCACGTTCAGCTCCTACCCAATGTCTTGG
    H1- GTGCGGCAAGCGCCCGGCAAGGGGCTTGAGTGGATCTCTACAATCAGCGCAGGA
    DR593 GGTGATACTACCCTGTATGCCGACTCTGTCAAGGGCAGATTCACCTCCAGCCGC
    GACAACGCCAAGAACACCCTTTATCTCCAACTGAACAGCCTCAAGACCGAAGAT
    GCCGCGATTTACTATTGTGCTAAGCGCATTGACTGCAACTCCGGCTATTGCTAC
    AGGCGCAACTACTGGGGCCAGGGCACTCAGGTGACTGTGTCCAGCGGCGGTTCT
    GGAGGCTCCGGGGGCAGCGGCCAGGTGCAGCTCCAGGAGTCTGGTGGAGGCTCC
    GTTCAGGCCGGAGGTTCCCTTCGCCTGTCTTGTGCTGCAAGCGGCTACCCATAC
    TCTAACGGCTACATGGGCTGGTTCCGGCAAGCGCCGGGTAAAGAACGCGAAGGG
    GTGGCCACGATCTACACCGGGGATGGCAGAACCTATTACGCCGATAGCGTGAAG
    GGTCGTTTCACTATTTCCCGTGACAATGCGAAGAACACCGTGGACCTCCAGATG
    AGTTCCTTGAAGCCTGAGGATACAGCTATGTACTATTGCGCCGCTCGCGCAGCC
    CCACTCTATTCCAGCGGTAGTCCCCTGACCCGTGCTCGCTACAACGTATGGGGA
    CAGGGTACACAGGTGACTGTGTCCTCC
    hIL27 1249 CAGGTCCAGCTCCAGGAATCCGGTGGGGGCCTCGTGCAGCCCGGAGGTTCTCTG
    Ra_VH CGCCTGTCTTGTGCCGCGAGCGGATTTACTTTCAGCTCCTACCCCATGTCCTGG
    H1- GTGCGTCAAGCCCCAGGTAAGGGGCTGGAGTGGATTTCTACTATTAGCGCTGGA
    DR594 GGCGACACAACCCTGTATGCCGACAGCGTGAAGGGTCGCTTTACTTCTAGCCGC
    GACAATGCAAAGAACACACTGTACCTTCAGCTCAACTCCCTGAAAACTGAAGAC
    GCGGCCATCTATTACTGCGCCAAGCGGATTGATTGTAACAGCGGATATTGCTAC
    AGACGCAACTACTGGGGCCAGGGGACCCAGGTGACAGTGTCAAGCGGGGGCGGG
    TCTCAGGTGCAGCTTCAGGAGAGCGGGGGAGGCAGCGTCCAGGCTGGTGGCTCC
    CTGAGGCTTTCTTGTGTGGCCTCCGCCAGTACCTACTGCACCTATGATATGCAC
    TGGTATCGGCAAGCGCCGGGCAAAGGGAGAGAGTTTGTGTCCGCTATCGACTCA
    GATGGCACAACCAGATACGCCGATAGCGTTAAGGGCAGGTTCACTATCAGTCAG
    GGGACCGCTAAGAACACCGTGTATCTCCAGATGAATAGCCTCCAGCCAGAGGAT
    ACCGCCATGTACTATTGTAAGACAGTGTGTGTTGTCGGATCACGCTGGAGCGAC
    TACTGGGGACAGGGCACCCAGGTGACCGTGTCCTCT
    hIL27 1250 CAGGTCCAGTTGCAAGAATCCGGCGGTGGCCTCGTGCAGCCTGGCGGGTCACTG
    Ra_VH CGTTTGTCTTGTGCCGCTAGTGGCTTCACATTTAGCTCCTACCCCATGAGCTGG
    H1- GTCCGGCAGGCCCCTGGCAAAGGCCTGGAGTGGATCAGTACCATCTCCGCAGGG
    DR594 GGCGACACAACCCTGTATGCGGACTCTGTGAAGGGTAGATTCACATCATCCAGG
    GACAACGCCAAGAACACACTTTATCTCCAGCTTAACTCTCTGAAGACAGAGGAT
    GCAGCCATCTACTATTGCGCTAAGCGTATCGACTGCAACTCCGGTTATTGTTAC
    CGTCGCAATTACTGGGGACAGGGAACACAGGTGACTGTTTCCTCTGGAGGCTCC
    GGTGGCTCCGGGGGCAGCGGCCAGGTGCAGCTCCAGGAGTCTGGAGGCGGAAGC
    GTGCAGGCTGGCGGTTCTCTGCGCCTGAGCTGTGTCGCAAGTGCCTCTACCTAC
    TGCACTTACGACATGCACTGGTATCGGCAAGCGCCCGGAAAAGGCAGGGAGTTT
    GTTAGCGCCATTGATTCCGACGGTACTACCCGCTATGCCGATAGCGTGAAAGGC
    AGGTTTACTATCAGCCAGGGCACTGCGAAGAACACCGTGTACCTCCAGATGAAC
    TCCCTCCAGCCCGAGGACACCGCCATGTATTACTGCAAAACCGTCTGCGTCGTG
    GGATCACGTTGGTCTGACTATTGGGGGCAGGGGACTCAGGTCACTGTGTCCAGC
    hIL27 1251 CAGGTGCAGCTTCAGGAGAGCGGCGGGGGTCTCGTGCAGCCTGGAGGCTCTCTG
    Ra_VH CGCCTGTCCTGTGCCGCGAGCGGATTCACTTTCTCTTCATACCCGATGTCCTGG
    H1- GTGCGCCAGGCCCCCGGCAAGGGACTGGAGTGGATCAGCACGATCTCCGCCGGA
    DR595 GGCGACACAACCCTGTATGCCGACTCTGTTAAGGGGAGGTTCACCAGTAGCCGT
    GACAATGCCAAGAACACTCTGTATCTGCAACTGAACTCTCTCAAGACTGAGGAT
    GCCGCTATCTATTACTGCGCGAAGCGCATTGACTGCAACAGTGGCTACTGCTAC
    CGCAGGAACTATTGGGGCCAGGGCACCCAGGTTACCGTTAGTTCTGGAGGCGGA
    TCACAAGTGCAGCTGCAAGAGTCTGGAGGTGGCAGTGTGCAAGCAGGTGGCTCT
    CTGACTCTGTCCTGCGCTGCCAGCGAGTATGCTTACTCTACGTGCAACATGGGC
    TGGTATCGCCAGGCCCCTGGGAAAGAGCGGGAACTGGTTTCCGCGTTCATCTCC
    GACGGCTCCACTTATTACGCCGACTCCGTGAAGGGGAGATTCACCATCACTCGG
    GACAACGCAAAAAATACTGTCTATCTCCAGATGAACTCCCTCAAGCCTGAGGAT
    ACAGCTATCTACTATTGCTCTGCTAACTGCTATCGTCGCCTGCGCAACTATTGG
    GGACAGGGCACACAGGTGACAGTTAGCAGC
    hIL27 1252 CAGGTGCAGTTGCAGGAATCTGGCGGGGGTCTTGTCCAGCCCGGTGGCTCACTC
    Ra_VH CGCCTGAGCTGCGCTGCCAGCGGTTTCACTTTCAGTTCCTATCCTATGAGTTGG
    H1- GTGCGGCAGGCCCCAGGCAAAGGACTGGAGTGGATCTCTACAATCTCAGCTGGT
    DR595 GGCGATACCACTCTTTATGCCGATTCTGTGAAGGGTCGTTTCACTTCTTCCAGA
    GACAACGCGAAGAACACGTTGTATTTGCAGCTGAACAGTCTGAAAACCGAAGAC
    GCGGCCATCTATTACTGTGCCAAGAGGATTGATTGTAACAGCGGGTATTGTTAT
    CGCCGTAACTATTGGGGGCAGGGCACTCAAGTTACCGTTAGCTCCGGTGGCTCC
    GGGGGTAGCGGGGGAAGCGGCCAGGTCCAGCTGCAAGAGTCTGGAGGGGGTTCC
    GTTCAGGCGGGAGGGTCTCTGACCCTGTCTTGCGCGGCCTCAGAATACGCCTAC
    TCCACCTGTAATATGGGTTGGTACAGACAGGCCCCTGGCAAAGAGAGGGAACTC
    GTTAGCGCTTTCATCTCCGATGGGTCCACTTATTACGCGGACAGCGTCAAGGGC
    CGCTTCACCATCACACGCGATAACGCCAAGAATACGGTTTATCTCCAGATGAAC
    TCCCTCAAGCCCGAGGATACTGCGATCTATTACTGTTCCGCGAACTGCTACAGA
    CGGCTGCGTAACTATTGGGGCCAGGGGACTCAGGTTACCGTGTCCAGC
    hIL27 1253 CAGGTTCAGCTCCAGGAGAGCGGTGGAGGTTTGGTCCAACCGGGAGGCAGCCTG
    Ra_VH AGACTCAGTTGTGCCGCTTCTGGCTTCACTTTCTCCTCTTACCCTATGTCCTGG
    H1- GTCAGACAAGCACCGGGGAAGGGTCTGGAATGGATCTCCACCATTTCAGCTGGA
    DR596 GGCGATACCACATTGTACGCCGACTCCGTGAAGGGACGCTTCACCTCTTCCCGC
    GATAATGCCAAGAACACCCTGTATTTGCAGTTGAATAGCCTGAAGACCGAGGAT
    GCCGCTATTTACTATTGTGCTAAGCGGATCGACTGTAACAGCGGTTACTGTTAC
    AGGCGCAACTACTGGGGTCAAGGCACCCAGGTAACCGTCAGCTCCGGCGGTGGG
    TCCCAGGTGCAGCTCCAGGAGTCAGGAGGCGGACTCGTGCAACCCGGTGGCTCC
    CTCCGCCTCAGCTGTACCGCTTCCGGTCTCACCTTTGATGACTCAGTTATGGGC
    TGGTTTAGGCAAGCGCCGGGCAAGGGCAGAGAAGCTGTGTCTTGTATCTCCTCA
    TCCGGTGCTAACGCCTTCTACGCTGACAGCGTGAAGGGTCGCTTTACAATCAGT
    AGAGATAACGCCAAAAACACTCTTTACTTGCAGATGAACTCTCTCAAGCCTGAG
    GATACCGCCACTTATTACTGTAAGAGGGGTCATGCTTGCGCTGGCTATTACCCC
    ATCCCCTATGATGACTATTGGGGCCAGGGCACCCAGGTGACTGTGTCTAGT
    hIL27 1254 CAGGTGCAGCTTCAGGAGAGCGGCGGAGGCCTCGTGCAGCCAGGAGGCTCCCTG
    Ra_VH AGACTCTCCTGCGCCGCAAGCGGATTTACATTTTCTAGCTACCCGATGTCCTGG
    H1- GTGAGACAAGCGCCCGGCAAAGGCCTTGAATGGATCTCTACTATCTCTGCTGGA
    DR596 GGCGACACAACCCTGTATGCCGATAGCGTTAAGGGACGTTTCACCTCTTCCAGA
    GACAATGCTAAGAACACCCTGTACTTGCAGCTGAACTCCCTCAAGACGGAGGAT
    GCAGCGATCTACTATTGCGCGAAGAGGATTGACTGTAACAGTGGCTATTGTTAC
    AGGCGCAATTACTGGGGCCAGGGAACTCAGGTGACCGTCTCCTCTGGCGGTTCC
    GGGGGATCAGGAGGCAGTGGCCAGGTGCAGTTGCAGGAAAGTGGCGGAGGGCTG
    GTGCAACCAGGCGGATCTTTGAGATTGTCCTGCACCGCCTCCGGCCTGACATTT
    GACGATTCAGTGATGGGCTGGTTCCGTCAGGCACCCGGCAAGGGCCGCGAGGCC
    GTGAGTTGTATCAGCTCCTCAGGCGCAAACGCCTTCTACGCCGACAGTGTTAAG
    GGCAGGTTCACTATCTCCAGAGACAATGCAAAGAACACTCTGTACCTTCAGATG
    AACAGCCTGAAGCCAGAGGACACAGCCACATACTATTGCAAGCGCGGCCACGCT
    TGCGCCGGGTACTATCCCATCCCCTACGACGATTACTGGGGACAGGGCACTCAG
    GTCACAGTGAGTAGC
    hIL27 1255 CAAGTACAACTTCAGGAATCTGGGGGCGGTCTCGTTCAGCCTGGGGGCTCTCTG
    Ra_VH AGGCTGTCTTGCGCCGCGAGCGGATTTACTTTTTCCCTCAGCGGCATGAGCTGG
    H2- GTCAGACAGGCCCCTGGCAAAGGGCTGGAATGGGTGTCCGCCATCTCCAGCGGG
    DR591 GGCGCTTCTACATACTATACTGACAGCGTGAAGGGCAGGTTCACTATTTCCCGC
    GACAATGCCAAGAACATTCTTTACCTTCAGCTGAACTCCCTCAAAACAGAGGAC
    ACCGCGATGTATTACTGTGCTAAGGGCGGGAGCGGTTATGGCGATGCGAGTCGC
    ATGACCTCCCCCGGCAGTCAGGGAACTCAGGTCACTGTCAGCTCTGGGGGCGGG
    TCCCAGGTTCAACTCCAGGAGTCAGGAGGGGGCTCTGTTCAGGCTGGCGGTAGC
    CTGAGGCTGTCCTGCACCGCCTCTGGAGCCATCGCCAGCGGCTATATTGATTCA
    CGCTGGTGTATGGCGTGGTTCCGCCAGGCTCCTGGCAAAGAAAGGGAAGGTGTA
    GCCGCTATTTGGCCTGGAGGCGGTCTGACCGTCTATGCCGATAGCGTGAAGGGC
    AGGTTTACTATCTCTCGGGATCACGCGAAGAACACCCTGTATCTTCAGATGAAC
    AATCTCAAGCCTGAGGACACAGCTATGTATTACTGCGCAGCGGGTTCCCCGCGC
    ATGTGCCCCAGCCTGGAGTTCGGATTCGATTACTGGGGGCAAGGCACCCAAGTC
    ACTGTTTCTAGC
    hIL27 1256 CAAGTTCAGCTCCAGGAGTCCGGTGGCGGACTCGTTCAGCCTGGAGGCAGTCTG
    Ra_VH AGGCTGTCTTGTGCCGCGTCAGGGTTCACCTTCAGCCTGTCTGGGATGAGCTGG
    H2- GTCCGCCAGGCCCCAGGCAAGGGCCTGGAATGGGTGTCAGCCATCAGCTCCGGC
    DR591 GGTGCCTCTACTTATTACACTGACTCAGTGAAGGGTCGTTTTACCATCTCCCGC
    GACAACGCCAAGAACATTCTGTATCTCCAGCTCAACAGCCTGAAAACGGAGGAC
    ACCGCTATGTATTACTGTGCTAAGGGTGGCTCAGGGTACGGGGACGCTTCTCGC
    ATGACATCTCCTGGCTCCCAGGGCACCCAGGTGACTGTCAGCTCAGGAGGCAGC
    GGAGGCAGTGGCGGATCTGGGCAGGTCCAGCTCCAAGAGTCTGGAGGGGGTTCA
    GTGCAGGCTGGAGGTTCTCTTAGGCTGAGCTGTACCGCCAGCGGAGCCATCGCT
    TCTGGGTATATTGACAGCCGCTGGTGCATGGCTTGGTTCCGGCAAGCTCCAGGT
    AAGGAGAGGGAGGGAGTGGCAGCCATTTGGCCCGGAGGCGGACTCACAGTGTAT
    GCCGATAGCGTTAAGGGCAGATTTACCATCAGCCGCGATCACGCAAAAAACACA
    CTCTACCTTCAGATGAATAACCTGAAGCCGGAGGACACCGCCATGTATTACTGT
    GCCGCTGGCTCTCCACGCATGTGCCCTAGCCTGGAGTTCGGTTTTGACTACTGG
    GGTCAAGGCACACAGGTGACCGTGTCTAGT
    hIL27 1257 CAGGTCCAGTTGCAGGAATCTGGAGGCGGACTGGTGCAACCTGGCGGTTCCCTG
    Ra_VH CGGCTGTCCTGTGCAGCCAGTGGCTTTACCTTCAGCCTGAGCGGCATGTCCTGG
    H2- GTGAGACAGGCCCCCGGAAAGGGTCTGGAATGGGTGAGTGCCATCAGCTCCGGC
    DR592 GGAGCCAGTACCTATTACACCGATAGTGTTAAGGGGCGCTTTACCATCTCCCGT
    GACAACGCTAAGAATATCCTTTATCTCCAACTGAACAGCCTGAAGACCGAAGAC
    ACCGCCATGTATTACTGTGCCAAGGGTGGCTCTGGATATGGCGATGCCAGCCGC
    ATGACCAGTCCTGGGTCCCAAGGCACACAGGTAACAGTGTCTAGCGGCGGAGGC
    AGCCAGGTGCAGCTGCAAGAAAGCGGCGGTGGCAGTGTCCAAGCTGGGGGCAGC
    TTGCGCCTCTCTTGCACTGCGCCCGGTTTCACCTCTAATAGCTGTGGCATGGAT
    TGGTATCGCCAGGCACCGGGCAAGGAGAGGGAGTTCGTGAGTTCCATCAGCACC
    GACGGCACTACGGGATATGCCGACAGCGTTAAGGGCCGCTTCACCATCTCAAAG
    GACAAGGCCAAGGATACTGTGTACCTGCAAATGAACAGTCTGAAGCCGGAGGAT
    ACCGGGATGTACTCTTGCAAGACCAAGGACGGAACCATCGCAACTATGGAGCTG
    TGTGACTTCGGCTACTGGGGCCAGGGAACCCAGGTGACAGTCTCTTCC
    hIL27 1258 CAGGTGCAGCTTCAGGAGTCCGGCGGTGGCCTGGTCCAGCCGGGCGGAAGCCTG
    Ra_VH CGCCTTTCCTGCGCCGCGTCTGGCTTCACCTTCTCTCTCAGCGGTATGAGTTGG
    H2- GTCCGCCAGGCCCCAGGGAAGGGCCTGGAGTGGGTGTCTGCTATCTCTAGCGGA
    DR592 GGCGCTAGTACCTATTACACAGATTCCGTCAAGGGCCGCTTTACAATCTCACGC
    GATAACGCCAAGAACATCCTGTACCTTCAGCTGAACAGCCTGAAAACCGAGGAT
    ACCGCTATGTACTATTGCGCTAAGGGAGGCTCTGGCTACGGAGACGCTTCACGT
    ATGACCAGTCCTGGCAGCCAGGGAACACAGGTCACAGTCAGCTCCGGCGGTAGC
    GGTGGCTCCGGCGGGAGCGGCCAGGTTCAACTCCAGGAATCTGGGGGCGGTTCC
    GTCCAGGCTGGGGGTTCTCTGAGACTGAGCTGCACAGCCCCTGGGTTCACCTCC
    AACAGTTGCGGAATGGATTGGTATCGTCAGGCCCCCGGCAAGGAGAGAGAGTTT
    GTTAGCTCTATCTCCACGGACGGGACCACTGGTTATGCTGACAGCGTTAAGGGC
    CGTTTTACTATCTCCAAGGACAAGGCCAAAGACACCGTGTACTTGCAGATGAAC
    TCTCTGAAGCCCGAGGATACCGGAATGTACTCATGCAAAACCAAAGATGGTACT
    ATTGCTACTATGGAGCTGTGTGACTTCGGCTATTGGGGCCAGGGGACCCAGGTG
    ACTGTGTCCTCT
    hIL27 1259 CAGGTTCAACTGCAAGAGTCTGGAGGCGGTCTCGTACAGCCAGGTGGGAGCCTC
    Ra_VH CGCCTGTCCTGTGCAGCCAGCGGTTTCACCTTCTCCCTCTCCGGTATGTCCTGG
    H2- GTGCGCCAGGCCCCTGGAAAAGGCTTGGAGTGGGTGTCTGCCATCAGCTCAGGA
    DR593 GGCGCGTCCACATATTACACCGACAGTGTCAAGGGCCGGTTCACCATCTCCAGG
    GACAATGCGAAGAATATCCTCTACTTGCAGCTGAACTCCCTCAAAACTGAGGAC
    ACTGCAATGTATTACTGCGCTAAAGGGGGCAGCGGATATGGGGATGCTTCCCGG
    ATGACATCCCCAGGCAGCCAGGGCACCCAAGTGACCGTGTCTTCCGGTGGGGGC
    TCCCAGGTGCAGCTCCAGGAAAGCGGAGGGGGAAGCGTGCAGGCAGGGGGTAGC
    CTTCGTCTGTCTTGTGCAGCCAGCGGCTACCCGTATTCTAATGGATACATGGGC
    TGGTTCAGGCAAGCCCCTGGCAAGGAACGCGAGGGCGTGGCCACGATCTATACC
    GGAGACGGCAGGACTTACTATGCCGATAGCGTGAAAGGGCGCTTCACCATCTCA
    CGTGACAACGCGAAAAATACCGTGGATCTTCAGATGTCCTCTCTCAAACCCGAG
    GACACCGCGATGTACTATTGCGCCGCACGGGCTGCCCCTCTGTACTCATCTGGC
    TCACCGTTGACTCGGGCAAGATATAACGTGTGGGGTCAGGGCACACAGGTCACC
    GTGTCTTCC
    hIL27 1260 CAGGTCCAACTCCAGGAAAGCGGCGGTGGCCTGGTGCAGCCTGGTGGGTCCCTC
    Ra_VH AGACTGTCTTGCGCCGCTTCTGGCTTCACCTTTTCTTTGTCCGGGATGTCTTGG
    H2- GTCCGCCAAGCGCCGGGCAAGGGCCTGGAGTGGGTGTCCGCCATTTCATCTGGT
    DR593 GGAGCTTCAACTTATTACACCGACTCTGTGAAGGGTCGTTTTACCATCTCCCGT
    GACAACGCGAAGAACATCCTGTATTTGCAGCTGAACTCCTTGAAAACCGAGGAT
    ACGGCCATGTACTATTGTGCAAAGGGCGGTTCCGGTTACGGCGACGCTTCACGC
    ATGACCTCCCCCGGTTCCCAGGGCACTCAGGTGACCGTCTCAAGTGGCGGTAGC
    GGTGGCTCTGGTGGCAGCGGACAGGTCCAGCTTCAGGAATCAGGCGGAGGGAGT
    GTGCAAGCAGGCGGATCTCTGAGACTGAGCTGTGCTGCCAGCGGTTACCCCTAC
    TCTAACGGCTATATGGGTTGGTTCAGGCAAGCGCCTGGTAAGGAGCGCGAGGGT
    GTGGCCACGATCTATACCGGGGATGGCAGGACCTACTATGCCGACTCTGTGAAG
    GGTCGGTTCACCATCAGCCGGGACAACGCGAAGAACACTGTGGATTTGCAGATG
    TCTTCCCTGAAACCCGAGGACACCGCCATGTATTACTGCGCTGCAAGAGCCGCT
    CCCCTGTATAGCTCTGGATCTCCTCTGACCCGTGCAAGATACAATGTATGGGGT
    CAGGGAACCCAGGTCACCGTCAGCAGT
    hIL27 1261 CAGGTGCAGCTTCAGGAGTCAGGTGGGGGCCTGGTCCAGCCAGGCGGTTCCTTG
    Ra_VH CGCCTGTCATGCGCCGCTAGTGGGTTCACTTTTAGCCTGTCCGGCATGTCCTGG
    H2- GTTCGGCAAGCACCCGGCAAGGGTTTGGAGTGGGTGTCCGCCATTTCTTCCGGG
    DR594 GGCGCATCTACCTATTACACTGATTCTGTCAAGGGGCGCTTTACCATTTCTCGT
    GACAACGCTAAAAACATTCTGTATCTGCAACTTAACTCACTGAAGACCGAGGAT
    ACAGCAATGTACTATTGCGCCAAGGGTGGCTCCGGGTACGGCGATGCGTCACGG
    ATGACATCTCCTGGGTCCCAGGGAACTCAGGTGACCGTGTCCTCAGGCGGGGGC
    AGTCAAGTGCAGCTCCAGGAGAGCGGAGGTGGCTCTGTGCAAGCTGGGGGAAGT
    CTCCGCTTGTCTTGTGTGGCCTCCGCAAGCACATATTGCACCTACGACATGCAC
    TGGTATAGGCAGGCTCCCGGCAAGGGCCGGGAGTTTGTTTCCGCAATCGACAGC
    GACGGCACCACTCGCTATGCCGATAGCGTGAAAGGTCGTTTTACCATCTCCCAG
    GGGACCGCAAAGAACACAGTCTACTTGCAGATGAACTCCCTTCAGCCTGAGGAC
    ACCGCTATGTATTACTGTAAGACCGTGTGCGTCGTGGGCAGTCGTTGGTCCGAT
    TACTGGGGCCAGGGAACACAGGTGACAGTCAGTTCT
    hIL27 1262 CAGGTGCAGCTCCAGGAGTCTGGCGGGGGCCTGGTCCAACCGGGTGGCTCACTC
    Ra_VH CGCCTGTCTTGCGCCGCGTCCGGCTTCACATTCAGTCTCTCCGGGATGTCCTGG
    H2- GTGCGCCAAGCTCCGGGCAAAGGCTTGGAGTGGGTATCTGCTATCTCTAGCGGT
    DR594 GGAGCTTCCACATACTATACCGACTCCGTGAAGGGCCGCTTCACCATTTCACGT
    GATAACGCGAAGAACATTCTGTATCTTCAGCTGAACAGCCTGAAAACCGAGGAC
    ACCGCTATGTACTATTGTGCCAAGGGAGGCAGCGGGTATGGGGACGCTTCCCGG
    ATGACCTCCCCCGGTTCTCAGGGTACTCAGGTGACCGTCTCTAGCGGTGGCTCT
    GGTGGCTCCGGCGGATCTGGACAGGTACAGCTCCAGGAGTCAGGTGGAGGGAGT
    GTGCAGGCAGGTGGCTCCCTGCGGTTGTCCTGTGTGGCCAGCGCCTCTACATAT
    TGCACCTACGACATGCACTGGTACAGGCAGGCCCCAGGTAAAGGGCGTGAATTT
    GTGAGTGCCATTGACTCTGATGGAACGACTAGATACGCGGATTCCGTCAAGGGG
    CGGTTTACAATCTCTCAGGGCACCGCCAAGAACACCGTGTATCTCCAAATGAAC
    TCATTGCAGCCTGAGGACACTGCCATGTATTACTGCAAGACCGTGTGCGTCGTG
    GGCTCCCGTTGGTCCGATTATTGGGGCCAGGGCACACAGGTAACCGTATCTTCC
    hIL27 1263 CAGGTACAGCTCCAGGAATCCGGTGGGGGCTTGGTCCAGCCAGGGGGTAGTCTG
    Ra_VH CGCCTTTCCTGCGCTGCCTCCGGCTTCACCTTCAGCCTGTCAGGCATGTCCTGG
    H2- GTCCGGCAAGCGCCTGGCAAGGGGCTGGAGTGGGTCTCCGCCATTAGCAGTGGT
    DR595 GGAGCGAGCACTTATTACACTGACAGCGTGAAGGGACGCTTTACAATTTCACGT
    GACAACGCCAAGAACATCCTCTACTTGCAGCTCAATTCTCTGAAGACCGAGGAT
    ACCGCAATGTACTATTGCGCCAAGGGTGGCTCCGGTTACGGGGACGCCAGCCGC
    ATGACATCTCCGGGTTCTCAGGGTACACAGGTGACTGTCTCATCCGGGGGCGGG
    AGCCAGGTCCAGCTCCAGGAGTCTGGTGGGGGCTCCGTGCAAGCTGGCGGTTCA
    CTGACACTGAGCTGTGCAGCGTCTGAGTATGCGTACTCTACGTGTAACATGGGA
    TGGTATAGGCAGGCTCCGGGGAAGGAGCGCGAACTCGTGTCAGCTTTTATTAGC
    GACGGCTCCACGTATTACGCAGATAGCGTCAAGGGACGGTTCACCATCACACGG
    GACAATGCGAAGAATACCGTGTATCTCCAGATGAACTCCCTCAAGCCCGAGGAC
    ACCGCAATCTATTACTGTAGCGCAAATTGCTACCGGAGACTGCGGAACTACTGG
    GGCCAGGGCACCCAGGTAACCGTGTCTTCC
    hIL27 1264 CAGGTGCAGTTGCAGGAATCAGGGGGCGGTCTCGTGCAGCCCGGTGGATCACTG
    Ra_VH AGACTGTCATGTGCTGCCTCCGGCTTCACATTCAGCCTGTCTGGTATGAGCTGG
    H2- GTCCGCCAGGCACCAGGCAAGGGACTGGAGTGGGTGAGTGCTATCTCATCCGGG
    DR595 GGTGCCAGCACCTATTACACCGACAGCGTAAAAGGACGTTTCACTATCTCCCGC
    GATAACGCTAAGAACATCCTGTACCTCCAGCTCAATTCTCTGAAAACAGAAGAT
    ACCGCCATGTATTACTGCGCTAAGGGAGGCAGCGGGTACGGCGATGCGTCCCGC
    ATGACATCCCCCGGAAGTCAGGGAACCCAAGTGACAGTGTCTTCCGGGGGCTCT
    GGCGGTTCCGGGGGTTCTGGCCAAGTGCAGCTCCAGGAATCCGGCGGGGGATCT
    GTGCAGGCGGGCGGGTCTCTGACATTGAGCTGCGCGGCCTCTGAGTATGCTTAC
    TCTACCTGCAACATGGGCTGGTATAGGCAGGCCCCCGGCAAGGAACGCGAACTG
    GTGTCCGCCTTCATTTCCGACGGGTCCACCTATTACGCCGACTCCGTGAAAGGC
    AGGTTCACTATCACCCGCGACAACGCCAAGAATACTGTGTACCTCCAGATGAAT
    AGCTTGAAGCCCGAGGATACCGCGATTTATTACTGCTCCGCAAATTGCTATCGT
    CGGCTCAGAAATTATTGGGGCCAGGGCACACAGGTTACCGTTAGCTCA
    hIL27 1265 CAAGTCCAACTCCAGGAGTCCGGCGGTGGCCTGGTGCAGCCCGGTGGGTCCCTG
    Ra_VH CGCCTGTCATGTGCTGCCAGTGGTTTCACATTCAGCCTCTCAGGCATGTCTTGG
    H2- GTACGCCAGGCCCCTGGGAAGGGCCTGGAGTGGGTCTCCGCCATCTCCAGCGGT
    DR596 GGCGCAAGTACATATTACACTGATTCCGTGAAGGGTCGTTTCACAATCTCTAGG
    GATAACGCTAAGAATATCCTGTACCTCCAGCTTAACTCCCTGAAGACCGAAGAT
    ACCGCTATGTATTACTGTGCGAAGGGCGGTTCTGGCTATGGGGATGCCTCACGC
    ATGACCTCTCCTGGGTCCCAGGGCACCCAGGTGACTGTCAGCTCAGGCGGGGGC
    AGCCAGGTGCAGCTCCAGGAGTCCGGTGGCGGGCTGGTGCAGCCTGGCGGAAGC
    CTCAGACTGTCATGTACCGCGAGTGGACTGACATTTGATGACAGCGTCATGGGC
    TGGTTCCGGCAGGCCCCAGGAAAGGGGAGGGAAGCTGTGAGCTGTATTTCTTCC
    TCTGGCGCTAACGCCTTCTACGCTGACAGTGTGAAGGGCCGTTTCACCATTTCC
    AGAGACAACGCAAAGAACACTCTGTACCTCCAGATGAACTCACTGAAGCCTGAG
    GACACCGCGACATACTATTGTAAGCGTGGTCACGCTTGTGCTGGCTACTATCCT
    ATCCCATACGATGACTATTGGGGTCAGGGCACACAGGTGACCGTGAGTAGC
    hIL27 1266 CAGGTCCAGTTGCAGGAATCTGGAGGTGGCCTGGTTCAGCCCGGAGGCAGCCTG
    Ra_VH AGACTGAGCTGCGCTGCGAGCGGATTCACCTTTAGCCTGTCTGGCATGAGCTGG
    H2- GTAAGGCAGGCTCCAGGCAAGGGACTGGAGTGGGTGTCTGCTATCTCCAGCGGA
    DR596 GGCGCTTCCACCTATTACACAGACTCTGTTAAAGGCCGTTTCACTATCAGTAGA
    GACAACGCGAAGAACATCCTCTATCTTCAGCTGAATAGCCTGAAGACAGAGGAT
    ACCGCCATGTATTACTGTGCCAAGGGAGGTAGCGGTTACGGCGACGCCAGCCGC
    ATGACAAGTCCGGGCTCCCAGGGCACACAGGTGACCGTATCCAGCGGTGGCTCC
    GGTGGGAGCGGCGGTTCCGGCCAGGTGCAGCTGCAAGAAAGCGGCGGTGGCCTG
    GTGCAGCCAGGGGGTTCTCTGCGTCTGAGCTGCACCGCGAGTGGGCTGACCTTC
    GACGATTCCGTTATGGGCTGGTTCCGCCAAGCTCCGGGAAAGGGCAGAGAGGCC
    GTATCCTGCATCAGCTCCAGCGGGGCCAACGCCTTCTATGCCGATAGTGTGAAG
    GGACGCTTTACCATTTCTCGCGATAACGCGAAAAACACACTGTATCTTCAGATG
    AACTCACTGAAGCCTGAGGACACCGCCACGTACTATTGTAAACGCGGCCACGCC
    TGCGCTGGTTATTACCCTATTCCATACGACGATTACTGGGGCCAGGGCACCCAG
    GTCACTGTGTCCTCA
    hIL27 1267 CAAGTGCAGCTCCAGGAGAGCGGAGGTGGCTCAGTGCAGGCAGGCGGTTCACTG
    Ra_VH CGTCTGTCCTGCGTCGCCTCTGGCTACGTTAGCTGTGATTATTTTCTCCCCTCC
    H3- TGGTATCGGCAGGCTCCTGGGAAAGAGCGCGAATTTGTAAGCATCATTGACGGC
    DR591 ACCGGCTCTACCAGCTATGCGGCCTCCGTCAAAGGACGCTTTACCGCATCCGAA
    GATAAGGGCAAGAACATCGCTTACTTGCAGATGAACTCTCTGAAACCAGAGGAT
    ACCGCTATGTACTATTGTAAGGCGTCATGCGTGCGTGGCCGCGCCGTGAGCGAA
    TACTGGGGCCAAGGAACCCAAGTTACCGTCTCCTCAGGGGGCGGGTCCCAAGTG
    CAGTTGCAAGAATCCGGTGGCGGATCTGTCCAAGCCGGAGGTTCCCTGAGACTC
    TCATGTACCGCAAGCGGTGCCATTGCAAGCGGCTATATTGATTCCCGCTGGTGC
    ATGGCTTGGTTCCGCCAGGCCCCAGGGAAGGAGCGTGAGGGTGTGGCCGCTATC
    TGGCCCGGAGGGGGCTTGACCGTGTATGCCGATTCCGTCAAAGGACGTTTCACT
    ATCAGCCGCGACCACGCCAAAAACACTCTTTATCTGCAAATGAATAACCTCAAG
    CCAGAGGACACAGCTATGTACTATTGCGCCGCAGGCTCCCCACGCATGTGTCCT
    TCCTTGGAGTTCGGCTTCGACTACTGGGGACAGGGTACTCAGGTTACTGTCTCC
    TCC
    hIL27 1268 CAGGTGCAGCTCCAGGAGTCTGGAGGCGGTTCCGTTCAGGCCGGTGGCTCCCTG
    Ra_VH CGTTTGTCTTGCGTGGCCAGTGGCTACGTCAGTTGTGACTACTTCCTGCCCTCA
    H3- TGGTATCGTCAAGCGCCAGGTAAGGAGCGCGAGTTCGTCTCCATTATCGACGGA
    DR591 ACAGGTTCTACTAGCTACGCCGCTTCTGTCAAGGGGCGCTTCACCGCTTCCGAG
    GATAAGGGTAAGAACATCGCGTATCTGCAAATGAACTCATTGAAGCCCGAGGAC
    ACCGCCATGTATTACTGTAAAGCCTCCTGTGTGCGTGGCCGCGCTGTGTCCGAG
    TACTGGGGCCAGGGCACACAGGTGACCGTTTCCAGCGGCGGTTCCGGCGGGTCC
    GGGGGCTCAGGGCAGGTGCAGCTTCAGGAGAGCGGAGGGGGATCTGTGCAGGCC
    GGTGGCTCCCTGCGGCTGTCCTGCACAGCATCTGGGGCCATCGCGTCCGGGTAC
    ATCGACTCCCGCTGGTGTATGGCCTGGTTCCGCCAAGCGCCTGGCAAGGAGCGT
    GAGGGCGTGGCCGCGATCTGGCCGGGTGGCGGACTCACAGTCTACGCTGACAGC
    GTCAAGGGGCGTTTCACTATTAGCAGAGACCACGCTAAGAACACCCTTTACCTT
    CAGATGAATAACCTGAAGCCTGAAGACACCGCGATGTACTATTGCGCAGCTGGT
    TCTCCCCGCATGTGCCCCTCACTTGAATTTGGTTTCGACTACTGGGGGCAGGGT
    ACGCAGGTCACGGTGTCCTCC
    hIL27 1269 CAAGTCCAGCTCCAGGAGAGCGGTGGCGGGTCCGTGCAGGCGGGAGGCAGCCTC
    Ra_VH CGCCTCAGTTGTGTCGCCTCTGGCTACGTGTCCTGCGATTATTTTCTTCCGTCC
    H3- TGGTATCGCCAGGCTCCCGGCAAAGAAAGGGAGTTCGTTAGCATCATTGATGGC
    DR592 ACGGGTTCCACAAGTTACGCTGCCAGCGTGAAAGGTAGGTTTACCGCTTCTGAA
    GACAAAGGAAAGAACATCGCCTACTTGCAGATGAACTCTCTGAAGCCCGAGGAC
    ACAGCCATGTACTATTGCAAAGCCTCTTGCGTGAGGGGACGGGCGGTGTCTGAA
    TACTGGGGGCAAGGAACCCAAGTGACCGTGTCCTCTGGAGGCGGTAGCCAGGTC
    CAGCTGCAAGAGTCCGGCGGAGGCTCTGTTCAGGCCGGTGGCTCACTGCGCCTG
    TCTTGTACCGCACCTGGCTTCACTAGCAACTCTTGTGGAATGGACTGGTATCGT
    CAGGCCCCCGGTAAGGAAAGAGAGTTCGTTTCTTCCATTTCTACAGACGGCACA
    ACGGGGTATGCGGACAGTGTGAAAGGAAGATTCACTATCAGTAAGGATAAGGCC
    AAAGACACCGTGTATCTCCAGATGAACTCCTTGAAACCAGAGGACACTGGAATG
    TATAGCTGCAAGACCAAGGACGGGACCATTGCTACGATGGAACTCTGCGATTTC
    GGCTACTGGGGGCAGGGGACACAGGTGACTGTGTCCTCC
    hIL27 1270 CAGGTGCAGTTGCAGGAGTCCGGCGGTGGGTCCGTGCAGGCTGGCGGTAGCCTG
    Ra_VH CGCCTGAGTTGCGTGGCCTCTGGATACGTCTCTTGCGATTACTTCTTGCCCTCT
    H3- TGGTATCGCCAGGCTCCCGGCAAGGAGCGCGAGTTCGTGAGCATCATTGACGGC
    DR592 ACGGGTAGCACCAGCTACGCTGCCAGCGTGAAGGGACGTTTTACAGCCTCTGAG
    GACAAGGGGAAGAACATTGCGTATCTTCAGATGAACTCCCTGAAGCCCGAGGAT
    ACCGCCATGTACTATTGCAAGGCCTCCTGCGTGCGTGGCCGGGCCGTTAGTGAG
    TATTGGGGCCAGGGGACGCAGGTCACCGTCAGTAGCGGTGGCTCCGGCGGTTCT
    GGTGGCAGTGGTCAGGTCCAGCTCCAGGAGAGCGGTGGAGGCAGCGTCCAAGCT
    GGCGGGTCCCTGAGGCTGTCTTGTACTGCGCCGGGATTTACTTCCAACAGCTGC
    GGTATGGACTGGTATCGGCAGGCCCCTGGGAAAGAGAGGGAGTTCGTGTCTTCC
    ATCTCTACGGATGGTACTACCGGCTACGCCGACAGCGTGAAGGGCCGTTTTACT
    ATTAGCAAAGACAAGGCTAAAGACACAGTCTACCTTCAGATGAACTCTCTCAAA
    CCAGAGGACACTGGTATGTATAGCTGTAAAACCAAAGATGGGACCATCGCTACA
    ATGGAACTCTGCGATTTCGGGTACTGGGGACAGGGCACCCAAGTCACTGTCTCT
    AGT
    hIL27 1271 CAGGTGCAGCTTCAGGAGTCCGGGGGAGGCAGCGTGCAGGCAGGAGGCAGCCTG
    Ra_VH CGCCTGTCTTGCGTCGCTTCCGGCTACGTGTCCTGCGACTATTTCCTGCCTTCT
    H3- TGGTACAGACAGGCACCTGGAAAGGAGCGCGAGTTCGTCTCTATTATCGACGGC
    DR593 ACCGGCAGCACTTCTTACGCTGCCTCCGTTAAGGGCCGCTTCACCGCAAGCGAG
    GACAAGGGAAAGAATATTGCCTACCTCCAGATGAACAGCCTGAAACCAGAGGAC
    ACCGCGATGTATTACTGTAAGGCATCATGCGTGCGCGGTCGCGCAGTGTCAGAG
    TATTGGGGTCAGGGAACCCAGGTGACAGTTTCTTCCGGCGGTGGCTCTCAGGTG
    CAGTTGCAGGAGAGTGGTGGAGGGTCAGTCCAGGCTGGAGGCTCCCTCAGACTT
    TCCTGTGCCGCTAGTGGATACCCCTATTCCAATGGATATATGGGTTGGTTTAGA
    CAAGCTCCAGGAAAGGAGCGTGAGGGCGTCGCGACCATCTACACTGGCGACGGT
    CGCACCTACTATGCGGATAGCGTGAAGGGCCGTTTCACCATCAGCCGTGACAAC
    GCCAAGAATACCGTCGATTTGCAGATGTCTTCCTTGAAACCGGAGGACACCGCT
    ATGTATTACTGTGCGGCCAGAGCTGCGCCATTGTATAGCTCCGGTTCCCCTCTG
    ACCCGCGCTCGCTACAATGTGTGGGGACAGGGCACTCAGGTCACCGTCTCATCC
    hIL27 1272 CAGGTGCAACTCCAGGAGAGCGGCGGGGGTTCCGTCCAGGCTGGTGGCTCTCTG
    Ra_VH AGGTTGAGCTGTGTAGCCAGCGGCTACGTGTCTTGTGACTACTTCCTCCCCAGC
    H3- TGGTATCGTCAGGCTCCTGGCAAGGAGCGCGAGTTTGTCAGTATCATTGATGGC
    DR593 ACCGGGAGCACCTCATACGCTGCCTCTGTGAAGGGTCGCTTCACTGCCAGCGAG
    GATAAGGGCAAGAACATCGCCTACCTTCAGATGAACTCTTTGAAGCCGGAAGAC
    ACTGCCATGTATTACTGCAAGGCTTCTTGCGTCAGGGGACGCGCAGTGTCAGAG
    TATTGGGGGCAGGGAACCCAGGTTACCGTCAGCTCCGGCGGAAGCGGAGGCAGC
    GGGGGCAGCGGGCAGGTGCAACTCCAGGAATCTGGGGGAGGCTCCGTTCAGGCT
    GGCGGTTCTCTCAGACTCAGCTGCGCGGCCTCCGGCTATCCATATTCCAACGGA
    TACATGGGCTGGTTCCGTCAGGCTCCCGGAAAGGAACGCGAAGGGGTGGCTACC
    ATCTACACCGGAGATGGCCGGACTTATTACGCGGACTCTGTGAAGGGTCGCTTC
    ACCATTTCAAGGGACAACGCAAAGAACACCGTGGACCTGCAAATGTCTTCCCTG
    AAACCAGAAGACACCGCCATGTACTATTGTGCTGCCCGCGCCGCACCCCTGTAT
    AGCTCCGGTTCCCCTCTTACGAGGGCACGTTACAACGTCTGGGGCCAGGGCACT
    CAGGTGACAGTTAGCTCC
    hIL27 1273 CAAGTGCAGCTGCAAGAGAGTGGCGGAGGCTCTGTGCAGGCTGGCGGTTCCCTG
    Ra_VH AGACTCAGTTGCGTTGCCTCAGGCTACGTGTCTTGTGACTACTTCTTGCCCTCT
    H3- TGGTATCGGCAGGCTCCCGGAAAGGAGCGCGAGTTTGTTTCAATCATTGATGGG
    DR594 ACAGGTTCTACCTCCTACGCCGCGTCAGTTAAGGGACGGTTTACTGCGTCCGAG
    GACAAGGGAAAGAACATTGCATACCTTCAGATGAACTCTCTGAAGCCCGAAGAT
    ACAGCCATGTATTACTGCAAGGCCTCCTGCGTCAGAGGTAGAGCAGTCTCCGAG
    TACTGGGGCCAGGGAACCCAGGTGACAGTGAGTAGCGGAGGGGGCTCTCAGGTG
    CAGCTGCAAGAGAGCGGCGGTGGCTCCGTTCAGGCCGGTGGGAGCCTCAGGCTC
    AGCTGTGTGGCGAGCGCTTCCACTTATTGCACCTACGACATGCACTGGTATCGG
    CAGGCTCCGGGAAAGGGCAGAGAGTTCGTATCTGCCATCGACTCAGACGGGACC
    ACACGTTACGCCGACTCTGTGAAGGGCCGCTTCACTATCAGCCAAGGCACCGCC
    AAAAACACTGTTTATTTGCAGATGAACAGCTTGCAGCCAGAGGACACCGCCATG
    TATTACTGTAAGACAGTTTGTGTGGTAGGCAGCAGATGGTCCGACTACTGGGGC
    CAGGGTACTCAAGTGACCGTCTCCAGC
    hIL27 1274 CAGGTCCAGCTCCAGGAAAGCGGCGGTGGCAGCGTGCAGGCTGGCGGATCTTTG
    Ra_VH CGTCTTTCATGCGTGGCCAGCGGTTATGTAAGCTGCGACTATTTTCTGCCAAGC
    H3- TGGTATCGGCAGGCACCTGGCAAGGAGCGTGAATTTGTCAGCATCATTGATGGC
    DR594 ACCGGATCTACCTCCTACGCAGCGAGCGTCAAGGGAAGATTCACCGCCTCAGAA
    GATAAGGGCAAAAACATCGCCTACCTCCAGATGAACTCCCTGAAGCCTGAAGAT
    ACAGCGATGTACTATTGCAAAGCCAGCTGTGTCCGTGGCAGAGCCGTGTCCGAG
    TATTGGGGCCAGGGAACACAAGTGACTGTTTCCTCTGGTGGATCAGGAGGCAGC
    GGTGGCTCTGGCCAGGTGCAGCTTCAGGAGAGCGGAGGTGGATCTGTGCAGGCT
    GGCGGTTCACTTCGTCTGTCCTGCGTCGCCTCTGCGTCTACCTATTGTACCTAC
    GATATGCACTGGTATCGCCAAGCCCCTGGCAAGGGCCGCGAGTTCGTGTCCGCT
    ATTGATTCCGACGGAACTACCCGGTACGCCGATTCTGTCAAGGGAAGATTTACA
    ATCTCCCAGGGGACCGCCAAGAATACCGTCTATCTGCAAATGAACAGTTTGCAG
    CCAGAGGACACTGCTATGTATTACTGCAAGACCGTGTGCGTGGTCGGAAGCCGC
    TGGTCTGACTATTGGGGTCAGGGCACCCAGGTGACCGTGTCCTCC
    hIL27 1275 CAGGTCCAGCTCCAGGAGTCAGGTGGCGGTTCCGTCCAGGCCGGAGGCAGCCTG
    Ra_VH CGGCTTTCCTGTGTGGCTTCTGGCTATGTTAGCTGCGACTACTTTCTCCCTTCC
    H3- TGGTATCGTCAAGCGCCTGGAAAGGAGAGGGAGTTCGTCTCCATCATTGACGGG
    DR595 ACGGGTTCCACCAGCTATGCAGCCTCCGTGAAGGGGAGATTCACTGCCAGTGAA
    GACAAGGGTAAGAACATCGCTTATTTGCAGATGAACTCCCTGAAACCAGAGGAT
    ACCGCTATGTATTACTGCAAGGCGTCTTGCGTGAGGGGCCGCGCTGTGTCCGAA
    TACTGGGGCCAGGGGACCCAGGTCACCGTTAGCTCTGGAGGCGGTTCCCAGGTG
    CAGCTTCAGGAAAGCGGAGGTGGCAGCGTGCAGGCTGGAGGCTCACTGACACTG
    TCTTGCGCAGCCTCCGAATACGCATATTCAACCTGCAACATGGGCTGGTATCGT
    CAGGCCCCTGGCAAGGAGAGAGAGCTGGTGTCTGCTTTCATCTCTGATGGCTCC
    ACGTATTACGCTGATTCTGTTAAGGGTCGTTTTACCATCACACGGGACAACGCT
    AAGAACACGGTGTATCTTCAGATGAACAGTTTGAAGCCCGAGGATACAGCGATC
    TACTATTGCAGCGCGAATTGTTATAGACGCCTGCGCAACTATTGGGGTCAGGGC
    ACACAGGTTACCGTAAGCTCA
    hIL27 1276 CAAGTTCAGCTGCAAGAATCTGGAGGCGGGTCTGTGCAGGCTGGCGGTTCCCTG
    Ra_VH CGTCTCTCATGCGTCGCCTCTGGCTACGTTTCCTGCGACTACTTTCTTCCTTCA
    H3- TGGTACAGGCAGGCCCCTGGCAAGGAGCGCGAGTTTGTGTCCATTATCGACGGG
    DR595 ACTGGTAGCACATCCTATGCTGCCTCCGTGAAAGGACGCTTTACAGCCAGTGAG
    GACAAGGGTAAGAACATCGCTTATCTGCAAATGAACTCACTCAAGCCCGAAGAC
    ACAGCTATGTATTACTGCAAGGCATCCTGTGTGCGTGGCCGCGCCGTGTCTGAG
    TACTGGGGGCAGGGGACACAGGTGACCGTGTCCTCTGGGGGCTCAGGTGGCTCC
    GGTGGCTCCGGCCAAGTTCAGCTCCAGGAGTCTGGAGGCGGTAGCGTGCAGGCT
    GGAGGCTCCCTGACCCTTAGCTGCGCCGCTAGTGAGTATGCGTATTCAACTTGC
    AACATGGGTTGGTACAGGCAGGCCCCAGGGAAGGAGAGAGAGCTGGTCAGCGCT
    TTCATTAGTGACGGGTCTACGTATTACGCCGACTCCGTGAAGGGGAGATTTACT
    ATTACCCGTGATAACGCGAAGAATACTGTGTATTTGCAGATGAACTCTCTCAAG
    CCGGAGGACACCGCCATCTATTACTGTAGCGCCAACTGTTACAGACGCCTGAGA
    AACTATTGGGGGCAAGGAACCCAGGTGACCGTGAGCAGC
    hIL27 1277 CAGGTGCAACTGCAAGAGTCAGGCGGGGGCAGTGTGCAGGCGGGTGGCAGTCTG
    Ra_VH CGCCTGTCCTGCGTAGCTTCTGGCTACGTGTCTTGCGACTACTTCCTCCCGTCC
    H3- TGGTATAGGCAAGCGCCGGGGAAGGAACGGGAGTTTGTCAGTATCATTGATGGT
    DR596 ACTGGTAGCACATCTTATGCTGCCTCTGTCAAGGGAAGATTTACTGCCAGCGAG
    GATAAGGGCAAGAACATTGCCTACCTGCAAATGAACTCTCTGAAGCCAGAGGAT
    ACCGCCATGTATTACTGCAAGGCCAGCTGCGTTAGGGGACGTGCTGTCTCTGAA
    TATTGGGGCCAGGGCACCCAGGTCACCGTGAGTAGCGGTGGGGGCTCTCAGGTT
    CAACTGCAAGAGTCTGGAGGTGGGCTCGTCCAGCCGGGCGGGTCTCTGAGGTTG
    TCTTGCACCGCGTCAGGGCTGACCTTCGACGATTCTGTGATGGGCTGGTTTCGC
    CAGGCCCCTGGCAAAGGGCGTGAGGCTGTGTCCTGCATCAGCTCAAGCGGAGCA
    AATGCCTTCTATGCCGACAGTGTCAAAGGCCGCTTCACAATCAGCAGAGACAAC
    GCTAAGAACACCCTGTACCTCCAGATGAACTCACTCAAGCCTGAAGATACGGCA
    ACCTATTACTGCAAAAGGGGCCACGCCTGCGCCGGGTATTACCCTATCCCCTAT
    GATGACTACTGGGGCCAGGGTACTCAAGTAACCGTGTCCTCC
    hIL27 1278 CAGGTCCAGCTTCAGGAGTCCGGCGGTGGCTCCGTGCAGGCTGGCGGGTCCCTG
    Ra_VH CGCCTGTCCTGCGTGGCCAGCGGCTACGTGTCCTGCGACTATTTCCTGCCCTCT
    H3- TGGTATCGCCAAGCGCCGGGCAAAGAAAGAGAGTTCGTATCAATCATTGATGGG
    DR596 ACCGGCTCAACCAGCTACGCAGCTTCCGTAAAGGGGAGATTCACAGCCTCCGAA
    GATAAAGGCAAGAACATCGCTTACCTCCAGATGAACTCTCTGAAGCCTGAGGAT
    ACTGCAATGTACTATTGTAAGGCCTCATGCGTGCGTGGCCGCGCAGTGTCTGAA
    TATTGGGGCCAGGGCACCCAGGTTACCGTCTCAAGCGGAGGCTCAGGAGGCTCA
    GGAGGCTCAGGACAGGTGCAGCTTCAGGAGTCCGGCGGAGGCCTGGTGCAGCCC
    GGCGGTAGCCTCCGTCTTAGTTGTACTGCCAGCGGGCTCACCTTTGATGACTCA
    GTGATGGGGTGGTTTCGCCAGGCTCCGGGCAAAGGCCGGGAGGCCGTGTCCTGC
    ATCTCTAGCTCCGGTGCCAATGCGTTCTACGCAGATAGCGTGAAGGGCAGATTC
    ACTATCAGTAGAGATAATGCCAAGAATACACTGTACTTGCAGATGAACTCCCTC
    AAGCCTGAAGACACGGCCACCTACTATTGTAAACGGGGCCACGCCTGCGCTGGC
    TATTACCCGATCCCGTATGATGACTACTGGGGACAGGGCACCCAAGTCACCGTC
    TCCTCT
    hIL27 1279 CAGGTTCAGTTGCAGGAATCTGGTGGGGGCCTCGTTCAGCCTGGGGAGAGCCTC
    Ra_VH CGTCTGTCCTGCACCGCTTCAGGATTCACTTTCTCAAACTACGCAATGTCTTGG
    H4- GTCCGGCAGGCTCCGGGCAAAGGCTTGGAATGGGTGTCAGGCATCAATGTTGCA
    DR591 TACGGCATTACCTCCTACGCAGATAGCGTGAAGGGCCGTTTCACCATCAGTCGT
    GACAACACCAAAAACACTCTCTACTTGCAGCTCAATTCACTCAAGACAGAGGAC
    ACCGCTATTTATTACTGTGTCAAACACTCCGGCACTACCATCCCACGCGGCTTC
    ATTAGCTATACCAAACGCGGCCAGGGCACCCAGGTCACCGTCTCCTCTGGTGGC
    GGTTCCCAGGTGCAGTTGCAGGAATCCGGCGGGGGAAGCGTGCAGGCCGGTGGC
    AGCCTGCGCCTGAGCTGCACAGCTTCCGGGGCTATCGCTTCTGGCTACATTGAT
    TCCCGGTGGTGTATGGCCTGGTTCCGCCAGGCCCCTGGCAAAGAGCGTGAGGGC
    GTGGCTGCGATCTGGCCTGGAGGGGGCCTGACCGTCTACGCCGATAGCGTTAAA
    GGCAGGTTTACCATCAGCCGCGACCATGCCAAGAACACCCTGTACCTCCAGATG
    AATAACCTGAAGCCTGAGGACACGGCCATGTATTACTGCGCCGCAGGCTCACCT
    AGAATGTGCCCTAGTTTGGAGTTCGGCTTTGACTATTGGGGTCAGGGTACGCAG
    GTGACTGTGTCCTCC
    hIL27 1280 CAAGTGCAGTTGCAGGAGTCCGGTGGCGGACTCGTCCAGCCTGGAGAATCCCTG
    Ra_VH AGGTTGAGCTGCACCGCGTCCGGGTTCACGTTCAGCAATTACGCCATGTCTTGG
    H4- GTGAGGCAAGCCCCAGGTAAAGGCCTTGAGTGGGTCAGCGGAATCAACGTGGCT
    DR591 TACGGGATCACCAGTTACGCAGATAGCGTCAAGGGGCGGTTCACTATTAGCAGA
    GATAACACTAAGAACACTCTGTACCTTCAGCTGAACTCACTCAAGACCGAAGAC
    ACCGCCATTTATTACTGCGTAAAGCACAGCGGTACTACGATCCCTCGCGGCTTT
    ATCAGCTATACTAAGCGCGGTCAAGGAACCCAAGTGACCGTGTCAAGCGGAGGG
    AGCGGTGGATCTGGGGGATCAGGCCAGGTGCAGCTTCAGGAGAGTGGCGGTGGC
    TCTGTGCAGGCCGGGGGCTCACTGAGACTGTCTTGCACTGCCAGCGGGGCTATC
    GCGTCTGGCTACATCGACAGTCGCTGGTGCATGGCCTGGTTCAGACAGGCCCCT
    GGTAAGGAGCGTGAAGGCGTGGCTGCCATTTGGCCTGGAGGCGGACTGACCGTC
    TATGCGGATAGCGTCAAGGGGAGGTTTACCATTAGCCGCGACCACGCCAAGAAT
    ACTCTGTACCTTCAGATGAATAACCTGAAACCCGAGGATACCGCGATGTATTAC
    TGTGCAGCTGGCAGTCCTCGGATGTGTCCGAGCTTGGAGTTCGGGTTCGATTAT
    TGGGGTCAGGGAACTCAGGTGACTGTGTCCTCC
    hIL27 1281 CAGGTACAGCTCCAGGAATCCGGCGGAGGCCTTGTCCAGCCCGGAGAGTCCTTG
    Ra_VH CGCCTCTCTTGCACCGCAAGCGGCTTCACCTTCTCCAACTATGCTATGTCTTGG
    H4- GTGCGTCAGGCCCCCGGCAAAGGCCTGGAATGGGTCAGCGGGATCAATGTGGCA
    DR592 TACGGGATCACTTCCTACGCCGATAGTGTCAAGGGTCGTTTTACCATTAGCCGT
    GATAACACGAAAAACACTCTGTACCTCCAGCTCAACAGCCTGAAGACGGAAGAT
    ACGGCTATCTATTACTGTGTCAAACACAGTGGCACGACTATTCCGCGCGGCTTC
    ATCTCATATACTAAGCGCGGACAGGGGACCCAAGTGACTGTCAGCAGTGGCGGA
    GGCTCCCAGGTGCAGCTCCAGGAATCCGGTGGCGGTTCCGTCCAAGCGGGCGGG
    TCTCTGCGTCTTTCCTGTACCGCTCCGGGGTTTACCAGCAACTCTTGTGGAATG
    GACTGGTACAGGCAGGCACCAGGGAAGGAGCGCGAGTTCGTTTCCAGCATCAGC
    ACCGACGGAACCACTGGCTATGCCGACAGCGTGAAGGGTCGCTTCACGATCTCT
    AAGGATAAGGCCAAAGATACTGTGTACCTGCAAATGAACTCTCTTAAACCGGAA
    GATACAGGTATGTACTCATGCAAAACAAAAGACGGCACCATCGCCACGATGGAG
    CTTTGCGATTTCGGATACTGGGGCCAGGGCACACAAGTGACGGTTAGTAGC
    hIL27 1282 CAGGTCCAGCTCCAGGAGAGCGGCGGGGGCCTGGTCCAGCCAGGTGAGTCTCTG
    Ra_VH CGTCTGTCTTGCACCGCTTCTGGTTTCACATTTTCCAATTATGCCATGTCCTGG
    H4- GTCCGCCAGGCTCCAGGGAAGGGCCTTGAGTGGGTCTCTGGCATCAACGTGGCC
    DR592 TATGGCATCACCTCTTATGCCGACAGCGTGAAGGGTCGTTTCACCATCTCCCGC
    GACAACACGAAGAACACACTGTACCTCCAGTTGAACAGCTTGAAGACCGAGGAC
    ACCGCGATCTACTATTGCGTGAAGCATAGCGGGACCACGATCCCTCGCGGATTC
    ATCAGCTATACGAAGCGCGGCCAGGGTACACAGGTCACCGTTAGCTCCGGCGGT
    AGTGGCGGGTCCGGTGGCAGCGGACAGGTGCAGCTCCAGGAGTCCGGTGGGGGT
    TCCGTACAAGCCGGAGGCTCACTGCGCCTGTCCTGCACAGCTCCGGGTTTCACT
    TCTAACAGTTGCGGCATGGACTGGTATCGCCAAGCCCCAGGCAAAGAAAGAGAG
    TTCGTTTCTAGCATCTCCACCGATGGCACCACAGGTTACGCCGACTCTGTCAAG
    GGCCGCTTTACTATCAGCAAGGATAAGGCCAAGGACACCGTGTATCTTCAGATG
    AACTCCCTGAAGCCCGAGGATACTGGGATGTACTCATGCAAGACCAAGGATGGA
    ACTATCGCCACGATGGAGCTGTGTGACTTCGGTTATTGGGGGCAGGGCACCCAG
    GTGACCGTCAGCAGC
    hIL27 1283 CAGGTGCAGCTCCAGGAGAGTGGCGGGGGCCTGGTTCAGCCAGGTGAAAGCCTG
    Ra_VH CGCTTGAGCTGCACCGCATCCGGCTTCACCTTCTCTAATTATGCCATGAGTTGG
    H4- GTGAGACAAGCCCCCGGCAAAGGACTGGAGTGGGTGTCTGGAATTAACGTAGCG
    DR593 TATGGCATCACGTCCTACGCTGATAGCGTCAAGGGGCGCTTCACCATCTCCCGC
    GACAACACGAAAAACACCCTGTACCTCCAGCTGAACTCCCTCAAGACTGAAGAT
    ACCGCGATTTATTACTGTGTGAAACACTCTGGAACAACCATCCCTCGCGGCTTC
    ATTAGTTACACCAAGCGCGGCCAGGGCACCCAGGTGACCGTCAGTTCCGGGGGC
    GGAAGCCAGGTGCAGTTGCAGGAGTCCGGCGGAGGTTCCGTGCAGGCTGGCGGG
    TCCCTGAGACTGTCCTGCGCAGCCAGCGGCTACCCTTATAGCAATGGCTACATG
    GGATGGTTTCGCCAGGCTCCTGGCAAGGAGCGCGAAGGTGTGGCCACTATTTAC
    ACGGGTGATGGACGCACCTATTACGCCGACAGCGTCAAGGGCCGCTTTACCATT
    AGCCGGGATAACGCCAAGAATACTGTCGATCTCCAGATGTCTTCACTGAAACCT
    GAAGACACCGCCATGTACTATTGCGCCGCACGCGCCGCGCCGTTGTACTCTTCC
    GGCAGCCCCCTGACCCGTGCTCGCTACAACGTCTGGGGGCAAGGCACACAGGTG
    ACAGTCTCCTCT
    hIL27 1284 CAGGTCCAGTTGCAGGAGAGCGGAGGGGGCCTGGTGCAGCCTGGGGAATCCCTC
    Ra_VH CGTCTCTCCTGCACCGCCAGCGGCTTCACCTTCAGCAACTACGCCATGAGCTGG
    H4- GTGCGCCAGGCTCCAGGGAAGGGCCTGGAGTGGGTGTCAGGCATTAACGTCGCC
    DR593 TACGGCATCACCAGTTATGCCGATAGTGTCAAGGGCCGCTTCACTATCTCCAGG
    GACAACACAAAGAACACTCTCTATCTTCAGCTTAATTCCCTGAAAACTGAAGAC
    ACCGCTATCTATTACTGTGTGAAACACAGCGGAACAACCATCCCGCGCGGTTTC
    ATCTCCTACACTAAGAGAGGCCAGGGCACCCAGGTTACCGTTTCTAGCGGCGGA
    TCTGGGGGCAGCGGGGGCTCCGGTCAGGTCCAACTCCAAGAGTCTGGCGGAGGC
    TCTGTCCAGGCTGGCGGGTCTTTGCGTCTGTCCTGTGCCGCTTCTGGCTACCCG
    TACAGCAACGGTTACATGGGTTGGTTCAGACAGGCCCCCGGCAAAGAGAGGGAG
    GGAGTGGCCACCATCTACACCGGCGACGGCAGGACATATTACGCTGATTCCGTG
    AAGGGTCGTTTCACTATCTCCCGCGATAACGCCAAGAACACCGTCGATCTTCAG
    ATGTCATCCCTGAAGCCTGAAGACACTGCGATGTATTACTGTGCAGCTCGCGCC
    GCGCCCCTCTACAGCTCAGGTAGCCCACTGACACGTGCCCGGTACAACGTCTGG
    GGGCAGGGCACCCAGGTGACGGTGTCTTCC
    hIL27 1285 CAGGTGCAGCTCCAGGAAAGCGGTGGCGGGCTGGTTCAGCCTGGCGAGTCCCTC
    Ra_VH CGTCTGTCCTGCACAGCTAGTGGTTTTACGTTTAGCAACTACGCGATGAGCTGG
    H4- GTCCGTCAAGCCCCTGGTAAGGGGCTGGAGTGGGTGTCCGGCATCAACGTGGCC
    DR594 TACGGCATCACCTCCTACGCTGACTCTGTGAAGGGCCGGTTCACTATCAGCCGG
    GATAACACTAAGAACACCTTGTATCTCCAACTGAACTCCCTGAAGACAGAGGAC
    ACCGCTATTTACTATTGTGTGAAGCACTCTGGCACGACCATCCCCAGGGGCTTC
    ATCAGCTACACCAAGCGTGGGCAGGGTACACAGGTGACAGTCTCCAGCGGCGGA
    GGCTCCCAAGTGCAGCTGCAAGAATCTGGCGGGGGAAGCGTCCAGGCCGGTGGA
    AGTCTGCGCCTTAGTTGCGTGGCTTCTGCAAGCACCTATTGCACCTATGACATG
    CACTGGTATAGGCAGGCCCCCGGCAAGGGGCGCGAGTTCGTTAGCGCCATCGAC
    AGTGATGGGACCACGCGCTACGCGGACAGTGTGAAGGGCAGGTTCACCATCAGC
    CAGGGTACTGCCAAAAATACAGTGTACTTGCAGATGAACTCCCTCCAGCCTGAG
    GACACCGCCATGTACTATTGCAAGACCGTGTGCGTCGTAGGCTCCCGTTGGAGC
    GACTACTGGGGCCAGGGCACACAGGTGACCGTCTCCTCC
    hIL27 1286 CAGGTCCAACTGCAAGAGTCTGGAGGTGGATTGGTCCAGCCCGGCGAAAGCCTG
    Ra_VH AGGTTGAGCTGCACCGCGAGCGGATTCACCTTTAGCAACTATGCCATGTCTTGG
    H4- GTTCGCCAAGCCCCTGGGAAGGGCCTGGAGTGGGTCAGTGGGATCAATGTGGCT
    DR594 TATGGAATCACCAGCTATGCGGACTCTGTGAAGGGAAGGTTCACTATCTCTCGT
    GACAATACTAAAAACACCCTGTACCTCCAGCTCAATTCCCTCAAGACTGAGGAC
    ACCGCTATTTACTATTGTGTGAAACACTCCGGCACCACGATCCCCCGTGGGTTC
    ATCAGCTACACCAAACGGGGCCAAGGCACCCAGGTCACCGTATCTAGTGGCGGT
    AGTGGTGGGAGTGGCGGTTCCGGGCAGGTGCAGCTCCAGGAGTCCGGCGGTGGC
    TCCGTGCAGGCAGGCGGTAGCCTGCGCCTGTCCTGTGTGGCGTCTGCAAGCACC
    TATTGTACTTATGATATGCACTGGTATCGTCAGGCTCCAGGCAAGGGCAGAGAG
    TTCGTCTCCGCAATCGACTCCGATGGCACCACGCGCTACGCCGATTCTGTGAAG
    GGCCGTTTCACTATCAGCCAGGGTACAGCCAAAAATACCGTGTATCTTCAGATG
    AACAGTCTCCAGCCAGAGGATACCGCTATGTACTATTGCAAGACTGTGTGCGTG
    GTTGGCTCCAGGTGGTCCGATTACTGGGGCCAGGGAACCCAGGTGACAGTGTCC
    AGC
    hIL27 1287 CAGGTGCAGCTCCAGGAGAGCGGAGGGGGTTTGGTCCAGCCTGGCGAGTCTCTC
    Ra_VH AGACTTTCTTGTACCGCATCTGGCTTTACTTTCAGCAATTACGCCATGTCCTGG
    H4- GTGCGGCAAGCCCCCGGCAAGGGCCTGGAATGGGTGAGCGGCATCAACGTGGCC
    DR595 TACGGCATCACCTCATACGCAGATTCCGTCAAGGGGCGTTTTACCATCAGTCGC
    GATAATACAAAGAACACATTGTACCTCCAACTGAACTCCCTCAAGACCGAGGAT
    ACCGCGATTTACTATTGCGTGAAACACAGCGGCACTACCATCCCACGCGGGTTT
    ATCAGCTACACGAAGAGAGGCCAGGGTACACAGGTCACCGTGTCAAGCGGCGGT
    GGATCTCAGGTACAGCTCCAGGAGTCTGGGGGTGGAAGCGTGCAGGCGGGCGGA
    TCTCTGACATTGTCCTGCGCCGCAAGTGAGTATGCTTATTCCACGTGCAACATG
    GGATGGTACAGGCAGGCCCCTGGTAAAGAGAGAGAACTCGTGAGCGCTTTTATT
    TCAGACGGCAGCACTTATTACGCCGACTCCGTCAAAGGACGCTTCACCATCACT
    CGTGACAACGCTAAGAATACGGTCTACCTTCAGATGAACTCCCTCAAACCTGAA
    GATACTGCAATCTACTATTGTAGTGCCAACTGCTATAGACGCCTCCGCAACTAT
    TGGGGGCAGGGAACACAGGTGACCGTTAGCAGC
    hIL27 1288 CAAGTTCAGCTGCAAGAGTCTGGCGGTGGCCTGGTGCAGCCCGGCGAATCTTTG
    Ra_VH CGCTTGAGTTGTACCGCCTCTGGTTTTACATTCTCAAACTATGCAATGAGCTGG
    H4- GTGAGACAGGCCCCAGGCAAGGGCTTGGAATGGGTCTCTGGGATCAACGTCGCT
    DR595 TACGGCATTACCTCATACGCCGATAGCGTCAAGGGTCGCTTCACTATCTCTCGG
    GATAATACGAAGAATACTCTCTACTTGCAGCTCAACTCACTGAAGACCGAGGAC
    ACTGCGATCTATTACTGCGTCAAACACTCCGGCACCACTATCCCTCGCGGCTTC
    ATCTCTTACACTAAACGCGGCCAGGGTACTCAGGTGACTGTGAGTTCAGGTGGC
    TCTGGAGGTAGCGGGGGTTCCGGTCAGGTGCAGCTCCAGGAGAGCGGGGGCGGA
    AGCGTACAGGCTGGAGGCAGCCTGACCTTGAGCTGTGCAGCTTCCGAGTATGCC
    TACTCCACCTGTAACATGGGATGGTATAGACAGGCTCCCGGCAAGGAACGTGAG
    CTGGTCAGCGCCTTTATCAGTGATGGGTCCACTTACTATGCCGATTCCGTGAAA
    GGCCGGTTCACCATCACTCGCGACAACGCCAAGAATACAGTGTACTTGCAGATG
    AACTCCCTCAAGCCCGAGGACACTGCTATCTATTACTGTTCTGCAAACTGCTAC
    CGTCGCCTGCGCAACTACTGGGGCCAAGGCACTCAGGTTACCGTGAGCAGC
    hIL27 1289 CAGGTGCAGTTGCAGGAGTCTGGAGGTGGCCTGGTCCAACCTGGAGAATCCCTG
    Ra_VH CGGCTCTCTTGTACCGCGAGTGGTTTCACCTTCAGCAACTATGCAATGAGCTGG
    H4- GTGCGCCAGGCTCCCGGCAAGGGATTGGAGTGGGTCAGCGGCATCAACGTGGCC
    DR596 TATGGCATCACCAGCTACGCTGATAGTGTGAAGGGCCGGTTTACCATCAGTAGG
    GACAACACCAAGAACACACTGTATCTTCAGCTCAACTCCCTGAAGACAGAAGAC
    ACCGCTATCTACTATTGTGTGAAGCATTCCGGCACTACCATCCCACGCGGGTTC
    ATCTCATACACCAAAAGGGGCCAGGGCACCCAGGTGACAGTTTCTAGCGGTGGC
    GGTTCCCAAGTGCAGTTGCAGGAGTCCGGTGGCGGTCTGGTTCAGCCTGGTGGG
    TCTCTTCGTCTGAGTTGTACCGCAAGCGGTCTTACCTTCGATGACAGCGTCATG
    GGGTGGTTCAGGCAGGCCCCCGGCAAGGGTCGCGAGGCAGTGAGCTGCATCAGC
    TCCAGTGGGGCTAACGCCTTTTATGCAGACTCCGTAAAAGGAAGATTCACTATC
    AGCAGGGACAACGCAAAGAACACCCTGTATCTCCAAATGAACAGTCTGAAACCG
    GAAGACACCGCCACTTATTACTGTAAACGCGGCCACGCCTGCGCAGGGTATTAC
    CCGATTCCTTATGATGACTACTGGGGCCAAGGCACCCAGGTGACAGTGTCTAGC
    hIL27 1290 CAGGTGCAGCTCCAGGAAAGCGGAGGCGGGCTGGTGCAGCCGGGAGAGAGTCTC
    Ra_VH AGGCTTTCTTGTACCGCCTCTGGATTTACATTCAGCAATTACGCCATGTCCTGG
    H4- GTTCGCCAAGCACCAGGGAAGGGCCTGGAGTGGGTGTCCGGCATCAACGTGGCA
    DR596 TACGGCATCACATCCTACGCGGATTCCGTCAAGGGTCGGTTTACCATCAGCCGC
    GATAATACAAAGAACACCTTGTATCTCCAGCTTAACAGCCTCAAGACAGAGGAC
    ACCGCCATCTACTATTGTGTGAAGCACTCCGGCACCACTATCCCTCGCGGTTTC
    ATTTCCTACACCAAAAGGGGTCAGGGCACTCAGGTAACAGTGTCCTCTGGGGGC
    TCCGGTGGATCAGGTGGCTCCGGCCAGGTACAACTCCAAGAGTCAGGAGGCGGT
    CTGGTACAGCCTGGTGGCTCCTTGCGCCTGTCTTGCACAGCAAGCGGCCTGACT
    TTCGATGACTCTGTGATGGGCTGGTTTCGTCAGGCCCCAGGGAAGGGCAGGGAG
    GCCGTCTCCTGCATTAGTAGCTCCGGCGCTAACGCCTTCTATGCCGATAGTGTG
    AAGGGGCGCTTTACCATCTCTCGTGACAATGCCAAGAACACCCTGTACTTGCAG
    ATGAACAGCCTGAAGCCGGAGGATACTGCCACCTATTACTGCAAGCGCGGCCAT
    GCGTGTGCTGGCTACTATCCCATCCCTTACGATGACTATTGGGGTCAGGGCACC
    CAGGTGACCGTGTCCAGC
    hIL27 1291 CAGGTCCAGCTTCAGGAAAGCGGGGGTGGATCTGTCCAGGCGGGCGGATCACTT
    Ra_VH CGCCTCAGTTGTACGGCCAGTGGCTATGTATCCTGCGACTACTTCCTCCCATCA
    H5- TGGTATCGCCAGGCTCCGGGAAAGGAAAGGGAGTTCGTGTCTGTGATCGACGGC
    DR591 ACTGGCTCCACCTCCTACGCTGCCAGCGTCAAGGGTCGCTTCACCGCCTCACAG
    GACAAGGGCAAAAACATCGCCTATCTTCAGATGAACTCCCTGAAACCCGAGGAC
    ACAGCCATGTATTACTGTAAGGCCTCCTGTGTGCGTGGCCGCGCAATTTCCGAA
    TATTGGGGCCAGGGCACTCAGGTGACTGTGAGTTCCGGCGGGGGTTCCCAGGTC
    CAGTTGCAGGAGTCCGGTGGCGGATCTGTGCAGGCCGGAGGGTCCCTGCGCCTG
    AGCTGCACAGCGAGCGGTGCCATCGCCTCCGGCTATATTGACTCCAGGTGGTGC
    ATGGCCTGGTTCAGGCAAGCGCCCGGAAAAGAGCGTGAAGGTGTAGCTGCCATC
    TGGCCTGGCGGAGGCCTGACCGTGTATGCCGATTCCGTCAAGGGCCGCTTCACC
    ATCAGCCGCGACCACGCAAAAAACACTCTGTACCTCCAGATGAATAACCTGAAG
    CCGGAGGACACCGCCATGTATTACTGTGCTGCCGGTTCTCCCCGTATGTGCCCC
    AGCCTGGAGTTCGGCTTCGACTACTGGGGCCAGGGAACTCAGGTCACTGTGTCA
    TCT
    hIL27 1292 CAGGTCCAGCTCCAAGAGTCTGGAGGTGGCTCTGTGCAGGCTGGCGGTTCCCTC
    Ra_VH CGCCTGAGCTGCACAGCGAGCGGGTACGTGAGCTGCGATTATTTTCTGCCGTCT
    H5- TGGTATCGTCAAGCGCCCGGAAAGGAGCGCGAGTTCGTGTCCGTGATCGACGGT
    DR591 ACGGGTAGCACCAGTTACGCGGCTTCTGTAAAAGGACGGTTCACCGCTTCCCAG
    GATAAGGGCAAAAACATCGCGTATTTGCAGATGAACAGCCTGAAGCCCGAGGAT
    ACCGCCATGTATTACTGTAAGGCCAGTTGTGTCAGAGGCCGCGCCATCTCCGAG
    TACTGGGGACAGGGCACTCAGGTGACCGTGTCCAGCGGTGGAAGCGGTGGCTCC
    GGGGGCTCCGGTCAGGTCCAGTTGCAAGAGTCAGGCGGTGGCTCCGTCCAGGCG
    GGCGGGAGCCTGCGCTTGTCCTGCACAGCTTCTGGGGCCATCGCCTCCGGCTAT
    ATCGACAGCCGCTGGTGCATGGCGTGGTTCCGCCAAGCGCCGGGCAAGGAACGT
    GAAGGCGTCGCAGCTATTTGGCCTGGGGGCGGGTTGACCGTGTACGCCGACTCC
    GTGAAGGGCCGTTTCACCATCAGTAGAGACCACGCCAAGAACACTCTCTACCTT
    CAGATGAATAACCTGAAACCGGAGGACACTGCTATGTATTACTGCGCTGCGGGC
    TCCCCCAGGATGTGTCCGAGCCTGGAGTTCGGCTTCGACTATTGGGGGCAGGGG
    ACCCAGGTCACCGTGTCCTCC
    hIL27 1293 CAGGTTCAGCTCCAGGAATCCGGCGGAGGCTCTGTCCAGGCTGGGGGTTCTTTG
    Ra_VH CGTTTGAGCTGTACCGCGAGCGGGTACGTGTCTTGCGACTACTTCTTGCCTTCC
    H5- TGGTATCGCCAGGCTCCTGGTAAGGAACGCGAGTTCGTCTCCGTCATTGATGGC
    DR592 ACCGGCTCTACGAGCTATGCTGCCTCAGTTAAGGGCCGCTTCACAGCCAGCCAG
    GATAAGGGCAAAAATATCGCTTACCTCCAGATGAACTCTCTGAAACCTGAAGAC
    ACTGCCATGTATTACTGTAAAGCGAGCTGCGTAAGAGGACGTGCCATCAGCGAG
    TACTGGGGCCAAGGGACACAGGTGACAGTTAGTAGCGGTGGCGGGTCCCAGGTG
    CAGTTGCAAGAGAGCGGTGGCGGAAGCGTGCAGGCAGGCGGATCTCTGCGGCTG
    TCCTGCACCGCCCCTGGATTCACCAGTAACTCTTGTGGTATGGACTGGTATCGT
    CAGGCTCCGGGTAAGGAGAGAGAGTTTGTTTCAAGTATCTCCACTGATGGCACA
    ACCGGGTATGCCGACTCCGTCAAGGGTCGTTTCACCATCTCCAAGGACAAGGCC
    AAGGACACTGTGTACCTTCAGATGAACTCACTGAAGCCTGAGGACACCGGGATG
    TATTCTTGCAAGACTAAAGATGGCACCATTGCCACTATGGAGCTGTGCGACTTC
    GGCTATTGGGGTCAGGGGACACAGGTCACTGTATCTAGC
    hIL27 1294 CAGGTGCAGCTTCAGGAGTCCGGCGGTGGGAGCGTTCAGGCTGGAGGCTCTCTC
    Ra_VH AGGCTGTCATGCACTGCAAGCGGGTACGTTAGTTGTGACTACTTTCTTCCAAGC
    H5- TGGTATCGCCAGGCTCCCGGAAAAGAGCGCGAGTTTGTTTCCGTTATTGATGGA
    DR592 ACTGGGAGTACGTCCTATGCCGCTTCAGTCAAGGGGCGCTTCACCGCATCCCAG
    GACAAGGGTAAGAATATCGCTTACCTTCAGATGAACTCCCTGAAGCCCGAAGAC
    ACCGCGATGTATTACTGTAAGGCTTCTTGCGTGAGGGGCCGCGCTATCAGTGAA
    TACTGGGGTCAGGGGACCCAGGTGACGGTTTCTAGCGGAGGCAGCGGCGGGAGC
    GGCGGGTCTGGACAGGTCCAGCTTCAGGAAAGTGGTGGGGGCTCCGTTCAGGCT
    GGCGGATCACTGCGCCTGAGCTGTACTGCTCCCGGCTTCACGAGCAACTCCTGC
    GGTATGGACTGGTATCGTCAGGCCCCAGGTAAGGAGCGTGAGTTCGTGTCTTCC
    ATCAGTACAGACGGGACAACCGGCTACGCAGACAGCGTAAAGGGCCGCTTCACC
    ATCTCCAAGGATAAGGCAAAGGACACCGTCTACCTCCAGATGAACAGCTTGAAG
    CCAGAGGACACGGGTATGTATAGCTGTAAGACCAAAGACGGTACAATCGCTACA
    ATGGAGCTGTGTGACTTCGGGTATTGGGGCCAGGGAACTCAGGTTACCGTCTCA
    TCC
    hIL27 1295 CAGGTGCAGCTCCAGGAGAGCGGGGGCGGTTCTGTGCAAGCTGGGGGAAGTCTG
    Ra_VH CGGCTCAGCTGTACCGCTAGTGGTTACGTGTCTTGCGACTATTTCCTGCCTTCA
    H5- TGGTATCGCCAGGCCCCAGGCAAAGAGCGCGAGTTCGTGTCCGTCATTGACGGA
    DR593 ACCGGGAGTACCTCCTATGCAGCCAGTGTTAAGGGCCGTTTTACAGCCAGCCAG
    GACAAGGGCAAAAATATCGCTTACCTCCAGATGAACAGCCTGAAGCCCGAGGAC
    ACTGCCATGTATTACTGTAAAGCGAGCTGTGTCAGGGGTAGAGCAATTAGTGAA
    TATTGGGGCCAAGGGACACAGGTGACAGTATCTTCAGGGGGCGGATCTCAGGTG
    CAGCTCCAGGAAAGTGGAGGTGGGTCCGTGCAGGCGGGCGGTTCTCTCAGACTG
    TCTTGCGCCGCGTCTGGCTATCCTTACAGCAACGGGTACATGGGATGGTTTAGA
    CAAGCCCCAGGGAAGGAGCGCGAGGGGGTGGCCACCATTTACACCGGCGATGGC
    CGGACTTACTATGCGGATTCCGTGAAGGGCCGCTTTACCATTTCAAGAGATAAC
    GCGAAAAATACCGTGGACCTCCAGATGTCCTCTTTGAAGCCAGAGGATACCGCG
    ATGTACTATTGCGCTGCCCGCGCCGCTCCTCTCTACAGTAGCGGCTCCCCACTT
    ACCCGCGCTCGCTATAACGTGTGGGGCCAGGGGACACAGGTGACTGTGTCCTCC
    hIL27 1296 CAGGTGCAGCTTCAGGAATCTGGGGGTGGGTCCGTCCAGGCTGGCGGATCTTTG
    Ra_VH AGACTGTCTTGCACTGCCAGTGGTTACGTGAGCTGTGATTACTTCCTGCCGTCT
    H5- TGGTATCGTCAAGCGCCAGGCAAGGAACGTGAGTTCGTGTCCGTGATCGACGGG
    DR593 ACAGGTTCCACATCTTACGCCGCATCTGTTAAGGGGAGGTTCACAGCTTCTCAG
    GACAAGGGTAAAAATATCGCCTATCTCCAGATGAACTCACTGAAGCCTGAAGAT
    ACCGCTATGTATTACTGCAAGGCTTCTTGTGTGCGGGGCCGCGCTATCAGCGAG
    TACTGGGGACAGGGCACTCAGGTGACGGTCTCCAGCGGCGGGAGCGGGGGCTCC
    GGGGGCAGCGGCCAGGTGCAGTTGCAGGAGAGCGGGGGAGGCTCTGTGCAAGCT
    GGAGGCTCTTTGCGCCTGTCCTGCGCTGCCAGCGGATATCCTTACTCTAATGGT
    TATATGGGATGGTTCAGGCAGGCCCCAGGAAAGGAGAGAGAAGGGGTTGCCACC
    ATTTATACTGGGGATGGCCGCACCTATTACGCCGATTCCGTGAAGGGGCGGTTC
    ACAATCTCTCGTGACAACGCCAAGAACACTGTCGATCTTCAGATGTCCAGTCTG
    AAACCGGAGGACACTGCCATGTATTACTGTGCCGCACGCGCAGCTCCCCTCTAT
    TCAAGCGGCTCCCCTCTCACTCGCGCACGCTATAACGTGTGGGGGCAGGGAACT
    CAGGTGACTGTGTCTAGC
    hIL27 1297 CAGGTGCAGCTGCAAGAGAGCGGCGGTGGCAGCGTGCAAGCCGGAGGTTCTCTG
    Ra_VH CGGCTGAGTTGTACCGCTTCTGGATACGTGTCCTGCGACTACTTTTTGCCTTCA
    H5- TGGTATCGGCAGGCCCCAGGCAAAGAACGCGAGTTTGTGTCAGTGATCGACGGC
    DR594 ACTGGTTCCACATCCTACGCAGCCAGCGTGAAGGGCCGTTTTACTGCGTCTCAG
    GATAAAGGCAAGAACATCGCTTATTTGCAAATGAACAGCCTGAAGCCTGAAGAC
    ACAGCCATGTATTACTGCAAGGCAAGCTGCGTTCGCGGTCGGGCGATCTCCGAG
    TACTGGGGGCAGGGTACACAGGTCACCGTCTCCAGTGGAGGTGGCTCCCAGGTG
    CAGCTTCAGGAAAGCGGTGGGGGAAGCGTCCAAGCTGGGGGCTCTCTCCGCCTC
    TCATGTGTGGCCTCTGCCTCCACCTACTGCACTTACGATATGCACTGGTATCGT
    CAGGCACCAGGGAAGGGACGCGAGTTCGTGTCCGCCATCGACAGCGACGGGACA
    ACCCGGTACGCCGACTCTGTGAAAGGCCGCTTCACCATCAGCCAGGGGACAGCT
    AAAAACACCGTGTACCTGCAAATGAACTCCCTCCAGCCAGAGGATACCGCCATG
    TACTATTGTAAGACCGTATGCGTAGTGGGCAGCAGATGGTCCGACTATTGGGGC
    CAGGGGACGCAGGTCACCGTGTCCAGC
    hIL27 1298 CAGGTCCAGCTCCAGGAATCCGGTGGCGGTTCCGTGCAGGCAGGCGGGAGCCTG
    Ra_VH CGTCTGAGTTGCACTGCCAGCGGCTACGTTTCATGTGATTACTTCCTGCCCAGT
    H5- TGGTACAGGCAGGCTCCTGGTAAAGAGCGCGAGTTCGTGAGCGTGATTGATGGG
    DR594 ACTGGTTCAACCAGTTACGCGGCCAGCGTGAAGGGGCGCTTCACCGCTTCCCAG
    GACAAGGGTAAGAACATCGCATATCTTCAGATGAACTCTCTCAAGCCTGAAGAC
    ACCGCTATGTACTATTGCAAAGCCAGCTGCGTGCGTGGCCGCGCCATCAGCGAA
    TACTGGGGGCAGGGCACCCAGGTCACTGTGTCTAGCGGTGGCTCAGGAGGGAGC
    GGAGGCTCCGGCCAGGTGCAGCTCCAGGAGTCTGGCGGTGGCAGCGTTCAGGCT
    GGCGGGAGCCTGCGCCTGAGCTGCGTGGCCTCTGCATCCACCTATTGCACCTAC
    GACATGCACTGGTATCGCCAGGCTCCTGGTAAGGGCCGTGAGTTCGTGAGCGCT
    ATTGATAGCGACGGGACTACCCGTTACGCGGATTCTGTGAAGGGCAGATTCACC
    ATCAGCCAGGGCACCGCCAAAAATACTGTTTATCTCCAGATGAATAGCCTGCAA
    CCAGAAGACACCGCCATGTATTACTGCAAGACCGTGTGCGTAGTGGGAAGTAGG
    TGGAGTGATTACTGGGGCCAGGGTACACAAGTCACAGTTTCAAGC
    hIL27 1299 CAGGTCCAGCTCCAGGAGAGCGGCGGAGGTAGCGTCCAGGCGGGCGGAAGCCTC
    Ra_VH AGACTGAGCTGCACAGCCTCTGGGTACGTCTCCTGCGACTATTTCCTGCCATCA
    H5- TGGTATAGGCAAGCACCAGGCAAGGAGAGGGAGTTCGTGAGTGTGATTGACGGA
    DR595 ACAGGGAGTACCTCCTACGCCGCATCTGTTAAGGGGCGGTTCACTGCAAGTCAG
    GATAAAGGTAAGAACATTGCCTACCTGCAAATGAACTCCCTGAAGCCAGAGGAC
    ACCGCAATGTATTACTGCAAGGCGAGCTGCGTTCGTGGTCGCGCAATCTCCGAG
    TACTGGGGCCAAGGGACCCAGGTGACCGTGTCTTCCGGTGGCGGTTCCCAGGTG
    CAGCTCCAGGAGTCCGGGGGTGGCTCTGTGCAGGCCGGGGGCTCTCTGACCCTC
    TCCTGTGCGGCCAGCGAGTACGCCTACTCTACTTGTAACATGGGGTGGTATCGC
    CAGGCTCCCGGCAAGGAGCGTGAGCTTGTTAGTGCATTTATCTCCGACGGTTCC
    ACCTATTACGCCGACAGCGTGAAGGGCCGCTTTACCATTACCCGTGACAATGCG
    AAGAACACTGTATATTTGCAGATGAACTCCTTGAAGCCCGAAGACACCGCCATC
    TACTATTGCAGCGCTAACTGTTACCGTCGCCTGCGCAACTATTGGGGGCAGGGG
    ACACAGGTGACAGTCTCCTCC
    hIL27 1300 CAGGTGCAGCTTCAGGAGAGCGGCGGAGGGTCCGTCCAAGCTGGCGGTTCCCTG
    Ra_VH AGACTGAGTTGCACCGCTTCAGGGTATGTTTCCTGTGACTATTTCCTTCCGAGC
    H5- TGGTATCGGCAAGCGCCAGGAAAGGAGCGTGAGTTTGTCAGCGTGATCGACGGC
    DR595 ACCGGAAGCACCTCCTACGCCGCGAGTGTGAAAGGCCGTTTTACTGCATCCCAA
    GACAAAGGCAAGAACATCGCCTACCTTCAAATGAACTCTCTGAAGCCGGAGGAC
    ACCGCCATGTACTATTGCAAGGCATCTTGCGTCAGGGGCAGGGCCATCTCAGAG
    TACTGGGGACAGGGAACCCAGGTGACAGTGTCTTCCGGCGGAAGTGGTGGCTCT
    GGTGGCTCTGGTCAGGTTCAGTTGCAGGAGTCCGGTGGAGGCTCAGTGCAGGCC
    GGTGGCTCCCTGACGCTGTCTTGCGCGGCCAGCGAGTATGCTTATTCCACCTGC
    AATATGGGGTGGTATCGCCAGGCCCCCGGAAAGGAACGTGAGCTGGTGAGCGCC
    TTCATCAGCGACGGGTCTACTTATTACGCTGATTCCGTCAAGGGTAGGTTTACC
    ATCACACGGGATAATGCCAAGAACACCGTCTACCTCCAGATGAACTCTCTGAAG
    CCCGAAGACACTGCCATCTACTATTGCTCCGCAAATTGCTACCGCAGACTGAGA
    AATTATTGGGGCCAGGGAACTCAGGTGACTGTGTCATCA
    hIL27 1301 CAGGTGCAGCTTCAGGAATCCGGGGGCGGGTCTGTGCAGGCTGGTGGCTCTCTG
    Ra_VH CGCCTCTCTTGCACCGCAAGCGGATACGTGTCCTGTGACTACTTCCTGCCGTCT
    H5- TGGTACAGACAAGCGCCCGGTAAAGAGCGCGAGTTCGTTTCCGTCATTGATGGC
    DR596 ACCGGGAGCACTTCCTACGCAGCCAGCGTAAAGGGCAGATTCACGGCTTCTCAA
    GACAAGGGCAAGAATATCGCGTACCTCCAGATGAACTCTCTGAAGCCCGAGGAC
    ACCGCGATGTACTATTGCAAGGCGAGCTGCGTGAGAGGCAGGGCCATCTCCGAA
    TACTGGGGCCAGGGCACCCAGGTGACCGTGTCTAGCGGTGGCGGTAGCCAGGTA
    CAGTTGCAGGAATCAGGCGGTGGATTGGTTCAGCCGGGTGGAAGCCTGAGGCTT
    AGCTGCACCGCCTCCGGGTTGACTTTCGACGATTCTGTAATGGGCTGGTTTCGC
    CAGGCCCCTGGTAAGGGGAGGGAGGCTGTGAGCTGCATTTCTTCCAGTGGAGCC
    AATGCTTTCTACGCCGACTCCGTCAAGGGGAGATTCACCATCAGCCGCGACAAT
    GCAAAAAACACTCTGTACCTCCAGATGAACTCCTTGAAGCCCGAGGACACTGCT
    ACTTATTACTGTAAAAGAGGACACGCTTGTGCTGGCTACTATCCTATCCCTTAC
    GATGACTATTGGGGTCAGGGCACTCAAGTGACCGTCTCCTCC
    hIL27 1302 CAGGTGCAGTTGCAGGAGTCTGGAGGCGGAAGCGTCCAAGCCGGGGGTTCCCTG
    Ra_VH AGACTCTCTTGCACCGCCTCCGGCTACGTATCCTGCGACTACTTCCTGCCCAGC
    H5- TGGTATCGCCAGGCTCCCGGTAAGGAGCGCGAGTTTGTCAGCGTGATCGACGGC
    DR596 ACCGGCTCCACCTCTTATGCCGCTAGTGTTAAGGGCCGCTTTACTGCCTCCCAG
    GACAAGGGCAAAAACATTGCCTACCTCCAGATGAACAGCCTGAAGCCCGAGGAC
    ACCGCAATGTATTACTGCAAGGCGTCCTGCGTGAGGGGTCGTGCCATTTCTGAG
    TACTGGGGCCAGGGGACCCAAGTCACCGTAAGTTCTGGGGGCTCTGGCGGTAGC
    GGAGGGAGTGGACAGGTGCAGCTCCAGGAGAGCGGCGGAGGCCTGGTGCAGCCT
    GGTGGGTCACTGAGACTGTCCTGCACAGCTTCAGGCCTGACCTTTGACGATTCT
    GTCATGGGGTGGTTCAGGCAAGCTCCGGGGAAAGGGCGCGAGGCCGTAAGCTGC
    ATCAGTAGCTCTGGTGCCAATGCTTTCTACGCGGACTCCGTGAAGGGGCGCTTT
    ACAATCTCTCGCGATAATGCTAAGAACACCTTGTATCTCCAAATGAACTCTTTG
    AAGCCCGAGGACACCGCCACCTACTATTGTAAGAGAGGGCACGCATGTGCTGGG
    TATTACCCTATCCCTTATGATGACTACTGGGGGCAAGGAACACAGGTTACTGTG
    TCTTCC
    hIL27 1303 CAGGTGCAGCTCCAGGAGTCTGGAGGTGGCCTGGTGCAGCCCGGCGGAAGCCTT
    Ra_VH CGCCTGAGTTGTGCGGCATCCGGCTTTTCCTTCTCATCTTACGCGATGAAGTGG
    H6- GTCCGCCAGGCCCCAGGGAAAGGCCTGGAGTGGGTGAGTACCATTTCATCCGGC
    DR591 GGTAGCTCCACCAATTATGCTGACAGCGTGAAGGGTAGGTTCACCATCAGCCGC
    GATAATGCCAAGAACACCCTCTACCTCCAGTTGAACTCCCTGAAGATCGAAGAC
    ACAGCTATGTATTACTGCGCCAAGGCCATCGTTCCCACTGGGGCCACAATGGAG
    AGGGGACAGGGGACGCAGGTGACTGTTAGCTCCGGTGGGGGCAGCCAAGTACAG
    TTGCAGGAGTCTGGTGGCGGTTCCGTGCAGGCCGGGGGCTCACTGCGTCTGTCC
    TGTACCGCTTCTGGTGCTATCGCCTCTGGATACATTGATTCTCGCTGGTGCATG
    GCGTGGTTCAGGCAAGCCCCTGGTAAAGAAAGAGAGGGTGTGGCTGCCATCTGG
    CCAGGAGGCGGGCTCACTGTATACGCAGATTCTGTGAAGGGAAGATTCACTATC
    TCACGGGATCACGCCAAAAATACGCTGTATTTGCAGATGAACAATTTGAAGCCG
    GAGGACACCGCGATGTACTATTGTGCTGCGGGCTCTCCTCGTATGTGCCCCTCC
    CTGGAGTTCGGATTCGATTATTGGGGCCAGGGCACGCAAGTTACCGTAAGCAGT
    hIL27 1304 CAGGTCCAGTTGCAGGAGAGTGGTGGCGGTCTCGTGCAACCGGGAGGCAGCCTC
    Ra_VH AGGCTGTCCTGCGCTGCCAGCGGGTTTTCCTTCAGCTCTTATGCGATGAAATGG
    H6- GTCCGCCAGGCTCCAGGCAAAGGTCTGGAGTGGGTGAGCACCATCAGCTCAGGA
    DR591 GGCTCCAGCACGAACTACGCTGACTCCGTTAAGGGACGGTTCACTATCTCAAGA
    GACAATGCAAAAAATACTCTGTATCTCCAGCTGAACTCCCTGAAGATCGAAGAC
    ACTGCTATGTATTACTGTGCCAAGGCCATCGTTCCTACAGGCGCGACAATGGAG
    CGTGGCCAGGGCACCCAGGTCACAGTGTCTTCAGGAGGCAGCGGTGGAAGCGGG
    GGCTCTGGCCAAGTGCAACTCCAGGAGTCAGGCGGGGGCTCCGTGCAGGCAGGA
    GGCAGCCTTCGCCTGTCCTGTACCGCATCAGGCGCTATTGCAAGCGGCTACATC
    GACTCCCGGTGGTGCATGGCCTGGTTCCGCCAAGCGCCGGGCAAAGAGCGCGAG
    GGCGTGGCTGCAATCTGGCCTGGTGGAGGCTTGACAGTGTATGCCGATAGTGTG
    AAGGGCCGCTTCACAATCAGCCGGGATCACGCAAAGAATACCCTGTACCTCCAG
    ATGAATAACCTGAAGCCTGAAGACACCGCCATGTACTATTGCGCAGCTGGCAGT
    CCTCGCATGTGTCCCAGCCTGGAGTTTGGATTCGATTACTGGGGTCAAGGTACA
    CAGGTGACTGTCTCATCC
    hIL27 1305 CAAGTGCAGCTCCAGGAGTCAGGCGGGGGCCTTGTGCAGCCTGGTGGCTCTCTG
    Ra_VH AGGCTGTCTTGTGCGGCTTCAGGCTTCTCCTTCTCCTCATACGCAATGAAGTGG
    H6- GTACGTCAGGCCCCCGGCAAAGGCCTTGAGTGGGTCTCCACTATCTCTTCCGGT
    DR592 GGCTCTTCCACCAACTACGCTGATTCAGTCAAAGGCCGGTTCACGATCTCTCGC
    GATAACGCCAAGAACACGCTGTACCTCCAGCTGAACTCCCTGAAGATCGAAGAC
    ACTGCCATGTACTATTGCGCCAAGGCCATTGTTCCCACCGGAGCCACTATGGAA
    CGCGGCCAGGGCACCCAGGTCACCGTGTCCTCTGGAGGCGGTTCACAGGTCCAA
    CTTCAGGAGAGCGGAGGCGGGTCCGTGCAGGCGGGAGGCTCCCTGCGTCTGTCC
    TGTACCGCTCCCGGTTTCACCAGTAACTCCTGCGGCATGGATTGGTACAGACAG
    GCCCCTGGTAAGGAAAGGGAATTTGTCAGCTCTATCAGCACCGACGGAACAACC
    GGCTATGCCGATAGCGTGAAGGGACGCTTTACTATCTCAAAGGACAAGGCTAAG
    GACACAGTGTACCTCCAGATGAACTCCCTCAAGCCCGAGGACACCGGCATGTAT
    TCCTGCAAGACAAAAGACGGCACCATTGCAACTATGGAGCTGTGTGATTTTGGT
    TATTGGGGCCAGGGAACACAGGTCACCGTCTCCAGC
    hIL27 1306 CAGGTTCAGCTTCAGGAGTCTGGCGGAGGCCTGGTTCAGCCCGGAGGCAGTCTG
    Ra_VH CGCCTTTCTTGCGCCGCGAGCGGCTTCTCATTCTCCAGCTACGCCATGAAGTGG
    H6- GTGCGCCAGGCTCCCGGAAAGGGACTGGAGTGGGTGTCCACAATCTCTTCAGGA
    DR592 GGCTCCAGCACAAATTACGCCGACAGCGTGAAGGGCCGCTTCACGATCTCACGG
    GATAACGCGAAGAACACTCTGTATCTTCAGCTCAACTCCCTGAAGATCGAGGAC
    ACAGCTATGTATTACTGTGCTAAGGCTATCGTTCCTACCGGCGCTACTATGGAA
    AGAGGGCAGGGCACCCAAGTGACTGTGTCTAGCGGAGGTAGCGGAGGGTCCGGT
    GGAAGTGGTCAGGTACAGCTCCAGGAATCTGGTGGAGGCAGTGTTCAGGCTGGA
    GGTTCTTTGAGACTGTCCTGCACAGCTCCTGGATTTACCAGCAACAGCTGTGGG
    ATGGACTGGTATCGCCAGGCACCGGGCAAGGAAAGAGAGTTTGTCTCTAGCATC
    TCTACCGACGGTACAACCGGCTATGCCGACTCTGTGAAGGGTAGGTTCACTATC
    TCCAAGGACAAAGCAAAGGATACTGTGTACCTCCAGATGAACTCCTTGAAGCCC
    GAGGACACCGGCATGTACTCATGTAAGACCAAGGATGGGACCATCGCTACTATG
    GAGCTGTGTGACTTCGGATACTGGGGCCAGGGTACTCAGGTCACCGTGTCTTCT
    hIL27 1307 CAAGTCCAGTTGCAGGAGTCCGGCGGGGGCCTGGTCCAGCCAGGAGGCAGCTTG
    Ra_VH CGTCTGTCATGTGCTGCCTCTGGTTTCTCATTTTCCAGCTACGCCATGAAGTGG
    H6- GTGAGACAGGCTCCAGGAAAGGGCCTGGAGTGGGTGTCTACAATCTCCTCTGGA
    DR593 GGGTCTTCCACTAACTATGCCGACTCCGTCAAAGGACGCTTCACAATTTCACGC
    GACAACGCGAAAAATACCTTGTACCTCCAGTTGAACTCACTCAAGATCGAAGAC
    ACGGCCATGTATTACTGCGCCAAAGCCATCGTGCCCACAGGTGCTACTATGGAG
    CGCGGCCAGGGCACCCAGGTTACCGTCAGCTCTGGCGGAGGCTCCCAAGTGCAG
    CTGCAAGAGAGCGGCGGGGGCAGCGTCCAGGCCGGTGGCTCCCTGAGGCTCTCC
    TGTGCTGCCTCCGGTTACCCATACTCCAATGGGTATATGGGCTGGTTCCGCCAA
    GCCCCAGGCAAGGAGAGGGAAGGAGTGGCAACCATCTACACCGGCGATGGCCGC
    ACATATTACGCAGACAGCGTCAAGGGCAGGTTTACCATTAGTCGCGACAACGCC
    AAGAACACTGTGGACCTCCAGATGTCTTCCCTGAAGCCCGAGGACACAGCTATG
    TATTACTGTGCGGCCAGGGCTGCACCGCTGTACTCCAGCGGTTCACCGCTGACA
    CGCGCCCGGTACAACGTCTGGGGCCAGGGCACACAGGTTACGGTCTCTTCT
    hIL27 1308 CAGGTCCAGCTCCAGGAATCCGGTGGGGGCCTGGTGCAGCCCGGTGGCTCCCTG
    Ra_VH CGCCTGTCCTGCGCTGCATCCGGCTTCAGCTTCAGCTCCTATGCTATGAAGTGG
    H6- GTCCGGCAAGCGCCTGGCAAGGGACTGGAGTGGGTGAGTACAATCAGCTCCGGG
    DR593 GGCTCCTCTACCAACTATGCCGATAGCGTGAAGGGTAGGTTCACCATTAGCCGC
    GACAACGCCAAGAACACTCTGTACCTTCAGCTGAACTCCCTGAAAATCGAAGAC
    ACAGCGATGTATTACTGCGCGAAGGCCATCGTGCCTACTGGTGCTACTATGGAA
    AGAGGGCAAGGCACACAGGTGACCGTTAGCTCCGGTGGCTCCGGCGGAAGCGGT
    GGGTCAGGTCAGGTTCAGCTCCAAGAAAGCGGCGGTGGCAGCGTGCAGGCTGGA
    GGCTCCCTTAGACTCTCCTGCGCCGCATCTGGATACCCTTATAGCAACGGCTAC
    ATGGGATGGTTTCGCCAAGCCCCTGGTAAGGAGCGCGAGGGCGTCGCTACTATT
    TATACTGGGGATGGCCGCACTTACTATGCCGATTCTGTGAAGGGGCGCTTTACT
    ATCTCACGCGACAACGCAAAGAACACCGTGGACCTCCAGATGTCATCTCTCAAG
    CCGGAAGATACCGCTATGTATTACTGTGCTGCCCGCGCAGCTCCCCTGTACTCT
    TCCGGCTCCCCACTCACCCGTGCCCGCTATAACGTGTGGGGACAGGGCACTCAG
    GTGACCGTCTCATCT
    hIL27 1309 CAGGTGCAGTTGCAGGAGAGCGGGGGTGGGCTGGTCCAGCCCGGCGGATCTCTG
    Ra_VH CGCCTCAGCTGCGCCGCAAGCGGCTTCTCCTTCTCCAGCTACGCTATGAAATGG
    H6- GTCCGCCAGGCCCCCGGTAAGGGGTTGGAGTGGGTGTCTACCATTTCCAGTGGC
    DR594 GGTTCCAGCACCAACTACGCTGACAGCGTGAAGGGCAGATTCACGATCTCTCGC
    GACAATGCTAAAAATACCCTGTACCTGCAACTCAACAGCCTGAAGATCGAGGAT
    ACCGCCATGTATTACTGTGCCAAGGCCATCGTTCCTACTGGGGCCACTATGGAG
    AGGGGACAAGGAACTCAGGTCACCGTCTCTTCCGGTGGGGGCAGCCAAGTCCAG
    CTCCAAGAATCTGGCGGAGGCTCTGTGCAGGCTGGCGGATCACTCAGACTGTCC
    TGTGTGGCGTCCGCTTCCACCTATTGCACCTACGACATGCACTGGTATCGCCAG
    GCCCCTGGCAAAGGCAGGGAATTTGTGTCTGCTATCGACAGCGACGGTACAACC
    CGCTATGCCGATTCAGTGAAGGGTCGGTTCACCATCTCACAAGGCACCGCCAAG
    AACACCGTGTACTTGCAGATGAACTCTCTGCAACCCGAGGACACTGCAATGTAT
    TACTGCAAGACTGTGTGCGTGGTCGGAAGCAGATGGTCTGATTATTGGGGCCAA
    GGCACACAGGTTACTGTGAGCAGT
    hIL27 1310 CAGGTGCAGCTCCAGGAGTCCGGGGGAGGCCTGGTGCAGCCTGGTGGGTCTCTG
    Ra_VH CGGCTGTCCTGTGCCGCTTCAGGATTTAGCTTCTCTTCCTATGCTATGAAGTGG
    H6- GTGCGCCAGGCTCCTGGTAAGGGACTGGAATGGGTGTCTACAATTAGTTCCGGC
    DR594 GGGTCCTCTACCAACTATGCCGACTCCGTGAAGGGTAGATTCACGATCAGCAGA
    GACAACGCCAAGAATACCCTCTACTTGCAGCTCAACTCCCTGAAAATTGAAGAC
    ACCGCGATGTATTACTGTGCCAAGGCCATCGTGCCCACGGGCGCTACAATGGAG
    CGCGGCCAGGGCACACAGGTGACCGTTTCTTCCGGTGGCAGCGGAGGCTCCGGG
    GGCTCCGGCCAGGTGCAGCTCCAGGAGTCAGGAGGCGGGTCCGTGCAGGCCGGT
    GGCAGTCTGCGTTTGTCCTGTGTGGCCAGCGCATCCACCTATTGTACCTACGAT
    ATGCACTGGTATCGTCAGGCCCCAGGCAAGGGCAGGGAGTTCGTTAGCGCTATT
    GACTCCGACGGCACCACTCGCTACGCTGACAGTGTCAAAGGCCGCTTCACTATC
    TCTCAGGGGACTGCCAAGAACACCGTGTATCTCCAGATGAACTCCCTGCAACCA
    GAGGACACAGCCATGTACTATTGCAAGACAGTGTGCGTTGTGGGCTCTCGCTGG
    TCCGACTATTGGGGCCAGGGCACCCAGGTGACAGTGTCTTCC
    hIL27 1311 CAAGTGCAGCTCCAGGAGTCTGGTGGAGGCCTGGTCCAGCCCGGTGGGAGCTTG
    Ra_VH AGATTGTCTTGCGCAGCCTCTGGATTCTCTTTCTCCAGCTACGCCATGAAATGG
    H6- GTGCGGCAGGCACCAGGGAAGGGCCTGGAATGGGTGTCTACCATTTCTTCCGGC
    DR595 GGTTCTTCCACTAATTACGCAGACTCCGTGAAGGGCCGGTTCACCATTTCCCGT
    GACAACGCTAAGAATACCCTGTACTTGCAGCTGAACTCCCTGAAGATCGAGGAC
    ACGGCTATGTATTACTGTGCTAAAGCCATTGTCCCTACAGGGGCCACAATGGAA
    CGCGGCCAGGGTACTCAAGTGACGGTCAGCTCTGGCGGGGGCAGCCAAGTGCAG
    CTCCAGGAGAGCGGAGGTGGGTCCGTGCAGGCTGGTGGCTCCCTGACCCTGAGC
    TGTGCCGCATCTGAATATGCGTATAGCACTTGTAATATGGGATGGTATCGCCAG
    GCTCCTGGTAAGGAGCGCGAGCTGGTGAGCGCTTTCATTTCCGACGGTAGCACA
    TATTACGCGGACTCCGTCAAAGGTCGCTTCACCATTACACGCGATAACGCCAAG
    AATACCGTGTATTTGCAGATGAACTCACTCAAGCCAGAAGACACTGCCATCTAC
    TATTGTTCAGCCAACTGTTATCGCAGACTCCGCAACTATTGGGGCCAGGGGACG
    CAGGTAACCGTGTCCTCC
    hIL27 1312 CAGGTGCAGCTCCAGGAATCTGGCGGTGGCCTGGTGCAGCCGGGCGGGTCCCTG
    Ra_VH AGACTGAGTTGCGCTGCCAGCGGGTTTTCCTTCAGTTCCTATGCCATGAAGTGG
    H6- GTCCGCCAAGCTCCGGGGAAGGGCCTGGAATGGGTCTCCACTATTAGTTCCGGT
    DR595 GGCTCTAGCACAAACTATGCGGATTCCGTGAAGGGACGCTTCACCATCTCTCGG
    GACAACGCCAAGAATACCCTGTACCTCCAGCTGAATAGTCTCAAGATCGAAGAC
    ACCGCGATGTACTATTGCGCCAAAGCCATCGTTCCTACTGGTGCTACAATGGAG
    CGTGGCCAGGGCACCCAGGTGACCGTCTCCTCTGGCGGATCTGGGGGTTCCGGG
    GGCTCCGGCCAGGTCCAGTTGCAGGAAAGCGGCGGGGGCTCCGTTCAGGCCGGG
    GGCAGTCTGACCCTGTCCTGTGCAGCCTCTGAGTACGCCTATTCCACCTGTAAC
    ATGGGCTGGTACAGACAAGCGCCCGGAAAAGAGCGCGAATTGGTCTCCGCCTTC
    ATCTCCGATGGTAGCACTTATTACGCGGACTCTGTAAAAGGCCGTTTCACTATT
    ACCCGCGACAACGCCAAGAACACCGTCTATCTCCAGATGAACAGCCTGAAGCCA
    GAAGATACGGCCATTTACTATTGCTCCGCTAACTGCTACAGACGCTTGAGGAAT
    TATTGGGGCCAGGGCACACAAGTGACTGTTTCCTCC
    hIL27 1313 CAGGTGCAGCTGCAAGAGAGCGGTGGCGGTCTGGTACAGCCAGGTGGCAGCCTG
    Ra_VH CGCCTGTCCTGCGCTGCATCAGGCTTCTCCTTCAGTTCCTATGCCATGAAGTGG
    H6- GTGCGCCAGGCTCCAGGCAAAGGATTGGAGTGGGTGTCTACCATTTCTTCCGGG
    DR596 GGCTCATCCACAAACTACGCCGACAGCGTGAAGGGCCGCTTCACCATCTCCCGC
    GACAACGCCAAGAACACTCTGTATCTTCAGCTGAACTCCCTGAAGATTGAGGAT
    ACCGCTATGTATTACTGCGCTAAGGCCATCGTTCCCACAGGCGCTACGATGGAA
    CGCGGTCAGGGGACACAAGTAACCGTAAGCAGTGGTGGCGGTAGCCAGGTGCAG
    CTCCAGGAGTCCGGCGGTGGCCTGGTGCAGCCGGGTGGGTCCCTGAGGCTGAGT
    TGCACAGCCAGCGGTCTGACCTTCGATGACTCCGTGATGGGGTGGTTCCGCCAG
    GCACCTGGCAAGGGCCGCGAGGCTGTGTCCTGCATTAGCTCTAGCGGTGCCAAT
    GCCTTCTACGCTGACTCAGTCAAGGGCCGCTTCACCATCTCCCGCGATAACGCC
    AAGAACACCCTGTACTTGCAGATGAACTCCCTGAAACCCGAGGATACAGCAACA
    TACTATTGCAAGCGGGGGCACGCCTGTGCAGGATACTATCCTATCCCCTATGAC
    GATTATTGGGGTCAGGGCACCCAGGTCACCGTCAGCAGC
    hIL27 1314 CAGGTGCAGCTCCAGGAGTCCGGCGGAGGTCTGGTTCAGCCCGGAGGCTCCCTT
    Ra_VH CGCCTCTCCTGTGCTGCGTCAGGATTCTCCTTTAGCTCCTACGCTATGAAGTGG
    H6- GTGCGCCAAGCCCCCGGCAAGGGCCTGGAGTGGGTATCCACCATTTCCAGTGGC
    DR596 GGTTCTTCAACCAACTATGCTGATTCCGTGAAAGGCCGCTTCACCATCTCCCGT
    GACAACGCAAAAAATACCTTGTATTTGCAGCTGAACAGCCTGAAGATCGAGGAC
    ACCGCGATGTACTATTGCGCCAAGGCCATCGTGCCTACTGGCGCAACAATGGAG
    CGTGGACAGGGCACTCAGGTCACTGTGAGTAGCGGAGGGAGTGGCGGTTCCGGC
    GGTTCAGGACAGGTGCAGCTCCAGGAGAGCGGGGGTGGGCTGGTACAGCCAGGT
    GGCTCTCTCAGGCTGAGTTGCACGGCCTCAGGCCTGACCTTCGATGACAGCGTC
    ATGGGCTGGTTCCGCCAGGCCCCAGGTAAAGGCCGTGAGGCTGTGTCCTGTATT
    AGCTCATCTGGGGCCAATGCGTTCTATGCTGACAGTGTCAAAGGCCGCTTCACA
    ATTTCCCGTGACAACGCCAAGAACACCCTGTATTTGCAGATGAACAGTCTGAAG
    CCGGAAGACACCGCCACCTACTATTGTAAGCGCGGTCACGCTTGTGCAGGTTAT
    TACCCTATTCCTTATGATGACTACTGGGGCCAGGGAACGCAGGTGACAGTGTCC
    TCT
    hIL27 1315 CAGGTCCAGTTGCAGGAGTCTGGAGGTGGCCTGGTGCAGCCGGGAGGTTCTCTG
    Ra_VH CGGCTGTCCTGCGCCGCATCTGGATTCACCTTCAGTTCTTATCCAATGTCTTGG
    H7- GTCAGGCAAGCGCCGGGCAAGGGCCTGGAATGGATTAGCACTATTTCCGCAGGT
    DR591 GGCGATACCACTCTGTATGCCGATTCAGTGAAAGGCCGCTTCACCAGCTCTCGG
    GATAACGCTAAGAACACCCTGTATCTCCAGCTGAATAGCCTTAAAACCGAAGAC
    ACCGCAATCTATTACTGTGCTAAAAGGATTGATTGTAATTCTGGCTATTGTTAC
    AGACGCAACTACTGGGGACAGGGCACCCAAGTGACCGTTTCCAGTGGGGGGGG
    AGCCAGGTACAACTCCAGGAGTCCGGTGGAGGTAGCGTGCAGGCCGGGGGCTCT
    CTCCGTCTGTCCTGCACCGCATCCGGGGCTATCGCCTCTGGGTACATTGACAGC
    CGCTGGTGCATGGCCTGGTTCCGTCAGGCCCCCGGCAAGGAACGCGAGGGCGTG
    GCTGCCATCTGGCCGGGCGGAGGGCTGACTGTGTATGCGGACTCCGTCAAGGGC
    AGGTTTACCATCAGCCGCGACCATGCTAAGAACACCCTGTACCTCCAGATGAAT
    AACTTGAAACCTGAAGACACCGCCATGTACTATTGCGCGGCTGGTTCCCCACGC
    ATGTGCCCCTCACTTGAGTTTGGGTTCGATTACTGGGGCCAGGGCACCCAGGTG
    ACTGTGTCCAGC
    hIL27 1316 CAGGTCCAGCTTCAGGAGTCCGGCGGTGGCCTTGTCCAGCCAGGAGGCAGCCTG
    Ra_VH CGGCTGTCCTGCGCCGCGAGCGGCTTCACGTTCTCATCCTACCCAATGTCCTGG
    H7- GTCCGTCAGGCCCCAGGGAAGGGGCTGGAGTGGATCAGTACCATCTCCGCCGGT
    DR591 GGCGATACCACTTTGTACGCCGACTCTGTGAAAGGGCGCTTTACCTCTTCCCGC
    GATAACGCGAAAAACACATTGTACCTCCAGCTCAACTCCCTGAAGACTGAGGAC
    ACTGCCATCTACTATTGCGCCAAGAGAATTGATTGCAACAGCGGGTATTGCTAC
    CGGCGCAACTACTGGGGCCAGGGAACCCAGGTGACGGTATCCTCTGGGGGCTCT
    GGAGGTTCAGGAGGCAGCGGACAAGTGCAGCTCCAGGAATCAGGAGGCGGTTCT
    GTGCAGGCGGGTGGCTCTCTGCGTCTGAGCTGCACTGCGTCTGGAGCCATCGCT
    TCTGGTTACATCGACAGCAGATGGTGCATGGCATGGTTCCGTCAGGCTCCGGGA
    AAGGAGAGGGAGGGAGTGGCCGCTATCTGGCCCGGAGGGGGCTTGACAGTCTAC
    GCTGATTCCGTGAAGGGAAGGTTCACGATCTCACGTGACCACGCTAAGAATACC
    CTGTACCTTCAGATGAATAACCTGAAGCCCGAGGACACCGCAATGTACTATTGT
    GCTGCCGGAAGCCCCAGGATGTGTCCCAGCCTGGAATTTGGCTTTGACTACTGG
    GGTCAGGGCACTCAGGTCACAGTCTCCTCT
    hIL27 1317 CAGGTGCAGTTGCAGGAGTCCGGCGGGGGCCTGGTGCAGCCAGGAGGGTCTCTG
    Ra_VH AGGCTGAGTTGCGCCGCTAGTGGCTTCACCTTCTCCAGCTATCCCATGTCTTGG
    H7- GTGCGCCAGGCTCCCGGTAAAGGACTTGAGTGGATTAGCACGATCTCCGCTGGA
    DR592 GGTGACACGACTCTCTACGCCGATAGCGTGAAGGGACGCTTCACCAGTTCTCGT
    GACAACGCCAAGAATACCCTGTACCTCCAACTGAACAGCCTGAAGACGGAGGAC
    ACCGCCATCTATTACTGTGCAAAGCGTATTGATTGTAACTCAGGATACTGCTAT
    CGGCGCAACTATTGGGGACAGGGCACGCAGGTGACAGTTAGCTCCGGTGGCGGA
    AGTCAGGTCCAACTTCAGGAAAGCGGAGGTGGCAGCGTTCAGGCTGGCGGTTCC
    TTGCGCCTGTCTTGTACCGCACCGGGCTTTACAAGCAACAGCTGCGGTATGGAC
    TGGTATAGACAAGCTCCAGGCAAAGAAAGGGAGTTCGTGTCCAGCATTAGCACT
    GACGGCACCACAGGCTATGCTGATTCCGTGAAGGGACGCTTCACTATCTCCAAA
    GATAAGGCGAAGGACACTGTATACCTCCAGATGAACTCCCTGAAGCCTGAGGAT
    ACCGGCATGTATAGTTGCAAGACCAAGGATGGCACCATCGCAACGATGGAACTC
    TGTGACTTCGGCTATTGGGGGCAGGGCACCCAGGTGACCGTGTCCTCT
    hIL27 1318 CAGGTGCAGCTGCAAGAATCCGGGGGCGGGCTCGTGCAGCCTGGGGGTTCCCTC
    Ra_VH CGTCTGAGCTGCGCGGCTTCCGGCTTCACTTTCTCTTCCTATCCCATGTCCTGG
    H7- GTGAGGCAGGCCCCTGGCAAGGGCTTGGAATGGATTAGCACCATCAGCGCCGGG
    DR592 GGCGACACAACCCTGTACGCTGACAGCGTGAAGGGAAGATTCACGTCCAGCCGG
    GATAACGCCAAGAACACCCTGTACCTCCAGTTGAACTCCCTGAAGACTGAAGAT
    ACCGCCATCTATTACTGTGCCAAGCGCATTGATTGCAACAGCGGCTACTGCTAT
    CGCCGGAACTACTGGGGGCAGGGTACACAGGTAACGGTGTCCTCAGGGGGCTCC
    GGCGGGAGTGGGGGCAGCGGGCAAGTTCAGTTGCAGGAGAGCGGCGGGGGCTCC
    GTCCAAGCAGGCGGAAGCCTTCGCCTCAGCTGCACCGCACCGGGTTTCACATCT
    AATAGCTGCGGAATGGATTGGTATCGGCAGGCCCCCGGTAAGGAGCGCGAGTTC
    GTGAGTTCCATCAGTACCGACGGCACAACCGGCTATGCTGACTCCGTGAAGGGT
    CGCTTCACCATTTCTAAGGATAAGGCCAAAGACACCGTGTACCTTCAGATGAAC
    TCACTGAAGCCAGAAGACACAGGAATGTACTCTTGTAAAACGAAGGATGGAACC
    ATCGCTACGATGGAGCTGTGCGACTTTGGCTACTGGGGCCAGGGCACCCAGGTG
    ACAGTAAGCTCT
    hIL27 1319 CAGGTCCAACTCCAGGAAAGCGGCGGTGGCCTGGTGCAGCCAGGTGGGTCTCTC
    Ra_VH CGTCTGAGCTGTGCTGCATCCGGCTTCACTTTTAGCTCTTACCCGATGAGCTGG
    H7- GTGCGCCAGGCTCCGGGAAAGGGCCTTGAGTGGATCAGCACCATCTCAGCCGGG
    DR593 GGCGATACAACCCTGTATGCAGACAGTGTTAAAGGCCGTTTTACCTCCTCTCGC
    GACAATGCTAAAAACACCCTTTATCTTCAGCTCAATAGTCTGAAGACTGAGGAC
    ACCGCCATTTATTACTGCGCTAAACGCATTGATTGCAACTCCGGGTACTGCTAC
    AGACGTAACTATTGGGGCCAGGGAACACAGGTGACCGTGTCCAGTGGCGGAGGT
    AGTCAGGTCCAGTTGCAAGAGAGCGGGGGAGGCAGCGTCCAGGCGGGTGGCTCC
    CTGCGCCTGAGCTGCGCAGCCTCTGGTTACCCATACAGCAACGGCTACATGGGC
    TGGTTCAGGCAAGCACCGGGTAAGGAGCGGGAAGGCGTGGCAACCATCTATACA
    GGTGATGGTCGCACCTATTACGCAGATTCCGTCAAGGGCCGGTTCACTATCAGC
    CGCGACAACGCAAAGAATACAGTCGATCTCCAGATGAGCAGTTTGAAACCTGAA
    GACACGGCGATGTATTACTGCGCCGCTCGTGCTGCGCCACTCTACTCCTCTGGC
    TCCCCTCTCACACGTGCTCGTTATAATGTATGGGGCCAGGGCACTCAAGTGACA
    GTCTCCAGT
    hIL27 1320 CAGGTGCAGTTGCAGGAGTCCGGCGGTGGACTGGTCCAACCAGGCGGTAGTCTC
    Ra_VH AGGCTGTCCTGTGCCGCTTCTGGTTTCACTTTCAGCTCCTACCCAATGTCCTGG
    H7- GTACGGCAAGCTCCTGGGAAGGGTCTGGAGTGGATCTCCACGATCTCCGCAGGC
    DR593 GGGGACACTACCCTCTACGCCGACTCTGTGAAGGGCCGTTTCACTTCTAGCAGA
    GATAATGCAAAAAACACTCTCTATCTTCAGCTGAACAGTCTGAAAACCGAAGAT
    ACTGCGATCTATTACTGCGCCAAGCGCATCGACTGCAATTCTGGTTACTGTTAC
    CGTCGCAATTACTGGGGCCAAGGAACCCAGGTCACGGTGTCCTCAGGTGGCAGC
    GGAGGTTCCGGCGGGTCCGGTCAGGTCCAGTTGCAGGAAAGCGGCGGAGGTTCT
    GTCCAAGCCGGAGGCAGCCTGAGGCTGTCTTGCGCTGCCAGTGGATACCCCTAT
    AGCAACGGCTACATGGGCTGGTTCCGCCAAGCGCCAGGGAAGGAACGTGAAGGT
    GTGGCCACCATCTACACCGGCGATGGCAGGACCTACTATGCTGACTCCGTGAAG
    GGTAGGTTCACCATCTCTCGCGATAACGCCAAGAACACTGTGGACCTCCAGATG
    TCTTCCTTGAAACCTGAGGACACCGCGATGTATTACTGCGCGGCCCGCGCCGCG
    CCCCTCTACAGTTCAGGCAGCCCCCTGACCAGAGCAAGGTATAACGTGTGGGGT
    CAGGGCACTCAGGTGACCGTTAGCAGT
    hIL27 1321 CAAGTTCAGCTCCAGGAATCTGGCGGTGGCCTGGTCCAGCCAGGTGGCTCCCTG
    Ra_VH CGCCTGAGTTGTGCGGCTAGTGGCTTCACCTTCAGCTCCTACCCGATGAGTTGG
    H7- GTGCGTCAGGCTCCAGGGAAGGGTCTGGAGTGGATCTCTACCATCAGCGCCGGT
    DR594 GGCGATACTACCCTGTATGCGGATTCCGTGAAGGGTCGCTTTACCAGCTCTCGG
    GACAACGCCAAGAACACGCTCTACTTGCAGCTGAACAGTCTGAAGACCGAGGAT
    ACCGCTATCTACTATTGTGCCAAGCGCATCGACTGTAACAGCGGGTACTGCTAC
    CGCCGTAACTATTGGGGCCAGGGAACACAAGTTACCGTGTCAAGCGGAGGCGGT
    TCCCAGGTGCAGCTCCAGGAATCTGGCGGAGGCAGCGTACAGGCGGGAGGCTCA
    CTGCGCCTGTCTTGTGTCGCATCAGCCAGCACCTACTGCACCTATGACATGCAC
    TGGTATCGGCAGGCTCCCGGCAAAGGCCGCGAGTTCGTCAGCGCCATTGATTCC
    GATGGCACCACGAGGTACGCCGATTCTGTAAAGGGCCGCTTTACTATCTCCCAG
    GGTACTGCCAAGAACACCGTGTACCTCCAGATGAACAGTCTTCAGCCAGAGGAT
    ACGGCTATGTATTACTGCAAGACTGTTTGTGTCGTTGGCTCCAGGTGGAGCGAC
    TACTGGGGTCAGGGAACCCAGGTCACTGTGAGTAGC
    hIL27 1322 CAGGTCCAACTTCAGGAATCCGGCGGGGGTCTGGTGCAACCTGGCGGTAGCCTC
    Ra_VH CGGCTTAGTTGCGCCGCAAGTGGATTCACCTTTTCCAGCTATCCCATGTCCTGG
    H7- GTGCGTCAAGCGCCGGGTAAGGGTCTCGAATGGATTTCAACAATCTCTGCCGGT
    DR594 GGCGACACCACTCTCTACGCGGATTCCGTGAAAGGGCGCTTCACCTCCTCTCGT
    GACAATGCCAAGAACACTCTGTATCTCCAGCTTAACTCCTTGAAGACAGAGGAT
    ACTGCCATCTATTACTGCGCCAAGCGCATCGACTGTAACTCTGGCTATTGTTAC
    CGCCGTAACTACTGGGGACAGGGCACTCAAGTCACCGTCTCCTCTGGAGGCAGC
    GGAGGTTCCGGGGGCTCTGGCCAGGTTCAGCTCCAGGAGAGCGGCGGAGGGAGC
    GTGCAGGCAGGTGGAAGCCTGCGTCTGTCCTGTGTGGCCTCCGCTTCAACCTAC
    TGCACCTATGATATGCACTGGTATCGTCAGGCCCCCGGCAAAGGTAGAGAGTTC
    GTGTCCGCCATTGATTCCGATGGTACTACCAGATATGCCGACAGCGTAAAGGGA
    CGTTTCACGATCTCTCAAGGCACCGCCAAGAACACCGTTTACCTCCAGATGAAT
    AGCCTCCAGCCGGAAGATACTGCAATGTATTACTGCAAGACTGTTTGCGTGGTT
    GGCAGCCGCTGGAGCGACTACTGGGGCCAGGGGACCCAGGTGACCGTCTCCTCT
    hIL27 1323 CAGGTCCAGTTGCAGGAATCCGGCGGAGGCCTGGTGCAGCCAGGGGGCTCTCTG
    Ra_VH AGGCTGAGCTGTGCCGCGAGCGGCTTCACATTCTCCAGCTACCCCATGTCTTGG
    H7- GTGCGTCAGGCCCCTGGCAAGGGTCTGGAGTGGATCTCCACCATCTCTGCTGGC
    DR595 GGTGACACCACTCTGTATGCCGACAGTGTTAAAGGGCGTTTCACGTCTTCCCGT
    GACAATGCCAAGAACACTCTCTACCTCCAGTTGAACTCACTGAAAACCGAGGAT
    ACCGCCATTTATTACTGCGCCAAGCGTATCGACTGCAACTCTGGCTACTGTTAT
    CGCCGGAACTACTGGGGCCAGGGGACCCAGGTGACTGTCAGTTCTGGCGGGGGC
    TCTCAGGTTCAGCTCCAGGAGTCAGGAGGCGGTTCAGTGCAAGCTGGAGGCTCC
    CTGACACTCAGCTGTGCCGCGAGTGAGTACGCATACTCCACCTGTAACATGGGT
    TGGTATCGCCAGGCTCCAGGTAAAGAGCGCGAGCTGGTCTCCGCCTTCATCTCC
    GACGGCTCCACGTATTACGCCGATTCTGTGAAAGGCCGTTTCACAATCACACGC
    GACAATGCAAAGAACACAGTGTATCTTCAGATGAACTCACTCAAGCCTGAAGAC
    ACCGCGATCTATTACTGCTCCGCAAACTGTTACAGACGCCTCCGCAACTACTGG
    GGGCAAGGCACTCAAGTGACTGTTTCCAGT
    hIL27 1324 CAGGTACAGTTGCAGGAGTCAGGAGGTGGCCTGGTGCAGCCTGGTGGCAGCTTG
    Ra_VH CGCCTGTCTTGCGCAGCCTCTGGCTTCACATTCAGCTCATACCCTATGTCTTGG
    H7- GTCAGGCAGGCTCCAGGTAAGGGGCTGGAATGGATTTCTACCATTAGTGCAGGC
    DR595 GGTGACACAACCCTGTACGCCGACTCAGTCAAGGGCCGGTTTACGTCCAGCCGC
    GACAATGCAAAGAACACTCTCTACTTGCAGCTCAACAGTCTGAAGACCGAGGAT
    ACTGCCATCTACTATTGTGCTAAGAGAATTGATTGCAACAGCGGCTATTGCTAC
    CGCAGAAATTACTGGGGGCAGGGCACCCAGGTGACTGTTTCTTCCGGGGGCAGC
    GGGGGTAGCGGTGGGTCCGGTCAGGTCCAGCTTCAGGAGTCCGGCGGAGGCAGC
    GTGCAGGCCGGAGGCAGCCTCACCCTGTCTTGTGCCGCTTCTGAATACGCTTAT
    TCTACTTGTAACATGGGCTGGTATCGGCAGGCTCCCGGTAAGGAGCGCGAGCTG
    GTCAGCGCCTTCATCTCTGACGGATCTACTTATTACGCCGATTCCGTCAAGGGT
    CGCTTCACCATCACCAGAGACAATGCCAAAAACACCGTCTATCTCCAGATGAAC
    TCTCTCAAGCCGGAGGACACCGCGATTTACTATTGCTCTGCGAACTGTTACCGT
    CGCCTCCGTAACTATTGGGGTCAGGGCACCCAGGTCACGGTGTCCAGC
    hIL27 1325 CAGGTACAACTCCAGGAGTCCGGCGGGGGACTGGTGCAGCCGGGTGGCTCCCTT
    Ra_VH CGTCTGAGCTGTGCTGCCAGCGGTTTCACCTTCAGCTCCTACCCAATGTCTTGG
    H7- GTCCGTCAAGCGCCTGGTAAGGGTCTTGAGTGGATTAGTACTATCAGCGCTGGT
    DR596 GGCGATACCACGCTCTACGCTGATTCCGTCAAAGGCCGCTTTACTTCTTCCAGG
    GATAACGCAAAAAACACTCTTTACCTCCAGCTGAACTCCCTGAAGACCGAAGAT
    ACCGCAATCTATTACTGTGCTAAACGGATTGATTGCAACTCCGGCTACTGTTAT
    CGCCGTAATTACTGGGGCCAGGGTACACAGGTGACCGTGTCCTCAGGCGGGGGC
    TCCCAAGTTCAGCTTCAGGAGAGTGGCGGTGGCCTGGTCCAGCCGGGCGGTTCC
    CTTCGCCTGTCCTGCACCGCGTCCGGCCTTACCTTCGACGATAGCGTGATGGGT
    TGGTTCCGCCAGGCTCCCGGCAAGGGCAGGGAAGCCGTGAGCTGCATTTCATCC
    TCAGGAGCCAACGCTTTCTACGCTGATTCTGTGAAGGGACGTTTTACTATCAGC
    CGCGATAACGCCAAGAACACTCTGTACCTCCAGATGAACTCCCTGAAGCCTGAG
    GATACGGCTACATATTACTGCAAGCGCGGTCACGCCTGCGCTGGATATTACCCG
    ATCCCATACGATGACTACTGGGGCCAGGGAACACAGGTAACAGTCTCCTCT
    hIL27 1326 CAGGTTCAACTGCAAGAGTCCGGCGGGGGACTTGTCCAGCCGGGAGGCAGTCTG
    Ra_VH AGATTGTCCTGCGCAGCGTCCGGGTTCACTTTCAGCTCTTATCCAATGTCATGG
    H7- GTCCGTCAGGCCCCTGGCAAAGGGCTGGAGTGGATCAGCACCATTTCTGCTGGA
    DR596 GGTGACACTACCCTGTACGCCGACAGCGTTAAGGGCCGCTTCACATCATCCAGG
    GACAACGCCAAGAACACACTGTACCTTCAGCTGAACTCCCTGAAAACAGAGGAC
    ACCGCTATCTATTACTGTGCGAAGCGCATTGACTGTAACAGCGGCTATTGTTAT
    CGCAGGAACTATTGGGGACAGGGAACCCAGGTGACTGTAAGCTCCGGTGGCTCT
    GGGGGCTCCGGCGGTTCTGGTCAGGTGCAACTCCAGGAGAGCGGGGGTGGCCTG
    GTGCAGCCTGGCGGGAGTCTGAGGCTTTCCTGCACCGCCAGCGGCCTTACCTTC
    GATGACTCCGTGATGGGGTGGTTCCGCCAAGCGCCAGGAAAAGGCCGCGAAGCC
    GTCTCCTGTATCTCCTCAAGCGGCGCGAACGCCTTCTATGCCGACTCAGTGAAG
    GGCCGTTTCACAATCTCCCGCGATAACGCCAAGAACACCCTGTATCTCCAGATG
    AACAGCCTGAAGCCGGAAGACACGGCAACCTACTATTGTAAGAGAGGCCACGCT
    TGCGCTGGGTATTACCCTATCCCTTACGACGATTACTGGGGACAGGGTACTCAG
    GTGACCGTTAGCTCT
    hIL27 1327 CAAGTTCAGCTTCAGGAGTCAGGTGGCGGATCAGTGCAAGTCGGAGGCTCCCTG
    Ra_VH CGCCTGTCTTGCGCTGCCTCCGGCTTTACATTCTCTTCCTACCCCATGTCCTGG
    H8- GTAAGGCAGGCTCCCGGCAAAGGCCTGGAGTGGATTAGCACAATCTCTGCCGGT
    DR591 GGCGACACCACTCTGTACGCTGATTCCGTGAAAGGTCGTTTCACGTCTAGCAGA
    GACAACGCTAAGAACACCCTCTACCTTCAGCTCAACAGCCTGAAGACGGAGGAC
    ACCGCTATTTATTACTGTGCGAAGCGCATCGACTGTAACTCTGGATACTGCTAT
    CGGCGCAACTATTGGGGTCAGGGTACTCAGGTTACAGTGTCATCCGGGGGCGGA
    TCACAAGTGCAACTGCAAGAATCCGGCGGGGGTAGCGTGCAGGCCGGTGGCTCA
    TTGCGTCTGTCCTGCACCGCCTCTGGCGCTATCGCTTCTGGCTATATCGACAGT
    CGGTGGTGCATGGCCTGGTTCCGCCAGGCCCCTGGGAAGGAGCGCGAGGGTGTG
    GCCGCGATCTGGCCCGGTGGGGGCCTCACAGTGTATGCAGACTCCGTAAAAGGC
    CGCTTCACAATTAGCCGCGACCACGCTAAGAACACCCTTTACTTGCAGATGAAC
    AATCTGAAGCCAGAAGACACTGCAATGTACTATTGTGCTGCGGGTTCCCCTCGT
    ATGTGCCCAAGTCTTGAGTTCGGTTTTGATTACTGGGGGCAGGGCACCCAGGTC
    ACCGTGTCCAGT
    hIL27 1328 CAGGTACAACTCCAGGAATCTGGCGGAGGCTCCGTTCAGGTGGGTGGGTCTCTG
    Ra_VH AGACTGAGCTGCGCTGCCAGCGGATTTACTTTCAGCTCCTACCCCATGAGTTGG
    H8- GTGAGGCAGGCTCCCGGTAAGGGCCTGGAATGGATTAGCACTATTAGCGCTGGC
    DR591 GGGGACACCACTCTGTACGCTGACAGTGTCAAGGGGCGCTTTACTAGCTCCCGC
    GACAACGCCAAGAACACTCTGTATCTCCAGCTCAACAGCCTCAAAACTGAGGAC
    ACAGCTATCTATTACTGTGCTAAGCGCATTGACTGTAACTCAGGCTATTGTTAC
    CGCCGGAACTACTGGGGACAAGGGACCCAAGTGACAGTTTCCTCTGGCGGTAGC
    GGCGGATCTGGGGGCTCTGGCCAGGTCCAGCTTCAGGAGTCCGGGGGAGGCTCC
    GTCCAGGCCGGTGGCTCTTTGAGGCTGTCATGCACAGCTTCCGGTGCCATCGCA
    AGTGGATATATTGACAGTCGCTGGTGCATGGCTTGGTTCCGGCAAGCCCCCGGA
    AAGGAGAGAGAGGGCGTTGCTGCAATCTGGCCGGGTGGGGGCTTGACCGTCTAT
    GCTGATTCTGTGAAGGGCCGTTTTACCATCAGTAGAGACCACGCTAAAAACACC
    CTGTACTTGCAGATGAATAACTTGAAACCCGAAGACACCGCCATGTATTACTGC
    GCCGCTGGCTCTCCCCGTATGTGCCCCAGCTTGGAGTTCGGCTTTGATTATTGG
    GGTCAGGGAACTCAGGTCACTGTGTCCAGC
    hIL27 1329 CAGGTGCAGCTCCAGGAGTCTGGCGGTGGAAGCGTGCAAGTAGGAGGCTCTCTG
    Ra_VH AGGCTGTCATGCGCAGCGAGCGGCTTCACCTTCAGCTCTTATCCAATGTCTTGG
    H8- GTTCGCCAGGCCCCCGGTAAGGGTCTGGAGTGGATCTCAACTATCAGCGCAGGC
    DR592 GGGGATACAACCCTTTACGCCGATAGTGTGAAGGGACGCTTTACCTCTAGCAGA
    GATAACGCTAAGAACACTCTGTACTTGCAGCTTAACTCCCTTAAAACCGAGGAC
    ACCGCGATCTATTACTGTGCCAAGCGCATTGACTGCAACTCTGGTTACTGCTAT
    AGAAGGAACTACTGGGGCCAGGGTACGCAGGTGACGGTTAGTTCCGGTGGAGGC
    TCACAAGTGCAGCTTCAGGAGTCCGGGGGTGGCTCTGTGCAGGCTGGCGGGTCC
    CTGCGGCTTTCCTGCACAGCCCCCGGCTTCACGTCTAACTCCTGTGGCATGGAC
    TGGTATCGCCAGGCCCCTGGTAAAGAGCGTGAGTTCGTGAGCAGTATTTCTACC
    GATGGAACGACCGGCTATGCTGACTCCGTGAAGGGTCGCTTCACCATCTCCAAG
    GACAAAGCCAAAGACACCGTTTATTTGCAGATGAACTCCCTCAAGCCAGAGGAC
    ACTGGCATGTATAGTTGCAAGACCAAGGACGGCACTATTGCGACGATGGAGCTG
    TGTGACTTCGGCTACTGGGGCCAGGGAACCCAGGTGACGGTGTCTTCT
    hIL27 1330 CAGGTGCAGCTCCAAGAGTCTGGTGGGGGAAGCGTTCAAGTCGGGGGCAGCCTG
    Ra_VH AGACTGTCCTGTGCAGCTTCTGGCTTCACCTTTTCTAGCTACCCTATGTCCTGG
    H8- GTGCGCCAGGCCCCCGGCAAAGGCCTGGAATGGATCTCCACCATCAGTGCGGGA
    DR592 GGTGACACAACTCTGTACGCGGATTCTGTGAAGGGCCGCTTCACATCTAGCCGT
    GATAACGCCAAGAATACTTTGTATCTCCAGCTCAACTCTCTGAAGACTGAAGAT
    ACAGCAATTTATTACTGCGCAAAACGGATTGATTGTAATAGCGGGTACTGTTAC
    CGCAGGAACTACTGGGGTCAAGGCACTCAGGTTACGGTGTCTTCCGGCGGATCT
    GGAGGTAGCGGTGGCAGCGGTCAGGTGCAGCTCCAGGAGTCAGGGGGCGGTTCC
    GTGCAGGCTGGCGGGTCCCTGCGCCTCTCTTGTACTGCCCCTGGGTTTACATCC
    AACTCCTGTGGTATGGACTGGTATAGGCAAGCTCCGGGAAAGGAGCGCGAGTTC
    GTGTCTTCCATCAGCACCGATGGCACCACTGGTTACGCCGATTCCGTGAAGGGA
    CGCTTTACAATTAGCAAGGACAAGGCCAAGGATACTGTGTACTTGCAGATGAAC
    AGCCTGAAGCCTGAGGACACTGGGATGTACTCTTGCAAGACCAAGGACGGGACC
    ATCGCCACGATGGAACTCTGCGACTTCGGATACTGGGGCCAGGGCACGCAAGTG
    ACCGTAAGCTCT
    hIL27 1331 CAGGTACAGCTCCAGGAGAGCGGCGGTGGCTCCGTCCAAGTAGGGGGCAGCCTC
    Ra_VH CGCCTTTCTTGTGCAGCCTCTGGTTTTACATTTTCCAGCTACCCAATGAGCTGG
    H8- GTCCGGCAAGCGCCTGGGAAAGGTCTGGAGTGGATTTCCACCATCTCCGCCGGG
    DR593 GGCGACACTACCCTGTACGCAGATAGCGTAAAGGGTCGCTTTACCAGTTCTCGT
    GATAACGCCAAGAACACTCTGTACCTTCAGCTGAATAGCCTCAAGACCGAGGAT
    ACCGCCATCTACTATTGCGCTAAGCGCATCGACTGCAACTCTGGCTATTGTTAC
    AGACGTAACTACTGGGGTCAAGGTACGCAGGTAACTGTATCCTCTGGAGGCGGT
    TCTCAGGTACAGCTTCAGGAGAGCGGCGGTGGCAGCGTGCAGGCCGGAGGGTCC
    CTGCGTCTCTCCTGCGCTGCCTCCGGCTACCCCTACTCCAATGGCTATATGGGT
    TGGTTCAGACAGGCTCCTGGCAAAGAACGGGAGGGGGTGGCCACAATTTACACT
    GGTGATGGCCGCACGTACTATGCCGACTCCGTGAAGGGGCGCTTTACCATTTCT
    CGCGATAACGCTAAAAACACCGTGGACCTCCAGATGTCCAGCCTGAAGCCTGAA
    GATACTGCAATGTATTACTGTGCCGCACGTGCTGCCCCACTGTACTCAAGTGGG
    AGCCCACTGACTCGCGCTAGATATAACGTGTGGGGTCAGGGCACTCAGGTGACC
    GTCTCCTCC
    hIL27 1332 CAAGTACAACTCCAGGAATCTGGGGGGGGAGTGTTCAGGTCGGTGGCAGCCTG
    Ra_VH CGTCTCAGTTGCGCCGCGTCTGGCTTCACATTTTCTTCCTATCCGATGTCTTGG
    H8- GTGAGGCAAGCCCCTGGGAAGGGTCTCGAATGGATCTCCACAATCTCTGCTGGC
    DR593 GGTGATACCACGCTCTACGCCGACTCTGTCAAAGGCCGCTTCACTTCTTCACGT
    GATAACGCCAAAAACACCCTGTACCTTCAGCTCAACTCCCTGAAGACCGAAGAC
    ACAGCAATCTATTACTGTGCGAAGCGGATTGATTGCAACTCCGGCTATTGTTAT
    CGGAGGAACTACTGGGGCCAGGGCACCCAAGTGACCGTCTCCTCTGGCGGTTCC
    GGTGGCTCCGGCGGTTCTGGACAAGTCCAACTCCAGGAGAGCGGCGGAGGCTCC
    GTTCAGGCAGGCGGGTCCTTGAGGCTGAGTTGTGCTGCATCAGGCTACCCCTAC
    TCAAACGGCTATATGGGCTGGTTCAGACAGGCTCCGGGCAAGGAGCGCGAGGGA
    GTGGCCACTATCTATACCGGCGACGGTCGCACTTATTACGCAGATAGCGTAAAG
    GGTCGCTTCACCATCAGCCGCGATAACGCCAAGAACACGGTTGACCTTCAAATG
    TCTAGTCTCAAACCTGAAGACACTGCCATGTACTATTGCGCCGCAAGAGCTGCC
    CCTCTGTATTCCAGCGGGAGCCCCCTGACCCGTGCCCGCTACAACGTGTGGGGT
    CAGGGCACCCAGGTGACTGTCAGCTCT
    hIL27 1333 CAGGTGCAACTCCAGGAGAGTGGCGGGGGCTCCGTACAGGTCGGGGGCTCTCTG
    Ra_VH AGACTCTCCTGTGCGGCCAGCGGATTTACCTTCAGCAGTTACCCGATGTCTTGG
    H8- GTGCGTCAGGCCCCAGGCAAGGGCCTGGAGTGGATTTCCACAATCAGCGCTGGC
    DR594 GGTGACACTACACTCTACGCAGATTCCGTGAAAGGGCGTTTCACCTCTAGCCGC
    GACAACGCTAAGAACACCCTGTACTTGCAGTTGAACTCCCTGAAGACCGAGGAC
    ACGGCCATCTACTATTGCGCGAAGCGCATCGACTGTAACAGCGGATACTGTTAC
    AGGCGCAACTATTGGGGACAGGGGACCCAAGTAACCGTGAGTTCAGGTGGGGGC
    TCCCAGGTGCAGTTGCAGGAGTCAGGTGGAGGCAGCGTCCAGGCCGGGGGCTCT
    CTTCGCCTGTCCTGTGTGGCCAGCGCCTCTACTTACTGTACGTATGATATGCAC
    TGGTATAGACAGGCCCCCGGTAAGGGAAGAGAGTTCGTCAGCGCTATTGATAGC
    GATGGCACCACACGCTATGCGGATTCCGTAAAGGGTAGGTTTACAATCAGCCAG
    GGAACCGCAAAAAACACTGTTTACTTGCAGATGAACAGCCTCCAGCCAGAGGAT
    ACCGCCATGTACTATTGTAAGACTGTGTGTGTCGTGGGTTCCCGTTGGTCCGAT
    TACTGGGGCCAGGGCACTCAAGTAACAGTTAGTAGT
    hIL27 1334 CAAGTTCAACTGCAAGAGTCCGGTGGCGGAAGCGTCCAGGTGGGAGGCTCCCTT
    Ra_VH CGCCTGAGCTGTGCTGCCAGCGGTTTCACATTCAGTTCCTATCCGATGTCCTGG
    H8- GTGCGTCAGGCCCCAGGCAAGGGTCTGGAGTGGATCTCTACCATCTCCGCTGGC
    DR594 GGTGACACGACTCTGTACGCTGATAGCGTTAAGGGGCGCTTTACCTCCTCTCGC
    GATAACGCTAAGAACACTCTCTACCTCCAGTTGAATAGCCTCAAGACTGAAGAT
    ACCGCTATCTACTATTGCGCTAAGCGGATTGATTGCAACTCTGGGTACTGCTAC
    CGCCGGAACTACTGGGGACAGGGAACCCAGGTGACTGTGTCCTCTGGTGGCTCT
    GGAGGCTCCGGCGGTTCCGGGCAGGTCCAACTCCAGGAATCCGGCGGTGGCAGC
    GTGCAGGCCGGTGGCTCCTTGCGTCTGTCCTGCGTGGCGAGCGCTTCCACCTAC
    TGCACCTACGACATGCACTGGTATCGCCAGGCTCCGGGTAAGGGCCGTGAATTT
    GTGTCTGCCATTGATTCTGACGGCACCACGCGGTACGCAGACTCTGTTAAGGGG
    CGCTTTACCATCAGTCAGGGCACGGCTAAGAACACCGTGTACCTGCAAATGAAC
    TCTCTCCAACCGGAGGACACTGCCATGTATTACTGTAAAACGGTTTGTGTTGTC
    GGCTCCCGCTGGTCCGATTACTGGGGCCAGGGAACCCAGGTGACAGTCTCAAGC
    hIL27 1335 CAGGTTCAACTCCAGGAGAGTGGCGGTGGCTCAGTGCAAGTAGGGGGCAGTCTG
    Ra_VH CGCCTGAGCTGTGCTGCATCCGGCTTCACCTTCTCTAGTTATCCCATGAGCTGG
    H8- GTACGTCAGGCTCCAGGCAAAGGTCTGGAGTGGATCAGCACCATTAGCGCTGGC
    DR595 GGAGACACGACTCTCTATGCCGACAGCGTGAAGGGCCGCTTCACCTCCAGTCGG
    GACAACGCCAAGAACACGCTGTACCTTCAGTTGAACTCACTCAAGACTGAGGAT
    ACCGCAATCTATTACTGCGCTAAACGCATCGACTGTAACTCCGGGTACTGTTAC
    CGTCGCAACTACTGGGGTCAGGGGACTCAGGTCACCGTGTCTTCCGGGGGTGGC
    AGTCAGGTGCAGCTTCAGGAATCCGGCGGAGGCTCTGTCCAGGCTGGCGGTTCC
    CTGACTCTGTCTTGCGCAGCCTCAGAGTATGCCTACAGCACTTGTAACATGGGT
    TGGTATCGCCAGGCTCCCGGCAAAGAACGTGAGCTTGTTAGCGCGTTCATCAGC
    GATGGCAGCACCTATTACGCTGACAGCGTGAAGGGTCGCTTTACAATCACCAGG
    GACAACGCGAAGAACACCGTGTATCTCCAGATGAACTCCCTCAAGCCCGAGGAC
    ACCGCCATCTATTACTGCTCCGCTAATTGCTACCGTCGGCTGCGCAACTACTGG
    GGCCAGGGGACCCAGGTAACAGTCTCCTCT
    hIL27 1336 CAGGTCCAGCTCCAGGAGTCCGGTGGGGGAAGCGTCCAAGTAGGGGGATCTCTG
    Ra_VH AGGCTGTCCTGTGCGGCCTCCGGCTTCACCTTCTCCAGCTACCCCATGTCCTGG
    H8- GTGAGACAAGCCCCTGGGAAAGGACTGGAATGGATTAGTACCATTTCAGCCGGG
    DR595 GGTGACACAACCCTGTACGCAGACTCCGTGAAAGGACGTTTTACCAGTTCCCGT
    GATAACGCCAAGAACACCTTGTACCTCCAGTTGAACTCCCTGAAGACAGAAGAC
    ACAGCCATCTATTACTGTGCCAAGCGCATTGATTGCAACAGCGGATACTGTTAC
    CGCAGAAACTATTGGGGCCAGGGCACCCAGGTGACAGTATCAAGCGGCGGTTCC
    GGCGGTAGCGGCGGTAGCGGGCAAGTGCAGTTGCAGGAGAGCGGCGGTGGCTCC
    GTTCAGGCAGGAGGCTCCCTGACTCTCTCCTGTGCTGCCTCTGAGTATGCGTAC
    TCCACTTGCAATATGGGCTGGTACAGGCAGGCTCCCGGCAAGGAACGCGAACTG
    GTGAGTGCATTCATCTCTGATGGCTCCACATATTACGCCGACAGCGTCAAGGGC
    CGGTTTACCATCACTCGGGATAATGCCAAGAACACCGTCTACTTGCAGATGAAC
    AGCCTGAAGCCAGAGGACACAGCCATCTATTACTGCTCTGCTAACTGCTACCGC
    AGACTGCGCAATTACTGGGGCCAGGGAACCCAGGTGACTGTGTCTAGC
    hIL27 1337 CAGGTGCAACTCCAGGAATCCGGCGGAGGCAGCGTGCAAGTTGGGGGCAGTCTT
    Ra_VH CGTCTGTCATGTGCAGCCAGCGGGTTCACCTTCTCAAGCTACCCGATGAGCTGG
    H8- GTGCGGCAGGCTCCCGGAAAGGGCCTGGAGTGGATTTCCACTATCTCCGCTGGC
    DR596 GGTGACACCACACTGTACGCTGACTCCGTGAAGGGGCGGTTCACGTCATCCCGT
    GATAACGCTAAGAACACACTGTATCTCCAGCTGAACAGCCTCAAGACCGAGGAC
    ACTGCAATCTACTATTGCGCTAAGAGAATTGATTGCAACTCCGGGTACTGTTAC
    AGGCGTAATTACTGGGGGCAGGGCACACAAGTGACCGTGTCCAGTGGCGGTGGC
    AGCCAGGTGCAGTTGCAGGAGAGTGGGGGTGGCCTTGTGCAGCCCGGTGGGAGT
    CTGCGCCTGTCCTGCACAGCCTCCGGGCTGACCTTCGACGATTCTGTAATGGGC
    TGGTTCCGCCAGGCTCCGGGGAAGGGCCGCGAGGCCGTCAGCTGTATCTCCAGC
    TCTGGAGCCAACGCATTTTACGCGGACAGCGTAAAGGGTAGATTCACAATTTCA
    CGTGACAACGCCAAGAACACCCTGTACCTCCAGATGAACAGCCTGAAGCCCGAG
    GATACCGCCACCTACTATTGTAAGCGCGGCCACGCTTGCGCGGGTTACTATCCG
    ATCCCATACGATGACTATTGGGGCCAGGGCACGCAGGTTACGGTGTCTTCC
    hIL27 1338 CAGGTCCAACTGCAAGAGTCTGGCGGGGGTTCCGTTCAGGTCGGTGGCTCCTTG
    Ra_VH CGGCTGAGCTGTGCTGCCTCCGGCTTTACTTTTAGTTCTTATCCGATGAGCTGG
    H8- GTGAGGCAGGCTCCTGGCAAGGGCCTGGAGTGGATCTCCACAATCAGCGCTGGC
    DR596 GGGGACACCACATTGTACGCCGACTCCGTCAAGGGCAGGTTCACCTCCTCACGC
    GATAATGCTAAGAACACTCTGTATCTCCAGCTTAACTCTCTCAAGACCGAGGAC
    ACCGCCATTTATTACTGCGCGAAGAGAATTGATTGTAACTCCGGCTACTGCTAC
    CGCCGTAATTACTGGGGTCAGGGAACCCAGGTTACGGTCAGCTCCGGTGGCAGT
    GGCGGTAGCGGAGGCTCCGGCCAGGTGCAGTTGCAGGAGTCTGGCGGTGGCCTG
    GTCCAGCCTGGAGGCAGCCTCCGGCTGAGCTGTACTGCTTCAGGCCTGACATTT
    GACGATAGCGTGATGGGGTGGTTCCGCCAAGCGCCGGGAAAGGGTCGCGAGGCC
    GTCTCTTGTATCAGTTCCTCTGGAGCCAACGCTTTCTATGCTGATAGCGTGAAG
    GGCCGCTTCACAATTAGCCGGGACAATGCAAAGAACACCTTGTACCTGCAAATG
    AACTCTCTGAAGCCCGAAGATACGGCTACCTACTATTGCAAGCGCGGCCATGCC
    TGCGCAGGATATTACCCAATCCCCTACGACGATTATTGGGGTCAGGGCACCCAG
    GTGACCGTGAGCAGC
    hIL27 1339 CAGGTCCAACTCCAGGAGAGCGGGGGTGGCAGTGTGCAGTCTGGCGGTTCCCTT
    Ra_VH AGGCTGAGTTGCGCAGCCAGCGGCTTCACATACAGCACCAGCAATTCATGGATG
    H9- GCGTGGTTCCGTCAGGCCCCCGGTAAGGAGCGGGAGGGCGTCGCCGCTATCTAC
    DR591 ACAGTGGGTGGGTCCATCTTTTACGCTGATTCCGTGCGTGGCCGTTTCACCATC
    TCCCAAGATGCGACAAAGAATATGTTCTACCTGCAAATGAACACACTCAAGCCC
    GAAGATACCGCTATGTATTACTGCGCGGCAGCTTCTGGCCGCCTCCGTGGAAAG
    TGGTTCTGGCCATACGAATATAACTATTGGGGCCAGGGAACTCAGGTGACAGTT
    AGTAGCGGCGGTGGCTCTCAGGTGCAACTCCAGGAGTCCGGCGGGGGAAGCGTG
    CAGGCGGGAGGGAGCCTGCGGCTGTCATGTACCGCCAGCGGAGCCATCGCCAGC
    GGATACATTGATTCCCGCTGGTGTATGGCTTGGTTTCGCCAGGCCCCCGGCAAG
    GAAAGGGAGGGAGTCGCCGCTATTTGGCCCGGTGGCGGTCTGACAGTGTACGCC
    GACAGCGTAAAGGGTCGCTTCACTATCAGCCGTGACCACGCTAAGAACACCCTG
    TACCTCCAGATGAATAACTTGAAGCCAGAGGACACCGCCATGTACTATTGCGCC
    GCTGGCTCCCCGAGAATGTGCCCTTCTCTCGAATTTGGTTTTGACTACTGGGGG
    CAGGGGACCCAGGTCACGGTTTCTTCC
    hIL27 1340 CAGGTGCAACTCCAGGAGAGTGGCGGGGGTTCCGTCCAGAGCGGTGGCAGTCTG
    Ra_VH AGGCTGTCCTGCGCCGCTTCCGGTTTCACATACTCCACCAGTAACAGCTGGATG
    H9- GCCTGGTTTCGCCAAGCCCCTGGGAAAGAGAGAGAAGGAGTCGCCGCAATCTAC
    DR591 ACTGTAGGAGGCTCCATTTTCTACGCAGACTCTGTCAGAGGCCGTTTCACCATT
    AGCCAGGATGCCACTAAGAATATGTTTTACCTCCAGATGAATACACTGAAGCCA
    GAAGACACCGCTATGTATTACTGTGCTGCGGCTTCCGGCAGGCTGCGCGGCAAG
    TGGTTCTGGCCTTACGAGTATAACTATTGGGGCCAAGGCACCCAGGTCACCGTG
    TCAAGCGGGGGTTCCGGTGGCAGCGGAGGGAGCGGCCAGGTGCAGCTGCAAGAG
    TCTGGTGGCGGTTCCGTCCAGGCTGGGGGCTCTCTCCGGCTGTCTTGTACGGCC
    AGCGGTGCCATCGCTAGTGGCTACATCGACAGCCGGTGGTGCATGGCCTGGTTC
    CGTCAGGCTCCTGGAAAGGAACGGGAAGGCGTCGCCGCTATTTGGCCAGGTGGC
    GGACTGACGGTCTATGCTGACTCTGTCAAGGGACGCTTCACCATCAGTCGCGAT
    CACGCTAAGAACACCCTCTACCTCCAGATGAATAACCTGAAGCCCGAGGATACG
    GCCATGTATTACTGCGCCGCTGGTTCCCCAAGAATGTGTCCCAGCCTGGAGTTC
    GGGTTCGACTATTGGGGACAGGGCACCCAGGTAACCGTGTCATCA
    hIL27 1341 CAGGTCCAGCTCCAGGAGAGCGGAGGCGGTAGTGTCCAGTCCGGTGGCTCCCTG
    Ra_VH CGTCTGAGTTGCGCAGCCAGTGGCTTCACTTATTCCACAAGCAACTCTTGGATG
    H9- GCATGGTTTCGCCAGGCCCCTGGGAAGGAACGCGAGGGTGTCGCTGCCATCTAC
    DR592 ACAGTGGGCGGTTCCATTTTCTACGCAGACTCCGTTAGAGGTAGGTTTACTATC
    AGCCAGGATGCTACCAAGAATATGTTCTACCTTCAGATGAACACACTCAAGCCC
    GAAGACACCGCCATGTATTACTGTGCCGCAGCCTCTGGCCGCCTGCGCGGTAAG
    TGGTTCTGGCCTTACGAGTACAATTACTGGGGTCAGGGCACCCAGGTGACAGTG
    TCCAGTGGTGGAGGCTCCCAGGTTCAGCTTCAGGAGTCTGGAGGGGGCTCCGTG
    CAGGCAGGAGGCTCTCTGAGACTCAGCTGCACCGCCCCAGGTTTTACCTCCAAC
    AGCTGCGGCATGGACTGGTATCGCCAGGCCCCCGGCAAGGAACGCGAGTTCGTG
    AGTTCTATCTCCACCGATGGAACAACGGGTTACGCCGATTCTGTGAAGGGCCGG
    TTTACAATCTCCAAGGATAAGGCCAAGGACACTGTGTACCTCCAGATGAACTCT
    TTGAAACCAGAAGACACAGGCATGTATAGCTGTAAGACCAAGGATGGGACCATC
    GCGACTATGGAACTGTGTGACTTCGGATACTGGGGCCAGGGGACCCAGGTCACA
    GTGTCCTCC
    hIL27 1342 CAGGTCCAGCTGCAAGAGAGCGGAGGCGGTAGTGTGCAGAGCGGCGGAAGCCTG
    Ra_VH CGCCTCAGCTGCGCCGCGTCCGGCTTTACCTACAGCACAAGTAACTCTTGGATG
    H9- GCCTGGTTCCGGCAGGCTCCCGGCAAGGAAAGGGAAGGCGTGGCCGCAATCTAC
    DR592 ACGGTCGGAGGTTCTATTTTCTACGCCGATAGCGTCAGAGGCCGCTTCACAATC
    TCTCAGGACGCAACCAAAAATATGTTCTACTTGCAGATGAACACACTCAAGCCC
    GAGGACACCGCGATGTATTACTGTGCCGCTGCATCCGGGCGGCTGAGAGGAAAG
    TGGTTCTGGCCTTATGAGTACAATTATTGGGGTCAGGGCACTCAGGTGACTGTG
    TCCTCTGGTGGCTCCGGTGGCAGTGGGGGCAGCGGTCAGGTGCAGCTTCAGGAG
    TCCGGTGGAGGGAGCGTCCAGGCTGGCGGTTCCCTCAGGCTGTCCTGCACAGCA
    CCGGGCTTCACTAGCAACAGCTGCGGTATGGATTGGTATCGCCAGGCACCGGGT
    AAGGAGCGCGAATTTGTCTCATCTATCAGCACCGATGGGACAACCGGGTACGCT
    GATAGCGTGAAAGGTAGGTTCACCATCTCCAAGGACAAGGCAAAAGATACCGTG
    TACCTCCAGATGAACTCTCTCAAGCCCGAGGACACCGGAATGTATAGCTGCAAG
    ACAAAGGACGGCACCATTGCAACAATGGAGCTTTGTGACTTTGGCTATTGGGGC
    CAGGGCACCCAGGTAACGGTCTCTTCA
    hIL27 1343 CAGGTCCAGCTTCAAGAATCCGGCGGGGGCTCCGTACAATCAGGAGGGTCACTC
    Ra_VH AGGCTGAGTTGCGCAGCCTCTGGATTCACGTACTCCACAAGCAATTCCTGGATG
    H9- GCCTGGTTTAGACAGGCACCCGGCAAGGAGCGTGAGGGGGTGGCTGCCATCTAC
    DR593 ACTGTGGGTGGCTCCATCTTCTATGCGGACAGTGTTCGCGGGCGTTTTACAATC
    TCCCAGGACGCCACCAAGAATATGTTCTACTTGCAGATGAACACACTGAAACCG
    GAGGACACCGCCATGTATTACTGTGCAGCCGCGTCAGGCCGCCTGCGGGGGAAG
    TGGTTCTGGCCATACGAGTACAACTACTGGGGTCAGGGCACCCAAGTGACCGTG
    AGTTCCGGGGGAGGTTCCCAGGTTCAGCTTCAGGAGTCCGGTGGCGGGTCTGTG
    CAGGCCGGTGGCTCCCTTCGGCTCTCCTGCGCCGCGAGTGGCTATCCTTATTCC
    AACGGCTACATGGGCTGGTTCCGTCAGGCACCCGGCAAGGAACGGGAAGGCGTC
    GCTACCATCTATACAGGTGATGGGCGGACTTATTACGCAGACTCCGTGAAGGGC
    CGCTTTACTATCAGTCGCGACAACGCAAAGAATACAGTGGACTTGCAAATGAGT
    TCCCTCAAGCCTGAGGACACTGCTATGTACTATTGTGCTGCCCGTGCAGCGCCA
    CTGTATAGTTCCGGCTCACCGCTGACCCGCGCTAGGTATAACGTATGGGGTCAG
    GGCACACAAGTGACGGTGTCAAGC
    hIL27 1344 CAGGTGCAACTCCAGGAGTCCGGCGGAGGCAGTGTGCAATCCGGGGGTTCTCTG
    Ra_VH CGCCTCTCTTGCGCTGCCTCTGGGTTTACATATTCCACATCCAACTCCTGGATG
    H9- GCCTGGTTCCGCCAGGCTCCCGGCAAGGAGAGAGAGGGGGTGGCCGCGATCTAC
    DR593 ACCGTTGGTGGCTCTATCTTCTATGCCGACAGCGTTCGGGGCCGCTTTACCATT
    AGCCAGGATGCAACTAAGAATATGTTCTACCTTCAGATGAACACACTGAAGCCA
    GAGGATACTGCAATGTATTACTGCGCCGCAGCTTCTGGCAGACTGCGCGGAAAA
    TGGTTCTGGCCTTATGAGTACAATTATTGGGGGCAGGGCACCCAGGTCACAGTA
    AGCTCCGGTGGCTCCGGCGGTAGCGGAGGCTCCGGCCAAGTCCAACTTCAGGAA
    AGCGGTGGCGGGTCTGTGCAGGCCGGTGGCTCCCTCCGCCTGTCTTGCGCGGCT
    TCCGGCTATCCATACAGTAACGGCTACATGGGTTGGTTCCGGCAGGCCCCTGGC
    AAGGAGCGTGAGGGCGTTGCTACGATCTATACAGGTGACGGAAGGACTTACTAT
    GCTGACAGCGTAAAGGGGCGCTTCACCATTTCTCGTGACAACGCAAAGAACACA
    GTGGACCTCCAGATGAGCAGTCTGAAGCCTGAGGACACCGCGATGTACTATTGT
    GCCGCTCGGGCCGCTCCTCTGTATTCCAGCGGCAGCCCTCTGACTAGGGCTAGA
    TACAACGTCTGGGGACAGGGCACTCAGGTGACTGTGAGCAGC
    hIL27 1345 CAGGTGCAACTCCAGGAGTCTGGAGGGGGCTCCGTGCAGAGTGGCGGAAGCCTG
    Ra_VH AGGTTGTCCTGTGCCGCGAGTGGATTCACCTACTCCACCTCCAACAGCTGGATG
    H9- GCCTGGTTTAGACAGGCTCCAGGTAAGGAAAGAGAGGGCGTGGCCGCGATCTAC
    DR594 ACCGTAGGGGGCTCCATCTTCTATGCAGATAGCGTGAGGGGCCGCTTCACAATC
    AGTCAGGATGCCACCAAAAATATGTTTTACCTCCAGATGAACACATTGAAGCCA
    GAGGACACCGCCATGTACTATTGCGCCGCTGCCTCTGGTAGGCTGAGGGGCAAA
    TGGTTCTGGCCCTATGAATATAACTACTGGGGGCAGGGCACCCAGGTAACGGTG
    TCAAGCGGTGGGGGCTCTCAGGTGCAGCTCCAGGAGTCCGGCGGGGGCAGCGTA
    CAGGCTGGAGGTAGTCTGCGCTTGAGTTGCGTCGCGTCAGCCTCTACCTATTGC
    ACATACGACATGCACTGGTATAGACAGGCCCCAGGCAAGGGAAGGGAGTTCGTG
    TCCGCAATCGACTCTGATGGCACAACCAGATACGCAGACTCCGTAAAGGGTCGC
    TTCACCATCAGCCAGGGCACAGCGAAGAACACAGTGTACCTCCAGATGAACTCC
    TTGCAGCCTGAGGATACTGCCATGTACTATTGCAAGACTGTGTGCGTTGTCGGA
    TCTCGCTGGTCAGACTACTGGGGCCAGGGAACACAGGTGACAGTGTCCTCC
    hIL27 1346 CAGGTGCAACTCCAGGAGTCTGGAGGTGGCTCTGTCCAAAGCGGTGGCTCCCTT
    Ra_VH CGCCTGAGCTGTGCCGCTAGTGGATTCACGTACTCTACGTCAAATAGCTGGATG
    H9- GCGTGGTTCAGACAGGCCCCTGGCAAGGAGAGGGAGGGTGTGGCTGCGATCTAT
    DR594 ACTGTGGGCGGTTCCATCTTCTATGCCGATTCCGTGCGCGGTCGGTTTACCATC
    TCTCAGGACGCTACCAAGAATATGTTTTACTTGCAGATGAACACTCTGAAGCCA
    GAGGATACCGCGATGTACTATTGCGCAGCGGCCTCTGGTAGGCTGAGAGGCAAA
    TGGTTCTGGCCTTATGAATACAACTATTGGGGACAGGGAACTCAGGTGACGGTC
    TCTTCCGGTGGCTCTGGGGGCAGCGGTGGGAGCGGCCAAGTGCAGCTTCAGGAG
    TCTGGCGGAGGCAGCGTTCAAGCAGGCGGTAGCCTGAGACTCTCATGTGTAGCC
    TCCGCTTCCACTTACTGCACCTACGACATGCACTGGTATCGTCAGGCTCCTGGC
    AAGGGCCGCGAGTTTGTGTCCGCCATCGACTCCGACGGCACAACGCGGTACGCT
    GACAGCGTGAAGGGCCGCTTTACCATTAGCCAAGGCACCGCCAAGAATACAGTG
    TACCTGCAAATGAATAGCCTGCAACCGGAGGATACCGCGATGTACTATTGCAAG
    ACGGTCTGTGTTGTGGGCAGTCGGTGGAGCGACTACTGGGGGCAAGGTACACAA
    GTCACTGTGTCCTCC
    hIL27 1347 CAGGTGCAGCTCCAGGAATCTGGAGGTGGCTCTGTGCAGAGTGGGGGCAGCCTT
    Ra_VH CGCCTGTCCTGCGCTGCCAGCGGCTTCACATACAGTACGTCAAACTCCTGGATG
    H9- GCCTGGTTCCGTCAAGCGCCTGGAAAGGAACGCGAGGGAGTGGCTGCGATTTAT
    DR595 ACCGTCGGCGGGTCTATTTTTTACGCCGACTCCGTCAGAGGACGTTTCACGATC
    TCCCAGGACGCCACGAAGAATATGTTTTATCTCCAGATGAACACACTTAAACCC
    GAAGACACCGCAATGTATTACTGCGCTGCCGCATCTGGCCGCCTCCGGGGCAAA
    TGGTTTTGGCCTTACGAGTACAATTACTGGGGCCAGGGAACACAGGTTACCGTG
    AGCAGTGGAGGCGGGTCCCAGGTTCAGTTGCAGGAGTCAGGCGGGGGAAGCGTG
    CAGGCCGGAGGTTCACTGACCCTGTCTTGTGCAGCGTCTGAATACGCCTACAGC
    ACCTGTAACATGGGATGGTATCGCCAGGCTCCTGGAAAGGAAAGGGAGCTGGTG
    TCTGCCTTTATCTCTGACGGCAGCACTTATTACGCTGACTCCGTGAAGGGACGC
    TTTACCATCACCCGCGACAACGCGAAGAACACTGTGTATCTTCAGATGAACTCC
    CTGAAGCCCGAAGACACCGCGATCTACTATTGCTCCGCTAATTGTTACCGTCGC
    CTCCGCAACTATTGGGGCCAAGGGACCCAGGTGACCGTTAGTTCC
    hIL27 1348 CAAGTCCAGCTTCAGGAGTCCGGCGGTGGCAGCGTGCAGTCTGGAGGCTCCCTG
    Ra_VH CGCTTGTCCTGCGCCGCTTCCGGTTTCACGTATTCCACAAGTAATAGTTGGATG
    H9- GCTTGGTTTAGACAGGCCCCCGGCAAAGAGCGCGAGGGTGTGGCTGCCATCTAT
    DR595 ACCGTCGGTGGGAGCATCTTTTACGCCGATTCCGTGCGTGGCCGCTTCACCATC
    AGCCAGGATGCCACAAAGAATATGTTTTACTTGCAGATGAACACCCTGAAGCCC
    GAAGACACCGCTATGTACTATTGCGCGGCAGCTTCTGGACGGCTGCGCGGTAAG
    TGGTTTTGGCCATACGAGTACAACTATTGGGGCCAGGGCACTCAGGTGACCGTG
    TCTTCCGGGGGCTCCGGCGGGAGCGGTGGCTCTGGCCAGGTGCAGCTCCAGGAG
    TCCGGGGGTGGCTCTGTCCAGGCTGGAGGCAGTCTGACCCTGTCCTGTGCCGCG
    TCTGAGTACGCCTACTCCACTTGTAATATGGGCTGGTATCGTCAGGCACCTGGC
    AAAGAACGCGAACTGGTGTCCGCATTTATTTCCGACGGTAGTACCTATTACGCT
    GATTCCGTGAAGGGACGCTTCACCATCACACGGGATAACGCCAAGAACACTGTG
    TATCTTCAGATGAACTCCTTGAAGCCCGAAGACACCGCTATCTACTATTGCAGC
    GCCAACTGCTACAGACGGCTGCGTAACTACTGGGGCCAGGGCACTCAGGTGACT
    GTCTCCTCT
    hIL27 1349 CAGGTGCAGCTTCAGGAATCCGGCGGGGGCAGCGTCCAGAGCGGCGGTTCCCTC
    Ra_VH CGCCTCAGCTGTGCGGCTTCTGGATTCACCTATTCTACAAGCAATTCATGGATG
    H9- GCGTGGTTTCGCCAAGCGCCGGGCAAAGAGCGTGAGGGCGTTGCGGCTATTTAC
    DR596 ACTGTCGGAGGCTCCATCTTCTACGCAGACTCAGTGCGTGGCCGTTTCACTATC
    TCCCAGGACGCCACTAAGAATATGTTCTATCTCCAGATGAATACCCTCAAACCA
    GAAGACACCGCAATGTATTACTGCGCTGCCGCATCTGGCCGTCTGAGAGGTAAG
    TGGTTTTGGCCTTACGAGTACAACTACTGGGGACAAGGCACTCAGGTCACAGTC
    TCCTCAGGCGGTGGCTCCCAGGTGCAGCTCCAAGAGTCAGGCGGGGGTCTGGTC
    CAGCCTGGCGGGTCCCTTAGGCTTAGCTGTACCGCGTCCGGTCTCACCTTCGAT
    GACAGCGTCATGGGATGGTTCCGCCAGGCCCCAGGCAAGGGGAGGGAGGCAGTG
    AGCTGCATCTCCAGCTCCGGCGCTAACGCCTTTTATGCGGACAGTGTCAAAGGC
    AGGTTCACGATTTCTAGGGATAACGCTAAGAACACCCTGTACCTCCAGATGAAC
    AGCCTCAAACCGGAGGATACCGCGACTTACTATTGCAAACGTGGTCACGCCTGC
    GCTGGTTATTACCCCATCCCGTATGATGACTATTGGGGCCAAGGCACCCAGGTG
    ACTGTTTCTTCC
    hIL27 1350 CAGGTCCAGTTGCAGGAGTCAGGCGGGGGCTCTGTGCAGTCTGGAGGCAGTCTC
    Ra_VH AGACTGTCTTGCGCGGCTTCCGGCTTCACATACTCCACTTCCAACAGTTGGATG
    H9- GCCTGGTTCAGGCAAGCGCCGGGCAAGGAGAGAGAGGGTGTAGCGGCAATCTAT
    DR596 ACTGTCGGCGGTTCAATTTTTTACGCGGACTCTGTTCGTGGCAGATTCACCATT
    TCCCAGGACGCCACAAAAAATATGTTCTACCTCCAAATGAACACCCTCAAGCCT
    GAGGACACTGCTATGTATTACTGTGCGGCTGCCTCAGGCCGTCTGCGGGGTAAG
    TGGTTTTGGCCCTACGAGTACAACTACTGGGGCCAGGGGACGCAGGTGACAGTC
    AGCTCAGGGGGCAGCGGCGGGTCCGGCGGGAGTGGCCAGGTGCAGCTCCAGGAA
    TCTGGCGGAGGTCTTGTCCAGCCTGGCGGGTCTTTGCGTCTGTCCTGTACCGCA
    AGTGGTCTGACCTTCGATGACTCAGTTATGGGATGGTTCAGACAAGCGCCTGGT
    AAGGGCCGCGAGGCGGTGTCATGTATCTCTTCCAGCGGAGCCAACGCTTTTTAC
    GCCGACTCCGTGAAAGGCAGGTTTACGATTAGTCGGGATAATGCCAAGAACACC
    TTGTACCTCCAGATGAACAGCTTGAAGCCCGAAGACACTGCTACCTATTACTGT
    AAGCGCGGTCACGCCTGCGCGGGCTATTACCCAATCCCCTACGATGACTACTGG
    GGCCAGGGAACCCAGGTGACAGTTTCCAGC
    hIL27 1351 CAGGTGCAGCTGCAAGAATCCGGCGGTGGCTCCGTTCAGGCCGGAGGCTCATTG
    Ra_VH CGTCTCTCCTGTCGTGCGTCTGGGTCCACCTACTCTAACTATTGCCTGGGGTGG
    H10- TTCCGGCAGATTACGGGTAAGGAACGCGAAGGAGTTGCCGTGATTAACTGGGTC
    DR591 GGTGGAATGCTGTACTTTGCTGACTCCGTCAAGGGTCGCTTCACCGTCTCCCAG
    GACCAGGCTAAGAACACCCTGTACTTGCAGATGAACTCCCTCAAGCCTGAGGAC
    ACCGCAATGTATTACTGTGCCGCTGAGTCAGTCAGCTCCTTCTCCTGCGGCGGG
    TGGCTCACTCGCCCCGACAGAGTCCCCTATTGGGGGCAGGGAACCCAGGTGACT
    GTCTCTAGCGGTGGGGGCTCCCAGGTGCAGTTGCAGGAATCTGGTGGGGGCTCC
    GTCCAAGCCGGTGGCTCACTTAGGCTGTCCTGTACGGCAAGCGGGGCCATCGCC
    TCTGGTTATATCGACTCACGGTGGTGTATGGCATGGTTCAGACAGGCTCCAGGG
    AAGGAGCGGGAGGGAGTCGCTGCCATCTGGCCGGGCGGGGGCCTCACCGTTTAC
    GCAGATAGCGTGAAGGGTAGGTTTACCATCTCTCGCGACCACGCCAAAAATACT
    CTGTACCTCCAAATGAATAACCTGAAGCCCGAAGATACCGCCATGTACTATTGC
    GCCGCTGGCTCCCCGCGCATGTGCCCTTCTCTGGAGTTCGGCTTCGATTATTGG
    GGACAAGGAACCCAGGTGACAGTGTCTTCC
    hIL27 1352 CAGGTACAGCTTCAGGAAAGCGGGGGAGGCTCAGTGCAGGCTGGCGGAAGCCTT
    Ra_VH CGCCTGTCATGTCGGGCCTCTGGTTCCACCTACAGTAACTACTGCCTGGGCTGG
    H10- TTCCGCCAGATCACTGGCAAGGAACGCGAGGGCGTCGCGGTCATCAACTGGGTC
    DR591 GGCGGAATGTTGTACTTCGCAGATAGCGTCAAGGGCAGGTTCACAGTCTCCCAG
    GATCAGGCCAAGAACACCCTGTATCTGCAAATGAACTCCCTCAAGCCTGAAGAT
    ACCGCCATGTATTACTGCGCAGCCGAGTCTGTCTCTTCATTCTCTTGCGGGGGT
    TGGCTGACCCGTCCTGACAGGGTGCCATACTGGGGCCAGGGTACACAAGTCACC
    GTGTCTTCAGGAGGTTCCGGTGGGTCAGGAGGTTCCGGGCAAGTTCAGCTCCAA
    GAGAGTGGTGGCGGTAGCGTGCAGGCAGGCGGTTCACTTCGTCTGTCTTGCACA
    GCCAGTGGGGCTATCGCCTCCGGCTACATTGACAGCAGATGGTGTATGGCCTGG
    TTCCGGCAGGCCCCAGGCAAAGAAAGAGAAGGGGTGGCAGCCATCTGGCCGGGT
    GGGGGCCTGACGGTCTATGCTGACAGCGTGAAGGGCCGCTTCACTATCTCAAGG
    GATCACGCCAAGAACACCTTGTACTTGCAGATGAACAATCTGAAGCCCGAAGAC
    ACCGCAATGTATTACTGTGCCGCAGGTAGCCCCCGCATGTGCCCATCCCTGGAG
    TTTGGATTCGACTACTGGGGCCAGGGAACCCAGGTGACCGTTAGCTCT
    hIL27 1353 CAGGTTCAGCTTCAGGAGAGCGGCGGTGGGTCCGTGCAGGCCGGTGGCTCCCTG
    Ra_VH CGCCTGAGCTGCCGCGCCAGCGGAAGCACTTACAGCAATTATTGTCTTGGCTGG
    H10- TTCCGTCAGATCACAGGCAAAGAGCGCGAAGGCGTGGCCGTTATCAACTGGGTC
    DR592 GGCGGTATGCTGTATTTCGCCGACTCTGTGAAAGGTCGCTTTACGGTCTCTCAG
    GATCAGGCCAAGAACACGCTTTACTTGCAAATGAACTCACTGAAGCCCGAAGAC
    ACCGCCATGTATTACTGTGCCGCAGAGTCTGTCAGCTCCTTTTCATGCGGAGGT
    TGGTTGACTCGCCCCGACCGTGTTCCTTACTGGGGCCAGGGCACGCAAGTGACC
    GTTTCCTCTGGAGGCGGAAGTCAGGTGCAGTTGCAGGAGTCCGGGGGCGGTAGC
    GTGCAGGCCGGTGGCAGTCTGCGTCTGAGTTGTACTGCCCCCGGCTTCACCTCC
    AACTCCTGTGGCATGGACTGGTATCGCCAGGCCCCCGGAAAAGAACGTGAGTTC
    GTATCTAGCATCTCCACCGATGGGACCACAGGTTATGCTGATTCCGTAAAGGGT
    AGGTTCACTATCAGCAAGGATAAAGCCAAAGATACCGTGTACCTCCAGATGAAT
    AGCCTTAAACCAGAGGATACGGGAATGTATAGTTGCAAGACCAAGGATGGAACT
    ATCGCGACAATGGAACTCTGCGACTTCGGCTACTGGGGCCAGGGAACTCAGGTG
    ACCGTGTCCTCC
    hIL27 1354 CAGGTTCAGTTGCAGGAATCCGGGGGCGGAAGCGTGCAAGCAGGGGGTAGTTTG
    Ra_VH CGCCTGTCATGCCGCGCCAGCGGCTCCACCTACAGCAATTATTGTCTGGGTTGG
    H10- TTCCGCCAGATCACTGGCAAGGAGCGCGAAGGGGTGGCCGTGATTAACTGGGTG
    DR592 GGCGGTATGTTGTACTTCGCTGACTCCGTAAAGGGACGCTTCACTGTCAGCCAG
    GACCAGGCTAAGAACACTCTGTATCTCCAGATGAACTCACTGAAGCCTGAGGAT
    ACCGCCATGTATTACTGCGCTGCCGAGTCCGTCTCCAGCTTTTCCTGCGGCGGA
    TGGCTGACTCGCCCTGACCGCGTGCCGTACTGGGGGCAAGGCACTCAGGTGACA
    GTGTCTAGCGGAGGGTCTGGGGGCTCTGGTGGAAGCGGGCAGGTGCAGCTTCAG
    GAATCTGGCGGTGGGAGCGTACAAGCGGGCGGATCTCTTCGTCTGTCCTGTACC
    GCTCCTGGCTTTACGTCCAATTCCTGTGGGATGGATTGGTACAGACAAGCCCCA
    GGTAAGGAGCGCGAGTTCGTGTCCTCTATCAGCACCGACGGAACTACCGGGTAC
    GCTGACTCAGTGAAGGGTCGCTTCACCATCAGCAAGGATAAGGCCAAGGATACC
    GTGTACCTGCAAATGAACAGTCTGAAGCCAGAAGATACCGGCATGTACTCATGC
    AAGACGAAAGATGGGACTATCGCCACTATGGAACTGTGCGATTTTGGCTACTGG
    GGGCAGGGCACTCAGGTGACTGTCTCAAGC
    hIL27 1355 CAGGTCCAGCTCCAGGAATCTGGTGGAGGTAGCGTTCAGGCCGGGGGCTCCCTC
    Ra_VH CGCCTGTCATGCAGGGCCAGCGGCTCTACCTATTCCAATTACTGCCTCGGGTGG
    H10- TTCAGACAGATCACAGGAAAGGAGCGCGAGGGCGTGGCAGTCATCAACTGGGTA
    DR593 GGCGGTATGCTGTATTTCGCGGATAGTGTGAAGGGAAGATTCACCGTGAGTCAG
    GATCAGGCTAAGAACACCCTGTATCTCCAGATGAACTCCTTGAAGCCCGAGGAC
    ACTGCCATGTATTACTGCGCAGCCGAATCTGTTAGCTCCTTCAGCTGTGGTGGC
    TGGCTGACCCGCCCAGATCGCGTGCCATATTGGGGCCAGGGCACACAGGTTACT
    GTCTCCAGTGGCGGGGGCAGCCAAGTGCAGTTGCAGGAGAGCGGAGGCGGAAGT
    GTGCAGGCAGGCGGATCTCTGAGACTCTCTTGTGCTGCCTCCGGCTATCCATAT
    TCTAATGGCTACATGGGATGGTTCCGCCAAGCACCGGGCAAAGAGAGAGAAGGG
    GTTGCTACCATCTATACCGGCGATGGCAGAACCTATTACGCGGACTCCGTGAAG
    GGACGCTTCACCATCAGCCGTGATAACGCCAAGAACACTGTGGACCTCCAGATG
    TCTTCCCTGAAGCCTGAAGACACCGCTATGTACTATTGTGCTGCACGCGCCGCG
    CCACTTTACAGTAGCGGTTCTCCTCTTACCCGCGCTCGCTACAACGTCTGGGGC
    CAGGGTACTCAGGTGACAGTTAGTAGC
    hIL27 1356 CAAGTGCAGTTGCAGGAAAGCGGAGGCGGGAGCGTACAGGCGGGCGGTTCTCTG
    Ra_VH CGGCTGAGCTGCCGCGCATCTGGTTCCACATACAGCAATTATTGTCTGGGTTGG
    H10- TTTAGGCAGATCACTGGTAAGGAGAGGGAAGGGGTCGCAGTTATAAATTGGGTG
    DR593 GGTGGGATGCTCTACTTCGCCGATTCAGTGAAGGGCCGCTTCACCGTGAGTCAG
    GATCAGGCGAAGAATACTCTGTACCTCCAGATGAATAGCCTGAAGCCCGAGGAC
    ACCGCCATGTATTACTGCGCCGCAGAGAGTGTCAGCTCCTTTAGCTGCGGGGGC
    TGGCTGACCCGCCCGGACCGCGTGCCCTACTGGGGCCAGGGGACCCAGGTTACC
    GTTAGCTCTGGCGGTAGCGGGGGCTCTGGAGGCAGCGGACAAGTCCAGCTGCAA
    GAATCCGGGGGAGGCAGCGTACAGGCTGGCGGGTCTCTGCGCCTGTCCTGCGCC
    GCTTCAGGATACCCGTATAGCAACGGCTATATGGGTTGGTTCAGACAGGCCCCC
    GGCAAGGAACGTGAAGGAGTGGCCACCATCTACACCGGCGACGGGCGCACCTAT
    TACGCTGATTCTGTGAAGGGCCGCTTTACAATCAGCCGCGATAACGCTAAGAAC
    ACCGTTGACCTTCAAATGTCCAGCCTGAAGCCGGAGGATACCGCCATGTATTAC
    TGTGCAGCCCGCGCCGCACCACTCTACAGCTCCGGTTCTCCCCTCACAAGGGCT
    CGGTACAATGTTTGGGGCCAGGGCACCCAGGTCACCGTCTCTAGC
    hIL27 1357 CAGGTGCAGCTCCAGGAATCAGGTGGGGGCAGCGTACAGGCAGGGGGTTCACTC
    Ra_VH CGCCTGTCTTGCCGGGCCTCTGGCAGTACATACTCCAATTATTGCCTGGGTTGG
    H10- TTTCGCCAAATTACCGGCAAGGAGCGGGAGGGCGTCGCTGTAATCAACTGGGTG
    DR594 GGCGGGATGCTCTATTTTGCTGACTCCGTTAAGGGTCGTTTCACGGTCAGCCAG
    GACCAGGCCAAAAATACACTGTATCTCCAGATGAACTCCCTCAAACCCGAAGAC
    ACCGCCATGTATTACTGTGCTGCCGAGAGTGTCAGCTCTTTTTCCTGCGGGGG
    TGGCTTACCCGCCCGGACCGTGTCCCATACTGGGGTCAAGGCACCCAGGTTACC
    GTCTCATCCGGCGGAGGCAGCCAGGTGCAACTCCAGGAGAGCGGGGGCGGTAGC
    GTGCAGGCAGGCGGAAGCCTGCGTCTCTCCTGTGTGGCTTCCGCGTCCACCTAC
    TGTACCTATGATATGCACTGGTATCGCCAGGCTCCTGGAAAGGGCCGCGAGTTC
    GTGAGTGCTATTGATTCCGATGGCACCACTCGCTACGCTGACTCCGTGAAGGGA
    CGTTTCACCATCTCCCAGGGTACAGCTAAGAACACCGTGTACCTCCAGATGAAC
    TCCCTCCAGCCCGAGGATACCGCAATGTATTACTGCAAGACCGTTTGTGTAGTG
    GGCTCACGCTGGTCCGACTATTGGGGCCAGGGGACCCAGGTGACTGTATCATCT
    hIL27 1358 CAGGTCCAGCTTCAGGAAAGCGGTGGGGGCTCCGTGCAGGCCGGAGGCTCCCTG
    Ra_VH CGTCTGAGCTGTCGGGCCTCTGGTTCCACCTACTCCAACTACTGTCTGGGCTGG
    H10- TTCCGCCAGATTACAGGCAAGGAACGCGAGGGTGTGGCGGTCATAAATTGGGTG
    DR594 GGTGGAATGCTGTATTTCGCGGATAGCGTGAAAGGGCGCTTCACCGTGTCTCAG
    GACCAGGCTAAGAACACACTGTACTTGCAGATGAACAGCCTGAAGCCCGAAGAC
    ACTGCCATGTACTATTGTGCCGCTGAGTCTGTCTCCTCTTTCTCCTGCGGCGGA
    TGGCTGACCCGCCCCGACAGGGTGCCTTACTGGGGTCAGGGCACCCAGGTGACG
    GTTTCTAGTGGTGGCTCAGGTGGCTCCGGCGGTTCCGGCCAGGTCCAGTTGCAG
    GAGTCTGGAGGTGGCAGCGTGCAGGCCGGTGGCAGCCTGCGCCTGTCATGTGTC
    GCTTCTGCGAGCACCTATTGTACCTATGATATGCACTGGTATCGCCAGGCCCCA
    GGCAAGGGTAGGGAGTTTGTGTCCGCGATTGACTCTGACGGCACCACGCGCTAT
    GCGGATTCCGTGAAGGGGCGTTTTACAATCTCCCAGGGCACCGCTAAGAACACT
    GTTTATCTTCAGATGAACAGCTTGCAGCCTGAGGACACCGCGATGTATTACTGT
    AAAACTGTCTGTGTAGTGGGCTCCAGGTGGTCTGACTACTGGGGTCAGGGCACC
    CAGGTGACGGTTTCCAGC
    hIL27 1359 CAGGTGCAGTTGCAGGAATCTGGGGGTGGCTCTGTGCAGGCGGGCGGGTCCCTG
    Ra_VH CGCTTGTCCTGCCGCGCTTCTGGTTCTACCTACTCCAACTATTGTCTGGGCTGG
    H10- TTTAGGCAGATCACCGGAAAGGAGCGCGAAGGTGTGGCTGTTATAAATTGGGTG
    DR595 GGCGGGATGCTCTATTTTGCAGACTCCGTCAAGGGCCGCTTCACCGTCTCACAG
    GATCAAGCCAAGAATACGCTGTATCTTCAGATGAACAGCCTGAAGCCCGAGGAT
    ACAGCCATGTATTACTGCGCCGCAGAGTCTGTGTCTTCCTTTTCTTGCGGAGGC
    TGGCTCACACGCCCGGACCGCGTGCCCTACTGGGGCCAGGGCACCCAGGTGACC
    GTATCCAGCGGGGGCGGTTCCCAAGTGCAGCTCCAGGAGTCTGGCGGAGGGTCC
    GTGCAGGCTGGTGGGAGTCTGACCTTGAGTTGCGCAGCCAGCGAATACGCTTAC
    TCCACTTGCAACATGGGTTGGTATCGTCAGGCTCCCGGTAAAGAGCGCGAGCTG
    GTCTCTGCATTCATCTCAGATGGCTCTACTTACTATGCTGACTCCGTGAAGGGT
    CGGTTTACTATCACCCGCGACAACGCCAAGAACACAGTGTACTTGCAGATGAAC
    TCCCTGAAGCCCGAGGATACCGCCATTTACTATTGTTCCGCCAACTGTTACAGA
    CGCCTGCGCAACTATTGGGGGCAGGGAACACAGGTTACTGTGTCCTCT
    hIL27 1360 CAGGTGCAGTTGCAGGAGAGCGGAGGTGGCAGCGTCCAGGCCGGAGGTTCTCTG
    Ra_VH CGTCTGAGCTGCCGTGCATCCGGTAGTACATACTCTAACTACTGTCTCGGCTGG
    H10- TTCAGGCAGATCACAGGCAAGGAAAGGGAGGGTGTTGCCGTAATCAACTGGGTT
    DR595 GGCGGTATGCTCTACTTCGCTGACTCCGTGAAGGGTAGATTTACCGTGTCTCAG
    GACCAAGCTAAGAACACCCTGTACTTGCAGATGAACAGCCTGAAACCGGAAGAT
    ACCGCCATGTACTATTGCGCTGCCGAGTCCGTGTCCTCTTTCAGCTGCGGGGGT
    TGGCTGACCAGACCTGATCGCGTTCCGTACTGGGGTCAAGGCACACAGGTTACC
    GTGTCAAGCGGTGGCTCTGGAGGCTCCGGTGGGTCCGGTCAGGTCCAGTTGCAA
    GAGTCTGGAGGTGGCAGCGTCCAGGCCGGAGGCTCCCTCACCCTGAGTTGTGCG
    GCCAGTGAGTACGCCTACTCCACTTGCAACATGGGATGGTATCGCCAGGCCCCA
    GGAAAGGAGCGCGAGCTGGTCTCCGCTTTCATCTCCGACGGATCTACCTATTAC
    GCCGACTCTGTGAAGGGACGTTTTACTATCACTAGGGATAACGCGAAAAACACT
    GTGTACCTCCAGATGAACTCTCTCAAGCCTGAGGACACGGCCATCTACTATTGC
    TCTGCGAACTGTTACAGACGGCTGAGAAATTATTGGGGACAGGGTACTCAGGTG
    ACCGTTAGCAGC
    hIL27 1361 CAGGTTCAGCTCCAGGAATCTGGGGGAGGCTCTGTCCAAGCTGGCGGTTCCTTG
    Ra_VH CGTCTGTCTTGTAGGGCCTCTGGGAGCACCTACTCCAATTACTGTCTGGGGTGG
    H10- TTTCGGCAGATCACCGGCAAAGAACGCGAGGGCGTGGCCGTCATCAACTGGGTG
    DR596 GGCGGAATGCTGTACTTTGCCGACTCTGTGAAGGGCCGCTTCACGGTGTCACAG
    GACCAGGCCAAGAATACCCTGTATCTTCAGATGAACTCTCTCAAGCCCGAGGAC
    ACTGCTATGTATTACTGTGCTGCGGAGAGCGTCTCATCCTTCAGCTGTGGTGGC
    TGGCTGACACGCCCGGACCGTGTCCCTTATTGGGGTCAGGGAACCCAGGTGACC
    GTTAGCTCAGGAGGTGGATCTCAGGTGCAACTCCAGGAGAGCGGCGGTGGCCTG
    GTGCAACCCGGAGGTAGCTTGCGCTTGTCCTGTACTGCCTCTGGACTCACCTTC
    GATGACTCAGTAATGGGTTGGTTCAGACAGGCCCCCGGAAAGGGCAGGGAGGCA
    GTGTCTTGTATTAGCTCCAGCGGGGCTAATGCGTTCTACGCCGATTCCGTCAAG
    GGCAGGTTTACCATTAGTCGCGATAACGCCAAGAACACCCTTTACTTGCAGATG
    AACAGCCTGAAGCCCGAGGACACAGCCACCTATTACTGTAAGAGAGGTCACGCC
    TGTGCTGGCTATTACCCAATTCCTTACGATGACTACTGGGGACAGGGAACCCAA
    GTCACTGTCTCTTCT
    hIL27 1362 CAGGTCCAGCTTCAGGAGTCCGGGGGCGGTTCCGTCCAGGCCGGGGGATCACTT
    Ra_VH CGCCTGTCTTGTCGCGCCTCAGGCTCTACTTACTCCAATTATTGCCTCGGTTGG
    H10- TTCCGCCAAATCACCGGCAAAGAACGGGAGGGAGTAGCCGTAATTAACTGGGTT
    DR596 GGGGGAATGCTGTATTTCGCCGACAGTGTGAAGGGCCGCTTCACCGTGTCTCAG
    GACCAGGCAAAGAATACCCTGTATCTCCAGATGAACTCCCTGAAGCCGGAGGAC
    ACTGCCATGTATTACTGCGCCGCTGAGTCCGTGTCCAGCTTCTCCTGCGGTGGC
    TGGCTGACCCGCCCAGATCGTGTTCCTTATTGGGGCCAGGGCACTCAGGTCACA
    GTCAGCTCTGGAGGCTCAGGAGGTTCTGGCGGTAGTGGTCAGGTTCAGCTCCAG
    GAAAGCGGAGGCGGATTGGTTCAGCCTGGTGGAAGTCTGCGCCTCTCTTGCACC
    GCCTCCGGCCTGACATTTGACGATAGCGTGATGGGCTGGTTCCGCCAGGCTCCG
    GGAAAGGGTAGAGAGGCTGTGTCTTGTATCAGCTCTTCCGGGGCGAACGCCTTC
    TACGCCGACTCCGTGAAGGGCCGTTTCACCATCTCACGCGACAACGCAAAGAAC
    ACTCTGTATCTCCAGATGAACAGTCTGAAGCCCGAAGACACGGCGACCTACTAT
    TGCAAGCGCGGCCACGCCTGCGCCGGGTACTATCCCATCCCATACGATGACTAT
    TGGGGCCAGGGAACCCAAGTGACCGTATCTTCA
    hIL27 1363 CAGGTGCAGCTTCAGGAGAGTGGTGGAGGCTCCGTGCAGGCCGGTGGCAGCCTC
    Ra_VH CGTCTCTCTTGCAGAGCCTCAGGAAGCACCTACAGCAATTACTGTTTGGGGTGG
    H11- TTTCGGCAGTCAACGGGCAAGGAGAGAGAGGGCGTGGCCGTTATCAACTGGGTG
    DR591 GGCGGTATGCTGTACTTCGCCGACTCTGTGAAGGGTCGCTTCACAGTGAGCCAG
    GACCACGCGAAGAATACAGTGACTCTCCAGATGAACTCCCTCAAGCCCGAGGAC
    ACCGCCATGTACTATTGTGCGGCTGAGTCCGTATCCTCTTTTTCCTGCGGGGGC
    TGGCTGACTAGGCCTGGCCGTGTCCCATACTGGGGGCAGGGCACTCAGGTCACA
    GTCAGCAGTGGAGGCGGTAGTCAGGTCCAGTTGCAGGAAAGCGGCGGAGGTTCC
    GTCCAGGCCGGAGGTTCCCTGCGCCTGAGCTGCACCGCTTCCGGCGCAATCGCC
    TCTGGTTACATCGACTCCCGCTGGTGTATGGCCTGGTTCCGCCAGGCCCCTGGA
    AAGGAGCGCGAGGGTGTCGCTGCGATCTGGCCTGGTGGAGGCCTGACTGTCTAT
    GCTGATTCCGTAAAGGGCCGTTTCACTATCTCTCGCGATCATGCCAAAAACACC
    CTGTACTTGCAGATGAATAACCTGAAGCCCGAAGACACTGCCATGTATTACTGT
    GCCGCAGGCTCTCCTAGAATGTGCCCTTCCCTGGAGTTCGGGTTTGATTATTGG
    GGGCAGGGCACCCAGGTTACTGTGTCTTCC
    hIL27 1364 CAAGTCCAGCTCCAGGAGAGCGGGGGAGGCTCCGTGCAGGCCGGTGGCAGCCTC
    Ra_VH CGCCTCAGCTGCCGTGCTTCAGGAAGCACCTACAGCAACTACTGCTTGGGTTGG
    H11- TTTCGTCAGAGCACCGGAAAAGAGCGCGAGGGTGTGGCTGTGATTAACTGGGTC
    DR591 GGAGGGATGCTGTATTTTGCGGATAGCGTGAAGGGGCGCTTCACAGTGTCTCAG
    GATCATGCCAAGAACACAGTGACCCTTCAGATGAACAGCCTCAAGCCTGAGGAC
    ACCGCCATGTATTACTGCGCTGCCGAGTCCGTCAGCTCCTTCAGCTGCGGGGGC
    TGGCTCACCCGCCCTGGCCGCGTGCCCTATTGGGGCCAGGGAACCCAGGTTACT
    GTTTCCAGTGGAGGGTCCGGGGGCTCTGGAGGCAGCGGCCAGGTACAGTTGCAG
    GAATCCGGCGGGGGCTCAGTCCAGGCGGGAGGTTCCTTGCGCCTGTCCTGTACC
    GCGTCCGGTGCAATCGCCTCCGGCTATATTGATTCCAGATGGTGTATGGCATGG
    TTCCGCCAGGCTCCCGGTAAGGAACGGGAGGGGGTTGCGGCCATCTGGCCAGGA
    GGGGGTCTCACCGTGTATGCCGACAGTGTTAAGGGCCGTTTCACTATCAGCAGG
    GACCATGCAAAGAACACGCTGTACCTCCAAATGAACAATCTGAAGCCGGAAGAC
    ACCGCCATGTATTACTGTGCTGCCGGTAGTCCTAGAATGTGTCCATCTCTGGAG
    TTCGGTTTTGATTACTGGGGTCAGGGCACACAAGTTACCGTGTCTAGC
    hIL27 1365 CAGGTACAACTCCAGGAGTCTGGTGGGGGCAGCGTACAGGCCGGAGGCTCTCTC
    Ra_VH AGACTCTCATGTCGCGCGAGCGGCTCCACCTATAGCAACTATTGCCTGGGGTGG
    H11- TTCAGACAGAGCACTGGTAAGGAGCGTGAAGGTGTGGCAGTTATCAACTGGGTC
    DR592 GGGGGAATGCTGTATTTCGCCGACAGCGTGAAGGGCCGGTTCACTGTGTCCCAG
    GATCATGCCAAAAACACCGTCACCCTCCAGATGAACTCCCTGAAGCCCGAGGAC
    ACAGCTATGTATTACTGTGCTGCGGAGAGCGTTAGCTCTTTCAGCTGTGGTGGC
    TGGCTCACCCGGCCAGGCCGTGTCCCATATTGGGGACAGGGCACCCAGGTGACA
    GTGTCTAGCGGCGGTGGCTCCCAGGTCCAGCTTCAGGAGTCCGGCGGTGGATCT
    GTGCAGGCAGGCGGTTCCCTCAGGCTGAGTTGTACCGCCCCCGGCTTCACCAGC
    AACAGCTGCGGTATGGACTGGTATCGCCAGGCTCCCGGAAAGGAGAGAGAGTTC
    GTGAGTTCTATCTCCACTGATGGGACGACCGGCTACGCCGACTCCGTGAAGGGG
    CGCTTCACTATCTCTAAAGATAAGGCTAAGGATACCGTCTACTTGCAGATGAAT
    AGCTTGAAACCTGAAGATACCGGCATGTACTCCTGCAAGACCAAGGATGGGACC
    ATTGCTACGATGGAACTCTGTGACTTCGGCTACTGGGGACAGGGCACTCAGGTG
    ACCGTCTCCAGT
    hIL27 1366 CAGGTGCAGCTTCAGGAGTCTGGAGGCGGATCTGTGCAGGCAGGCGGTAGTCTG
    Ra_VH CGTCTTAGCTGCCGTGCCTCTGGCTCAACCTATTCCAATTATTGCCTCGGCTGG
    H11- TTTCGGCAGTCCACCGGCAAGGAAAGGGAAGGCGTGGCGGTCATCAACTGGGTT
    DR592 GGGGGTATGCTGTATTTCGCCGACAGCGTGAAGGGCCGTTTTACAGTGTCTCAA
    GACCATGCTAAGAATACCGTTACCCTCCAGATGAACTCTCTCAAACCGGAAGAC
    ACTGCTATGTATTACTGCGCAGCCGAATCCGTTTCTAGCTTCAGCTGCGGGGGT
    TGGCTGACTAGGCCTGGGCGCGTGCCCTATTGGGGGCAGGGTACACAGGTAACC
    GTTTCCAGCGGAGGCTCTGGCGGGAGTGGCGGATCTGGCCAGGTGCAGTTGCAG
    GAATCTGGAGGCGGATCTGTCCAAGCTGGGGGCAGCCTCCGTCTGTCATGTACC
    GCCCCTGGGTTCACTTCCAACTCCTGCGGCATGGATTGGTATCGCCAGGCACCT
    GGGAAGGAGCGCGAATTTGTAAGCTCAATCTCCACAGATGGCACCACTGGCTAT
    GCTGACAGTGTTAAAGGCCGGTTCACCATCTCCAAGGATAAGGCTAAGGATACT
    GTATACCTTCAGATGAACTCTCTGAAACCTGAAGACACAGGAATGTATTCCTGT
    AAGACGAAGGATGGCACCATCGCTACAATGGAGCTTTGCGATTTTGGCTATTGG
    GGACAGGGCACACAGGTGACGGTTAGTAGC
    hIL27 1367 CAGGTGCAGCTCCAGGAGTCTGGTGGCGGTTCCGTGCAGGCCGGAGGCAGCCTG
    Ra_VH CGCCTGTCCTGCCGCGCCTCTGGATCTACATACTCCAATTACTGTCTGGGGTGG
    H11- TTCAGACAGAGTACTGGAAAAGAGCGCGAAGGTGTAGCCGTCATAAATTGGGTC
    DR593 GGCGGTATGCTGTACTTCGCCGACAGCGTGAAGGGAAGGTTTACTGTGTCCCAG
    GACCATGCTAAGAATACCGTGACCCTGCAAATGAACTCCCTTAAACCCGAGGAC
    ACCGCTATGTACTATTGCGCGGCTGAGTCCGTGTCCAGCTTTTCTTGCGGAGGC
    TGGCTCACCCGTCCAGGCCGTGTTCCTTATTGGGGACAGGGCACCCAGGTGACG
    GTCTCCTCTGGTGGAGGTTCCCAGGTGCAGCTCCAGGAGAGTGGAGGCGGGTCA
    GTACAGGCTGGCGGAAGCCTCCGCTTGAGCTGCGCTGCCTCCGGCTATCCCTAC
    TCAAACGGCTATATGGGATGGTTTCGCCAGGCCCCCGGAAAGGAACGCGAGGGC
    GTGGCCACCATTTATACTGGCGATGGCCGGACCTACTATGCTGACTCTGTGAAA
    GGCCGCTTTACCATCAGCCGTGACAACGCCAAGAACACTGTTGATTTGCAGATG
    TCTAGCCTGAAGCCCGAAGACACCGCTATGTATTACTGTGCAGCTCGGGCTGCC
    CCTCTGTACTCCTCTGGAAGCCCCCTCACTCGGGCCAGATACAACGTGTGGGGA
    CAGGGGACCCAGGTCACCGTGTCAAGT
    hIL27 1368 CAGGTGCAGTTGCAGGAGTCTGGCGGTGGGTCCGTCCAGGCTGGCGGTTCCCTT
    Ra_VH CGCCTGTCTTGCCGTGCCTCAGGCAGTACCTACAGCAACTACTGTCTCGGTTGG
    H11- TTCCGCCAGTCCACGGGCAAGGAGCGCGAAGGTGTGGCTGTTATCAACTGGGTG
    DR593 GGAGGTATGCTGTACTTTGCCGACTCCGTTAAGGGGCGCTTTACCGTGAGCCAA
    GACCACGCGAAAAACACGGTAACTTTGCAGATGAACTCTCTTAAACCCGAAGAT
    ACCGCTATGTATTACTGCGCGGCAGAGTCTGTGTCTTCCTTCTCCTGTGGCGGA
    TGGCTGACCAGGCCTGGGCGCGTCCCGTACTGGGGTCAGGGCACTCAGGTGACA
    GTCAGCTCCGGCGGAAGCGGTGGCTCCGGTGGCAGTGGGCAAGTGCAACTCCAG
    GAGTCAGGAGGTGGGAGCGTTCAAGCGGGCGGTAGTCTTCGGCTGAGTTGTGCT
    GCGAGTGGCTATCCGTACTCCAACGGCTATATGGGTTGGTTCCGCCAGGCCCCT
    GGCAAGGAGCGGGAGGGCGTGGCCACTATCTACACCGGCGATGGCCGTACCTAT
    TACGCCGACTCCGTGAAGGGACGGTTTACCATCTCACGCGACAACGCGAAGAAC
    ACAGTTGACCTCCAGATGTCCTCACTGAAGCCAGAGGATACTGCCATGTATTAC
    TGTGCTGCCCGCGCAGCCCCTCTGTACTCTAGTGGTTCCCCTCTCACAAGAGCC
    AGATACAACGTCTGGGGACAAGGCACACAGGTGACTGTGAGTTCC
    hIL27 1369 CAGGTACAGCTCCAGGAGTCAGGTGGCGGTTCCGTCCAGGCAGGAGGTAGTTTG
    Ra_VH CGTCTGTCCTGTCGTGCCAGCGGATCTACCTACTCTAACTACTGCCTGGGATGG
    H11- TTCCGCCAGTCTACCGGCAAGGAGAGAGAGGGGGTTGCTGTTATCAACTGGGTC
    DR594 GGCGGGATGCTCTATTTCGCCGACTCTGTGAAAGGCCGCTTTACTGTGTCCCAG
    GATCACGCTAAGAACACCGTAACGCTCCAGATGAACAGCCTGAAGCCTGAAGAC
    ACAGCCATGTATTACTGTGCCGCTGAGAGCGTGTCCAGCTTCTCTTGTGGCGGA
    TGGCTCACCCGCCCCGGTCGTGTGCCCTACTGGGGGCAGGGAACCCAGGTCACA
    GTAAGCTCCGGCGGTGGCAGCCAGGTGCAGTTGCAGGAGTCTGGTGGCGGGTCT
    GTTCAGGCGGGAGGCTCCCTGAGACTTAGCTGTGTTGCGTCCGCATCCACCTAC
    TGCACTTACGATATGCACTGGTATCGCCAGGCTCCTGGCAAGGGCCGTGAGTTC
    GTGTCCGCTATTGATTCCGACGGCACCACTCGCTATGCCGATAGTGTCAAGGGG
    AGGTTTACCATCTCCCAAGGTACAGCGAAAAATACAGTTTACCTCCAGATGAAC
    AGCTTGCAGCCCGAGGACACGGCTATGTATTACTGTAAGACGGTGTGCGTCGTG
    GGCAGTCGGTGGTCCGATTACTGGGGCCAGGGGACCCAGGTTACTGTCTCCAGC
    hIL27 1370 CAGGTACAGCTTCAGGAGTCCGGCGGTGGCTCTGTCCAGGCTGGCGGTTCCCTC
    Ra_VH AGGCTGTCTTGCAGGGCTTCTGGTTCCACCTACAGCAACTACTGTTTGGGATGG
    H11- TTCCGCCAGTCCACAGGTAAGGAGCGCGAGGGAGTGGCGGTCATCAACTGGGTA
    DR594 GGAGGCATGTTGTACTTCGCCGACTCTGTGAAAGGCAGATTCACTGTCAGCCAG
    GACCATGCCAAGAACACAGTCACTTTGCAGATGAACTCTCTGAAACCAGAGGAC
    ACTGCTATGTATTACTGTGCTGCCGAGTCAGTCAGCTCCTTCTCCTGCGGAGGG
    TGGCTCACCAGACCTGGCCGCGTGCCGTACTGGGGCCAGGGGACGCAGGTGACC
    GTGTCCAGTGGCGGGAGCGGAGGTTCTGGTGGCTCAGGCCAGGTTCAACTGCAA
    GAGTCCGGTGGAGGTTCTGTGCAGGCCGGTGGCTCCCTGCGTCTCTCCTGCGTG
    GCCTCTGCCTCCACTTACTGTACCTATGATATGCACTGGTATCGCCAGGCCCCA
    GGCAAGGGCCGTGAGTTTGTGAGCGCCATTGACAGTGATGGCACCACTAGGTAT
    GCCGATTCCGTGAAGGGTCGCTTCACCATCAGTCAGGGCACTGCCAAGAACACT
    GTGTATCTCCAGATGAACAGCTTGCAGCCCGAGGACACCGCCATGTATTACTGC
    AAGACCGTCTGCGTCGTGGGAAGCCGCTGGAGCGACTATTGGGGCCAGGGGACC
    CAGGTGACCGTCTCATCC
    hIL27 1371 CAGGTGCAACTGCAAGAGTCCGGCGGAGGCTCCGTTCAGGCTGGCGGGTCTCTG
    Ra_VH CGGCTCTCCTGCCGCGCCAGCGGCTCTACTTATAGCAACTACTGCCTGGGATGG
    H11- TTCAGACAGAGTACAGGTAAGGAGAGGGAGGGAGTCGCTGTTATCAACTGGGTT
    DR595 GGCGGTATGCTCTATTTCGCGGACTCCGTGAAGGGCCGGTTCACCGTGAGCCAG
    GACCACGCCAAGAACACCGTGACACTCCAGATGAACAGCCTTAAACCTGAGGAC
    ACCGCTATGTACTATTGCGCAGCCGAAAGTGTTAGCTCTTTTTCCTGTGGTGGC
    TGGCTGACTCGCCCTGGGCGCGTTCCATATTGGGGTCAGGGCACCCAGGTGACG
    GTTTCATCCGGCGGAGGCAGTCAAGTGCAGCTTCAGGAATCCGGCGGGGGATCT
    GTGCAGGCTGGGGGCAGTCTGACCCTGTCCTGTGCTGCCAGCGAGTACGCCTAC
    TCCACTTGCAATATGGGATGGTATCGCCAGGCACCGGGAAAGGAGCGTGAGCTG
    GTCAGTGCATTTATCAGCGATGGCTCCACCTATTACGCCGATTCTGTTAAGGGC
    CGCTTCACCATCACCCGCGACAACGCCAAAAACACCGTATATTTGCAGATGAAT
    AGCTTGAAGCCCGAAGATACTGCCATTTATTACTGCTCTGCTAATTGCTACAGA
    CGCCTGCGCAACTATTGGGGCCAAGGCACACAGGTGACAGTAAGCTCC
    hIL27 1372 CAGGTGCAGCTCCAGGAATCTGGCGGTGGGAGCGTCCAGGCGGGCGGGAGCCTC
    Ra_VH CGCTTGAGCTGCCGCGCTAGTGGTAGCACCTACAGTAACTATTGCCTCGGCTGG
    H11- TTCAGGCAGTCCACCGGCAAGGAGCGCGAAGGCGTTGCCGTCATTAACTGGGTT
    DR595 GGAGGTATGCTGTACTTTGCCGACAGCGTAAAGGGTCGTTTTACGGTAAGTCAA
    GATCATGCTAAGAACACTGTGACATTGCAGATGAACAGCCTGAAGCCGGAGGAT
    ACTGCCATGTATTACTGCGCGGCTGAGTCTGTAAGCTCTTTCTCATGCGGTGGA
    TGGCTCACCCGTCCGGGTCGCGTTCCGTACTGGGGTCAGGGCACGCAAGTTACC
    GTTTCTAGCGGAGGCAGTGGGGGCTCTGGGGGTTCCGGCCAGGTCCAGCTTCAG
    GAGTCTGGCGGTGGCTCCGTTCAAGCCGGTGGCTCTCTGACACTGTCCTGTGCC
    GCTTCTGAGTATGCGTACAGCACTTGCAACATGGGATGGTATCGCCAGGCCCCC
    GGAAAAGAGCGCGAGCTGGTTTCCGCATTTATTTCCGACGGCAGCACCTATTAC
    GCCGATTCCGTGAAGGGAAGGTTCACTATTACCCGCGACAACGCAAAGAATACC
    GTCTACTTGCAGATGAACTCCCTGAAGCCCGAGGACACCGCTATCTACTATTGC
    TCCGCAAATTGCTACCGGCGTCTCCGCAACTACTGGGGCCAGGGTACGCAGGTG
    ACAGTCAGCTCC
    hIL27 1373 CAGGTCCAGCTTCAGGAGAGCGGCGGTGGCTCCGTCCAGGCCGGAGGCTCTCTG
    Ra_VH CGCTTGTCCTGCCGTGCCTCCGGTTCCACATACAGCAACTACTGTCTGGGGTGG
    H11- TTCCGTCAGAGCACTGGGAAGGAGAGAGAGGGCGTGGCTGTCATCAACTGGGTT
    DR596 GGCGGGATGCTGTACTTTGCGGATTCAGTCAAGGGAAGGTTCACTGTTAGCCAG
    GACCACGCTAAGAACACCGTAACTCTCCAGATGAACTCCCTGAAGCCCGAGGAT
    ACAGCCATGTATTACTGTGCTGCCGAGTCCGTGTCCAGCTTCTCCTGTGGTGGC
    TGGCTCACTCGCCCAGGGAGAGTCCCATACTGGGGACAGGGGACCCAGGTCACA
    GTGAGTTCCGGCGGAGGCTCTCAGGTGCAGCTGCAAGAGTCTGGCGGAGGTCTT
    GTGCAGCCTGGCGGTTCCCTGCGTCTGAGTTGTACCGCATCTGGTCTCACTTTT
    GACGATAGCGTCATGGGATGGTTCCGCCAGGCACCGGGGAAAGGCCGCGAGGCC
    GTCTCCTGTATTAGTTCCTCTGGTGCCAACGCTTTCTACGCTGATTCCGTGAAA
    GGACGGTTTACCATCTCCCGCGATAACGCCAAAAACACCCTGTATCTCCAGATG
    AACTCTCTGAAGCCAGAGGACACTGCGACCTATTACTGTAAACGCGGTCATGCT
    TGTGCCGGATATTACCCCATCCCCTATGACGATTACTGGGGACAGGGCACCCAA
    GTTACCGTGTCTAGT
    hIL27 1374 CAGGTGCAGCTCCAGGAAAGCGGAGGGGGCTCAGTCCAGGCCGGAGGCTCTCTG
    Ra_VH AGACTCTCTTGCCGTGCATCCGGCAGCACTTATTCCAACTATTGTCTGGGCTGG
    H11- TTTAGGCAGAGCACAGGCAAGGAGCGCGAAGGTGTCGCAGTGATTAACTGGGTC
    DR596 GGCGGGATGTTGTACTTCGCCGATAGCGTCAAGGGGCGGTTTACAGTGTCCCAG
    GACCACGCCAAGAACACCGTGACCCTTCAGATGAATAGCCTGAAGCCCGAAGAT
    ACAGCAATGTATTACTGTGCGGCTGAGTCCGTGTCTTCCTTCAGCTGCGGGGGC
    TGGCTGACCAGACCTGGCCGCGTTCCGTACTGGGGACAGGGAACTCAGGTGACC
    GTTTCCTCTGGCGGATCAGGAGGCTCCGGCGGTTCTGGCCAGGTGCAGTTGCAG
    GAGTCTGGTGGAGGCCTGGTACAACCCGGCGGTTCTTTGCGCCTCTCATGCACT
    GCGAGCGGTCTTACATTTGATGACTCTGTAATGGGCTGGTTCCGTCAGGCTCCT
    GGCAAGGGACGTGAGGCCGTGAGCTGCATTTCCAGCTCCGGCGCGAATGCCTTT
    TACGCTGATTCCGTGAAGGGAAGATTCACCATTAGTAGAGACAACGCTAAGAAC
    ACCCTGTATTTGCAGATGAACTCTCTGAAACCTGAGGATACAGCTACCTATTAC
    TGCAAGCGCGGTCACGCTTGTGCTGGCTATTACCCGATCCCTTACGATGACTAC
    TGGGGACAGGGCACCCAAGTGACAGTCTCTTCC
    hIL27 1375 CAGGTGCAGCTTCAGGAGTCCGGCGGTGGCTCCGTGCAGGCGGGCGAATCCCTT
    Ra_VH CGTCTGAGCTGCCGCGCTTCTGGCTCCACCTACTCTAACTATTGTCTGGGCTGG
    H12- TTTCGTCAGATCACCGGCAAAGAGCGCGAGGGAGTGGCCGTTATAAATTGGGTA
    DR591 GGCGGTATGCTGTACTTTGCTGACTCCGTGAAGGGGCGGTTCACAGTTTCCCAG
    GATCAGGCAAAGAATACTGTTTATCTGGAAATGAACTCCCTGAAGCCTGAGGAC
    ACTGCTATGTATTACTGCGCCACCGAGTCCGTGTCCAGCTTTTCATGTGGCGGT
    TGGCTGACCCGCCCTGATCGGGTCCCTTACTGGGGTCAGGGGACACAGGTAACA
    GTGTCCAGTGGTGGCGGGTCCCAGGTGCAACTCCAGGAATCTGGGGGCGGTTCC
    GTTCAGGCTGGCGGGTCCCTTCGCCTGTCCTGCACCGCGTCCGGTGCTATCGCT
    TCAGGTTATATCGACTCCCGTTGGTGTATGGCTTGGTTTAGACAAGCTCCTGGC
    AAAGAACGCGAGGGCGTCGCTGCCATCTGGCCAGGAGGCGGTCTTACCGTCTAC
    GCCGACAGCGTGAAGGGCCGGTTTACCATCTCACGTGACCACGCCAAGAACACA
    CTGTACCTCCAGATGAATAACCTGAAGCCGGAAGATACGGCCATGTATTACTGT
    GCAGCCGGAAGCCCCCGCATGTGCCCATCTCTTGAGTTCGGGTTTGACTATTGG
    GGACAGGGAACCCAAGTCACTGTGTCCTCT
    hIL27 1376 CAGGTCCAGCTCCAGGAGTCAGGAGGGGGCAGCGTACAGGCCGGAGAGTCCCTG
    Ra_VH AGACTTAGTTGCCGCGCCAGCGGATCTACCTACTCTAACTACTGCCTCGGCTGG
    H12- TTCAGGCAGATCACCGGCAAGGAGAGAGAGGGTGTGGCCGTAATCAACTGGGTT
    DR591 GGGGGAATGCTGTACTTCGCCGACTCCGTGAAGGGTAGGTTCACTGTTTCTCAG
    GACCAGGCAAAGAATACTGTGTATCTGGAGATGAACTCCCTGAAACCCGAAGAT
    ACTGCCATGTATTACTGTGCCACCGAGAGCGTGTCCTCTTTCTCCTGTGGAGGC
    TGGCTCACGCGCCCTGATCGCGTGCCCTATTGGGGACAGGGTACTCAAGTCACC
    GTGTCAAGCGGAGGCAGCGGGGGCTCTGGAGGCAGCGGTCAGGTCCAGCTGCAA
    GAGAGCGGTGGAGGTTCAGTACAGGCTGGCGGGTCACTGCGTCTGAGTTGTACT
    GCCAGTGGAGCCATCGCGTCTGGCTACATCGACTCTAGGTGGTGCATGGCCTGG
    TTCCGGCAGGCTCCTGGGAAGGAGAGAGAGGGAGTGGCCGCGATTTGGCCAGGT
    GGGGGCCTGACCGTCTACGCCGATAGCGTCAAGGGGCGGTTCACCATCAGCCGC
    GATCACGCTAAAAATACCCTGTACCTTCAGATGAATAACCTGAAGCCAGAAGAC
    ACAGCTATGTACTATTGTGCCGCTGGGTCTCCCCGGATGTGTCCAAGTCTGGAA
    TTTGGCTTCGACTACTGGGGGCAGGGCACACAGGTTACTGTGAGTTCC
    hIL27 1377 CAGGTCCAGTTGCAGGAGTCCGGCGGTGGCTCCGTGCAGGCCGGTGAGTCTCTG
    Ra_VH AGACTGTCTTGCCGCGCTAGTGGGTCCACATACAGTAACTACTGCCTGGGCTGG
    H12- TTCCGCCAGATCACTGGTAAGGAAAGGGAAGGCGTTGCTGTTATCAACTGGGTG
    DR592 GGCGGTATGCTGTACTTCGCTGACTCCGTCAAGGGCCGCTTCACCGTCTCTCAG
    GATCAGGCTAAGAATACAGTCTATCTGGAAATGAACAGCCTGAAGCCCGAAGAT
    ACTGCTATGTACTATTGTGCTACCGAGTCTGTCTCTAGCTTTTCTTGCGGAGGC
    TGGCTGACCCGCCCGGACAGGGTCCCTTACTGGGGCCAGGGCACTCAGGTGACC
    GTATCTAGCGGTGGCGGTTCACAGGTGCAACTCCAGGAGAGCGGTGGCGGATCT
    GTGCAGGCCGGAGGCAGCCTTCGCTTGAGCTGCACGGCCCCCGGCTTTACCAGT
    AACAGCTGTGGCATGGACTGGTATCGCCAGGCCCCCGGAAAGGAGCGCGAGTTC
    GTCAGCTCCATCTCCACTGACGGAACTACCGGATATGCTGACTCTGTCAAAGGT
    CGCTTCACCATCTCTAAGGATAAGGCAAAGGACACAGTCTATCTGCAAATGAAC
    AGTCTCAAGCCAGAGGACACAGGTATGTACTCCTGCAAGACCAAGGATGGCACT
    ATTGCCACAATGGAACTTTGTGATTTCGGCTACTGGGGACAGGGCACCCAAGTT
    ACTGTTTCTAGC
    hIL27 1378 CAGGTGCAACTTCAGGAATCAGGGGGTGGCTCCGTGCAGGCTGGTGAGTCACTG
    Ra_VH CGTCTTTCTTGCAGGGCCTCTGGGTCCACCTACTCCAACTACTGCCTGGGTTGG
    H12- TTCAGGCAGATCACCGGCAAGGAGAGAGAGGGCGTGGCCGTTATAAATTGGGTA
    DR592 GGAGGTATGCTGTACTTCGCCGACAGCGTCAAGGGACGCTTCACTGTCAGTCAG
    GATCAGGCCAAGAACACTGTGTACCTTGAGATGAACTCTCTGAAGCCTGAAGAC
    ACAGCCATGTATTACTGTGCCACAGAGAGTGTCTCTAGCTTCAGCTGCGGTGGA
    TGGCTGACCCGTCCTGACCGCGTTCCCTACTGGGGCCAGGGCACTCAGGTTACT
    GTGTCTAGCGGAGGGAGCGGAGGGTCAGGTGGCTCTGGCCAGGTCCAGTTGCAG
    GAGTCTGGTGGGGGCTCTGTGCAAGCTGGCGGGTCTCTGAGACTGTCCTGTACC
    GCACCCGGCTTCACATCCAATAGCTGCGGCATGGACTGGTATAGACAAGCGCCT
    GGGAAGGAGCGCGAGTTTGTTAGCTCCATCAGCACAGACGGCACAACGGGCTAT
    GCCGACTCTGTGAAAGGGCGCTTTACCATTTCTAAGGACAAGGCCAAGGACACC
    GTCTATCTCCAGATGAACAGCCTGAAGCCTGAGGACACAGGCATGTATAGCTGC
    AAAACGAAGGACGGGACCATCGCAACGATGGAGCTGTGTGACTTTGGGTACTGG
    GGGCAGGGCACCCAGGTTACCGTCTCTTCC
    hIL27 1379 CAGGTGCAACTCCAGGAGAGCGGTGGAGGTAGCGTGCAAGCTGGTGAGAGTCTG
    Ra_VH CGCCTCAGCTGCCGCGCTTCCGGCTCAACTTACAGCAATTACTGCCTGGGTTGG
    H12- TTCCGTCAGATCACCGGAAAGGAGAGAGAGGGGGTAGCAGTCATCAACTGGGTC
    DR593 GGCGGAATGCTCTATTTTGCCGACTCCGTTAAAGGACGCTTCACCGTGTCTCAA
    GACCAGGCTAAGAACACAGTGTATCTGGAGATGAACTCTCTCAAGCCAGAGGAT
    ACCGCCATGTACTATTGCGCCACTGAATCCGTGTCTTCCTTCTCATGTGGCGGG
    TGGCTCACTCGTCCTGATCGGGTGCCATACTGGGGGCAGGGCACCCAGGTCACC
    GTCTCTAGTGGTGGAGGCAGCCAGGTCCAGTTGCAGGAGTCTGGGGGCGGTTCT
    GTCCAAGCTGGTGGCTCACTCCGTCTGTCCTGCGCCGCGAGCGGGTATCCATAC
    TCAAATGGCTACATGGGATGGTTCCGTCAGGCTCCAGGAAAGGAGCGTGAGGGG
    GTCGCGACCATTTATACCGGCGACGGACGCACCTACTATGCCGACTCCGTGAAG
    GGGAGGTTTACCATCAGTCGCGATAACGCCAAGAACACCGTGGATCTCCAGATG
    AGTTCCCTGAAGCCTGAAGACACCGCTATGTATTACTGCGCGGCACGTGCCGCA
    CCGCTTTACAGTAGCGGCAGTCCCCTGACCCGCGCGAGGTATAACGTGTGGGGC
    CAGGGCACCCAGGTTACAGTGTCTTCT
    hIL27 1380 CAGGTGCAGCTCCAGGAGTCTGGGGGCGGTTCTGTCCAAGCTGGCGAGAGCCTG
    Ra_VH CGCCTGTCCTGCCGGGCTTCCGGTTCCACCTATTCTAACTATTGTCTGGGTTGG
    H12- TTTCGCCAGATCACTGGAAAGGAGAGGGAGGGTGTGGCAGTTATCAACTGGGTG
    DR593 GGTGGGATGCTCTATTTCGCCGATTCAGTTAAGGGACGCTTCACAGTGAGCCAA
    GACCAGGCTAAGAACACAGTCTACCTGGAGATGAACAGCCTGAAACCGGAAGAC
    ACGGCAATGTATTACTGCGCGACCGAGAGCGTGTCTAGTTTTAGCTGTGGGGGC
    TGGCTGACGAGACCCGACAGGGTGCCTTACTGGGGGCAGGGTACTCAGGTTACC
    GTCTCTTCCGGTGGCAGTGGTGGCAGCGGAGGCAGCGGCCAGGTGCAGCTGCAA
    GAATCTGGCGGTGGCAGCGTTCAGGCGGGAGGTTCCCTTCGCCTGTCTTGTGCT
    GCATCCGGCTACCCTTACTCTAACGGTTACATGGGCTGGTTTCGTCAAGCCCCC
    GGCAAGGAACGTGAGGGGGTGGCGACAATTTATACAGGTGATGGCCGCACTTAT
    TACGCTGACTCCGTTAAGGGACGCTTCACCATCTCCCGCGATAACGCCAAGAAT
    ACGGTGGACCTCCAGATGTCCTCTCTCAAACCTGAGGACACCGCAATGTACTAT
    TGCGCCGCTCGCGCCGCGCCGCTCTACAGTAGCGGCAGCCCACTGACTCGCGCC
    CGCTACAATGTGTGGGGACAGGGAACCCAGGTGACCGTGAGCAGT
    hIL27 1381 CAAGTGCAGCTCCAAGAGTCCGGTGGAGGCTCCGTGCAGGCTGGCGAGTCCCTG
    Ra_VH CGTCTGTCCTGCCGCGCGTCTGGTAGTACTTACTCTAACTATTGTCTCGGTTGG
    H12- TTCAGGCAGATCACCGGCAAAGAGCGCGAAGGAGTTGCCGTTATCAACTGGGTG
    DR594 GGCGGTATGCTCTATTTCGCCGACAGCGTGAAAGGGAGATTCACTGTGAGCCAG
    GACCAAGCTAAGAACACAGTGTATCTTGAGATGAACAGCCTCAAGCCTGAGGAC
    ACCGCTATGTATTACTGTGCCACAGAATCTGTGTCTTCCTTCTCATGTGGGGGT
    TGGCTCACCAGGCCGGACAGGGTCCCATACTGGGGCCAGGGCACCCAGGTGACC
    GTGTCTAGCGGAGGTGGCAGCCAGGTGCAGTTGCAGGAGTCCGGTGGGGGCTCC
    GTGCAGGCTGGAGGCTCACTTCGGCTCAGCTGCGTGGCCTCAGCGTCTACCTAC
    TGCACATACGATATGCACTGGTATCGTCAAGCACCCGGCAAAGGCCGCGAGTTC
    GTCAGCGCCATTGATTCCGACGGTACAACCCGTTACGCTGACTCCGTCAAGGGG
    CGTTTTACCATTTCCCAGGGGACCGCTAAGAACACCGTTTATCTTCAGATGAAC
    AGCCTCCAGCCGGAAGACACAGCCATGTATTACTGTAAAACCGTGTGCGTAGTG
    GGCTCCAGATGGTCAGACTATTGGGGGCAGGGCACCCAGGTAACCGTGTCCTCT
    hIL27 1382 CAGGTTCAGCTTCAGGAATCAGGAGGTGGCTCAGTGCAGGCAGGAGAGTCTCTC
    Ra_VH CGCCTGTCCTGTCGTGCCAGCGGATCTACGTATTCCAACTACTGCCTCGGTTGG
    H12- TTCAGGCAGATCACCGGCAAAGAGCGCGAAGGAGTGGCGGTTATCAACTGGGTT
    DR594 GGCGGAATGCTGTACTTCGCAGACAGTGTCAAGGGCAGATTCACTGTGTCCCAG
    GACCAGGCCAAAAACACAGTGTACCTGGAGATGAATAGTTTGAAGCCGGAAGAT
    ACAGCCATGTATTACTGCGCCACCGAGTCTGTCTCCAGCTTTTCTTGCGGAGGC
    TGGCTGACCCGCCCAGACCGCGTCCCCTACTGGGGCCAGGGAACTCAAGTCACC
    GTGTCTTCCGGTGGGAGTGGTGGCAGCGGGGGCTCCGGCCAGGTGCAGTTGCAG
    GAGTCCGGTGGCGGAAGTGTCCAGGCCGGGGGCTCCTTGAGACTTTCATGCGTC
    GCCTCTGCCTCCACCTACTGCACTTACGACATGCACTGGTATCGCCAGGCTCCG
    GGTAAGGGACGGGAGTTCGTATCTGCCATCGACTCCGACGGGACCACACGCTAC
    GCGGACAGCGTGAAAGGCAGGTTCACCATCAGTCAGGGGACCGCCAAGAATACG
    GTTTACCTCCAGATGAACTCTCTTCAGCCGGAGGACACGGCTATGTATTACTGC
    AAAACTGTGTGCGTGGTTGGAAGCAGATGGTCTGATTACTGGGGTCAGGGCACC
    CAGGTGACTGTATCAAGC
    hIL27 1383 CAAGTGCAGCTGCAAGAAAGTGGCGGTGGCAGTGTGCAAGCTGGAGAGTCCCTC
    Ra_VH AGACTGAGTTGTAGAGCCAGTGGTAGCACATATAGCAATTACTGCCTGGGTTGG
    H12- TTTCGTCAGATCACCGGCAAGGAGAGAGAAGGCGTGGCCGTCATAAATTGGGTC
    DR595 GGCGGTATGCTGTACTTTGCAGATTCCGTCAAGGGCCGCTTTACGGTCAGCCAA
    GATCAGGCCAAGAATACTGTGTATCTGGAAATGAACAGTCTGAAACCGGAGGAC
    ACCGCTATGTATTACTGCGCTACTGAATCCGTCTCCTCTTTTAGTTGCGGTGGG
    TGGCTCACCAGACCGGATCGCGTGCCCTATTGGGGCCAGGGCACCCAGGTGACG
    GTGTCCTCAGGAGGCGGATCACAGGTGCAGCTCCAGGAGAGCGGGGGCGGGAGT
    GTGCAGGCCGGTGGCAGCCTGACCTTGTCATGTGCGGCTAGTGAGTACGCCTAT
    TCTACCTGTAATATGGGCTGGTATCGCCAGGCACCCGGAAAAGAGCGCGAGCTG
    GTGTCCGCGTTCATTAGCGATGGGTCTACCTATTACGCCGATTCCGTGAAGGGC
    AGGTTCACCATCACACGCGACAACGCTAAGAACACCGTATACCTCCAGATGAAC
    AGCCTGAAGCCAGAAGACACGGCCATCTATTACTGCTCTGCTAATTGCTACCGC
    AGGCTGCGCAACTACTGGGGACAGGGCACTCAGGTGACTGTGTCTAGT
    hIL27 1384 CAGGTGCAACTTCAGGAGTCCGGTGGCGGTAGTGTGCAGGCTGGCGAGTCTCTG
    Ra_VH CGTCTGTCTTGCCGCGCGTCCGGCTCCACCTACTCCAACTACTGCCTGGGTTGG
    H12- TTCCGCCAGATTACCGGCAAAGAAAGGGAGGGCGTTGCGGTTATTAACTGGGTG
    DR595 GGCGGGATGCTGTACTTCGCAGATTCTGTGAAGGGTAGGTTTACAGTCTCACAG
    GACCAGGCTAAGAACACGGTGTACCTGGAAATGAACAGTCTCAAGCCCGAAGAC
    ACCGCCATGTATTACTGCGCTACAGAGTCTGTTTCCTCTTTTAGCTGCGGTGGG
    TGGCTGACCCGCCCTGACCGTGTGCCTTACTGGGGACAGGGGACCCAGGTCACT
    GTAAGCTCTGGAGGGTCCGGTGGCTCCGGCGGGAGCGGCCAGGTACAGCTCCAG
    GAGTCCGGCGGGGGAAGTGTGCAGGCCGGAGGCAGCCTCACCCTGAGCTGCGCG
    GCATCCGAGTACGCCTATTCTACCTGTAACATGGGGTGGTACAGGCAGGCTCCG
    GGCAAGGAGAGAGAGTTGGTTTCTGCTTTTATCAGTGATGGCAGTACCTATTAC
    GCGGATTCCGTGAAAGGGAGATTCACCATTACACGTGACAACGCTAAGAACACC
    GTTTATTTGCAGATGAACTCCCTCAAGCCCGAGGATACAGCCATTTACTATTGC
    TCTGCCAACTGCTATCGTCGCCTGCGCAACTACTGGGGACAGGGGACACAGGTG
    ACCGTGTCCAGT
    hIL27 1385 CAGGTCCAGCTCCAGGAGTCCGGGGGTGGCTCCGTGCAGGCTGGCGAATCTTTG
    Ra_VH CGCCTCTCATGCAGAGCTTCCGGCTCCACCTATAGCAACTATTGTCTGGGTTGG
    H12- TTTCGCCAGATCACCGGCAAAGAGCGTGAAGGCGTCGCCGTCATCAACTGGGTC
    DR596 GGCGGGATGCTGTACTTTGCGGACTCTGTTAAGGGTCGTTTCACAGTCAGTCAG
    GATCAAGCGAAGAACACCGTGTACCTGGAGATGAACTCCCTGAAGCCGGAGGAC
    ACCGCAATGTATTACTGTGCCACTGAATCTGTGAGCAGTTTTAGCTGTGGCGGT
    TGGCTGACCCGCCCTGACCGCGTTCCCTACTGGGGGCAGGGCACCCAAGTAACC
    GTGTCTTCCGGGGGCGGGTCTCAGGTCCAGCTCCAGGAGTCTGGAGGGGGCCTT
    GTCCAGCCCGGAGGCAGCCTGCGCCTGTCTTGCACGGCTAGTGGCCTGACATTC
    GACGATAGCGTGATGGGCTGGTTCAGACAGGCTCCGGGGAAGGGCCGTGAGGCC
    GTTTCTTGTATCTCTAGCTCTGGTGCTAACGCCTTCTATGCCGACTCCGTGAAG
    GGCCGCTTCACAATCAGCCGTGACAACGCCAAGAACACGCTGTATCTTCAGATG
    AACTCCCTGAAGCCTGAGGATACCGCCACATATTACTGTAAGCGCGGTCACGCC
    TGTGCAGGCTATTACCCCATCCCCTACGATGACTACTGGGGTCAGGGAACCCAG
    GTTACGGTTTCATCT
    hIL27 1386 CAGGTGCAACTTCAGGAGAGCGGGGGTGGGAGCGTGCAGGCGGGCGAGAGCCTG
    Ra_VH CGCCTGTCCTGCCGTGCGTCTGGCTCCACCTACAGTAACTACTGCCTCGGGTGG
    H12- TTTCGCCAGATTACGGGCAAGGAGCGCGAAGGTGTGGCCGTTATCAACTGGGTG
    DR596 GGTGGAATGCTCTACTTTGCCGATTCTGTGAAAGGACGCTTTACCGTGTCTCAG
    GATCAGGCTAAGAATACAGTTTACCTGGAGATGAACTCTCTCAAGCCTGAGGAT
    ACAGCGATGTACTATTGTGCAACCGAGTCCGTCTCTTCCTTCAGCTGCGGCGGG
    TGGCTGACCCGTCCTGACCGCGTGCCATACTGGGGTCAAGGTACACAGGTGACA
    GTCAGCTCTGGTGGCAGCGGCGGTAGCGGGGGCAGTGGCCAGGTCCAGTTGCAG
    GAAAGTGGAGGCGGTCTGGTTCAACCTGGGGGCTCCCTGCGCCTGTCTTGCACA
    GCCTCTGGACTGACGTTTGATGACTCCGTGATGGGCTGGTTCAGACAGGCTCCT
    GGTAAGGGCCGCGAGGCCGTCAGCTGTATCAGTAGCTCCGGGGCCAACGCTTTC
    TATGCAGACTCTGTCAAAGGCAGATTCACTATCAGCCGCGACAACGCCAAGAAC
    ACACTGTATTTGCAGATGAACAGCCTGAAACCTGAAGATACTGCTACATACTAT
    TGTAAGCGCGGCCATGCCTGTGCTGGGTATTACCCTATCCCCTACGATGACTAC
    TGGGGCCAGGGCACGCAGGTTACAGTAAGCAGT
    hIL27 1387 CAGGTGCAGCTCCAGGAATCCGGTGGCGGGTCCGTGCAGGCTGGCGGTTCCCTC
    Ra_VH CGTCTGTCCTGTGTGGCCTCCGGGTACGTCAGCTGTGACTACTTTCTGCCATCC
    H13- TGGTATCGCCAGGCCCCCGGTAAGGAGAGAGAGTTCGTGTCTATCATTGATGGC
    DR591 ACTGGCAGCACTTCTTACGCCGCATCTGTGAAGGGGCGCTTCACAGCCTCCCAG
    GATAGAGGCAAAAACATTGCCTACCTTCAGATGAACTCTTTGAAACCCGAGGAT
    ACTGCCATGTATTACTGCAAAGCGAGCTGTGTCCGGGGCCGCACCATCTCCGAA
    TACTGGGGACAGGGAACCCAGGTCACGGTCTCCTCTGGTGGCGGGTCCCAGGTG
    CAGCTTCAGGAGAGCGGGGGAGGTTCCGTGCAGGCCGGAGGCTCTCTCAGGCTC
    AGCTGCACAGCGTCCGGCGCTATTGCCAGCGGATATATCGACAGTCGTTGGTGT
    ATGGCCTGGTTTCGCCAGGCTCCGGGCAAGGAGCGTGAGGGAGTCGCTGCCATT
    TGGCCCGGCGGGGGACTGACCGTGTATGCGGACTCTGTGAAAGGAAGATTCACC
    ATCTCTCGGGATCACGCTAAGAATACCCTGTATCTCCAGATGAATAACCTGAAG
    CCCGAGGACACCGCCATGTATTACTGCGCCGCAGGATCACCCCGCATGTGTCCG
    TCTCTGGAGTTCGGTTTCGACTACTGGGGCCAAGGCACCCAAGTCACTGTGTCT
    TCT
    hIL27 1388 CAGGTGCAACTCCAGGAGTCCGGGGGTGGCTCCGTACAGGCTGGAGGCAGCCTC
    Ra_VH CGTCTCAGTTGTGTTGCCAGCGGCTATGTAAGCTGCGACTATTTCCTGCCTTCT
    H13- TGGTATCGCCAGGCACCTGGGAAGGAGCGTGAGTTCGTGTCCATCATTGATGGC
    DR591 ACAGGCAGCACCTCCTATGCCGCTTCAGTCAAGGGACGCTTTACAGCCTCCCAG
    GACCGTGGCAAGAACATCGCCTACCTTCAGATGAACTCCCTGAAGCCTGAGGAC
    ACAGCCATGTATTACTGTAAGGCTTCCTGTGTGCGTGGCCGGACCATCTCTGAA
    TACTGGGGACAGGGCACGCAGGTGACGGTCAGCTCTGGGGGTAGTGGCGGGTCC
    GGCGGGAGTGGACAGGTGCAGCTTCAGGAGAGCGGTGGCGGATCTGTCCAAGCC
    GGTGGCAGCCTTAGGCTCTCTTGCACTGCCAGCGGGGCCATCGCTTCAGGATAT
    ATTGATAGCCGCTGGTGCATGGCCTGGTTCCGCCAGGCCCCAGGGAAAGAGCGT
    GAAGGCGTGGCAGCCATCTGGCCGGGTGGCGGTCTGACCGTCTACGCCGACTCT
    GTTAAAGGAAGATTTACCATTTCCCGCGATCACGCTAAGAACACTCTGTATCTT
    CAAATGAATAACCTGAAACCTGAAGACACCGCTATGTATTACTGTGCTGCCGGT
    AGCCCGAGGATGTGCCCAAGCCTTGAGTTCGGCTTCGACTATTGGGGCCAGGGA
    ACTCAAGTGACCGTGAGCAGC
    hIL27 1389 CAGGTGCAGCTCCAGGAGTCTGGTGGGGGTTCCGTCCAGGCTGGCGGTTCCCTG
    Ra_VH AGGCTCTCATGCGTGGCCAGCGGTTACGTGTCTTGCGACTATTTCCTGCCCTCA
    H13- TGGTATCGTCAGGCCCCTGGCAAGGAGCGCGAGTTCGTGTCAATTATCGACGGC
    DR592 ACAGGCAGTACCAGCTATGCAGCCAGCGTTAAGGGCCGTTTTACCGCGTCACAG
    GATCGCGGGAAGAATATCGCCTACCTCCAGATGAACAGTCTGAAACCTGAAGAT
    ACAGCGATGTATTACTGTAAGGCCAGCTGTGTGAGGGGTCGGACGATCTCTGAA
    TACTGGGGCCAAGGAACCCAAGTAACTGTGTCCAGCGGAGGCGGATCTCAGGTG
    CAGCTTCAGGAATCCGGCGGTGGCAGCGTCCAGGCCGGAGGGAGCCTGCGTCTT
    TCCTGCACCGCTCCTGGCTTCACCAGCAACAGTTGCGGGATGGATTGGTATCGT
    CAGGCTCCCGGCAAGGAACGGGAGTTCGTGTCCAGTATCAGCACTGATGGCACT
    ACCGGATACGCTGATTCCGTTAAGGGTCGTTTCACCATCTCCAAAGATAAGGCC
    AAAGACACCGTGTATCTCCAGATGAACTCCCTGAAACCAGAAGACACAGGTATG
    TATTCTTGTAAGACTAAAGACGGCACCATCGCGACAATGGAGCTGTGTGATTTC
    GGATACTGGGGTCAGGGAACACAGGTGACTGTGTCCTCT
    hIL27 1390 CAAGTACAGTTGCAGGAGTCTGGCGGAGGCTCCGTGCAGGCGGGCGGGAGCCTG
    Ra_VH AGGCTGAGTTGTGTGGCCTCAGGGTATGTGTCCTGTGACTACTTTCTCCCGAGC
    H13- TGGTATCGCCAGGCTCCAGGGAAGGAGCGTGAGTTCGTGTCTATTATCGACGGG
    DR592 ACTGGATCTACCTCTTATGCCGCATCTGTCAAGGGGCGCTTCACCGCCTCTCAG
    GATCGCGGAAAGAACATCGCCTACTTGCAAATGAACAGCCTGAAGCCCGAGGAC
    ACTGCCATGTATTACTGTAAAGCCTCTTGTGTGAGAGGCCGCACTATTTCAGAG
    TACTGGGGACAGGGAACCCAGGTCACTGTCAGCAGTGGAGGTTCTGGCGGTTCT
    GGTGGGTCAGGACAGGTACAGTTGCAGGAAAGCGGAGGCGGTTCCGTGCAGGCC
    GGAGGCTCCCTGAGGCTGTCTTGCACAGCTCCTGGTTTCACATCTAACAGTTGC
    GGCATGGACTGGTATCGCCAGGCCCCAGGGAAGGAGAGGGAATTTGTGTCTAGC
    ATCAGCACCGACGGAACCACAGGATACGCCGACTCCGTCAAGGGTCGTTTTACT
    ATCAGTAAGGACAAGGCTAAGGATACTGTCTACCTGCAAATGAACAGTCTGAAG
    CCCGAGGACACCGGCATGTATAGCTGTAAGACTAAGGATGGAACTATTGCGACT
    ATGGAGCTGTGTGACTTCGGGTATTGGGGCCAGGGTACACAAGTAACTGTGAGT
    TCT
    hIL27 1391 CAGGTACAGCTCCAGGAGAGCGGTGGCGGTTCCGTCCAAGCAGGCGGTTCCCTC
    Ra_VH AGACTGTCATGCGTCGCAAGCGGCTACGTGTCATGTGATTACTTCCTGCCCTCC
    H13- TGGTACAGGCAAGCGCCAGGAAAGGAAAGGGAGTTTGTCTCCATTATCGACGGC
    DR593 ACCGGAAGCACAAGTTACGCCGCGTCTGTTAAGGGCCGCTTCACCGCTTCTCAA
    GATCGCGGCAAAAACATCGCCTACCTGCAAATGAACAGCCTCAAACCAGAGGAC
    ACCGCGATGTATTACTGCAAGGCTTCTTGTGTGCGTGGTCGGACGATTTCCGAA
    TACTGGGGCCAAGGCACCCAGGTGACTGTTTCTAGCGGTGGGGGCAGCCAGGTC
    CAGTTGCAGGAGAGTGGCGGTGGCAGCGTTCAGGCTGGCGGGAGCCTGAGACTC
    AGCTGCGCTGCGTCTGGTTACCCCTATTCCAACGGCTATATGGGCTGGTTCAGA
    CAGGCACCAGGGAAGGAGCGCGAGGGGGTGGCCACCATCTACACCGGCGATGGC
    CGCACATATTACGCTGATTCAGTGAAGGGAAGATTCACTATCAGTAGGGACAAC
    GCTAAGAATACCGTGGATCTCCAGATGAGTTCACTGAAGCCGGAGGATACCGCG
    ATGTATTACTGCGCGGCTCGCGCAGCCCCTCTCTACAGTAGCGGCTCCCCTCTT
    ACGCGGGCTAGATACAACGTGTGGGGCCAGGGAACCCAGGTTACTGTGAGCAGT
    hIL27 1392 CAGGTTCAGCTGCAAGAGTCCGGCGGGGGCTCCGTTCAGGCCGGAGGCTCTCTC
    Ra_VH AGGCTGAGCTGTGTCGCCTCCGGCTATGTGAGCTGTGACTACTTTCTGCCATCC
    H13- TGGTATCGCCAGGCCCCTGGCAAGGAACGCGAGTTTGTCTCCATCATTGACGGC
    DR593 ACCGGCTCCACATCCTACGCGGCTTCCGTGAAGGGGCGTTTCACCGCGTCCCAA
    GATCGCGGGAAGAATATCGCCTACCTCCAAATGAACTCTCTCAAGCCGGAGGAC
    ACTGCTATGTATTACTGTAAGGCATCCTGTGTTCGCGGGCGGACAATCAGCGAA
    TACTGGGGCCAGGGCACCCAGGTAACTGTATCCAGCGGAGGCTCTGGAGGTTCT
    GGTGGCTCCGGGCAGGTCCAGCTCCAGGAGTCTGGCGGTGGCTCCGTGCAGGCT
    GGTGGCAGCCTTCGTCTGTCTTGCGCTGCCTCTGGTTATCCTTACTCCAATGGC
    TACATGGGCTGGTTTCGCCAGGCCCCAGGGAAGGAGAGGGAGGGCGTGGCCACT
    ATCTACACCGGCGATGGCCGCACCTACTATGCTGACAGCGTGAAGGGCAGATTC
    ACCATCAGCAGGGATAACGCAAAGAACACAGTGGACCTTCAGATGAGTAGCCTG
    AAGCCAGAGGACACCGCTATGTATTACTGTGCGGCCAGGGCAGCTCCGTTGTAC
    TCTTCCGGTTCCCCTCTGACCAGAGCGAGATATAATGTGTGGGGACAGGGCACC
    CAGGTTACCGTCAGTTCC
    hIL27 1393 CAAGTGCAGTTGCAGGAGAGCGGGGGTGGGTCCGTCCAGGCTGGGGGCTCACTG
    Ra_VH CGTCTGAGCTGTGTGGCCTCTGGTTACGTGTCCTGTGACTATTTCCTGCCTTCT
    H13- TGGTATAGACAGGCCCCAGGCAAAGAAAGGGAGTTCGTGTCTATTATCGACGGC
    DR594 ACCGGCAGCACTAGCTATGCGGCCAGCGTTAAGGGGCGTTTCACAGCCAGCCAG
    GATCGCGGCAAGAACATCGCCTATTTGCAGATGAACTCCTTGAAGCCCGAGGAC
    ACCGCCATGTACTATTGCAAGGCCAGCTGCGTGCGCGGCAGGACCATTTCCGAG
    TACTGGGGCCAAGGCACTCAGGTGACAGTGTCTTCCGGTGGCGGTAGTCAGGTG
    CAGTTGCAGGAGTCCGGGGGAGGCAGCGTGCAGGCCGGTGGGTCCCTCCGCCTG
    AGCTGTGTGGCGTCCGCAAGCACCTACTGTACCTATGATATGCACTGGTACAGG
    CAAGCCCCTGGCAAGGGCCGCGAGTTTGTCTCTGCTATCGACTCAGACGGGACC
    ACTCGCTACGCTGACAGTGTAAAGGGGCGCTTCACTATTAGCCAGGGCACAGCC
    AAGAACACCGTGTACCTCCAGATGAATAGCCTCCAGCCCGAGGACACTGCCATG
    TATTACTGCAAGACCGTATGCGTGGTTGGGAGTCGCTGGTCAGATTACTGGGGT
    CAGGGTACTCAGGTGACCGTCTCCAGC
    hIL27 1394 CAGGTGCAGTTGCAGGAATCCGGCGGTGGCTCAGTCCAGGCCGGGGGCTCCCTG
    Ra_VH AGGCTGTCATGCGTCGCCAGCGGATATGTGTCTTGCGACTATTTTCTGCCCTCC
    H13- TGGTATCGCCAAGCTCCCGGCAAGGAGAGAGAATTTGTTTCTATCATTGACGGG
    DR594 ACAGGTTCCACTTCCTACGCTGCCAGCGTCAAAGGCCGCTTCACGGCGAGCCAG
    GATAGGGGCAAAAACATCGCCTACCTGCAAATGAACTCTCTCAAGCCCGAGGAC
    ACTGCCATGTATTACTGTAAAGCCAGCTGTGTGCGCGGTCGCACTATCTCTGAA
    TATTGGGGCCAGGGCACCCAGGTGACCGTCTCCTCTGGAGGTTCAGGGGGCTCC
    GGTGGCAGCGGTCAGGTCCAGCTCCAAGAGTCTGGGGGCGGTAGTGTGCAGGCG
    GGCGGTTCCCTCAGACTCTCCTGCGTGGCCTCCGCCTCTACCTATTGCACCTAC
    GATATGCACTGGTATCGGCAGGCTCCAGGAAAGGGCCGGGAGTTCGTGAGCGCG
    ATTGACTCCGATGGCACTACCCGTTATGCCGATTCCGTTAAGGGACGGTTCACA
    ATTAGCCAGGGAACCGCGAAGAACACCGTGTACCTGCAAATGAACTCTCTCCAG
    CCGGAGGATACTGCCATGTATTACTGTAAGACTGTGTGCGTCGTTGGGTCCAGG
    TGGTCCGATTATTGGGGCCAGGGAACTCAGGTTACCGTGTCCAGC
    hIL27 1395 CAAGTGCAGCTCCAGGAGTCTGGCGGTGGCTCTGTGCAAGCGGGCGGTTCTCTC
    Ra_VH AGACTCAGCTGCGTGGCCAGCGGCTACGTGTCCTGCGATTACTTCCTGCCTAGC
    H13- TGGTATCGTCAGGCCCCCGGCAAGGAACGCGAGTTCGTCAGCATTATCGACGGG
    DR595 ACTGGGTCAACCTCCTATGCAGCCTCCGTAAAAGGCAGGTTCACCGCCAGTCAG
    GATCGCGGCAAGAATATCGCGTACCTCCAGATGAACTCTTTGAAACCTGAGGAT
    ACAGCTATGTATTACTGTAAGGCTAGTTGTGTGCGTGGGCGCACCATCTCCGAA
    TACTGGGGCCAGGGAACTCAGGTCACTGTTTCTAGTGGGGGCGGAAGTCAGGTG
    CAGTTGCAGGAGTCTGGAGGCGGTTCAGTCCAGGCTGGCGGATCTCTGACGCTC
    TCTTGTGCAGCCTCTGAGTATGCCTATAGCACCTGCAACATGGGATGGTACAGA
    CAGGCTCCTGGTAAGGAGCGCGAATTGGTGAGCGCTTTCATCTCTGATGGTTCC
    ACATATTACGCTGATTCCGTGAAGGGCCGCTTTACGATTACACGCGACAATGCG
    AAAAACACAGTGTACCTCCAGATGAACTCCCTCAAACCAGAAGACACTGCAATC
    TACTATTGTTCTGCTAACTGCTATCGCCGTCTGCGCAACTACTGGGGGCAAGGT
    ACGCAAGTGACCGTCTCCAGC
    hIL27 1396 CAGGTCCAGCTGCAAGAGAGCGGCGGTGGGTCTGTGCAGGCCGGAGGCAGCCTG
    Ra_VH CGTCTCAGCTGCGTCGCTTCTGGATATGTCAGCTGTGACTACTTCCTCCCATCT
    H13- TGGTACAGACAAGCGCCGGGGAAGGAACGCGAGTTCGTTAGCATTATCGACGGC
    DR595 ACTGGAAGTACCTCTTATGCCGCTTCCGTTAAAGGACGCTTCACGGCCTCTCAG
    GATCGCGGCAAGAATATCGCCTACCTTCAGATGAACAGCCTGAAGCCAGAGGAC
    ACCGCTATGTATTACTGCAAGGCCAGCTGTGTGAGAGGGCGCACCATCAGCGAA
    TACTGGGGCCAGGGCACCCAGGTGACCGTATCTAGTGGCGGGAGCGGTGGCTCC
    GGTGGCAGTGGCCAGGTGCAGCTGCAAGAGAGTGGTGGGGGCAGTGTGCAGGCT
    GGGGGTTCCCTGACGCTGTCCTGTGCGGCCAGCGAGTATGCTTACTCAACGTGC
    AATATGGGTTGGTATCGCCAGGCCCCTGGTAAGGAGCGCGAACTCGTCTCTGCA
    TTTATTAGCGACGGCTCCACTTATTACGCCGACAGCGTGAAGGGGAGATTCACT
    ATTACCCGCGACAATGCCAAGAACACTGTGTACCTCCAAATGAACTCCCTGAAG
    CCCGAGGACACAGCCATCTATTACTGCTCCGCGAACTGCTATCGCCGTCTGCGT
    AACTACTGGGGCCAGGGGACCCAGGTCACAGTCTCCTCT
    hIL27 1397 CAGGTACAGCTCCAGGAGTCCGGCGGTGGCTCTGTGCAGGCAGGAGGCTCACTG
    Ra_VH CGCTTGAGTTGCGTGGCCAGCGGCTACGTGTCCTGCGACTACTTCCTGCCATCC
    H13- TGGTATAGGCAGGCTCCGGGTAAGGAAAGGGAGTTCGTCTCCATTATCGACGGT
    DR596 ACTGGCAGCACCTCTTACGCAGCCTCCGTGAAGGGGCGTTTCACCGCCAGCCAG
    GATCGGGGCAAGAACATCGCCTACTTGCAGATGAACTCCCTGAAGCCAGAGGAC
    ACTGCAATGTATTACTGCAAAGCCAGCTGTGTGAGAGGACGCACCATCTCTGAG
    TACTGGGGGCAAGGCACACAGGTCACGGTCTCTAGTGGCGGGGGTAGCCAGGTC
    CAGCTCCAGGAAAGCGGAGGTGGCCTGGTTCAGCCGGGAGGGTCACTGAGACTG
    TCCTGTACCGCCAGCGGGCTGACCTTCGATGACAGCGTCATGGGTTGGTTCCGG
    CAGGCCCCCGGTAAAGGAAGAGAGGCGGTGAGCTGCATCAGCTCCTCTGGAGCT
    AACGCCTTCTATGCTGACTCCGTGAAGGGTCGCTTCACCATCTCCAGAGATAAC
    GCTAAGAATACTCTCTACCTCCAGATGAACTCTCTGAAACCGGAGGACACCGCA
    ACCTATTACTGCAAGCGCGGGCACGCCTGCGCGGGATACTATCCAATCCCATAC
    GATGACTACTGGGGTCAGGGAACCCAGGTCACCGTGAGTTCT
    hIL27 1398 CAGGTGCAGCTCCAGGAGAGCGGCGGTGGCTCTGTCCAGGCAGGCGGTTCCCTG
    Ra_VH CGCCTCTCTTGCGTGGCGAGTGGCTATGTTAGTTGTGACTACTTCCTGCCCTCA
    H13- TGGTATCGGCAAGCTCCGGGAAAAGAGCGCGAGTTTGTCTCCATCATTGATGGA
    DR596 ACAGGATCTACGTCCTATGCCGCAAGTGTCAAGGGGCGGTTCACCGCTTCTCAG
    GACAGAGGAAAGAATATCGCTTATCTCCAGATGAACTCCCTGAAGCCAGAAGAC
    ACCGCTATGTACTATTGCAAGGCTTCTTGTGTGCGCGGCAGAACCATCTCTGAG
    TACTGGGGCCAGGGCACCCAGGTGACCGTTAGTTCAGGAGGGAGCGGAGGCAGT
    GGAGGCTCAGGTCAGGTGCAGCTCCAGGAATCTGGCGGAGGTCTGGTCCAGCCA
    GGTGGGTCCCTGCGCCTCAGCTGTACTGCCTCCGGTCTCACCTTCGATGACAGC
    GTCATGGGCTGGTTCCGCCAAGCGCCGGGTAAGGGGCGTGAAGCCGTGAGCTGC
    ATTTCCTCTAGCGGAGCCAACGCTTTTTACGCCGACAGCGTGAAGGGTAGATTT
    ACAATCTCTCGCGATAACGCGAAGAACACCCTGTATCTCCAAATGAACAGCCTG
    AAGCCAGAGGACACCGCTACTTATTACTGCAAGAGGGGACATGCGTGTGCGGGG
    TATTACCCCATTCCCTATGATGACTACTGGGGCCAGGGCACCCAGGTGACCGTT
    AGTTCT
    hIL27 1399 CAGGTGCAACTCCAGGAATCCGGCGGTGGCTCCGTGCAAGCCGGTGGCAGTCTT
    Ra_VH AGGCTGTCCTGTGTGGCATCAGGGTATGTGTCCTGCGACTACTTCCTGCCTAGC
    H14- TGGTACAGACAAGCTCCCGGTAAGGAGAGAGAGTTCGTGTCAATCATTGATGGC
    DR591 ACCGGCTCCACTTCCTACGCCGCTTCTGTGAAGGGACGTTTTACTGCCAGCCAA
    GATAAGGGCAAGAACATTGCCTATTTGCAGATGAACTCCTTGAAGCCGGAGGAC
    ACCGCTATGTATTACTGCAAGGCCTCCTGTGTACGTGGCCGGGCCATTTCCGAA
    TACTGGGGCCAAGGAACGCAGGTCACAGTGTCCTCTGGAGGTGGGTCCCAGGTG
    CAGTTGCAGGAAAGCGGCGGAGGGTCCGTCCAGGCTGGTGGCTCTCTGCGCCTT
    TCCTGCACCGCCTCTGGGGCTATCGCCTCCGGCTACATTGATTCTCGCTGGTGC
    ATGGCATGGTTCCGCCAAGCTCCTGGCAAGGAACGCGAGGGAGTGGCCGCGATT
    TGGCCCGGTGGGGGTCTGACTGTCTACGCAGACTCTGTAAAGGGTCGCTTCACA
    ATTTCCAGAGATCACGCGAAGAATACCCTCTACCTCCAGATGAACAATCTCAAG
    CCCGAGGACACTGCCATGTACTATTGCGCCGCTGGATCTCCGCGCATGTGCCCT
    AGTCTGGAATTTGGCTTCGATTACTGGGGCCAGGGTACTCAGGTGACAGTGTCT
    AGC
    hIL27 1400 CAGGTGCAGTTGCAGGAGTCAGGAGGTGGCAGCGTCCAGGCAGGAGGTAGCTTG
    Ra_VH CGGCTCTCCTGCGTTGCGTCCGGCTATGTGAGTTGTGACTATTTTCTCCCATCT
    H14- TGGTATCGTCAAGCGCCAGGTAAGGAACGTGAATTTGTGTCCATCATTGATGGA
    DR591 ACTGGCTCCACTAGCTACGCCGCGAGCGTGAAGGGCCGCTTCACGGCCTCTCAG
    GATAAGGGGAAGAACATCGCATACCTCCAGATGAACTCCTTGAAGCCAGAGGAT
    ACCGCCATGTATTACTGCAAGGCCTCCTGCGTCCGTGGTCGGGCGATCTCCGAG
    TACTGGGGCCAGGGAACTCAGGTGACAGTCAGCTCTGGTGGCAGCGGAGGGTCC
    GGCGGAAGCGGACAGGTGCAGCTCCAGGAAAGTGGAGGGGGAAGCGTGCAGGCA
    GGGGGCAGCCTGCGGCTGTCTTGTACCGCATCCGGGGCCATTGCTTCCGGCTAT
    ATTGATTCCAGATGGTGCATGGCTTGGTTTAGGCAAGCGCCTGGCAAAGAGCGT
    GAAGGTGTCGCCGCAATCTGGCCGGGCGGGGGTCTGACAGTGTACGCCGACTCT
    GTGAAGGGTAGATTCACAATCAGCCGCGACCATGCTAAAAACACTTTGTACCTC
    CAGATGAATAACCTGAAGCCTGAAGACACCGCCATGTATTACTGCGCTGCCGGA
    AGCCCTCGCATGTGCCCCAGCCTGGAGTTTGGCTTCGATTACTGGGGCCAGGGG
    ACCCAGGTGACGGTGAGCAGC
    hIL27 1401 CAGGTACAGTTGCAAGAGAGCGGAGGCGGTTCTGTGCAGGCTGGAGGCAGCCTT
    Ra_VH CGCCTGTCCTGCGTGGCCTCTGGATACGTGTCATGTGACTACTTCCTGCCGAGT
    H14- TGGTATCGCCAGGCTCCTGGGAAGGAGCGGGAGTTCGTGAGCATTATCGACGGC
    DR592 ACAGGCAGTACGTCCTACGCGGCCAGCGTGAAAGGTAGGTTCACTGCTTCCCAG
    GATAAAGGCAAAAACATCGCGTACTTGCAGATGAACTCACTGAAGCCTGAGGAC
    ACAGCCATGTATTACTGTAAGGCCAGCTGTGTGCGTGGCCGCGCTATCTCTGAG
    TACTGGGGGCAAGGCACTCAGGTCACTGTCAGCAGTGGTGGAGGTAGCCAGGTG
    CAGCTCCAGGAGTCAGGAGGCGGGTCCGTGCAGGCTGGTGGCAGCCTGCGCCTC
    AGCTGCACCGCTCCCGGCTTCACTTCTAACAGCTGCGGCATGGACTGGTATAGG
    CAAGCCCCAGGGAAGGAGCGCGAGTTCGTTTCCAGTATCTCCACCGATGGAACC
    ACGGGCTATGCTGATTCCGTGAAAGGACGTTTCACTATTAGCAAGGACAAGGCG
    AAAGACACTGTGTATCTCCAGATGAACTCTCTGAAGCCTGAGGATACCGGCATG
    TATAGCTGTAAAACAAAAGATGGGACCATCGCAACTATGGAACTTTGTGACTTC
    GGCTATTGGGGCCAGGGTACTCAGGTAACCGTGTCCTCT
    hIL27 1402 CAGGTTCAGTTGCAAGAAAGTGGTGGGGGCAGCGTGCAGGCGGGAGGCAGCTTG
    Ra_VH AGGCTGAGCTGCGTGGCATCCGGCTACGTTTCCTGTGATTACTTTCTGCCCTCC
    H14- TGGTATCGCCAAGCGCCTGGAAAAGAGAGGGAGTTCGTTTCTATTATCGACGGC
    DR592 ACAGGCTCCACGAGTTATGCGGCCTCTGTCAAGGGACGCTTTACTGCTTCCCAA
    GACAAGGGGAAGAATATCGCCTATCTCCAGATGAACTCTCTGAAGCCTGAAGAC
    ACCGCTATGTATTACTGCAAGGCCAGCTGTGTGAGAGGTCGCGCTATCTCCGAG
    TACTGGGGACAAGGCACTCAAGTAACGGTGTCATCCGGTGGCTCTGGAGGCTCC
    GGCGGGTCTGGCCAAGTCCAGTTGCAGGAATCTGGTGGAGGGTCTGTCCAGGCA
    GGAGGCAGTCTGCGCCTGTCATGTACCGCGCCCGGATTTACCAGTAATAGCTGC
    GGAATGGATTGGTATCGCCAGGCTCCTGGCAAGGAAAGAGAGTTCGTCTCTTCC
    ATCAGCACTGACGGCACTACAGGCTACGCCGATTCTGTGAAAGGGCGCTTCACA
    ATCTCCAAGGACAAAGCTAAGGATACCGTGTATCTGCAAATGAATAGTCTGAAG
    CCTGAGGATACAGGAATGTACTCCTGTAAGACCAAGGACGGCACCATCGCTACA
    ATGGAGCTGTGCGACTTTGGCTACTGGGGCCAGGGCACCCAAGTGACCGTCTCT
    TCA
    hIL27 1403 CAGGTGCAGCTCCAGGAGAGTGGTGGAGGGAGCGTGCAGGCTGGAGGCTCCCTG
    Ra_VH CGTCTTAGCTGCGTTGCCAGCGGGTACGTCTCCTGCGACTACTTTCTGCCGTCC
    TGGTATCGTCAAGCCCCTGGTAAAGAAAGAGAGTTCGTCTCCATCATTGATGGA
    H14- ACAGGCAGCACATCCTATGCGGCCTCCGTGAAGGGCCGCTTTACCGCAAGCCAA
    DR593 GATAAAGGTAAGAATATCGCCTACCTCCAGATGAACAGTTTGAAGCCCGAGGAT
    ACAGCCATGTATTACTGTAAGGCCAGTTGTGTGCGCGGGAGAGCCATCAGCGAG
    TACTGGGGCCAGGGCACACAGGTGACTGTATCTTCCGGCGGTGGCTCCCAGGTG
    CAGCTGCAAGAGAGCGGAGGCGGGTCCGTGCAGGCCGGAGGTAGCCTGCGCCTG
    TCATGCGCGGCCTCCGGTTACCCTTACTCCAACGGCTACATGGGGTGGTTTAGA
    CAGGCTCCAGGTAAGGAGCGGGAGGGGGTCGCCACAATCTACACGGGTGATGGC
    AGGACTTACTATGCCGACTCAGTGAAAGGCAGGTTTACCATTAGTCGCGACAAC
    GCCAAGAACACAGTTGACCTTCAGATGTCCTCACTGAAGCCTGAAGACACCGCC
    ATGTATTACTGCGCTGCACGCGCCGCTCCGCTGTACTCCAGCGGCTCCCCATTG
    ACTCGCGCACGCTACAATGTGTGGGGGCAAGGAACCCAGGTGACGGTGTCCTCT
    hIL27 1404 CAGGTGCAGCTCCAAGAGTCAGGCGGGGGTTCCGTTCAAGCCGGTGGGAGCCTG
    Ra_VH CGCCTGTCATGTGTGGCATCTGGATACGTGTCTTGTGACTACTTCCTGCCATCC
    H14- TGGTATCGGCAGGCCCCTGGGAAGGAGCGCGAATTTGTGTCTATCATTGATGGA
    DR593 ACCGGATCTACAAGCTACGCCGCATCCGTTAAGGGGAGGTTCACAGCCTCCCAG
    GACAAGGGAAAGAACATTGCATACCTCCAGATGAACTCCCTCAAGCCCGAGGAT
    ACTGCTATGTATTACTGTAAGGCCAGTTGTGTGCGTGGACGCGCCATCTCCGAG
    TACTGGGGCCAGGGAACCCAGGTGACCGTGTCCAGCGGTGGCAGCGGCGGTTCC
    GGCGGATCTGGACAGGTGCAGCTCCAGGAGTCTGGAGGCGGGTCCGTTCAGGCT
    GGGGGCAGCTTGCGTTTGAGTTGCGCCGCTTCCGGCTACCCTTACTCTAACGGT
    TACATGGGCTGGTTTCGCCAAGCACCGGGCAAGGAACGGGAAGGTGTCGCTACG
    ATTTACACCGGCGACGGACGCACATATTACGCGGATAGCGTGAAGGGGCGCTTC
    ACAATCTCTAGGGACAACGCGAAGAACACTGTGGACCTCCAGATGTCAAGCCTG
    AAGCCTGAGGATACCGCCATGTACTATTGCGCCGCTCGTGCTGCGCCCCTGTAT
    TCTAGCGGCAGCCCTCTTACTCGGGCACGCTACAACGTGTGGGGTCAAGGCACA
    CAGGTGACCGTCTCCTCC
    hIL27 1405 CAGGTGCAGCTTCAAGAATCAGGTGGGGGATCTGTGCAGGCAGGCGGGTCACTT
    Ra_VH CGCCTGTCCTGCGTGGCCTCCGGCTATGTCTCTTGTGATTACTTCCTGCCTAGC
    H14- TGGTATCGCCAGGCTCCAGGCAAGGAGAGAGAGTTCGTGAGCATCATTGACGGG
    DR594 ACGGGCTCCACTTCTTACGCCGCAAGCGTCAAGGGGCGCTTCACCGCGTCCCAG
    GACAAGGGAAAGAACATCGCGTACTTGCAGATGAACTCCCTGAAGCCAGAAGAC
    ACAGCTATGTATTACTGTAAGGCGTCTTGCGTCCGTGGCCGTGCAATCTCTGAG
    TACTGGGGCCAGGGCACTCAGGTGACTGTCAGCTCTGGCGGTGGCAGTCAGGTT
    CAGCTTCAGGAATCTGGCGGGGGCTCTGTGCAGGCAGGCGGTAGCCTGAGGTTG
    TCCTGTGTGGCTTCCGCTTCTACCTACTGCACCTACGATATGCACTGGTATCGT
    CAGGCCCCCGGTAAAGGGCGCGAGTTTGTGTCTGCTATTGATTCTGACGGCACC
    ACACGTTATGCCGACTCTGTCAAAGGCAGGTTCACAATCTCTCAAGGTACTGCT
    AAAAACACGGTATACCTTCAAATGAACTCTCTGCAACCTGAAGATACAGCGATG
    TATTACTGTAAGACTGTGTGCGTTGTGGGTAGCAGATGGAGCGACTACTGGGGC
    CAGGGTACACAGGTGACAGTCTCTTCT
    hIL27 1406 CAGGTCCAGCTTCAGGAGTCTGGGGGCGGTTCTGTGCAGGCTGGGGGCTCTCTC
    Ra_VH CGGCTGAGCTGTGTGGCAAGCGGTTATGTGTCATGCGACTACTTTCTGCCCAGC
    H14- TGGTATCGCCAAGCTCCCGGCAAGGAGAGGGAGTTCGTGTCTATTATCGACGGG
    DR594 ACAGGCTCCACCAGTTACGCGGCCTCAGTGAAGGGACGTTTCACTGCATCTCAA
    GACAAGGGCAAGAACATCGCCTACCTCCAGATGAATAGCCTGAAGCCTGAGGAC
    ACAGCTATGTATTACTGTAAGGCCTCCTGTGTGCGCGGGCGTGCTATCAGCGAA
    TACTGGGGTCAGGGGACTCAAGTCACGGTCTCCTCAGGAGGGTCCGGGGGCAGC
    GGAGGGTCAGGCCAGGTGCAGTTGCAGGAATCTGGAGGCGGTAGTGTTCAGGCC
    GGTGGCTCTCTGCGCCTGTCCTGCGTCGCGAGTGCATCTACGTACTGTACCTAC
    GATATGCACTGGTATCGGCAAGCCCCTGGGAAGGGCCGTGAGTTTGTCAGCGCC
    ATTGATTCTGACGGCACTACCCGCTACGCAGATAGCGTTAAAGGCCGCTTTACT
    ATCAGTCAGGGCACCGCCAAGAACACCGTCTACCTCCAGATGAACTCTCTCCAG
    CCCGAGGATACCGCCATGTACTATTGCAAAACAGTGTGCGTCGTGGGCTCCCGG
    TGGTCCGACTACTGGGGCCAAGGCACTCAAGTGACTGTTTCTTCC
    hIL27 1407 CAGGTCCAGCTCCAGGAGTCTGGCGGGGGCTCCGTGCAAGCTGGTGGCAGCCTC
    Ra_VH CGTCTGAGCTGCGTAGCCTCTGGTTACGTGTCATGCGACTACTTCCTGCCGTCC
    H14- TGGTATCGGCAGGCCCCCGGCAAAGAACGTGAGTTCGTAAGCATCATTGATGGT
    DR595 ACTGGGAGTACGTCCTATGCAGCCAGCGTGAAGGGCCGCTTTACCGCAAGCCAG
    GACAAGGGTAAAAATATTGCTTATCTTCAGATGAACAGCCTGAAACCTGAAGAT
    ACCGCAATGTATTACTGTAAGGCCAGCTGCGTAAGGGGCCGTGCCATTTCAGAA
    TACTGGGGACAGGGTACACAGGTGACTGTGTCATCTGGCGGGGGTAGCCAGGTG
    CAGCTCCAGGAGTCCGGCGGTGGGAGCGTGCAGGCAGGGGGCTCCCTGACCCTG
    TCCTGTGCGGCCAGCGAGTACGCCTATAGCACCTGTAATATGGGGTGGTATCGT
    CAGGCCCCTGGGAAAGAGCGCGAGCTGGTGTCTGCCTTCATCAGTGACGGCTCC
    ACTTATTACGCCGACTCCGTCAAGGGCCGGTTCACCATTACCCGTGATAACGCC
    AAGAATACCGTTTACCTCCAGATGAATAGCCTCAAACCCGAGGACACCGCGATT
    TACTATTGCTCCGCTAACTGTTACCGCAGGCTGCGTAACTACTGGGGACAGGGC
    ACTCAGGTGACTGTCTCTTCC
    hIL27 1408 CAGGTCCAGCTCCAGGAGAGCGGCGGGGGTTCCGTCCAGGCCGGTGGCAGCCTG
    Ra_VH CGTCTCTCTTGTGTGGCGAGCGGGTACGTCAGCTGCGATTACTTCCTGCCCTCC
    H14- TGGTATCGCCAGGCCCCTGGTAAGGAGAGGGAGTTCGTGTCTATCATTGATGGG
    DR595 ACTGGATCAACTAGCTACGCTGCGTCTGTTAAAGGGCGGTTTACTGCAAGCCAG
    GACAAGGGCAAGAACATTGCCTACCTTCAGATGAACAGCCTGAAGCCGGAGGAC
    ACCGCCATGTATTACTGTAAGGCCTCTTGTGTACGCGGTCGCGCCATCTCCGAA
    TACTGGGGTCAGGGTACACAGGTGACAGTCAGCTCAGGAGGTTCCGGTGGCTCC
    GGGGGTTCCGGCCAGGTCCAGTTGCAGGAATCCGGTGGCGGAAGCGTGCAGGCT
    GGTGGCTCCCTGACACTGTCTTGCGCAGCCAGCGAATATGCTTATAGTACTTGC
    AACATGGGCTGGTATCGCCAGGCCCCCGGCAAAGAACGCGAACTCGTGAGTGCC
    TTCATCTCCGACGGTAGCACTTATTACGCCGATTCTGTGAAGGGAAGGTTCACT
    ATTACGCGCGACAACGCCAAGAACACCGTCTACTTGCAGATGAACTCCCTGAAG
    CCCGAAGACACTGCCATCTACTATTGCTCCGCCAACTGCTACCGTCGCCTGCGG
    AACTATTGGGGACAGGGCACCCAGGTCACTGTCAGCTCC
    hIL27 1409 CAAGTGCAGCTGCAAGAGAGTGGAGGTGGCTCCGTACAGGCAGGCGGGAGCCTC
    Ra_VH CGCCTCAGCTGCGTAGCCAGCGGCTATGTCAGTTGCGACTACTTCCTCCCCTCT
    H14- TGGTACAGGCAGGCCCCAGGCAAGGAACGCGAGTTTGTGAGCATTATCGACGGC
    DR596 ACAGGGAGCACGAGTTACGCTGCCAGCGTCAAAGGCAGATTCACAGCCTCTCAA
    GACAAAGGGAAAAACATCGCCTACTTGCAGATGAACTCTCTGAAGCCCGAGGAT
    ACCGCCATGTATTACTGCAAGGCCTCTTGTGTGCGGGGCCGCGCTATCTCCGAA
    TACTGGGGACAGGGGACCCAGGTGACTGTGTCCAGTGGAGGTGGCTCCCAAGTT
    CAGCTCCAGGAGTCCGGTGGCGGGCTTGTGCAGCCGGGCGGTTCCCTGCGCCTG
    TCCTGCACTGCATCTGGTCTGACTTTCGACGATTCCGTAATGGGCTGGTTCCGC
    CAAGCACCTGGCAAAGGTCGCGAGGCTGTATCCTGTATCTCTAGCTCTGGTGCC
    AACGCATTCTACGCTGACTCCGTCAAAGGCCGTTTTACCATTAGTCGCGATAAC
    GCTAAAAACACACTGTACCTGCAAATGAACTCCCTCAAACCGGAAGATACTGCC
    ACCTACTATTGCAAGCGCGGGCACGCCTGTGCGGGCTATTACCCTATCCCATAC
    GATGACTACTGGGGCCAGGGCACCCAGGTCACTGTTAGCTCC
    hIL27 1410 CAGGTCCAACTCCAGGAGTCCGGCGGGGGCAGTGTGCAGGCTGGCGGGTCTCTG
    Ra_VH CGTCTGTCCTGCGTCGCGAGCGGCTACGTCAGCTGCGACTATTTTCTGCCTAGC
    H14- TGGTATCGCCAGGCCCCAGGTAAGGAAAGAGAGTTCGTGAGCATTATCGACGGG
    DR596 ACAGGTTCCACCTCCTACGCCGCGTCTGTGAAGGGCCGGTTTACTGCTTCCCAG
    GATAAAGGTAAGAACATTGCATATCTGCAAATGAACTCTCTGAAGCCCGAGGAC
    ACTGCTATGTATTACTGTAAAGCAAGTTGTGTGCGCGGCAGAGCAATTTCTGAA
    TACTGGGGCCAGGGCACCCAGGTGACTGTGTCCAGCGGGGGCAGTGGTGGCAGT
    GGAGGTAGCGGCCAAGTCCAGTTGCAGGAGAGTGGCGGTGGCCTGGTGCAGCCA
    GGTGGCTCCCTCCGTCTGAGCTGCACAGCCAGCGGGCTGACGTTCGATGACTCT
    GTGATGGGTTGGTTTCGCCAGGCTCCCGGCAAGGGCCGCGAAGCTGTTTCCTGT
    ATCTCTTCCTCTGGCGCGAATGCTTTTTACGCCGACTCCGTGAAGGGGAGGTTC
    ACTATTTCCAGAGACAATGCCAAGAACACTCTGTACCTTCAGATGAACTCCCTC
    AAGCCTGAAGACACCGCCACCTACTATTGTAAGCGCGGCCATGCCTGTGCCGGG
    TACTATCCTATTCCTTATGATGACTACTGGGGCCAGGGCACTCAGGTGACCGTG
    TCCTCC
    hIL27 1411 CAGGTGCAGCTCCAGGAGAGCGGCGGTGGCTCCGTGCAGGCCGGTGGCTCCCTC
    Ra_VH CGCCTCAGCTGCGTGGCCTCAGGTTACGTCAGCTGCGATTACTTTCTGCCAAGC
    H15- TGGTATCGCCAAGCGCCGGGGAAGGAGCGCGAGTTTGTGTCTATTATCGACGGA
    DR591 ACTGGCTCCACTAGCTATGCTGCCAGCGTGAAGGGACGCTTCACAGCTTCCCAG
    GATAAGGGAAAAAACATCGCCTACCTCCAGATGAACACCCTGAAACCCGAGGAC
    ACCGCCATGTATTACTGCAAGGCAAGCTGCGTGCGCGGCAGAGCTATCTCCGAG
    TACTGGGGCCAGGGAACCCAGGTTACCGTCAGCTCAGGCGGAGGGTCACAGGTT
    CAGTTGCAAGAAAGCGGCGGTGGGAGCGTGCAGGCTGGTGGAAGCCTGCGTCTG
    TCCTGCACAGCATCCGGCGCAATCGCTAGTGGATACATTGATAGCCGCTGGTGC
    ATGGCCTGGTTCCGCCAAGCTCCAGGTAAAGAGCGCGAGGGGGTGGCGGCCATC
    TGGCCTGGCGGAGGCCTGACTGTTTACGCCGACTCAGTGAAGGGGCGCTTTACC
    ATCTCACGGGACCATGCTAAGAACACCCTGTACTTGCAGATGAACAATCTGAAA
    CCTGAGGACACCGCGATGTATTACTGCGCAGCGGGCTCACCTCGTATGTGCCCT
    AGCTTGGAGTTTGGCTTCGACTACTGGGGCCAAGGCACCCAGGTGACTGTGAGC
    AGC
    hIL27 1412 CAAGTGCAGTTGCAGGAGAGTGGTGGGGGCTCTGTGCAGGCCGGGGGTTCCCTG
    Ra_VH AGGCTCTCTTGCGTGGCCAGCGGATACGTGTCCTGTGACTACTTCCTGCCCTCT
    H15- TGGTATCGCCAAGCGCCAGGGAAGGAACGCGAGTTCGTGAGCATTATCGACGGC
    DR591 ACTGGTTCCACCTCTTACGCAGCGTCTGTAAAGGGCCGTTTCACCGCCAGCCAG
    GACAAGGGGAAGAACATCGCTTACCTTCAGATGAATACGTTGAAGCCTGAGGAC
    ACTGCGATGTATTACTGTAAAGCGTCTTGCGTTCGTGGCCGTGCCATCTCCGAA
    TACTGGGGCCAAGGCACTCAGGTAACTGTGTCCAGCGGCGGTTCCGGTGGCTCT
    GGAGGTAGCGGTCAGGTGCAGCTCCAGGAATCTGGCGGTGGGAGTGTGCAGGCT
    GGCGGTAGTCTCCGGCTGTCCTGTACCGCCAGTGGAGCTATTGCCAGCGGATAC
    ATTGATTCCCGGTGGTGTATGGCATGGTTCCGGCAGGCCCCCGGCAAGGAACGC
    GAGGGGGTCGCCGCTATTTGGCCCGGAGGCGGGCTGACCGTGTACGCGGACAGT
    GTCAAGGGCCGCTTCACGATCAGTAGGGATCACGCCAAGAACACCCTCTACTTG
    CAGATGAATAACCTCAAACCAGAGGACACTGCAATGTATTACTGCGCCGCTGGC
    AGCCCGAGGATGTGCCCGTCCCTGGAGTTCGGCTTCGACTATTGGGGTCAGGGC
    ACTCAGGTCACCGTGTCCTCC
    hIL27 1413 CAGGTCCAGCTCCAGGAGAGCGGCGGAGGCTCTGTTCAGGCTGGGGGCAGCCTC
    Ra_VH CGCCTGTCTTGCGTGGCCTCCGGCTACGTAAGCTGCGACTACTTCTTGCCTTCC
    H15- TGGTATCGCCAGGCTCCGGGCAAAGAAAGGGAATTTGTATCCATTATCGACGGC
    DR592 ACGGGTAGCACTTCCTACGCCGCTAGTGTAAAGGGTCGGTTCACCGCCTCTCAG
    GACAAGGGCAAAAACATCGCGTACCTCCAGATGAACACACTGAAGCCAGAGGAT
    ACCGCCATGTATTACTGCAAGGCTTCCTGCGTGCGCGGGCGGGCCATTAGCGAG
    TACTGGGGACAAGGAACCCAAGTGACTGTGTCCAGCGGTGGAGGCTCTCAGGTC
    CAGCTGCAAGAGTCTGGAGGCGGTTCAGTGCAGGCCGGTGGAAGCCTTAGGCTG
    AGCTGCACCGCCCCTGGATTTACCTCTAACTCTTGCGGCATGGACTGGTATCGT
    CAGGCCCCCGGCAAGGAACGCGAGTTCGTGTCTAGCATCTCCACCGATGGCACC
    ACAGGCTATGCTGACAGTGTGAAAGGCCGTTTTACCATCTCCAAGGACAAAGCC
    AAGGACACGGTGTACCTCCAGATGAACTCCTTGAAGCCTGAAGACACGGGTATG
    TATTCTTGCAAGACTAAGGACGGCACCATCGCTACTATGGAGCTGTGCGACTTT
    GGTTATTGGGGACAGGGGACCCAGGTGACTGTATCTTCT
    hIL27 1414 CAGGTGCAGCTGCAAGAGTCTGGAGGTGGGTCAGTCCAGGCTGGGGGCAGCCTC
    Ra_VH AGGCTGTCCTGCGTCGCTTCTGGATACGTGTCCTGCGACTACTTCCTCCCCTCC
    H15- TGGTATCGCCAGGCCCCAGGTAAAGAACGCGAGTTCGTGTCCATCATTGATGGC
    DR592 ACCGGGTCTACTTCCTATGCTGCGTCCGTGAAGGGCCGTTTTACCGCTTCACAG
    GATAAAGGAAAGAACATTGCTTACCTCCAGATGAACACACTCAAGCCGGAAGAC
    ACCGCCATGTATTACTGTAAAGCGAGCTGTGTCCGTGGCAGAGCCATCAGTGAG
    TATTGGGGCCAGGGAACTCAGGTGACCGTGTCCTCTGGAGGCAGCGGCGGTAGT
    GGTGGCTCCGGGCAAGTTCAACTTCAGGAGAGTGGGGGTGGGTCCGTGCAGGCT
    GGGGGTTCTCTCCGCCTCAGCTGTACCGCGCCCGGCTTCACCTCTAACAGCTGC
    GGTATGGACTGGTATCGCCAAGCGCCGGGTAAAGAGCGTGAGTTCGTTAGCTCC
    ATCTCCACCGACGGCACCACAGGATATGCCGATAGCGTTAAGGGACGCTTTACT
    ATTAGTAAGGACAAGGCTAAGGATACCGTCTACCTCCAGATGAACTCTCTGAAA
    CCTGAAGACACAGGCATGTACTCCTGTAAAACCAAGGACGGCACCATTGCTACA
    ATGGAGCTTTGTGATTTCGGCTATTGGGGCCAGGGTACACAGGTTACCGTGTCC
    TCC
    hIL27 1415 CAAGTGCAGTTGCAGGAGTCCGGCGGAGGTTCAGTTCAGGCTGGCGGGTCCCTG
    Ra_VH AGACTGAGTTGTGTGGCCTCCGGCTATGTGAGCTGCGACTACTTTCTGCCTTCT
    H15- TGGTACAGACAAGCACCAGGCAAAGAGCGGGAGTTCGTGAGTATCATTGATGGG
    DR593 ACCGGCTCCACCAGCTATGCTGCCAGCGTGAAGGGTCGCTTTACCGCTTCTCAG
    GACAAAGGCAAAAACATCGCTTACCTCCAGATGAATACATTGAAGCCTGAAGAC
    ACCGCCATGTATTACTGTAAGGCATCATGTGTGCGTGGCCGCGCCATTTCTGAG
    TACTGGGGCCAGGGAACTCAGGTGACAGTGTCTAGTGGCGGAGGCTCCCAGGTC
    CAGTTGCAGGAGAGCGGCGGTGGATCTGTCCAGGCGGGTGGCAGCCTCCGTCTG
    TCCTGTGCGGCCAGCGGGTATCCTTATTCCAACGGGTACATGGGGTGGTTCCGC
    CAGGCCCCCGGTAAGGAACGCGAGGGCGTGGCCACTATTTACACAGGTGACGGG
    CGTACCTATTACGCAGACTCTGTAAAGGGTCGCTTCACAATTTCCCGCGACAAC
    GCCAAGAACACCGTCGATCTCCAGATGTCTAGTCTCAAACCTGAGGACACCGCC
    ATGTATTACTGTGCCGCTCGCGCCGCGCCACTTTACAGCTCTGGTTCTCCCCTC
    ACACGCGCTCGCTACAATGTTTGGGGCCAAGGCACACAGGTGACCGTGAGCAGT
    hIL27 1416 CAGGTGCAGTTGCAGGAATCTGGTGGAGGCTCCGTGCAGGCTGGGGGCTCCCTG
    Ra_VH AGGCTTTCATGTGTGGCAAGCGGCTACGTGAGTTGTGATTACTTTCTGCCTTCC
    H15- TGGTATCGCCAGGCCCCTGGCAAGGAGCGGGAATTTGTCTCAATCATTGATGGT
    DR593 ACTGGTTCCACTTCTTATGCGGCCAGTGTGAAAGGGCGTTTTACTGCCAGCCAG
    GATAAGGGCAAGAATATTGCTTACTTGCAGATGAACACCCTGAAGCCCGAAGAT
    ACCGCTATGTACTATTGCAAGGCCAGTTGTGTAAGGGGTCGGGCGATTAGTGAG
    TATTGGGGCCAGGGCACGCAGGTCACCGTGTCATCCGGGGGCAGCGGCGGGTCC
    GGGGGTTCTGGCCAGGTGCAGCTCCAGGAGAGCGGTGGAGGCAGCGTGCAGGCC
    GGTGGAAGCCTTCGTCTGTCCTGCGCCGCTTCAGGCTATCCTTACTCTAATGGC
    TACATGGGTTGGTTTCGCCAAGCCCCAGGGAAAGAGCGCGAGGGCGTTGCCACA
    ATTTACACAGGTGATGGAAGGACCTACTATGCGGACAGCGTCAAGGGCCGCTTT
    ACAATCAGCCGTGATAATGCTAAGAACACCGTCGATCTCCAGATGTCCAGCCTG
    AAGCCTGAGGATACTGCTATGTACTATTGCGCTGCCCGCGCAGCCCCACTCTAC
    AGCTCCGGCAGTCCCCTGACGAGGGCTCGCTATAACGTGTGGGGTCAGGGCACA
    CAGGTCACCGTGTCCAGC
    hIL27 1417 CAGGTGCAACTCCAGGAATCCGGGGGAGGCAGCGTGCAAGCCGGTGGCTCCCTG
    Ra_VH CGCCTGTCCTGCGTCGCCAGCGGCTACGTCAGCTGCGACTACTTTCTGCCCTCC
    H15- TGGTATCGCCAGGCTCCTGGGAAAGAGCGCGAGTTTGTTTCCATCATTGATGGA
    DR594 ACCGGCAGCACATCCTATGCCGCGAGCGTTAAGGGCAGATTTACCGCCTCTCAA
    GACAAGGGTAAGAACATCGCCTACCTCCAAATGAACACCCTGAAGCCTGAGGAC
    ACGGCAATGTATTACTGTAAAGCAAGCTGTGTGCGGGGTCGGGCCATCAGCGAG
    TACTGGGGTCAGGGCACCCAGGTCACTGTAAGCTCCGGGGGAGGGTCCCAGGTG
    CAGCTCCAGGAGTCAGGCGGAGGCTCCGTGCAGGCCGGAGGCTCCTTGCGTTTG
    AGCTGCGTGGCGTCTGCGTCTACCTACTGCACTTACGACATGCACTGGTATCGC
    CAGGCTCCGGGGAAGGGCCGCGAGTTCGTGAGCGCTATCGACTCCGATGGCACA
    ACTCGCTACGCCGACAGCGTGAAGGGGCGTTTTACCATTTCCCAGGGCACCGCC
    AAGAACACCGTGTATCTCCAGATGAACTCTCTGCAACCGGAGGATACAGCTATG
    TATTACTGCAAGACAGTCTGTGTGGTTGGTAGCCGCTGGTCTGACTACTGGGGC
    CAGGGCACCCAGGTCACGGTGTCCTCT
    hIL27 1418 CAGGTGCAGCTTCAAGAGTCTGGTGGCGGGTCCGTCCAGGCGGGTGGCAGTTTG
    Ra_VH AGACTCAGTTGTGTGGCCAGTGGCTACGTCAGCTGTGACTATTTTCTGCCTAGC
    TGGTATCGCCAGGCACCCGGTAAAGAGAGGGAGTTCGTGAGCATCATTGATGGG
    H15- ACAGGGTCTACATCTTATGCTGCCTCCGTGAAAGGGCGGTTCACAGCTTCCCAG
    DR594 GATAAGGGCAAGAACATTGCGTATCTCCAGATGAACACCCTCAAGCCGGAGGAT
    ACCGCGATGTATTACTGTAAGGCGTCTTGTGTGCGCGGGCGTGCTATTAGCGAG
    TATTGGGGACAGGGGACGCAAGTGACGGTCTCCTCAGGCGGGTCTGGTGGCTCT
    GGCGGGTCCGGGCAGGTCCAGCTCCAGGAGTCTGGCGGTGGCTCCGTCCAAGCC
    GGAGGCAGCCTCCGTCTCTCCTGTGTTGCATCAGCCTCCACGTACTGCACCTAT
    GATATGCACTGGTATCGGCAAGCGCCCGGCAAGGGCCGCGAGTTTGTGTCTGCC
    ATCGACAGTGATGGTACAACGCGGTACGCTGATAGCGTGAAAGGCCGCTTCACC
    ATCAGTCAGGGCACGGCCAAAAACACAGTGTATCTCCAGATGAACTCTCTCCAG
    CCTGAAGATACAGCCATGTACTATTGTAAGACGGTCTGCGTCGTGGGCAGCCGG
    TGGTCCGACTACTGGGGCCAGGGAACCCAAGTGACTGTCTCAAGT
    hIL27 1419 CAGGTGCAGTTGCAGGAGAGCGGCGGAGGCTCTGTGCAGGCAGGAGGCTCACTG
    Ra_VH AGACTGTCCTGCGTGGCAAGCGGCTATGTGAGCTGCGACTACTTTCTGCCAAGT
    H15- TGGTATCGTCAGGCTCCTGGCAAAGAAAGGGAGTTTGTGAGCATCATTGATGGA
    DR595 ACCGGAAGCACAAGTTATGCGGCCTCCGTGAAGGGTCGCTTCACCGCCTCACAG
    GATAAGGGCAAGAACATTGCTTACCTCCAGATGAACACACTCAAGCCTGAAGAC
    ACCGCGATGTACTATTGTAAAGCAAGTTGTGTGAGAGGCCGCGCCATTAGCGAG
    TATTGGGGCCAGGGCACTCAGGTGACCGTCAGCTCTGGCGGGGGAAGCCAGGTA
    CAACTCCAGGAGAGTGGTGGAGGCTCAGTGCAGGCCGGGGGAAGCCTGACCCTG
    TCCTGTGCCGCTTCCGAGTACGCATACAGCACTTGCAACATGGGCTGGTATCGC
    CAAGCCCCTGGCAAAGAACGGGAACTCGTGTCCGCCTTCATCTCCGATGGTTCT
    ACCTATTACGCTGATAGCGTGAAAGGACGCTTCACCATTACCCGTGATAACGCT
    AAGAACACAGTTTACTTGCAGATGAACTCTCTGAAGCCCGAAGACACCGCCATT
    TATTACTGTAGCGCCAACTGTTATCGCAGGCTTCGGAATTACTGGGGACAGGGG
    ACCCAGGTGACAGTGAGTAGC
    hIL27 1420 CAGGTGCAGTTGCAGGAGTCTGGGGGCGGTAGCGTCCAGGCTGGCGGATCACTG
    Ra_VH CGCCTGAGTTGTGTCGCGTCCGGCTACGTCAGCTGCGACTATTTCTTGCCCTCC
    H15- TGGTATCGCCAGGCCCCTGGCAAGGAACGTGAGTTCGTAAGCATCATTGACGGC
    DR595 ACTGGTAGCACTTCCTACGCCGCTAGTGTGAAGGGGCGGTTCACCGCAAGCCAG
    GACAAGGGGAAGAACATCGCCTACCTCCAGATGAACACACTGAAGCCCGAGGAC
    ACGGCCATGTACTATTGCAAAGCCTCTTGCGTGCGGGGGCGTGCGATCTCTGAA
    TATTGGGGCCAGGGAACTCAGGTGACCGTGTCTAGTGGTGGCAGTGGTGGGTCC
    GGCGGGAGCGGTCAGGTTCAGTTGCAGGAGAGCGGCGGTGGCTCCGTTCAGGCC
    GGGGGCTCTCTGACGCTGTCTTGCGCGGCCAGCGAATACGCTTACTCAACTTGT
    AATATGGGTTGGTATCGTCAGGCACCCGGCAAGGAGCGGGAGCTGGTCTCCGCT
    TTCATCAGCGACGGCTCCACCTATTACGCAGACAGCGTTAAGGGTCGCTTTACT
    ATCACGCGCGACAACGCCAAGAACACCGTGTACCTCCAGATGAACTCTCTGAAA
    CCCGAGGATACCGCCATTTACTATTGCTCTGCTAACTGCTACCGCAGGTTGAGA
    AATTACTGGGGCCAAGGAACTCAGGTGACGGTCTCAAGC
    hIL27 1421 CAGGTGCAGCTCCAGGAATCTGGCGGTGGCTCCGTACAGGCTGGCGGTTCCCTG
    Ra_VH AGGCTCTCTTGTGTCGCCAGCGGCTACGTCAGCTGTGACTATTTCCTCCCTTCT
    H15- TGGTATCGTCAGGCCCCAGGGAAGGAGCGCGAGTTCGTGTCCATTATCGACGGG
    DR596 ACCGGAAGCACCTCCTATGCTGCATCAGTGAAAGGCCGGTTTACCGCGTCTCAG
    GACAAAGGAAAGAACATTGCATATCTGCAAATGAACACACTCAAGCCAGAGGAC
    ACCGCTATGTACTATTGTAAGGCCTCCTGTGTGAGAGGTCGCGCAATTTCTGAA
    TATTGGGGCCAGGGAACCCAGGTGACCGTGTCCTCTGGGGGCGGTTCTCAGGTC
    CAACTTCAGGAAAGCGGTGGCGGGCTCGTGCAACCCGGTGGCAGCCTTCGGCTG
    TCTTGTACTGCCTCCGGTTTGACATTCGATGACTCTGTGATGGGATGGTTTAGG
    CAGGCTCCTGGCAAAGGCCGCGAGGCAGTATCTTGTATCAGTTCTTCCGGCGCT
    AACGCATTTTATGCCGACAGTGTGAAGGGCCGTTTCACAATCTCCCGCGATAAC
    GCCAAGAACACCCTCTACCTCCAGATGAACTCCCTGAAGCCTGAGGACACCGCC
    ACTTATTACTGCAAGCGGGGTCATGCCTGTGCTGGCTATTACCCTATTCCATAC
    GATGACTACTGGGGACAGGGCACCCAAGTTACCGTGTCTAGC
    hIL27 1422 CAGGTGCAGCTTCAGGAGTCAGGAGGTGGCTCAGTGCAGGCTGGTGGCAGTCTG
    Ra_VH CGCCTGTCCTGTGTCGCCAGTGGATATGTCAGTTGTGACTATTTTCTCCCCAGT
    H15- TGGTATCGCCAAGCGCCCGGTAAAGAGCGGGAGTTTGTCTCAATCATTGACGGC
    DR596 ACCGGCAGCACCTCCTACGCCGCTTCCGTGAAGGGTCGCTTCACCGCGTCCCAG
    GACAAAGGCAAGAACATCGCGTATCTTCAGATGAACACCCTCAAGCCCGAAGAT
    ACAGCTATGTATTACTGCAAGGCCTCCTGCGTGCGGGGACGCGCGATCTCTGAA
    TACTGGGGCCAGGGCACACAGGTCACCGTCTCTTCAGGGGGTTCCGGTGGCTCC
    GGTGGCTCCGGCCAGGTGCAGTTGCAGGAAAGCGGTGGCGGGCTGGTGCAGCCG
    GGCGGGAGTCTCCGCCTGTCCTGCACAGCGTCAGGGCTGACTTTTGATGACTCT
    GTTATGGGCTGGTTTAGGCAGGCTCCGGGTAAGGGCAGAGAGGCCGTTAGCTGC
    ATCTCTTCCAGCGGGGCTAACGCCTTCTATGCCGACAGCGTGAAGGGTCGCTTC
    ACAATTAGCCGGGACAACGCTAAGAACACTCTGTACCTTCAGATGAACTCCCTG
    AAGCCCGAAGATACTGCTACTTACTATTGCAAGAGAGGTCATGCTTGCGCCGGA
    TACTATCCAATCCCTTACGATGACTACTGGGGCCAAGGCACCCAAGTTACCGTG
    TCTTCT
    hIL27 1423 CAGGTGCAGTTGCAGGAAAGTGGCGGTGGATCTGTGCAGGCAGGCGGAAGTCTG
    Ra_VH AGACTGAGCTGCCGGGCCAGCGGTTCAACTTATAGCAATTACTGTCTGGGTTGG
    H16- TTCAGGCAGATTACTGGTAAGGAACGCGAAGGCGTTGCTGTTATCAACTGGGTT
    DR591 GGGGGAATGCTGTACTTTGCTGACTCCGTTAAGGGCAGATTCACTGTCAGCCAG
    GACCAGGCCAAGAATACCGTGTACTTGCAGATGAACAGCCTGAAGCCCGAGGAT
    ACAGCCATGTATTACTGTGCTGCCGAGTCAGCCTCCTCTTTCTCATGTGGGGGA
    TGGCTTACAAGGCCCGACCGCGTTCCATATTGGGGCCAGGGCACCCAGGTGACT
    GTAAGCTCCGGTGGAGGCAGTCAGGTCCAGCTCCAGGAGAGCGGCGGAGGCTCT
    GTTCAGGCTGGAGGTAGCCTGCGCCTTAGCTGCACAGCCTCAGGTGCCATCGCC
    AGCGGTTATATTGATTCACGCTGGTGTATGGCCTGGTTTCGCCAGGCCCCTGGG
    AAGGAGAGGGAAGGTGTGGCTGCCATTTGGCCCGGAGGCGGTCTGACAGTCTAC
    GCAGACTCCGTGAAGGGCCGCTTTACCATCAGCCGGGACCACGCGAAGAACACT
    CTGTATTTGCAAATGAATAACCTCAAACCCGAGGACACCGCAATGTACTATTGT
    GCCGCTGGCTCTCCTCGTATGTGTCCATCTCTGGAGTTCGGCTTTGACTACTGG
    GGCCAGGGGACCCAGGTGACTGTGAGTAGC
    hIL27 1424 CAAGTGCAGTTGCAGGAGTCTGGTGGCGGTTCCGTGCAGGCTGGTGGAAGCCTG
    Ra_VH AGGCTGTCTTGTCGTGCATCTGGAAGCACCTATTCCAACTATTGTCTTGGGTGG
    H16- TTCAGACAGATCACTGGCAAAGAGAGAGAAGGGGTTGCGGTTATCAACTGGGTG
    DR591 GGCGGTATGCTGTACTTCGCTGATTCCGTGAAGGGCCGCTTCACGGTATCCCAG
    GACCAAGCAAAGAATACCGTCTATTTGCAGATGAACAGCCTGAAACCGGAGGAT
    ACCGCCATGTACTATTGTGCAGCCGAGAGCGCCAGCTCCTTCTCTTGTGGCGGT
    TGGCTGACTCGTCCAGATCGCGTGCCCTACTGGGGCCAAGGGACCCAGGTGACA
    GTCAGCTCCGGCGGTAGCGGTGGCTCTGGGGGCTCCGGGCAGGTGCAGCTCCAG
    GAAAGTGGGGGCGGTTCAGTGCAGGCAGGTGGCAGTCTGCGTCTGTCCTGCACC
    GCAAGCGGCGCAATCGCTTCCGGTTATATTGATTCTCGCTGGTGCATGGCTTGG
    TTTCGCCAGGCCCCCGGCAAGGAACGCGAGGGGGTGGCAGCCATCTGGCCGGGA
    GGGGGACTGACCGTTTACGCTGACAGCGTGAAGGGCCGCTTCACGATCAGTAGG
    GATCACGCGAAGAACACCCTTTACCTCCAGATGAATAACCTGAAGCCAGAGGAC
    ACAGCGATGTATTACTGCGCCGCTGGTTCTCCCCGGATGTGTCCATCCCTGGAG
    TTCGGGTTCGATTACTGGGGCCAGGGGACGCAAGTGACAGTTAGCTCC
    hIL27 1425 CAGGTACAGCTGCAAGAAAGCGGCGGAGGGTCCGTGCAGGCTGGCGGTTCTCTT
    Ra_VH CGTCTGTCTTGCCGCGCCTCCGGTAGTACCTACTCCAACTACTGCTTGGGCTGG
    H16- TTCCGCCAGATCACAGGCAAGGAGCGTGAGGGGGTGGCCGTAATAAATTGGGTG
    DR592 GGCGGTATGCTGTATTTCGCAGATTCCGTGAAAGGCCGCTTTACCGTCTCCCAG
    GACCAGGCCAAAAACACCGTGTACCTCCAGATGAACTCTCTGAAGCCGGAGGAC
    ACAGCGATGTACTATTGTGCTGCCGAAAGCGCTTCTAGTTTTAGCTGTGGCGGT
    TGGCTGACCCGTCCTGATCGCGTTCCATACTGGGGACAGGGTACTCAGGTCACC
    GTGTCTTCCGGCGGTGGCTCCCAGGTTCAGCTCCAGGAATCTGGCGGTGGGAGT
    GTCCAGGCTGGAGGTAGTCTGCGCCTGTCATGTACCGCCCCCGGTTTTACCTCT
    AACTCTTGCGGTATGGACTGGTATCGCCAGGCTCCCGGTAAGGAGAGGGAGTTC
    GTCAGCTCTATCAGTACTGACGGCACTACAGGATACGCCGACTCTGTGAAGGGC
    CGTTTCACCATCTCTAAGGACAAGGCTAAAGACACCGTCTACCTCCAGATGAAC
    AGTCTCAAGCCCGAGGACACGGGTATGTATTCCTGCAAAACAAAGGATGGGACT
    ATTGCCACAATGGAGCTTTGTGACTTTGGCTACTGGGGACAGGGAACACAGGTG
    ACTGTCTCAAGC
    hIL27 1426 CAGGTGCAGTTGCAGGAGTCAGGAGGTGGGTCCGTGCAGGCCGGTGGCAGCCTG
    Ra_VH CGGCTCTCTTGTCGGGCCAGTGGCAGCACTTATAGTAACTACTGTCTGGGGTGG
    H16- TTCCGCCAGATCACTGGTAAAGAGCGGGAGGGGGTGGCTGTCATTAACTGGGTC
    DR592 GGCGGTATGCTGTACTTCGCCGATTCCGTGAAGGGCCGTTTCACAGTGTCCCAA
    GACCAGGCCAAGAACACAGTTTACCTTCAGATGAACAGCCTGAAGCCAGAGGAC
    ACCGCCATGTACTATTGCGCCGCAGAATCTGCTTCTAGCTTCAGCTGCGGCGGT
    TGGCTGACACGCCCGGACCGCGTGCCGTACTGGGGGCAGGGCACACAGGTAACC
    GTGTCCTCTGGCGGGAGTGGCGGGTCCGGCGGTAGCGGCCAAGTCCAGCTCCAG
    GAGTCAGGCGGAGGCTCCGTCCAGGCTGGTGGCAGCTTGAGGTTGTCCTGCACT
    GCTCCTGGTTTTACATCTAACTCCTGCGGCATGGATTGGTATCGCCAGGCTCCC
    GGAAAGGAGCGCGAGTTCGTGTCCTCTATTAGTACCGATGGCACTACCGGGTAT
    GCCGACTCTGTTAAGGGTCGTTTCACAATCAGTAAAGATAAGGCCAAGGACACA
    GTGTACTTGCAGATGAACTCACTGAAACCAGAGGATACAGGCATGTATAGCTGT
    AAGACCAAAGACGGGACCATCGCAACTATGGAGCTGTGCGATTTCGGCTACTGG
    GGCCAGGGCACCCAGGTAACCGTCAGCTCA
    hIL27 1427 CAGGTACAGTTGCAGGAGTCCGGCGGGGGAAGCGTGCAGGCTGGAGGTAGCCTG
    Ra_VH CGTCTGAGCTGTCGCGCCAGCGGCTCCACCTACTCAAACTACTGTCTTGGATGG
    H16- TTCCGTCAGATTACTGGCAAGGAGAGGGAAGGGGTCGCCGTTATCAACTGGGTG
    DR593 GGCGGTATGCTGTACTTCGCCGACTCTGTTAAAGGCCGTTTCACAGTGAGCCAG
    GATCAGGCCAAGAACACCGTCTACCTTCAGATGAACTCTTTGAAGCCTGAAGAT
    ACGGCCATGTATTACTGTGCAGCCGAGTCTGCCTCCAGCTTCTCCTGCGGGGGC
    TGGCTCACACGCCCCGACCGTGTGCCTTATTGGGGACAGGGGACACAAGTCACT
    GTCTCCTCTGGAGGGGGATCTCAAGTGCAGCTGCAAGAGTCTGGAGGCGGTAGC
    GTGCAGGCTGGCGGGTCCCTCAGACTGAGCTGTGCTGCCTCCGGTTACCCCTAC
    TCCAACGGATATATGGGCTGGTTCCGCCAGGCACCAGGCAAGGAGCGCGAGGGC
    GTGGCTACTATCTATACAGGTGATGGCCGCACCTATTACGCTGATTCCGTGAAG
    GGTCGCTTCACCATCAGCCGCGACAATGCTAAGAACACCGTGGACCTTCAGATG
    TCTAGCCTCAAGCCTGAGGACACTGCAATGTATTACTGTGCTGCACGGGCAGCG
    CCCCTTTATTCCTCTGGCTCCCCTCTCACCCGCGCACGTTACAACGTATGGGGT
    CAAGGCACCCAGGTGACTGTCTCCAGC
    hIL27 1428 CAGGTCCAGCTCCAGGAGAGTGGTGGCGGGTCAGTGCAGGCGGGAGGCTCACTG
    Ra_VH CGTCTGTCCTGTCGGGCCTCCGGCTCCACTTACTCTAACTATTGCTTGGGCTGG
    H16- TTCAGGCAGATTACAGGTAAGGAGCGCGAAGGGGTGGCTGTTATCAACTGGGTA
    DR593 GGGGGTATGCTGTATTTCGCCGATTCAGTTAAGGGCCGTTTCACGGTGAGTCAG
    GATCAGGCCAAAAACACTGTTTATCTTCAAATGAACTCCCTGAAGCCCGAGGAC
    ACCGCGATGTACTATTGCGCAGCCGAGAGCGCCTCTAGCTTCAGCTGTGGGGGT
    TGGCTGACACGGCCTGACCGCGTCCCTTATTGGGGCCAGGGAACCCAAGTGACC
    GTGTCTAGCGGAGGCTCCGGCGGATCTGGAGGTTCCGGTCAGGTGCAGTTGCAA
    GAGTCCGGCGGAGGCTCTGTGCAGGCGGGTGGCAGCCTGCGCCTGTCCTGCGCG
    GCCTCTGGATATCCGTACAGCAACGGCTACATGGGCTGGTTCAGACAAGCACCG
    GGGAAAGAGAGAGAGGGCGTGGCCACCATCTACACCGGGGACGGGCGTACTTAC
    TATGCCGACAGTGTAAAGGGGCGCTTCACTATCTCACGCGACAATGCGAAAAAC
    ACAGTGGACCTCCAGATGTCAAGTTTGAAGCCGGAGGACACTGCAATGTATTAC
    TGTGCTGCCAGAGCCGCACCTCTGTACTCCAGCGGCTCTCCTCTGACTCGTGCC
    CGCTACAACGTGTGGGGTCAGGGCACTCAGGTCACAGTCAGCAGT
    hIL27 1429 CAAGTGCAGCTCCAGGAATCTGGAGGCGGAAGCGTCCAGGCGGGCGGTTCTCTG
    Ra_VH CGTCTGTCTTGTCGGGCCAGCGGCTCTACTTACTCTAATTACTGTCTGGGTTGG
    H16- TTCCGCCAGATCACTGGTAAGGAGAGAGAGGGGGTGGCCGTTATCAACTGGGTC
    DR594 GGCGGGATGCTGTACTTTGCTGATTCAGTGAAAGGCCGGTTCACAGTAAGCCAG
    GATCAGGCCAAGAACACAGTTTACCTCCAGATGAACTCTTTGAAGCCTGAGGAC
    ACCGCCATGTACTATTGTGCGGCAGAATCCGCCTCTAGCTTCAGCTGTGGCGGT
    TGGCTGACCCGTCCTGACAGAGTGCCATACTGGGGCCAGGGCACCCAGGTGACA
    GTGTCCTCTGGCGGAGGCTCCCAGGTGCAGCTCCAGGAATCAGGGGGAGGCAGT
    GTGCAGGCGGGTGGCTCCCTGAGATTGTCCTGTGTCGCCAGCGCGTCCACCTAT
    TGCACCTACGATATGCACTGGTACAGACAGGCACCCGGAAAGGGCCGTGAGTTT
    GTGAGTGCTATTGATTCCGACGGTACAACTCGCTACGCGGATTCAGTGAAAGGG
    AGATTCACGATTTCTCAAGGCACGGCCAAGAATACTGTGTACCTCCAGATGAAC
    AGCCTCCAGCCAGAAGACACGGCTATGTACTATTGCAAGACCGTGTGTGTGGTC
    GGCAGCAGGTGGTCCGACTATTGGGGCCAGGGTACACAGGTGACCGTGAGCAGC
    hIL27 1430 CAAGTGCAACTCCAGGAGAGCGGCGGTGGCTCCGTGCAGGCGGGCGGAAGCCTC
    Ra_VH CGCCTTAGTTGCAGAGCGAGCGGCAGCACCTACTCCAACTACTGCTTGGGCTGG
    H16- TTTAGACAGATTACGGGCAAGGAACGTGAGGGTGTCGCCGTAATCAACTGGGTT
    DR594 GGCGGTATGCTCTACTTTGCTGACTCCGTTAAGGGACGCTTTACTGTTTCTCAG
    GATCAGGCGAAGAACACCGTCTACCTTCAGATGAACTCCCTCAAACCCGAGGAC
    ACCGCTATGTACTATTGCGCAGCCGAATCTGCAAGCTCTTTCTCATGCGGTGGG
    TGGCTGACCCGCCCGGACCGTGTGCCTTACTGGGGCCAGGGGACACAGGTGACC
    GTTAGCTCCGGGGGCTCCGGGGGTTCAGGTGGATCTGGGCAGGTTCAGCTGCAA
    GAGTCAGGTGGGGGCTCTGTCCAAGCCGGGGGATCTCTGAGACTGTCATGCGTG
    GCCTCCGCATCAACCTACTGCACCTATGATATGCACTGGTATCGCCAAGCTCCG
    GGTAAAGGCAGGGAGTTTGTGAGCGCCATCGACAGCGATGGAACGACCCGCTAC
    GCCGATAGCGTGAAGGGGAGATTTACTATTTCCCAAGGAACAGCCAAAAACACA
    GTCTACCTTCAGATGAACTCCCTGCAACCCGAAGACACAGCCATGTATTACTGC
    AAGACAGTTTGCGTGGTTGGTTCCCGTTGGAGCGACTACTGGGGCCAGGGCACC
    CAGGTGACTGTCTCCTCT
    hIL27 1431 CAGGTCCAGCTGCAAGAATCAGGCGGTGGGTCCGTGCAAGCTGGTGGATCTCTC
    Ra_VH CGTCTGTCTTGCCGCGCTTCTGGAAGCACTTATTCAAATTATTGCCTGGGCTGG
    H16- TTTAGGCAGATTACTGGGAAGGAGCGCGAGGGCGTCGCCGTGATAAATTGGGTC
    DR595 GGTGGGATGCTGTATTTCGCGGACAGCGTGAAGGGCCGGTTCACAGTCTCCCAA
    GATCAGGCTAAGAACACAGTGTACTTGCAGATGAACTCCCTGAAGCCAGAGGAC
    ACTGCCATGTACTATTGCGCGGCTGAAAGCGCCTCTTCCTTCTCCTGTGGGGGC
    TGGCTCACACGCCCAGATCGCGTACCATACTGGGGTCAGGGCACACAGGTGACC
    GTGTCATCTGGTGGCGGGAGCCAGGTGCAGCTCCAGGAGTCAGGAGGCGGGTCC
    GTACAGGCTGGTGGCTCCCTGACCCTGTCTTGCGCTGCATCAGAGTACGCCTAC
    TCCACCTGCAACATGGGTTGGTATCGTCAGGCTCCCGGCAAAGAAAGGGAACTC
    GTGAGTGCCTTCATTAGCGATGGATCAACCTATTACGCGGACTCCGTGAAGGGC
    CGCTTCACCATCACCCGCGACAACGCGAAAAATACGGTCTACTTGCAGATGAAT
    AGTCTGAAACCAGAGGACACAGCCATCTATTACTGCTCTGCCAACTGTTACCGT
    CGCCTGCGGAATTATTGGGGCCAGGGCACCCAGGTGACTGTCTCCTCT
    hIL27 1432 CAGGTCCAGTTGCAGGAGTCCGGGGGTGGCTCTGTCCAAGCAGGTGGCAGCCTG
    Ra_VH CGGCTGTCTTGCCGCGCGAGCGGGTCCACTTATAGTAACTATTGCCTGGGCTGG
    H16- TTTCGTCAGATCACAGGCAAGGAGCGCGAAGGCGTCGCCGTTATCAACTGGGTG
    DR595 GGCGGGATGCTGTATTTCGCCGACAGCGTGAAGGGACGTTTTACAGTGTCACAG
    GACCAGGCCAAGAACACCGTCTACCTCCAGATGAACTCCCTGAAGCCTGAAGAC
    ACTGCCATGTACTATTGTGCCGCAGAGTCAGCCAGCTCCTTCAGCTGCGGCGGA
    TGGTTGACCCGCCCGGACAGGGTTCCCTACTGGGGTCAGGGCACTCAGGTTACG
    GTGAGCAGTGGTGGCTCTGGTGGCTCTGGAGGCTCCGGCCAGGTGCAGCTTCAG
    GAGAGTGGCGGTGGAAGTGTGCAAGCGGGAGGTAGTCTGACCCTCTCTTGCGCT
    GCCTCTGAATACGCATACAGTACATGCAATATGGGATGGTATCGCCAGGCCCCT
    GGCAAAGAGCGTGAACTCGTGAGCGCCTTCATCTCAGATGGGAGCACCTATTAC
    GCTGACTCTGTCAAGGGCAGGTTCACGATTACCCGCGATAACGCAAAGAACACC
    GTGTATTTGCAGATGAACTCCCTGAAGCCTGAAGACACAGCCATTTATTACTGC
    TCCGCCAACTGTTATCGCAGACTGCGGAACTATTGGGGCCAGGGCACCCAGGTC
    ACCGTGTCTTCC
    hIL27 1433 CAGGTGCAGTTGCAGGAGTCTGGAGGTGGCTCCGTCCAGGCTGGTGGCTCTCTG
    Ra_VH CGGCTGAGCTGCCGCGCGAGTGGCAGCACCTACTCCAACTACTGCCTGGGCTGG
    H16- TTTCGCCAGATTACAGGAAAGGAGAGAGAGGGAGTGGCCGTCATCAACTGGGTG
    DR596 GGCGGGATGTTGTATTTCGCTGACAGTGTGAAGGGAAGATTTACCGTTAGTCAG
    GACCAGGCTAAGAACACCGTATACCTCCAGATGAACTCTCTGAAGCCAGAGGAT
    ACAGCCATGTACTATTGTGCCGCAGAGTCTGCCTCCTCTTTTTCATGCGGCGGG
    TGGTTGACTCGCCCAGACAGAGTACCATACTGGGGCCAGGGGACCCAAGTGACC
    GTCTCCAGCGGCGGGGGCAGCCAGGTCCAGCTCCAGGAGTCAGGTGGCGGGCTG
    GTCCAGCCTGGCGGTTCTCTGCGCCTGTCCTGCACCGCCAGTGGGCTCACCTTC
    GATGACTCCGTGATGGGTTGGTTCCGGCAGGCTCCGGGTAAGGGACGTGAGGCT
    GTGTCCTGTATTTCTTCCAGCGGAGCCAACGCATTTTATGCGGACAGTGTAAAG
    GGTCGCTTTACCATCAGTCGTGACAACGCCAAGAACACCCTCTATCTTCAGATG
    AACTCCCTGAAGCCAGAGGATACTGCCACGTATTACTGCAAGCGTGGTCATGCG
    TGCGCAGGCTATTACCCCATCCCCTACGACGATTATTGGGGCCAAGGCACGCAG
    GTGACCGTTTCCTCC
    hIL27 1434 CAGGTGCAGCTTCAGGAGTCCGGTGGGGGCAGCGTGCAAGCTGGAGGCAGTCTG
    Ra_VH AGGCTGAGCTGTCGTGCGTCAGGGTCTACCTACTCCAACTATTGTCTGGGCTGG
    H16- TTTCGCCAGATCACTGGTAAGGAGCGCGAGGGCGTTGCCGTTATCAACTGGGTC
    DR596 GGAGGTATGCTGTACTTCGCTGACTCCGTGAAGGGACGTTTCACTGTGAGCCAG
    GATCAGGCCAAGAACACCGTGTACCTCCAGATGAACAGCCTGAAGCCTGAAGAT
    ACCGCCATGTATTACTGTGCAGCCGAATCCGCCTCTTCCTTTAGCTGTGGGGGC
    TGGCTGACTAGGCCTGACCGCGTGCCTTACTGGGGCCAGGGGACCCAAGTAACC
    GTCAGCTCTGGTGGCAGCGGAGGTAGCGGTGGGAGTGGCCAGGTTCAGCTTCAG
    GAGAGCGGTGGAGGTCTGGTGCAGCCAGGGGGTAGTCTGCGCCTTAGCTGCACT
    GCCTCCGGTCTGACCTTCGATGACAGTGTGATGGGTTGGTTTCGTCAGGCTCCA
    GGCAAGGGGCGCGAAGCAGTGTCTTGTATCAGCTCCAGCGGCGCTAATGCCTTT
    TACGCCGATTCCGTGAAAGGCCGCTTTACGATTAGCCGCGATAACGCCAAGAAC
    ACACTGTATTTGCAGATGAACAGCCTCAAACCCGAAGACACGGCCACCTACTAT
    TGTAAGCGGGGTCATGCCTGCGCTGGGTATTACCCAATTCCCTACGATGACTAT
    TGGGGGCAGGGCACCCAGGTTACTGTCTCCTCC
    hIL27 1435 CAGGTTCAGTTGCAGGAAAGCGGAGGTGGCTTGGTGCAGCCCGGTGGCTCTCTC
    Ra_VH CGTCTGTCTTGCGCGGCCAGTGGGTTCACATTCTCCCTGAGCGGAATGTCTTGG
    H17- GTGCGTCAGGCCCCAGGCAAAGGTCTGGAATGGGTTAGCGCGATCAGCTCTGGT
    DR591 GGCGCTTCCACCTACTATACGGACAGCGTTAAGGGCAGATTTACTATTTCTCGC
    GACAACGCCAAGAACATGCTTTACCTCCAGTTGAACAGCCTGAAGACCGAAGAT
    ACCGCTATGTATTACTGTGCCAAGGGTGGGTCCGGCTACGGCGATGCCTCCCGT
    ATGACATCCCCTGGCAGCCAGGGCACTCAAGTGACCGTGTCCAGCGGCGGTGGC
    AGTCAAGTCCAGCTCCAGGAGTCTGGGGGTGGATCTGTCCAGGCCGGGGGCTCC
    CTCCGCCTGAGTTGCACTGCGAGCGGTGCTATCGCCAGCGGCTACATCGACTCC
    AGGTGGTGCATGGCCTGGTTCCGCCAGGCTCCGGGAAAAGAGCGTGAGGGTGTT
    GCCGCTATCTGGCCCGGAGGCGGGCTGACCGTCTATGCCGACTCCGTAAAGGGC
    CGGTTCACCATCAGCCGCGACCATGCCAAGAACACCCTGTACCTTCAGATGAAT
    AACTTGAAACCTGAGGACACTGCTATGTATTACTGCGCGGCTGGTAGCCCTCGC
    ATGTGCCCGAGCCTGGAATTTGGGTTCGATTACTGGGGACAGGGCACCCAGGTC
    ACGGTGTCCAGC
    hIL27 1436 CAGGTGCAGTTGCAAGAAAGTGGCGGGGGTCTGGTACAGCCTGGAGGCTCTCTG
    Ra_VH CGCCTCTCCTGTGCTGCCAGCGGCTTTACTTTTAGCCTGTCAGGTATGTCCTGG
    H17- GTCCGCCAGGCCCCCGGTAAAGGTCTTGAGTGGGTCTCCGCTATTTCCAGCGGA
    DR591 GGTGCCAGTACCTATTACACCGACTCAGTGAAAGGACGTTTCACCATTTCCCGC
    GATAATGCTAAGAATATGTTGTATTTGCAGCTCAACAGCCTGAAGACAGAGGAT
    ACCGCTATGTACTATTGCGCTAAAGGCGGATCTGGTTATGGAGACGCCTCCCGT
    ATGACATCCCCTGGGTCTCAGGGAACGCAGGTGACCGTGTCTAGCGGCGGGTCT
    GGAGGCTCCGGTGGCTCCGGCCAGGTCCAGCTCCAGGAAAGCGGTGGCGGGTCT
    GTGCAGGCAGGCGGTTCCCTGAGGCTGAGCTGCACAGCCTCCGGGGCAATCGCC
    AGCGGTTATATCGACAGCAGATGGTGCATGGCCTGGTTCCGTCAGGCCCCCGGC
    AAAGAGAGGGAGGGAGTGGCGGCCATCTGGCCAGGAGGCGGACTGACCGTGTAT
    GCCGACTCTGTGAAGGGTCGCTTTACCATCAGCAGAGACCACGCCAAGAACACC
    CTGTACTTGCAGATGAATAACCTCAAGCCCGAGGACACCGCAATGTATTACTGC
    GCCGCAGGCAGCCCTCGCATGTGTCCGTCTCTGGAGTTCGGATTCGATTACTGG
    GGCCAGGGGACCCAGGTGACCGTTTCCTCC
    hIL27 1437 CAAGTGCAGCTCCAGGAGTCAGGTGGAGGCCTGGTTCAGCCTGGGGGAAGTCTG
    Ra_VH CGCCTTTCATGTGCAGCTTCTGGTTTTACCTTCTCTCTGAGCGGCATGTCCTGG
    H17- GTCCGGCAGGCACCGGGCAAGGGCCTGGAGTGGGTGAGTGCCATCTCATCTGGC
    DR592 GGTGCGAGCACCTACTATACCGACTCTGTTAAAGGAAGGTTTACCATCTCCCGC
    GATAACGCTAAAAATATGTTGTACTTGCAGCTCAACTCACTGAAGACCGAAGAC
    ACCGCTATGTATTACTGCGCCAAGGGTGGCTCCGGGTACGGCGATGCCTCCCGC
    ATGACCAGCCCCGGTAGTCAGGGCACTCAGGTCACTGTTAGCTCCGGCGGTGGC
    TCTCAGGTCCAGCTCCAGGAGTCTGGTGGAGGCTCCGTGCAGGCTGGCGGTTCC
    CTGAGATTGTCTTGTACTGCCCCCGGCTTCACAAGTAACTCCTGTGGTATGGAC
    TGGTATCGTCAAGCGCCTGGAAAGGAGCGCGAGTTCGTTAGCTCCATTTCTACC
    GATGGGACCACTGGGTATGCAGACAGCGTGAAAGGTCGCTTTACCATCTCCAAG
    GACAAGGCTAAGGACACCGTGTACCTCCAAATGAACTCCCTGAAGCCCGAGGAC
    ACCGGGATGTATTCCTGCAAGACCAAGGACGGGACCATCGCCACTATGGAGTTG
    TGTGACTTCGGATATTGGGGGCAGGGCACCCAAGTGACTGTGTCTAGC
    hIL27 1438 CAGGTCCAGCTTCAGGAGTCTGGCGGGGGTCTGGTCCAGCCTGGGGGTTCTCTC
    Ra_VH CGCCTGTCCTGCGCAGCTAGTGGATTCACCTTCTCTCTCTCCGGTATGTCTTGG
    H17- GTGCGCCAGGCCCCTGGCAAGGGGCTGGAGTGGGTGAGTGCAATTAGCTCCGGG
    DR592 GGAGCAAGCACCTACTATACAGACTCAGTCAAGGGAAGATTCACAATTTCCCGC
    GATAACGCTAAAAACATGCTGTATCTCCAGCTCAACAGCCTGAAGACGGAAGAC
    ACGGCTATGTACTATTGTGCCAAAGGGGGCAGCGGCTATGGCGACGCCAGCCGC
    ATGACCTCTCCGGGCAGCCAGGGTACGCAGGTGACCGTGTCCAGCGGAGGCTCC
    GGGGGCTCTGGAGGTTCAGGGCAGGTACAGCTCCAAGAATCCGGGGGCGGTTCT
    GTGCAGGCTGGAGGCTCCCTGCGCCTGAGCTGCACAGCTCCGGGCTTTACCTCC
    AACAGTTGCGGAATGGATTGGTACAGGCAAGCGCCCGGCAAGGAGAGGGAGTTC
    GTGTCCAGTATTTCAACCGACGGCACAACCGGCTACGCGGATTCCGTGAAAGGA
    CGCTTCACCATTTCCAAAGACAAGGCCAAGGACACCGTGTATTTGCAGATGAAC
    TCACTGAAGCCCGAGGATACCGGAATGTATTCTTGTAAAACGAAGGATGGGACC
    ATCGCTACAATGGAGCTGTGTGACTTTGGTTACTGGGGCCAGGGCACTCAGGTC
    ACTGTCTCTTCT
    hIL27 1439 CAGGTGCAGCTCCAGGAAAGCGGTGGCGGTTTGGTGCAGCCTGGGGGCTCCCTG
    Ra_VH CGCCTGTCTTGTGCGGCTAGTGGCTTCACCTTCTCTCTGTCCGGCATGAGCTGG
    H17- GTGCGGCAAGCGCCGGGCAAGGGCCTCGAATGGGTGAGCGCAATCAGCTCTGGA
    DR593 GGCGCATCAACCTACTATACCGATTCAGTCAAGGGAAGGTTTACCATCTCCAGA
    GATAACGCCAAGAATATGCTGTACCTCCAGCTCAATTCACTGAAGACCGAGGAT
    ACCGCCATGTATTACTGCGCTAAGGGTGGCAGCGGATACGGAGATGCGTCCCGC
    ATGACAAGCCCCGGCTCACAGGGCACACAGGTGACTGTGTCCTCAGGAGGTGGC
    TCCCAAGTGCAGCTTCAGGAGAGCGGTGGAGGCTCCGTCCAAGCTGGAGGGTCC
    CTCCGTCTCTCTTGTGCAGCTTCCGGCTATCCTTACTCCAATGGGTACATGGGA
    TGGTTCCGCCAAGCTCCTGGCAAGGAGAGGGAGGGGGTGGCTACCATCTACACT
    GGCGATGGCCGCACCTATTACGCCGACAGCGTGAAAGGACGTTTCACCATTTCC
    CGTGACAATGCAAAGAACACTGTGGACCTCCAGATGTCAAGCCTCAAGCCAGAA
    GACACCGCGATGTACTATTGTGCTGCCAGAGCAGCGCCCCTGTATTCTTCAGGC
    TCTCCCCTGACACGCGCACGTTACAACGTCTGGGGCCAGGGTACTCAGGTCACC
    GTGTCTAGC
    hIL27 1440 CAGGTGCAGCTCCAGGAATCCGGCGGAGGCCTGGTCCAGCCCGGCGGGTCTCTG
    Ra_VH CGCCTGTCTTGTGCTGCCAGCGGCTTCACCTTCAGTCTGAGTGGAATGAGCTGG
    H17- GTGCGTCAGGCTCCAGGAAAGGGCCTGGAGTGGGTGTCCGCCATTAGCTCTGGA
    DR593 GGCGCGTCCACATATTACACCGATAGCGTAAAAGGCCGTTTCACTATCTCACGC
    GACAACGCTAAGAATATGCTGTATCTCCAGCTGAACTCCCTGAAAACCGAGGAT
    ACGGCCATGTATTACTGTGCGAAAGGGGGTTCAGGGTACGGCGACGCATCCAGG
    ATGACCAGCCCAGGTTCCCAAGGGACCCAGGTGACAGTGTCTTCCGGCGGAAGC
    GGAGGCTCCGGTGGCAGCGGCCAGGTGCAGTTGCAGGAATCTGGCGGTGGGAGC
    GTGCAGGCTGGCGGGAGCCTGCGCCTGAGCTGTGCTGCGAGCGGCTACCCCTAT
    TCTAACGGGTACATGGGTTGGTTCCGGCAGGCTCCCGGTAAAGAGCGCGAGGGA
    GTGGCCACGATTTACACGGGTGATGGGCGCACTTATTACGCAGACTCCGTTAAG
    GGCCGGTTTACCATTAGTCGTGATAACGCGAAGAACACCGTGGACCTTCAGATG
    TCCAGCTTGAAGCCAGAGGACACCGCTATGTATTACTGTGCTGCACGCGCTGCG
    CCTCTCTACAGTAGCGGCTCCCCTCTGACCCGCGCTCGCTATAACGTGTGGGGC
    CAGGGCACTCAGGTGACAGTAAGCTCC
    hIL27 1441 CAAGTTCAGCTCCAGGAGTCTGGAGGCGGTCTCGTGCAGCCCGGTGGCTCCCTC
    Ra_VH CGCCTGTCTTGCGCCGCGAGCGGCTTCACCTTCTCTTTGAGCGGAATGAGCTGG
    H17- GTCAGGCAGGCTCCCGGCAAAGGCCTGGAGTGGGTGTCCGCCATTAGTAGCGGC
    DR594 GGAGCCTCTACCTATTACACCGATTCTGTGAAGGGTCGTTTCACCATTTCTCGC
    GATAACGCAAAGAACATGCTGTACCTCCAGCTGAACTCTCTGAAGACCGAGGAT
    ACTGCAATGTATTACTGCGCCAAAGGCGGTAGTGGTTACGGTGACGCCAGCAGG
    ATGACCTCCCCAGGATCACAGGGAACCCAGGTCACCGTCAGCTCTGGTGGAGGC
    AGCCAGGTGCAGTTGCAGGAAAGCGGCGGAGGCAGTGTGCAGGCCGGAGGGTCT
    CTGAGGCTCTCTTGCGTCGCCAGCGCCTCCACTTACTGCACTTATGACATGCAC
    TGGTATCGGCAAGCTCCTGGGAAGGGCCGTGAATTTGTGAGCGCTATCGACAGC
    GACGGCACCACTAGGTATGCTGATTCTGTGAAAGGGAGGTTTACCATTTCCCAG
    GGCACCGCCAAGAACACGGTGTATCTCCAGATGAACTCTCTCCAGCCGGAAGAC
    ACTGCCATGTATTACTGTAAGACCGTGTGCGTGGTCGGATCTCGCTGGTCTGAT
    TATTGGGGCCAGGGAACCCAGGTGACGGTTTCTTCC
    hIL27 1442 CAGGTCCAGTTGCAGGAGTCCGGCGGAGGGCTGGTACAGCCCGGCGGAAGCCTG
    Ra_VH CGCCTGAGTTGCGCCGCGTCTGGATTTACTTTCTCTCTCTCTGGTATGAGCTGG
    H17- GTGCGCCAGGCTCCCGGCAAGGGACTTGAGTGGGTAAGCGCAATCTCCTCTGGC
    DR594 GGGGCGAGCACCTATTACACCGACAGCGTTAAGGGCAGGTTCACAATTAGCCGT
    GACAACGCTAAGAATATGCTTTATCTTCAGCTGAACAGCCTGAAGACTGAAGAC
    ACGGCCATGTATTACTGTGCCAAGGGCGGTTCCGGCTACGGAGACGCTAGTCGC
    ATGACCTCCCCAGGCTCCCAGGGCACCCAGGTCACCGTGTCTAGCGGAGGCTCT
    GGCGGTAGTGGTGGCTCCGGTCAGGTGCAACTTCAGGAGAGTGGCGGTGGCTCC
    GTTCAAGCTGGGGGTTCCCTGCGTCTGTCTTGTGTCGCTAGTGCGTCCACTTAT
    TGCACCTACGACATGCACTGGTATCGTCAAGCGCCGGGCAAGGGAAGGGAGTTC
    GTCAGCGCCATTGATTCCGACGGCACCACTCGCTACGCCGACTCTGTCAAGGGA
    CGCTTCACCATCTCCCAGGGCACTGCCAAAAATACCGTGTATTTGCAGATGAAC
    TCACTTCAGCCAGAGGACACTGCCATGTATTACTGCAAGACCGTCTGCGTCGTG
    GGCAGCAGGTGGTCTGATTACTGGGGCCAAGGCACCCAGGTGACCGTCAGCAGC
    hIL27 1443 CAGGTGCAACTTCAGGAATCAGGCGGGGGACTGGTGCAGCCAGGTGGCTCTCTG
    Ra_VH CGCCTCAGCTGTGCGGCCTCTGGCTTTACCTTCTCTTTGAGCGGTATGAGTTGG
    H17- GTGCGCCAGGCTCCGGGAAAAGGTCTGGAGTGGGTCTCTGCCATCTCTTCCGGC
    DR595 GGTGCCTCCACGTACTATACCGACTCCGTGAAGGGCCGGTTTACCATTTCCAGG
    GACAACGCCAAGAACATGCTTTATCTCCAGCTGAACTCTCTGAAGACAGAAGAT
    ACCGCCATGTACTATTGCGCCAAAGGTGGCTCCGGTTACGGCGACGCGAGCCGC
    ATGACTAGCCCTGGCTCCCAGGGAACCCAGGTCACAGTGTCCTCTGGCGGTGGC
    TCTCAGGTCCAGCTCCAGGAGTCTGGTGGCGGGTCCGTGCAGGCCGGTGGCTCC
    CTGACCCTGTCTTGTGCTGCCAGTGAGTATGCGTACAGTACCTGTAATATGGGT
    TGGTACAGGCAAGCGCCCGGCAAGGAACGCGAGCTGGTCTCCGCTTTTATCTCC
    GACGGAAGCACCTATTACGCAGACTCAGTGAAGGGTCGTTTCACCATCACCCGT
    GATAATGCTAAAAACACTGTGTACCTCCAGATGAATAGTCTGAAGCCCGAGGAT
    ACCGCTATTTATTACTGCTCCGCCAACTGTTACCGTCGCCTGAGAAACTACTGG
    GGACAAGGCACCCAGGTAACCGTCAGCTCT
    hIL27 1444 CAGGTGCAGTTGCAGGAGTCTGGCGGAGGTCTGGTACAGCCTGGTGGCAGCCTC
    Ra_VH CGCTTGAGCTGCGCGGCCAGTGGCTTCACTTTTTCCCTGTCAGGCATGAGCTGG
    H17- GTGCGTCAGGCTCCTGGCAAAGGACTGGAGTGGGTGTCCGCTATCTCCTCTGGA
    DR595 GGCGCATCCACTTATTACACCGATTCTGTCAAAGGTCGTTTCACCATTTCCCGC
    GATAATGCTAAGAACATGCTGTATTTGCAGTTGAACTCCCTGAAGACAGAGGAC
    ACCGCTATGTATTACTGCGCTAAGGGTGGCAGCGGGTATGGGGATGCCAGCCGC
    ATGACAAGCCCCGGCTCCCAGGGTACACAGGTCACCGTCTCCTCAGGAGGCAGT
    GGAGGTAGCGGGGGCTCCGGCCAAGTCCAGCTCCAGGAGTCCGGGGGTGGATCT
    GTCCAGGCCGGGGGCAGTCTCACTCTGTCCTGTGCCGCTTCAGAGTACGCCTAT
    AGTACCTGTAACATGGGCTGGTATAGGCAGGCTCCCGGCAAGGAGAGAGAACTG
    GTCAGCGCGTTTATCTCCGACGGCAGTACCTACTATGCTGACTCTGTGAAGGGA
    CGTTTTACCATCACCCGCGACAACGCCAAGAATACCGTCTACCTCCAGATGAAC
    TCTCTCAAACCGGAGGACACCGCCATCTATTACTGCTCTGCAAACTGTTATAGA
    AGGCTGCGTAACTACTGGGGACAAGGCACGCAAGTGACAGTGTCCTCA
    hIL27 1445 CAGGTGCAGTTGCAGGAGAGCGGTGGCGGTCTCGTGCAGCCAGGTGGCTCTCTG
    Ra_VH CGGCTGAGTTGCGCTGCCTCTGGCTTCACATTCTCTCTGTCCGGCATGTCTTGG
    H17- GTGCGCCAGGCTCCGGGTAAAGGGCTGGAGTGGGTGAGCGCAATCTCCTCTGGA
    DR596 GGTGCATCCACCTATTACACCGACTCTGTGAAGGGTCGCTTTACGATCTCCCGC
    GACAACGCAAAGAATATGCTTTACCTGCAACTGAACTCCCTGAAAACAGAGGAC
    ACGGCCATGTACTATTGTGCCAAGGGCGGGTCTGGCTACGGCGACGCTTCCAGG
    ATGACCAGTCCGGGCTCTCAGGGCACCCAGGTGACAGTCTCTAGCGGTGGGGGC
    TCCCAGGTCCAGCTTCAGGAAAGCGGAGGTGGCCTTGTTCAACCGGGCGGTTCA
    CTTCGCTTGAGCTGCACAGCTTCAGGTCTGACCTTCGACGATTCTGTCATGGGC
    TGGTTTAGGCAGGCCCCTGGGAAGGGCAGAGAAGCGGTGTCTTGTATCAGTTCC
    TCAGGGGCCAACGCTTTCTATGCAGACTCCGTGAAGGGACGTTTTACAATTTCA
    CGCGATAATGCCAAGAACACATTGTACCTCCAGATGAACTCCCTGAAACCCGAG
    GACACTGCTACATACTATTGTAAACGCGGCCACGCTTGTGCAGGCTACTATCCC
    ATCCCTTACGATGACTACTGGGGTCAGGGAACCCAGGTTACCGTTAGCTCC
    hIL27 1446 CAGGTTCAGCTCCAGGAGAGCGGAGGTGGCCTGGTTCAGCCTGGTGGCAGCCTG
    Ra_VH CGCCTGTCTTGCGCTGCCAGCGGTTTTACCTTTAGTTTGTCCGGTATGTCATGG
    H17- GTTCGTCAAGCTCCTGGCAAGGGTCTCGAATGGGTGTCCGCGATTTCCTCAGGA
    DR596 GGTGCCTCTACTTATTACACCGATAGTGTGAAGGGTCGCTTTACTATCTCTCGC
    GACAACGCGAAGAACATGCTGTACCTCCAACTGAACAGCCTGAAGACTGAAGAT
    ACCGCGATGTACTATTGCGCGAAGGGAGGCTCTGGGTATGGAGATGCCTCCCGT
    ATGACATCTCCTGGCTCTCAAGGCACCCAGGTGACCGTCTCCAGCGGCGGTTCC
    GGGGGCTCAGGGGGATCTGGCCAGGTTCAGTTGCAGGAGTCCGGCGGTGGCCTG
    GTCCAACCGGGCGGGAGCCTGAGGCTGTCCTGCACTGCGAGCGGGTTGACATTC
    GACGATAGCGTGATGGGTTGGTTTCGCCAGGCTCCCGGAAAGGGTCGGGAGGCC
    GTCAGCTGTATCTCCAGCAGTGGGGCTAATGCCTTCTACGCCGATTCCGTTAAA
    GGGAGATTTACCATCTCACGGGATAACGCTAAGAACACGCTGTACTTGCAGATG
    AACAGTCTCAAGCCAGAGGACACAGCGACTTACTATTGTAAACGCGGACATGCC
    TGTGCCGGGTACTATCCTATTCCCTACGATGACTATTGGGGTCAGGGCACCCAG
    GTGACCGTATCTTCT
    hIL27 1447 CAGGTTCAGTTGCAAGAGTCCGGCGGTGGAAGCGTCCAGGCCGGGGGTAGTCTT
    Ra_VH CGGCTGTCATGCGTGGCGAGTGGCTATGTGTCTTGCGACTATTTTCTGCCGAGC
    H18- TGGTATCGCCAGGCTCCAGGTAAGGAACGCGAGTTCGTGAGCATCATTGATGGC
    DR591 ACAGGTTCAACATCCTACGCTGCGTCCGTGAAGGGACGGTTCACCGCGAGCCAG
    GACAAGGGTAAGAACATCGCTTACCTCCAGATGAACTCCCTGAAGCCGGAGGAC
    ACCGCCATGTACTATTGTAAGGCTTCCTGTGTGCGCGGCAGGGGAATCAGTGAA
    TACTGGGGCCAAGGAACACAGGTGACTGTCAGTTCCGGTGGCGGAAGCCAGGTG
    CAGTTGCAAGAGTCCGGGGGCGGTTCCGTGCAGGCTGGTGGCTCCCTGAGACTC
    TCTTGTACCGCTTCAGGTGCTATTGCCAGTGGATACATTGATTCCCGCTGGTGC
    ATGGCCTGGTTCCGCCAGGCCCCCGGCAAGGAGAGGGAAGGAGTCGCCGCTATC
    TGGCCTGGGGGTGGCCTGACCGTGTATGCTGATAGCGTGAAGGGCAGATTCACC
    ATCAGCCGCGATCATGCTAAGAACACACTCTACCTTCAGATGAATAACCTGAAG
    CCTGAGGACACCGCTATGTATTACTGCGCAGCCGGTTCCCCTCGCATGTGCCCC
    TCTTTGGAGTTTGGCTTCGACTACTGGGGCCAGGGCACTCAGGTTACCGTAAGC
    TCC
    hIL27 1448 CAAGTCCAGCTCCAGGAATCCGGCGGTGGCTCCGTCCAGGCGGGCGGTTCCCTC
    Ra_VH AGGCTCTCCTGCGTGGCCAGCGGCTACGTAAGCTGCGATTATTTCCTGCCATCT
    H18- TGGTATCGCCAAGCCCCTGGTAAGGAGAGAGAATTTGTCTCAATCATTGATGGT
    DR591 ACAGGTAGCACCTCCTACGCAGCCTCAGTGAAGGGACGTTTTACCGCGAGCCAA
    GACAAAGGCAAGAACATCGCGTATTTGCAGATGAACTCTCTGAAGCCGGAGGAT
    ACCGCGATGTACTATTGCAAAGCCTCCTGTGTACGCGGCAGGGGAATCTCAGAG
    TATTGGGGCCAGGGCACTCAAGTGACAGTCAGCTCTGGCGGGAGCGGCGGGTCT
    GGAGGTAGCGGTCAGGTGCAACTCCAGGAATCTGGCGGAGGCTCTGTGCAGGCC
    GGTGGCAGCCTGCGTCTCAGCTGCACAGCCAGCGGGGCCATTGCCAGCGGCTAC
    ATCGACTCCCGCTGGTGCATGGCTTGGTTCCGGCAAGCGCCGGGAAAGGAAAGA
    GAGGGAGTCGCCGCGATCTGGCCGGGCGGTGGCCTGACTGTGTACGCTGACAGC
    GTGAAGGGTCGCTTCACCATCAGTCGGGACCATGCGAAAAACACGCTGTACTTG
    CAGATGAACAATCTGAAGCCTGAGGACACTGCCATGTATTACTGCGCTGCCGGT
    AGTCCACGCATGTGCCCGTCTCTGGAGTTCGGCTTTGACTACTGGGGCCAGGGC
    ACTCAGGTCACGGTTAGCTCT
    hIL27 1449 CAGGTGCAACTGCAAGAAAGTGGTGGAGGTTCCGTGCAAGCTGGCGGATCTTTG
    Ra_VH CGCCTCAGCTGCGTGGCCTCTGGCTATGTGAGTTGTGATTACTTCCTGCCTTCT
    H18- TGGTATCGTCAGGCCCCTGGTAAGGAACGGGAGTTCGTGTCCATTATCGACGGC
    DR592 ACCGGATCTACGAGCTACGCTGCATCCGTCAAGGGTCGTTTTACCGCTTCCCAA
    GACAAAGGCAAAAATATTGCCTACTTGCAAATGAACTCTCTGAAACCCGAAGAT
    ACAGCAATGTATTACTGTAAAGCCAGTTGTGTGCGCGGACGCGGCATTTCCGAG
    TATTGGGGACAGGGCACTCAGGTGACTGTCTCATCTGGCGGGGGCTCCCAGGTG
    CAACTTCAGGAATCTGGCGGGGGTTCTGTTCAAGCAGGCGGTTCTCTGCGTCTG
    AGTTGCACCGCTCCCGGATTTACCTCCAACAGTTGCGGAATGGATTGGTATCGC
    CAGGCTCCTGGCAAGGAGCGTGAGTTCGTAAGTAGCATTTCAACTGATGGTACT
    ACCGGATACGCTGACTCAGTTAAGGGTCGGTTCACTATCAGCAAGGATAAAGCT
    AAGGACACAGTGTACCTTCAGATGAACTCCCTGAAGCCTGAGGACACCGGAATG
    TACTCCTGTAAAACCAAAGACGGGACCATCGCCACGATGGAACTGTGTGATTTC
    GGATATTGGGGTCAGGGCACCCAGGTGACCGTGAGTAGC
    hIL27 1450 CAGGTGCAGCTTCAAGAGAGCGGCGGGGGCTCCGTCCAGGCCGGTGGGTCCTTG
    Ra_VH CGCTTGTCTTGTGTGGCCAGCGGATACGTGTCTTGCGATTATTTCCTGCCCTCT
    H18- TGGTACAGACAGGCCCCAGGCAAGGAGCGCGAGTTCGTATCCATCATTGACGGC
    DR592 ACTGGTTCTACAAGTTACGCTGCATCTGTGAAGGGCCGCTTTACCGCCTCTCAG
    GATAAGGGTAAAAACATCGCTTATTTGCAGATGAACTCACTCAAGCCTGAGGAC
    ACCGCCATGTACTATTGTAAGGCCTCTTGTGTCAGAGGGAGAGGCATTAGTGAA
    TATTGGGGTCAGGGGACCCAGGTGACTGTGTCCAGCGGCGGGAGCGGGGGCAGC
    GGTGGCAGCGGCCAGGTTCAACTTCAGGAGAGCGGGGGTGGAAGCGTCCAAGCA
    GGCGGGTCCCTGCGCTTGAGTTGTACCGCTCCGGGATTCACTAGCAACAGCTGC
    GGGATGGACTGGTATCGGCAGGCCCCAGGGAAGGAGCGTGAGTTCGTCAGCTCC
    ATCTCTACAGACGGCACAACCGGCTACGCCGACAGCGTTAAGGGCAGGTTCACA
    ATCAGCAAGGACAAGGCCAAGGATACCGTGTATTTGCAGATGAACAGCCTGAAG
    CCAGAGGATACAGGAATGTATAGCTGCAAGACTAAGGACGGCACTATTGCAACT
    ATGGAACTGTGTGATTTTGGCTACTGGGGTCAAGGCACGCAGGTGACCGTGAGT
    TCC
    hIL27 1451 CAGGTGCAGCTCCAGGAGTCCGGTGGGGGCTCCGTACAGGCGGGCGGTTCCCTG
    Ra_VH CGCCTTTCTTGTGTGGCCAGCGGTTACGTGAGCTGCGACTACTTCCTCCCTTCC
    H18- TGGTATCGTCAAGCCCCTGGTAAAGAGAGGGAGTTCGTGTCAATCATTGATGGC
    DR593 ACCGGCTCTACCTCTTATGCTGCCTCTGTGAAAGGACGCTTTACTGCTTCTCAG
    GATAAGGGCAAGAATATTGCTTACTTGCAGATGAACAGTCTGAAACCTGAGGAT
    ACTGCCATGTACTATTGCAAGGCCTCCTGTGTGCGTGGCCGGGGCATTAGCGAA
    TACTGGGGCCAGGGAACCCAGGTCACCGTCAGCTCTGGGGGTGGCTCTCAGGTG
    CAGCTGCAAGAATCCGGCGGTGGCTCCGTTCAGGCTGGCGGTTCCCTGCGGCTG
    TCCTGTGCAGCCTCCGGCTACCCGTACTCCAACGGCTATATGGGCTGGTTTCGC
    CAGGCCCCTGGCAAAGAGCGCGAGGGAGTTGCCACCATCTACACCGGGGATGGC
    CGCACTTATTACGCTGACTCTGTGAAAGGGCGCTTCACTATCAGCCGGGATAAC
    GCCAAGAATACCGTGGACCTCCAAATGAGTTCCCTCAAGCCGGAAGACACTGCA
    ATGTACTATTGCGCGGCTCGTGCAGCTCCACTGTACTCCTCTGGCTCTCCCCTG
    ACCCGCGCACGTTATAATGTCTGGGGCCAGGGCACCCAGGTGACCGTCTCAAGT
    hIL27 1452 CAGGTGCAGCTGCAAGAATCTGGCGGGGGCTCCGTGCAGGCAGGGGGTAGCCTG
    Ra_VH AGGCTGAGCTGCGTGGCTAGTGGCTACGTCTCCTGCGACTACTTTCTGCCCAGC
    H18- TGGTATCGTCAGGCACCTGGGAAGGAACGCGAGTTCGTATCCATCATTGATGGC
    DR593 ACTGGCTCTACCAGCTACGCAGCCTCCGTGAAAGGACGCTTCACTGCGAGCCAG
    GACAAGGGCAAGAACATCGCCTACTTGCAGATGAACTCCCTGAAGCCGGAAGAC
    ACCGCCATGTATTACTGTAAGGCTTCTTGTGTACGCGGGCGCGGTATCTCTGAA
    TATTGGGGCCAGGGCACTCAGGTGACGGTGTCCAGCGGAGGTAGCGGGGGCTCC
    GGCGGGAGCGGGCAGGTTCAGCTCCAGGAGTCTGGGGGTGGCTCCGTGCAGGCC
    GGAGGCTCCCTGCGCCTGTCCTGCGCCGCTTCAGGTTACCCTTATTCTAACGGT
    TATATGGGTTGGTTCCGTCAAGCGCCCGGCAAAGAAAGGGAGGGTGTGGCTACC
    ATTTACACTGGTGATGGTCGCACCTACTATGCTGATTCCGTGAAGGGCCGTTTC
    ACCATCTCTCGCGATAACGCTAAGAATACCGTGGACTTGCAGATGAGTTCTCTG
    AAACCTGAAGATACCGCCATGTACTATTGTGCCGCACGCGCCGCTCCGCTCTAC
    TCTAGCGGGTCTCCCCTGACGAGGGCTAGGTACAACGTGTGGGGACAGGGCACC
    CAGGTGACCGTGTCCAGC
    hIL27 1453 CAGGTGCAGTTGCAGGAAAGCGGCGGGGGCAGCGTCCAGGCTGGGGGAAGTCTC
    Ra_VH CGCCTGTCCTGCGTGGCCAGTGGCTACGTCAGCTGTGACTATTTTCTGCCGAGC
    H18- TGGTACAGGCAGGCCCCTGGGAAGGAGCGGGAGTTCGTGTCTATCATTGATGGG
    DR594 ACCGGCTCCACCAGCTACGCGGCCTCCGTGAAAGGACGTTTCACGGCCAGCCAG
    GATAAGGGAAAGAATATCGCTTACCTCCAGATGAACTCTCTGAAACCTGAGGAT
    ACTGCCATGTATTACTGCAAGGCCTCATGTGTGCGCGGACGCGGCATCTCAGAA
    TATTGGGGTCAGGGAACCCAGGTGACTGTCAGTTCTGGAGGTGGCTCCCAGGTA
    CAGCTCCAGGAGTCCGGTGGGGGCTCCGTGCAAGCAGGGGGTTCTTTGCGGCTT
    TCCTGTGTAGCCAGCGCCTCTACCTACTGCACCTACGACATGCACTGGTATCGC
    CAAGCGCCGGGCAAAGGCCGCGAGTTTGTCTCTGCCATTGATTCCGATGGTACA
    ACCCGTTATGCAGATTCCGTGAAGGGCAGATTCACCATCAGCCAGGGCACGGCG
    AAGAATACGGTCTACTTGCAGATGAACTCTTTGCAGCCCGAGGACACAGCCATG
    TATTACTGTAAGACAGTTTGTGTGGTAGGTTCTCGCTGGTCAGATTACTGGGGT
    CAGGGCACACAGGTGACGGTTTCTAGT
    hIL27 1454 CAGGTCCAGCTTCAGGAGTCTGGCGGGGGTTCCGTTCAGGCAGGCGGGTCCCTC
    Ra_VH AGGCTCTCTTGTGTCGCCTCCGGCTACGTGTCTTGCGACTATTTCCTGCCCTCT
    H18- TGGTATCGGCAGGCTCCGGGCAAGGAGCGCGAGTTCGTGAGCATCATTGATGGC
    DR594 ACAGGCAGTACTTCCTATGCGGCATCCGTGAAAGGGCGCTTCACTGCCAGTCAA
    GACAAGGGCAAAAACATTGCATACCTCCAGATGAACTCCCTGAAGCCTGAAGAC
    ACAGCTATGTATTACTGTAAGGCGAGTTGTGTACGTGGACGTGGTATCAGTGAA
    TACTGGGGCCAGGGCACCCAGGTGACCGTGTCAAGCGGCGGTTCTGGCGGGTCA
    GGCGGTTCCGGCCAGGTGCAGCTCCAGGAGTCCGGGGGAGGGAGCGTCCAGGCT
    GGCGGGTCTCTGCGCCTGTCATGCGTCGCCAGCGCATCTACTTACTGTACCTAC
    GATATGCACTGGTATCGCCAAGCGCCCGGCAAGGGCCGCGAGTTTGTCTCCGCC
    ATTGATTCAGACGGGACAACCCGGTATGCCGATAGTGTGAAGGGCCGTTTTACC
    ATCAGTCAGGGCACTGCTAAGAACACTGTGTATCTCCAGATGAACAGTCTTCAG
    CCTGAAGATACTGCTATGTATTACTGCAAAACTGTGTGTGTGGTTGGATCTCGT
    TGGAGCGACTATTGGGGTCAGGGTACTCAGGTCACAGTGTCTTCT
    hIL27 1455 CAAGTTCAGTTGCAGGAGTCTGGAGGTGGGTCTGTGCAGGCTGGGGGCTCCCTG
    Ra_VH CGTTTGTCTTGTGTTGCGAGCGGCTACGTCTCTTGTGACTATTTCCTGCCTAGC
    H18- TGGTATCGGCAGGCCCCCGGCAAAGAACGCGAGTTTGTGAGCATTATCGACGGT
    DR595 ACTGGCTCCACCAGCTATGCGGCCTCCGTGAAGGGACGCTTTACCGCCTCCCAG
    GATAAGGGCAAGAACATCGCGTACCTCCAGATGAACTCACTGAAGCCAGAGGAC
    ACCGCTATGTACTATTGCAAAGCAAGCTGTGTTCGCGGTAGGGGAATTTCAGAG
    TATTGGGGCCAAGGAACCCAGGTCACCGTCAGCAGTGGAGGTGGCAGCCAGGTG
    CAGCTCCAGGAGAGTGGCGGGGGTTCTGTGCAGGCCGGAGGCTCCCTGACCCTG
    TCTTGCGCCGCAAGTGAGTATGCGTACTCCACATGCAACATGGGATGGTATCGC
    CAGGCTCCCGGTAAGGAGCGCGAGCTGGTGAGCGCTTTTATCTCAGACGGCTCT
    ACCTACTATGCCGACTCCGTCAAGGGCCGTTTCACAATCACCCGTGATAACGCC
    AAGAATACCGTCTACTTGCAGATGAACTCTTTGAAGCCTGAGGACACAGCCATT
    TACTATTGCTCTGCGAACTGTTACCGCCGTCTGCGGAACTATTGGGGCCAGGGC
    ACCCAGGTGACTGTGTCCTCC
    hIL27 1456 CAGGTGCAGCTGCAAGAGTCCGGCGGTGGCAGTGTCCAAGCTGGCGGGTCCCTG
    Ra_VH AGGTTGTCCTGCGTGGCATCCGGCTATGTTAGTTGTGACTACTTTCTGCCCTCC
    H18- TGGTATCGCCAGGCTCCTGGCAAGGAGCGCGAATTTGTGTCTATCATTGATGGC
    DR595 ACCGGCAGCACTTCTTATGCTGCATCTGTGAAAGGACGGTTCACCGCGAGCCAG
    GACAAGGGTAAGAATATCGCCTACCTCCAGATGAACAGCCTGAAACCCGAGGAT
    ACTGCCATGTACTATTGTAAGGCCAGTTGCGTGCGCGGTCGTGGCATCAGCGAG
    TATTGGGGCCAGGGGACACAGGTGACCGTGTCCAGTGGAGGTAGCGGTGGAAGC
    GGCGGTTCCGGCCAGGTCCAGCTCCAGGAGAGCGGGGGAGGCTCAGTGCAGGCC
    GGAGGCAGCCTGACACTGTCCTGCGCCGCAAGCGAATATGCGTACAGCACCTGC
    AACATGGGCTGGTATCGCCAGGCCCCAGGCAAGGAGCGTGAACTTGTGTCAGCC
    TTCATCAGCGACGGTAGCACATATTACGCTGACTCAGTGAAGGGACGCTTCACA
    ATCACCAGGGATAACGCCAAGAACACAGTTTACCTCCAGATGAACTCCCTGAAG
    CCAGAGGATACCGCTATTTATTACTGTTCCGCAAATTGTTACCGTAGACTGCGC
    AATTATTGGGGACAAGGCACACAGGTGACAGTGAGTTCT
    hIL27 1457 CAGGTCCAGTTGCAGGAGTCTGGGGGAGGCAGCGTCCAGGCCGGGGGCAGTCTC
    Ra_VH CGCCTGTCCTGTGTCGCGAGCGGGTACGTGTCTTGCGATTACTTCCTCCCCTCC
    H18- TGGTATCGCCAAGCGCCAGGCAAGGAACGCGAGTTCGTTTCCATCATTGACGGC
    DR596 ACCGGAAGCACTTCCTACGCTGCCTCCGTGAAGGGGCGTTTCACAGCGTCCCAG
    GATAAGGGAAAGAATATCGCTTATTTGCAGATGAACTCTCTGAAGCCTGAGGAT
    ACCGCCATGTACTATTGTAAAGCCTCCTGTGTGAGGGGTCGCGGGATCTCTGAG
    TACTGGGGCCAAGGAACTCAGGTGACGGTGTCTAGCGGCGGAGGCTCCCAGGTG
    CAGCTGCAAGAATCTGGCGGAGGCTTGGTGCAGCCGGGAGGCTCACTGCGTCTC
    TCCTGCACCGCCAGCGGCCTCACTTTTGACGATAGCGTGATGGGATGGTTCCGT
    CAGGCCCCTGGCAAGGGCCGTGAGGCGGTCAGCTGCATCTCTTCCAGTGGTGCC
    AACGCTTTCTACGCAGACAGCGTGAAGGGTAGGTTCACCATCAGCAGAGATAAC
    GCCAAGAACACGCTGTATCTCCAGATGAACTCCCTGAAGCCTGAGGACACTGCC
    ACCTACTATTGCAAGCGGGGCCATGCGTGTGCTGGCTATTACCCAATTCCCTAC
    GATGACTACTGGGGCCAGGGCACACAAGTCACGGTAAGCAGC
    hIL27 1458 CAGGTCCAGCTCCAGGAATCAGGTGGCGGAAGCGTGCAGGCTGGGGGCTCTCTG
    Ra_VH CGCCTGTCTTGTGTGGCCAGTGGCTACGTTAGCTGCGATTATTTCCTGCCATCT
    H18- TGGTACAGGCAGGCCCCTGGCAAGGAGCGTGAGTTCGTCTCTATCATTGATGGA
    DR596 ACAGGTTCCACCAGTTACGCCGCTTCTGTTAAGGGCCGCTTCACCGCCTCACAG
    GATAAGGGCAAGAACATCGCTTACCTCCAAATGAACTCCCTGAAGCCCGAGGAC
    ACTGCCATGTATTACTGTAAGGCTTCTTGTGTGCGCGGTCGCGGCATTTCCGAA
    TACTGGGGACAAGGAACCCAGGTAACAGTGTCCTCTGGAGGCAGTGGAGGCTCA
    GGGGGCTCTGGTCAGGTCCAACTCCAGGAGAGCGGCGGTGGACTGGTGCAGCCC
    GGTGGCTCTCTCAGGCTGTCCTGTACGGCGAGCGGCCTCACCTTTGATGACTCT
    GTTATGGGCTGGTTCCGCCAAGCCCCTGGGAAGGGGCGGGAGGCTGTGAGCTGT
    ATTTCCTCTAGCGGGGCGAACGCTTTCTACGCCGATTCAGTGAAAGGCCGTTTC
    ACCATCAGTCGCGACAACGCCAAAAACACGCTGTACTTGCAGATGAACTCTTTG
    AAACCAGAGGACACCGCAACTTACTATTGTAAACGCGGCCACGCATGTGCTGGC
    TATTACCCTATCCCCTACGATGACTACTGGGGCCAGGGCACCCAGGTTACAGTG
    TCATCT
    hIL27 1459 CAAGTCCAGTTGCAGGAATCCGGCGGTGGATCAGTGCAGGCAGGCGGTAGCTTG
    Ra_VH AGGCTGTCTTGTAGAGCGTCCGGTTCAACTTACTCCAACTACTGCCTGGGCTGG
    H19- TTTCGGCAGATTACAGGCAAGGAGCGCGAGGGAGTGGCCGTGATAAATTGGGTG
    DR591 GGTGGAATGCTGTATTTTGCCGACTCCGTGAAGGGCCGGTTCACCGTGTCTCAG
    GACCAGGCCAAGAACACCGTCTACCTTCAGATGAACTCCCTGAAGCCTGAGGAT
    ACCGCCATGTATTACTGCGCCGCTGAGAGTGTCAGCTCTTTTAGTTGCGGTGGC
    TGGCTGACCCGCCCCGACCGTGTGCCGTACTGGGGCCAGGGAACACAGGTGACA
    GTGAGTTCCGGTGGGGGCTCCCAAGTGCAACTTCAGGAGTCTGGCGGTGGCAGC
    GTGCAGGCAGGGGGCTCTCTGCGTCTGTCATGCACCGCCAGCGGAGCCATCGCC
    TCCGGTTACATCGACTCCCGCTGGTGTATGGCTTGGTTTCGCCAGGCTCCCGGC
    AAGGAGCGTGAAGGCGTGGCCGCGATCTGGCCTGGCGGGGGCTTGACTGTTTAT
    GCTGACTCAGTGAAGGGTCGCTTTACCATCTCCCGCGACCACGCAAAGAACACC
    CTTTATTTGCAGATGAATAACCTGAAGCCGGAAGACACTGCCATGTACTATTGC
    GCAGCTGGCTCTCCCCGCATGTGTCCGTCTCTGGAGTTCGGTTTCGATTACTGG
    GGTCAGGGCACTCAGGTTACCGTGTCCAGC
    hIL27 1460 CAGGTGCAGTTGCAGGAAAGTGGAGGCGGGTCAGTTCAGGCTGGCGGTTCCCTG
    Ra_VH AGGCTGTCCTGTCGTGCAAGTGGCTCAACGTATTCAAACTATTGCCTTGGTTGG
    H19- TTTAGGCAGATCACCGGCAAGGAGCGCGAGGGCGTTGCTGTCATCAACTGGGTC
    DR591 GGCGGGATGCTGTACTTTGCCGACAGCGTCAAGGGCAGATTTACCGTCTCCCAG
    GATCAGGCCAAGAACACAGTGTATCTCCAGATGAACTCTTTGAAGCCCGAAGAC
    ACAGCAATGTACTATTGTGCGGCTGAATCTGTTAGCTCCTTTTCCTGCGGCGGT
    TGGTTGACGAGACCGGATCGGGTCCCGTACTGGGGTCAGGGGACCCAGGTCACG
    GTCAGCTCCGGGGGCAGCGGCGGTAGTGGAGGCTCCGGTCAGGTGCAGCTCCAG
    GAGAGCGGGGGCGGTAGCGTGCAAGCAGGGGGCAGTCTGCGGCTGAGCTGTACT
    GCGAGCGGAGCCATCGCCAGCGGATATATCGACAGCCGCTGGTGTATGGCCTGG
    TTCCGCCAGGCTCCCGGAAAAGAGCGCGAGGGAGTCGCTGCGATTTGGCCAGGG
    GGCGGATTGACAGTATACGCCGACTCTGTGAAAGGCAGATTTACTATCAGCCGC
    GATCACGCCAAGAACACTCTGTACCTCCAGATGAATAACCTCAAACCGGAGGAC
    ACCGCCATGTATTACTGCGCTGCCGGGTCCCCCAGGATGTGTCCTAGTCTGGAG
    TTCGGTTTCGACTACTGGGGCCAAGGAACCCAGGTGACCGTCTCTAGC
    hIL27 1461 CAGGTGCAGTTGCAGGAGTCAGGAGGTGGGAGTGTTCAGGCCGGAGGCAGCCTG
    Ra_VH CGCTTGAGCTGCCGGGCGTCTGGCAGCACCTACAGCAACTATTGCCTGGGTTGG
    H19- TTCCGTCAGATCACCGGCAAGGAGCGGGAGGGCGTGGCTGTCATCAACTGGGTG
    DR592 GGTGGAATGCTGTATTTTGCGGATAGTGTGAAGGGACGGTTCACAGTCTCTCAG
    GATCAGGCAAAGAATACCGTGTACCTTCAGATGAACTCCCTGAAGCCTGAAGAC
    ACTGCCATGTACTATTGCGCCGCTGAGAGCGTGTCCAGCTTCTCTTGCGGTGGC
    TGGCTCACCAGGCCTGACCGTGTGCCTTACTGGGGCCAGGGTACGCAGGTGACC
    GTATCTAGCGGCGGGGGTTCTCAGGTCCAGTTGCAGGAGTCCGGTGGCGGGTCC
    GTCCAGGCGGGCGGTAGCCTGCGGCTGAGTTGCACCGCTCCTGGATTTACCAGC
    AACAGTTGTGGCATGGACTGGTATCGTCAGGCCCCCGGAAAGGAACGCGAGTTC
    GTGAGCAGTATCTCCACAGACGGCACGACCGGCTACGCTGACTCCGTCAAGGGC
    CGTTTTACCATCTCCAAAGACAAAGCAAAGGATACAGTGTATCTCCAGATGAAC
    TCACTGAAGCCCGAGGACACGGGTATGTATAGCTGCAAGACTAAGGACGGAACC
    ATTGCCACAATGGAGCTTTGTGACTTCGGGTACTGGGGACAGGGAACACAAGTA
    ACGGTCAGCTCC
    hIL27 1462 CAGGTCCAGTTGCAGGAATCCGGCGGGGGATCAGTGCAGGCTGGCGGGTCTCTG
    Ra_VH CGCCTCTCATGCAGAGCCTCCGGCTCCACCTATTCTAACTACTGCTTGGGCTGG
    H19- TTCAGACAGATCACCGGCAAAGAGCGCGAGGGCGTTGCAGTGATAAATTGGGTG
    DR592 GGTGGAATGCTGTATTTTGCAGACTCCGTCAAGGGAAGGTTCACCGTGAGTCAG
    GATCAAGCCAAGAACACCGTGTATCTGCAAATGAACTCTCTGAAGCCCGAGGAC
    ACCGCTATGTATTACTGTGCAGCTGAAAGCGTGTCCTCTTTCTCTTGCGGAGGC
    TGGCTTACTAGACCTGATCGTGTGCCATATTGGGGTCAGGGCACCCAGGTCACA
    GTTTCTTCCGGTGGCTCAGGCGGATCTGGCGGGTCCGGGCAGGTACAGCTCCAG
    GAGTCTGGTGGCGGTTCCGTTCAGGCTGGGGGCTCCCTGCGTCTCTCCTGCACC
    GCGCCCGGCTTCACAAGCAACTCCTGCGGTATGGACTGGTATCGCCAAGCGCCT
    GGAAAAGAGCGCGAGTTCGTCTCTAGCATTTCCACTGACGGTACTACCGGCTAC
    GCCGACTCCGTGAAGGGGCGCTTCACTATTTCTAAGGATAAGGCGAAGGATACT
    GTGTACCTCCAGATGAACTCACTGAAGCCCGAGGACACTGGGATGTATAGTTGC
    AAGACCAAGGATGGCACAATCGCCACTATGGAATTGTGTGACTTCGGCTACTGG
    GGGCAGGGCACCCAGGTGACAGTGTCCAGC
    hIL27 1463 CAGGTCCAGTTGCAGGAGTCCGGTGGCGGTTCCGTCCAAGCCGGAGGCTCACTC
    Ra_VH AGACTCTCTTGTCGCGCCTCAGGAAGCACTTACTCCAACTACTGCCTGGGGTGG
    H19- TTTCGCCAGATCACTGGCAAGGAGCGGGAGGGTGTCGCGGTAATAAATTGGGTC
    DR593 GGCGGTATGCTGTATTTCGCGGACTCCGTGAAGGGCCGTTTCACCGTATCACAG
    GACCAGGCCAAGAACACTGTGTATCTCCAGATGAACTCACTGAAGCCCGAAGAT
    ACTGCAATGTATTACTGCGCGGCTGAGAGCGTGTCTTCCTTCTCTTGCGGCGGA
    TGGCTCACACGGCCAGACCGTGTGCCATACTGGGGTCAGGGCACCCAAGTTACA
    GTCTCCAGCGGGGGTGGCTCCCAAGTCCAGCTGCAAGAGAGCGGCGGGGGCTCC
    GTGCAGGCTGGAGGTTCTCTGCGTTTGTCCTGTGCTGCCTCAGGATACCCTTAT
    AGTAACGGTTACATGGGCTGGTTTCGGCAGGCTCCAGGGAAGGAAAGGGAGGGG
    GTGGCTACAATTTACACCGGCGACGGAAGGACCTATTACGCCGACTCTGTGAAA
    GGTCGCTTCACCATTTCCCGTGACAACGCGAAGAATACAGTTGATCTTCAGATG
    TCTTCCCTGAAGCCCGAGGACACAGCGATGTATTACTGCGCTGCCCGTGCTGCC
    CCTCTCTACAGCTCTGGCTCTCCCCTGACCCGCGCCCGTTACAACGTGTGGGGC
    CAGGGGACTCAGGTCACAGTCTCATCC
    hIL27 1464 CAAGTGCAGCTGCAAGAGAGCGGAGGTGGATCTGTGCAGGCTGGTGGGTCTCTG
    Ra_VH CGCCTCTCTTGCCGTGCGTCAGGCTCCACCTACTCTAATTATTGCCTCGGTTGG
    H19- TTCCGGCAGATTACGGGCAAGGAGCGCGAGGGTGTGGCAGTTATCAACTGGGTT
    DR593 GGGGGTATGTTGTACTTTGCTGACTCCGTCAAGGGACGTTTCACTGTGAGTCAA
    GACCAGGCTAAGAACACTGTGTACCTCCAGATGAATAGTCTGAAGCCTGAGGAT
    ACCGCCATGTATTACTGCGCAGCTGAGAGCGTGAGCAGTTTTTCCTGTGGCGGA
    TGGCTTACCAGACCTGATCGCGTGCCGTACTGGGGCCAGGGGACCCAGGTGACT
    GTTAGTTCTGGAGGCAGCGGAGGCTCCGGTGGCAGCGGTCAGGTACAGCTCCAG
    GAATCTGGTGGCGGTAGCGTGCAGGCAGGGGGCTCTCTTCGCCTGAGCTGTGCA
    GCTTCTGGATACCCATATAGCAACGGTTACATGGGCTGGTTTCGCCAAGCCCCC
    GGCAAGGAGAGAGAAGGTGTGGCTACCATTTATACCGGCGACGGGCGCACTTAC
    TATGCAGACTCCGTCAAAGGGCGGTTTACAATCTCTAGGGACAACGCCAAGAAT
    ACCGTCGATCTTCAGATGTCTTCCCTGAAGCCGGAGGATACCGCCATGTATTAC
    TGTGCGGCCAGGGCTGCCCCTCTCTACTCCTCTGGATCACCTCTGACTAGGGCT
    CGCTATAACGTATGGGGTCAGGGAACACAGGTCACGGTGTCATCT
    hIL27 1465 CAGGTTCAGCTCCAAGAGAGCGGCGGTGGCTCAGTGCAGGCAGGTGGCTCACTT
    Ra_VH AGGCTGAGTTGCAGAGCTTCCGGCTCAACATACTCCAACTATTGTCTCGGCTGG
    H19- TTCAGGCAGATCACTGGTAAGGAGCGCGAGGGGGTGGCCGTCATCAACTGGGTG
    DR594 GGTGGAATGCTGTACTTTGCCGACTCTGTAAAGGGTCGTTTTACTGTGTCTCAG
    GACCAGGCCAAGAACACAGTGTACCTTCAGATGAACTCTCTGAAGCCGGAGGAT
    ACGGCAATGTACTATTGCGCTGCCGAGAGTGTTAGTTCATTCTCCTGTGGAGGC
    TGGCTGACTCGCCCGGATCGTGTGCCGTACTGGGGCCAGGGCACCCAGGTGACC
    GTTAGCTCCGGCGGTGGCTCCCAGGTGCAGCTGCAAGAGAGTGGTGGAGGCTCC
    GTGCAGGCAGGTGGCTCCCTTCGTCTTTCTTGTGTCGCCTCTGCTTCAACCTAC
    TGCACATACGACATGCACTGGTATCGCCAGGCCCCTGGCAAGGGGCGCGAGTTC
    GTTAGTGCCATCGACAGTGACGGCACTACCAGATACGCCGACAGCGTCAAGGGC
    CGCTTCACCATCAGCCAGGGAACAGCTAAAAACACCGTCTACCTCCAGATGAAC
    TCCTTGCAGCCAGAGGACACAGCCATGTATTACTGCAAAACTGTCTGCGTCGTG
    GGGTCCAGATGGAGCGACTACTGGGGCCAAGGCACGCAGGTTACCGTGAGCAGC
    hIL27 1466 CAGGTCCAGTTGCAGGAGTCCGGCGGGGGTTCTGTGCAGGCTGGAGGCAGCCTC
    Ra_VH AGACTCTCTTGCAGGGCTTCTGGATCAACTTATTCTAATTATTGCCTCGGTTGG
    H19- TTCCGCCAAATCACAGGCAAGGAGAGGGAGGGAGTGGCGGTGATTAACTGGGTG
    DR594 GGCGGTATGCTGTACTTCGCCGACTCCGTGAAAGGTCGTTTCACTGTCTCTCAG
    GATCAGGCCAAGAACACTGTTTACCTCCAGATGAACTCTCTGAAGCCCGAAGAT
    ACGGCCATGTACTATTGCGCTGCCGAATCCGTCTCCTCTTTTTCCTGCGGAGGC
    TGGCTGACACGCCCCGACCGCGTCCCCTATTGGGGTCAGGGGACTCAGGTCACC
    GTCAGCTCTGGCGGGAGCGGAGGCAGCGGGGGCAGCGGCCAGGTCCAGCTTCAG
    GAAAGCGGAGGTGGCTCCGTGCAGGCTGGCGGAAGCCTGAGACTGTCCTGCGTG
    GCTTCAGCTTCCACCTACTGCACCTATGACATGCACTGGTATAGGCAAGCGCCA
    GGAAAGGGCAGGGAGTTCGTTTCTGCTATTGATTCTGACGGAACAACTAGATAC
    GCAGACTCCGTCAAGGGAAGGTTCACCATCTCCCAGGGCACCGCCAAGAACACT
    GTCTACCTCCAGATGAACAGTCTGCAACCAGAAGACACCGCTATGTATTACTGC
    AAGACCGTGTGCGTGGTCGGGTCCAGATGGTCCGATTACTGGGGCCAGGGAACA
    CAGGTGACTGTCTCATCT
    hIL27 1467 CAGGTGCAGCTCCAGGAATCTGGGGGAGGTTCAGTGCAGGCAGGTGGCTCCCTG
    Ra_VH CGCCTGAGTTGCAGGGCGTCCGGTAGTACCTACTCAAACTACTGCCTGGGGTGG
    H19- TTTAGACAAATCACCGGAAAGGAAAGGGAGGGCGTCGCAGTGATAAATTGGGTG
    DR595 GGCGGTATGCTGTACTTCGCCGACTCTGTGAAGGGACGCTTTACCGTCTCCCAG
    GATCAGGCTAAGAACACTGTGTATTTGCAGATGAACTCCCTGAAACCAGAGGAC
    ACAGCCATGTATTACTGTGCTGCCGAAAGCGTCTCTAGTTTTTCCTGCGGAGGG
    TGGCTTACCCGTCCCGACAGAGTTCCTTATTGGGGCCAGGGAACCCAGGTGACA
    GTTTCCTCTGGTGGCGGGTCTCAGGTTCAGCTTCAGGAGTCTGGCGGGGGCTCT
    GTGCAGGCTGGCGGATCTCTGACTCTGAGCTGCGCCGCGAGCGAGTACGCCTAC
    TCAACCTGCAACATGGGCTGGTATCGCCAGGCACCGGGCAAGGAACGGGAGCTG
    GTGTCTGCATTCATCTCAGACGGTTCTACGTATTACGCCGACTCCGTGAAGGGT
    CGCTTTACTATTACCCGCGACAACGCTAAGAACACGGTGTACTTGCAGATGAAC
    AGCCTGAAGCCTGAGGATACTGCCATCTATTACTGTTCCGCTAACTGCTATAGA
    CGCCTGCGCAATTACTGGGGACAGGGGACGCAAGTGACAGTGTCTAGC
    hIL27 1468 CAAGTGCAGTTGCAGGAATCCGGCGGAGGCTCCGTACAGGCCGGTGGATCACTG
    Ra_VH CGCCTGTCTTGTCGGGCCTCCGGGTCAACCTATAGCAACTACTGTCTGGGCTGG
    H19- TTTCGTCAGATCACAGGTAAAGAGCGCGAGGGGGTCGCCGTCATCAACTGGGTG
    DR595 GGCGGTATGCTGTACTTCGCTGACAGTGTGAAGGGTCGGTTCACCGTTTCCCAG
    GATCAAGCCAAAAACACCGTCTACCTCCAGATGAACTCCTTGAAGCCCGAAGAC
    ACCGCCATGTATTACTGCGCCGCAGAGAGTGTGTCCTCTTTCTCCTGCGGTGGG
    TGGTTGACTAGGCCGGACCGTGTTCCCTACTGGGGCCAGGGAACCCAAGTGACC
    GTTAGCTCAGGGGGCTCCGGTGGCTCTGGTGGCTCTGGTCAGGTGCAGCTCCAG
    GAGTCTGGAGGCGGGTCAGTTCAGGCTGGGGGCAGTCTGACTCTGTCCTGTGCT
    GCAAGCGAGTACGCTTACTCTACCTGTAACATGGGTTGGTATCGCCAGGCCCCA
    GGGAAGGAACGCGAGCTTGTGTCAGCCTTTATCTCCGATGGCAGCACTTATTAC
    GCAGATTCCGTAAAGGGACGCTTCACCATCACCCGTGACAACGCCAAGAATACC
    GTCTACCTCCAGATGAACAGCCTGAAGCCGGAGGACACCGCCATCTATTACTGC
    TCCGCCAACTGCTACCGGCGTCTGCGCAACTACTGGGGCCAGGGCACCCAGGTG
    ACCGTTTCATCA
    hIL27 1469 CAGGTTCAACTCCAGGAGTCCGGCGGAGGGTCCGTGCAGGCTGGAGGTTCCCTC
    Ra_VH CGGTTGTCCTGTCGTGCGTCCGGTTCCACCTACTCAAATTATTGTCTGGGCTGG
    H19- TTCCGCCAGATTACTGGCAAGGAAAGAGAGGGCGTAGCCGTCATCAACTGGGTT
    DR596 GGGGGAATGTTGTACTTCGCCGACAGCGTGAAAGGCCGCTTTACGGTTTCCCAG
    GACCAGGCTAAGAACACTGTATACCTTCAGATGAACTCCCTGAAGCCGGAGGAC
    ACCGCTATGTACTATTGCGCCGCTGAGTCTGTCTCCAGCTTCTCTTGCGGGGGA
    TGGTTGACCCGCCCTGATCGCGTGCCATACTGGGGGCAGGGTACTCAAGTGACA
    GTGTCCTCTGGCGGAGGCTCCCAGGTTCAGTTGCAGGAGAGCGGCGGTGGACTG
    GTTCAGCCTGGTGGGAGTCTCCGCCTGAGCTGCACAGCCAGCGGACTGACTTTC
    GATGACTCAGTGATGGGATGGTTCAGACAGGCTCCGGGAAAGGGCCGTGAGGCG
    GTCAGCTGTATCTCCTCTTCCGGCGCTAACGCCTTCTACGCTGATTCCGTAAAG
    GGACGGTTTACCATTTCTCGGGATAACGCCAAGAATACCCTGTATCTCCAGATG
    AACTCTCTCAAGCCCGAGGATACCGCCACCTATTACTGTAAAAGGGGCCACGCA
    TGTGCTGGATATTACCCGATTCCCTATGATGACTATTGGGGGCAAGGAACGCAG
    GTTACCGTTAGTTCT
    hIL27 1470 CAGGTGCAGCTCCAGGAGTCCGGTGGCGGTTCCGTCCAGGCAGGTGGCTCCCTG
    Ra_VH CGGCTGTCTTGTAGGGCTTCTGGCTCTACCTACTCCAACTACTGTCTGGGATGG
    H19- TTCCGCCAGATCACAGGCAAGGAGAGGGAGGGCGTAGCAGTGATTAACTGGGTT
    DR596 GGGGGTATGCTGTATTTCGCCGATTCCGTGAAGGGTCGCTTCACCGTGTCCCAG
    GATCAGGCCAAAAACACTGTTTATTTGCAGATGAACTCCCTGAAGCCTGAGGAC
    ACCGCTATGTATTACTGTGCAGCGGAGTCCGTGTCATCCTTCTCCTGTGGTGGC
    TGGCTGACTCGTCCAGACCGTGTGCCTTATTGGGGACAGGGCACCCAGGTGACC
    GTGTCCTCAGGCGGTTCCGGTGGCTCCGGTGGCAGCGGTCAGGTGCAGCTTCAG
    GAGAGCGGTGGGGGCCTGGTGCAGCCCGGAGGTTCACTGAGACTGAGCTGCACG
    GCCAGCGGTCTGACCTTCGATGACAGCGTGATGGGTTGGTTCCGTCAAGCGCCG
    GGCAAGGGACGCGAAGCAGTGTCCTGTATCAGTTCCTCTGGTGCTAACGCCTTC
    TATGCTGACAGTGTGAAGGGACGCTTTACTATCTCCCGCGACAACGCCAAGAAT
    ACCCTGTACCTCCAGATGAACTCTCTGAAGCCCGAGGATACCGCCACGTATTAC
    TGTAAGCGCGGTCACGCCTGTGCAGGGTACTATCCCATCCCCTACGATGACTAC
    TGGGGCCAGGGAACTCAGGTCACGGTCTCCTCA
    hIL27 1471 CAGGTTCAGCTCCAGGAGAGTGGGGGCGGGCTGGTGCAGCCCGGCGGATCACTC
    Ra_VH CGGCTGTCCTGTGCCGCGAGTGGGTTTACGTTTTCCTCATACCCTATGTCCTGG
    H20- GTCCGCCAGGCTCCGGGCAAAGGACTGGAATGGGTAAGCACAATTAGCTCTGGG
    DR591 GGCGATACAACTCTGTATGCGGACTCTGTAAAAGGACGCTTCACCAGCTCTCGC
    GACAACGCAAAGAATACACTCTACCTCCAGCTTAACTCTCTGAAAACAGAGGAC
    ACAGCAATGTATTACTGTGCAAAGCGCATTGATTGCAATTCCGGCTACTGCTAC
    AAGCGCTCTTATTGGGGGCAAGGTACGCAGGTGACGGTTAGCTCCGGCGGAGGC
    TCCCAGGTGCAGTTGCAGGAATCCGGCGGAGGCTCAGTGCAAGCGGGAGGGTCC
    CTGAGACTGAGCTGTACTGCATCCGGGGCTATCGCCAGCGGATACATTGATTCA
    CGGTGGTGTATGGCTTGGTTCCGGCAAGCCCCTGGCAAGGAGCGCGAGGGCGTG
    GCGGCTATCTGGCCCGGCGGTGGACTGACCGTGTACGCTGACTCCGTCAAGGGC
    CGCTTTACTATCAGCCGCGACCACGCTAAGAACACGCTGTACCTCCAGATGAAC
    AATCTGAAGCCCGAGGACACCGCTATGTACTATTGCGCAGCTGGCTCACCTCGG
    ATGTGCCCTTCCCTTGAGTTTGGGTTCGATTACTGGGGCCAAGGCACCCAGGTG
    ACCGTTAGCAGT
    hIL27 1472 CAGGTGCAGCTGCAAGAATCCGGCGGTGGCCTGGTGCAGCCAGGAGGCTCCCTG
    Ra_VH CGGCTGTCCTGTGCTGCGTCTGGCTTCACCTTTAGCTCTTATCCCATGTCTTGG
    H20- GTGCGTCAGGCTCCGGGAAAGGGCTTGGAATGGGTGTCCACCATTTCTAGCGGA
    DR591 GGCGACACCACTCTCTACGCTGACTCCGTGAAAGGGCGCTTCACCTCCAGCAGA
    GACAACGCTAAGAACACCCTGTACTTGCAGCTTAATTCTCTGAAGACCGAGGAT
    ACAGCAATGTACTATTGCGCCAAGCGGATTGATTGCAACTCCGGCTATTGTTAC
    AAGAGGTCCTATTGGGGCCAGGGAACTCAGGTAACTGTTAGTTCAGGAGGCTCC
    GGTGGATCTGGCGGAAGCGGACAGGTGCAGCTTCAGGAATCTGGCGGTGGAAGC
    GTCCAGGCTGGAGGTTCCCTGAGGCTCAGCTGCACCGCCTCTGGTGCCATTGCG
    TCCGGGTACATTGATAGCCGCTGGTGCATGGCCTGGTTTAGACAAGCGCCAGGC
    AAGGAAAGAGAGGGTGTGGCAGCCATCTGGCCGGGCGGAGGTCTGACTGTGTAC
    GCCGACAGCGTGAAGGGCCGTTTCACTATCTCTCGCGACCACGCCAAGAACACT
    TTGTATCTTCAGATGAACAATCTGAAGCCCGAAGATACAGCCATGTATTACTGT
    GCAGCCGGTAGCCCTAGAATGTGCCCCAGTCTGGAGTTCGGCTTCGATTATTGG
    GGTCAGGGTACTCAGGTCACCGTCAGCTCT
    hIL27 1473 CAGGTGCAGCTTCAAGAATCTGGAGGGGGCCTGGTTCAGCCAGGGGGTTCTCTG
    Ra_VH CGTCTGAGCTGTGCCGCGTCTGGATTCACATTCTCATCCTATCCAATGAGCTGG
    H20- GTGCGTCAGGCTCCCGGTAAAGGGCTGGAATGGGTGTCTACTATCTCCAGCGGA
    DR592 GGCGACACTACCCTGTATGCGGACAGCGTCAAGGGACGCTTCACGTCCAGCAGA
    GACAACGCCAAAAATACCTTGTACTTGCAGCTGAACAGCCTGAAGACGGAGGAT
    ACAGCTATGTACTATTGCGCTAAAAGAATCGACTGCAACTCCGGCTACTGTTAC
    AAGAGAAGCTATTGGGGCCAGGGTACTCAGGTCACCGTGTCTAGCGGAGGTGGC
    TCCCAAGTGCAGTTGCAGGAGTCTGGCGGGGGTTCCGTCCAGGCTGGTGGCTCC
    TTGCGTCTTTCCTGTACTGCGCCGGGGTTTACCAGCAACTCATGCGGCATGGAT
    TGGTATCGTCAAGCGCCTGGTAAGGAGAGGGAATTTGTCTCATCCATCTCCACC
    GACGGCACGACCGGCTATGCTGACAGCGTTAAAGGTCGTTTTACCATTTCTAAG
    GATAAGGCCAAGGATACCGTCTACCTCCAGATGAACTCTCTGAAGCCTGAGGAT
    ACTGGCATGTACTCCTGCAAGACTAAGGATGGCACCATTGCCACGATGGAACTG
    TGTGATTTCGGGTACTGGGGTCAAGGCACCCAGGTTACCGTCTCCAGC
    hIL27 1474 CAGGTCCAGCTTCAGGAAAGTGGCGGAGGCCTTGTCCAACCTGGGGGTTCACTC
    Ra_VH AGACTGTCTTGCGCTGCCAGTGGTTTCACCTTTTCTTCCTACCCCATGTCATGG
    H20- GTGCGCCAGGCCCCAGGGAAGGGATTGGAATGGGTCTCCACAATCTCCTCTGGC
    DR592 GGTGATACCACACTGTACGCTGACTCTGTCAAGGGACGCTTCACTTCCAGCCGT
    GATAACGCCAAGAACACCCTGTACTTGCAACTGAACAGTTTGAAAACCGAGGAT
    ACCGCTATGTATTACTGCGCCAAGCGCATTGATTGCAACTCCGGCTATTGTTAC
    AAGCGCAGCTATTGGGGCCAGGGCACCCAGGTGACTGTCTCCTCTGGTGGCTCA
    GGCGGAAGCGGAGGCTCAGGGCAAGTACAGCTCCAGGAGTCAGGTGGCGGTTCC
    GTACAAGCCGGGGGCAGCCTGCGTCTTAGTTGCACCGCACCAGGGTTCACCTCT
    AACAGCTGCGGAATGGATTGGTACAGGCAAGCGCCCGGCAAGGAACGCGAGTTT
    GTAAGCTCCATCTCCACCGATGGCACAACCGGGTACGCAGACTCTGTGAAGGGG
    CGCTTCACGATCAGCAAGGACAAAGCGAAGGATACTGTGTACCTGCAAATGAAC
    TCCCTCAAGCCCGAAGACACCGGCATGTATTCCTGTAAGACCAAGGACGGCACC
    ATCGCCACTATGGAGCTGTGCGATTTTGGATACTGGGGACAGGGCACCCAGGTG
    ACTGTCTCCTCC
    hIL27 1475 CAAGTACAGTTGCAGGAGAGCGGTGGCGGACTGGTACAGCCAGGCGGTTCCCTG
    Ra_VH CGCTTGAGCTGTGCTGCCTCCGGCTTCACCTTCTCCAGCTACCCTATGTCATGG
    H20- GTGCGCCAGGCCCCTGGCAAAGGTCTGGAATGGGTCTCTACCATCTCATCTGGA
    DR593 GGGGACACAACCCTTTATGCAGACAGCGTCAAAGGACGTTTCACTTCTTCACGG
    GACAACGCGAAGAACACCCTGTACCTTCAGCTGAACTCCCTGAAGACTGAGGAT
    ACCGCAATGTACTATTGCGCCAAGCGGATTGATTGTAATTCCGGCTATTGTTAT
    AAGCGCTCCTATTGGGGGCAGGGGACCCAGGTAACTGTTTCCTCAGGAGGCGGT
    TCCCAGGTTCAGCTCCAGGAGTCTGGTGGAGGCTCCGTCCAAGCCGGGGGCTCA
    CTGCGCCTGTCATGCGCAGCCAGCGGTTACCCCTATAGCAACGGTTATATGGGT
    TGGTTCAGGCAGGCCCCCGGTAAAGAACGCGAGGGCGTCGCTACCATCTACACG
    GGCGACGGCAGGACTTATTACGCCGACTCTGTCAAGGGGCGTTTTACTATCTCT
    CGCGACAATGCCAAGAACACGGTGGACCTTCAAATGTCCAGTCTGAAGCCGGAA
    GACACTGCCATGTATTACTGCGCAGCGCGTGCGGCCCCTCTGTATTCCTCAGGC
    AGCCCTCTGACCCGCGCTCGCTACAACGTGTGGGGCCAAGGCACGCAAGTAACT
    GTGTCCTCT
    hIL27 1476 CAGGTGCAGCTCCAGGAGTCTGGCGGTGGCCTGGTACAGCCGGGAGGCTCCCTG
    Ra_VH CGCCTGAGCTGTGCAGCTTCTGGCTTCACCTTCTCTTCCTACCCAATGTCCTGG
    H20- GTGCGTCAGGCTCCCGGTAAGGGCCTTGAGTGGGTGTCTACCATTTCTTCCGGG
    DR593 GGTGATACCACGTTGTACGCAGACTCCGTGAAGGGCAGGTTCACCAGCTCTCGG
    GACAATGCCAAGAACACTCTGTACTTGCAGCTGAACTCTTTGAAGACCGAGGAT
    ACCGCAATGTACTATTGTGCAAAGAGGATCGACTGTAACTCTGGCTATTGTTAT
    AAGAGAAGCTACTGGGGGCAGGGTACTCAGGTGACCGTCTCAAGCGGCGGAAGC
    GGTGGGTCTGGAGGGAGTGGGCAGGTGCAGCTCCAGGAGTCTGGAGGCGGGAGC
    GTGCAGGCAGGCGGTAGCCTCCGGCTGTCATGCGCCGCTTCCGGTTATCCCTAT
    AGCAACGGATACATGGGATGGTTCCGTCAGGCTCCCGGCAAGGAAAGGGAGGGT
    GTGGCCACGATCTACACAGGGGATGGGAGAACTTATTACGCCGACTCCGTTAAG
    GGACGCTTCACTATCAGCCGCGACAACGCTAAAAACACTGTGGACCTTCAGATG
    TCCAGCTTGAAGCCTGAGGATACCGCCATGTATTACTGTGCAGCTCGCGCCGCT
    CCCCTGTACTCAAGCGGTTCACCCCTCACCCGCGCTCGCTACAACGTCTGGGGG
    CAGGGCACACAGGTGACTGTGTCCTCT
    hIL27 1477 CAGGTGCAGTTGCAAGAGAGCGGCGGGGGCCTGGTCCAGCCTGGGGGCTCACTG
    Ra_VH CGTCTCTCCTGCGCCGCATCTGGATTTACCTTCTCCTCTTATCCTATGAGTTGG
    H20- GTACGCCAGGCTCCTGGCAAGGGTTTGGAGTGGGTTTCCACAATCTCTAGCGGA
    DR594 GGTGACACTACACTTTACGCTGATAGCGTCAAGGGACGCTTTACCTCATCCAGG
    GACAACGCTAAGAACACCCTCTATCTCCAGCTGAACTCCCTCAAGACTGAGGAT
    ACAGCCATGTACTATTGCGCTAAACGCATCGACTGTAACAGCGGATACTGCTAC
    AAGCGTAGCTACTGGGGCCAGGGCACCCAGGTTACCGTCAGCTCTGGAGGTGGG
    TCCCAGGTCCAGTTGCAGGAAAGTGGCGGTGGCTCAGTGCAAGCTGGCGGATCT
    CTGCGCCTGTCCTGTGTGGCCAGCGCGTCTACCTACTGTACCTACGATATGCAC
    TGGTACAGACAAGCGCCTGGTAAAGGTAGGGAGTTTGTGAGCGCTATCGACTCC
    GATGGAACCACGAGGTATGCAGACTCCGTCAAGGGAAGGTTCACTATTTCCCAG
    GGCACAGCCAAAAACACCGTCTACTTGCAGATGAACAGCTTGCAGCCCGAGGAC
    ACCGCGATGTACTATTGCAAAACGGTGTGCGTAGTGGGGTCCCGCTGGAGCGAC
    TACTGGGGCCAGGGAACTCAGGTAACAGTCTCCTCC
    hIL27 1478 CAGGTCCAGCTGCAAGAGTCTGGGGGCGGACTCGTTCAGCCTGGGGGCAGCCTG
    Ra_VH CGGCTCAGCTGTGCAGCCTCCGGCTTCACTTTTTCCAGCTACCCTATGTCTTGG
    H20- GTGCGCCAGGCTCCCGGTAAGGGCCTGGAGTGGGTGTCCACGATTTCTAGTGGG
    DR594 GGTGATACGACCCTGTATGCCGACAGTGTAAAGGGTCGCTTCACAAGCAGTCGT
    GACAACGCTAAAAACACCCTGTACCTTCAGCTCAATTCCCTGAAAACAGAGGAC
    ACTGCTATGTATTACTGCGCGAAGCGTATCGACTGTAACAGCGGGTATTGCTAT
    AAGCGCAGTTATTGGGGCCAGGGCACGCAGGTCACCGTGAGTTCCGGGGGTTCT
    GGTGGCAGCGGCGGTTCTGGGCAGGTTCAGCTTCAGGAGAGTGGTGGCGGGTCC
    GTTCAGGCCGGGGGCTCTTTGCGGCTGTCATGCGTGGCGTCCGCTTCTACCTAC
    TGCACCTATGATATGCACTGGTATCGCCAAGCGCCCGGCAAGGGTCGCGAGTTT
    GTCAGCGCCATCGACTCCGACGGCACGACTCGGTACGCCGACTCTGTCAAGGGG
    CGGTTCACGATCTCCCAGGGCACCGCCAAGAACACAGTGTATCTTCAGATGAAC
    TCTCTGCAACCTGAAGATACTGCAATGTACTATTGTAAGACCGTGTGCGTGGTC
    GGCTCCAGATGGAGCGACTACTGGGGTCAGGGCACCCAGGTGACTGTGAGTAGT
    hIL27 1479 CAGGTGCAACTGCAAGAGTCTGGAGGCGGTCTGGTGCAGCCAGGAGGTAGTCTT
    Ra_VH CGTCTGTCTTGCGCGGCCTCCGGCTTTACATTCTCCAGCTACCCAATGTCCTGG
    H20- GTGCGTCAGGCCCCCGGCAAGGGCCTGGAGTGGGTTTCTACCATCTCTAGTGGC
    DR595 GGTGACACAACCCTGTACGCTGACTCTGTTAAAGGAAGATTTACCTCCAGTCGC
    GACAACGCCAAGAACACACTTTACTTGCAACTGAACTCTCTGAAAACCGAGGAC
    ACCGCCATGTATTACTGCGCTAAGCGTATTGACTGCAATTCAGGCTACTGTTAT
    AAGCGCTCTTACTGGGGCCAGGGCACTCAGGTCACCGTGTCTTCAGGCGGTGGC
    TCTCAGGTGCAGCTCCAGGAAAGCGGTGGGGGCTCCGTCCAAGCCGGTGGCAGC
    CTGACACTTTCCTGTGCTGCCTCCGAATACGCTTACTCAACCTGTAACATGGGC
    TGGTACAGACAGGCTCCTGGCAAGGAAAGAGAGTTGGTGTCCGCTTTCATCTCT
    GACGGCTCCACTTATTACGCCGACTCTGTAAAGGGCAGGTTCACGATCACCCGC
    GACAATGCCAAAAACACCGTCTACTTGCAGATGAACAGCCTGAAGCCGGAAGAC
    ACAGCAATCTACTATTGTAGCGCGAACTGCTATCGGCGTCTGCGCAACTATTGG
    GGCCAGGGCACCCAGGTCACCGTCTCCTCC
    hIL27 1480 CAGGTGCAGCTCCAGGAATCTGGGGGCGGTCTGGTTCAGCCGGGCGGTAGTCTG
    Ra_VH CGGCTCTCCTGTGCCGCAAGCGGTTTTACTTTCTCTAGCTATCCCATGAGTTGG
    H20- GTTCGGCAGGCCCCAGGTAAAGGGTTGGAGTGGGTATCTACCATCAGCTCTGGA
    DR595 GGTGACACTACCCTGTACGCCGACTCTGTGAAGGGCCGTTTCACCTCTTCACGC
    GACAACGCAAAAAATACGCTGTACCTCCAGCTCAATTCACTGAAAACTGAGGAC
    ACCGCTATGTATTACTGTGCGAAGCGCATTGATTGTAACAGCGGATATTGCTAC
    AAGCGCTCCTACTGGGGACAAGGTACGCAGGTGACTGTCTCCAGCGGCGGTAGC
    GGGGGTTCTGGAGGTTCCGGCCAGGTGCAACTGCAAGAGTCCGGGGGTGGCTCC
    GTGCAGGCCGGTGGGTCCCTGACTCTGTCCTGTGCTGCATCAGAATATGCGTAT
    TCCACTTGCAACATGGGTTGGTACAGGCAGGCTCCCGGAAAAGAGCGCGAGCTG
    GTCTCCGCCTTCATCAGTGACGGGTCTACCTATTACGCGGACAGTGTGAAGGGC
    CGCTTCACCATCACACGTGATAACGCCAAGAATACCGTGTATTTGCAAATGAAC
    TCTCTGAAACCCGAGGACACCGCAATCTATTACTGTAGCGCTAACTGCTACCGC
    CGTCTCAGGAACTATTGGGGACAGGGCACGCAGGTCACAGTTTCCTCC
    hIL27 1481 CAGGTACAGCTTCAAGAGTCTGGGGGAGGTTTGGTGCAGCCTGGTGGGTCCTTG
    Ra_VH CGGCTGTCCTGTGCCGCGAGCGGGTTTACGTTCTCTTCCTATCCTATGTCTTGG
    H20- GTGAGGCAAGCGCCGGGCAAGGGCCTTGAATGGGTGTCCACCATCTCTAGCGGA
    DR596 GGCGACACGACCCTTTACGCTGACTCTGTGAAGGGACGCTTTACATCAAGTAGA
    GACAACGCCAAGAATACACTGTATTTGCAGCTGAACTCCCTGAAGACTGAGGAC
    ACTGCCATGTATTACTGCGCTAAGAGAATTGACTGCAACTCAGGCTACTGCTAC
    AAGCGCAGCTACTGGGGCCAGGGAACTCAGGTGACCGTTAGCTCCGGTGGCGGA
    TCTCAGGTACAGTTGCAAGAGTCAGGAGGTGGCCTGGTGCAGCCCGGCGGTAGC
    CTGCGTCTTAGCTGTACTGCCAGCGGCTTGACATTCGATGACTCCGTGATGGGT
    TGGTTTAGACAGGCCCCTGGCAAAGGACGGGAGGCTGTGAGCTGTATCAGCTCT
    TCAGGAGCTAATGCTTTCTACGCCGACTCCGTCAAGGGACGTTTTACAATCTCT
    CGTGATAACGCTAAGAATACTCTGTATTTGCAAATGAACTCTCTGAAGCCAGAG
    GATACCGCTACCTATTACTGCAAGAGAGGCCACGCCTGCGCGGGCTATTACCCC
    ATTCCTTACGACGATTACTGGGGTCAGGGTACACAGGTGACCGTCAGTTCT
    hIL27 1482 CAGGTACAGTTGCAGGAGTCTGGAGGCGGACTGGTGCAACCCGGAGGCAGCCTG
    Ra_VH AGGCTGAGCTGCGCAGCCAGCGGATTTACCTTCTCCTCTTATCCCATGAGCTGG
    H20- GTTCGCCAAGCGCCAGGTAAAGGTCTGGAATGGGTCAGCACAATCAGCTCAGGC
    DR596 GGTGACACTACCCTGTACGCAGACTCTGTGAAAGGCCGGTTCACCTCTTCCAGG
    GATAACGCCAAGAATACGCTCTACCTCCAGCTGAACTCCCTCAAGACTGAAGAC
    ACCGCGATGTACTATTGCGCAAAGAGAATTGATTGTAACAGCGGTTATTGTTAC
    AAACGTAGCTACTGGGGTCAGGGCACCCAGGTCACCGTGTCTTCCGGGGGAAGT
    GGAGGTTCTGGTGGCTCTGGACAGGTACAGTTGCAGGAGAGCGGCGGTGGCCTG
    GTGCAGCCTGGGGGAAGCCTGCGGCTGAGCTGCACTGCGAGCGGTTTGACTTTC
    GATGACTCTGTTATGGGTTGGTTCCGTCAGGCCCCTGGTAAGGGCCGTGAGGCG
    GTTTCCTGCATCTCTTCATCCGGTGCTAACGCTTTTTATGCAGACTCCGTGAAG
    GGTCGCTTTACAATCAGCAGGGATAACGCGAAAAACACCCTCTACCTGCAAATG
    AACTCCCTGAAACCCGAAGACACTGCTACCTATTACTGCAAGAGGGGGCACGCC
    TGCGCTGGCTATTACCCTATCCCTTACGATGACTACTGGGGTCAGGGAACCCAG
    GTCACCGTGTCCTCC
    hIL27 1483 CAAGTGCAGTTGCAGGAAAGCGGAGGCGGACTTGTTCAGCCAGGGGGATCTTTG
    Ra_VH CGCCTCAGCTGTGCCGCTTCAGGGTTTACATTCTCCCTGTCTAGCATGAGCTGG
    H21- GTCCGTCAGGCTCCTGGAAAGGGTCTGGAATGGGTTTCCGCCATTAGCTCCGGC
    DR591 GGTGCCTCCACTTATTACACCGACAGTGTGAAAGGCCGCTTTACAATCAGCCGC
    GACAACGCCAAGAACATGCTGTACTTGCAACTGAACAGCCTGAAAACCGAGGAC
    ACCGCCATGTACTATTGTGCCAAGGGTGGGTCCGGCTACGGCGACGCGAGCCGG
    ATGACCTCCCCAGGCTCCCAGGGCACCCAGGTCACCGTGAGCAGTGGCGGAGGC
    TCCCAGGTTCAGTTGCAGGAGTCTGGAGGGGGCTCCGTGCAGGCTGGCGGAAGC
    CTGCGCCTGAGCTGCACTGCCTCCGGCGCTATCGCTTCAGGATATATTGATTCC
    CGTTGGTGTATGGCCTGGTTTAGGCAGGCTCCTGGAAAGGAGCGCGAAGGCGTG
    GCAGCTATCTGGCCTGGCGGTGGCCTGACCGTATACGCAGATAGTGTCAAGGGC
    CGCTTCACTATCTCCCGCGACCACGCAAAGAACACGCTGTACCTCCAGATGAAT
    AACCTGAAGCCTGAGGACACCGCCATGTATTACTGTGCCGCTGGCTCACCTCGT
    ATGTGCCCCTCCCTGGAGTTCGGCTTTGACTACTGGGGCCAGGGAACCCAGGTC
    ACCGTCTCTTCT
    hIL27 1484 CAGGTGCAGCTTCAGGAGAGCGGAGGTGGCCTGGTTCAGCCTGGTGGGTCACTC
    Ra_VH CGCCTGAGTTGTGCGGCCTCAGGATTTACATTCTCCCTCTCCAGCATGTCTTGG
    H21- GTTAGACAAGCTCCTGGCAAAGGTCTGGAGTGGGTATCCGCCATTAGCTCCGGT
    DR591 GGCGCTTCTACTTACTATACCGACAGCGTGAAGGGTCGCTTCACTATCTCCCGC
    GACAATGCCAAGAACATGCTGTACCTTCAGCTCAATTCTCTGAAGACCGAGGAC
    ACTGCGATGTACTATTGCGCCAAGGGAGGCTCTGGTTATGGCGACGCATCTCGC
    ATGACCTCCCCCGGTTCCCAAGGCACCCAGGTCACGGTCTCCAGCGGAGGCAGT
    GGCGGTTCAGGCGGGAGCGGACAGGTGCAGCTCCAGGAGTCCGGCGGGGGCTCT
    GTGCAGGCTGGAGGCTCCCTTCGTCTGAGCTGCACTGCTTCCGGGGCAATCGCG
    AGCGGCTACATTGATTCTCGTTGGTGTATGGCCTGGTTTCGTCAGGCACCCGGC
    AAGGAGCGCGAAGGCGTTGCTGCAATTTGGCCGGGAGGCGGGTTGACGGTCTAT
    GCGGACTCCGTGAAGGGCCGCTTCACTATCTCCCGCGACCATGCCAAGAACACA
    CTGTATCTTCAGATGAATAACCTGAAGCCTGAGGACACTGCAATGTACTATTGT
    GCCGCAGGCTCTCCCCGTATGTGCCCGTCACTGGAATTTGGGTTTGACTATTGG
    GGCCAAGGCACACAAGTAACCGTGTCCAGC
    hIL27 1485 CAGGTCCAGCTGCAAGAGTCTGGCGGTGGCCTCGTGCAGCCCGGAGGCAGCCTG
    Ra_VH AGGCTCAGCTGTGCCGCAAGTGGATTTACCTTTTCACTCAGCTCTATGTCCTGG
    H21- GTGCGTCAGGCTCCAGGAAAGGGACTGGAGTGGGTGTCTGCTATCTCATCTGGA
    DR592 GGGGCGTCTACATATTACACTGATAGTGTGAAGGGGCGGTTCACCATCAGTCGT
    GATAACGCGAAAAACATGCTGTACCTGCAACTGAACAGTCTGAAGACTGAGGAC
    ACCGCCATGTACTATTGTGCGAAGGGTGGAAGTGGCTACGGTGATGCGTCAAGA
    ATGACCTCTCCCGGTAGTCAGGGAACTCAGGTCACTGTGTCCAGTGGCGGAGGC
    AGCCAGGTGCAGCTCCAGGAAAGTGGAGGGGGTTCTGTCCAGGCAGGGGGCTCC
    CTGCGCCTGAGCTGTACCGCCCCCGGCTTCACCTCCAACTCCTGTGGAATGGAT
    TGGTACAGACAGGCTCCCGGCAAGGAGAGGGAGTTCGTTAGCTCCATCTCTACA
    GACGGAACCACTGGGTACGCCGATAGCGTGAAGGGGCGTTTTACCATCTCCAAA
    GATAAAGCCAAGGATACTGTGTATTTGCAGATGAACTCCCTCAAGCCCGAGGAT
    ACCGGAATGTATAGCTGCAAAACCAAGGACGGTACTATCGCTACGATGGAGCTG
    TGCGACTTTGGCTACTGGGGCCAAGGCACCCAGGTGACCGTTTCTAGC
    hIL27 1486 CAGGTCCAGTTGCAGGAGTCCGGCGGGGGCCTGGTTCAGCCGGGTGGCTCTCTG
    Ra_VH CGCCTGAGCTGCGCCGCTTCTGGCTTCACTTTCTCTCTCAGCTCTATGTCCTGG
    H21- GTCAGACAAGCGCCGGGCAAAGGTTTGGAGTGGGTGTCTGCTATTTCATCCGGT
    DR592 GGCGCGAGTACCTACTATACCGATTCCGTGAAGGGCCGCTTCACTATTAGCCGG
    GACAATGCTAAGAACATGCTGTACCTTCAGCTCAATTCTCTGAAAACCGAGGAC
    ACTGCCATGTATTACTGCGCTAAGGGAGGTTCAGGATACGGCGATGCCTCCAGG
    ATGACTAGCCCAGGCAGCCAAGGGACACAGGTCACCGTTTCCAGTGGGGGCTCC
    GGCGGTTCTGGCGGTAGCGGCCAAGTGCAGCTGCAAGAGTCCGGCGGGGGCAGC
    GTTCAAGCTGGGGGTAGCCTCAGGCTTTCCTGCACAGCTCCAGGTTTCACCAGC
    AACAGTTGCGGAATGGACTGGTATCGCCAAGCGCCAGGTAAGGAGAGGGAGTTT
    GTTTCCAGCATCTCTACCGACGGCACCACGGGATATGCTGATTCTGTGAAGGGA
    CGCTTTACCATCTCTAAGGATAAAGCGAAGGACACCGTGTACTTGCAGATGAAC
    AGCCTGAAGCCCGAGGATACCGGCATGTATAGCTGCAAAACTAAGGACGGAACC
    ATTGCGACAATGGAACTCTGCGATTTCGGATACTGGGGTCAGGGAACCCAGGTG
    ACTGTGTCTAGC
    hIL27 1487 CAGGTCCAGCTCCAGGAATCTGGCGGAGGGCTGGTGCAGCCGGGCGGTAGCCTC
    Ra_VH CGGTTGTCCTGCGCTGCCAGCGGCTTTACCTTTTCCCTCAGCTCCATGTCTTGG
    H21- GTGCGCCAGGCACCCGGAAAAGGATTGGAGTGGGTGTCCGCTATCTCATCCGGG
    DR593 GGAGCCAGCACGTATTACACTGATTCCGTGAAGGGCCGCTTCACCATTTCTCGC
    GATAACGCTAAAAACATGCTGTATTTGCAGCTTAACTCCCTGAAAACAGAAGAT
    ACCGCGATGTATTACTGTGCTAAGGGTGGGTCCGGCTACGGCGACGCATCTCGT
    ATGACCAGCCCTGGCAGCCAGGGCACGCAGGTCACCGTGTCAAGCGGAGGCGGT
    TCCCAGGTTCAGTTGCAGGAGAGCGGTGGCGGTAGCGTGCAGGCTGGGGGTTCC
    CTTCGCCTCTCTTGCGCGGCTTCCGGTTATCCATACAGCAACGGCTATATGGGG
    TGGTTCAGACAGGCACCCGGCAAGGAACGCGAAGGCGTGGCAACCATCTACACT
    GGCGACGGACGCACGTACTATGCTGACAGCGTTAAAGGCCGTTTTACTATCAGC
    CGCGACAATGCGAAGAACACCGTCGATTTGCAGATGTCAAGTCTGAAGCCAGAA
    GACACAGCCATGTACTATTGCGCTGCGAGAGCCGCTCCCCTCTACTCTAGCGGC
    AGCCCCCTGACCCGCGCACGTTACAATGTGTGGGGCCAGGGCACCCAGGTGACC
    GTCTCCTCC
    hIL27 1488 CAGGTGCAGCTTCAAGAATCTGGCGGGGGCTTGGTGCAGCCCGGCGGTAGCCTC
    Ra_VH CGGTTGAGCTGCGCCGCTTCAGGGTTTACCTTCAGCTTGTCATCCATGTCATGG
    H21- GTGCGCCAGGCCCCCGGCAAGGGACTGGAGTGGGTCAGCGCCATCAGTAGCGGG
    DR593 GGAGCGTCAACTTATTACACTGACTCCGTCAAGGGTCGCTTCACAATTAGCCGG
    GACAACGCCAAGAACATGCTGTACCTCCAGTTGAACTCCCTGAAAACTGAGGAC
    ACAGCCATGTACTATTGCGCCAAAGGGGGTAGCGGTTATGGCGACGCTTCCCGC
    ATGACCTCTCCCGGCTCCCAAGGCACCCAGGTCACTGTAAGCTCAGGAGGGAGC
    GGCGGTTCCGGTGGCAGCGGACAGGTCCAGCTCCAGGAGAGTGGAGGCGGATCA
    GTGCAAGCCGGTGGCTCCCTCAGGCTCTCCTGCGCTGCGTCTGGCTACCCATAT
    AGCAACGGCTACATGGGATGGTTCCGCCAGGCCCCAGGCAAAGAGCGGGAGGGC
    GTTGCCACCATCTACACCGGGGATGGCCGTACCTATTACGCAGACTCCGTGAAG
    GGGAGGTTTACCATCTCTCGGGACAATGCCAAAAACACGGTGGACCTCCAGATG
    AGTTCCCTGAAGCCCGAAGACACCGCCATGTATTACTGCGCAGCCAGAGCCGCT
    CCTTTGTACTCCTCAGGTAGCCCCCTCACCCGTGCTCGCTATAATGTATGGGGA
    CAGGGCACTCAAGTGACCGTGTCCTCC
    hIL27 1489 CAGGTTCAGCTTCAGGAGTCTGGTGGGGGCCTGGTGCAGCCAGGTGGCAGCTTG
    Ra_VH CGCCTGTCCTGCGCGGCCAGCGGATTTACTTTCTCTCTCAGCTCCATGTCTTGG
    H21- GTGAGGCAGGCTCCAGGTAAGGGCCTGGAGTGGGTTTCTGCTATTAGCTCCGGG
    DR594 GGAGCTTCCACATATTACACAGATTCTGTGAAAGGTCGTTTCACGATCTCTCGC
    GACAACGCCAAAAACATGCTGTACCTTCAGCTGAACAGCCTGAAAACCGAAGAC
    ACAGCTATGTACTATTGCGCCAAGGGAGGTAGCGGGTACGGCGACGCCTCCAGG
    ATGACAAGTCCCGGTTCCCAGGGCACCCAGGTGACGGTCAGCTCCGGTGGAGGT
    AGTCAAGTCCAACTTCAGGAGTCCGGCGGTGGCTCCGTTCAGGCTGGCGGTTCT
    CTGCGTCTGTCTTGTGTGGCGTCCGCTTCCACCTACTGCACTTATGATATGCAC
    TGGTACAGGCAAGCGCCCGGTAAGGGGCGCGAGTTTGTTTCCGCCATTGATTCC
    GATGGGACCACTCGGTATGCGGACAGCGTCAAGGGCCGCTTCACTATCTCACAG
    GGTACAGCCAAGAACACAGTGTACCTCCAGATGAACTCATTGCAACCCGAGGAC
    ACGGCCATGTACTATTGTAAGACAGTCTGCGTGGTCGGTTCCAGATGGTCAGAC
    TACTGGGGCCAAGGGACCCAAGTCACAGTCTCCTCA
    hIL27 1490 CAGGTGCAACTCCAGGAAAGTGGCGGTGGCCTTGTTCAGCCTGGAGGCTCCCTG
    Ra_VH CGGCTTAGCTGCGCTGCCTCCGGGTTTACTTTCTCACTGTCATCTATGAGCTGG
    H21- GTCCGGCAAGCTCCAGGGAAGGGCCTGGAATGGGTCAGCGCTATCTCTTCCGGC
    DR594 GGAGCCTCAACTTACTATACTGACTCCGTGAAGGGCCGGTTTACCATCAGTCGC
    GACAACGCTAAGAACATGCTGTACCTTCAGCTGAACAGCCTGAAGACTGAAGAT
    ACTGCTATGTACTATTGCGCCAAAGGCGGTTCCGGGTACGGCGACGCCTCTCGG
    ATGACCTCTCCGGGTTCCCAAGGCACCCAGGTTACCGTGTCCAGTGGGGGCTCC
    GGGGGTAGCGGTGGCTCTGGCCAGGTGCAGCTCCAGGAATCCGGTGGCGGGTCC
    GTGCAGGCTGGAGGGTCACTGCGCCTGTCCTGCGTGGCCAGCGCCTCTACCTAC
    TGCACATACGACATGCACTGGTACAGGCAAGCTCCAGGTAAGGGTCGGGAGTTT
    GTCAGCGCTATCGACAGCGACGGCACAACTCGCTATGCGGATAGCGTCAAGGGG
    CGTTTTACCATCAGCCAAGGGACTGCCAAAAACACAGTGTATCTCCAGATGAAC
    TCTCTCCAGCCAGAGGATACTGCCATGTATTACTGCAAGACCGTGTGCGTTGTG
    GGTTCACGTTGGTCCGACTATTGGGGCCAAGGCACACAGGTGACCGTGTCCTCA
    hIL27 1491 CAGGTGCAGCTCCAGGAATCTGGCGGGGGTCTGGTGCAGCCCGGGGGTCTTTG
    Ra_VH CGCCTCTCATGTGCAGCCTCTGGGTTTACCTTCTCTCTGTCCAGCATGTCTTGG
    H21- GTTAGGCAGGCCCCAGGTAAGGGGCTGGAGTGGGTTTCCGCCATCTCATCCGGC
    DR595 GGTGCCAGCACATATTACACCGACTCCGTCAAGGGGAGATTCACCATCAGCCGG
    GACAACGCCAAGAACATGCTGTATCTCCAGCTCAACTCCCTGAAAACCGAGGAC
    ACCGCCATGTATTACTGCGCCAAGGGCGGTTCCGGCTATGGTGATGCTTCAAGG
    ATGACTAGCCCCGGTTCCCAGGGCACCCAAGTCACTGTATCCAGCGGGGGAGGC
    TCCCAGGTGCAGCTTCAGGAGTCTGGCGGTGGCAGCGTGCAGGCCGGGGGCTCC
    CTGACACTGTCCTGTGCCGCTTCCGAGTACGCCTATTCCACGTGTAACATGGGA
    TGGTATCGCCAGGCTCCTGGCAAGGAGCGCGAGCTGGTCAGCGCCTTTATCTCC
    GACGGCAGCACTTATTACGCCGACTCCGTGAAGGGACGCTTCACAATCACTCGC
    GACAACGCCAAGAATACTGTGTACCTCCAGATGAACAGCCTCAAGCCTGAGGAT
    ACCGCCATCTATTACTGCTCTGCTAATTGCTATCGTCGGCTGCGCAACTACTGG
    GGACAAGGAACACAGGTGACCGTGTCATCT
    hIL27 1492 CAGGTTCAACTCCAGGAAAGCGGAGGTGGACTTGTGCAGCCTGGCGGTTCCCTT
    Ra_VH CGGCTGTCCTGCGCTGCCTCTGGCTTCACTTTCTCACTCTCATCCATGAGCTGG
    H21- GTCCGCCAGGCCCCCGGCAAAGGCCTGGAGTGGGTGAGTGCTATCTCCTCTGGC
    DR595 GGAGCTTCCACCTACTATACTGACTCTGTGAAGGGCCGCTTCACCATTAGTCGG
    GACAACGCCAAGAACATGCTGTACTTGCAGCTGAACTCACTGAAGACCGAGGAC
    ACTGCCATGTACTATTGCGCTAAGGGAGGCTCCGGGTACGGCGACGCCTCCAGA
    ATGACATCTCCCGGCTCTCAGGGGACCCAGGTCACGGTGTCCAGCGGCGGGTCC
    GGGGGCTCCGGCGGATCTGGTCAGGTACAACTTCAGGAGTCAGGCGGAGGCAGC
    GTTCAAGCCGGAGGCTCCTTGACACTGTCCTGCGCGGCCTCTGAGTACGCATAC
    AGTACCTGCAACATGGGCTGGTATCGGCAGGCCCCCGGAAAGGAGCGCGAATTG
    GTTTCTGCTTTCATCAGCGATGGATCTACTTATTACGCCGACTCTGTAAAAGGT
    AGATTCACTATTACTCGTGACAACGCTAAAAACACGGTGTATCTGCAAATGAAC
    AGCCTGAAGCCCGAGGACACTGCCATTTATTACTGTTCCGCTAATTGTTACCGT
    AGGCTGCGCAATTACTGGGGTCAGGGTACTCAGGTCACTGTATCCAGC
    hIL27 1493 CAAGTCCAACTGCAAGAGTCTGGTGGAGGCTTGGTACAGCCCGGAGGGAGCCTG
    Ra_VH CGCCTCTCCTGCGCAGCCTCTGGCTTCACCTTCTCTCTCAGCTCAATGTCCTGG
    H21- GTGAGGCAGGCCCCCGGAAAGGGCCTTGAGTGGGTGTCTGCTATCTCCTCTGGA
    DR596 GGGGCCAGCACCTACTATACAGACAGCGTCAAGGGCAGATTTACCATTAGTCGT
    GATAATGCTAAAAATATGCTCTACTTGCAGCTGAACTCCCTGAAAACAGAGGAC
    ACCGCCATGTACTATTGCGCCAAGGGCGGTTCAGGATATGGAGATGCCAGTCGC
    ATGACCAGCCCCGGTAGTCAGGGTACACAAGTGACCGTATCTAGCGGCGGAGGC
    TCTCAGGTGCAGCTCCAGGAGTCTGGAGGGGGCTTGGTGCAGCCGGGAGGCTCT
    CTCCGCCTTAGTTGTACTGCCTCTGGACTGACTTTCGATGACTCAGTGATGGGC
    TGGTTCCGCCAGGCCCCAGGCAAGGGCAGAGAGGCCGTGTCTTGTATCAGCAGT
    AGCGGGGCCAACGCTTTCTATGCCGACTCTGTCAAGGGCCGTTTCACCATCTCT
    CGCGACAACGCTAAGAATACCCTGTACCTCCAAATGAACTCCCTGAAACCCGAG
    GACACAGCAACGTATTACTGTAAGAGAGGTCATGCTTGTGCGGGGTATTACCCA
    ATTCCCTATGACGATTACTGGGGCCAGGGGACCCAGGTAACAGTAAGCTCC
    hIL27 1494 CAGGTGCAGTTGCAGGAGTCCGGCGGTGGGCTGGTCCAGCCTGGGGGCAGCCTG
    Ra_VH CGCCTTAGTTGCGCCGCTTCCGGCTTCACCTTTAGCCTTAGCAGTATGAGCTGG
    H21- GTGAGACAGGCCCCAGGCAAGGGGCTGGAGTGGGTGTCCGCAATTTCTTCCGGG
    DR596 GGTGCGAGCACCTATTACACTGATAGCGTTAAGGGACGTTTCACCATTTCTCGC
    GACAACGCTAAGAACATGCTGTACCTCCAGCTCAACAGCCTGAAGACAGAAGAT
    ACTGCTATGTATTACTGTGCAAAGGGAGGCAGCGGCTACGGCGATGCGAGCCGG
    ATGACCAGTCCGGGGTCCCAGGGCACTCAGGTCACCGTTAGCTCCGGCGGGTCT
    GGCGGTTCCGGCGGTTCCGGTCAAGTTCAGCTGCAAGAGAGCGGTGGGGGACTG
    GTGCAGCCGGGAGGCTCCCTGCGCCTGAGTTGCACCGCTTCCGGTCTGACCTTT
    GACGATTCCGTTATGGGCTGGTTTCGCCAAGCCCCTGGCAAGGGGAGGGAAGCT
    GTGTCCTGCATTTCTAGCTCTGGCGCTAACGCCTTCTATGCCGATTCCGTGAAG
    GGCCGCTTCACGATCAGCCGCGACAACGCCAAGAACACCCTGTACCTGCAAATG
    AACTCATTGAAGCCCGAGGATACCGCCACCTATTACTGCAAACGCGGCCATGCT
    TGCGCGGGCTATTACCCGATTCCTTACGACGATTACTGGGGTCAAGGCACCCAG
    GTGACAGTCTCCTCC
    hIL27 1495 CAGGTGCAGCTCCAGGAATCCGGCGGAGGCTCTGTGCAGGCTGGTGGCAGCCTG
    Ra_VH AGGCTGAGTTGCCGCGCTTCCGGCTCCACTTATAGCAACTACTGTCTGGGCTGG
    H22- TTTCGCCAGACAACCGGAAAAGAAAGAGAAGGCGTGGCCGTGATTAACTGGGTC
    DR591 GGCGGGATGCTCTACTTTGCCGATAGTGTGAAAGGTCGTTTCACGGTCTCCCAG
    GACCAGGCCAAAAACACCGTCTACCTCCAGATGAACTCCCTCAAGCCTGAGGAT
    ACTGCGATGTATTACTGCGCCGCTGAGTCCGTCTCTTCCTTCTCCTGCGGGGGC
    TGGCTGACACGCCCCGACAGAGTCCCTTATTGGGGCCAAGGAACTCAGGTAACA
    GTGTCTTCCGGTGGCGGTTCCCAGGTACAGCTTCAGGAGTCTGGTGGCGGTTCT
    GTTCAGGCCGGGGGCTCCCTGCGCCTGTCCTGCACTGCTTCTGGCGCTATCGCA
    AGCGGATATATTGATAGTCGCTGGTGTATGGCATGGTTCAGACAAGCCCCTGGG
    AAGGAGCGCGAAGGCGTGGCGGCCATCTGGCCAGGCGGTGGGCTGACTGTCTAC
    GCTGACAGCGTTAAAGGTCGCTTCACCATCTCAAGAGATCATGCTAAGAACACT
    CTCTACCTCCAGATGAACAATCTGAAGCCTGAGGACACCGCCATGTATTACTGT
    GCTGCGGGAAGCCCCCGCATGTGTCCTAGCCTGGAGTTCGGGTTCGACTACTGG
    GGTCAGGGGACCCAGGTCACAGTGTCCAGC
    hIL27 1496 CAAGTGCAACTCCAAGAATCTGGAGGTGGCTCTGTGCAGGCGGGCGGTTCCCTG
    Ra_VH AGACTGTCTTGCAGAGCAAGCGGCAGTACTTACTCTAACTACTGTTTGGGATGG
    H22- TTCCGGCAGACAACCGGCAAAGAGAGGGAAGGCGTGGCCGTAATCAACTGGGTG
    DR591 GGTGGCATGTTGTACTTCGCGGATAGCGTTAAGGGCCGCTTCACAGTTTCCCAG
    GATCAGGCCAAGAACACCGTGTACTTGCAAATGAACTCTCTGAAGCCGGAGGAC
    ACCGCCATGTATTACTGCGCTGCCGAGTCAGTATCTTCATTTAGCTGTGGCGGA
    TGGTTGACTAGGCCGGACAGGGTCCCTTACTGGGGCCAGGGCACACAGGTGACT
    GTGTCCTCTGGCGGAAGCGGGGGTTCAGGAGGCTCTGGGCAGGTGCAGTTGCAG
    GAGAGCGGCGGGGGCTCTGTCCAGGCTGGAGGGAGCCTCAGGCTCTCATGCACA
    GCCTCTGGGGCTATCGCATCAGGATATATTGATTCTCGGTGGTGCATGGCTTGG
    TTCAGACAGGCACCGGGAAAGGAGCGCGAAGGTGTGGCGGCCATCTGGCCTGGC
    GGGGGCCTGACCGTGTATGCCGATTCCGTGAAGGGTCGTTTCACCATCTCCCGT
    GACCACGCGAAGAATACCCTGTATTTGCAGATGAATAACCTGAAGCCCGAAGAT
    ACCGCCATGTATTACTGCGCTGCCGGGAGCCCACGTATGTGCCCTTCTTTGGAG
    TTCGGTTTCGATTACTGGGGTCAGGGGACCCAGGTGACCGTCTCCTCC
    hIL27 1497 CAGGTGCAACTCCAGGAGAGCGGCGGGGGCAGTGTGCAGGCCGGAGGTTCCTTG
    Ra_VH CGCCTGTCTTGTCGTGCGTCAGGAAGCACATACAGCAACTACTGCCTCGGGTGG
    H22- TTCAGGCAGACTACCGGCAAGGAACGTGAAGGTGTAGCCGTGATTAACTGGGTG
    DR592 GGCGGAATGCTGTACTTCGCGGACTCCGTGAAGGGCCGCTTCACCGTGTCTCAG
    GACCAGGCCAAGAACACCGTTTATCTCCAGATGAACTCCCTGAAGCCGGAGGAC
    ACGGCCATGTATTACTGCGCTGCCGAGTCCGTGTCTTCATTCTCCTGCGGTGGC
    TGGTTGACTCGCCCTGATCGCGTGCCCTATTGGGGTCAGGGCACACAGGTGACA
    GTCAGCTCTGGTGGAGGTTCACAGGTCCAGCTCCAGGAGAGTGGCGGGGGTAGC
    GTTCAGGCCGGAGGCTCCCTGCGCCTGAGCTGTACCGCCCCAGGCTTTACCTCT
    AATAGCTGTGGAATGGACTGGTATCGTCAGGCTCCTGGTAAGGAACGCGAGTTC
    GTCTCTAGCATCTCAACCGACGGGACTACCGGCTATGCGGACTCTGTGAAGGGT
    CGTTTCACCATTAGCAAGGACAAGGCCAAGGACACAGTGTACCTTCAGATGAAC
    TCACTGAAGCCCGAGGACACTGGCATGTATAGCTGCAAAACTAAAGATGGAACC
    ATCGCCACTATGGAACTGTGCGATTTCGGCTACTGGGGCCAGGGCACGCAGGTG
    ACCGTGTCTTCC
    hIL27 1498 CAGGTGCAGTTGCAGGAGAGTGGTGGAGGCAGTGTGCAGGCCGGTGGCTCTCTT
    Ra_VH AGACTGAGCTGCCGCGCCAGTGGCTCCACCTACTCCAACTATTGTCTGGGATGG
    H22- TTTCGTCAGACCACTGGTAAAGAGCGGGAGGGGGTGGCCGTCATCAACTGGGTT
    DR592 GGGGGTATGCTGTACTTTGCTGACTCTGTCAAGGGGCGGTTCACAGTCTCACAG
    GACCAAGCCAAGAATACCGTGTACCTCCAGATGAACAGTCTGAAGCCGGAGGAT
    ACCGCTATGTATTACTGCGCAGCCGAATCCGTCAGCTCTTTCTCCTGCGGAGGC
    TGGCTCACGCGCCCTGACAGGGTTCCCTACTGGGGCCAAGGAACGCAGGTGACA
    GTTTCTAGTGGTGGGTCCGGCGGTAGCGGAGGCTCCGGCCAGGTGCAGCTCCAG
    GAATCCGGCGGAGGTTCCGTGCAGGCCGGAGGCTCCCTCCGCCTGAGCTGCACA
    GCCCCCGGTTTCACCTCCAATTCTTGCGGCATGGACTGGTATCGCCAGGCTCCG
    GGCAAGGAGCGTGAGTTCGTGTCCAGTATTTCTACGGACGGCACTACCGGGTAC
    GCTGACTCCGTTAAGGGCCGCTTTACCATTAGCAAAGACAAGGCGAAGGACACA
    GTCTATCTCCAGATGAATAGTCTGAAGCCGGAGGATACCGGCATGTACTCATGC
    AAAACAAAGGATGGCACGATTGCGACAATGGAGCTGTGCGACTTCGGGTATTGG
    GGCCAGGGCACGCAGGTGACGGTGTCCTCC
    hIL27 1499 CAGGTACAGCTCCAGGAATCCGGTGGGGGTTCAGTTCAGGCCGGGGGTAGCCTT
    Ra_VH CGGCTGTCCTGCCGCGCGAGTGGCTCCACCTATAGCAACTACTGCCTGGGATGG
    H22- TTCCGCCAGACCACAGGCAAGGAGCGTGAGGGCGTCGCTGTAATAAATTGGGTT
    DR593 GGGGGAATGTTGTACTTTGCGGACAGTGTGAAGGGACGTTTCACCGTCAGTCAG
    GACCAGGCCAAGAACACCGTTTACCTCCAGATGAACAGCCTCAAGCCCGAGGAT
    ACCGCCATGTATTACTGCGCGGCTGAGTCTGTTTCTTCCTTCTCTTGTGGGGGC
    TGGCTGACCAGGCCCGACAGAGTCCCATACTGGGGCCAGGGGACCCAGGTGACA
    GTTAGCTCCGGCGGTGGCTCACAGGTGCAGCTGCAAGAGAGCGGCGGTGGCTCC
    GTCCAAGCGGGCGGGTCACTCAGACTGTCTTGCGCAGCTAGTGGTTACCCGTAT
    TCAAACGGTTACATGGGATGGTTTAGACAGGCACCAGGCAAAGAGCGCGAAGGC
    GTCGCTACCATCTACACAGGAGATGGCCGCACCTATTACGCCGACAGCGTGAAA
    GGCAGGTTTACAATTAGTCGCGACAACGCCAAGAACACTGTCGATCTTCAGATG
    TCTTCCTTGAAGCCAGAAGACACCGCCATGTATTACTGTGCAGCGCGGGCAGCC
    CCACTTTATTCCAGCGGCTCTCCCCTCACCCGCGCCCGGTATAACGTCTGGGGC
    CAAGGTACTCAGGTGACCGTGAGTTCT
    hIL27 1500 CAGGTGCAGTTGCAGGAATCAGGTGGAGGCTCTGTGCAGGCCGGTGGATCTCTG
    Ra_VH CGGCTCAGCTGCCGGGCGTCCGGGAGCACTTACAGCAATTACTGTTTGGGGTGG
    H22- TTTCGGCAGACCACTGGTAAGGAGAGAGAGGGAGTGGCCGTTATCAACTGGGTC
    DR593 GGAGGTATGCTCTACTTCGCTGACAGCGTCAAGGGACGCTTCACCGTGTCCCAG
    GACCAGGCTAAGAATACCGTTTATCTCCAGATGAATAGCCTGAAGCCTGAGGAC
    ACCGCTATGTATTACTGTGCGGCTGAGAGCGTCAGCTCTTTCTCCTGCGGTGGA
    TGGCTCACACGCCCCGACCGTGTCCCATATTGGGGACAAGGCACTCAGGTGACC
    GTCAGCTCAGGAGGCAGCGGGGGTAGCGGGGGTTCCGGCCAAGTGCAGCTCCAG
    GAGTCTGGGGGCGGAAGCGTGCAGGCCGGTGGGAGCTTGCGCCTGTCCTGTGCT
    GCGTCTGGCTACCCTTACAGTAACGGCTATATGGGCTGGTTCCGGCAGGCCCCT
    GGCAAGGAAAGGGAGGGTGTGGCCACTATCTACACTGGTGATGGTAGGACATAT
    TACGCCGATAGCGTGAAGGGCCGGTTCACGATCTCTCGTGATAACGCCAAAAAT
    ACCGTGGATCTTCAGATGTCATCCCTCAAGCCCGAGGATACCGCTATGTACTAT
    TGCGCAGCCCGCGCTGCCCCGCTCTACAGCAGTGGAAGCCCGTTGACCCGCGCC
    CGTTACAACGTGTGGGGTCAGGGCACACAAGTCACTGTCTCCTCA
    hIL27 1501 CAAGTCCAACTTCAGGAGTCAGGGGGAGGTTCTGTTCAAGCCGGGGGTTCACTG
    Ra_VH AGGCTCTCTTGCCGCGCCTCCGGCTCAACATACTCCAACTATTGTCTGGGCTGG
    H22- TTCAGGCAGACAACCGGGAAGGAGCGCGAGGGTGTGGCCGTCATCAACTGGGTC
    DR594 GGCGGGATGCTGTACTTTGCAGATTCCGTGAAGGGCCGGTTTACAGTGAGCCAG
    GACCAGGCTAAGAACACCGTGTACCTGCAAATGAACTCTCTGAAACCCGAGGAT
    ACAGCGATGTATTACTGCGCTGCGGAGTCCGTGTCTAGCTTCTCTTGCGGGGGC
    TGGCTGACCCGTCCTGATAGAGTCCCATACTGGGGACAGGGGACACAGGTGACC
    GTGAGCAGTGGGGGTGGCAGCCAGGTGCAGCTTCAGGAAAGCGGAGGTGGCTCA
    GTACAGGCGGGAGGCAGTCTGCGCCTGTCTTGCGTGGCCTCCGCATCCACCTAT
    TGCACCTACGACATGCACTGGTACAGGCAGGCACCTGGCAAGGGTCGCGAGTTT
    GTCAGTGCTATCGACTCCGACGGCACCACTCGGTACGCAGATTCCGTCAAGGGC
    CGGTTTACCATCTCCCAGGGCACAGCTAAAAACACTGTTTACCTCCAAATGAAC
    TCCCTCCAGCCTGAGGATACCGCTATGTATTACTGCAAGACAGTCTGTGTAGTG
    GGCTCCCGTTGGTCCGATTACTGGGGCCAGGGGACCCAAGTTACGGTTTCTAGC
    hIL27 1502 CAAGTCCAACTCCAGGAAAGCGGGGGTGGCTCAGTCCAAGCAGGGGGCTCTCTC
    Ra_VH AGACTGAGTTGCAGGGCAAGCGGTTCCACCTACTCAAACTACTGCCTCGGTTGG
    H22- TTTCGGCAGACTACCGGCAAGGAAAGGGAGGGCGTGGCGGTCATTAACTGGGTA
    DR594 GGGGGTATGCTCTACTTTGCAGACTCCGTGAAGGGCAGATTTACAGTATCCCAG
    GACCAGGCTAAGAACACGGTGTACCTGCAAATGAACTCTCTGAAGCCAGAGGAC
    ACCGCCATGTACTATTGCGCGGCAGAGTCAGTGAGCAGTTTTTCTTGTGGGGGC
    TGGCTCACCCGCCCGGACCGCGTGCCTTACTGGGGACAAGGAACGCAGGTTACA
    GTCTCTTCCGGCGGAAGCGGGGGCAGTGGTGGCAGCGGTCAGGTTCAGCTTCAG
    GAGAGTGGCGGAGGCAGCGTGCAGGCAGGGGGTTCCCTGAGGCTGTCCTGTGTG
    GCCTCTGCGAGTACGTATTGCACCTACGACATGCACTGGTATCGCCAGGCTCCT
    GGTAAGGGCCGTGAGTTCGTGTCCGCCATCGACAGCGACGGAACCACACGGTAC
    GCTGATTCCGTGAAAGGCAGGTTCACTATTTCCCAAGGAACTGCCAAAAACACT
    GTCTACCTCCAGATGAACAGCCTCCAGCCTGAGGATACAGCCATGTACTATTGC
    AAGACTGTGTGCGTGGTCGGCTCTCGTTGGTCCGACTACTGGGGCCAGGGCACC
    CAGGTCACCGTGTCCAGT
    hIL27 1503 CAGGTGCAGCTCCAGGAGAGCGGTGGCGGGAGTGTTCAGGCGGGCGGTAGCCTG
    Ra_VH AGACTGTCATGCAGAGCATCTGGCTCTACGTACTCTAACTACTGTCTTGGCTGG
    H22- TTCCGCCAGACGACCGGAAAGGAGCGTGAGGGCGTCGCTGTGATTAACTGGGTG
    DR595 GGCGGGATGTTGTACTTCGCCGATTCCGTGAAGGGCAGATTCACTGTGAGCCAG
    GATCAGGCTAAGAACACTGTGTACCTTCAGATGAACAGCTTGAAGCCCGAAGAC
    ACTGCCATGTACTATTGTGCAGCTGAATCTGTGAGCAGTTTCTCATGCGGTGGG
    TGGCTTACCAGACCGGATAGAGTGCCTTACTGGGGCCAGGGGACCCAGGTTACC
    GTGTCTAGCGGGGGTGGATCTCAGGTGCAGCTCCAGGAGTCCGGCGGGGGCTCC
    GTTCAGGCTGGGGGTAGTCTCACTCTGTCCTGTGCCGCTTCTGAGTACGCCTAC
    AGTACATGCAACATGGGCTGGTATCGCCAGGCTCCGGGGAAGGAACGCGAACTT
    GTGAGCGCCTTCATCTCCGATGGCTCTACCTATTACGCCGACTCCGTGAAGGGC
    AGGTTTACCATCACTCGCGACAACGCTAAGAACACTGTCTACTTGCAGATGAAC
    TCACTGAAACCCGAGGATACTGCCATCTATTACTGTTCCGCTAACTGCTATAGG
    CGGCTGAGAAACTATTGGGGACAGGGGACCCAGGTGACTGTCTCTAGC
    hIL27 1504 CAAGTGCAACTCCAGGAAAGTGGAGGTGGCTCCGTGCAAGCCGGAGGCAGTCTC
    Ra_VH CGCCTGAGCTGTCGTGCGAGCGGTTCCACCTATAGCAACTACTGCCTGGGATGG
    H22- TTTAGACAGACAACCGGGAAGGAGCGGGAGGGAGTCGCGGTGATAAATTGGGTG
    DR595 GGCGGTATGCTGTACTTCGCGGATTCTGTCAAGGGGAGATTCACCGTGAGCCAG
    GATCAGGCGAAGAACACTGTGTACCTTCAGATGAACTCTCTCAAGCCGGAGGAC
    ACAGCCATGTACTATTGTGCTGCCGAGTCTGTTTCATCCTTCTCCTGTGGCGGT
    TGGCTGACCCGCCCAGATCGCGTGCCTTACTGGGGCCAGGGTACTCAGGTCACC
    GTCTCTTCCGGGGGTTCAGGCGGTAGCGGTGGCTCCGGCCAGGTTCAACTCCAG
    GAAAGCGGAGGCGGTTCTGTGCAAGCCGGGGGCTCCCTGACCCTGTCCTGTGCT
    GCCAGCGAGTACGCCTATAGCACTTGTAACATGGGATGGTATCGCCAGGCCCCA
    GGAAAAGAACGCGAGCTTGTGAGTGCTTTTATCTCTGACGGGTCCACCTATTAC
    GCGGACTCTGTGAAAGGTCGCTTCACAATCACCCGCGATAACGCAAAGAACACT
    GTCTACCTTCAGATGAACTCCCTGAAGCCCGAGGACACTGCGATTTATTACTGT
    AGCGCCAACTGTTACCGCCGTCTCCGCAACTACTGGGGACAGGGGACCCAGGTG
    ACCGTCTCATCC
    hIL27 1505 CAGGTCCAACTTCAGGAGTCTGGCGGAGGCAGCGTGCAAGCGGGTGGGAGCCTG
    Ra_VH CGCCTTTCCTGCCGCGCGTCTGGCAGCACCTACTCCAACTACTGCCTGGGATGG
    H22- TTTCGCCAGACCACAGGTAAGGAGCGTGAAGGTGTGGCCGTCATCAACTGGGTC
    DR596 GGCGGTATGCTGTATTTCGCTGATTCCGTTAAGGGCAGATTTACTGTGAGTCAG
    GACCAGGCAAAGAACACAGTGTACCTTCAGATGAATAGCCTGAAGCCCGAAGAC
    ACTGCCATGTACTATTGCGCAGCCGAATCTGTGTCTAGCTTTTCCTGCGGTGGG
    TGGCTGACCCGCCCTGATCGCGTGCCATACTGGGGGCAGGGCACCCAGGTGACT
    GTATCTTCCGGGGGAGGCTCCCAGGTCCAGTTGCAGGAGTCCGGCGGAGGCCTG
    GTACAGCCTGGTGGATCTCTCCGCCTCTCTTGCACCGCGTCCGGGCTTACCTTC
    GATGACTCTGTCATGGGCTGGTTTCGGCAGGCTCCTGGTAAGGGCCGTGAAGCC
    GTGTCCTGCATCTCCTCTTCAGGAGCGAACGCTTTCTATGCTGATAGCGTTAAA
    GGCCGTTTCACCATCTCCCGTGATAACGCTAAGAACACCCTCTACCTTCAAATG
    AACTCCCTCAAGCCAGAGGACACCGCCACATATTACTGTAAACGCGGCCATGCT
    TGCGCGGGATATTACCCCATCCCTTATGACGATTACTGGGGTCAAGGGACACAG
    GTCACTGTCAGCTCC
    hIL27 1506 CAGGTGCAACTTCAGGAGTCCGGTGGCGGTTCCGTGCAGGCTGGTGGCAGCCTG
    Ra_VH AGGCTGAGCTGTCGCGCCAGCGGGTCCACCTACTCTAACTATTGTCTGGGATGG
    H22- TTCCGGCAGACCACAGGCAAGGAGCGCGAGGGAGTCGCTGTAATCAACTGGGTA
    DR596 GGTGGGATGCTGTACTTCGCCGATAGTGTAAAAGGCCGCTTCACCGTGTCACAG
    GACCAAGCCAAGAACACAGTCTACCTCCAGATGAACTCCCTGAAGCCAGAGGAC
    ACCGCCATGTATTACTGCGCCGCTGAATCCGTCAGCTCTTTCTCTTGCGGCGGT
    TGGCTGACCCGCCCCGACCGTGTCCCCTACTGGGGCCAGGGCACTCAGGTGACT
    GTGAGCAGTGGTGGCAGCGGGGGCTCCGGTGGAAGCGGCCAGGTTCAGCTCCAG
    GAATCCGGGGGCGGACTCGTCCAGCCAGGGGGCAGCCTGCGGCTGTCCTGCACC
    GCAAGCGGCCTGACCTTCGACGATAGCGTCATGGGATGGTTCCGTCAAGCCCCT
    GGCAAGGGGAGGGAGGCCGTCAGCTGTATTAGCTCTAGCGGCGCTAACGCCTTC
    TATGCCGATTCTGTTAAGGGTAGGTTCACAATCTCCCGCGACAACGCCAAAAAT
    ACGCTGTATCTCCAGATGAACAGCCTGAAGCCCGAGGACACCGCAACCTATTAC
    TGTAAGAGGGGACACGCATGTGCCGGTTATTACCCTATCCCCTACGATGACTAC
    TGGGGGCAAGGTACTCAGGTCACCGTTTCCTCA
    hIL27 1507 CAGGTGCAACTTCAGGAGAGTGGAGGCGGTAGCGTCCAAGCTGGGGGTTCCCTG
    Ra_VH AGACTTTCATGTAGAGCTTCCCGTTCTCCTTACGGAAATTACTGTCTGGGCTGG
    H23- TTCCGCCAGTCCACTGGTAAGGAACGCGAGGGTGTGGCTGTGATAAATTGGGTG
    DR591 GGTGGAATGCTGTACTTTGCCGACTCTGTTAAGGGTAGATTCACTGTGTCCCAA
    GATCATGCCAAGAACACCGTCACCCTTCAGATGAACTCCCTGAAGCCGGAAGAC
    ACCGCTATGTACTATTGTGCTGCCGAGTCCGTGTCCTCTTTCTCTTGCGGCGGT
    TGGCTGACCAGACCGGACAGGGTTCCGTATTGGGGCCAAGGCACCCAGGTCACT
    GTGAGTTCTGGAGGGGGTTCCCAGGTCCAACTCCAAGAAAGCGGAGGCGGTTCC
    GTCCAGGCTGGCGGTTCTCTGCGCCTGAGCTGCACCGCCAGCGGGGCCATTGCG
    TCTGGTTACATCGACAGTAGATGGTGTATGGCGTGGTTTCGGCAGGCTCCTGGA
    AAGGAACGCGAGGGCGTTGCTGCCATCTGGCCAGGGGGTGGCCTGACAGTCTAT
    GCGGACTCCGTGAAGGGGCGCTTCACCATTAGCAGAGACCACGCAAAAAACACT
    CTGTATTTGCAGATGAATAACCTGAAGCCCGAAGACACTGCCATGTACTATTGT
    GCTGCCGGTTCTCCGCGCATGTGCCCATCCCTGGAGTTCGGATTCGACTACTGG
    GGACAGGGCACCCAGGTGACGGTGTCCAGT
    hIL27 1508 CAGGTCCAGTTGCAGGAGTCAGGGGGCGGTAGCGTCCAGGCAGGGGGCAGCCTG
    Ra_VH CGCCTGTCCTGCCGGGCCAGCAGAAGCCCCTACGGAAATTACTGTCTGGGCTGG
    H23- TTCCGGCAGAGCACTGGGAAGGAGCGCGAGGGCGTCGCCGTAATCAACTGGGTC
    DR591 GGCGGGATGCTGTATTTCGCCGACAGTGTGAAGGGACGCTTTACTGTGAGTCAG
    GACCACGCAAAGAATACAGTCACGTTGCAGATGAACTCCCTGAAGCCTGAGGAC
    ACCGCTATGTACTATTGCGCGGCTGAGTCAGTGTCTAGCTTCAGCTGTGGTGGC
    TGGCTCACTCGTCCTGATCGCGTACCATATTGGGGTCAGGGGACTCAGGTCACC
    GTGAGTAGCGGCGGAAGTGGAGGCAGCGGTGGGAGCGGCCAAGTTCAGTTGCAG
    GAGAGCGGCGGGGGCTCTGTGCAGGCTGGTGGCTCCCTGCGTCTGTCCTGCACC
    GCGTCCGGGGCCATCGCCAGCGGATACATCGACAGTAGGTGGTGTATGGCATGG
    TTCCGTCAGGCCCCTGGTAAGGAGCGCGAGGGCGTGGCCGCTATTTGGCCGGGT
    GGGGGACTCACCGTGTATGCTGACTCCGTAAAGGGTCGCTTCACTATCTCTCGC
    GATCACGCCAAGAACACCCTGTACTTGCAGATGAACAATCTGAAGCCCGAGGAC
    ACCGCTATGTATTACTGCGCAGCTGGAAGCCCCAGGATGTGTCCGAGCCTGGAG
    TTCGGCTTCGACTACTGGGGGCAGGGGACTCAGGTGACCGTGTCCTCT
    hIL27 1509 CAAGTCCAGCTTCAGGAAAGCGGCGGTGGAAGCGTGCAGGCTGGAGGCAGCCTG
    Ra_VH AGACTCAGCTGCCGCGCTTCAAGGTCCCCCTACGGTAACTACTGCCTGGGCTGG
    H23- TTTCGCCAGAGTACAGGCAAGGAAAGGGAAGGTGTGGCCGTTATCAACTGGGTG
    DR592 GGCGGTATGCTGTACTTTGCCGACTCCGTCAAGGGCCGTTTTACAGTGTCCCAG
    GACCACGCCAAGAACACGGTCACGCTTCAGATGAACAGCCTGAAGCCCGAGGAC
    ACCGCTATGTATTACTGTGCTGCCGAGTCCGTTAGCAGTTTCTCCTGCGGCGGA
    TGGCTGACCCGCCCTGACCGCGTTCCCTACTGGGGGCAGGGCACTCAGGTGACG
    GTCAGCTCTGGGGGCGGGTCCCAGGTTCAGCTGCAAGAGAGTGGTGGAGGCTCC
    GTACAGGCCGGGGGATCTCTTCGCCTGTCCTGTACTGCTCCGGGCTTCACGAGT
    AACTCCTGTGGGATGGACTGGTATCGCCAAGCGCCCGGCAAGGAGCGCGAGTTC
    GTAAGTAGCATCTCAACAGACGGCACGACCGGCTACGCCGATTCCGTGAAGGGC
    CGCTTTACCATTAGCAAGGACAAGGCCAAGGACACTGTGTATCTGCAAATGAAC
    TCCCTGAAACCCGAGGATACGGGCATGTACTCTTGCAAGACTAAGGATGGCACG
    ATTGCCACAATGGAGCTGTGCGATTTCGGATATTGGGGCCAGGGCACCCAGGTG
    ACTGTCTCCTCT
    hIL27 1510 CAGGTGCAACTTCAGGAAAGTGGGGGCGGTTCCGTGCAGGCAGGGGGCTCTCTG
    Ra_VH CGTCTGTCTTGCAGAGCCAGCAGGTCTCCTTATGGTAACTACTGCCTCGGGTGG
    H23- TTTCGTCAGTCTACCGGAAAGGAGCGCGAAGGAGTCGCAGTGATAAATTGGGTC
    DR592 GGCGGTATGCTCTATTTCGCCGACAGCGTCAAGGGGCGTTTCACCGTCAGCCAA
    GATCACGCTAAGAACACCGTAACACTGCAAATGAACTCCCTCAAACCTGAAGAC
    ACGGCTATGTATTACTGCGCAGCGGAAAGTGTGAGCAGTTTCAGTTGTGGTGGA
    TGGCTGACCCGCCCAGATCGCGTCCCTTACTGGGGGCAGGGCACCCAGGTGACT
    GTCTCCAGTGGAGGGTCCGGTGGCAGCGGGGGAAGCGGCCAGGTGCAGTTGCAG
    GAGTCTGGGGGCGGTTCTGTCCAGGCTGGAGGTAGCCTCCGCCTGTCTTGCACA
    GCCCCCGGCTTTACGTCCAACTCTTGTGGCATGGACTGGTATCGGCAGGCTCCA
    GGCAAAGAACGCGAGTTCGTCAGCTCTATCTCTACTGATGGAACTACAGGATAC
    GCAGACAGCGTTAAGGGGCGTTTCACCATCTCCAAAGATAAAGCTAAGGACACC
    GTTTACCTGCAAATGAACTCACTGAAGCCAGAGGATACAGGTATGTACTCTTGC
    AAGACTAAGGATGGGACCATCGCCACTATGGAACTGTGTGATTTCGGCTACTGG
    GGCCAGGGCACCCAGGTCACCGTGAGCAGC
    hIL27 1511 CAGGTGCAACTGCAAGAAAGTGGCGGTGGAAGCGTGCAGGCAGGTGGAAGCCTG
    Ra_VH CGCCTCTCTTGTCGTGCTTCCAGAAGTCCGTATGGCAATTATTGTCTGGGCTGG
    H23- TTTAGACAGTCCACTGGTAAGGAAAGGGAAGGAGTGGCTGTCATCAACTGGGTG
    DR593 GGCGGTATGCTGTACTTCGCCGATTCCGTCAAGGGCCGTTTCACAGTCTCCCAA
    GACCATGCAAAGAACACAGTGACACTCCAGATGAACTCCCTCAAGCCCGAGGAC
    ACTGCTATGTATTACTGCGCCGCTGAGTCTGTCTCCAGCTTCTCTTGCGGCGGA
    TGGCTGACTCGCCCGGATCGCGTTCCCTATTGGGGCCAGGGGACGCAGGTGACC
    GTGTCCTCAGGCGGGGGCTCCCAGGTTCAGCTCCAGGAGTCTGGCGGGGGCTCA
    GTACAGGCCGGTGGCTCCCTCCGCCTCTCATGCGCAGCCTCCGGCTACCCGTAT
    AGCAACGGTTACATGGGCTGGTTCAGGCAGGCCCCTGGGAAGGAACGCGAGGGC
    GTGGCGACTATCTACACTGGCGACGGTAGGACTTATTACGCTGATTCAGTGAAG
    GGCAGGTTCACAATTTCTCGCGACAACGCTAAAAATACCGTGGATCTCCAGATG
    TCCAGCCTGAAACCTGAGGATACTGCCATGTATTACTGTGCCGCTCGCGCAGCT
    CCTCTGTATAGTAGCGGCAGCCCCTTGACCCGCGCTAGATACAATGTCTGGGGT
    CAGGGCACCCAGGTAACCGTTAGTTCC
    hIL27 1512 CAGGTACAACTTCAGGAAAGCGGAGGTGGGTCCGTGCAGGCCGGTGGCTCACTG
    Ra_VH CGCTTGAGTTGTCGCGCCAGCCGCTCCCCTTATGGGAACTACTGCCTTGGGTGG
    H23- TTCCGCCAGAGCACTGGAAAGGAGCGCGAGGGCGTCGCAGTCATCAACTGGGTT
    DR593 GGCGGGATGCTCTATTTCGCCGACAGCGTGAAAGGGCGGTTTACCGTTAGCCAA
    GACCACGCCAAGAACACAGTGACCCTTCAAATGAACTCCCTGAAGCCCGAAGAC
    ACCGCTATGTACTATTGCGCCGCAGAGTCAGTCTCCAGTTTTAGCTGCGGAGGC
    TGGTTGACTCGCCCTGACCGCGTGCCTTATTGGGGCCAGGGCACCCAGGTGACA
    GTAAGCAGTGGAGGCAGCGGCGGTTCCGGTGGAAGCGGCCAGGTGCAGCTTCAG
    GAGAGCGGCGGTGGCAGTGTTCAGGCTGGCGGGTCCCTGAGGCTGTCCTGTGCT
    GCCTCCGGCTACCCCTACTCCAACGGTTACATGGGTTGGTTCCGCCAAGCGCCA
    GGAAAGGAACGCGAGGGTGTGGCTACCATCTACACCGGCGATGGTCGCACTTAT
    TACGCTGACAGCGTGAAAGGCCGGTTCACAATCAGCCGGGACAACGCCAAGAAC
    ACAGTGGACCTGCAAATGTCCAGTTTGAAGCCTGAAGACACAGCCATGTATTAC
    TGTGCGGCTCGGGCCGCGCCCCTCTACAGCTCCGGCTCACCACTGACACGCGCG
    AGATACAACGTGTGGGGACAGGGCACCCAGGTGACAGTTAGCAGC
    hIL27 1513 CAGGTTCAGTTGCAGGAGTCTGGTGGCGGTTCCGTCCAGGCTGGCGGAAGTCTG
    Ra_VH CGCCTCAGTTGTCGTGCCAGCCGCTCTCCTTACGGCAACTATTGCCTCGGCTGG
    H23- TTCCGGCAGTCCACTGGCAAGGAGAGGGAAGGAGTCGCCGTTATCAACTGGGTG
    DR594 GGTGGAATGCTCTACTTTGCTGATAGCGTGAAGGGCCGCTTCACAGTTTCTCAG
    GACCATGCGAAGAACACTGTTACTTTGCAGATGAACTCCCTGAAGCCAGAGGAT
    ACGGCTATGTATTACTGTGCAGCCGAGTCCGTGAGTTCCTTTTCCTGCGGGGGT
    TGGCTCACCCGTCCTGACCGTGTGCCTTATTGGGGCCAGGGTACGCAAGTCACC
    GTAAGTAGCGGAGGGGGCAGCCAGGTCCAGTTGCAGGAGTCCGGCGGAGGCTCC
    GTGCAGGCCGGGGGTTCTCTGCGTCTCTCATGTGTGGCATCTGCTTCTACTTAC
    TGCACTTACGACATGCACTGGTATCGGCAGGCTCCTGGGAAAGGACGGGAGTTC
    GTTAGTGCCATCGACAGCGACGGCACTACACGCTATGCTGATTCCGTTAAGGGC
    CGCTTTACGATTTCACAGGGGACGGCCAAGAACACTGTGTACCTCCAGATGAAC
    TCTTTGCAGCCTGAGGACACGGCTATGTATTACTGCAAAACCGTTTGTGTAGTG
    GGCAGCCGCTGGTCAGACTATTGGGGCCAGGGCACACAGGTCACCGTGAGTTCT
    hIL27 1514 CAGGTGCAACTGCAAGAGTCCGGCGGAGGCTCCGTGCAGGCTGGTGGCTCACTC
    Ra_VH CGGCTCTCCTGTCGCGCCTCTCGCAGCCCTTATGGGAATTACTGCCTGGGTTGG
    H23- TTCCGTCAGAGTACCGGCAAGGAGCGTGAGGGAGTCGCAGTAATCAACTGGGTC
    DR594 GGAGGTATGCTGTACTTCGCCGACTCCGTGAAGGGAAGGTTCACTGTGTCCCAG
    GACCACGCCAAGAACACGGTAACGCTCCAGATGAACTCCCTGAAGCCCGAAGAC
    ACCGCTATGTATTACTGTGCTGCCGAGTCCGTGTCCTCATTCTCCTGCGGCGGT
    TGGCTGACACGCCCAGACCGCGTGCCCTATTGGGGACAGGGTACACAGGTTACC
    GTCAGCTCTGGCGGGTCTGGTGGCAGTGGGGGCTCCGGTCAGGTGCAGTTGCAG
    GAGTCCGGCGGAGGCTCTGTGCAGGCTGGTGGGAGTCTGCGCCTGTCTTGCGTC
    GCCAGCGCCAGTACTTATTGTACTTACGACATGCACTGGTATAGACAGGCCCCC
    GGTAAGGGAAGGGAGTTCGTGTCAGCTATCGACAGCGATGGGACCACTAGATAT
    GCGGATAGCGTCAAGGGGCGCTTCACCATCTCCCAGGGAACCGCAAAAAACACT
    GTCTACCTTCAGATGAACAGCCTCCAGCCTGAGGACACGGCTATGTATTACTGC
    AAGACCGTGTGTGTCGTTGGATCTCGCTGGTCTGACTATTGGGGGCAGGGCACC
    CAGGTGACGGTGTCCAGC
    hIL27 1515 CAGGTTCAGCTCCAGGAGTCTGGAGGGGGCAGCGTGCAGGCGGGAGGGTCTCTT
    Ra_VH CGTCTTAGCTGCCGTGCCAGTCGCTCCCCCTACGGTAACTACTGCCTGGGGTGG
    H23- TTTCGCCAGAGTACCGGCAAGGAGCGCGAAGGTGTGGCTGTAATCAACTGGGTT
    DR595 GGGGGTATGCTGTATTTCGCCGACTCCGTGAAAGGTAGGTTTACAGTGAGCCAG
    GACCACGCTAAGAACACCGTCACCCTCCAGATGAACTCTCTCAAACCGGAGGAT
    ACCGCTATGTATTACTGCGCTGCCGAGAGTGTGAGTAGCTTCTCTTGTGGCGGT
    TGGCTGACCAGGCCTGACCGCGTACCCTACTGGGGCCAGGGCACCCAGGTCACA
    GTCAGCTCTGGTGGAGGCTCACAGGTGCAGCTTCAGGAGTCCGGCGGGGGCAGC
    GTGCAGGCCGGGGGCTCACTGACCCTGAGCTGTGCTGCCAGCGAATACGCATAC
    TCTACCTGCAATATGGGCTGGTATCGGCAGGCCCCTGGGAAAGAAAGGGAACTG
    GTTTCTGCCTTTATCAGCGATGGATCAACATATTACGCCGACTCCGTGAAAGGG
    AGGTTCACGATCACCCGCGACAACGCCAAGAACACTGTGTACCTCCAAATGAAC
    AGCCTGAAGCCTGAGGACACCGCGATCTATTACTGCTCTGCTAACTGCTACCGC
    AGGCTGCGCAATTATTGGGGTCAAGGCACCCAGGTTACCGTGTCTTCC
    hIL27 1516 CAGGTCCAGCTCCAGGAGTCTGGCGGAGGCTCCGTGCAGGCTGGAGGCAGCCTC
    Ra_VH AGACTTTCTTGCAGAGCTTCCCGGTCTCCCTATGGAAACTACTGCTTGGGTTGG
    H23- TTCCGCCAATCCACTGGCAAGGAGAGGGAGGGTGTTGCTGTCATCAACTGGGTG
    DR595 GGCGGGATGCTTTATTTCGCCGACAGTGTCAAGGGACGGTTCACCGTCTCTCAG
    GATCACGCCAAGAACACTGTGACCTTGCAGATGAACTCACTCAAACCCGAAGAT
    ACCGCTATGTACTATTGTGCCGCAGAAAGCGTGTCTAGCTTCAGCTGTGGTGGC
    TGGCTCACACGCCCTGACCGGGTGCCATACTGGGGCCAGGGCACGCAGGTGACC
    GTAAGCTCAGGCGGGAGTGGTGGCTCTGGAGGCTCTGGACAGGTGCAGCTCCAG
    GAGAGCGGGGGCGGGAGCGTGCAGGCTGGCGGTAGTCTGACCCTGTCATGCGCT
    GCAAGCGAATACGCCTACAGCACCTGCAATATGGGGTGGTATCGTCAGGCTCCT
    GGCAAGGAGCGTGAGCTGGTTTCCGCCTTCATCTCCGATGGCTCTACCTATTAC
    GCCGACTCAGTGAAGGGCCGCTTCACTATCACTAGGGACAATGCCAAGAACACA
    GTATACCTCCAGATGAACTCTCTGAAGCCAGAGGATACTGCCATCTATTACTGT
    AGCGCCAACTGTTATCGTCGCCTGCGCAACTATTGGGGTCAAGGCACACAGGTG
    ACAGTCTCTAGC
    hIL27 1517 CAGGTGCAACTCCAGGAATCCGGGGGTGGATCAGTACAGGCAGGCGGAAGCCTG
    Ra_VH AGGCTGTCTTGTCGCGCTTCCCGTTCTCCCTACGGAAATTACTGTCTGGGCTGG
    H23- TTCCGGCAGTCCACTGGAAAAGAGAGGGAGGGAGTGGCCGTTATCAACTGGGTA
    DR596 GGAGGTATGCTGTACTTTGCCGACAGCGTGAAAGGAAGGTTCACCGTGAGCCAG
    GACCACGCCAAGAATACCGTGACCTTGCAGATGAACAGCCTGAAGCCCGAAGAC
    ACTGCCATGTACTATTGTGCCGCTGAGAGTGTATCATCTTTCTCCTGCGGTGGC
    TGGTTGACTCGCCCAGACAGAGTGCCTTATTGGGGGCAGGGCACTCAGGTGACC
    GTGTCTTCCGGTGGAGGCTCCCAGGTTCAACTTCAGGAGTCCGGTGGAGGCCTG
    GTACAGCCTGGCGGATCTCTCAGGCTCAGCTGCACTGCCTCTGGACTGACCTTC
    GATGACTCTGTTATGGGCTGGTTTAGGCAGGCCCCTGGAAAAGGCCGGGAGGCG
    GTCAGCTGCATCAGCTCTAGCGGGGCCAATGCGTTTTACGCTGATTCCGTGAAG
    GGCCGCTTCACTATCTCTAGGGACAACGCGAAGAACACCCTCTACTTGCAGATG
    AACTCCCTCAAGCCCGAGGACACGGCGACTTATTACTGCAAAAGAGGACACGCT
    TGTGCCGGATATTACCCGATTCCCTATGATGACTATTGGGGCCAGGGCACCCAG
    GTGACAGTGAGCAGC
    hIL27 1518 CAGGTGCAACTCCAGGAAAGCGGCGGTGGAAGCGTGCAGGCTGGAGGGTCCCTC
    Ra_VH AGACTGAGTTGCCGGGCCTCACGGTCCCCCTATGGGAACTATTGCCTGGGTTGG
    H23- TTCCGTCAGTCCACTGGCAAGGAGCGCGAGGGCGTGGCCGTTATCAACTGGGTG
    DR596 GGAGGGATGCTGTACTTTGCAGACAGCGTTAAGGGTCGGTTTACCGTGAGCCAG
    GACCACGCCAAGAATACCGTGACCTTGCAGATGAACTCCCTGAAGCCTGAGGAC
    ACCGCCATGTATTACTGCGCTGCCGAATCCGTGTCTAGCTTTAGCTGTGGGGGC
    TGGCTCACCAGACCTGATCGCGTGCCGTACTGGGGCCAGGGCACTCAAGTGACG
    GTCAGCTCCGGTGGAAGCGGTGGCTCCGGCGGTTCCGGGCAGGTGCAGTTGCAG
    GAGTCAGGGGGAGGGTTGGTTCAGCCCGGTGGCTCCTTGCGTCTGTCCTGTACT
    GCAAGCGGGCTGACCTTCGACGATTCTGTGATGGGCTGGTTTCGTCAGGCTCCT
    GGCAAGGGCAGAGAGGCGGTGAGCTGTATCTCCAGCTCCGGCGCTAATGCCTTC
    TACGCAGACAGTGTTAAGGGTAGGTTTACTATCTCCAGGGACAATGCTAAAAAC
    ACTCTGTATCTTCAGATGAACAGCCTGAAGCCGGAGGATACTGCTACCTATTAC
    TGTAAGCGGGGCCATGCTTGCGCCGGGTACTATCCAATCCCCTACGATGACTAT
    TGGGGTCAAGGCACACAGGTGACAGTGTCCTCC
    hIL27 1519 CAGGTCCAGTTGCAGGAGAGCGGTGGGGGCCTGGTGCAGCCTGGCGGTTCCCTG
    Ra_VH CGCCTGTCTTGTGCTGCGAGCGGGTTCACTTTCAGCCATTCTGGTATGAGTTGG
    H24- GTACGCCAGGCTCCAGGCAAGGGCCTGGAATGGGTGAGCACCATCAACTCTGGA
    DR591 GGTGCCTCTACTTATTACACCGACAGTGTCAAGGGACGCTTTACAATCTCCAGA
    GACAACGCGAAGAATATGCTTTACTTGCAGCTCAACTCACTGAAGACCGAGGAT
    ACTGCCATGTATTACTGCGCTAAGGGAGGCTCAGGATATGGTGATGCCTCTCGC
    ATGACCTCTCCTGGCTCACAGGGAACCCAGGTGACCGTCAGTTCCGGTGGAGGT
    TCTCAGGTCCAGCTCCAGGAGTCCGGCGGTGGCAGCGTGCAGGCCGGAGGCAGC
    CTGCGCCTGTCATGCACAGCCTCTGGCGCTATCGCCAGTGGTTACATCGACAGC
    AGGTGGTGCATGGCCTGGTTCAGACAGGCCCCTGGTAAGGAACGCGAGGGAGTT
    GCTGCCATTTGGCCAGGCGGTGGCCTGACAGTGTACGCCGATAGCGTCAAGGGG
    CGCTTCACTATCTCACGGGATCACGCTAAAAACACTTTGTACCTCCAGATGAAT
    AACCTCAAACCAGAGGACACCGCGATGTATTACTGCGCTGCGGGCTCTCCCCGC
    ATGTGTCCCTCTCTGGAGTTCGGGTTCGATTATTGGGGTCAGGGAACGCAGGTG
    ACTGTGTCCTCC
    hIL27 1520 CAGGTGCAGCTTCAGGAGTCCGGGGGAGGCCTGGTTCAGCCCGGCGGTTCTCTC
    Ra_VH CGCCTCAGCTGTGCCGCTTCCGGGTTTACATTCAGCCACAGTGGAATGTCTTGG
    H24- GTACGTCAAGCGCCAGGTAAGGGCCTGGAGTGGGTCTCTACAATCAACAGCGGT
    DR591 GGCGCAAGTACATACTATACCGACTCCGTGAAAGGGCGGTTTACCATCTCCCGT
    GACAACGCTAAGAATATGCTCTATCTTCAGCTGAACTCACTCAAGACTGAGGAT
    ACTGCTATGTATTACTGTGCGAAAGGGGGATCTGGGTACGGCGATGCGAGCCGC
    ATGACCTCCCCCGGCAGTCAGGGCACTCAAGTGACCGTATCATCCGGGGGTTCC
    GGTGGCTCAGGAGGTAGCGGCCAGGTTCAACTGCAAGAGAGTGGCGGGGGCTCC
    GTGCAGGCGGGCGGTTCCCTCAGGCTCTCTTGCACTGCAAGCGGCGCTATTGCG
    AGTGGGTACATCGACTCCAGATGGTGTATGGCCTGGTTCCGCCAGGCACCTGGC
    AAGGAGCGCGAAGGCGTGGCAGCCATCTGGCCTGGGGGCGGTCTTACCGTCTAC
    GCTGACTCCGTGAAAGGCCGCTTCACTATTTCTCGCGACCATGCCAAGAACACC
    CTGTACTTGCAAATGAATAACCTGAAGCCTGAAGACACCGCGATGTATTACTGC
    GCCGCTGGATCTCCCAGGATGTGCCCGAGCCTGGAGTTCGGTTTCGACTACTGG
    GGCCAAGGCACACAGGTTACAGTCTCCTCC
    hIL27 1521 CAAGTGCAGCTCCAGGAGAGCGGTGGCGGTCTCGTGCAACCAGGAGGTTCCTTG
    Ra_VH CGGCTGAGCTGTGCCGCGTCAGGTTTTACATTTAGCCACAGTGGGATGTCTTGG
    H24- GTGAGACAGGCTCCGGGTAAGGGTCTCGAATGGGTCAGTACTATCAATTCCGGC
    DR592 GGAGCAAGCACATACTATACCGACTCTGTCAAGGGGAGATTTACCATCTCCAGA
    GACAATGCCAAAAACATGCTGTATTTGCAACTCAACAGTCTGAAGACCGAAGAC
    ACCGCGATGTATTACTGCGCCAAGGGCGGTTCCGGGTACGGAGACGCGAGCCGC
    ATGACTTCCCCTGGATCTCAGGGCACCCAGGTGACTGTCTCCAGCGGTGGCGGT
    TCCCAAGTCCAACTCCAGGAAAGCGGAGGCGGTTCTGTGCAGGCAGGCGGGTCC
    CTTCGGTTGAGCTGTACCGCACCCGGCTTTACCAGCAACTCTTGTGGTATGGAC
    TGGTATCGGCAGGCTCCTGGCAAAGAGCGCGAGTTCGTGTCTTCCATTTCCACC
    GACGGCACTACCGGGTACGCGGATTCCGTGAAGGGCAGGTTCACGATCAGCAAG
    GATAAGGCAAAAGATACTGTTTATCTCCAGATGAACTCACTCAAGCCCGAAGAC
    ACTGGCATGTACTCCTGCAAGACCAAAGACGGCACCATTGCCACTATGGAGCTG
    TGCGATTTTGGCTACTGGGGTCAGGGCACCCAGGTCACCGTGTCATCC
    hIL27 1522 CAGGTGCAGCTTCAGGAGAGTGGTGGGGGTCTGGTTCAGCCTGGGGGTAGCCTG
    Ra_VH AGGCTGAGTTGTGCCGCGAGCGGATTTACTTTCTCTCATAGCGGCATGAGTTGG
    H24- GTGCGCCAGGCCCCTGGCAAGGGTCTGGAATGGGTGAGTACAATCAACTCTGGC
    DR592 GGTGCCTCTACCTATTACACCGACAGCGTGAAGGGGAGATTCACTATTAGCCGC
    GACAATGCTAAGAATATGCTCTATCTTCAGCTGAACTCCCTGAAAACCGAAGAC
    ACCGCAATGTATTACTGTGCAAAGGGTGGAAGCGGCTACGGCGACGCCAGCCGC
    ATGACTTCCCCCGGCTCTCAGGGAACTCAGGTTACCGTCTCTTCCGGCGGTAGC
    GGGGGCTCTGGAGGCTCTGGCCAGGTTCAGTTGCAGGAAAGTGGAGGCGGTTCA
    GTTCAGGCTGGAGGCAGCTTGCGCTTGTCCTGTACCGCGCCAGGCTTCACAAGT
    AATAGCTGTGGCATGGATTGGTATCGTCAGGCACCGGGAAAGGAGCGCGAGTTT
    GTGTCTAGCATCAGCACAGACGGGACAACCGGCTATGCGGATTCCGTAAAAGGA
    CGGTTTACTATCTCCAAGGATAAGGCTAAGGACACAGTGTACCTGCAAATGAAC
    AGCCTGAAGCCCGAAGATACTGGTATGTATAGCTGCAAGACCAAGGATGGCACA
    ATCGCCACTATGGAGCTGTGTGACTTCGGCTATTGGGGTCAGGGCACCCAGGTG
    ACAGTGTCTTCT
    hIL27 1523 CAGGTGCAGCTCCAGGAAAGCGGAGGTGGCCTGGTACAGCCCGGCGGTAGTCTG
    Ra_VH AGGCTGAGTTGTGCTGCCTCAGGTTTTACTTTCTCACACTCCGGGATGTCCTGG
    H24- GTGAGACAAGCGCCGGGCAAGGGCCTGGAGTGGGTATCAACTATTAACAGTGGC
    DR593 GGGGCGTCTACCTATTACACTGACAGCGTGAAGGGCCGGTTCACTATCAGCAGA
    GATAACGCTAAAAATATGTTGTATCTTCAGCTCAATTCCCTGAAAACCGAAGAT
    ACCGCGATGTATTACTGTGCTAAAGGGGGTTCTGGATACGGCGATGCGTCTCGC
    ATGACCTCTCCTGGAAGCCAGGGCACCCAGGTCACCGTGTCTAGTGGCGGAGGT
    AGTCAGGTTCAGCTCCAAGAGTCCGGCGGAGGTAGCGTCCAGGCCGGGGGCTCA
    CTCCGCCTGTCCTGCGCAGCCAGCGGATACCCCTATTCAAACGGCTACATGGGC
    TGGTTCCGCCAGGCCCCCGGAAAAGAGCGTGAAGGAGTGGCTACAATCTATACC
    GGCGACGGGAGGACCTATTACGCAGATTCCGTGAAAGGCCGTTTCACCATCTCC
    CGTGACAACGCCAAAAATACCGTGGACCTTCAGATGAGTTCTCTGAAGCCAGAG
    GACACCGCTATGTACTATTGTGCTGCCAGAGCTGCACCACTGTATTCCTCTGGC
    AGCCCCCTGACCAGAGCCCGCTACAACGTCTGGGGACAGGGCACCCAGGTCACA
    GTCAGCTCT
    hIL27 1524 CAGGTTCAGCTCCAGGAATCTGGCGGTGGCCTCGTTCAGCCGGGTGGCAGTCTT
    Ra_VH CGTCTGAGCTGTGCAGCCTCTGGCTTCACCTTCTCTCACTCCGGCATGAGCTGG
    H24- GTCAGACAGGCCCCAGGCAAGGGTCTGGAGTGGGTGTCTACGATCAATAGCGGA
    DR593 GGCGCTTCTACCTATTACACCGACAGCGTGAAGGGCAGATTTACCATTTCCCGT
    GACAACGCCAAAAACATGCTGTATCTGCAACTGAACTCTCTGAAGACCGAGGAC
    ACCGCCATGTACTATTGCGCTAAGGGCGGTAGCGGATATGGCGACGCGAGCAGA
    ATGACTTCTCCGGGGAGCCAGGGTACACAGGTGACCGTGTCCAGCGGCGGTAGT
    GGGGGCAGCGGTGGCAGCGGACAGGTCCAGTTGCAGGAATCCGGCGGAGGCAGC
    GTGCAGGCTGGCGGTTCACTGAGACTCTCTTGCGCGGCCAGCGGCTATCCCTAT
    TCTAACGGTTATATGGGCTGGTTTAGGCAGGCTCCCGGCAAGGAAAGGGAGGGC
    GTGGCTACTATCTATACTGGCGATGGCCGCACTTACTATGCCGATAGTGTCAAG
    GGCCGTTTCACTATCTCTCGCGACAACGCTAAGAACACAGTGGATCTTCAGATG
    TCTTCCCTGAAGCCAGAGGATACCGCGATGTATTACTGTGCCGCGAGGGCTGCA
    CCACTGTACTCTAGCGGATCTCCCCTGACCCGCGCCAGATACAACGTGTGGGGC
    CAGGGGACGCAGGTTACCGTTTCTTCT
    hIL27 1525 CAGGTGCAGTTGCAGGAGAGTGGAGGCGGACTGGTGCAGCCAGGAGGTTCACTG
    Ra_VH CGTCTTTCTTGCGCAGCCAGCGGTTTTACATTCAGCCACTCTGGAATGTCTTGG
    H24- GTTCGCCAGGCACCGGGGAAGGGCCTGGAGTGGGTGTCCACAATCAACAGTGGG
    DR594 GGTGCCTCTACTTACTATACAGACTCCGTGAAAGGCAGGTTTACCATCTCCAGG
    GACAACGCCAAAAATATGCTTTATCTTCAGCTCAATTCTCTGAAGACCGAGGAT
    ACTGCGATGTATTACTGTGCAAAAGGGGGCTCAGGATATGGCGATGCCTCCCGC
    ATGACCAGCCCAGGGAGCCAGGGCACCCAGGTGACCGTCTCCAGTGGCGGAGGC
    TCTCAGGTGCAGCTCCAGGAGTCAGGCGGTGGCTCCGTCCAGGCTGGCGGGAGC
    TTGCGCTTGTCCTGTGTTGCCTCCGCTAGTACCTATTGCACCTATGATATGCAC
    TGGTACAGACAGGCTCCGGGTAAGGGCCGTGAGTTCGTGTCCGCCATTGATAGC
    GACGGCACAACTCGCTACGCTGATTCCGTGAAAGGCCGCTTCACCATTAGCCAG
    GGCACCGCTAAGAACACAGTGTACTTGCAGATGAACAGCTTGCAGCCAGAGGAT
    ACCGCGATGTATTACTGCAAAACTGTGTGCGTAGTGGGCAGTAGATGGTCCGAC
    TACTGGGGCCAGGGCACACAGGTCACCGTGAGCAGC
    hIL27 1526 CAGGTACAGCTCCAAGAGTCTGGCGGTGGCCTGGTGCAACCAGGGGGCTCATTG
    Ra_VH AGATTGTCTTGCGCCGCTTCTGGATTCACATTCTCCCACTCAGGTATGAGTTGG
    H24- GTGCGGCAAGCCCCAGGCAAGGGCCTGGAGTGGGTTTCTACCATCAACAGTGGG
    DR594 GGAGCTAGTACCTACTATACAGACTCCGTGAAAGGCCGCTTCACCATTAGCCGC
    GATAACGCTAAGAACATGCTGTACTTGCAGCTCAATTCCCTGAAGACCGAGGAC
    ACAGCTATGTACTATTGCGCCAAGGGAGGCAGTGGTTACGGGGACGCCAGCCGG
    ATGACCTCTCCCGGCTCTCAAGGGACGCAGGTTACCGTGTCAAGCGGCGGTTCC
    GGTGGGTCCGGTGGCTCCGGTCAAGTGCAGCTCCAGGAGAGTGGGGGTGGCAGC
    GTCCAGGCCGGAGGCTCCCTCAGGCTGTCCTGCGTGGCCTCTGCCAGCACATAT
    TGCACATACGACATGCACTGGTATCGTCAGGCTCCTGGCAAAGGGCGCGAGTTC
    GTGTCCGCTATTGATTCCGATGGTACAACCCGGTACGCTGACAGTGTGAAGGGC
    CGTTTCACAATTAGCCAGGGCACCGCTAAAAACACCGTGTACCTCCAGATGAAC
    TCCCTCCAACCTGAGGATACTGCCATGTATTACTGCAAAACGGTGTGCGTCGTG
    GGCTCTCGCTGGTCCGATTACTGGGGGCAGGGCACTCAGGTGACCGTGTCCAGC
    hIL27 1527 CAGGTGCAGTTGCAGGAGAGCGGAGGCGGGCTGGTGCAGCCTGGAGGCTCTCTG
    Ra_VH CGCCTGTCCTGCGCAGCCTCAGGATTTACATTCTCTCACAGTGGGATGTCTTGG
    H24- GTGCGGCAGGCTCCGGGCAAAGGCCTGGAATGGGTGTCCACCATTAACTCTGGT
    DR595 GGCGCGAGCACTTACTATACCGATAGTGTCAAAGGCCGCTTCACCATCAGCCGG
    GACAACGCTAAGAACATGCTGTATCTCCAGCTGAACAGCCTGAAGACCGAAGAC
    ACTGCTATGTATTACTGTGCCAAGGGCGGTTCAGGTTATGGGGACGCCTCTCGG
    ATGACATCACCGGGCTCCCAAGGAACTCAGGTCACCGTCAGCAGTGGCGGTGGC
    TCCCAGGTGCAACTTCAGGAGTCCGGGGGTGGAAGCGTGCAGGCTGGAGGCTCC
    CTGACACTGTCTTGCGCTGCCAGCGAATACGCTTATTCCACCTGTAACATGGGG
    TGGTATCGCCAAGCTCCTGGGAAGGAACGTGAACTGGTCAGTGCCTTCATCTCT
    GATGGGTCCACGTATTACGCTGATTCAGTAAAGGGACGTTTCACAATCACCCGC
    GACAACGCCAAAAACACTGTGTACTTGCAGATGAACAGCCTGAAGCCAGAGGAT
    ACCGCTATCTACTATTGCAGCGCCAACTGTTACCGTCGGCTGCGCAACTACTGG
    GGGCAGGGCACACAAGTCACAGTGTCCAGC
    hIL27 1528 CAGGTCCAGCTCCAGGAGTCAGGGGGTGGACTTGTTCAACCCGGTGGCTCCCTC
    Ra_VH CGTCTCTCCTGTGCTGCGTCTGGTTTCACCTTCAGCCACTCTGGAATGAGCTGG
    H24- GTTAGACAAGCACCTGGCAAAGGCCTCGAATGGGTCTCTACCATCAACAGCGGC
    DR595 GGAGCCTCCACTTATTACACCGACTCCGTGAAGGGTCGCTTCACGATCAGCAGA
    GACAACGCCAAGAACATGCTGTACCTCCAACTGAATAGCCTGAAAACCGAGGAT
    ACTGCCATGTATTACTGTGCAAAGGGCGGAAGTGGTTACGGAGACGCCAGCAGG
    ATGACATCTCCGGGTTCTCAAGGCACCCAGGTCACCGTGAGTAGCGGCGGATCT
    GGGGGCAGCGGAGGCAGCGGCCAGGTGCAGCTTCAGGAAAGCGGAGGGGGTTCC
    GTTCAGGCCGGGGGCTCACTGACACTGAGTTGCGCGGCCTCCGAATACGCCTAT
    TCTACTTGTAACATGGGCTGGTACAGACAAGCTCCTGGGAAGGAGAGAGAACTG
    GTGAGCGCTTTTATTTCTGACGGCTCAACCTATTACGCAGACTCCGTCAAGGGC
    CGCTTCACCATTACCCGCGACAACGCTAAGAATACGGTGTACCTCCAGATGAAC
    TCCCTGAAGCCCGAAGACACCGCAATTTACTATTGCAGCGCCAACTGCTACCGC
    CGGTTGCGCAACTACTGGGGCCAGGGAACTCAGGTTACCGTATCCTCC
    hIL27 1529 CAGGTGCAACTCCAGGAGTCCGGCGGTGGACTGGTGCAGCCTGGCGGTAGCTTG
    Ra_VH AGGCTGTCTTGCGCCGCATCCGGCTTCACATTCAGCCACTCTGGAATGTCATGG
    H24- GTCAGACAGGCTCCGGGCAAGGGCCTGGAATGGGTCTCAACCATCAATAGTGGA
    DR596 GGTGCCTCAACTTACTATACCGACTCCGTGAAAGGTCGTTTCACAATTTCACGC
    GACAACGCTAAGAACATGCTGTACCTCCAGCTGAATAGTCTCAAAACTGAGGAC
    ACCGCTATGTATTACTGTGCTAAGGGCGGTTCCGGGTATGGGGACGCCTCCAGG
    ATGACTTCACCGGGTAGCCAGGGGACCCAGGTGACGGTTTCTAGCGGGGGGGG
    TCCCAGGTGCAGCTTCAGGAAAGCGGAGGGGGCCTGGTGCAGCCCGGCGGGTCC
    CTGAGACTGAGCTGCACGGCAAGCGGCCTGACGTTTGATGACTCCGTGATGGGC
    TGGTTCAGACAGGCCCCCGGCAAGGGGCGCGAAGCCGTCTCCTGTATTAGCTCC
    AGCGGGGCCAACGCTTTCTACGCGGACAGCGTCAAAGGCCGCTTCACCATTAGC
    AGAGACAACGCTAAGAACACTCTGTACCTCCAGATGAACAGCCTGAAACCAGAG
    GATACCGCAACGTATTACTGCAAGCGCGGACATGCTTGCGCGGGCTATTACCCA
    ATCCCTTATGACGATTACTGGGGCCAGGGCACTCAGGTGACGGTAAGCTCC
    hIL27 1530 CAGGTCCAACTCCAGGAGTCCGGCGGTGGCCTGGTTCAGCCAGGAGGTTCCCTG
    Ra_VH CGCCTGTCCTGTGCCGCTTCCGGCTTTACCTTCTCCCATTCCGGCATGAGCTGG
    H24- GTGAGGCAGGCCCCTGGCAAAGGCCTGGAGTGGGTGTCTACCATTAACTCTGGC
    DR596 GGAGCCAGCACATACTATACAGACTCAGTAAAGGGACGCTTCACCATCAGCAGG
    GACAACGCCAAAAACATGCTGTATCTCCAGCTGAACTCTCTCAAGACCGAAGAC
    ACCGCTATGTATTACTGTGCTAAGGGCGGTAGCGGCTATGGGGACGCATCTCGT
    ATGACCTCTCCCGGCTCTCAAGGCACCCAGGTGACTGTGTCTAGTGGTGGGTCT
    GGCGGGTCTGGCGGATCTGGTCAAGTCCAGTTGCAGGAGAGTGGAGGCGGTCTC
    GTCCAGCCAGGCGGAAGCCTGCGCCTGTCTTGTACTGCCAGCGGTTTGACCTTT
    GATGACTCTGTGATGGGCTGGTTTCGTCAGGCCCCCGGCAAGGGCCGTGAGGCC
    GTGTCATGTATCTCATCTTCAGGAGCCAACGCCTTTTATGCCGATAGCGTGAAA
    GGGAGATTCACCATCTCTCGTGATAACGCAAAGAACACCCTGTACCTTCAGATG
    AACTCTCTGAAGCCTGAGGACACTGCTACCTACTATTGTAAGCGTGGGCACGCC
    TGCGCTGGATATTACCCTATCCCTTACGATGACTATTGGGGGCAGGGCACTCAG
    GTGACCGTCAGCAGC
  • In some embodiments, a bispecific VHH2 comprises:
      • an anti-gp130 VHH antibody comprising a CDR1 having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity, or having 0, 1, 2, or 3 amino acid changes, optionally conservative amino acid changes relative, to the sequence of any one of SEQ ID NOS: 193-198; a CDR2 having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity, or having 0, 1, 2, or 3 amino acid changes, optionally conservative amino acid changes relative, to the sequence of any one of SEQ ID NOS: 199-204; and a CDR3 having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity, or having 0, 1, 2, or 3 amino acid changes optionally conservative amino acid changes relative, to the sequence of any one of SEQ ID NOS:205-210; and
      • an anti-IL27Rα VHH antibody comprising a CDR1 having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity, or having 0, 1, 2, or 3 amino acid changes, optionally conservative amino acid changes relative, to the sequence of any one of SEQ ID NOS:211-217; a CDR2 having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity, or having 0, 1, 2, or 3 amino acid changes, optionally conservative amino acid changes relative, to the sequence of any one of SEQ ID NOS:218-224; and a CDR3 having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity, or having 0, 1, 2, or 3 amino acid changes optionally conservative amino acid changes relative, to the sequence of any one of SEQ ID NOS:225-231.
  • In certain embodiments, a bispecific VHH2 described herein comprises an anti-gp130 VHH antibody comprising a CDR1, a CDR2, and a CDR3 and an anti-IL27Rα VHH antibody comprising a CDR1, a CDR2, and a CDR3 as described in each row of Table 1 below. In some embodiments, the CDR1, CDR2, and CDR3 in the anti-gp130 VHH antibody and CDR1, CDR2, and CDR3 in the anti-IL27Rα VHH antibody can each, independently, comprise at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity, or have 0, 1, 2, or 3 amino acid changes, optionally conservative amino acid changes, relative to the sequence described in each row of Table 1.
  • In some embodiments, the bispecific VHH2 comprises an anti-gp130 VHH antibody at the N-terminus and an anti-IL27Rα VHH antibody at the C-terminus. In some embodiments, the bispecific VHH2 comprises an anti-IL27Rα VHH antibody at the N-terminus and an anti-gp130 VHH antibody at the C-terminus.
  • TABLE 1
    Anti-gp130 VHH Anti-gp130 VHH Anti-gp130 VHH Anti-IL27Rα VHH Anti-IL27Rα VHH Anti-IL27Rα VHH
    CDR1 CDR2 CDR3 CDR1 CDR2 CDR3
    AIASGYIDSR AIWPGGGLTVY GSPRMCPSLEFG FTFSSYPMS TISAGGDTTLYA GYCYRRNY
    (SEQ ID NO: 193) ADSVKG (SEQ FDY (SEQ ID (SEQ ID NO: 211) DSVKG (SEQ ID (SEQ ID NO: 225)
    ID NO: 199) NO: 205) NO: 218)
    AIASGYIDSR AIWPGGGLTVY GSPRMCPSLEFG FTFSNYAMS GINVAYGITSYA HSGTTIPRGFISY
    (SEQ ID NO: 193) ADSVKG (SEQ FDY (SEQ ID (SEQ ID NO: 212) DSVKG (SEQ ID TK (SEQ ID
    ID NO: 199) NO: 205) NO: 219) NO: 226)
    AIASGYIDSR AIWPGGGLTVY GSPRMCPSLEFG FSFSSYAMK TISSGGSSTNYA AIVPTGATME
    (SEQ ID NO: 193) ADSVKG (SEQ FDY (SEQ ID (SEQ ID NO: 213) DSVKG (SEQ ID (SEQ ID NO: 227)
    ID NO: 199) NO: 205) NO: 220)
    AIASGYIDSR AIWPGGGLTVY GSPRMCPSLEFG FTYSTSNSWMA AIYTVGGSIFYA ASGRLRGKWFW
    (SEQ ID NO: 193) ADSVKG (SEQ FDY (SEQ ID (SEQ ID NO: 214) DSVRG (SEQ ID PYEYNY (SEQ ID
    ID NO: 199) NO: 205) NO: 221) NO: 228)
    AIASGYIDSR AIWPGGGLTVY GSPRMCPSLEFG YVSCDYFLPS IIDGTGSTSYAA SCVRGRAISEY
    (SEQ ID NO: 193) ADSVKG (SEQ FDY (SEQ ID (SEQ ID NO: 215) SVKG (SEQ ID (SEQ ID NO: 229)
    ID NO: 199) NO: 205) NO: 222)
    AIASGYIDSR AIWPGGGLTVY GSPRMCPSLEFG STYSNYCLG VINWVGGMLYF ESVSSFSCGGWL
    (SEQ ID NO: 193) ADSVKG (SEQ FDY (SEQ ID (SEQ ID NO: 216) ADSVKG (SEQ TRPDRVPY (SEQ
    ID NO: 199) NO: 205) ID NO: 223) ID NO: 230)
    AIASGYIDSR AIWPGGGLTVY GSPRMCPSLEFG FTFSLSSMS AISSGGASTYYT GGSGYGDASRM
    (SEQ ID NO: 193) ADSVKG (SEQ FDY (SEQ ID (SEQ ID NO: 217) DSVKG (SEQ ID TSP (SEQ ID
    ID NO: 199) NO: 205) NO: 224) NO: 231)
    FTSNSCGMD SISTDGTTGYAD KDGTIATMELC FTFSSYPMS TISAGGDTTLYA GYCYRRNY
    (SEQ ID NO: 194) SVKG (SEQ ID DFGY (SEQ ID (SEQ ID NO: 211) DSVKG (SEQ ID (SEQ ID NO: 225)
    NO: 200) NO: 206) NO: 218)
    FTSNSCGMD SISTDGTTGYAD KDGTIATMELC FTFSNYAMS GINVAYGITSYA HSGTTIPRGFISY
    (SEQ ID NO: 194) SVKG (SEQ ID DFGY (SEQ ID (SEQ ID NO: 212) DSVKG (SEQ ID TK (SEQ ID
    NO: 200) NO: 206) NO: 219) NO: 226)
    FTSNSCGMD SISTDGTTGYAD KDGTIATMELC FSFSSYAMK TISSGGSSTNYA AIVPTGATME
    (SEQ ID NO: 194) SVKG (SEQ ID DFGY (SEQ ID (SEQ ID NO: 213) DSVKG (SEQ ID (SEQ ID NO: 227)
    NO: 200) NO: 206) NO: 220)
    FTSNSCGMD SISTDGTTGYAD KDGTIATMELC FTYSTSNSWMA AIYTVGGSIFYA ASGRLRGKWFW
    (SEQ ID NO: 194) SVKG (SEQ ID DFGY (SEQ ID (SEQ ID NO: 214) DSVRG (SEQ ID PYEYNY (SEQ ID
    NO: 200) NO: 206) NO: 221) NO: 228)
    FTSNSCGMD SISTDGTTGYAD KDGTIATMELC YVSCDYFLPS IIDGTGSTSYAA SCVRGRAISEY
    (SEQ ID NO: 194) SVKG (SEQ ID DFGY (SEQ ID (SEQ ID NO: 215) SVKG (SEQ ID (SEQ ID NO: 229)
    NO: 200) NO: 206) NO: 222)
    FTSNSCGMD SISTDGTTGYAD KDGTIATMELC STYSNYCLG VINWVGGMLYF ESVSSFSCGGWL
    (SEQ ID NO: 194) SVKG (SEQ ID DFGY (SEQ ID (SEQ ID NO: 216) ADSVKG (SEQ TRPDRVPY (SEQ
    NO: 200) NO: 206) ID NO: 223) ID NO: 230)
    FTSNSCGMD SISTDGTTGYAD KDGTIATMELC FTFSLSSMS AISSGGASTYYT GGSGYGDASRM
    (SEQ ID NO: 194) SVKG (SEQ ID DFGY (SEQ ID (SEQ ID NO: 217) DSVKG (SEQ ID TSP (SEQ ID
    NO: 200) NO: 206) NO: 224) NO: 231)
    YPYSNGYMG TIYTGDGRTYY RAAPLYSSGSPL FTFSSYPMS TISAGGDTTLYA GYCYRRNY
    (SEQ ID NO: 195) ADSVKG (SEQ TRARYNV (SEQ (SEQ ID NO: 211) DSVKG (SEQ ID (SEQ ID NO: 225)
    ID NO: 201) ID NO: 207) NO: 218)
    YPYSNGYMG TIYTGDGRTYY RAAPLYSSGSPL FTFSNYAMS GINVAYGITSYA HSGTTIPRGFISY
    (SEQ ID NO: 195) ADSVKG (SEQ TRARYNV (SEQ (SEQ ID NO: 212) DSVKG (SEQ ID TK (SEQ ID
    ID NO: 201) ID NO: 207) NO: 219) NO: 226)
    YPYSNGYMG TIYTGDGRTYY RAAPLYSSGSPL FSFSSYAMK TISSGGSSTNYA AIVPTGATME
    (SEQ ID NO: 195) ADSVKG (SEQ TRARYNV (SEQ (SEQ ID NO: 213) DSVKG (SEQ ID (SEQ ID NO: 227)
    ID NO: 201) ID NO: 207) NO: 220)
    YPYSNGYMG TIYTGDGRTYY RAAPLYSSGSPL FTYSTSNSWMA AIYTVGGSIFYA ASGRLRGKWFW
    (SEQ ID NO: 195) ADSVKG (SEQ TRARYNV (SEQ (SEQ ID NO: 214) DSVRG (SEQ ID PYEYNY (SEQ ID
    ID NO: 201) ID NO: 207) NO: 221) NO: 228)
    YPYSNGYMG TIYTGDGRTYY RAAPLYSSGSPL YVSCDYFLPS IIDGTGSTSYAA SCVRGRAISEY
    (SEQ ID NO: 195) ADSVKG (SEQ TRARYNV (SEQ (SEQ ID NO: 215) SVKG (SEQ ID (SEQ ID NO: 229)
    ID NO: 201) ID NO: 207) NO: 222)
    YPYSNGYMG TIYTGDGRTYY RAAPLYSSGSPL STYSNYCLG VINWVGGMLYF ESVSSFSCGGWL
    (SEQ ID NO: 195) ADSVKG (SEQ TRARYNV (SEQ (SEQ ID NO: 216) ADSVKG (SEQ TRPDRVPY (SEQ
    ID NO: 201) ID NO: 207) ID NO: 223) ID NO: 230)
    YPYSNGYMG TIYTGDGRTYY RAAPLYSSGSPL FTFSLSSMS AISSGGASTYYT GGSGYGDASRM
    (SEQ ID NO: 195) ADSVKG (SEQ TRARYNV (SEQ (SEQ ID NO: 217) DSVKG (SEQ ID TSP (SEQ ID
    ID NO: 201) ID NO: 207) NO: 224) NO: 231)
    STYCTYDMH AIDSDGTTRYAD GSRWSDY (SEQ FTFSSYPMS TISAGGDTTLYA GYCYRRNY
    (SEQ ID NO: 196) SVKG (SEQ ID ID NO: 208) (SEQ ID NO: 211) DSVKG (SEQ ID (SEQ ID NO: 225)
    NO: 202) NO: 218)
    STYCTYDMH AIDSDGTTRYAD GSRWSDY (SEQ FTFSNYAMS GINVAYGITSYA HSGTTIPRGFISY
    (SEQ ID NO: 196) SVKG (SEQ ID ID NO: 208) (SEQ ID NO: 212) DSVKG (SEQ ID TK (SEQ ID
    NO: 202) NO: 219) NO: 226)
    STYCTYDMH AIDSDGTTRYAD GSRWSDY (SEQ FSFSSYAMK TISSGGSSTNYA AIVPTGATME
    (SEQ ID NO: 196) SVKG (SEQ ID ID NO: 208) (SEQ ID NO: 213) DSVKG (SEQ ID (SEQ ID NO: 227)
    NO: 202) NO: 220)
    STYCTYDMH AIDSDGTTRYAD GSRWSDY (SEQ FTYSTSNSWMA AIYTVGGSIFYA ASGRLRGKWFW
    (SEQ ID NO: 196) SVKG (SEQ ID ID NO: 208) (SEQ ID NO: 214) DSVRG (SEQ ID PYEYNY (SEQ ID
    NO: 202) NO: 221) NO: 228)
    STYCTYDMH AIDSDGTTRYAD GSRWSDY (SEQ YVSCDYFLPS IIDGTGSTSYAA SCVRGRAISEY
    (SEQ ID NO: 196) SVKG (SEQ ID ID NO: 208) (SEQ ID NO: 215) SVKG (SEQ ID (SEQ ID NO: 229)
    NO: 202) NO: 222)
    STYCTYDMH AIDSDGTTRYAD GSRWSDY (SEQ STYSNYCLG VINWVGGMLYF ESVSSFSCGGWL
    (SEQ ID NO: 196) SVKG (SEQ ID ID NO: 208) (SEQ ID NO: 216) ADSVKG (SEQ TRPDRVPY (SEQ
    NO: 202) ID NO: 223) ID NO: 230)
    STYCTYDMH AIDSDGTTRYAD GSRWSDY (SEQ FTFSLSSMS AISSGGASTYYT GGSGYGDASRM
    (SEQ ID NO: 196) SVKG (SEQ ID ID NO: 208) (SEQ ID NO: 217) DSVKG (SEQ ID TSP (SEQ ID
    NO: 202) NO: 224) NO: 231)
    YAYSTCNMG AFISDGSTYYAD NCYRRLRNY FTFSSYPMS TISAGGDTTLYA GYCYRRNY
    (SEQ ID NO: 197) SVKG (SEQ ID (SEQ ID (SEQ ID NO: 211) DSVKG (SEQ ID (SEQ ID NO: 225)
    NO: 203) NO: 209) NO: 218)
    YAYSTCNMG AFISDGSTYYAD NCYRRLRNY FTFSNYAMS GINVAYGITSYA HSGTTIPRGFISY
    (SEQ ID NO: 197) SVKG (SEQ ID (SEQ ID (SEQ ID NO: 212) DSVKG (SEQ ID TK (SEQ ID
    NO: 203) NO: 209) NO: 219) NO: 226)
    YAYSTCNMG AFISDGSTYYAD NCYRRLRNY FSFSSYAMK TISSGGSSTNYA AIVPTGATME
    (SEQ ID NO: 197) SVKG (SEQ ID (SEQ ID (SEQ ID NO: 213) DSVKG (SEQ ID (SEQ ID NO: 227)
    NO: 203) NO: 209) NO: 220)
    YAYSTCNMG AFISDGSTYYAD NCYRRLRNY FTYSTSNSWMA AIYTVGGSIFYA ASGRLRGKWFW
    (SEQ ID NO: 197) SVKG (SEQ ID (SEQ ID (SEQ ID NO: 214) DSVRG (SEQ ID PYEYNY (SEQ ID
    NO: 203) NO: 209) NO: 221) NO: 228)
    YAYSTCNMG AFISDGSTYYAD NCYRRLRNY YVSCDYFLPS IIDGTGSTSYAA SCVRGRAISEY
    (SEQ ID NO: 197) SVKG (SEQ ID (SEQ ID (SEQ ID NO: 215) SVKG (SEQ ID (SEQ ID NO: 229)
    NO: 203) NO: 209) NO: 222)
    YAYSTCNMG AFISDGSTYYAD NCYRRLRNY STYSNYCLG VINWVGGMLYF ESVSSFSCGGWL
    (SEQ ID NO: 197) SVKG (SEQ ID (SEQ ID (SEQ ID NO: 216) ADSVKG (SEQ TRPDRVPY (SEQ
    NO: 203) NO: 209) ID NO: 223) ID NO: 230)
    YAYSTCNMG AFISDGSTYYAD NCYRRLRNY FTFSLSSMS AISSGGASTYYT GGSGYGDASRM
    (SEQ ID NO: 197) SVKG (SEQ ID (SEQ ID (SEQ ID NO: 217) DSVKG (SEQ ID TSP (SEQ ID
    NO: 203) NO: 209) NO: 224) NO: 231)
    LTFDDSVMG CISSSGANAFYA GHACAGYYPIP FTFSSYPMS TISAGGDTTLYA GYCYRRNY
    (SEQ ID NO: 198) DSVKG (SEQ ID YDDY (SEQ ID (SEQ ID NO: 211) DSVKG (SEQ ID (SEQ ID NO: 225)
    NO: 204) NO: 210) NO: 218)
    LTFDDSVMG CISSSGANAFYA GHACAGYYPIP FTFSNYAMS GINVAYGITSYA HSGTTIPRGFISY
    (SEQ ID NO: 198) DSVKG (SEQ ID YDDY (SEQ ID (SEQ ID NO: 212) DSVKG (SEQ ID TK (SEQ ID
    NO: 204) NO: 210) NO: 219) NO: 226)
    LTFDDSVMG CISSSGANAFYA GHACAGYYPIP FSFSSYAMK TISSGGSSTNYA AIVPTGATME
    (SEQ ID NO: 198) DSVKG (SEQ ID YDDY (SEQ ID (SEQ ID NO: 213) DSVKG (SEQ ID (SEQ ID NO: 227)
    NO: 204) NO: 210) NO: 220)
    LTFDDSVMG CISSSGANAFYA GHACAGYYPIP FTYSTSNSWMA AIYTVGGSIFYA ASGRLRGKWFW
    (SEQ ID NO: 198) DSVKG (SEQ ID YDDY (SEQ ID (SEQ ID NO: 214) DSVRG (SEQ ID PYEYNY (SEQ ID
    NO: 204) NO: 210) NO: 221) NO: 228)
    LTFDDSVMG CISSSGANAFYA GHACAGYYPIP YVSCDYFLPS IIDGTGSTSYAA SCVRGRAISEY
    (SEQ ID NO: 198) DSVKG (SEQ ID YDDY (SEQ ID (SEQ ID NO: 215) SVKG (SEQ ID (SEQ ID NO: 229)
    NO: 204) NO: 210) NO: 222)
    LTFDDSVMG CISSSGANAFYA GHACAGYYPIP STYSNYCLG VINWVGGMLYF ESVSSFSCGGWL
    (SEQ ID NO: 198) DSVKG (SEQ ID YDDY (SEQ ID (SEQ ID NO: 216) ADSVKG (SEQ TRPDRVPY (SEQ
    NO: 204) NO: 210) ID NO: 223) ID NO: 230)
    LTFDDSVMG CISSSGANAFYA GHACAGYYPIP FTFSLSSMS AISSGGASTYYT GGSGYGDASRM
    (SEQ ID NO: 198) DSVKG (SEQ ID YDDY (SEQ ID (SEQ ID NO: 217) DSVKG (SEQ ID TSP (SEQ ID
    NO: 204) NO: 210) NO: 224) NO: 231)
  • Anti-GP130-Linker-Anti-Il27Rα VHH
  • A bispecific VHH2 can contain, from the N-terminus to the C-terminus, a first VHH binding to gp130 (an anti-gp130 VHH antibody), a linker, and a second VHH binding to IL27Rα (an anti-IL27Rα VHH antibody). In other words, the linker joins the C-terminus of the anti-gp130 VHH in the binding protein to the N-terminus of the anti-IL27Rα VHH in the binding protein. In some embodiments, a purification peptide, e.g., a six-histidine peptide ((His)6 (SEQ ID NO: 1531) or His-tag) can be included, or not, in the bispecific VHH2.
  • In certain embodiments, a bispecific VHH2 described herein comprises an anti-gp130 VHH antibody comprising a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity to a sequence of any one of SEQ ID NOS:232-237; and an anti-IL27Rα VHH antibody comprising a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity to a sequence of any one of SEQ ID NOS:238-244.
  • In certain embodiments, a bispecific VHH2 described herein comprises an anti-gp130 VHH antibody and an anti-IL27Rα VHH antibody as described in each row of Table 2A below or Table 1A above. In some embodiments, in each row of Table 2A, the anti-gp130 VHH antibody and the anti-IL27Rα VHH antibody can each, independently, comprise at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity to the sequence described in each row of Table 2A. In some embodiments, the bispecific VHH2 can comprise a linker (e.g., linkers described in Section IV) between the anti-gp130 VHH antibody and the anti-IL27Rα VHH antibody as described in each row of Table 2A below. In particular embodiments, the linker is GGGS (SEQ ID NO:108) or (GGGS)n (SEQ ID NO: 1532), (GGS)nG (SEQ ID NO: 1533), (GGGGS)n (SEQ ID NO: 1534) as described elwhere herein. The sequence of the anti-gp130 VHH is N-terminus to the linker and the sequence of the anti-IL27Rα VHH is C-terminus to the linker. Examples of linkers are further described in Section IV below. The CDR sequences in each VHH are underlined.
  • TABLE 2A
    N-terminal Anti-gp130 VHH C-terminal Anti-IL27Rα VHH
    QVQLQESGGGSVQAGGSLRLSCTASGAIASGY QVQLQESGGGLVQPGGSLRLSCAASGFTFSSY
    IDSRWCMAWFRQAPGKEREGVAAIWPGGGLT PMSWVRQAPGKGLEWISTISAGGDTTLYADSV
    VYADSVKGRFTISRDHAKNTLYLQMNNLKPE KGRFTSSRDNAKNTLYLQLNSLKTEDAAIYYC
    DTAMYYCAAGSPRMCPSLEFGFDYWGQGTQV AKRIDCNSGYCYRRNYWGQGTQVTVS (SEQ
    TVSS (SEQ ID NO: 232) ID NO: 238)
    QVQLQESGGGSVQAGGSLRLSCTASGAIASGY QVQLQESGGGLVQPGESLRLSCTASGFTFSNY
    IDSRWCMAWFRQAPGKEREGVAAIWPGGGLT AMSWVRQAPGKGLEWVSGINVAYGITSYADS
    VYADSVKGRFTISRDHAKNTLYLQMNNLKPE VKGRFTISRDNTKNTLYLQLNSLKTEDTAIYYC
    DTAMYYCAAGSPRMCPSLEFGFDYWGQGTQV VKHSGTTIPRGFISYTKRGQGTQVTVS (SEQ ID
    TVSS (SEQ ID NO: 232) NO: 239)
    QVQLQESGGGSVQAGGSLRLSCTASGAIASGY QVQLQESGGGLVQPGGSLRLSCAASGFSFSSY
    IDSRWCMAWFRQAPGKEREGVAAIWPGGGLT AMKWVRQAPGKGLEWVSTISSGGSSTNYADS
    VYADSVKGRFTISRDHAKNTLYLQMNNLKPE VKGRFTISRDNAKNTLYLQLNSLKIEDTAMYY
    DTAMYYCAAGSPRMCPSLEFGFDYWGQGTQV CAKAIVPTGATMERGQGTQVTVS (SEQ ID
    TVSS (SEQ ID NO: 232) NO: 240)
    QVQLQESGGGSVQAGGSLRLSCTASGAIASGY QVQLQESGGGSVQSGGSLRLSCAASGFTYSTS
    IDSRWCMAWFRQAPGKEREGVAAIWPGGGLT NSWMAWFRQAPGKEREGVAAIYTVGGSIFYA
    VYADSVKGRFTISRDHAKNTLYLQMNNLKPE DSVRGRFTISQDATKNMFYLQMNTLKPEDTA
    DTAMYYCAAGSPRMCPSLEFGFDYWGQGTQV MYYCAAASGRLRGKWFWPYEYNYWGQGTQ
    TVSS (SEQ ID NO: 232) VTVS (SEQ ID NO: 241)
    QVQLQESGGGSVQAGGSLRLSCTASGAIASGY QVQLQESGGGSVQAGGSLRLSCVASGYVSCD
    IDSRWCMAWFRQAPGKEREGVAAIWPGGGLT YFLPSWYRQAPGKEREFVSIIDGTGSTSYAASV
    VYADSVKGRFTISRDHAKNTLYLQMNNLKPE KGRFTASQDKGKNIAYLQMNTLKPEDTAMYY
    DTAMYYCAAGSPRMCPSLEFGFDYWGQGTQV CKASCVRGRAISEYWGQGTQVTVS (SEQ ID
    TVSS (SEQ ID NO: 232) NO: 242)
    QVQLQESGGGSVQAGGSLRLSCTASGAIASGY QVQLQESGGGSVQAGGSLRLSCRASGSTYSNY
    IDSRWCMAWFRQAPGKEREGVAAIWPGGGLT CLGWFRQITGKEREGVAVINWVGGMLYFADS
    VYADSVKGRFTISRDHAKNTLYLQMNNLKPE VKGRFTVSQDQAKNTVYLQMNSLKPEDTAMY
    DTAMYYCAAGSPRMCPSLEFGFDYWGQGTQV YCAAESVSSFSCGGWLTRPDRVPYWGQGTQV
    TVSS (SEQ ID NO: 232) TVS (SEQ ID NO: 243)
    QVQLQESGGGSVQAGGSLRLSCTASGAIASGY QVQLQESGGGLVQPGGSLRLSCAASGFTFSLSS
    IDSRWCMAWFRQAPGKEREGVAAIWPGGGLT MSWVRQAPGKGLEWVSAISSGGASTYYTDSV
    VYADSVKGRFTISRDHAKNTLYLQMNNLKPE KGRFTISRDNAKNMLYLQLNSLKTEDTAMYY
    DTAMYYCAAGSPRMCPSLEFGFDYWGQGTQV CAKGGSGYGDASRMTSPGSQGTQVTVS (SEQ
    TVSS (SEQ ID NO: 232) ID NO: 244)
    QVQLQESGGGSVQAGGSLRLSCTAPGFTSNSC QVQLQESGGGLVQPGGSLRLSCAASGFTFSSY
    GMDWYRQAPGKEREFVSSISTDGTTGYADSV PMSWVRQAPGKGLEWISTISAGGDTTLYADSV
    KGRFTISKDKAKDTVYLQMNSLKPEDTGMYS KGRFTSSRDNAKNTLYLQLNSLKTEDAAIYYC
    CKTKDGTIATMELCDFGYWGQGTQVTVSS AKRIDCNSGYCYRRNYWGQGTQVTVS (SEQ
    (SEQ ID NO: 233) ID NO: 238)
    QVQLQESGGGSVQAGGSLRLSCTAPGFTSNSC QVQLQESGGGLVQPGESLRLSCTASGFTFSNY
    GMDWYRQAPGKEREFVSSISTDGTTGYADSV AMSWVRQAPGKGLEWVSGINVAYGITSYADS
    KGRFTISKDKAKDTVYLQMNSLKPEDTGMYS VKGRFTISRDNTKNTLYLQLNSLKTEDTAIYYC
    CKTKDGTIATMELCDFGYWGQGTQVTVSS VKHSGTTIPRGFISYTKRGQGTQVTVS (SEQ ID
    (SEQ ID NO: 233) NO: 239)
    QVQLQESGGGSVQAGGSLRLSCTAPGFTSNSC QVQLQESGGGLVQPGGSLRLSCAASGFSFSSY
    GMDWYRQAPGKEREFVSSISTDGTTGYADSV AMKWVRQAPGKGLEWVSTISSGGSSTNYADS
    KGRFTISKDKAKDTVYLQMNSLKPEDTGMYS VKGRFTISRDNAKNTLYLQLNSLKIEDTAMYY
    CKTKDGTIATMELCDFGYWGQGTQVTVSS CAKAIVPTGATMERGQGTQVTVS (SEQ ID
    (SEQ ID NO: 233) NO: 240)
    QVQLQESGGGSVQAGGSLRLSCTAPGFTSNSC QVQLQESGGGSVQSGGSLRLSCAASGFTYSTS
    GMDWYRQAPGKEREFVSSISTDGTTGYADSV NSWMAWFRQAPGKEREGVAAIYTVGGSIFYA
    KGRFTISKDKAKDTVYLQMNSLKPEDTGMYS DSVRGRFTISQDATKNMFYLQMNTLKPEDTA
    CKTKDGTIATMELCDFGYWGQGTQVTVSS MYYCAAASGRLRGKWFWPYEYNYWGQGTQ
    (SEQ ID NO: 233) VTVS (SEQ ID NO: 241)
    QVQLQESGGGSVQAGGSLRLSCTAPGFTSNSC QVQLQESGGGSVQAGGSLRLSCVASGYVSCD
    GMDWYRQAPGKEREFVSSISTDGTTGYADSV YFLPSWYRQAPGKEREFVSIIDGTGSTSYAASV
    KGRFTISKDKAKDTVYLQMNSLKPEDTGMYS KGRFTASQDKGKNIAYLQMNTLKPEDTAMYY
    CKTKDGTIATMELCDFGYWGQGTQVTVSS CKASCVRGRAISEYWGQGTQVTVS (SEQ ID
    (SEQ ID NO: 233) NO: 242)
    QVQLQESGGGSVQAGGSLRLSCTAPGFTSNSC QVQLQESGGGSVQAGGSLRLSCRASGSTYSNY
    GMDWYRQAPGKEREFVSSISTDGTTGYADSV CLGWFRQITGKEREGVAVINWVGGMLYFADS
    KGRFTISKDKAKDTVYLQMNSLKPEDTGMYS VKGRFTVSQDQAKNTVYLQMNSLKPEDTAMY
    CKTKDGTIATMELCDFGYWGQGTQVTVSS YCAAESVSSFSCGGWLTRPDRVPYWGQGTQV
    (SEQ ID NO: 233) TVS (SEQ ID NO: 243)
    QVQLQESGGGSVQAGGSLRLSCTAPGFTSNSC QVQLQESGGGLVQPGGSLRLSCAASGFTFSLSS
    GMDWYRQAPGKEREFVSSISTDGTTGYADSV MSWVRQAPGKGLEWVSAISSGGASTYYTDSV
    KGRFTISKDKAKDTVYLQMNSLKPEDTGMYS KGRFTISRDNAKNMLYLQLNSLKTEDTAMYY
    CKTKDGTIATMELCDFGYWGQGTQVTVSS CAKGGSGYGDASRMTSPGSQGTQVTVS (SEQ
    (SEQ ID NO: 233) ID NO: 244)
    QVQLQESGGGSVQAGGSLRLSCAASGYPYSN QVQLQESGGGLVQPGGSLRLSCAASGFTFSSY
    GYMGWFRQAPGKEREGVATIYTGDGRTYYAD PMSWVRQAPGKGLEWISTISAGGDTTLYADSV
    SVKGRFTISRDNAKNTVDLQMSSLKPEDTAMY KGRFTSSRDNAKNTLYLQLNSLKTEDAAIYYC
    YCAARAAPLYSSGSPLTRARYNVWGQGTQVT AKRIDCNSGYCYRRNYWGQGTQVTVS (SEQ
    VSS (SEQ ID NO: 234) ID NO: 238)
    QVQLQESGGGSVQAGGSLRLSCAASGYPYSN QVQLQESGGGLVQPGESLRLSCTASGFTFSNY
    GYMGWFRQAPGKEREGVATIYTGDGRTYYAD AMSWVRQAPGKGLEWVSGINVAYGITSYADS
    SVKGRFTISRDNAKNTVDLQMSSLKPEDTAMY VKGRFTISRDNTKNTLYLQLNSLKTEDTAIYYC
    YCAARAAPLYSSGSPLTRARYNVWGQGTQVT VKHSGTTIPRGFISYTKRGQGTQVTVS (SEQ ID
    VSS (SEQ ID NO: 234) NO: 239)
    QVQLQESGGGSVQAGGSLRLSCAASGYPYSN QVQLQESGGGLVQPGGSLRLSCAASGFSFSSY
    GYMGWFRQAPGKEREGVATIYTGDGRTYYAD AMKWVRQAPGKGLEWVSTISSGGSSTNYADS
    SVKGRFTISRDNAKNTVDLQMSSLKPEDTAMY VKGRFTISRDNAKNTLYLQLNSLKIEDTAMYY
    YCAARAAPLYSSGSPLTRARYNVWGQGTQVT CAKAIVPTGATMERGQGTQVTVS (SEQ ID
    VSS (SEQ ID NO: 234) NO: 240)
    QVQLQESGGGSVQAGGSLRLSCAASGYPYSN QVQLQESGGGSVQSGGSLRLSCAASGFTYSTS
    GYMGWFRQAPGKEREGVATIYTGDGRTYYAD NSWMAWFRQAPGKEREGVAAIYTVGGSIFYA
    SVKGRFTISRDNAKNTVDLQMSSLKPEDTAMY DSVRGRFTISQDATKNMFYLQMNTLKPEDTA
    YCAARAAPLYSSGSPLTRARYNVWGQGTQVT MYYCAAASGRLRGKWFWPYEYNYWGQGTQ
    VSS (SEQ ID NO: 234) VTVS (SEQ ID NO: 241)
    QVQLQESGGGSVQAGGSLRLSCAASGYPYSN QVQLQESGGGSVQAGGSLRLSCVASGYVSCD
    GYMGWFRQAPGKEREGVATIYTGDGRTYYAD YFLPSWYRQAPGKEREFVSIIDGTGSTSYAASV
    SVKGRFTISRDNAKNTVDLQMSSLKPEDTAMY KGRFTASQDKGKNIAYLQMNTLKPEDTAMYY
    YCAARAAPLYSSGSPLTRARYNVWGQGTQVT CKASCVRGRAISEYWGQGTQVTVS (SEQ ID
    VSS (SEQ ID NO: 234) NO: 242)
    QVQLQESGGGSVQAGGSLRLSCAASGYPYSN QVQLQESGGGSVQAGGSLRLSCRASGSTYSNY
    GYMGWFRQAPGKEREGVATIYTGDGRTYYAD CLGWFRQITGKEREGVAVINWVGGMLYFADS
    SVKGRFTISRDNAKNTVDLQMSSLKPEDTAMY VKGRFTVSQDQAKNTVYLQMNSLKPEDTAMY
    YCAARAAPLYSSGSPLTRARYNVWGQGTQVT YCAAESVSSFSCGGWLTRPDRVPYWGQGTQV
    VSS (SEQ ID NO: 234) TVS (SEQ ID NO: 243)
    QVQLQESGGGSVQAGGSLRLSCAASGYPYSN QVQLQESGGGLVQPGGSLRLSCAASGFTFSLSS
    GYMGWFRQAPGKEREGVATIYTGDGRTYYAD MSWVRQAPGKGLEWVSAISSGGASTYYTDSV
    SVKGRFTISRDNAKNTVDLQMSSLKPEDTAMY KGRFTISRDNAKNMLYLQLNSLKTEDTAMYY
    YCAARAAPLYSSGSPLTRARYNVWGQGTQVT CAKGGSGYGDASRMTSPGSQGTQVTVS (SEQ
    VSS (SEQ ID NO: 234) ID NO: 244)
    QVQLQESGGGSVQAGGSLRLSCVASASTYCTY QVQLQESGGGLVQPGGSLRLSCAASGFTFSSY
    DMHWYRQAPGKGREFVSAIDSDGTTRYADSV PMSWVRQAPGKGLEWISTISAGGDTTLYADSV
    KGRFTISQGTAKNTVYLQMNSLQPEDTAMYY KGRFTSSRDNAKNTLYLQLNSLKTEDAAIYYC
    CKTVCVVGSRWSDYWGQGTQVTVSS (SEQ ID AKRIDCNSGYCYRRNYWGQGTQVTVS (SEQ
    NO: 235) ID NO: 238)
    QVQLQESGGGSVQAGGSLRLSCVASASTYCTY QVQLQESGGGLVQPGESLRLSCTASGFTFSNY
    DMHWYRQAPGKGREFVSAIDSDGTTRYADSV AMSWVRQAPGKGLEWVSGINVAYGITSYADS
    KGRFTISQGTAKNTVYLQMNSLQPEDTAMYY VKGRFTISRDNTKNTLYLQLNSLKTEDTAIYYC
    CKTVCVVGSRWSDYWGQGTQVTVSS (SEQ ID VKHSGTTIPRGFISYTKRGQGTQVTVS (SEQ ID
    NO: 235) NO: 239)
    QVQLQESGGGSVQAGGSLRLSCVASASTYCTY QVQLQESGGGLVQPGGSLRLSCAASGFSFSSY
    DMHWYRQAPGKGREFVSAIDSDGTTRYADSV AMKWVRQAPGKGLEWVSTISSGGSSTNYADS
    KGRFTISQGTAKNTVYLQMNSLQPEDTAMYY VKGRFTISRDNAKNTLYLQLNSLKIEDTAMYY
    CKTVCVVGSRWSDYWGQGTQVTVSS (SEQ ID CAKAIVPTGATMERGQGTQVTVS (SEQ ID
    NO: 235) NO: 240)
    QVQLQESGGGSVQAGGSLRLSCVASASTYCTY QVQLQESGGGSVQSGGSLRLSCAASGFTYSTS
    DMHWYRQAPGKGREFVSAIDSDGTTRYADSV NSWMAWFRQAPGKEREGVAAIYTVGGSIFYA
    KGRFTISQGTAKNTVYLQMNSLQPEDTAMYY DSVRGRFTISQDATKNMFYLQMNTLKPEDTA
    CKTVCVVGSRWSDYWGQGTQVTVSS (SEQ ID MYYCAAASGRLRGKWFWPYEYNYWGQGTQ
    NO: 235) VTVS (SEQ ID NO: 241)
    QVQLQESGGGSVQAGGSLRLSCVASASTYCTY QVQLQESGGGSVQAGGSLRLSCVASGYVSCD
    DMHWYRQAPGKGREFVSAIDSDGTTRYADSV YFLPSWYRQAPGKEREFVSIIDGTGSTSYAASV
    KGRFTISQGTAKNTVYLQMNSLQPEDTAMYY KGRFTASQDKGKNIAYLQMNTLKPEDTAMYY
    CKTVCVVGSRWSDYWGQGTQVTVSS (SEQ ID CKASCVRGRAISEYWGQGTQVTVS (SEQ ID
    NO: 235) NO: 242)
    QVQLQESGGGSVQAGGSLRLSCVASASTYCTY QVQLQESGGGSVQAGGSLRLSCRASGSTYSNY
    DMHWYRQAPGKGREFVSAIDSDGTTRYADSV CLGWFRQITGKEREGVAVINWVGGMLYFADS
    KGRFTISQGTAKNTVYLQMNSLQPEDTAMYY VKGRFTVSQDQAKNTVYLQMNSLKPEDTAMY
    CKTVCVVGSRWSDYWGQGTQVTVSS (SEQ ID YCAAESVSSFSCGGWLTRPDRVPYWGQGTQV
    NO: 235) TVS (SEQ ID NO: 243)
    QVQLQESGGGSVQAGGSLRLSCVASASTYCTY QVQLQESGGGLVQPGGSLRLSCAASGFTFSLSS
    DMHWYRQAPGKGREFVSAIDSDGTTRYADSV MSWVRQAPGKGLEWVSAISSGGASTYYTDSV
    KGRFTISQGTAKNTVYLQMNSLQPEDTAMYY KGRFTISRDNAKNMLYLQLNSLKTEDTAMYY
    CKTVCVVGSRWSDYWGQGTQVTVSS (SEQ ID CAKGGSGYGDASRMTSPGSQGTQVTVS (SEQ
    NO: 235) ID NO: 244)
    QVQLQESGGGSVQAGGSLTLSCAASEYAYSTC QVQLQESGGGLVQPGGSLRLSCAASGFTFSSY
    NMGWYRQAPGKERELVSAFISDGSTYYADSV PMSWVRQAPGKGLEWISTISAGGDTTLYADSV
    KGRFTITRDNAKNTVYLQMNSLKPEDTAIYYC KGRFTSSRDNAKNTLYLQLNSLKTEDAAIYYC
    SANCYRRLRNYWGQGTQVTVSS (SEQ ID AKRIDCNSGYCYRRNYWGQGTQVTVS (SEQ
    NO: 236) ID NO: 238)
    QVQLQESGGGSVQAGGSLTLSCAASEYAYSTC QVQLQESGGGLVQPGESLRLSCTASGFTFSNY
    NMGWYRQAPGKERELVSAFISDGSTYYADSV AMSWVRQAPGKGLEWVSGINVAYGITSYADS
    KGRFTITRDNAKNTVYLQMNSLKPEDTAIYYC VKGRFTISRDNTKNTLYLQLNSLKTEDTAIYYC
    SANCYRRLRNYWGQGTQVTVSS (SEQ ID VKHSGTTIPRGFISYTKRGQGTQVTVS (SEQ ID
    NO: 236) NO: 239)
    QVQLQESGGGSVQAGGSLTLSCAASEYAYSTC QVQLQESGGGLVQPGGSLRLSCAASGFSFSSY
    NMGWYRQAPGKERELVSAFISDGSTYYADSV AMKWVRQAPGKGLEWVSTISSGGSSTNYADS
    KGRFTITRDNAKNTVYLQMNSLKPEDTAIYYC VKGRFTISRDNAKNTLYLQLNSLKIEDTAMYY
    SANCYRRLRNYWGQGTQVTVSS (SEQ ID CAKAIVPTGATMERGQGTQVTVS (SEQ ID
    NO: 236) NO: 240)
    QVQLQESGGGSVQAGGSLTLSCAASEYAYSTC QVQLQESGGGSVQSGGSLRLSCAASGFTYSTS
    NMGWYRQAPGKERELVSAFISDGSTYYADSV NSWMAWFRQAPGKEREGVAAIYTVGGSIFYA
    KGRFTITRDNAKNTVYLQMNSLKPEDTAIYYC DSVRGRFTISQDATKNMFYLQMNTLKPEDTA
    SANCYRRLRNYWGQGTQVTVSS (SEQ ID MYYCAAASGRLRGKWFWPYEYNYWGQGTQ
    NO: 236) VTVS (SEQ ID NO: 241)
    QVQLQESGGGSVQAGGSLTLSCAASEYAYSTC QVQLQESGGGSVQAGGSLRLSCVASGYVSCD
    NMGWYRQAPGKERELVSAFISDGSTYYADSV YFLPSWYRQAPGKEREFVSIIDGTGSTSYAASV
    KGRFTITRDNAKNTVYLQMNSLKPEDTAIYYC KGRFTASQDKGKNIAYLQMNTLKPEDTAMYY
    SANCYRRLRNYWGQGTQVTVSS (SEQ ID CKASCVRGRAISEYWGQGTQVTVS (SEQ ID
    NO: 236) NO: 242)
    QVQLQESGGGSVQAGGSLTLSCAASEYAYSTC QVQLQESGGGSVQAGGSLRLSCRASGSTYSNY
    NMGWYRQAPGKERELVSAFISDGSTYYADSV CLGWFRQITGKEREGVAVINWVGGMLYFADS
    KGRFTITRDNAKNTVYLQMNSLKPEDTAIYYC VKGRFTVSQDQAKNTVYLQMNSLKPEDTAMY
    SANCYRRLRNYWGQGTQVTVSS (SEQ ID YCAAESVSSFSCGGWLTRPDRVPYWGQGTQV
    NO: 236) TVS (SEQ ID NO: 243)
    QVQLQESGGGSVQAGGSLTLSCAASEYAYSTC QVQLQESGGGLVQPGGSLRLSCAASGFTFSLSS
    NMGWYRQAPGKERELVSAFISDGSTYYADSV MSWVRQAPGKGLEWVSAISSGGASTYYTDSV
    KGRFTITRDNAKNTVYLQMNSLKPEDTAIYYC KGRFTISRDNAKNMLYLQLNSLKTEDTAMYY
    SANCYRRLRNYWGQGTQVTVSS (SEQ ID CAKGGSGYGDASRMTSPGSQGTQVTVS (SEQ
    NO: 236) ID NO: 244)
    QVQLQESGGGLVQPGGSLRLSCTASGLTFDDS QVQLQESGGGLVQPGGSLRLSCAASGFTFSSY
    VMGWFRQAPGKGREAVSCISSSGANAFYADS PMSWVRQAPGKGLEWISTISAGGDTTLYADSV
    VKGRFTISRDNAKNTLYLQMNSLKPEDTATYY KGRFTSSRDNAKNTLYLQLNSLKTEDAAIYYC
    CKRGHACAGYYPIPYDDYWGQGTQVTVSS AKRIDCNSGYCYRRNYWGQGTQVTVS (SEQ
    (SEQ ID NO: 237) ID NO: 238)
    QVQLQESGGGLVQPGGSLRLSCTASGLTFDDS QVQLQESGGGLVQPGESLRLSCTASGFTFSNY
    VMGWFRQAPGKGREAVSCISSSGANAFYADS AMSWVRQAPGKGLEWVSGINVAYGITSYADS
    VKGRFTISRDNAKNTLYLQMNSLKPEDTATYY VKGRFTISRDNTKNTLYLQLNSLKTEDTAIYYC
    CKRGHACAGYYPIPYDDYWGQGTQVTVSS VKHSGTTIPRGFISYTKRGQGTQVTVS (SEQ ID
    (SEQ ID NO: 237) NO: 239)
    QVQLQESGGGLVQPGGSLRLSCTASGLTFDDS QVQLQESGGGLVQPGGSLRLSCAASGFSFSSY
    VMGWFRQAPGKGREAVSCISSSGANAFYADS AMKWVRQAPGKGLEWVSTISSGGSSTNYADS
    VKGRFTISRDNAKNTLYLQMNSLKPEDTATYY VKGRFTISRDNAKNTLYLQLNSLKIEDTAMYY
    CKRGHACAGYYPIPYDDYWGQGTQVTVSS CAKAIVPTGATMERGQGTQVTVS (SEQ ID
    (SEQ ID NO: 237) NO: 240)
    QVQLQESGGGLVQPGGSLRLSCTASGLTFDDS QVQLQESGGGSVQSGGSLRLSCAASGFTYSTS
    VMGWFRQAPGKGREAVSCISSSGANAFYADS NSWMAWFRQAPGKEREGVAAIYTVGGSIFYA
    VKGRFTISRDNAKNTLYLQMNSLKPEDTATYY DSVRGRFTISQDATKNMFYLQMNTLKPEDTA
    CKRGHACAGYYPIPYDDYWGQGTQVTVSS MYYCAAASGRLRGKWFWPYEYNYWGQGTQ
    (SEQ ID NO: 237) VTVS (SEQ ID NO: 241)
    QVQLQESGGGLVQPGGSLRLSCTASGLTFDDS QVQLQESGGGSVQAGGSLRLSCVASGYVSCD
    VMGWFRQAPGKGREAVSCISSSGANAFYADS YFLPSWYRQAPGKEREFVSIIDGTGSTSYAASV
    VKGRFTISRDNAKNTLYLQMNSLKPEDTATYY KGRFTASQDKGKNIAYLQMNTLKPEDTAMYY
    CKRGHACAGYYPIPYDDYWGQGTQVTVSS CKASCVRGRAISEYWGQGTQVTVS (SEQ ID
    (SEQ ID NO: 237) NO: 242)
    QVQLQESGGGLVQPGGSLRLSCTASGLTFDDS QVQLQESGGGSVQAGGSLRLSCRASGSTYSNY
    VMGWFRQAPGKGREAVSCISSSGANAFYADS CLGWFRQITGKEREGVAVINWVGGMLYFADS
    VKGRFTISRDNAKNTLYLQMNSLKPEDTATYY VKGRFTVSQDQAKNTVYLQMNSLKPEDTAMY
    CKRGHACAGYYPIPYDDYWGQGTQVTVSS YCAAESVSSFSCGGWLTRPDRVPYWGQGTQV
    (SEQ ID NO: 237) TVS (SEQ ID NO: 243)
    QVQLQESGGGLVQPGGSLRLSCTASGLTFDDS QVQLQESGGGLVQPGGSLRLSCAASGFTFSLSS
    VMGWFRQAPGKGREAVSCISSSGANAFYADS MSWVRQAPGKGLEWVSAISSGGASTYYTDSV
    VKGRFTISRDNAKNTLYLQMNSLKPEDTATYY KGRFTISRDNAKNMLYLQLNSLKTEDTAMYY
    CKRGHACAGYYPIPYDDYWGQGTQVTVSS CAKGGSGYGDASRMTSPGSQGTQVTVS (SEQ
    (SEQ ID NO: 237) ID NO: 244)
  • In certain embodiments, the bispecific VHHZ Comprises a sequence that is substantially identical to a sequence of any one of SEQ ID NOS: 1-42. Such a bispecific VHH2 can have a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 9900, or 1000%) sequence identity to a sequence of any one of SEQ ID NOS: 1-42, as shown in Table 2B below. In each of sequences of SEQ ID NOS: 1-42, the linker GGGS (SEQ ID NO: 108) is in bold. The sequence of the anti-gp130 VHH is N-terminus to the linker and the sequence of the anti-IL27Rα VHH is C-terminus to the linker. The CDR sequences in each VHH are underlined.
  • TABLE 2B
    SEQ
    ID
    NO Sequence
     1 QVQLQESGGGSVQAGGSLRLSCTASGAIASGYIDSRWCMAWFRQAPGKEREGVAAIWPGG
    GLTVYADSVKGRFTISRDHAKNTLYLQMNNLKPEDTAMYYCAAGSPRMCPSLEFGFDYW
    GQGTQVTVSSGGGSQVQLQESGGGLVQPGGSLRLSCAASGFTFSSYPMSWVRQAPGKGLE
    WISTISAGGDTTLYADSVKGRFTSSRDNAKNTLYLQLNSLKTEDAAIYYCAKRIDCNSGYC
    YRRNY WGQGTQVTVSS
     2 QVQLQESGGGSVQAGGSLRLSCTASGAIASGYIDSRWCMAWFRQAPGKEREGVAAIWPGG
    GLTVYADSVKGRFTISRDHAKNTLYLQMNNLKPEDTAMYYCAAGSPRMCPSLEFGFDYW
    GQGTQVTVSSGGGSQVQLQESGGGLVQPGESLRLSCTASGFTFSNYAMSWVRQAPGKGLE
    WVSGINVAYGITSYADSVKGRFTISRDNTKNTLYLQLNSLKTEDTAIYYCVKHSGTTIPRGFI
    SYTK RGQGTQVTVSS
     3 QVQLQESGGGSVQAGGSLRLSCTASGAIASGYIDSRWCMAWFRQAPGKEREGVAAIWPGG
    GLTVYADSVKGRFTISRDHAKNTLYLQMNNLKPEDTAMYYCAAGSPRMCPSLEFGFDYW
    GQGTQVTVSSGGGSQVQLQESGGGLVQPGGSLRLSCAASGFSFSSYAMKWVRQAPGKGL
    EWVSTISSGGSSTNYADSVKGRFTISRDNAKNTLYLQLNSLKIEDTAMYYCAKAIVPTGAT
    ME RGQGTQVTVSS
     4 QVQLQESGGGSVQAGGSLRLSCTASGAIASGYIDSRWCMAWFRQAPGKEREGVAAIWPGG
    GLTVYADSVKGRFTISRDHAKNTLYLQMNNLKPEDTAMYYCAAGSPRMCPSLEFGFDYW
    GQGTQVTVSSGGGSQVQLQESGGGSVQSGGSLRLSCAASGFTYSTSNSWMAWFRQAPGK
    EREGVAAIYTVGGSIFYADSVRGRFTISQDATKNMFYLQMNTLKPEDTAMYYCAAASGRL
    RGKWFWPYEYNYWGQGTQVTVSS
     5 QVQLQESGGGSVQAGGSLRLSCTASGAIASGYIDSRWCMAWFRQAPGKEREGVAAIWPGG
    GLTVYADSVKGRFTISRDHAKNTLYLQMNNLKPEDTAMYYCAAGSPRMCPSLEFGFDYW
    GQGTQVTVSSGGGSQVQLQESGGGSVQAGGSLRLSCVASGYVSCDYFLPSWYRQAPGKE
    REFVSIIDGTGSTSYAASVKGRFTASQDKGKNIAYLQMNTLKPEDTAMYYCKASCVRGRAI
    SEY WGQGTQVTVSS
     6 QVQLQESGGGSVQAGGSLRLSCTASGAIASGYIDSRWCMAWFRQAPGKEREGVAAIWPGG
    GLTVYADSVKGRFTISRDHAKNTLYLQMNNLKPEDTAMYYCAAGSPRMCPSLEFGFDYW
    GQGTQVTVSSGGGSQVQLQESGGGSVQAGGSLRLSCRASGSTYSNYCLGWFRQITGKERE
    GVAVINWVGGMLYFADSVKGRFTVSQDQAKNTVYLQMNSLKPEDTAMYYCAAESVSSFS
    CGGWLTRPDRVPYWGQGTQVTVSS
     7 QVQLQESGGGSVQAGGSLRLSCTASGAIASGYIDSRWCMAWFRQAPGKEREGVAAIWPGG
    GLTVYADSVKGRFTISRDHAKNTLYLQMNNLKPEDTAMYYCAAGSPRMCPSLEFGFDYW
    GQGTQVTVSSGGGSQVQLQESGGGLVQPGGSLRLSCAASGFTFSLSSMSWVRQAPGKGLE
    WVSAISSGGASTYYTDSVKGRFTISRDNAKNMLYLQLNSLKTEDTAMYYCAKGGSGYGDA
    SRMTSP GSQGTQVTVSS
     8 QVQLQESGGGSVQAGGSLRLSCTAPGFTSNSCGMDWYRQAPGKEREFVSSISTDGTTGYA
    DSVKGRFTISKDKAKDTVYLQMNSLKPEDTGMYSCKTKDGTIATMELCDFGYWGQGTQV
    TVSSGGGSQVQLQESGGGLVQPGGSLRLSCAASGFTFSSYPMSWVRQAPGKGLEWISTISA
    GGDTTLYADSVKGRFTSSRDNAKNTLYLQLNSLKTEDAAIYYCAKRIDCNSGYCYRRNYW
    GQGTQVTVSS
     9 QVQLQESGGGSVQAGGSLRLSCTAPGFTSNSCGMDWYRQAPGKEREFVSSISTDGTTGYA
    DSVKGRFTISKDKAKDTVYLQMNSLKPEDTGMYSCKTKDGTIATMELCDFGYWGQGTQV
    TVSSGGGSQVQLQESGGGLVQPGESLRLSCTASGFTFSNYAMSWVRQAPGKGLEWVSGIN
    VAYGITSYADSVKGRFTISRDNTKNTLYLQLNSLKTEDTAIYYCVKHSGTTIPRGFISYTKRG
    QGTQVTVSS
    10 QVQLQESGGGSVQAGGSLRLSCTAPGFTSNSCGMDWYRQAPGKEREFVSSISTDGTTGYA
    DSVKGRFTISKDKAKDTVYLQMNSLKPEDTGMYSCKTKDGTIATMELCDFGYWGQGTQV
    TVSSGGGSQVQLQESGGGLVQPGGSLRLSCAASGFSFSSYAMKWVRQAPGKGLEWVSTIS
    SGGSSTNYADSVKG RFTISRDNAKNTLYLQLNSLKIEDTAMYYCAKAIVPTGATMERGQGT
    QVTVSS
    11 QVQLQESGGGSVQAGGSLRLSCTAPGFTSNSCGMDWYRQAPGKEREFVSSISTDGTTGYA
    DSVKGRFTISKDKAKDTVYLQMNSLKPEDTGMYSCKTKDGTIATMELCDFGYWGQGTQV
    TVSSGGGSQVQLQESGGGSVQSGGSLRLSCAASGFTYSTSNSWMAWFRQAPGKEREGVA
    AIYTVGGSIFYADSVRGRFTISQDATKNMFYLQMNTLKPEDTAMYYCAAASGRLRGKWFW
    PYEYNY WGQGTQVTVSS
    12 QVQLQESGGGSVQAGGSLRLSCTAPGFTSNSCGMDWYRQAPGKEREFVSSISTDGTTGYA
    DSVKGRFTISKDKAKDTVYLQMNSLKPEDTGMYSCKTKDGTIATMELCDFGYWGQGTQV
    TVSSGGGSQVQLQESGGGSVQAGGSLRLSCVASGYVSCDYFLPSWYRQAPGKEREFVSIID
    GTGSTSYAASVKGRFTASQDKGKNIAYLQMNTLKPEDTAMYYCKASCVRGRAISEYWGQ
    GTQVTVSS
    13 QVQLQESGGGSVQAGGSLRLSCTAPGFTSNSCGMDWYRQAPGKEREFVSSISTDGTTGYA
    DSVKGRFTISKDKAKDTVYLQMNSLKPEDTGMYSCKTKDGTIATMELCDFGYWGQGTQV
    TVSSGGGSQVQLQESGGGSVQAGGSLRLSCRASGSTYSNYCLGWFRQITGKEREGVAVIN
    WVGGMLYFADSVKG RFTVSQDQAKNTVYLQMNSLKPEDTAMYYCAAESVSSFSCGGWL
    TRPDRVPYWGQGTQVTVSS
    14 QVQLQESGGGSVQAGGSLRLSCTAPGFTSNSCGMDWYRQAPGKEREFVSSISTDGTTGYA
    DSVKGRFTISKDKAKDTVYLQMNSLKPEDTGMYSCKTKDGTIATMELCDFGYWGQGTQV
    TVSSGGGSQVQLQESGGGLVQPGGSLRLSCAASGFTFSLSSMSWVRQAPGKGLEWVSAISS
    GGASTYYTDSVKGRFTISRDNAKNMLYLQLNSLKTEDTAMYYCAKGGSGYGDASRMTSP
    GSQGTQVTVSS
    15 QVQLQESGGGSVQAGGSLRLSCAASGYPYSNGYMGWFRQAPGKEREGVATIYTGDGRTY
    YADSVKGRFTISRDNAKNTVDLQMSSLKPEDTAMYYCAARAAPLYSSGSPLTRARYNVWG
    QGTQVTVSSGGGSQVQLQESGGGLVQPGGSLRLSCAASGFTFSSYPMSWVRQAPGKGLEW
    ISTISAGGDTTLYADSVKGRFTSSRDNAKNTLYLQLNSLKTEDAAIYYCAKRIDCNSGYCYR
    RNYWGQGTQVTVSS
    16 QVQLQESGGGSVQAGGSLRLSCAASGYPYSNGYMGWFRQAPGKEREGVATIYTGDGRTY
    YADSVKGRFTISRDNAKNTVDLQMSSLKPEDTAMYYCAARAAPLYSSGSPLTRARYNVWG
    QGTQVTVSSGGGSQVQLQESGGGLVQPGESLRLSCTASGFTFSNYAMSWVRQAPGKGLE
    WVSGINVAYGITSYADSVKGRFTISRDNTKNTLYLQLNSLKTEDTAIYYCVKHSGTTIPRGFI
    SYTK RGQGTQVTVSS
    17 QVQLQESGGGSVQAGGSLRLSCAASGYPYSNGYMGWFRQAPGKEREGVATIYTGDGRTY
    YADSVKGRFTISRDNAKNTVDLQMSSLKPEDTAMYYCAARAAPLYSSGSPLTRARYNVWG
    QGTQVTVSSGGGSQVQLQESGGGLVQPGGSLRLSCAASGFSFSSYAMKWVRQAPGKGLE
    WVSTISSGGSSTNYADSVKGRFTISRDNAKNTLYLQLNSLKIEDTAMYYCAKAIVPTGATM
    E RGQGTQVTVSS
    18 QVQLQESGGGSVQAGGSLRLSCAASGYPYSNGYMGWFRQAPGKEREGVATIYTGDGRTY
    YADSVKGRFTISRDNAKNTVDLQMSSLKPEDTAMYYCAARAAPLYSSGSPLTRARYNVWG
    QGTQVTVSSGGGSQVQLQESGGGSVQSGGSLRLSCAASGFTYSTSNSWMAWFRQAPGKE
    REGVAAIYTVGGSIFYADSVRGRFTISQDATKNMFYLQMNTLKPEDTAMYYCAAASGRLR
    GKWFWPYEYNYWGQGTQVTVSS
    19 QVQLQESGGGSVQAGGSLRLSCAASGYPYSNGYMGWFRQAPGKEREGVATIYTGDGRTY
    YADSVKGRFTISRDNAKNTVDLQMSSLKPEDTAMYYCAARAAPLYSSGSPLTRARYNVWG
    QGTQVTVSSGGGSQVQLQESGGGSVQAGGSLRLSCVASGYVSCDYFLPSWYRQAPGKERE
    FVSIIDGTGSTSYAASVKGRFTASQDKGKNIAYLQMNTLKPEDTAMYYCKASCVRGRAISE
    YWGQGTQVTVSS
    20 QVQLQESGGGSVQAGGSLRLSCAASGYPYSNGYMGWFRQAPGKEREGVATIYTGDGRTY
    YADSVKGRFTISRDNAKNTVDLQMSSLKPEDTAMYYCAARAAPLYSSGSPLTRARYNVWG
    QGTQVTVSSGGGSQVQLQESGGGSVQAGGSLRLSCRASGSTYSNYCLGWFRQITGKEREG
    VAVINWVGGMLYFADSVKGRFTVSQDQAKNTVYLQMNSLKPEDTAMYYCAAESVSSFSC
    GGWLTRPDRVPYWGQGTQVTVSS
    21 QVQLQESGGGSVQAGGSLRLSCAASGYPYSNGYMGWFRQAPGKEREGVATIYTGDGRTY
    YADSVKGRFTISRDNAKNTVDLQMSSLKPEDTAMYYCAARAAPLYSSGSPLTRARYNVWG
    QGTQVTVSSGGGSQVQLQESGGGLVQPGGSLRLSCAASGFTFSLSSMSWVRQAPGKGLEW
    VSAISSGGASTYYTDSVKGRFTISRDNAKNMLYLQLNSLKTEDTAMYYCAKGGSGYGDAS
    RMTSPGSQGTQVTVSS
    22 QVQLQESGGGSVQAGGSLRLSCVASASTYCTYDMHWYRQAPGKGREFVSAIDSDGTTRYA
    DSVKGRFTISQGTAKNTVYLQMNSLQPEDTAMYYCKTVCVVGSRWSDYWGQGTQVTVSS
    GGGSQVQLQESGGGLVQPGGSLRLSCAASGFTFSSYPMSWVRQAPGKGLEWISTISAGGDT
    TLYADSVKGRFTSSRDNAKNTLYLQLNSLKTEDAAIYYCAKRIDCNSGYCYRRNYWGQGT
    QVTVSS
    23 QVQLQESGGGSVQAGGSLRLSCVASASTYCTYDMHWYRQAPGKGREFVSAIDSDGTTRYA
    DSVKGRFTISQGTAKNTVYLQMNSLQPEDTAMYYCKTVCVVGSRWSDYWGQGTQVTVSS
    GGGSQVQLQESGGGLVQPGESLRLSCTASGFTFSNYAMSWVRQAPGKGLEWVSGINVAY
    GITSYADSVKGRFTISRDNTKNTLYLQLNSLKTEDTAIYYCVKHSGTTIPRGFISYTKRGQGT
    QVTVSS
    24 QVQLQESGGGSVQAGGSLRLSCVASASTYCTYDMHWYRQAPGKGREFVSAIDSDGTTRYA
    DSVKGRFTISQGTAKNTVYLQMNSLQPEDTAMYYCKTVCVVGSRWSDYWGQGTQVTVSS
    GGGSQVQLQESGGGLVQPGGSLRLSCAASGFSFSSYAMKWVRQAPGKGLEWVSTISSGGS
    STNYADSVKGRFTISRDNAKNTLYLQLNSLKIEDTAMYYCAKAIVPTGATMERGQGTQVT
    VSS
    25 QVQLQESGGGSVQAGGSLRLSCVASASTYCTYDMHWYRQAPGKGREFVSAIDSDGTTRYA
    DSVKGRFTISQGTAKNTVYLQMNSLQPEDTAMYYCKTVCVVGSRWSDYWGQGTQVTVSS
    GGGSQVQLQESGGGSVQSGGSLRLSCAASGFTYSTSNSWMAWFRQAPGKEREGVAAIYTV
    GGSIFYADSVRGRFTISQDATKNMFYLQMNTLKPEDTAMYYCAAASGRLRGKWFWPYEY
    NYWGQGTQVTVSS
    26 QVQLQESGGGSVQAGGSLRLSCVASASTYCTYDMHWYRQAPGKGREFVSAIDSDGTTRYA
    DSVKGRFTISQGTAKNTVYLQMNSLQPEDTAMYYCKTVCVVGSRWSDYWGQGTQVTVSS
    GGGSQVQLQESGGGSVQAGGSLRLSCVASGYVSCDYFLPSWYRQAPGKEREFVSIIDGTGS
    TSYAASVKGRFTASQDKGKNIAYLQMNTLKPEDTAMYYCKASCVRGRAISEYWGQGTQV
    TVSS
    27 QVQLQESGGGSVQAGGSLRLSCVASASTYCTYDMHWYRQAPGKGREFVSAIDSDGTTRYA
    DSVKGRFTISQGTAKNTVYLQMNSLQPEDTAMYYCKTVCVVGSRWSDYWGQGTQVTVSS
    GGGSQVQLQESGGGSVQAGGSLRLSCRASGSTYSNYCLGWFRQITGKEREGVAVINWVGG
    MLYFADSVKGRFTVSQDQAKNTVYLQMNSLKPEDTAMYYCAAESVSSFSCGGWLTRPDR
    VPYWGQGTQVTVSS
    28 QVQLQESGGGSVQAGGSLRLSCVASASTYCTYDMHWYRQAPGKGREFVSAIDSDGTTRYA
    DSVKGRFTISQGTAKNTVYLQMNSLQPEDTAMYYCKTVCVVGSRWSDYWGQGTQVTVSS
    GGGSQVQLQESGGGLVQPGGSLRLSCAASGFTFSLSSMSWVRQAPGKGLEWVSAISSGGA
    STYYTDSVKGRFTISRDNAKNMLYLQLNSLKTEDTAMYYCAKGGSGYGDASRMTSPGSQG
    TQVTVSS
    29 QVQLQESGGGSVQAGGSLTLSCAASEYAYSTCNMGWYRQAPGKERELVSAFISDGSTYYA
    DSVKGRFTITRDNAKNTVYLQMNSLKPEDTAIYYCSANCYRRLRNYWGQGTQVTVSSGG
    GSQVQLQESGGGLVQPGGSLRLSCAASGFTFSSYPMSWVRQAPGKGLEWISTISAGGDTTL
    YADSVKGRFTSSRDNAKNTLYLQLNSLKTEDAAIYYCAKRIDCNSGYCYRRNYWGQGTQV
    TVSS
    30 QVQLQESGGGSVQAGGSLTLSCAASEYAYSTCNMGWYRQAPGKERELVSAFISDGSTYYA
    DSVKGRFTITRDNAKNTVYLQMNSLKPEDTAIYYCSANCYRRLRNYWGQGTQVTVSSGG
    GSQVQLQESGGGLVQPGESLRLSCTASGFTFSNYAMSWVRQAPGKGLEWVSGINVAYGIT
    SYADSVKGRFTISRDNTKNTLYLQLNSLKTEDTAIYYCVKHSGTTIPRGFISYTKRGQGTQV
    TVSS
    31 QVQLQESGGGSVQAGGSLTLSCAASEYAYSTCNMGWYRQAPGKERELVSAFISDGSTYYA
    DSVKGRFTITRDNAKNTVYLQMNSLKPEDTAIYYCSANCYRRLRNYWGQGTQVTVSSGG
    GSQVQLQESGGGLVQPGGSLRLSCAASGFSFSSYAMKWVRQAPGKGLEWVSTISSGGSSTN
    YADSVKGRFTISRDNAKNTLYLQLNSLKIEDTAMYYCAKAIVPTGATMERGQGTQVTVSS
    32 QVQLQESGGGSVQAGGSLTLSCAASEYAYSTCNMGWYRQAPGKERELVSAFISDGSTYYA
    DSVKGRFTITRDNAKNTVYLQMNSLKPEDTAIYYCSANCYRRLRNYWGQGTQVTVSSGG
    GSQVQLQESGGGSVQSGGSLRLSCAASGFTYSTSNSWMAWFRQAPGKEREGVAAIYTVGG
    SIFYADSVRGRFTISQDATKNMFYLQMNTLKPEDTAMYYCAAASGRLRGKWFWPYEYNY
    WGQGTQVTVSS
    33 QVQLQESGGGSVQAGGSLTLSCAASEYAYSTCNMGWYRQAPGKERELVSAFISDGSTYYA
    DSVKGRFTITRDNAKNTVYLQMNSLKPEDTAIYYCSANCYRRLRNYWGQGTQVTVSSGG
    GSQVQLQESGGGSVQAGGSLRLSCVASGYVSCDYFLPSWYRQAPGKEREFVSIIDGTGSTS
    YAASVKGRFTASQDKGKNIAYLQMNTLKPEDTAMYYCKASCVRGRAISEYWGQGTQVTV
    SS
    34 QVQLQESGGGSVQAGGSLTLSCAASEYAYSTCNMGWYRQAPGKERELVSAFISDGSTYYA
    DSVKGRFTITRDNAKNTVYLQMNSLKPEDTAIYYCSANCYRRLRNYWGQGTQVTVSSGG
    GSQVQLQESGGGSVQAGGSLRLSCRASGSTYSNYCLGWFRQITGKEREGVAVINWVGGML
    YFADSVKGRFTVSQDQAKNTVYLQMNSLKPEDTAMYYCAAESVSSFSCGGWLTRPDRVP
    YWGQGTQVTVSS
    35 QVQLQESGGGSVQAGGSLTLSCAASEYAYSTCNMGWYRQAPGKERELVSAFISDGSTYYA
    DSVKGRFTITRDNAKNTVYLQMNSLKPEDTAIYYCSANCYRRLRNYWGQGTQVTVSSGG
    GSQVQLQESGGGLVQPGGSLRLSCAASGFTFSLSSMSWVRQAPGKGLEWVSAISSGGASTY
    YTDSVKGRFTISRDNAKNMLYLQLNSLKTEDTAMYYCAKGGSGYGDASRMTSPGSQGTQ
    VTVSS
    36 QVQLQESGGGLVQPGGSLRLSCTASGLTFDDSVMGWFRQAPGKGREAVSCISSSGANAFY
    ADSVKGRFTISRDNAKNTLYLQMNSLKPEDTATYYCKRGHACAGYYPIPYDDYWGQGTQ
    VTVSSGGGSQVQLQESGGGLVQPGGSLRLSCAASGFTFSSYPMSWVRQAPGKGLEWISTIS
    AGGDTTLYADSVKGRFTSSRDNAKNTLYLQLNSLKTEDAAIYYCAKRIDCNSGYCYRRNY
    WGQGTQVTVSS
    37 QVQLQESGGGLVQPGGSLRLSCTASGLTFDDSVMGWFRQAPGKGREAVSCISSSGANAFY
    ADSVKGRFTISRDNAKNTLYLQMNSLKPEDTATYYCKRGHACAGYYPIPYDDYWGQGTQ
    VTVSSGGGSQVQLQESGGGLVQPGESLRLSCTASGFTFSNYAMSWVRQAPGKGLEWVSGI
    NVAYGITSYADSVKGRFTISRDNTKNTLYLQLNSLKTEDTAIYYCVKHSGTTIPRGFISYTKR
    GQGTQVTVSS
    38 QVQLQESGGGLVQPGGSLRLSCTASGLTFDDSVMGWFRQAPGKGREAVSCISSSGANAFY
    ADSVKGRFTISRDNAKNTLYLQMNSLKPEDTATYYCKRGHACAGYYPIPYDDYWGQGTQ
    VTVSSGGGSQVQLQESGGGLVQPGGSLRLSCAASGFSFSSYAMKWVRQAPGKGLEWVSTI
    SSGGSSTNYADSVKGRFTISRDNAKNTLYLQLNSLKIEDTAMYYCAKAIVPTGATMERGQG
    TQVTVSS
    39 QVQLQESGGGLVQPGGSLRLSCTASGLTFDDSVMGWFRQAPGKGREAVSCISSSGANAFY
    ADSVKGRFTISRDNAKNTLYLQMNSLKPEDTATYYCKRGHACAGYYPIPYDDYWGQGTQ
    VTVSSGGGSQVQLQESGGGSVQSGGSLRLSCAASGFTYSTSNSWMAWFRQAPGKEREGV
    AAIYTVGGSIFYADSVRGRFTISQDATKNMFYLQMNTLKPEDTAMYYCAAASGRLRGKWF
    WPYEYNYWGQGTQVTVSS
    40 QVQLQESGGGLVQPGGSLRLSCTASGLTFDDSVMGWFRQAPGKGREAVSCISSSGANAFY
    ADSVKGRFTISRDNAKNTLYLQMNSLKPEDTATYYCKRGHACAGYYPIPYDDYWGQGTQ
    VTVSSGGGSQVQLQESGGGSVQAGGSLRLSCVASGYVSCDYFLPSWYRQAPGKEREFVSII
    DGTGSTSYAASVKGRFTASQDKGKNIAYLQMNTLKPEDTAMYYCKASCVRGRAISEYWG
    QGTQVTVSS
    41 QVQLQESGGGLVQPGGSLRLSCTASGLTFDDSVMGWFRQAPGKGREAVSCISSSGANAFY
    ADSVKGRFTISRDNAKNTLYLQMNSLKPEDTATYYCKRGHACAGYYPIPYDDYWGQGTQ
    VTVSSGGGSQVQLQESGGGSVQAGGSLRLSCRASGSTYSNYCLGWFRQITGKEREGVAVI
    NWVGGMLYFADSVKGRFTVSQDQAKNTVYLQMNSLKPEDTAMYYCAAESVSSFSCGGW
    LTRPDRVPYWGQGTQVTVSS
    42 QVQLQESGGGLVQPGGSLRLSCTASGLTFDDSVMGWFRQAPGKGREAVSCISSSGANAFY
    ADSVKGRFTISRDNAKNTLYLQMNSLKPEDTATYYCKRGHACAGYYPIPYDDYWGQGTQ
    VTVSSGGGSQVQLQESGGGLVQPGGSLRLSCAASGFTFSLSSMSWVRQAPGKGLEWVSAIS
    SGGASTYYTDSVKGRFTISRDNAKNMLYLQLNSLKTEDTAMYYCAKGGSGYGDASRMTSP
    GSQGTQVTVSS
  • In some embodiments, an IL27R binding protein described herein (e.g., an IL27R binding protein comprising a sequence of any one of SEQ ID NOS: 1-42) is encoded by an isolated nucleic acid that is substantially identical to a sequence of any one of SEQ ID NOS: 109-150, as listed in Table 2C below. In some embodiments, an IL27R binding protein described herein (e.g., an IL27R binding protein comprising a sequence of any one of SEQ ID NOS: 1-42) is encoded by an isolated nucleic acid comprising a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity to a sequence of any one of SEQ ID NOS: 109-150, as listed in Table 2C below.
  • TABLE 2C
    SEQ
    ID
    NO Sequence
    109 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCACCGCCAGCGGCGCCATCGCCAGCGGCTACATCGACAGCAGGTGGTGCA
    TGGCCTGGTTCAGGCAGGCCCCCGGCAAGGAGAGGGAGGGCGTGGCCGCCATCTGGCC
    CGGCGGCGGCCTGACCGTGTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGG
    GACCACGCCAAGAACACCCTGTACCTGCAGATGAACAACCTGAAGCCCGAGGACACCG
    CCATGTACTACTGCGCCGCCGGCAGCCCCAGGATGTGCCCCAGCCTGGAGTTCGGCTTC
    GACTACTGGGGCCAGGGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGC
    AGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGCTGAGCTG
    CGCCGCCAGCGGCTTCACCTTCAGCAGCTACCCCATGAGCTGGGTGAGGCAGGCCCCC
    GGCAAGGGCCTGGAGTGGATCAGCACCATCAGCGCCGGCGGCGACACCACCCTGTACG
    CCGACAGCGTGAAGGGCAGGTTCACCAGCAGCAGGGACAACGCCAAGAACACCCTGTA
    CCTGCAGCTGAACAGCCTGAAGACCGAGGACGCCGCCATCTACTACTGCGCCAAGAGG
    ATCGACTGCAACAGCGGCTACTGCTACAGGAGGAACTACTGGGGCCAGGGCACCCAGG
    TGACCGTGAGCGCTAGCCACCACCACCACCACCACCACCAC
    110 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCACCGCCAGCGGCGCCATCGCCAGCGGCTACATCGACAGCAGGTGGTGCA
    TGGCCTGGTTCAGGCAGGCCCCCGGCAAGGAGAGGGAGGGCGTGGCCGCCATCTGGCC
    CGGCGGCGGCCTGACCGTGTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGG
    GACCACGCCAAGAACACCCTGTACCTGCAGATGAACAACCTGAAGCCCGAGGACACCG
    CCATGTACTACTGCGCCGCCGGCAGCCCCAGGATGTGCCCCAGCCTGGAGTTCGGCTTC
    GACTACTGGGGCCAGGGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGC
    AGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGAGAGCCTGAGGCTGAGCTG
    CACCGCCAGCGGCTTCACCTTCAGCAACTACGCCATGAGCTGGGTGAGGCAGGCCCCC
    GGCAAGGGCCTGGAGTGGGTGAGCGGCATCAACGTGGCCTACGGCATCACCAGCTACG
    CCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACACCAAGAACACCCTGTA
    CCTGCAGCTGAACAGCCTGAAGACCGAGGACACCGCCATCTACTACTGCGTGAAGCAC
    AGCGGCACCACCATCCCCAGGGGCTTCATCAGCTACACCAAGAGGGGCCAGGGCACCC
    AGGTGACCGTGAGCGCTAGCCACCACCACCACCACCACCACCAC
    111 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCACCGCCAGCGGCGCCATCGCCAGCGGCTACATCGACAGCAGGTGGTGCA
    TGGCCTGGTTCAGGCAGGCCCCCGGCAAGGAGAGGGAGGGCGTGGCCGCCATCTGGCC
    CGGCGGCGGCCTGACCGTGTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGG
    GACCACGCCAAGAACACCCTGTACCTGCAGATGAACAACCTGAAGCCCGAGGACACCG
    CCATGTACTACTGCGCCGCCGGCAGCCCCAGGATGTGCCCCAGCCTGGAGTTCGGCTTC
    GACTACTGGGGCCAGGGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGC
    AGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGCTGAGCTG
    CGCCGCCAGCGGCTTCAGCTTCAGCAGCTACGCCATGAAGTGGGTGAGGCAGGCCCCC
    GGCAAGGGCCTGGAGTGGGTGAGCACCATCAGCAGCGGCGGCAGCAGCACCAACTAC
    GCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAACACCCTGT
    ACCTGCAGCTGAACAGCCTGAAGATCGAGGACACCGCCATGTACTACTGCGCCAAGGC
    CATCGTGCCCACCGGCGCCACCATGGAGAGGGGCCAGGGCACCCAGGTGACCGTGAGC
    GCTAGCCACCACCACCACCACCACCACCAC
    112 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCACCGCCAGCGGCGCCATCGCCAGCGGCTACATCGACAGCAGGTGGTGCA
    TGGCCTGGTTCAGGCAGGCCCCCGGCAAGGAGAGGGAGGGCGTGGCCGCCATCTGGCC
    CGGCGGCGGCCTGACCGTGTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGG
    GACCACGCCAAGAACACCCTGTACCTGCAGATGAACAACCTGAAGCCCGAGGACACCG
    CCATGTACTACTGCGCCGCCGGCAGCCCCAGGATGTGCCCCAGCCTGGAGTTCGGCTTC
    GACTACTGGGGCCAGGGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGC
    AGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGAGCGGCGGCAGCCTGAGGCTGAGCT
    GCGCCGCCAGCGGCTTCACCTACAGCACCAGCAACAGCTGGATGGCCTGGTTCAGGCA
    GGCCCCCGGCAAGGAGAGGGAGGGCGTGGCCGCCATCTACACCGTGGGCGGCAGCATC
    TTCTACGCCGACAGCGTGAGGGGCAGGTTCACCATCAGCCAGGACGCCACCAAGAACA
    TGTTCTACCTGCAGATGAACACCCTGAAGCCCGAGGACACCGCCATGTACTACTGCGCC
    GCCGCCAGCGGCAGGCTGAGGGGCAAGTGGTTCTGGCCCTACGAGTACAACTACTGGG
    GCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCACCACCACCACCACCACCAC
    113 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCACCGCCAGCGGCGCCATCGCCAGCGGCTACATCGACAGCAGGTGGTGCA
    TGGCCTGGTTCAGGCAGGCCCCCGGCAAGGAGAGGGAGGGCGTGGCCGCCATCTGGCC
    CGGCGGCGGCCTGACCGTGTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGG
    GACCACGCCAAGAACACCCTGTACCTGCAGATGAACAACCTGAAGCCCGAGGACACCG
    CCATGTACTACTGCGCCGCCGGCAGCCCCAGGATGTGCCCCAGCCTGGAGTTCGGCTTC
    GACTACTGGGGCCAGGGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGC
    AGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGGCTGAGCT
    GCGTGGCCAGCGGCTACGTGAGCTGCGACTACTTCCTGCCCAGCTGGTACAGGCAGGC
    CCCCGGCAAGGAGAGGGAGTTCGTGAGCATCATCGACGGCACCGGCAGCACCAGCTAC
    GCCGCCAGCGTGAAGGGCAGGTTCACCGCCAGCCAGGACAAGGGCAAGAACATCGCCT
    ACCTGCAGATGAACACCCTGAAGCCCGAGGACACCGCCATGTACTACTGCAAGGCCAG
    CTGCGTGAGGGGCAGGGCCATCAGCGAGTACTGGGGCCAGGGCACCCAGGTGACCGTG
    AGCGCTAGCCACCACCACCACCACCACCACCAC
    114 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCACCGCCAGCGGCGCCATCGCCAGCGGCTACATCGACAGCAGGTGGTGCA
    TGGCCTGGTTCAGGCAGGCCCCCGGCAAGGAGAGGGAGGGCGTGGCCGCCATCTGGCC
    CGGCGGCGGCCTGACCGTGTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGG
    GACCACGCCAAGAACACCCTGTACCTGCAGATGAACAACCTGAAGCCCGAGGACACCG
    CCATGTACTACTGCGCCGCCGGCAGCCCCAGGATGTGCCCCAGCCTGGAGTTCGGCTTC
    GACTACTGGGGCCAGGGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGC
    AGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGGCTGAGCT
    GCAGGGCCAGCGGCAGCACCTACAGCAACTACTGCCTGGGCTGGTTCAGGCAGATCAC
    CGGCAAGGAGAGGGAGGGCGTGGCCGTGATCAACTGGGTGGGCGGCATGCTGTACTTC
    GCCGACAGCGTGAAGGGCAGGTTCACCGTGAGCCAGGACCAGGCCAAGAACACCGTGT
    ACCTGCAGATGAACAGCCTGAAGCCCGAGGACACCGCCATGTACTACTGCGCCGCCGA
    GAGCGTGAGCAGCTTCAGCTGCGGCGGCTGGCTGACCAGGCCCGACAGGGTGCCCTAC
    TGGGGCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCACCACCACCACCACCACC
    AC
    115 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCACCGCCAGCGGCGCCATCGCCAGCGGCTACATCGACAGCAGGTGGTGCA
    TGGCCTGGTTCAGGCAGGCCCCCGGCAAGGAGAGGGAGGGCGTGGCCGCCATCTGGCC
    CGGCGGCGGCCTGACCGTGTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGG
    GACCACGCCAAGAACACCCTGTACCTGCAGATGAACAACCTGAAGCCCGAGGACACCG
    CCATGTACTACTGCGCCGCCGGCAGCCCCAGGATGTGCCCCAGCCTGGAGTTCGGCTTC
    GACTACTGGGGCCAGGGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGC
    AGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGCTGAGCTG
    CGCCGCCAGCGGCTTCACCTTCAGCCTGAGCAGCATGAGCTGGGTGAGGCAGGCCCCC
    GGCAAGGGCCTGGAGTGGGTGAGCGCCATCAGCAGCGGCGGCGCCAGCACCTACTACA
    CCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAACATGCTGTA
    CCTGCAGCTGAACAGCCTGAAGACCGAGGACACCGCCATGTACTACTGCGCCAAGGGC
    GGCAGCGGCTACGGCGACGCCAGCAGGATGACCAGCCCCGGCAGCCAGGGCACCCAG
    GTGACCGTGAGCGCTAGCCACCACCACCACCACCACCACCAC
    116 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCACCGCCCCCGGCTTCACCAGCAACAGCTGCGGCATGGACTGGTACAGGC
    AGGCCCCCGGCAAGGAGAGGGAGTTCGTGAGCAGCATCAGCACCGACGGCACCACCG
    GCTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAAGGACAAGGCCAAGGACA
    CCGTGTACCTGCAGATGAACAGCCTGAAGCCCGAGGACACCGGCATGTACAGCTGCAA
    GACCAAGGACGGCACCATCGCCACCATGGAGCTGTGCGACTTCGGCTACTGGGGCCAG
    GGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCG
    GCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGCTGAGCTGCGCCGCCAGCGGCTT
    CACCTTCAGCAGCTACCCCATGAGCTGGGTGAGGCAGGCCCCCGGCAAGGGCCTGGAG
    TGGATCAGCACCATCAGCGCCGGCGGCGACACCACCCTGTACGCCGACAGCGTGAAGG
    GCAGGTTCACCAGCAGCAGGGACAACGCCAAGAACACCCTGTACCTGCAGCTGAACAG
    CCTGAAGACCGAGGACGCCGCCATCTACTACTGCGCCAAGAGGATCGACTGCAACAGC
    GGCTACTGCTACAGGAGGAACTACTGGGGCCAGGGCACCCAGGTGACCGTGAGCGCTA
    GCCACCACCACCACCACCACCACCAC
    117 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCACCGCCCCCGGCTTCACCAGCAACAGCTGCGGCATGGACTGGTACAGGC
    AGGCCCCCGGCAAGGAGAGGGAGTTCGTGAGCAGCATCAGCACCGACGGCACCACCG
    GCTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAAGGACAAGGCCAAGGACA
    CCGTGTACCTGCAGATGAACAGCCTGAAGCCCGAGGACACCGGCATGTACAGCTGCAA
    GACCAAGGACGGCACCATCGCCACCATGGAGCTGTGCGACTTCGGCTACTGGGGCCAG
    GGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCG
    GCGGCGGCCTGGTGCAGCCCGGCGAGAGCCTGAGGCTGAGCTGCACCGCCAGCGGCTT
    CACCTTCAGCAACTACGCCATGAGCTGGGTGAGGCAGGCCCCCGGCAAGGGCCTGGAG
    TGGGTGAGCGGCATCAACGTGGCCTACGGCATCACCAGCTACGCCGACAGCGTGAAGG
    GCAGGTTCACCATCAGCAGGGACAACACCAAGAACACCCTGTACCTGCAGCTGAACAG
    CCTGAAGACCGAGGACACCGCCATCTACTACTGCGTGAAGCACAGCGGCACCACCATC
    CCCAGGGGCTTCATCAGCTACACCAAGAGGGGCCAGGGCACCCAGGTGACCGTGAGCG
    CTAGCCACCACCACCACCACCACCACCAC
    118 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCACCGCCCCCGGCTTCACCAGCAACAGCTGCGGCATGGACTGGTACAGGC
    AGGCCCCCGGCAAGGAGAGGGAGTTCGTGAGCAGCATCAGCACCGACGGCACCACCG
    GCTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAAGGACAAGGCCAAGGACA
    CCGTGTACCTGCAGATGAACAGCCTGAAGCCCGAGGACACCGGCATGTACAGCTGCAA
    GACCAAGGACGGCACCATCGCCACCATGGAGCTGTGCGACTTCGGCTACTGGGGCCAG
    GGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCG
    GCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGCTGAGCTGCGCCGCCAGCGGCTT
    CAGCTTCAGCAGCTACGCCATGAAGTGGGTGAGGCAGGCCCCCGGCAAGGGCCTGGAG
    TGGGTGAGCACCATCAGCAGCGGCGGCAGCAGCACCAACTACGCCGACAGCGTGAAGG
    GCAGGTTCACCATCAGCAGGGACAACGCCAAGAACACCCTGTACCTGCAGCTGAACAG
    CCTGAAGATCGAGGACACCGCCATGTACTACTGCGCCAAGGCCATCGTGCCCACCGGC
    GCCACCATGGAGAGGGGCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCACCACC
    ACCACCACCACCAC
    119 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCACCGCCCCCGGCTTCACCAGCAACAGCTGCGGCATGGACTGGTACAGGC
    AGGCCCCCGGCAAGGAGAGGGAGTTCGTGAGCAGCATCAGCACCGACGGCACCACCG
    GCTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAAGGACAAGGCCAAGGACA
    CCGTGTACCTGCAGATGAACAGCCTGAAGCCCGAGGACACCGGCATGTACAGCTGCAA
    GACCAAGGACGGCACCATCGCCACCATGGAGCTGTGCGACTTCGGCTACTGGGGCCAG
    GGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCG
    GCGGCGGCAGCGTGCAGAGCGGCGGCAGCCTGAGGCTGAGCTGCGCCGCCAGCGGCTT
    CACCTACAGCACCAGCAACAGCTGGATGGCCTGGTTCAGGCAGGCCCCCGGCAAGGAG
    AGGGAGGGCGTGGCCGCCATCTACACCGTGGGCGGCAGCATCTTCTACGCCGACAGCG
    TGAGGGGCAGGTTCACCATCAGCCAGGACGCCACCAAGAACATGTTCTACCTGCAGAT
    GAACACCCTGAAGCCCGAGGACACCGCCATGTACTACTGCGCCGCCGCCAGCGGCAGG
    CTGAGGGGCAAGTGGTTCTGGCCCTACGAGTACAACTACTGGGGCCAGGGCACCCAGG
    TGACCGTGAGCGCTAGCCACCACCACCACCACCACCACCAC
    120 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCACCGCCCCCGGCTTCACCAGCAACAGCTGCGGCATGGACTGGTACAGGC
    AGGCCCCCGGCAAGGAGAGGGAGTTCGTGAGCAGCATCAGCACCGACGGCACCACCG
    GCTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAAGGACAAGGCCAAGGACA
    CCGTGTACCTGCAGATGAACAGCCTGAAGCCCGAGGACACCGGCATGTACAGCTGCAA
    GACCAAGGACGGCACCATCGCCACCATGGAGCTGTGCGACTTCGGCTACTGGGGCCAG
    GGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCG
    GCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGGCTGAGCTGCGTGGCCAGCGGCTA
    CGTGAGCTGCGACTACTTCCTGCCCAGCTGGTACAGGCAGGCCCCCGGCAAGGAGAGG
    GAGTTCGTGAGCATCATCGACGGCACCGGCAGCACCAGCTACGCCGCCAGCGTGAAGG
    GCAGGTTCACCGCCAGCCAGGACAAGGGCAAGAACATCGCCTACCTGCAGATGAACAC
    CCTGAAGCCCGAGGACACCGCCATGTACTACTGCAAGGCCAGCTGCGTGAGGGGCAGG
    GCCATCAGCGAGTACTGGGGCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCACC
    ACCACCACCACCACCAC
    121 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCACCGCCCCCGGCTTCACCAGCAACAGCTGCGGCATGGACTGGTACAGGC
    AGGCCCCCGGCAAGGAGAGGGAGTTCGTGAGCAGCATCAGCACCGACGGCACCACCG
    GCTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAAGGACAAGGCCAAGGACA
    CCGTGTACCTGCAGATGAACAGCCTGAAGCCCGAGGACACCGGCATGTACAGCTGCAA
    GACCAAGGACGGCACCATCGCCACCATGGAGCTGTGCGACTTCGGCTACTGGGGCCAG
    GGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCG
    GCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGGCTGAGCTGCAGGGCCAGCGGCA
    GCACCTACAGCAACTACTGCCTGGGCTGGTTCAGGCAGATCACCGGCAAGGAGAGGGA
    GGGCGTGGCCGTGATCAACTGGGTGGGCGGCATGCTGTACTTCGCCGACAGCGTGAAG
    GGCAGGTTCACCGTGAGCCAGGACCAGGCCAAGAACACCGTGTACCTGCAGATGAACA
    GCCTGAAGCCCGAGGACACCGCCATGTACTACTGCGCCGCCGAGAGCGTGAGCAGCTT
    CAGCTGCGGCGGCTGGCTGACCAGGCCCGACAGGGTGCCCTACTGGGGCCAGGGCACC
    CAGGTGACCGTGAGCGCTAGCCACCACCACCACCACCACCACCAC
    122 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCACCGCCCCCGGCTTCACCAGCAACAGCTGCGGCATGGACTGGTACAGGC
    AGGCCCCCGGCAAGGAGAGGGAGTTCGTGAGCAGCATCAGCACCGACGGCACCACCG
    GCTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAAGGACAAGGCCAAGGACA
    CCGTGTACCTGCAGATGAACAGCCTGAAGCCCGAGGACACCGGCATGTACAGCTGCAA
    GACCAAGGACGGCACCATCGCCACCATGGAGCTGTGCGACTTCGGCTACTGGGGCCAG
    GGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCG
    GCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGCTGAGCTGCGCCGCCAGCGGCTT
    CACCTTCAGCCTGAGCAGCATGAGCTGGGTGAGGCAGGCCCCCGGCAAGGGCCTGGAG
    TGGGTGAGCGCCATCAGCAGCGGCGGCGCCAGCACCTACTACACCGACAGCGTGAAGG
    GCAGGTTCACCATCAGCAGGGACAACGCCAAGAACATGCTGTACCTGCAGCTGAACAG
    CCTGAAGACCGAGGACACCGCCATGTACTACTGCGCCAAGGGCGGCAGCGGCTACGGC
    GACGCCAGCAGGATGACCAGCCCCGGCAGCCAGGGCACCCAGGTGACCGTGAGCGCTA
    GCCACCACCACCACCACCACCACCAC
    123 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCGCCGCCAGCGGCTACCCCTACAGCAACGGCTACATGGGCTGGTTCAGGC
    AGGCCCCCGGCAAGGAGAGGGAGGGCGTGGCCACCATCTACACCGGCGACGGCAGGA
    CCTACTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAA
    CACCGTGGACCTGCAGATGAGCAGCCTGAAGCCCGAGGACACCGCCATGTACTACTGC
    GCCGCCAGGGCCGCCCCCCTGTACAGCAGCGGCAGCCCCCTGACCAGGGCCAGGTACA
    ACGTGTGGGGCCAGGGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCA
    GCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGCTGAGCTGC
    GCCGCCAGCGGCTTCACCTTCAGCAGCTACCCCATGAGCTGGGTGAGGCAGGCCCCCG
    GCAAGGGCCTGGAGTGGATCAGCACCATCAGCGCCGGCGGCGACACCACCCTGTACGC
    CGACAGCGTGAAGGGCAGGTTCACCAGCAGCAGGGACAACGCCAAGAACACCCTGTAC
    CTGCAGCTGAACAGCCTGAAGACCGAGGACGCCGCCATCTACTACTGCGCCAAGAGGA
    TCGACTGCAACAGCGGCTACTGCTACAGGAGGAACTACTGGGGCCAGGGCACCCAGGT
    GACCGTGAGCGCTAGCCACCACCACCACCACCACCACCAC
    124 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCGCCGCCAGCGGCTACCCCTACAGCAACGGCTACATGGGCTGGTTCAGGC
    AGGCCCCCGGCAAGGAGAGGGAGGGCGTGGCCACCATCTACACCGGCGACGGCAGGA
    CCTACTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAA
    CACCGTGGACCTGCAGATGAGCAGCCTGAAGCCCGAGGACACCGCCATGTACTACTGC
    GCCGCCAGGGCCGCCCCCCTGTACAGCAGCGGCAGCCCCCTGACCAGGGCCAGGTACA
    ACGTGTGGGGCCAGGGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCA
    GCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGAGAGCCTGAGGCTGAGCTGC
    ACCGCCAGCGGCTTCACCTTCAGCAACTACGCCATGAGCTGGGTGAGGCAGGCCCCCG
    GCAAGGGCCTGGAGTGGGTGAGCGGCATCAACGTGGCCTACGGCATCACCAGCTACGC
    CGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACACCAAGAACACCCTGTAC
    CTGCAGCTGAACAGCCTGAAGACCGAGGACACCGCCATCTACTACTGCGTGAAGCACA
    GCGGCACCACCATCCCCAGGGGCTTCATCAGCTACACCAAGAGGGGCCAGGGCACCCA
    GGTGACCGTGAGCGCTAGCCACCACCACCACCACCACCACCAC
    125 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCGCCGCCAGCGGCTACCCCTACAGCAACGGCTACATGGGCTGGTTCAGGC
    AGGCCCCCGGCAAGGAGAGGGAGGGCGTGGCCACCATCTACACCGGCGACGGCAGGA
    CCTACTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAA
    CACCGTGGACCTGCAGATGAGCAGCCTGAAGCCCGAGGACACCGCCATGTACTACTGC
    GCCGCCAGGGCCGCCCCCCTGTACAGCAGCGGCAGCCCCCTGACCAGGGCCAGGTACA
    ACGTGTGGGGCCAGGGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCA
    GCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGCTGAGCTGC
    GCCGCCAGCGGCTTCAGCTTCAGCAGCTACGCCATGAAGTGGGTGAGGCAGGCCCCCG
    GCAAGGGCCTGGAGTGGGTGAGCACCATCAGCAGCGGCGGCAGCAGCACCAACTACGC
    CGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAACACCCTGTAC
    CTGCAGCTGAACAGCCTGAAGATCGAGGACACCGCCATGTACTACTGCGCCAAGGCCA
    TCGTGCCCACCGGCGCCACCATGGAGAGGGGCCAGGGCACCCAGGTGACCGTGAGCGC
    TAGCCACCACCACCACCACCACCACCAC
    126 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCGCCGCCAGCGGCTACCCCTACAGCAACGGCTACATGGGCTGGTTCAGGC
    AGGCCCCCGGCAAGGAGAGGGAGGGCGTGGCCACCATCTACACCGGCGACGGCAGGA
    CCTACTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAA
    CACCGTGGACCTGCAGATGAGCAGCCTGAAGCCCGAGGACACCGCCATGTACTACTGC
    GCCGCCAGGGCCGCCCCCCTGTACAGCAGCGGCAGCCCCCTGACCAGGGCCAGGTACA
    ACGTGTGGGGCCAGGGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCA
    GCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGAGCGGCGGCAGCCTGAGGCTGAGCTG
    CGCCGCCAGCGGCTTCACCTACAGCACCAGCAACAGCTGGATGGCCTGGTTCAGGCAG
    GCCCCCGGCAAGGAGAGGGAGGGCGTGGCCGCCATCTACACCGTGGGCGGCAGCATCT
    TCTACGCCGACAGCGTGAGGGGCAGGTTCACCATCAGCCAGGACGCCACCAAGAACAT
    GTTCTACCTGCAGATGAACACCCTGAAGCCCGAGGACACCGCCATGTACTACTGCGCCG
    CCGCCAGCGGCAGGCTGAGGGGCAAGTGGTTCTGGCCCTACGAGTACAACTACTGGGG
    CCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCACCACCACCACCACCACCAC
    127 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCGCCGCCAGCGGCTACCCCTACAGCAACGGCTACATGGGCTGGTTCAGGC
    AGGCCCCCGGCAAGGAGAGGGAGGGCGTGGCCACCATCTACACCGGCGACGGCAGGA
    CCTACTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAA
    CACCGTGGACCTGCAGATGAGCAGCCTGAAGCCCGAGGACACCGCCATGTACTACTGC
    GCCGCCAGGGCCGCCCCCCTGTACAGCAGCGGCAGCCCCCTGACCAGGGCCAGGTACA
    ACGTGTGGGGCCAGGGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCA
    GCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGGCTGAGCTG
    CGTGGCCAGCGGCTACGTGAGCTGCGACTACTTCCTGCCCAGCTGGTACAGGCAGGCCC
    CCGGCAAGGAGAGGGAGTTCGTGAGCATCATCGACGGCACCGGCAGCACCAGCTACGC
    CGCCAGCGTGAAGGGCAGGTTCACCGCCAGCCAGGACAAGGGCAAGAACATCGCCTAC
    CTGCAGATGAACACCCTGAAGCCCGAGGACACCGCCATGTACTACTGCAAGGCCAGCT
    GCGTGAGGGGCAGGGCCATCAGCGAGTACTGGGGCCAGGGCACCCAGGTGACCGTGA
    GCGCTAGCCACCACCACCACCACCACCACCAC
    128 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCGCCGCCAGCGGCTACCCCTACAGCAACGGCTACATGGGCTGGTTCAGGC
    AGGCCCCCGGCAAGGAGAGGGAGGGCGTGGCCACCATCTACACCGGCGACGGCAGGA
    CCTACTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAA
    CACCGTGGACCTGCAGATGAGCAGCCTGAAGCCCGAGGACACCGCCATGTACTACTGC
    GCCGCCAGGGCCGCCCCCCTGTACAGCAGCGGCAGCCCCCTGACCAGGGCCAGGTACA
    ACGTGTGGGGCCAGGGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCA
    GCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGGCTGAGCTG
    CAGGGCCAGCGGCAGCACCTACAGCAACTACTGCCTGGGCTGGTTCAGGCAGATCACC
    GGCAAGGAGAGGGAGGGCGTGGCCGTGATCAACTGGGTGGGCGGCATGCTGTACTTCG
    CCGACAGCGTGAAGGGCAGGTTCACCGTGAGCCAGGACCAGGCCAAGAACACCGTGTA
    CCTGCAGATGAACAGCCTGAAGCCCGAGGACACCGCCATGTACTACTGCGCCGCCGAG
    AGCGTGAGCAGCTTCAGCTGCGGCGGCTGGCTGACCAGGCCCGACAGGGTGCCCTACT
    GGGGCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCACCACCACCACCACCACCA
    C
    129 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCGCCGCCAGCGGCTACCCCTACAGCAACGGCTACATGGGCTGGTTCAGGC
    AGGCCCCCGGCAAGGAGAGGGAGGGCGTGGCCACCATCTACACCGGCGACGGCAGGA
    CCTACTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAA
    CACCGTGGACCTGCAGATGAGCAGCCTGAAGCCCGAGGACACCGCCATGTACTACTGC
    GCCGCCAGGGCCGCCCCCCTGTACAGCAGCGGCAGCCCCCTGACCAGGGCCAGGTACA
    ACGTGTGGGGCCAGGGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCA
    GCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGCTGAGCTGC
    GCCGCCAGCGGCTTCACCTTCAGCCTGAGCAGCATGAGCTGGGTGAGGCAGGCCCCCG
    GCAAGGGCCTGGAGTGGGTGAGCGCCATCAGCAGCGGCGGCGCCAGCACCTACTACAC
    CGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAACATGCTGTAC
    CTGCAGCTGAACAGCCTGAAGACCGAGGACACCGCCATGTACTACTGCGCCAAGGGCG
    GCAGCGGCTACGGCGACGCCAGCAGGATGACCAGCCCCGGCAGCCAGGGCACCCAGGT
    GACCGTGAGCGCTAGCCACCACCACCACCACCACCACCAC
    130 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCGTGGCCAGCGCCAGCACCTACTGCACCTACGACATGCACTGGTACAGGC
    AGGCCCCCGGCAAGGGCAGGGAGTTCGTGAGCGCCATCGACAGCGACGGCACCACCAG
    GTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCCAGGGCACCGCCAAGAACACC
    GTGTACCTGCAGATGAACAGCCTGCAGCCCGAGGACACCGCCATGTACTACTGCAAGA
    CCGTGTGCGTGGTGGGCAGCAGGTGGAGCGACTACTGGGGCCAGGGCACCCAGGTGAC
    CGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTG
    CAGCCCGGCGGCAGCCTGAGGCTGAGCTGCGCCGCCAGCGGCTTCACCTTCAGCAGCT
    ACCCCATGAGCTGGGTGAGGCAGGCCCCCGGCAAGGGCCTGGAGTGGATCAGCACCAT
    CAGCGCCGGCGGCGACACCACCCTGTACGCCGACAGCGTGAAGGGCAGGTTCACCAGC
    AGCAGGGACAACGCCAAGAACACCCTGTACCTGCAGCTGAACAGCCTGAAGACCGAGG
    ACGCCGCCATCTACTACTGCGCCAAGAGGATCGACTGCAACAGCGGCTACTGCTACAG
    GAGGAACTACTGGGGCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCACCACCAC
    CACCACCACCAC
    131 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCGTGGCCAGCGCCAGCACCTACTGCACCTACGACATGCACTGGTACAGGC
    AGGCCCCCGGCAAGGGCAGGGAGTTCGTGAGCGCCATCGACAGCGACGGCACCACCAG
    GTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCCAGGGCACCGCCAAGAACACC
    GTGTACCTGCAGATGAACAGCCTGCAGCCCGAGGACACCGCCATGTACTACTGCAAGA
    CCGTGTGCGTGGTGGGCAGCAGGTGGAGCGACTACTGGGGCCAGGGCACCCAGGTGAC
    CGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTG
    CAGCCCGGCGAGAGCCTGAGGCTGAGCTGCACCGCCAGCGGCTTCACCTTCAGCAACT
    ACGCCATGAGCTGGGTGAGGCAGGCCCCCGGCAAGGGCCTGGAGTGGGTGAGCGGCAT
    CAACGTGGCCTACGGCATCACCAGCTACGCCGACAGCGTGAAGGGCAGGTTCACCATC
    AGCAGGGACAACACCAAGAACACCCTGTACCTGCAGCTGAACAGCCTGAAGACCGAGG
    ACACCGCCATCTACTACTGCGTGAAGCACAGCGGCACCACCATCCCCAGGGGCTTCATC
    AGCTACACCAAGAGGGGCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCACCACC
    ACCACCACCACCAC
    132 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCGTGGCCAGCGCCAGCACCTACTGCACCTACGACATGCACTGGTACAGGC
    AGGCCCCCGGCAAGGGCAGGGAGTTCGTGAGCGCCATCGACAGCGACGGCACCACCAG
    GTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCCAGGGCACCGCCAAGAACACC
    GTGTACCTGCAGATGAACAGCCTGCAGCCCGAGGACACCGCCATGTACTACTGCAAGA
    CCGTGTGCGTGGTGGGCAGCAGGTGGAGCGACTACTGGGGCCAGGGCACCCAGGTGAC
    CGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTG
    CAGCCCGGCGGCAGCCTGAGGCTGAGCTGCGCCGCCAGCGGCTTCAGCTTCAGCAGCT
    ACGCCATGAAGTGGGTGAGGCAGGCCCCCGGCAAGGGCCTGGAGTGGGTGAGCACCAT
    CAGCAGCGGCGGCAGCAGCACCAACTACGCCGACAGCGTGAAGGGCAGGTTCACCATC
    AGCAGGGACAACGCCAAGAACACCCTGTACCTGCAGCTGAACAGCCTGAAGATCGAGG
    ACACCGCCATGTACTACTGCGCCAAGGCCATCGTGCCCACCGGCGCCACCATGGAGAG
    GGGCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCACCACCACCACCACCACCAC
    133 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCGTGGCCAGCGCCAGCACCTACTGCACCTACGACATGCACTGGTACAGGC
    AGGCCCCCGGCAAGGGCAGGGAGTTCGTGAGCGCCATCGACAGCGACGGCACCACCAG
    GTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCCAGGGCACCGCCAAGAACACC
    GTGTACCTGCAGATGAACAGCCTGCAGCCCGAGGACACCGCCATGTACTACTGCAAGA
    CCGTGTGCGTGGTGGGCAGCAGGTGGAGCGACTACTGGGGCCAGGGCACCCAGGTGAC
    CGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTG
    CAGAGCGGCGGCAGCCTGAGGCTGAGCTGCGCCGCCAGCGGCTTCACCTACAGCACCA
    GCAACAGCTGGATGGCCTGGTTCAGGCAGGCCCCCGGCAAGGAGAGGGAGGGCGTGG
    CCGCCATCTACACCGTGGGCGGCAGCATCTTCTACGCCGACAGCGTGAGGGGCAGGTT
    CACCATCAGCCAGGACGCCACCAAGAACATGTTCTACCTGCAGATGAACACCCTGAAG
    CCCGAGGACACCGCCATGTACTACTGCGCCGCCGCCAGCGGCAGGCTGAGGGGCAAGT
    GGTTCTGGCCCTACGAGTACAACTACTGGGGCCAGGGCACCCAGGTGACCGTGAGCGC
    TAGCCACCACCACCACCACCACCACCAC
    134 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCGTGGCCAGCGCCAGCACCTACTGCACCTACGACATGCACTGGTACAGGC
    AGGCCCCCGGCAAGGGCAGGGAGTTCGTGAGCGCCATCGACAGCGACGGCACCACCAG
    GTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCCAGGGCACCGCCAAGAACACC
    GTGTACCTGCAGATGAACAGCCTGCAGCCCGAGGACACCGCCATGTACTACTGCAAGA
    CCGTGTGCGTGGTGGGCAGCAGGTGGAGCGACTACTGGGGCCAGGGCACCCAGGTGAC
    CGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTG
    CAGGCCGGCGGCAGCCTGAGGCTGAGCTGCGTGGCCAGCGGCTACGTGAGCTGCGACT
    ACTTCCTGCCCAGCTGGTACAGGCAGGCCCCCGGCAAGGAGAGGGAGTTCGTGAGCAT
    CATCGACGGCACCGGCAGCACCAGCTACGCCGCCAGCGTGAAGGGCAGGTTCACCGCC
    AGCCAGGACAAGGGCAAGAACATCGCCTACCTGCAGATGAACACCCTGAAGCCCGAGG
    ACACCGCCATGTACTACTGCAAGGCCAGCTGCGTGAGGGGCAGGGCCATCAGCGAGTA
    CTGGGGCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCACCACCACCACCACCAC
    CAC
    135 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCGTGGCCAGCGCCAGCACCTACTGCACCTACGACATGCACTGGTACAGGC
    AGGCCCCCGGCAAGGGCAGGGAGTTCGTGAGCGCCATCGACAGCGACGGCACCACCAG
    GTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCCAGGGCACCGCCAAGAACACC
    GTGTACCTGCAGATGAACAGCCTGCAGCCCGAGGACACCGCCATGTACTACTGCAAGA
    CCGTGTGCGTGGTGGGCAGCAGGTGGAGCGACTACTGGGGCCAGGGCACCCAGGTGAC
    CGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTG
    CAGGCCGGCGGCAGCCTGAGGCTGAGCTGCAGGGCCAGCGGCAGCACCTACAGCAACT
    ACTGCCTGGGCTGGTTCAGGCAGATCACCGGCAAGGAGAGGGAGGGCGTGGCCGTGAT
    CAACTGGGTGGGCGGCATGCTGTACTTCGCCGACAGCGTGAAGGGCAGGTTCACCGTG
    AGCCAGGACCAGGCCAAGAACACCGTGTACCTGCAGATGAACAGCCTGAAGCCCGAGG
    ACACCGCCATGTACTACTGCGCCGCCGAGAGCGTGAGCAGCTTCAGCTGCGGCGGCTG
    GCTGACCAGGCCCGACAGGGTGCCCTACTGGGGCCAGGGCACCCAGGTGACCGTGAGC
    GCTAGCCACCACCACCACCACCACCACCAC
    136 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCGTGGCCAGCGCCAGCACCTACTGCACCTACGACATGCACTGGTACAGGC
    AGGCCCCCGGCAAGGGCAGGGAGTTCGTGAGCGCCATCGACAGCGACGGCACCACCAG
    GTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCCAGGGCACCGCCAAGAACACC
    GTGTACCTGCAGATGAACAGCCTGCAGCCCGAGGACACCGCCATGTACTACTGCAAGA
    CCGTGTGCGTGGTGGGCAGCAGGTGGAGCGACTACTGGGGCCAGGGCACCCAGGTGAC
    CGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTG
    CAGCCCGGCGGCAGCCTGAGGCTGAGCTGCGCCGCCAGCGGCTTCACCTTCAGCCTGA
    GCAGCATGAGCTGGGTGAGGCAGGCCCCCGGCAAGGGCCTGGAGTGGGTGAGCGCCAT
    CAGCAGCGGCGGCGCCAGCACCTACTACACCGACAGCGTGAAGGGCAGGTTCACCATC
    AGCAGGGACAACGCCAAGAACATGCTGTACCTGCAGCTGAACAGCCTGAAGACCGAGG
    ACACCGCCATGTACTACTGCGCCAAGGGCGGCAGCGGCTACGGCGACGCCAGCAGGAT
    GACCAGCCCCGGCAGCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCACCACCAC
    CACCACCACCAC
    137 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGACC
    CTGAGCTGCGCCGCCAGCGAGTACGCCTACAGCACCTGCAACATGGGCTGGTACAGGC
    AGGCCCCCGGCAAGGAGAGGGAGCTGGTGAGCGCCTTCATCAGCGACGGCAGCACCTA
    CTACGCCGACAGCGTGAAGGGCAGGTTCACCATCACCAGGGACAACGCCAAGAACACC
    GTGTACCTGCAGATGAACAGCCTGAAGCCCGAGGACACCGCCATCTACTACTGCAGCG
    CCAACTGCTACAGGAGGCTGAGGAACTACTGGGGCCAGGGCACCCAGGTGACCGTCTC
    GAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCC
    GGCGGCAGCCTGAGGCTGAGCTGCGCCGCCAGCGGCTTCACCTTCAGCAGCTACCCCAT
    GAGCTGGGTGAGGCAGGCCCCCGGCAAGGGCCTGGAGTGGATCAGCACCATCAGCGCC
    GGCGGCGACACCACCCTGTACGCCGACAGCGTGAAGGGCAGGTTCACCAGCAGCAGGG
    ACAACGCCAAGAACACCCTGTACCTGCAGCTGAACAGCCTGAAGACCGAGGACGCCGC
    CATCTACTACTGCGCCAAGAGGATCGACTGCAACAGCGGCTACTGCTACAGGAGGAAC
    TACTGGGGCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCACCACCACCACCACC
    ACCAC
    138 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGACC
    CTGAGCTGCGCCGCCAGCGAGTACGCCTACAGCACCTGCAACATGGGCTGGTACAGGC
    AGGCCCCCGGCAAGGAGAGGGAGCTGGTGAGCGCCTTCATCAGCGACGGCAGCACCTA
    CTACGCCGACAGCGTGAAGGGCAGGTTCACCATCACCAGGGACAACGCCAAGAACACC
    GTGTACCTGCAGATGAACAGCCTGAAGCCCGAGGACACCGCCATCTACTACTGCAGCG
    CCAACTGCTACAGGAGGCTGAGGAACTACTGGGGCCAGGGCACCCAGGTGACCGTCTC
    GAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCC
    GGCGAGAGCCTGAGGCTGAGCTGCACCGCCAGCGGCTTCACCTTCAGCAACTACGCCA
    TGAGCTGGGTGAGGCAGGCCCCCGGCAAGGGCCTGGAGTGGGTGAGCGGCATCAACGT
    GGCCTACGGCATCACCAGCTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGG
    GACAACACCAAGAACACCCTGTACCTGCAGCTGAACAGCCTGAAGACCGAGGACACCG
    CCATCTACTACTGCGTGAAGCACAGCGGCACCACCATCCCCAGGGGCTTCATCAGCTAC
    ACCAAGAGGGGCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCACCACCACCACC
    ACCACCAC
    139 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGACC
    CTGAGCTGCGCCGCCAGCGAGTACGCCTACAGCACCTGCAACATGGGCTGGTACAGGC
    AGGCCCCCGGCAAGGAGAGGGAGCTGGTGAGCGCCTTCATCAGCGACGGCAGCACCTA
    CTACGCCGACAGCGTGAAGGGCAGGTTCACCATCACCAGGGACAACGCCAAGAACACC
    GTGTACCTGCAGATGAACAGCCTGAAGCCCGAGGACACCGCCATCTACTACTGCAGCG
    CCAACTGCTACAGGAGGCTGAGGAACTACTGGGGCCAGGGCACCCAGGTGACCGTCTC
    GAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCC
    GGCGGCAGCCTGAGGCTGAGCTGCGCCGCCAGCGGCTTCAGCTTCAGCAGCTACGCCA
    TGAAGTGGGTGAGGCAGGCCCCCGGCAAGGGCCTGGAGTGGGTGAGCACCATCAGCAG
    CGGCGGCAGCAGCACCAACTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGG
    GACAACGCCAAGAACACCCTGTACCTGCAGCTGAACAGCCTGAAGATCGAGGACACCG
    CCATGTACTACTGCGCCAAGGCCATCGTGCCCACCGGCGCCACCATGGAGAGGGGCCA
    GGGCACCCAGGTGACCGTGAGCGCTAGCCACCACCACCACCACCACCACCAC
    140 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGACC
    CTGAGCTGCGCCGCCAGCGAGTACGCCTACAGCACCTGCAACATGGGCTGGTACAGGC
    AGGCCCCCGGCAAGGAGAGGGAGCTGGTGAGCGCCTTCATCAGCGACGGCAGCACCTA
    CTACGCCGACAGCGTGAAGGGCAGGTTCACCATCACCAGGGACAACGCCAAGAACACC
    GTGTACCTGCAGATGAACAGCCTGAAGCCCGAGGACACCGCCATCTACTACTGCAGCG
    CCAACTGCTACAGGAGGCTGAGGAACTACTGGGGCCAGGGCACCCAGGTGACCGTCTC
    GAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGAG
    CGGCGGCAGCCTGAGGCTGAGCTGCGCCGCCAGCGGCTTCACCTACAGCACCAGCAAC
    AGCTGGATGGCCTGGTTCAGGCAGGCCCCCGGCAAGGAGAGGGAGGGCGTGGCCGCCA
    TCTACACCGTGGGCGGCAGCATCTTCTACGCCGACAGCGTGAGGGGCAGGTTCACCATC
    AGCCAGGACGCCACCAAGAACATGTTCTACCTGCAGATGAACACCCTGAAGCCCGAGG
    ACACCGCCATGTACTACTGCGCCGCCGCCAGCGGCAGGCTGAGGGGCAAGTGGTTCTG
    GCCCTACGAGTACAACTACTGGGGCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCAC
    CACCACCACCACCACCACCAC
    141 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGACC
    CTGAGCTGCGCCGCCAGCGAGTACGCCTACAGCACCTGCAACATGGGCTGGTACAGGC
    AGGCCCCCGGCAAGGAGAGGGAGCTGGTGAGCGCCTTCATCAGCGACGGCAGCACCTA
    CTACGCCGACAGCGTGAAGGGCAGGTTCACCATCACCAGGGACAACGCCAAGAACACC
    GTGTACCTGCAGATGAACAGCCTGAAGCCCGAGGACACCGCCATCTACTACTGCAGCG
    CCAACTGCTACAGGAGGCTGAGGAACTACTGGGGCCAGGGCACCCAGGTGACCGTCTC
    GAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGC
    CGGCGGCAGCCTGAGGCTGAGCTGCGTGGCCAGCGGCTACGTGAGCTGCGACTACTTC
    CTGCCCAGCTGGTACAGGCAGGCCCCCGGCAAGGAGAGGGAGTTCGTGAGCATCATCG
    ACGGCACCGGCAGCACCAGCTACGCCGCCAGCGTGAAGGGCAGGTTCACCGCCAGCCA
    GGACAAGGGCAAGAACATCGCCTACCTGCAGATGAACACCCTGAAGCCCGAGGACACC
    GCCATGTACTACTGCAAGGCCAGCTGCGTGAGGGGCAGGGCCATCAGCGAGTACTGGG
    GCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCACCACCACCACCACCACCAC
    142 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGACC
    CTGAGCTGCGCCGCCAGCGAGTACGCCTACAGCACCTGCAACATGGGCTGGTACAGGC
    AGGCCCCCGGCAAGGAGAGGGAGCTGGTGAGCGCCTTCATCAGCGACGGCAGCACCTA
    CTACGCCGACAGCGTGAAGGGCAGGTTCACCATCACCAGGGACAACGCCAAGAACACC
    GTGTACCTGCAGATGAACAGCCTGAAGCCCGAGGACACCGCCATCTACTACTGCAGCG
    CCAACTGCTACAGGAGGCTGAGGAACTACTGGGGCCAGGGCACCCAGGTGACCGTCTC
    GAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGC
    CGGCGGCAGCCTGAGGCTGAGCTGCAGGGCCAGCGGCAGCACCTACAGCAACTACTGC
    CTGGGCTGGTTCAGGCAGATCACCGGCAAGGAGAGGGAGGGCGTGGCCGTGATCAACT
    GGGTGGGCGGCATGCTGTACTTCGCCGACAGCGTGAAGGGCAGGTTCACCGTGAGCCA
    GGACCAGGCCAAGAACACCGTGTACCTGCAGATGAACAGCCTGAAGCCCGAGGACACC
    GCCATGTACTACTGCGCCGCCGAGAGCGTGAGCAGCTTCAGCTGCGGCGGCTGGCTGA
    CCAGGCCCGACAGGGTGCCCTACTGGGGCCAGGGCACCCAGGTGACCGTGAGCGCTAG
    CCACCACCACCACCACCACCACCAC
    143 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGACC
    CTGAGCTGCGCCGCCAGCGAGTACGCCTACAGCACCTGCAACATGGGCTGGTACAGGC
    AGGCCCCCGGCAAGGAGAGGGAGCTGGTGAGCGCCTTCATCAGCGACGGCAGCACCTA
    CTACGCCGACAGCGTGAAGGGCAGGTTCACCATCACCAGGGACAACGCCAAGAACACC
    GTGTACCTGCAGATGAACAGCCTGAAGCCCGAGGACACCGCCATCTACTACTGCAGCG
    CCAACTGCTACAGGAGGCTGAGGAACTACTGGGGCCAGGGCACCCAGGTGACCGTCTC
    GAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCC
    GGCGGCAGCCTGAGGCTGAGCTGCGCCGCCAGCGGCTTCACCTTCAGCCTGAGCAGCA
    TGAGCTGGGTGAGGCAGGCCCCCGGCAAGGGCCTGGAGTGGGTGAGCGCCATCAGCAG
    CGGCGGCGCCAGCACCTACTACACCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGG
    GACAACGCCAAGAACATGCTGTACCTGCAGCTGAACAGCCTGAAGACCGAGGACACCG
    CCATGTACTACTGCGCCAAGGGCGGCAGCGGCTACGGCGACGCCAGCAGGATGACCAG
    CCCCGGCAGCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCACCACCACCACCAC
    CACCAC
    144 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGC
    TGAGCTGCACCGCCAGCGGCCTGACCTTCGACGACAGCGTGATGGGCTGGTTCAGGCA
    GGCCCCCGGCAAGGGCAGGGAGGCCGTGAGCTGCATCAGCAGCAGCGGCGCCAACGC
    CTTCTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAAC
    ACCCTGTACCTGCAGATGAACAGCCTGAAGCCCGAGGACACCGCCACCTACTACTGCA
    AGAGGGGCCACGCCTGCGCCGGCTACTACCCCATCCCCTACGACGACTACTGGGGCCA
    GGGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGC
    GGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGCTGAGCTGCGCCGCCAGCGGCT
    TCACCTTCAGCAGCTACCCCATGAGCTGGGTGAGGCAGGCCCCCGGCAAGGGCCTGGA
    GTGGATCAGCACCATCAGCGCCGGCGGCGACACCACCCTGTACGCCGACAGCGTGAAG
    GGCAGGTTCACCAGCAGCAGGGACAACGCCAAGAACACCCTGTACCTGCAGCTGAACA
    GCCTGAAGACCGAGGACGCCGCCATCTACTACTGCGCCAAGAGGATCGACTGCAACAG
    CGGCTACTGCTACAGGAGGAACTACTGGGGCCAGGGCACCCAGGTGACCGTGAGCGCT
    AGCCACCACCACCACCACCACCACCAC
    145 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGC
    TGAGCTGCACCGCCAGCGGCCTGACCTTCGACGACAGCGTGATGGGCTGGTTCAGGCA
    GGCCCCCGGCAAGGGCAGGGAGGCCGTGAGCTGCATCAGCAGCAGCGGCGCCAACGC
    CTTCTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAAC
    ACCCTGTACCTGCAGATGAACAGCCTGAAGCCCGAGGACACCGCCACCTACTACTGCA
    AGAGGGGCCACGCCTGCGCCGGCTACTACCCCATCCCCTACGACGACTACTGGGGCCA
    GGGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGC
    GGCGGCGGCCTGGTGCAGCCCGGCGAGAGCCTGAGGCTGAGCTGCACCGCCAGCGGCT
    TCACCTTCAGCAACTACGCCATGAGCTGGGTGAGGCAGGCCCCCGGCAAGGGCCTGGA
    GTGGGTGAGCGGCATCAACGTGGCCTACGGCATCACCAGCTACGCCGACAGCGTGAAG
    GGCAGGTTCACCATCAGCAGGGACAACACCAAGAACACCCTGTACCTGCAGCTGAACA
    GCCTGAAGACCGAGGACACCGCCATCTACTACTGCGTGAAGCACAGCGGCACCACCAT
    CCCCAGGGGCTTCATCAGCTACACCAAGAGGGGCCAGGGCACCCAGGTGACCGTGAGC
    GCTAGCCACCACCACCACCACCACCACCAC
    146 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGC
    TGAGCTGCACCGCCAGCGGCCTGACCTTCGACGACAGCGTGATGGGCTGGTTCAGGCA
    GGCCCCCGGCAAGGGCAGGGAGGCCGTGAGCTGCATCAGCAGCAGCGGCGCCAACGC
    CTTCTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAAC
    ACCCTGTACCTGCAGATGAACAGCCTGAAGCCCGAGGACACCGCCACCTACTACTGCA
    AGAGGGGCCACGCCTGCGCCGGCTACTACCCCATCCCCTACGACGACTACTGGGGCCA
    GGGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGC
    GGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGCTGAGCTGCGCCGCCAGCGGCT
    TCAGCTTCAGCAGCTACGCCATGAAGTGGGTGAGGCAGGCCCCCGGCAAGGGCCTGGA
    GTGGGTGAGCACCATCAGCAGCGGCGGCAGCAGCACCAACTACGCCGACAGCGTGAAG
    GGCAGGTTCACCATCAGCAGGGACAACGCCAAGAACACCCTGTACCTGCAGCTGAACA
    GCCTGAAGATCGAGGACACCGCCATGTACTACTGCGCCAAGGCCATCGTGCCCACCGG
    CGCCACCATGGAGAGGGGCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCACCAC
    CACCACCACCACCAC
    147 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGC
    TGAGCTGCACCGCCAGCGGCCTGACCTTCGACGACAGCGTGATGGGCTGGTTCAGGCA
    GGCCCCCGGCAAGGGCAGGGAGGCCGTGAGCTGCATCAGCAGCAGCGGCGCCAACGC
    CTTCTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAAC
    ACCCTGTACCTGCAGATGAACAGCCTGAAGCCCGAGGACACCGCCACCTACTACTGCA
    AGAGGGGCCACGCCTGCGCCGGCTACTACCCCATCCCCTACGACGACTACTGGGGCCA
    GGGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGC
    GGCGGCGGCAGCGTGCAGAGCGGCGGCAGCCTGAGGCTGAGCTGCGCCGCCAGCGGCT
    TCACCTACAGCACCAGCAACAGCTGGATGGCCTGGTTCAGGCAGGCCCCCGGCAAGGA
    GAGGGAGGGCGTGGCCGCCATCTACACCGTGGGCGGCAGCATCTTCTACGCCGACAGC
    GTGAGGGGCAGGTTCACCATCAGCCAGGACGCCACCAAGAACATGTTCTACCTGCAGA
    TGAACACCCTGAAGCCCGAGGACACCGCCATGTACTACTGCGCCGCCGCCAGCGGCAG
    GCTGAGGGGCAAGTGGTTCTGGCCCTACGAGTACAACTACTGGGGCCAGGGCACCCAG
    GTGACCGTGAGCGCTAGCCACCACCACCACCACCACCACCAC
    148 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGC
    TGAGCTGCACCGCCAGCGGCCTGACCTTCGACGACAGCGTGATGGGCTGGTTCAGGCA
    GGCCCCCGGCAAGGGCAGGGAGGCCGTGAGCTGCATCAGCAGCAGCGGCGCCAACGC
    CTTCTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAAC
    ACCCTGTACCTGCAGATGAACAGCCTGAAGCCCGAGGACACCGCCACCTACTACTGCA
    AGAGGGGCCACGCCTGCGCCGGCTACTACCCCATCCCCTACGACGACTACTGGGGCCA
    GGGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGC
    GGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGGCTGAGCTGCGTGGCCAGCGGCT
    ACGTGAGCTGCGACTACTTCCTGCCCAGCTGGTACAGGCAGGCCCCCGGCAAGGAGAG
    GGAGTTCGTGAGCATCATCGACGGCACCGGCAGCACCAGCTACGCCGCCAGCGTGAAG
    GGCAGGTTCACCGCCAGCCAGGACAAGGGCAAGAACATCGCCTACCTGCAGATGAACA
    CCCTGAAGCCCGAGGACACCGCCATGTACTACTGCAAGGCCAGCTGCGTGAGGGGCAG
    GGCCATCAGCGAGTACTGGGGCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCAC
    CACCACCACCACCACCAC
    149 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGC
    TGAGCTGCACCGCCAGCGGCCTGACCTTCGACGACAGCGTGATGGGCTGGTTCAGGCA
    GGCCCCCGGCAAGGGCAGGGAGGCCGTGAGCTGCATCAGCAGCAGCGGCGCCAACGC
    CTTCTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAAC
    ACCCTGTACCTGCAGATGAACAGCCTGAAGCCCGAGGACACCGCCACCTACTACTGCA
    AGAGGGGCCACGCCTGCGCCGGCTACTACCCCATCCCCTACGACGACTACTGGGGCCA
    GGGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGC
    GGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGGCTGAGCTGCAGGGCCAGCGGC
    AGCACCTACAGCAACTACTGCCTGGGCTGGTTCAGGCAGATCACCGGCAAGGAGAGGG
    AGGGCGTGGCCGTGATCAACTGGGTGGGCGGCATGCTGTACTTCGCCGACAGCGTGAA
    GGGCAGGTTCACCGTGAGCCAGGACCAGGCCAAGAACACCGTGTACCTGCAGATGAAC
    AGCCTGAAGCCCGAGGACACCGCCATGTACTACTGCGCCGCCGAGAGCGTGAGCAGCT
    TCAGCTGCGGCGGCTGGCTGACCAGGCCCGACAGGGTGCCCTACTGGGGCCAGGGCAC
    CCAGGTGACCGTGAGCGCTAGCCACCACCACCACCACCACCACCAC
    150 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGC
    TGAGCTGCACCGCCAGCGGCCTGACCTTCGACGACAGCGTGATGGGCTGGTTCAGGCA
    GGCCCCCGGCAAGGGCAGGGAGGCCGTGAGCTGCATCAGCAGCAGCGGCGCCAACGC
    CTTCTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAAC
    ACCCTGTACCTGCAGATGAACAGCCTGAAGCCCGAGGACACCGCCACCTACTACTGCA
    AGAGGGGCCACGCCTGCGCCGGCTACTACCCCATCCCCTACGACGACTACTGGGGCCA
    GGGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGC
    GGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGCTGAGCTGCGCCGCCAGCGGCT
    TCACCTTCAGCCTGAGCAGCATGAGCTGGGTGAGGCAGGCCCCCGGCAAGGGCCTGGA
    GTGGGTGAGCGCCATCAGCAGCGGCGGCGCCAGCACCTACTACACCGACAGCGTGAAG
    GGCAGGTTCACCATCAGCAGGGACAACGCCAAGAACATGCTGTACCTGCAGCTGAACA
    GCCTGAAGACCGAGGACACCGCCATGTACTACTGCGCCAAGGGCGGCAGCGGCTACGG
    CGACGCCAGCAGGATGACCAGCCCCGGCAGCCAGGGCACCCAGGTGACCGTGAGCGCT
    AGCCACCACCACCACCACCACCACCAC
  • Anti-IL27Rα VHH-Linker-Anti-GP130 VHH
  • A bispecific VHH2 can contain, from the N-terminus to the C-terminus, a first VHH binding to IL27Rα (an anti-TL27Rα VHH antibody), a linker, and a second VHH binding to gp130 (an anti-gp130 VHH antibody). In other words, the linker joins the C-terminus of the anti-IL27Rα VHH in the binding protein to the N-terminus of the anti-gp 130 VHH in the binding protein. In some embodiments, a purification peptide, e.g., a six-histidine peptide ((His)6 (SEQ ID NO: 1531) or His-tag) or an Fc tag can be included in the bispecific VHH2.
  • In certain embodiments, a bispecific VHH2 described herein comprises an anti-IL27Rα VHH antibody comprising a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity to a sequence of any one of SEQ ID NOS:245-251; and an anti-gp130 VHH antibody comprising a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity to a sequence of any one of SEQ ID NOS:252-257.
  • In certain embodiments, a bispecific VHH2 described herein comprises an anti-IL27Rα VHH antibody and an anti-gp130 VHH antibody as described in each row of Table 3A below or Table A above. In some embodiments, in each row of Table 3A, the anti-IL27Ra VHH antibody and the anti-gp130 VHH antibody can each, independently, comprise at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity to the sequence described in each row of Table 3A. In some embodiments, the bispecific VHH2 can comprise a linker (e.g., linkers described in Section IV) between the anti-IL27Rα VHH antibody and the anti-gp130 VHH antibody as described in each row of Table 3A below. In particular embodiments, the linker is GGGS (SEQ ID NO:108). The sequence of the anti-IL27Rα VHH is N-terminal to the linker and the sequence of the anti-gp130 VHH is C-terminal to the linker. Examples of linkers are further described in Section IV below. The CDR sequences in each VHH are underlined.
  • TABLE 3A
    N-terminal Anti-IL27Rα VHH C-terminal Anti-gp130 VHH
    QVQLQESGGGLVQPGGSLRLSCAASGFTFSSY QVQLQESGGGSVQAGGSLRLSCTASGAIASGY
    PMSWVRQAPGKGLEWISTISAGGDTTLYADSV IDSRWCMAWFRQAPGKEREGVAAIWPGGGLT
    KGRFTSSRDNAKNTLYLQLNSLKTEDAAIYYC VYADSVKGRFTISRDHAKNTLYLQMNNLKPE
    AKRIDCNSGYCYRRNYWGQGTQVTVSS (SEQ DTAMYYCAAGSPRMCPSLEFGFDYWGQGTQV
    ID NO: 245) TVS (SEQ ID NO: 252)
    QVQLQESGGGLVQPGGSLRLSCAASGFTFSSY QVQLQESGGGSVQAGGSLRLSCTAPGFTSNSC
    PMSWVRQAPGKGLEWISTISAGGDTTLYADSV GMDWYRQAPGKEREFVSSISTDGTTGYADSV
    KGRFTSSRDNAKNTLYLQLNSLKTEDAAIYYC KGRFTISKDKAKDTVYLQMNSLKPEDTGMYS
    AKRIDCNSGYCYRRNYWGQGTQVTVSS (SEQ CKTKDGTIATMELCDFGYWGQGTQVTVS
    ID NO: 245) (SEQ ID NO: 253)
    QVQLQESGGGLVQPGGSLRLSCAASGFTFSSY QVQLQESGGGSVQAGGSLRLSCAASGYPYSN
    PMSWVRQAPGKGLEWISTISAGGDTTLYADSV GYMGWFRQAPGKEREGVATIYTGDGRTYYAD
    KGRFTSSRDNAKNTLYLQLNSLKTEDAAIYYC SVKGRFTISRDNAKNTVDLQMSSLKPEDTAMY
    AKRIDCNSGYCYRRNYWGQGTQVTVSS (SEQ YCAARAAPLYSSGSPLTRARYNVWGQGTQVT
    ID NO: 245) VS (SEQ ID NO: 254)
    QVQLQESGGGLVQPGGSLRLSCAASGFTFSSY QVQLQESGGGSVQAGGSLRLSCVASASTYCTY
    PMSWVRQAPGKGLEWISTISAGGDTTLYADSV DMHWYRQAPGKGREFVSAIDSDGTTRYADSV
    KGRFTSSRDNAKNTLYLQLNSLKTEDAAIYYC KGRFTISQGTAKNTVYLQMNSLOPEDTAMYY
    AKRIDCNSGYCYRRNYWGQGTQVTVSS (SEQ CKTVCVVGSRWSDYWGQGTQVTVS (SEQ ID
    ID NO: 245) NO: 255)
    QVQLQESGGGLVQPGGSLRLSCAASGFTFSSY QVQLQESGGGSVQAGGSLTLSCAASEYAYSTC
    PMSWVRQAPGKGLEWISTISAGGDTTLYADSV NMGWYRQAPGKERELVSAFISDGSTYYADSV
    KGRFTSSRDNAKNTLYLQLNSLKTEDAAIYYC KGRFTITRDNAKNTVYLQMNSLKPEDTAIYYC
    AKRIDCNSGYCYRRNYWGQGTQVTVSS (SEQ SANCYRRLRNYWGQGTQVTVS(SEQ ID
    ID NO: 245) NO: 256)
    QVQLQESGGGLVQPGGSLRLSCAASGFTFSSY QVQLQESGGGLVQPGGSLRLSCTASGLTFDDS
    PMSWVRQAPGKGLEWISTISAGGDTTLYADSV VMGWFRQAPGKGREAVSCISSSGANAFYADS
    KGRFTSSRDNAKNTLYLQLNSLKTEDAAIYYC VKGRFTISRDNAKNTLYLQMNSLKPEDTATYY
    AKRIDCNSGYCYRRNYWGQGTQVTVSS (SEQ CKRGHACAGYYPIPYDDYWGQGTQVTVS
    ID NO: 245) (SEQ ID NO: 257)
    QVQLQESGGGLVQPGESLRLSCTASGFTFSNY QVQLQESGGGSVQAGGSLRLSCTASGAIASGY
    AMSWVRQAPGKGLEWVSGINVAYGITSYADS IDSRWCMAWFRQAPGKEREGVAAIWPGGGLT
    VKGRFTISRDNTKNTLYLQLNSLKTEDTAIYYC VYADSVKGRFTISRDHAKNTLYLQMNNLKPE
    VKHSGTTIPRGFISYTKRGQGTQVTVSS (SEQ DTAMYYCAAGSPRMCPSLEFGFDYWGQGTQV
    ID NO: 246) TVS (SEQ ID NO: 252)
    QVQLQESGGGLVQPGESLRLSCTASGFTFSNY QVQLQESGGGSVQAGGSLRLSCTAPGFTSNSC
    AMSWVRQAPGKGLEWVSGINVAYGITSYADS GMDWYRQAPGKEREFVSSISTDGTTGYADSV
    VKGRFTISRDNTKNTLYLQLNSLKTEDTAIYYC KGRFTISKDKAKDTVYLQMNSLKPEDTGMYS
    VKHSGTTIPRGFISYTKRGQGTQVTVSS (SEQ CKTKDGTIATMELCDFGYWGQGTQVTVS
    ID NO: 246) (SEQ ID NO: 253)
    QVQLQESGGGLVQPGESLRLSCTASGFTFSNY QVQLQESGGGSVQAGGSLRLSCAASGYPYSN
    AMSWVRQAPGKGLEWVSGINVAYGITSYADS GYMGWFRQAPGKEREGVATIYTGDGRTYYAD
    VKGRFTISRDNTKNTLYLQLNSLKTEDTAIYYC SVKGRFTISRDNAKNTVDLQMSSLKPEDTAMY
    VKHSGTTIPRGFISYTKRGQGTQVTVSS (SEQ YCAARAAPLYSSGSPLTRARYNVWGQGTQVT
    ID NO: 246) VS (SEQ ID NO: 254)
    QVQLQESGGGLVQPGESLRLSCTASGFTFSNY QVQLQESGGGSVQAGGSLRLSCVASASTYCTY
    AMSWVRQAPGKGLEWVSGINVAYGITSYADS DMHWYRQAPGKGREFVSAIDSDGTTRYADSV
    VKGRFTISRDNTKNTLYLQLNSLKTEDTAIYYC KGRFTISQGTAKNTVYLQMNSLOPEDTAMYY
    VKHSGTTIPRGFISYTKRGQGTQVTVSS (SEQ CKTVCVVGSRWSDYWGQGTQVTVS (SEQ ID
    ID NO: 246) NO: 255)
    QVQLQESGGGLVQPGESLRLSCTASGFTFSNY QVQLQESGGGSVQAGGSLTLSCAASEYAYSTC
    AMSWVRQAPGKGLEWVSGINVAYGITSYADS NMGWYRQAPGKERELVSAFISDGSTYYADSV
    VKGRFTISRDNTKNTLYLQLNSLKTEDTAIYYC KGRFTITRDNAKNTVYLQMNSLKPEDTAIYYC
    VKHSGTTIPRGFISYTKRGQGTQVTVSS (SEQ SANCYRRLRNYWGQGTQVTVS(SEQ ID
    ID NO: 246) NO: 256)
    QVQLQESGGGLVQPGESLRLSCTASGFTFSNY QVQLQESGGGLVQPGGSLRLSCTASGLTFDDS
    AMSWVRQAPGKGLEWVSGINVAYGITSYADS VMGWFRQAPGKGREAVSCISSSGANAFYADS
    VKGRFTISRDNTKNTLYLQLNSLKTEDTAIYYC VKGRFTISRDNAKNTLYLQMNSLKPEDTATYY
    VKHSGTTIPRGFISYTKRGQGTQVTVSS (SEQ CKRGHACAGYYPIPYDDYWGQGTQVTVS
    ID NO: 246) (SEQ ID NO: 257)
    QVQLQESGGGLVQPGGSLRLSCAASGFSFSSY QVQLQESGGGSVQAGGSLRLSCTASGAIASGY
    AMKWVRQAPGKGLEWVSTISSGGSSTNYADS IDSRWCMAWFRQAPGKEREGVAAIWPGGGLT
    VKGRFTISRDNAKNTLYLQLNSLKIEDTAMYY VYADSVKGRFTISRDHAKNTLYLQMNNLKPE
    CAKAIVPTGATMERGQGTQVTVSS (SEQ ID DTAMYYCAAGSPRMCPSLEFGFDYWGQGTQV
    NO: 247) TVS (SEQ ID NO: 252)
    QVQLQESGGGLVQPGGSLRLSCAASGFSFSSY QVQLQESGGGSVQAGGSLRLSCTAPGFTSNSC
    AMKWVRQAPGKGLEWVSTISSGGSSTNYADS GMDWYRQAPGKEREFVSSISTDGTTGYADSV
    VKGRFTISRDNAKNTLYLQLNSLKIEDTAMYY KGRFTISKDKAKDTVYLQMNSLKPEDTGMYS
    CAKAIVPTGATMERGQGTQVTVSS (SEQ ID CKTKDGTIATMELCDFGYWGQGTQVTVS
    NO: 247) (SEQ ID NO: 253)
    QVQLQESGGGLVQPGGSLRLSCAASGFSFSSY QVQLQESGGGSVQAGGSLRLSCAASGYPYSN
    AMKWVRQAPGKGLEWVSTISSGGSSTNYADS GYMGWFRQAPGKEREGVATIYTGDGRTYYAD
    VKGRFTISRDNAKNTLYLQLNSLKIEDTAMYY SVKGRFTISRDNAKNTVDLQMSSLKPEDTAMY
    CAKAIVPTGATMERGQGTQVTVSS (SEQ ID YCAARAAPLYSSGSPLTRARYNVWGQGTQVT
    NO: 247) VS (SEQ ID NO: 254)
    QVQLQESGGGLVQPGGSLRLSCAASGFSFSSY QVQLQESGGGSVQAGGSLRLSCVASASTYCTY
    AMKWVRQAPGKGLEWVSTISSGGSSTNYADS DMHWYRQAPGKGREFVSAIDSDGTTRYADSV
    VKGRFTISRDNAKNTLYLQLNSLKIEDTAMYY KGRFTISQGTAKNTVYLQMNSLOPEDTAMYY
    CAKAIVPTGATMERGQGTQVTVSS (SEQ ID CKTVCVVGSRWSDYWGQGTQVTVS (SEQ ID
    NO: 247) NO: 255)
    QVQLQESGGGLVQPGGSLRLSCAASGFSFSSY QVQLQESGGGSVQAGGSLTLSCAASEYAYSTC
    AMKWVRQAPGKGLEWVSTISSGGSSTNYADS NMGWYRQAPGKERELVSAFISDGSTYYADSV
    VKGRFTISRDNAKNTLYLQLNSLKIEDTAMYY KGRFTITRDNAKNTVYLQMNSLKPEDTAIYYC
    CAKAIVPTGATMERGQGTQVTVSS (SEQ ID SANCYRRLRNYWGQGTQVTVS(SEQ ID
    NO: 247) NO: 256)
    QVQLQESGGGLVQPGGSLRLSCAASGFSFSSY QVQLQESGGGLVQPGGSLRLSCTASGLTFDDS
    AMKWVRQAPGKGLEWVSTISSGGSSTNYADS VMGWFRQAPGKGREAVSCISSSGANAFYADS
    VKGRFTISRDNAKNTLYLQLNSLKIEDTAMYY VKGRFTISRDNAKNTLYLQMNSLKPEDTATYY
    CAKAIVPTGATMERGQGTQVTVSS (SEQ ID CKRGHACAGYYPIPYDDYWGQGTQVTVS
    NO: 247) (SEQ ID NO: 257)
    QVQLQESGGGSVQSGGSLRLSCAASGFTYSTS QVQLQESGGGSVQAGGSLRLSCTASGAIASGY
    NSWMAWFRQAPGKEREGVAAIYTVGGSIFYA IDSRWCMAWFRQAPGKEREGVAAIWPGGGLT
    DSVRGRFTISQDATKNMFYLQMNTLKPEDTA VYADSVKGRFTISRDHAKNTLYLQMNNLKPE
    MYYCAAASGRLRGKWFWPYEYNYWGQGTQ DTAMYYCAAGSPRMCPSLEFGFDYWGQGTQV
    VTVSS (SEQ ID NO: 248) TVS (SEQ ID NO: 252)
    QVQLQESGGGSVQSGGSLRLSCAASGFTYSTS QVQLQESGGGSVQAGGSLRLSCTAPGFTSNSC
    NSWMAWFRQAPGKEREGVAAIYTVGGSIFYA GMDWYRQAPGKEREFVSSISTDGTTGYADSV
    DSVRGRFTISQDATKNMFYLQMNTLKPEDTA KGRFTISKDKAKDTVYLQMNSLKPEDTGMYS
    MYYCAAASGRLRGKWFWPYEYNYWGQGTQ CKTKDGTIATMELCDFGYWGQGTQVTVS
    VTVSS (SEQ ID NO: 248) (SEQ ID NO: 253)
    QVQLQESGGGSVQSGGSLRLSCAASGFTYSTS QVQLQESGGGSVQAGGSLRLSCAASGYPYSN
    NSWMAWFRQAPGKEREGVAAIYTVGGSIFYA GYMGWFRQAPGKEREGVATIYTGDGRTYYAD
    DSVRGRFTISQDATKNMFYLQMNTLKPEDTA SVKGRFTISRDNAKNTVDLQMSSLKPEDTAMY
    MYYCAAASGRLRGKWFWPYEYNYWGQGTQ YCAARAAPLYSSGSPLTRARYNVWGQGTQVT
    VTVSS (SEQ ID NO: 248) VS (SEQ ID NO: 254)
    QVQLQESGGGSVQSGGSLRLSCAASGFTYSTS QVQLQESGGGSVQAGGSLRLSCVASASTYCTY
    NSWMAWFRQAPGKEREGVAAIYTVGGSIFYA DMHWYRQAPGKGREFVSAIDSDGTTRYADSV
    DSVRGRFTISQDATKNMFYLQMNTLKPEDTA KGRFTISQGTAKNTVYLQMNSLOPEDTAMYY
    MYYCAAASGRLRGKWFWPYEYNYWGQGTQ CKTVCVVGSRWSDYWGQGTQVTVS (SEQ ID
    VTVSS (SEQ ID NO: 248) NO: 255)
    QVQLQESGGGSVQSGGSLRLSCAASGFTYSTS QVQLQESGGGSVQAGGSLTLSCAASEYAYSTC
    NSWMAWFRQAPGKEREGVAAIYTVGGSIFYA NMGWYRQAPGKERELVSAFISDGSTYYADSV
    DSVRGRFTISQDATKNMFYLQMNTLKPEDTA KGRFTITRDNAKNTVYLQMNSLKPEDTAIYYC
    MYYCAAASGRLRGKWFWPYEYNYWGQGTQ SANCYRRLRNYWGQGTQVTVS(SEQ ID
    VTVSS (SEQ ID NO: 248) NO: 256)
    QVQLQESGGGSVQSGGSLRLSCAASGFTYSTS QVQLQESGGGLVQPGGSLRLSCTASGLTFDDS
    NSWMAWFRQAPGKEREGVAAIYTVGGSIFYA VMGWFRQAPGKGREAVSCISSSGANAFYADS
    DSVRGRFTISQDATKNMFYLQMNTLKPEDTA VKGRFTISRDNAKNTLYLQMNSLKPEDTATYY
    MYYCAAASGRLRGKWFWPYEYNYWGQGTQ CKRGHACAGYYPIPYDDYWGQGTQVTVS
    VTVSS (SEQ ID NO: 248) (SEQ ID NO: 257)
    QVQLQESGGGSVQAGGSLRLSCVASGYVSCD QVQLQESGGGSVQAGGSLRLSCTASGAIASGY
    YFLPSWYRQAPGKEREFVSIIDGTGSTSYAASV IDSRWCMAWFRQAPGKEREGVAAIWPGGGLT
    KGRFTASQDKGKNIAYLQMNTLKPEDTAMYY VYADSVKGRFTISRDHAKNTLYLQMNNLKPE
    CKASCVRGRAISEYWGQGTQVTVSS (SEQ ID DTAMYYCAAGSPRMCPSLEFGFDYWGQGTQV
    NO: 249) TVS (SEQ ID NO: 252)
    QVQLQESGGGSVQAGGSLRLSCVASGYVSCD QVQLQESGGGSVQAGGSLRLSCTAPGFTSNSC
    YFLPSWYRQAPGKEREFVSIIDGTGSTSYAASV GMDWYRQAPGKEREFVSSISTDGTTGYADSV
    KGRFTASQDKGKNIAYLQMNTLKPEDTAMYY KGRFTISKDKAKDTVYLQMNSLKPEDTGMYS
    CKASCVRGRAISEYWGQGTQVTVSS (SEQ ID CKTKDGTIATMELCDFGYWGQGTQVTVS
    NO: 249) (SEQ ID NO: 253)
    QVQLQESGGGSVQAGGSLRLSCVASGYVSCD QVQLQESGGGSVQAGGSLRLSCAASGYPYSN
    YFLPSWYRQAPGKEREFVSIIDGTGSTSYAASV GYMGWFRQAPGKEREGVATIYTGDGRTYYAD
    KGRFTASQDKGKNIAYLQMNTLKPEDTAMYY SVKGRFTISRDNAKNTVDLQMSSLKPEDTAMY
    CKASCVRGRAISEYWGQGTQVTVSS (SEQ ID YCAARAAPLYSSGSPLTRARYNVWGQGTQVT
    NO: 249) VS (SEQ ID NO: 254)
    QVQLQESGGGSVQAGGSLRLSCVASGYVSCD QVQLQESGGGSVQAGGSLRLSCVASASTYCTY
    YFLPSWYRQAPGKEREFVSIIDGTGSTSYAASV DMHWYRQAPGKGREFVSAIDSDGTTRYADSV
    KGRFTASQDKGKNIAYLQMNTLKPEDTAMYY KGRFTISQGTAKNTVYLQMNSLOPEDTAMYY
    CKASCVRGRAISEYWGQGTQVTVSS (SEQ ID CKTVCVVGSRWSDYWGQGTQVTVS (SEQ ID
    NO: 249) NO: 255)
    QVQLQESGGGSVQAGGSLRLSCVASGYVSCD QVQLQESGGGSVQAGGSLTLSCAASEYAYSTC
    YFLPSWYRQAPGKEREFVSIIDGTGSTSYAASV NMGWYRQAPGKERELVSAFISDGSTYYADSV
    KGRFTASQDKGKNIAYLQMNTLKPEDTAMYY KGRFTITRDNAKNTVYLQMNSLKPEDTAIYYC
    CKASCVRGRAISEYWGQGTQVTVSS (SEQ ID SANCYRRLRNYWGQGTQVTVS(SEQ ID
    NO: 249) NO: 256)
    QVQLQESGGGSVQAGGSLRLSCVASGYVSCD QVQLQESGGGLVQPGGSLRLSCTASGLTFDDS
    YFLPSWYRQAPGKEREFVSIIDGTGSTSYAASV VMGWFRQAPGKGREAVSCISSSGANAFYADS
    KGRFTASQDKGKNIAYLQMNTLKPEDTAMYY VKGRFTISRDNAKNTLYLQMNSLKPEDTATYY
    CKASCVRGRAISEYWGQGTQVTVSS (SEQ ID CKRGHACAGYYPIPYDDYWGQGTQVTVS
    NO: 249) (SEQ ID NO: 257)
    QVQLQESGGGSVQAGGSLRLSCRASGSTYSNY QVQLQESGGGSVQAGGSLRLSCTASGAIASGY
    CLGWFRQITGKEREGVAVINWVGGMLYFADS IDSRWCMAWFRQAPGKEREGVAAIWPGGGLT
    VKGRFTVSQDQAKNTVYLQMNSLKPEDTAMY VYADSVKGRFTISRDHAKNTLYLQMNNLKPE
    YCAAESVSSFSCGGWLTRPDRVPYWGQGTQV DTAMYYCAAGSPRMCPSLEFGFDYWGQGTQV
    TVSS (SEQ ID NO: 250) TVS (SEQ ID NO: 252)
    QVQLQESGGGSVQAGGSLRLSCRASGSTYSNY QVQLQESGGGSVQAGGSLRLSCTAPGFTSNSC
    CLGWFRQITGKEREGVAVINWVGGMLYFADS GMDWYRQAPGKEREFVSSISTDGTTGYADSV
    VKGRFTVSQDQAKNTVYLQMNSLKPEDTAMY KGRFTISKDKAKDTVYLQMNSLKPEDTGMYS
    YCAAESVSSFSCGGWLTRPDRVPYWGQGTQV CKTKDGTIATMELCDFGYWGQGTQVTVS
    TVSS (SEQ ID NO: 250) (SEQ ID NO: 253)
    QVQLQESGGGSVQAGGSLRLSCRASGSTYSNY QVQLQESGGGSVQAGGSLRLSCAASGYPYSN
    CLGWFRQITGKEREGVAVINWVGGMLYFADS GYMGWFRQAPGKEREGVATIYTGDGRTYYAD
    VKGRFTVSQDQAKNTVYLQMNSLKPEDTAMY SVKGRFTISRDNAKNTVDLQMSSLKPEDTAMY
    YCAAESVSSFSCGGWLTRPDRVPYWGQGTQV YCAARAAPLYSSGSPLTRARYNVWGQGTQVT
    TVSS (SEQ ID NO: 250) VS (SEQ ID NO: 254)
    QVQLQESGGGSVQAGGSLRLSCRASGSTYSNY QVQLQESGGGSVQAGGSLRLSCVASASTYCTY
    CLGWFRQITGKEREGVAVINWVGGMLYFADS DMHWYRQAPGKGREFVSAIDSDGTTRYADSV
    VKGRFTVSQDQAKNTVYLQMNSLKPEDTAMY KGRFTISQGTAKNTVYLQMNSLOPEDTAMYY
    YCAAESVSSFSCGGWLTRPDRVPYWGQGTQV CKTVCVVGSRWSDYWGQGTQVTVS (SEQ ID
    TVSS (SEQ ID NO: 250) NO: 255)
    QVQLQESGGGSVQAGGSLRLSCRASGSTYSNY QVQLQESGGGSVQAGGSLTLSCAASEYAYSTC
    CLGWFRQITGKEREGVAVINWVGGMLYFADS NMGWYRQAPGKERELVSAFISDGSTYYADSV
    VKGRFTVSQDQAKNTVYLQMNSLKPEDTAMY KGRFTITRDNAKNTVYLQMNSLKPEDTAIYYC
    YCAAESVSSFSCGGWLTRPDRVPYWGQGTQV SANCYRRLRNYWGQGTQVTVS(SEQ ID
    TVSS (SEQ ID NO: 250) NO: 256)
    QVQLQESGGGSVQAGGSLRLSCRASGSTYSNY QVQLQESGGGLVQPGGSLRLSCTASGLTFDDS
    CLGWFRQITGKEREGVAVINWVGGMLYFADS VMGWFRQAPGKGREAVSCISSSGANAFYADS
    VKGRFTVSQDQAKNTVYLQMNSLKPEDTAMY VKGRFTISRDNAKNTLYLQMNSLKPEDTATYY
    YCAAESVSSFSCGGWLTRPDRVPYWGQGTQV CKRGHACAGYYPIPYDDYWGQGTQVTVS
    TVSS (SEQ ID NO: 250) (SEQ ID NO: 257)
    QVQLQESGGGLVQPGGSLRLSCAASGFTFSLSS QVQLQESGGGSVQAGGSLRLSCTASGAIASGY
    MSWVRQAPGKGLEWVSAISSGGASTYYTDSV IDSRWCMAWFRQAPGKEREGVAAIWPGGGLT
    KGRFTISRDNAKNMLYLQLNSLKTEDTAMYY VYADSVKGRFTISRDHAKNTLYLQMNNLKPE
    CAKGGSGYGDASRMTSPGSQGTQVTVSS (SEQ DTAMYYCAAGSPRMCPSLEFGFDYWGQGTQV
    ID NO: 251) TVS (SEQ ID NO: 252)
    QVQLQESGGGLVQPGGSLRLSCAASGFTFSLSS QVQLQESGGGSVQAGGSLRLSCTAPGFTSNSC
    MSWVRQAPGKGLEWVSAISSGGASTYYTDSV GMDWYRQAPGKEREFVSSISTDGTTGYADSV
    KGRFTISRDNAKNMLYLQLNSLKTEDTAMYY KGRFTISKDKAKDTVYLQMNSLKPEDTGMYS
    CAKGGSGYGDASRMTSPGSQGTQVTVSS (SEQ CKTKDGTIATMELCDFGYWGQGTQVTVS
    ID NO: 251) (SEQ ID NO: 253)
    QVQLQESGGGLVQPGGSLRLSCAASGFTFSLSS QVQLQESGGGSVQAGGSLRLSCAASGYPYSN
    MSWVRQAPGKGLEWVSAISSGGASTYYTDSV GYMGWFRQAPGKEREGVATIYTGDGRTYYAD
    KGRFTISRDNAKNMLYLQLNSLKTEDTAMYY SVKGRFTISRDNAKNTVDLQMSSLKPEDTAMY
    CAKGGSGYGDASRMTSPGSQGTQVTVSS (SEQ YCAARAAPLYSSGSPLTRARYNVWGQGTQVT
    ID NO: 251) VS (SEQ ID NO: 254)
    QVQLQESGGGLVQPGGSLRLSCAASGFTFSLSS QVQLQESGGGSVQAGGSLRLSCVASASTYCTY
    MSWVRQAPGKGLEWVSAISSGGASTYYTDSV DMHWYRQAPGKGREFVSAIDSDGTTRYADSV
    KGRFTISRDNAKNMLYLQLNSLKTEDTAMYY KGRFTISQGTAKNTVYLQMNSLOPEDTAMYY
    CAKGGSGYGDASRMTSPGSQGTQVTVSS (SEQ CKTVCVVGSRWSDYWGQGTQVTVS (SEQ ID
    ID NO: 251) NO: 255)
    QVQLQESGGGLVQPGGSLRLSCAASGFTFSLSS QVQLQESGGGSVQAGGSLTLSCAASEYAYSTC
    MSWVRQAPGKGLEWVSAISSGGASTYYTDSV NMGWYRQAPGKERELVSAFISDGSTYYADSV
    KGRFTISRDNAKNMLYLQLNSLKTEDTAMYY KGRFTITRDNAKNTVYLQMNSLKPEDTAIYYC
    CAKGGSGYGDASRMTSPGSQGTQVTVSS (SEQ SANCYRRLRNYWGQGTQVTVS(SEQ ID
    ID NO: 251) NO: 256)
    QVQLQESGGGLVQPGGSLRLSCAASGFTFSLSS QVQLQESGGGLVQPGGSLRLSCTASGLTFDDS
    MSWVRQAPGKGLEWVSAISSGGASTYYTDSV VMGWFRQAPGKGREAVSCISSSGANAFYADS
    KGRFTISRDNAKNMLYLQLNSLKTEDTAMYY VKGRFTISRDNAKNTLYLQMNSLKPEDTATYY
    CAKGGSGYGDASRMTSPGSQGTQVTVSS (SEQ CKRGHACAGYYPIPYDDYWGQGTQVTVS
    ID NO: 251) (SEQ ID NO: 257)
  • In certain embodiments, the bispecific VHH2 Comprises a sequence that is substantially identical to a sequence of any one of SEQ ID NOS:43-84. Such a bispecific VHH2 can have a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity to the sequence of any one of SEQ ID NOS:43-84, as shown in Table 3B below. In each of sequences of SEQ ID NOS:43-84, the linker GGGS (SEQ ID NO: 108) is in bold. The sequence of the anti-IL27Rα VHH is N-terminus to the linker and the sequence of the anti-gp130 VHH is C-terminus to the linker. The CDR sequences in each VHH are underlined.
  • TABLE 3B
    SEQ
    ID
    NO Sequence
    43 QVQLQESGGGLVQPGGSLRLSCAASGFTFSSYPMSWVRQAPGKGLEWISTISAGGDTTLYA
    DSVKGRFTSSRDNAKNTLYLQLNSLKTEDAAIYYCAKRIDCNSGYCYRRNYWGQGTQVTV
    SSGGGSQVQLQESGGGSVQAGGSLRLSCTASGAIASGYIDSRWCMAWFRQAPGKEREGVA
    AIWPGGGLTVYADSVKGRFTISRDHAKNTLYLQMNNLKPEDTAMYYCAAGSPRMCPSLEF
    GFDYWGQGTQVTVS
    44 QVQLQESGGGLVQPGGSLRLSCAASGFTFSSYPMSWVRQAPGKGLEWISTISAGGDTTLYA
    DSVKGRFTSSRDNAKNTLYLQLNSLKTEDAAIYYCAKRIDCNSGYCYRRNYWGQGTQVTV
    SSGGGSQVQLQESGGGSVQAGGSLRLSCTAPGFTSNSCGMDWYRQAPGKEREFVSSISTDG
    TTGYADSVKGRFTISKDKAKDTVYLQMNSLKPEDTGMYSCKTKDGTIATMELCDFGYWG
    QGTQVTVS
    45 QVQLQESGGGLVQPGGSLRLSCAASGFTFSSYPMSWVRQAPGKGLEWISTISAGGDTTLYA
    DSVKGRFTSSRDNAKNTLYLQLNSLKTEDAAIYYCAKRIDCNSGYCYRRNYWGQGTQVTV
    SSGGGSQVQLQESGGGSVQAGGSLRLSCAASGYPYSNGYMGWFRQAPGKEREGVATIYT
    GDGRTYYADSVKGRFTISRDNAKNTVDLQMSSLKPEDTAMYYCAARAAPLYSSGSPLTRA
    RYNVWGQGTQVTVS
    46 QVQLQESGGGLVQPGGSLRLSCAASGFTFSSYPMSWVRQAPGKGLEWISTISAGGDTTLYA
    DSVKGRFTSSRDNAKNTLYLQLNSLKTEDAAIYYCAKRIDCNSGYCYRRNYWGQGTQVTV
    SSGGGSQVQLQESGGGSVQAGGSLRLSCVASASTYCTYDMHWYRQAPGKGREFVSAIDSD
    GTTRYADSVKGRFTISQGTAKNTVYLQMNSLQPEDTAMYYCKTVCVVGSRWSDYWGQGT
    QVTVS
    47 QVQLQESGGGLVQPGGSLRLSCAASGFTFSSYPMSWVRQAPGKGLEWISTISAGGDTTLYA
    DSVKGRFTSSRDNAKNTLYLQLNSLKTEDAAIYYCAKRIDCNSGYCYRRNYWGQGTQVTV
    SSGGGSQVQLQESGGGSVQAGGSLTLSCAASEYAYSTCNMGWYRQAPGKERELVSAFISD
    GSTYYADSVKGRFTITRDNAKNTVYLQMNSLKPEDTAIYYCSANCYRRLRNYWGQGTQVT
    VS
    48 QVQLQESGGGLVQPGGSLRLSCAASGFTFSSYPMSWVRQAPGKGLEWISTISAGGDTTLYA
    DSVKGRFTSSRDNAKNTLYLQLNSLKTEDAAIYYCAKRIDCNSGYCYRRNYWGQGTQVTV
    SSGGGSQVQLQESGGGLVQPGGSLRLSCTASGLTFDDSVMGWFRQAPGKGREAVSCISSSG
    ANAFYADSVKGRFTISRDNAKNTLYLQMNSLKPEDTATYYCKRGHACAGYYPIPYDDYW
    GQGTQVTVS
    49 QVQLQESGGGLVQPGESLRLSCTASGFTFSNYAMSWVRQAPGKGLEWVSGINVAYGITSY
    ADSVKGRFTISRDNTKNTLYLQLNSLKTEDTAIYYCVKHSGTTIPRGFISYTKRGQGTQVTV
    SSGGGSQVQLQESGGGSVQAGGSLRLSCTASGAIASGYIDSRWCMAWFRQAPGKEREGVA
    AIWPGGGLTVYADSVKGRFTISRDHAKNTLYLQMNNLKPEDTAMYYCAAGSPRMCPSLEF
    GFDYWGQGTQVTVS
    50 QVQLQESGGGLVQPGESLRLSCTASGFTFSNYAMSWVRQAPGKGLEWVSGINVAYGITSY
    ADSVKGRFTISRDNTKNTLYLQLNSLKTEDTAIYYCVKHSGTTIPRGFISYTKRGQGTQVTV
    SSGGGSQVQLQESGGGSVQAGGSLRLSCTAPGFTSNSCGMDWYRQAPGKEREFVSSISTDG
    TTGYADSVKGRFTISKDKAKDTVYLQMNSLKPEDTGMYSCKTKDGTIATMELCDFGYWG
    QGTQVTVS
    51 QVQLQESGGGLVQPGESLRLSCTASGFTFSNYAMSWVRQAPGKGLEWVSGINVAYGITSY
    ADSVKGRFTISRDNTKNTLYLQLNSLKTEDTAIYYCVKHSGTTIPRGFISYTKRGQGTQVTV
    SSGGGSQVQLQESGGGSVQAGGSLRLSCAASGYPYSNGYMGWFRQAPGKEREGVATIYT
    GDGRTYYADSVKGRFTISRDNAKNTVDLQMSSLKPEDTAMYYCAARAAPLYSSGSPLTRA
    RYNVWGQGTQVTVS
    52 QVQLQESGGGLVQPGESLRLSCTASGFTFSNYAMSWVRQAPGKGLEWVSGINVAYGITSYA
    DSVKGRFTISRDNTKNTLYLQLNSLKTEDTAIYYCVKHSGTTIPRGFISYTKRGQGTQVTV
    SSGGGSQVQLQESGGGSVQAGGSLRLSCVASASTYCTYDMHWYRQAPGKGREFVSAIDSD
    GTTRYADSVKGRFTISQGTAKNTVYLQMNSLQPEDTAMYYCKTVCVVGSRWSDYWGQGT
    QVTVS
    53 QVQLQESGGGLVQPGESLRLSCTASGFTFSNYAMSWVRQAPGKGLEWVSGINVAYGITSY
    ADSVKGRFTISRDNTKNTLYLQLNSLKTEDTAIYYCVKHSGTTIPRGFISYTKRGQGTQVTV
    SSGGGSQVQLQESGGGSVQAGGSLTLSCAASEYAYSTCNMGWYRQAPGKERELVSAFISD
    GSTYYADSVKGRFTITRDNAKNTVYLQMNSLKPEDTAIYYCSANCYRRLRNYWGQGTQVT
    VS
    54 QVQLQESGGGLVQPGESLRLSCTASGFTFSNYAMSWVRQAPGKGLEWVSGINVAYGITSY
    ADSVKGRFTISRDNTKNTLYLQLNSLKTEDTAIYYCVKHSGTTIPRGFISYTKRGQGTQVTV
    SSGGGSQVQLQESGGGLVQPGGSLRLSCTASGLTFDDSVMGWFRQAPGKGREAVSCISSSG
    ANAFYADSVKGRFTISRDNAKNTLYLQMNSLKPEDTATYYCKRGHACAGYYPIPYDDYW
    GQGTQVTVS
    55 QVQLQESGGGLVQPGGSLRLSCAASGFSFSSYAMKWVRQAPGKGLEWVSTISSGGSSTNY
    ADSVKGRFTISRDNAKNTLYLQLNSLKIEDTAMYYCAKAIVPTGATMERGQGTQVTVSSG
    GGSQVQLQESGGGSVQAGGSLRLSCTASGAIASGYIDSRWCMAWFRQAPGKEREGVAAIW
    PGGGLTVYADSVKGRFTISRDHAKNTLYLQMNNLKPEDTAMYYCAAGSPRMCPSLEFGFD
    YWGQGTQVTVS
    56 QVQLQESGGGLVQPGGSLRLSCAASGFSFSSYAMKWVRQAPGKGLEWVSTISSGGSSTNY
    ADSVKGRFTISRDNAKNTLYLQLNSLKIEDTAMYYCAKAIVPTGATMERGQGTQVTVSSG
    GGSQVQLQESGGGSVQAGGSLRLSCTAPGFTSNSCGMDWYRQAPGKEREFVSSISTDGTTG
    YADSVKGRFTISKDKAKDTVYLQMNSLKPEDTGMYSCKTKDGTIATMELCDFGYWGQGT
    QVTVS
    57 QVQLQESGGGLVQPGGSLRLSCAASGFSFSSYAMKWVRQAPGKGLEWVSTISSGGSSTNY
    ADSVKGRFTISRDNAKNTLYLQLNSLKIEDTAMYYCAKAIVPTGATMERGQGTQVTVSSG
    GGSQVQLQESGGGSVQAGGSLRLSCAASGYPYSNGYMGWFRQAPGKEREGVATIYTGDG
    RTYYADSVKGRFTISRDNAKNTVDLQMSSLKPEDTAMYYCAARAAPLYSSGSPLTRARYN
    VWGQGTQVTVS
    58 QVQLQESGGGLVQPGGSLRLSCAASGFSFSSYAMKWVRQAPGKGLEWVSTISSGGSSTNY
    ADSVKGRFTISRDNAKNTLYLQLNSLKIEDTAMYYCAKAIVPTGATMERGQGTQVTVSSG
    GGSQVQLQESGGGSVQAGGSLRLSCVASASTYCTYDMHWYRQAPGKGREFVSAIDSDGTT
    RYADSVKGRFTISQGTAKNTVYLQMNSLQPEDTAMYYCKTVCVVGSRWSDYWGQGTQV
    TVS
    59 QVQLQESGGGLVQPGGSLRLSCAASGFSFSSYAMKWVRQAPGKGLEWVSTISSGGSSTNY
    ADSVKGRFTISRDNAKNTLYLQLNSLKIEDTAMYYCAKAIVPTGATMERGQGTQVTVSSG
    GGSQVQLQESGGGSVQAGGSLTLSCAASEYAYSTCNMGWYRQAPGKERELVSAFISDGST
    YYADSVKGRFTITRDNAKNTVYLQMNSLKPEDTAIYYCSANCYRRLRNYWGQGTQVTVS
    60 QVQLQESGGGLVQPGGSLRLSCAASGFSFSSYAMKWVRQAPGKGLEWVSTISSGGSSTNY
    ADSVKGRFTISRDNAKNTLYLQLNSLKIEDTAMYYCAKAIVPTGATMERGQGTQVTVSSG
    GGSQVQLQESGGGLVQPGGSLRLSCTASGLTFDDSVMGWFRQAPGKGREAVSCISSSGAN
    AFYADSVKGRFTISRDNAKNTLYLQMNSLKPEDTATYYCKRGHACAGYYPIPYDDYWGQ
    GTQVTVS
    61 QVQLQESGGGSVQSGGSLRLSCAASGFTYSTSNSWMAWFRQAPGKEREGVAAIYTVGGS
    IFYADSVRGRFTISQDATKNMFYLQMNTLKPEDTAMYYCAAASGRLRGKWFWPYEYNYWG
    QGTQVTVSSGGGSQVQLQESGGGSVQAGGSLRLSCTASGAIASGYIDSRWCMAWFRQAPG
    KEREGVAAIWPGGGLTVYADSVKGRFTISRDHAKNTLYLQMNNLKPEDTAMYYCAAGSP
    RMCPSLEFGFDYWGQGTQVTVS
    62 QVQLQESGGGSVQSGGSLRLSCAASGFTYSTSNSWMAWFRQAPGKEREGVAAIYTVGGSI
    FYADSVRGRFTISQDATKNMFYLQMNTLKPEDTAMYYCAAASGRLRGKWFWPYEYNYWG
    QGTQVTVSSGGGSQVQLQESGGGSVQAGGSLRLSCTAPGFTSNSCGMDWYRQAPGKEREF
    VSSISTDGTTGYADSVKGRFTISKDKAKDTVYLQMNSLKPEDTGMYSCKTKDGTIATMEL
    CDFGYWGQGTQVTVS
    63 QVQLQESGGGSVQSGGSLRLSCAASGFTYSTSNSWMAWFRQAPGKEREGVAAIYTVGGSI
    FYADSVRGRFTISQDATKNMFYLQMNTLKPEDTAMYYCAAASGRLRGKWFWPYEYNYWG
    QGTQVTVSSGGGSQVQLQESGGGSVQAGGSLRLSCAASGYPYSNGYMGWFRQAPGKERE
    GVATIYTGDGRTYYADSVKGRFTISRDNAKNTVDLQMSSLKPEDTAMYYCAARAAPLYSS
    GSPLTRARYNVWGQGTQVTVS
    64 QVQLQESGGGSVQSGGSLRLSCAASGFTYSTSNSWMAWFRQAPGKEREGVAAIYTVGGSI
    FYADSVRGRFTISQDATKNMFYLQMNTLKPEDTAMYYCAAASGRLRGKWFWPYEYNYWG
    QGTQVTVSSGGGSQVQLQESGGGSVQAGGSLRLSCVASASTYCTYDMHWYRQAPGKGRE
    FVSAIDSDGTTRYADSVKGRFTISQGTAKNTVYLQMNSLQPEDTAMYYCKTVCVVGSRWS
    DYWGQGTQVTVS
    65 QVQLQESGGGSVQSGGSLRLSCAASGFTYSTSNSWMAWFRQAPGKEREGVAAIYTVGGSI
    FYADSVRGRFTISQDATKNMFYLQMNTLKPEDTAMYYCAAASGRLRGKWFWPYEYNYWG
    QGTQVTVSSGGGSQVQLQESGGGSVQAGGSLTLSCAASEYAYSTCNMGWYRQAPGKERE
    LVSAFISDGSTYYADSVKGRFTITRDNAKNTVYLQMNSLKPEDTAIYYCSANCYRRLRN
    YWGQGTQVTVS
    66 QVQLQESGGGSVQSGGSLRLSCAASGFTYSTSNSWMAWFRQAPGKEREGVAAIYTVGGSI
    FYADSVRGRFTISQDATKNMFYLQMNTLKPEDTAMYYCAAASGRLRGKWFWPYEYNYWG
    QGTQVTVSSGGGSQVQLQESGGGLVQPGGSLRLSCTASGLTFDDSVMGWFRQAPGKGRE
    AVSCISSSGANAFYADSVKGRFTISRDNAKNTLYLQMNSLKPEDTATYYCKRGHACAGY
    YPIPYDDYWGQGTQVTVS
    67 QVQLQESGGGSVQAGGSLRLSCVASGYVSCDYFLPSWYRQAPGKEREFVSIIDGTGSTSY
    AASVKGRFTASQDKGKNIAYLQMNTLKPEDTAMYYCKASCVRGRAISEYWGQGTQVTVSS
    GGGSQVQLQESGGGSVQAGGSLRLSCTASGAIASGYIDSRWCMAWFRQAPGKEREGVAAI
    WPGGGLTVYADSVKGRFTISRDHAKNTLYLQMNNLKPEDTAMYYCAAGSPRMCPSLEFGF
    DYWGQGTQVTVS
    68 QVQLQESGGGSVQAGGSLRLSCVASGYVSCDYFLPSWYRQAPGKEREFVSIIDGTGSTSY
    AASVKGRFTASQDKGKNIAYLQMNTLKPEDTAMYYCKASCVRGRAISEYWGQGTQVTVSS
    GGGSQVQLQESGGGSVQAGGSLRLSCTAPGFTSNSCGMDWYRQAPGKEREFVSSISTDGT
    TGYADSVKGRFTISKDKAKDTVYLQMNSLKPEDTGMYSCKTKDGTIATMELCDFGYWGQ
    GTQVTVS
    69 QVQLQESGGGSVQAGGSLRLSCVASGYVSCDYFLPSWYRQAPGKEREFVSIIDGTGSTSY
    AASVKGRFTASQDKGKNIAYLQMNTLKPEDTAMYYCKASCVRGRAISEYWGQGTQVTVSS
    GGGSQVQLQESGGGSVQAGGSLRLSCAASGYPYSNGYMGWFRQAPGKEREGVATIYTGD
    GRTYYADSVKGRFTISRDNAKNTVDLQMSSLKPEDTAMYYCAARAAPLYSSGSPLTRARY
    NVWGQGTQVTVS
    70 QVQLQESGGGSVQAGGSLRLSCVASGYVSCDYFLPSWYRQAPGKEREFVSIIDGTGSTSY
    AASVKGRFTASQDKGKNIAYLQMNTLKPEDTAMYYCKASCVRGRAISEYWGQGTQVTVSS
    GGGSQVQLQESGGGSVQAGGSLRLSCVASASTYCTYDMHWYRQAPGKGREFVSAIDSDG
    TTRYADSVKGRFTISQGTAKNTVYLQMNSLQPEDTAMYYCKTVCVVGSRWSDYWGQGTQ
    VTVS
    71 QVQLQESGGGSVQAGGSLRLSCVASGYVSCDYFLPSWYRQAPGKEREFVSIIDGTGSTSY
    AASVKGRFTASQDKGKNIAYLQMNTLKPEDTAMYYCKASCVRGRAISEYWGQGTQVTVSS
    GGGSQVQLQESGGGSVQAGGSLTLSCAASEYAYSTCNMGWYRQAPGKERELVSAFISDGS
    TYYADSVKGRFTITRDNAKNTVYLQMNSLKPEDTAIYYCSANCYRRLRNYWGQGTQVTVS
    72 QVQLQESGGGSVQAGGSLRLSCVASGYVSCDYFLPSWYRQAPGKEREFVSIIDGTGSTSY
    AASVKGRFTASQDKGKNIAYLQMNTLKPEDTAMYYCKASCVRGRAISEYWGQGTQVTVSS
    GGGSQVQLQESGGGLVQPGGSLRLSCTASGLTFDDSVMGWFRQAPGKGREAVSCISSSGA
    NAFYADSVKGRFTISRDNAKNTLYLQMNSLKPEDTATYYCKRGHACAGYYPIPYDDYWG
    QGTQVTVS
    73 QVQLQESGGGSVQAGGSLRLSCRASGSTYSNYCLGWFRQITGKEREGVAVINWVGGMLYF
    ADSVKGRFTVSQDQAKNTVYLQMNSLKPEDTAMYYCAAESVSSFSCGGWLTRPDRVPYW
    GQGTQVTVSSGGGSQVQLQESGGGSVQAGGSLRLSCTASGAIASGYIDSRWCMAWFRQAP
    GKEREGVAAIWPGGGLTVYADSVKGRFTISRDHAKNTLYLQMNNLKPEDTAMYYCAAGS
    PRMCPSLEFGFDYWGQGTQVTVS
    74 QVQLQESGGGSVQAGGSLRLSCRASGSTYSNYCLGWFRQITGKEREGVAVINWVGGMLYF
    ADSVKGRFTVSQDQAKNTVYLQMNSLKPEDTAMYYCAAESVSSFSCGGWLTRPDRVPYW
    GQGTQVTVSSGGGSQVQLQESGGGSVQAGGSLRLSCTAPGFTSNSCGMDWYRQAPGKER
    EFVSSISTDGTTGYADSVKGRFTISKDKAKDTVYLQMNSLKPEDTGMYSCKTKDGTIAT
    MELCDFGYWGQGTQVTVS
    75 QVQLQESGGGSVQAGGSLRLSCRASGSTYSNYCLGWFRQITGKEREGVAVINWVGGMLYF
    ADSVKGRFTVSQDQAKNTVYLQMNSLKPEDTAMYYCAAESVSSFSCGGWLTRPDRVPYW
    GQGTQVTVSSGGGSQVQLQESGGGSVQAGGSLRLSCAASGYPYSNGYMGWFRQAPGKER
    EGVATIYTGDGRTYYADSVKGRFTISRDNAKNTVDLQMSSLKPEDTAMYYCAARAAPLYS
    SGSPLTRARYNVWGQGTQVTVS
    76 QVQLQESGGGSVQAGGSLRLSCRASGSTYSNYCLGWFRQITGKEREGVAVINWVGGMLYF
    ADSVKGRFTVSQDQAKNTVYLQMNSLKPEDTAMYYCAAESVSSFSCGGWLTRPDRVPYW
    GQGTQVTVSSGGGSQVQLQESGGGSVQAGGSLRLSCVASASTYCTYDMHWYRQAPGKGR
    EFVSAIDSDGTTRYADSVKGRFTISQGTAKNTVYLQMNSLQPEDTAMYYCKTVCVVGSRW
    SDYWGQGTQVTVS
    77 QVQLQESGGGSVQAGGSLRLSCRASGSTYSNYCLGWFRQITGKEREGVAVINWVGGMLYF
    ADSVKGRFTVSQDQAKNTVYLQMNSLKPEDTAMYYCAAESVSSFSCGGWLTRPDRVPYW
    GQGTQVTVSSGGGSQVQLQESGGGSVQAGGSLTLSCAASEYAYSTCNMGWYRQAPGKER
    ELVSAFISDGSTYYADSVKGRFTITRDNAKNTVYLQMNSLKPEDTAIYYCSANCYRRLR
    NYWGQGTQVTVS
    78 QVQLQESGGGSVQAGGSLRLSCRASGSTYSNYCLGWFRQITGKEREGVAVINWVGGMLYF
    ADSVKGRFTVSQDQAKNTVYLQMNSLKPEDTAMYYCAAESVSSFSCGGWLTRPDRVPYW
    GQGTQVTVSSGGGSQVQLQESGGGLVQPGGSLRLSCTASGLTFDDSVMGWFRQAPGKGR
    EAVSCISSSGANAFYADSVKGRFTISRDNAKNTLYLQMNSLKPEDTATYYCKRGHACAG
    YYPIPYDDYWGQGTQVTVS
    79 QVQLQESGGGLVQPGGSLRLSCAASGFTFSLSSMSWVRQAPGKGLEWVSAISSGGASTYY
    TDSVKGRFTISRDNAKNMLYLQLNSLKTEDTAMYYCAKGGSGYGDASRMTSPGSQGTQVT
    VSSGGGSQVQLQESGGGSVQAGGSLRLSCTASGAIASGYIDSRWCMAWFRQAPGKEREGV
    AAIWPGGGLTVYADSVKGRFTISRDHAKNTLYLQMNNLKPEDTAMYYCAAGSPRMCPSLE
    FGFDYWGQGTQVTVS
    80 QVQLQESGGGLVQPGGSLRLSCAASGFTFSLSSMSWVRQAPGKGLEWVSAISSGGASTYY
    TDSVKGRFTISRDNAKNMLYLQLNSLKTEDTAMYYCAKGGSGYGDASRMTSPGSQGTQVT
    VSSGGGSQVQLQESGGGSVQAGGSLRLSCTAPGFTSNSCGMDWYRQAPGKEREFVSSIST
    DGTTGYADSVKGRFTISKDKAKDTVYLQMNSLKPEDTGMYSCKTKDGTIATMELCDFGYW
    GQGTQVTVS
    81 QVQLQESGGGLVQPGGSLRLSCAASGFTFSLSSMSWVRQAPGKGLEWVSAISSGGASTYY
    TDSVKGRFTISRDNAKNMLYLQLNSLKTEDTAMYYCAKGGSGYGDASRMTSPGSQGTQVT
    VSSGGGSQVQLQESGGGSVQAGGSLRLSCAASGYPYSNGYMGWFRQAPGKEREGVATIY
    TGDGRTYYADSVKGRFTISRDNAKNTVDLQMSSLKPEDTAMYYCAARAAPLYSSGSPLTR
    ARYNVWGQGTQVTVS
    82 QVQLQESGGGLVQPGGSLRLSCAASGFTFSLSSMSWVRQAPGKGLEWVSAISSGGASTYY
    TDSVKGRFTISRDNAKNMLYLQLNSLKTEDTAMYYCAKGGSGYGDASRMTSPGSQGTQVT
    VSSGGGSQVQLQESGGGSVQAGGSLRLSCVASASTYCTYDMHWYRQAPGKGREFVSAIDS
    DGTTRYADSVKGRFTISQGTAKNTVYLQMNSLQPEDTAMYYCKTVCVVGSRWSDYWGQ
    GTQVTVS
    83 QVQLQESGGGLVQPGGSLRLSCAASGFTFSLSSMSWVRQAPGKGLEWVSAISSGGASTYY
    DTSVKGRFTISRDNAKNMLYLQLNSLKTEDTAMYYCAKGGSGYGDASRMTSPGSQGTQVT
    VSSGGGSQVQLQESGGGSVQAGGSLTLSCAASEYAYSTCNMGWYRQAPGKERELVSAFIS
    DGSTYYADSVKGRFTITRDNAKNTVYLQMNSLKPEDTAIYYCSANCYRRLRNYWGQGTQ
    VTVS
    84 QVQLQESGGGLVQPGGSLRLSCAASGFTFSLSSMSWVRQAPGKGLEWVSAISSGGASTYY
    TDSVKGRFTISRDNAKNMLYLQLNSLKTEDTAMYYCAKGGSGYGDASRMTSPGSQGTQVT
    VSSGGGSQVQLQESGGGLVQPGGSLRLSCTASGLTFDDSVMGWFRQAPGKGREAVSCISS
    SGANAFYADSVKGRFTISRDNAKNTLYLQMNSLKPEDTATYYCKRGHACAGYYPIPYDDY
    WGQGTQVTVS
  • In some embodiments, an IL27R binding protein described herein (e.g., an IL27R binding protein comprising a sequence of any one of SEQ ID NOS:43-84) is encoded by an isolated nucleic acid that is substantially identical to a sequence of any one of SEQ ID NOS: 151-192, as listed in Table 3C below. In some embodiments, an IL27R binding protein described herein (e.g., an IL27R binding protein comprising a sequence of any one of SEQ ID NOS:43-84) is encoded by an isolated nucleic acid comprising a sequence having at least 90% (e.g., 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%) sequence identity to a sequence of any one of SEQ ID NOS: 151-192, as listed in Table 3C below.
  • TABLE 3C
    SEQ
    ID
    NO Sequence
    151 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGC
    TGAGCTGCGCCGCCAGCGGCTTCACCTTCAGCAGCTACCCCATGAGCTGGGTGAGGCA
    GGCCCCCGGCAAGGGCCTGGAGTGGATCAGCACCATCAGCGCCGGCGGCGACACCACC
    CTGTACGCCGACAGCGTGAAGGGCAGGTTCACCAGCAGCAGGGACAACGCCAAGAAC
    ACCCTGTACCTGCAGCTGAACAGCCTGAAGACCGAGGACGCCGCCATCTACTACTGCG
    CCAAGAGGATCGACTGCAACAGCGGCTACTGCTACAGGAGGAACTACTGGGGCCAGGG
    CACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGC
    GGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGGCTGAGCTGCACCGCCAGCGGCGCCA
    TCGCCAGCGGCTACATCGACAGCAGGTGGTGCATGGCCTGGTTCAGGCAGGCCCCCGG
    CAAGGAGAGGGAGGGCGTGGCCGCCATCTGGCCCGGCGGCGGCCTGACCGTGTACGCC
    GACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACCACGCCAAGAACACCCTGTACC
    TGCAGATGAACAACCTGAAGCCCGAGGACACCGCCATGTACTACTGCGCCGCCGGCAG
    CCCCAGGATGTGCCCCAGCCTGGAGTTCGGCTTCGACTACTGGGGCCAGGGCACCCAG
    GTGACCGTGAGCGCTAGCCACCACCACCACCACCACCACCAC
    152 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGC
    TGAGCTGCGCCGCCAGCGGCTTCACCTTCAGCAGCTACCCCATGAGCTGGGTGAGGCA
    GGCCCCCGGCAAGGGCCTGGAGTGGATCAGCACCATCAGCGCCGGCGGCGACACCACC
    CTGTACGCCGACAGCGTGAAGGGCAGGTTCACCAGCAGCAGGGACAACGCCAAGAAC
    ACCCTGTACCTGCAGCTGAACAGCCTGAAGACCGAGGACGCCGCCATCTACTACTGCG
    CCAAGAGGATCGACTGCAACAGCGGCTACTGCTACAGGAGGAACTACTGGGGCCAGGG
    CACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGC
    GGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGGCTGAGCTGCACCGCCCCCGGCTTCA
    CCAGCAACAGCTGCGGCATGGACTGGTACAGGCAGGCCCCCGGCAAGGAGAGGGAGTT
    CGTGAGCAGCATCAGCACCGACGGCACCACCGGCTACGCCGACAGCGTGAAGGGCAGG
    TTCACCATCAGCAAGGACAAGGCCAAGGACACCGTGTACCTGCAGATGAACAGCCTGA
    AGCCCGAGGACACCGGCATGTACAGCTGCAAGACCAAGGACGGCACCATCGCCACCAT
    GGAGCTGTGCGACTTCGGCTACTGGGGCCAGGGCACCCAGGTGACCGTGAGCGCTAGC
    CACCACCACCACCACCACCACCAC
    153 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGC
    TGAGCTGCGCCGCCAGCGGCTTCACCTTCAGCAGCTACCCCATGAGCTGGGTGAGGCA
    GGCCCCCGGCAAGGGCCTGGAGTGGATCAGCACCATCAGCGCCGGCGGCGACACCACC
    CTGTACGCCGACAGCGTGAAGGGCAGGTTCACCAGCAGCAGGGACAACGCCAAGAAC
    ACCCTGTACCTGCAGCTGAACAGCCTGAAGACCGAGGACGCCGCCATCTACTACTGCG
    CCAAGAGGATCGACTGCAACAGCGGCTACTGCTACAGGAGGAACTACTGGGGCCAGGG
    CACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGC
    GGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGGCTGAGCTGCGCCGCCAGCGGCTACC
    CCTACAGCAACGGCTACATGGGCTGGTTCAGGCAGGCCCCCGGCAAGGAGAGGGAGGG
    CGTGGCCACCATCTACACCGGCGACGGCAGGACCTACTACGCCGACAGCGTGAAGGGC
    AGGTTCACCATCAGCAGGGACAACGCCAAGAACACCGTGGACCTGCAGATGAGCAGCC
    TGAAGCCCGAGGACACCGCCATGTACTACTGCGCCGCCAGGGCCGCCCCCCTGTACAG
    CAGCGGCAGCCCCCTGACCAGGGCCAGGTACAACGTGTGGGGCCAGGGCACCCAGGTG
    ACCGTGAGCGCTAGCCACCACCACCACCACCACCACCAC
    154 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGC
    TGAGCTGCGCCGCCAGCGGCTTCACCTTCAGCAGCTACCCCATGAGCTGGGTGAGGCA
    GGCCCCCGGCAAGGGCCTGGAGTGGATCAGCACCATCAGCGCCGGCGGCGACACCACC
    CTGTACGCCGACAGCGTGAAGGGCAGGTTCACCAGCAGCAGGGACAACGCCAAGAAC
    ACCCTGTACCTGCAGCTGAACAGCCTGAAGACCGAGGACGCCGCCATCTACTACTGCG
    CCAAGAGGATCGACTGCAACAGCGGCTACTGCTACAGGAGGAACTACTGGGGCCAGGG
    CACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGC
    GGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGGCTGAGCTGCGTGGCCAGCGCCAGCA
    CCTACTGCACCTACGACATGCACTGGTACAGGCAGGCCCCCGGCAAGGGCAGGGAGTT
    CGTGAGCGCCATCGACAGCGACGGCACCACCAGGTACGCCGACAGCGTGAAGGGCAG
    GTTCACCATCAGCCAGGGCACCGCCAAGAACACCGTGTACCTGCAGATGAACAGCCTG
    CAGCCCGAGGACACCGCCATGTACTACTGCAAGACCGTGTGCGTGGTGGGCAGCAGGT
    GGAGCGACTACTGGGGCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCACCACCA
    CCACCACCACCAC
    155 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGC
    TGAGCTGCGCCGCCAGCGGCTTCACCTTCAGCAGCTACCCCATGAGCTGGGTGAGGCA
    GGCCCCCGGCAAGGGCCTGGAGTGGATCAGCACCATCAGCGCCGGCGGCGACACCACC
    CTGTACGCCGACAGCGTGAAGGGCAGGTTCACCAGCAGCAGGGACAACGCCAAGAAC
    ACCCTGTACCTGCAGCTGAACAGCCTGAAGACCGAGGACGCCGCCATCTACTACTGCG
    CCAAGAGGATCGACTGCAACAGCGGCTACTGCTACAGGAGGAACTACTGGGGCCAGGG
    CACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGC
    GGCGGCAGCGTGCAGGCCGGCGGCAGCCTGACCCTGAGCTGCGCCGCCAGCGAGTACG
    CCTACAGCACCTGCAACATGGGCTGGTACAGGCAGGCCCCCGGCAAGGAGAGGGAGCT
    GGTGAGCGCCTTCATCAGCGACGGCAGCACCTACTACGCCGACAGCGTGAAGGGCAGG
    TTCACCATCACCAGGGACAACGCCAAGAACACCGTGTACCTGCAGATGAACAGCCTGA
    AGCCCGAGGACACCGCCATCTACTACTGCAGCGCCAACTGCTACAGGAGGCTGAGGAA
    CTACTGGGGCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCACCACCACCACCAC
    CACCAC
    156 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGC
    TGAGCTGCGCCGCCAGCGGCTTCACCTTCAGCAGCTACCCCATGAGCTGGGTGAGGCA
    GGCCCCCGGCAAGGGCCTGGAGTGGATCAGCACCATCAGCGCCGGCGGCGACACCACC
    CTGTACGCCGACAGCGTGAAGGGCAGGTTCACCAGCAGCAGGGACAACGCCAAGAAC
    ACCCTGTACCTGCAGCTGAACAGCCTGAAGACCGAGGACGCCGCCATCTACTACTGCG
    CCAAGAGGATCGACTGCAACAGCGGCTACTGCTACAGGAGGAACTACTGGGGCCAGGG
    CACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGC
    GGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGCTGAGCTGCACCGCCAGCGGCCTGA
    CCTTCGACGACAGCGTGATGGGCTGGTTCAGGCAGGCCCCCGGCAAGGGCAGGGAGGC
    CGTGAGCTGCATCAGCAGCAGCGGCGCCAACGCCTTCTACGCCGACAGCGTGAAGGGC
    AGGTTCACCATCAGCAGGGACAACGCCAAGAACACCCTGTACCTGCAGATGAACAGCC
    TGAAGCCCGAGGACACCGCCACCTACTACTGCAAGAGGGGCCACGCCTGCGCCGGCTA
    CTACCCCATCCCCTACGACGACTACTGGGGCCAGGGCACCCAGGTGACCGTGAGCGCT
    AGCCACCACCACCACCACCACCACCAC
    157 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGAGAGCCTGAGG
    CTGAGCTGCACCGCCAGCGGCTTCACCTTCAGCAACTACGCCATGAGCTGGGTGAGGC
    AGGCCCCCGGCAAGGGCCTGGAGTGGGTGAGCGGCATCAACGTGGCCTACGGCATCAC
    CAGCTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACACCAAGAAC
    ACCCTGTACCTGCAGCTGAACAGCCTGAAGACCGAGGACACCGCCATCTACTACTGCGT
    GAAGCACAGCGGCACCACCATCCCCAGGGGCTTCATCAGCTACACCAAGAGGGGCCAG
    GGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCG
    GCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGGCTGAGCTGCACCGCCAGCGGCGC
    CATCGCCAGCGGCTACATCGACAGCAGGTGGTGCATGGCCTGGTTCAGGCAGGCCCCC
    GGCAAGGAGAGGGAGGGCGTGGCCGCCATCTGGCCCGGCGGCGGCCTGACCGTGTACG
    CCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACCACGCCAAGAACACCCTGTA
    CCTGCAGATGAACAACCTGAAGCCCGAGGACACCGCCATGTACTACTGCGCCGCCGGC
    AGCCCCAGGATGTGCCCCAGCCTGGAGTTCGGCTTCGACTACTGGGGCCAGGGCACCC
    AGGTGACCGTGAGCGCTAGCCACCACCACCACCACCACCACCAC
    158 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGAGAGCCTGAGG
    CTGAGCTGCACCGCCAGCGGCTTCACCTTCAGCAACTACGCCATGAGCTGGGTGAGGC
    AGGCCCCCGGCAAGGGCCTGGAGTGGGTGAGCGGCATCAACGTGGCCTACGGCATCAC
    CAGCTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACACCAAGAAC
    ACCCTGTACCTGCAGCTGAACAGCCTGAAGACCGAGGACACCGCCATCTACTACTGCGT
    GAAGCACAGCGGCACCACCATCCCCAGGGGCTTCATCAGCTACACCAAGAGGGGCCAG
    GGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCG
    GCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGGCTGAGCTGCACCGCCCCCGGCTT
    CACCAGCAACAGCTGCGGCATGGACTGGTACAGGCAGGCCCCCGGCAAGGAGAGGGA
    GTTCGTGAGCAGCATCAGCACCGACGGCACCACCGGCTACGCCGACAGCGTGAAGGGC
    AGGTTCACCATCAGCAAGGACAAGGCCAAGGACACCGTGTACCTGCAGATGAACAGCC
    TGAAGCCCGAGGACACCGGCATGTACAGCTGCAAGACCAAGGACGGCACCATCGCCAC
    CATGGAGCTGTGCGACTTCGGCTACTGGGGCCAGGGCACCCAGGTGACCGTGAGCGCT
    AGCCACCACCACCACCACCACCACCAC
    159 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGAGAGCCTGAGG
    CTGAGCTGCACCGCCAGCGGCTTCACCTTCAGCAACTACGCCATGAGCTGGGTGAGGC
    AGGCCCCCGGCAAGGGCCTGGAGTGGGTGAGCGGCATCAACGTGGCCTACGGCATCAC
    CAGCTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACACCAAGAAC
    ACCCTGTACCTGCAGCTGAACAGCCTGAAGACCGAGGACACCGCCATCTACTACTGCGT
    GAAGCACAGCGGCACCACCATCCCCAGGGGCTTCATCAGCTACACCAAGAGGGGCCAG
    GGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCG
    GCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGGCTGAGCTGCGCCGCCAGCGGCTA
    CCCCTACAGCAACGGCTACATGGGCTGGTTCAGGCAGGCCCCCGGCAAGGAGAGGGAG
    GGCGTGGCCACCATCTACACCGGCGACGGCAGGACCTACTACGCCGACAGCGTGAAGG
    GCAGGTTCACCATCAGCAGGGACAACGCCAAGAACACCGTGGACCTGCAGATGAGCAG
    CCTGAAGCCCGAGGACACCGCCATGTACTACTGCGCCGCCAGGGCCGCCCCCCTGTAC
    AGCAGCGGCAGCCCCCTGACCAGGGCCAGGTACAACGTGTGGGGCCAGGGCACCCAGG
    TGACCGTGAGCGCTAGCCACCACCACCACCACCACCACCAC
    160 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGAGAGCCTGAGG
    CTGAGCTGCACCGCCAGCGGCTTCACCTTCAGCAACTACGCCATGAGCTGGGTGAGGC
    AGGCCCCCGGCAAGGGCCTGGAGTGGGTGAGCGGCATCAACGTGGCCTACGGCATCAC
    CAGCTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACACCAAGAAC
    ACCCTGTACCTGCAGCTGAACAGCCTGAAGACCGAGGACACCGCCATCTACTACTGCGT
    GAAGCACAGCGGCACCACCATCCCCAGGGGCTTCATCAGCTACACCAAGAGGGGCCAG
    GGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCG
    GCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGGCTGAGCTGCGTGGCCAGCGCCAG
    CACCTACTGCACCTACGACATGCACTGGTACAGGCAGGCCCCCGGCAAGGGCAGGGAG
    TTCGTGAGCGCCATCGACAGCGACGGCACCACCAGGTACGCCGACAGCGTGAAGGGCA
    GGTTCACCATCAGCCAGGGCACCGCCAAGAACACCGTGTACCTGCAGATGAACAGCCT
    GCAGCCCGAGGACACCGCCATGTACTACTGCAAGACCGTGTGCGTGGTGGGCAGCAGG
    TGGAGCGACTACTGGGGCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCACCACC
    ACCACCACCACCAC
    161 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGAGAGCCTGAGG
    CTGAGCTGCACCGCCAGCGGCTTCACCTTCAGCAACTACGCCATGAGCTGGGTGAGGC
    AGGCCCCCGGCAAGGGCCTGGAGTGGGTGAGCGGCATCAACGTGGCCTACGGCATCAC
    CAGCTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACACCAAGAAC
    ACCCTGTACCTGCAGCTGAACAGCCTGAAGACCGAGGACACCGCCATCTACTACTGCGT
    GAAGCACAGCGGCACCACCATCCCCAGGGGCTTCATCAGCTACACCAAGAGGGGCCAG
    GGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCG
    GCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGACCCTGAGCTGCGCCGCCAGCGAGTA
    CGCCTACAGCACCTGCAACATGGGCTGGTACAGGCAGGCCCCCGGCAAGGAGAGGGAG
    CTGGTGAGCGCCTTCATCAGCGACGGCAGCACCTACTACGCCGACAGCGTGAAGGGCA
    GGTTCACCATCACCAGGGACAACGCCAAGAACACCGTGTACCTGCAGATGAACAGCCT
    GAAGCCCGAGGACACCGCCATCTACTACTGCAGCGCCAACTGCTACAGGAGGCTGAGG
    AACTACTGGGGCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCACCACCACCACC
    ACCACCAC
    162 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGAGAGCCTGAGG
    CTGAGCTGCACCGCCAGCGGCTTCACCTTCAGCAACTACGCCATGAGCTGGGTGAGGC
    AGGCCCCCGGCAAGGGCCTGGAGTGGGTGAGCGGCATCAACGTGGCCTACGGCATCAC
    CAGCTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACACCAAGAAC
    ACCCTGTACCTGCAGCTGAACAGCCTGAAGACCGAGGACACCGCCATCTACTACTGCGT
    GAAGCACAGCGGCACCACCATCCCCAGGGGCTTCATCAGCTACACCAAGAGGGGCCAG
    GGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCG
    GCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGCTGAGCTGCACCGCCAGCGGCCT
    GACCTTCGACGACAGCGTGATGGGCTGGTTCAGGCAGGCCCCCGGCAAGGGCAGGGAG
    GCCGTGAGCTGCATCAGCAGCAGCGGCGCCAACGCCTTCTACGCCGACAGCGTGAAGG
    GCAGGTTCACCATCAGCAGGGACAACGCCAAGAACACCCTGTACCTGCAGATGAACAG
    CCTGAAGCCCGAGGACACCGCCACCTACTACTGCAAGAGGGGCCACGCCTGCGCCGGC
    TACTACCCCATCCCCTACGACGACTACTGGGGCCAGGGCACCCAGGTGACCGTGAGCG
    CTAGCCACCACCACCACCACCACCACCAC
    163 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGC
    TGAGCTGCGCCGCCAGCGGCTTCAGCTTCAGCAGCTACGCCATGAAGTGGGTGAGGCA
    GGCCCCCGGCAAGGGCCTGGAGTGGGTGAGCACCATCAGCAGCGGCGGCAGCAGCACC
    AACTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAAC
    ACCCTGTACCTGCAGCTGAACAGCCTGAAGATCGAGGACACCGCCATGTACTACTGCG
    CCAAGGCCATCGTGCCCACCGGCGCCACCATGGAGAGGGGCCAGGGCACCCAGGTGAC
    CGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTG
    CAGGCCGGCGGCAGCCTGAGGCTGAGCTGCACCGCCAGCGGCGCCATCGCCAGCGGCT
    ACATCGACAGCAGGTGGTGCATGGCCTGGTTCAGGCAGGCCCCCGGCAAGGAGAGGGA
    GGGCGTGGCCGCCATCTGGCCCGGCGGCGGCCTGACCGTGTACGCCGACAGCGTGAAG
    GGCAGGTTCACCATCAGCAGGGACCACGCCAAGAACACCCTGTACCTGCAGATGAACA
    ACCTGAAGCCCGAGGACACCGCCATGTACTACTGCGCCGCCGGCAGCCCCAGGATGTG
    CCCCAGCCTGGAGTTCGGCTTCGACTACTGGGGCCAGGGCACCCAGGTGACCGTGAGC
    GCTAGCCACCACCACCACCACCACCACCAC
    164 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGC
    TGAGCTGCGCCGCCAGCGGCTTCAGCTTCAGCAGCTACGCCATGAAGTGGGTGAGGCA
    GGCCCCCGGCAAGGGCCTGGAGTGGGTGAGCACCATCAGCAGCGGCGGCAGCAGCACC
    AACTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAAC
    ACCCTGTACCTGCAGCTGAACAGCCTGAAGATCGAGGACACCGCCATGTACTACTGCG
    CCAAGGCCATCGTGCCCACCGGCGCCACCATGGAGAGGGGCCAGGGCACCCAGGTGAC
    CGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTG
    CAGGCCGGCGGCAGCCTGAGGCTGAGCTGCACCGCCCCCGGCTTCACCAGCAACAGCT
    GCGGCATGGACTGGTACAGGCAGGCCCCCGGCAAGGAGAGGGAGTTCGTGAGCAGCAT
    CAGCACCGACGGCACCACCGGCTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGC
    AAGGACAAGGCCAAGGACACCGTGTACCTGCAGATGAACAGCCTGAAGCCCGAGGAC
    ACCGGCATGTACAGCTGCAAGACCAAGGACGGCACCATCGCCACCATGGAGCTGTGCG
    ACTTCGGCTACTGGGGCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCACCACCA
    CCACCACCACCAC
    165 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGC
    TGAGCTGCGCCGCCAGCGGCTTCAGCTTCAGCAGCTACGCCATGAAGTGGGTGAGGCA
    GGCCCCCGGCAAGGGCCTGGAGTGGGTGAGCACCATCAGCAGCGGCGGCAGCAGCACC
    AACTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAAC
    ACCCTGTACCTGCAGCTGAACAGCCTGAAGATCGAGGACACCGCCATGTACTACTGCG
    CCAAGGCCATCGTGCCCACCGGCGCCACCATGGAGAGGGGCCAGGGCACCCAGGTGAC
    CGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTG
    CAGGCCGGCGGCAGCCTGAGGCTGAGCTGCGCCGCCAGCGGCTACCCCTACAGCAACG
    GCTACATGGGCTGGTTCAGGCAGGCCCCCGGCAAGGAGAGGGAGGGCGTGGCCACCAT
    CTACACCGGCGACGGCAGGACCTACTACGCCGACAGCGTGAAGGGCAGGTTCACCATC
    AGCAGGGACAACGCCAAGAACACCGTGGACCTGCAGATGAGCAGCCTGAAGCCCGAG
    GACACCGCCATGTACTACTGCGCCGCCAGGGCCGCCCCCCTGTACAGCAGCGGCAGCC
    CCCTGACCAGGGCCAGGTACAACGTGTGGGGCCAGGGCACCCAGGTGACCGTGAGCGC
    TAGCCACCACCACCACCACCACCACCAC
    166 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGC
    TGAGCTGCGCCGCCAGCGGCTTCAGCTTCAGCAGCTACGCCATGAAGTGGGTGAGGCA
    GGCCCCCGGCAAGGGCCTGGAGTGGGTGAGCACCATCAGCAGCGGCGGCAGCAGCACC
    AACTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAAC
    ACCCTGTACCTGCAGCTGAACAGCCTGAAGATCGAGGACACCGCCATGTACTACTGCG
    CCAAGGCCATCGTGCCCACCGGCGCCACCATGGAGAGGGGCCAGGGCACCCAGGTGAC
    CGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTG
    CAGGCCGGCGGCAGCCTGAGGCTGAGCTGCGTGGCCAGCGCCAGCACCTACTGCACCT
    ACGACATGCACTGGTACAGGCAGGCCCCCGGCAAGGGCAGGGAGTTCGTGAGCGCCAT
    CGACAGCGACGGCACCACCAGGTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGC
    CAGGGCACCGCCAAGAACACCGTGTACCTGCAGATGAACAGCCTGCAGCCCGAGGACA
    CCGCCATGTACTACTGCAAGACCGTGTGCGTGGTGGGCAGCAGGTGGAGCGACTACTG
    GGGCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCACCACCACCACCACCACCAC
    167 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGC
    TGAGCTGCGCCGCCAGCGGCTTCAGCTTCAGCAGCTACGCCATGAAGTGGGTGAGGCA
    GGCCCCCGGCAAGGGCCTGGAGTGGGTGAGCACCATCAGCAGCGGCGGCAGCAGCACC
    AACTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAAC
    ACCCTGTACCTGCAGCTGAACAGCCTGAAGATCGAGGACACCGCCATGTACTACTGCG
    CCAAGGCCATCGTGCCCACCGGCGCCACCATGGAGAGGGGCCAGGGCACCCAGGTGAC
    CGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTG
    CAGGCCGGCGGCAGCCTGACCCTGAGCTGCGCCGCCAGCGAGTACGCCTACAGCACCT
    GCAACATGGGCTGGTACAGGCAGGCCCCCGGCAAGGAGAGGGAGCTGGTGAGCGCCTT
    CATCAGCGACGGCAGCACCTACTACGCCGACAGCGTGAAGGGCAGGTTCACCATCACC
    AGGGACAACGCCAAGAACACCGTGTACCTGCAGATGAACAGCCTGAAGCCCGAGGAC
    ACCGCCATCTACTACTGCAGCGCCAACTGCTACAGGAGGCTGAGGAACTACTGGGGCC
    AGGGCACCCAGGTGACCGTGAGCGCTAGCCACCACCACCACCACCACCACCAC
    168 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGC
    TGAGCTGCGCCGCCAGCGGCTTCAGCTTCAGCAGCTACGCCATGAAGTGGGTGAGGCA
    GGCCCCCGGCAAGGGCCTGGAGTGGGTGAGCACCATCAGCAGCGGCGGCAGCAGCACC
    AACTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAAC
    ACCCTGTACCTGCAGCTGAACAGCCTGAAGATCGAGGACACCGCCATGTACTACTGCG
    CCAAGGCCATCGTGCCCACCGGCGCCACCATGGAGAGGGGCCAGGGCACCCAGGTGAC
    CGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTG
    CAGCCCGGCGGCAGCCTGAGGCTGAGCTGCACCGCCAGCGGCCTGACCTTCGACGACA
    GCGTGATGGGCTGGTTCAGGCAGGCCCCCGGCAAGGGCAGGGAGGCCGTGAGCTGCAT
    CAGCAGCAGCGGCGCCAACGCCTTCTACGCCGACAGCGTGAAGGGCAGGTTCACCATC
    AGCAGGGACAACGCCAAGAACACCCTGTACCTGCAGATGAACAGCCTGAAGCCCGAGG
    ACACCGCCACCTACTACTGCAAGAGGGGCCACGCCTGCGCCGGCTACTACCCCATCCCC
    TACGACGACTACTGGGGCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCACCACC
    ACCACCACCACCAC
    169 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGAGCGGCGGCAGCCTGAGG
    CTGAGCTGCGCCGCCAGCGGCTTCACCTACAGCACCAGCAACAGCTGGATGGCCTGGTT
    CAGGCAGGCCCCCGGCAAGGAGAGGGAGGGCGTGGCCGCCATCTACACCGTGGGCGG
    CAGCATCTTCTACGCCGACAGCGTGAGGGGCAGGTTCACCATCAGCCAGGACGCCACC
    AAGAACATGTTCTACCTGCAGATGAACACCCTGAAGCCCGAGGACACCGCCATGTACT
    ACTGCGCCGCCGCCAGCGGCAGGCTGAGGGGCAAGTGGTTCTGGCCCTACGAGTACAA
    CTACTGGGGCCAGGGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAG
    CTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGGCTGAGCTGC
    ACCGCCAGCGGCGCCATCGCCAGCGGCTACATCGACAGCAGGTGGTGCATGGCCTGGT
    TCAGGCAGGCCCCCGGCAAGGAGAGGGAGGGCGTGGCCGCCATCTGGCCCGGCGGCG
    GCCTGACCGTGTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACCACGC
    CAAGAACACCCTGTACCTGCAGATGAACAACCTGAAGCCCGAGGACACCGCCATGTAC
    TACTGCGCCGCCGGCAGCCCCAGGATGTGCCCCAGCCTGGAGTTCGGCTTCGACTACTG
    GGGCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCACCACCACCACCACCACCAC
    170 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGAGCGGCGGCAGCCTGAGG
    CTGAGCTGCGCCGCCAGCGGCTTCACCTACAGCACCAGCAACAGCTGGATGGCCTGGTT
    CAGGCAGGCCCCCGGCAAGGAGAGGGAGGGCGTGGCCGCCATCTACACCGTGGGCGG
    CAGCATCTTCTACGCCGACAGCGTGAGGGGCAGGTTCACCATCAGCCAGGACGCCACC
    AAGAACATGTTCTACCTGCAGATGAACACCCTGAAGCCCGAGGACACCGCCATGTACT
    ACTGCGCCGCCGCCAGCGGCAGGCTGAGGGGCAAGTGGTTCTGGCCCTACGAGTACAA
    CTACTGGGGCCAGGGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAG
    CTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGGCTGAGCTGC
    ACCGCCCCCGGCTTCACCAGCAACAGCTGCGGCATGGACTGGTACAGGCAGGCCCCCG
    GCAAGGAGAGGGAGTTCGTGAGCAGCATCAGCACCGACGGCACCACCGGCTACGCCGA
    CAGCGTGAAGGGCAGGTTCACCATCAGCAAGGACAAGGCCAAGGACACCGTGTACCTG
    CAGATGAACAGCCTGAAGCCCGAGGACACCGGCATGTACAGCTGCAAGACCAAGGAC
    GGCACCATCGCCACCATGGAGCTGTGCGACTTCGGCTACTGGGGCCAGGGCACCCAGG
    TGACCGTGAGCGCTAGCCACCACCACCACCACCACCACCAC
    171 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGAGCGGCGGCAGCCTGAGG
    CTGAGCTGCGCCGCCAGCGGCTTCACCTACAGCACCAGCAACAGCTGGATGGCCTGGTT
    CAGGCAGGCCCCCGGCAAGGAGAGGGAGGGCGTGGCCGCCATCTACACCGTGGGCGG
    CAGCATCTTCTACGCCGACAGCGTGAGGGGCAGGTTCACCATCAGCCAGGACGCCACC
    AAGAACATGTTCTACCTGCAGATGAACACCCTGAAGCCCGAGGACACCGCCATGTACT
    ACTGCGCCGCCGCCAGCGGCAGGCTGAGGGGCAAGTGGTTCTGGCCCTACGAGTACAA
    CTACTGGGGCCAGGGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAG
    CTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGGCTGAGCTGC
    GCCGCCAGCGGCTACCCCTACAGCAACGGCTACATGGGCTGGTTCAGGCAGGCCCCCG
    GCAAGGAGAGGGAGGGCGTGGCCACCATCTACACCGGCGACGGCAGGACCTACTACGC
    CGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAACACCGTGGA
    CCTGCAGATGAGCAGCCTGAAGCCCGAGGACACCGCCATGTACTACTGCGCCGCCAGG
    GCCGCCCCCCTGTACAGCAGCGGCAGCCCCCTGACCAGGGCCAGGTACAACGTGTGGG
    GCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCACCACCACCACCACCACCAC
    172 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGAGCGGCGGCAGCCTGAGG
    CTGAGCTGCGCCGCCAGCGGCTTCACCTACAGCACCAGCAACAGCTGGATGGCCTGGTT
    CAGGCAGGCCCCCGGCAAGGAGAGGGAGGGCGTGGCCGCCATCTACACCGTGGGCGG
    CAGCATCTTCTACGCCGACAGCGTGAGGGGCAGGTTCACCATCAGCCAGGACGCCACC
    AAGAACATGTTCTACCTGCAGATGAACACCCTGAAGCCCGAGGACACCGCCATGTACT
    ACTGCGCCGCCGCCAGCGGCAGGCTGAGGGGCAAGTGGTTCTGGCCCTACGAGTACAA
    CTACTGGGGCCAGGGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAG
    CTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGGCTGAGCTGC
    GTGGCCAGCGCCAGCACCTACTGCACCTACGACATGCACTGGTACAGGCAGGCCCCCG
    GCAAGGGCAGGGAGTTCGTGAGCGCCATCGACAGCGACGGCACCACCAGGTACGCCGA
    CAGCGTGAAGGGCAGGTTCACCATCAGCCAGGGCACCGCCAAGAACACCGTGTACCTG
    CAGATGAACAGCCTGCAGCCCGAGGACACCGCCATGTACTACTGCAAGACCGTGTGCG
    TGGTGGGCAGCAGGTGGAGCGACTACTGGGGCCAGGGCACCCAGGTGACCGTGAGCGC
    TAGCCACCACCACCACCACCACCACCAC
    173 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGAGCGGCGGCAGCCTGAGG
    CTGAGCTGCGCCGCCAGCGGCTTCACCTACAGCACCAGCAACAGCTGGATGGCCTGGTT
    CAGGCAGGCCCCCGGCAAGGAGAGGGAGGGCGTGGCCGCCATCTACACCGTGGGCGG
    CAGCATCTTCTACGCCGACAGCGTGAGGGGCAGGTTCACCATCAGCCAGGACGCCACC
    AAGAACATGTTCTACCTGCAGATGAACACCCTGAAGCCCGAGGACACCGCCATGTACT
    ACTGCGCCGCCGCCAGCGGCAGGCTGAGGGGCAAGTGGTTCTGGCCCTACGAGTACAA
    CTACTGGGGCCAGGGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAG
    CTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGACCCTGAGCTGCG
    CCGCCAGCGAGTACGCCTACAGCACCTGCAACATGGGCTGGTACAGGCAGGCCCCCGG
    CAAGGAGAGGGAGCTGGTGAGCGCCTTCATCAGCGACGGCAGCACCTACTACGCCGAC
    AGCGTGAAGGGCAGGTTCACCATCACCAGGGACAACGCCAAGAACACCGTGTACCTGC
    AGATGAACAGCCTGAAGCCCGAGGACACCGCCATCTACTACTGCAGCGCCAACTGCTA
    CAGGAGGCTGAGGAACTACTGGGGCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCAC
    CACCACCACCACCACCACCAC
    174 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGAGCGGCGGCAGCCTGAGG
    CTGAGCTGCGCCGCCAGCGGCTTCACCTACAGCACCAGCAACAGCTGGATGGCCTGGTT
    CAGGCAGGCCCCCGGCAAGGAGAGGGAGGGCGTGGCCGCCATCTACACCGTGGGCGG
    CAGCATCTTCTACGCCGACAGCGTGAGGGGCAGGTTCACCATCAGCCAGGACGCCACC
    AAGAACATGTTCTACCTGCAGATGAACACCCTGAAGCCCGAGGACACCGCCATGTACT
    ACTGCGCCGCCGCCAGCGGCAGGCTGAGGGGCAAGTGGTTCTGGCCCTACGAGTACAA
    CTACTGGGGCCAGGGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAG
    CTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGCTGAGCTGCA
    CCGCCAGCGGCCTGACCTTCGACGACAGCGTGATGGGCTGGTTCAGGCAGGCCCCCGG
    CAAGGGCAGGGAGGCCGTGAGCTGCATCAGCAGCAGCGGCGCCAACGCCTTCTACGCC
    GACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAACACCCTGTACC
    TGCAGATGAACAGCCTGAAGCCCGAGGACACCGCCACCTACTACTGCAAGAGGGGCCA
    CGCCTGCGCCGGCTACTACCCCATCCCCTACGACGACTACTGGGGCCAGGGCACCCAG
    GTGACCGTGAGCGCTAGCCACCACCACCACCACCACCACCAC
    175 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCGTGGCCAGCGGCTACGTGAGCTGCGACTACTTCCTGCCCAGCTGGTACAG
    GCAGGCCCCCGGCAAGGAGAGGGAGTTCGTGAGCATCATCGACGGCACCGGCAGCACC
    AGCTACGCCGCCAGCGTGAAGGGCAGGTTCACCGCCAGCCAGGACAAGGGCAAGAAC
    ATCGCCTACCTGCAGATGAACACCCTGAAGCCCGAGGACACCGCCATGTACTACTGCA
    AGGCCAGCTGCGTGAGGGGCAGGGCCATCAGCGAGTACTGGGGCCAGGGCACCCAGGT
    GACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGC
    GTGCAGGCCGGCGGCAGCCTGAGGCTGAGCTGCACCGCCAGCGGCGCCATCGCCAGCG
    GCTACATCGACAGCAGGTGGTGCATGGCCTGGTTCAGGCAGGCCCCCGGCAAGGAGAG
    GGAGGGCGTGGCCGCCATCTGGCCCGGCGGCGGCCTGACCGTGTACGCCGACAGCGTG
    AAGGGCAGGTTCACCATCAGCAGGGACCACGCCAAGAACACCCTGTACCTGCAGATGA
    ACAACCTGAAGCCCGAGGACACCGCCATGTACTACTGCGCCGCCGGCAGCCCCAGGAT
    GTGCCCCAGCCTGGAGTTCGGCTTCGACTACTGGGGCCAGGGCACCCAGGTGACCGTG
    AGCGCTAGCCACCACCACCACCACCACCACCAC
    176 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCGTGGCCAGCGGCTACGTGAGCTGCGACTACTTCCTGCCCAGCTGGTACAG
    GCAGGCCCCCGGCAAGGAGAGGGAGTTCGTGAGCATCATCGACGGCACCGGCAGCACC
    AGCTACGCCGCCAGCGTGAAGGGCAGGTTCACCGCCAGCCAGGACAAGGGCAAGAAC
    ATCGCCTACCTGCAGATGAACACCCTGAAGCCCGAGGACACCGCCATGTACTACTGCA
    AGGCCAGCTGCGTGAGGGGCAGGGCCATCAGCGAGTACTGGGGCCAGGGCACCCAGGT
    GACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGC
    GTGCAGGCCGGCGGCAGCCTGAGGCTGAGCTGCACCGCCCCCGGCTTCACCAGCAACA
    GCTGCGGCATGGACTGGTACAGGCAGGCCCCCGGCAAGGAGAGGGAGTTCGTGAGCAG
    CATCAGCACCGACGGCACCACCGGCTACGCCGACAGCGTGAAGGGCAGGTTCACCATC
    AGCAAGGACAAGGCCAAGGACACCGTGTACCTGCAGATGAACAGCCTGAAGCCCGAG
    GACACCGGCATGTACAGCTGCAAGACCAAGGACGGCACCATCGCCACCATGGAGCTGT
    GCGACTTCGGCTACTGGGGCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCACCA
    CCACCACCACCACCAC
    177 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCGTGGCCAGCGGCTACGTGAGCTGCGACTACTTCCTGCCCAGCTGGTACAG
    GCAGGCCCCCGGCAAGGAGAGGGAGTTCGTGAGCATCATCGACGGCACCGGCAGCACC
    AGCTACGCCGCCAGCGTGAAGGGCAGGTTCACCGCCAGCCAGGACAAGGGCAAGAAC
    ATCGCCTACCTGCAGATGAACACCCTGAAGCCCGAGGACACCGCCATGTACTACTGCA
    AGGCCAGCTGCGTGAGGGGCAGGGCCATCAGCGAGTACTGGGGCCAGGGCACCCAGGT
    GACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGC
    GTGCAGGCCGGCGGCAGCCTGAGGCTGAGCTGCGCCGCCAGCGGCTACCCCTACAGCA
    ACGGCTACATGGGCTGGTTCAGGCAGGCCCCCGGCAAGGAGAGGGAGGGCGTGGCCAC
    CATCTACACCGGCGACGGCAGGACCTACTACGCCGACAGCGTGAAGGGCAGGTTCACC
    ATCAGCAGGGACAACGCCAAGAACACCGTGGACCTGCAGATGAGCAGCCTGAAGCCCG
    AGGACACCGCCATGTACTACTGCGCCGCCAGGGCCGCCCCCCTGTACAGCAGCGGCAG
    CCCCCTGACCAGGGCCAGGTACAACGTGTGGGGCCAGGGCACCCAGGTGACCGTGAGC
    GCTAGCCACCACCACCACCACCACCACCAC
    178 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCGTGGCCAGCGGCTACGTGAGCTGCGACTACTTCCTGCCCAGCTGGTACAG
    GCAGGCCCCCGGCAAGGAGAGGGAGTTCGTGAGCATCATCGACGGCACCGGCAGCACC
    AGCTACGCCGCCAGCGTGAAGGGCAGGTTCACCGCCAGCCAGGACAAGGGCAAGAAC
    ATCGCCTACCTGCAGATGAACACCCTGAAGCCCGAGGACACCGCCATGTACTACTGCA
    AGGCCAGCTGCGTGAGGGGCAGGGCCATCAGCGAGTACTGGGGCCAGGGCACCCAGGT
    GACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGC
    GTGCAGGCCGGCGGCAGCCTGAGGCTGAGCTGCGTGGCCAGCGCCAGCACCTACTGCA
    CCTACGACATGCACTGGTACAGGCAGGCCCCCGGCAAGGGCAGGGAGTTCGTGAGCGC
    CATCGACAGCGACGGCACCACCAGGTACGCCGACAGCGTGAAGGGCAGGTTCACCATC
    AGCCAGGGCACCGCCAAGAACACCGTGTACCTGCAGATGAACAGCCTGCAGCCCGAGG
    ACACCGCCATGTACTACTGCAAGACCGTGTGCGTGGTGGGCAGCAGGTGGAGCGACTA
    CTGGGGCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCACCACCACCACCACCAC
    CAC
    179 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCGTGGCCAGCGGCTACGTGAGCTGCGACTACTTCCTGCCCAGCTGGTACAG
    GCAGGCCCCCGGCAAGGAGAGGGAGTTCGTGAGCATCATCGACGGCACCGGCAGCACC
    AGCTACGCCGCCAGCGTGAAGGGCAGGTTCACCGCCAGCCAGGACAAGGGCAAGAAC
    ATCGCCTACCTGCAGATGAACACCCTGAAGCCCGAGGACACCGCCATGTACTACTGCA
    AGGCCAGCTGCGTGAGGGGCAGGGCCATCAGCGAGTACTGGGGCCAGGGCACCCAGGT
    GACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGC
    GTGCAGGCCGGCGGCAGCCTGACCCTGAGCTGCGCCGCCAGCGAGTACGCCTACAGCA
    CCTGCAACATGGGCTGGTACAGGCAGGCCCCCGGCAAGGAGAGGGAGCTGGTGAGCGC
    CTTCATCAGCGACGGCAGCACCTACTACGCCGACAGCGTGAAGGGCAGGTTCACCATC
    ACCAGGGACAACGCCAAGAACACCGTGTACCTGCAGATGAACAGCCTGAAGCCCGAGG
    ACACCGCCATCTACTACTGCAGCGCCAACTGCTACAGGAGGCTGAGGAACTACTGGGG
    CCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCACCACCACCACCACCACCAC
    180 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCGTGGCCAGCGGCTACGTGAGCTGCGACTACTTCCTGCCCAGCTGGTACAG
    GCAGGCCCCCGGCAAGGAGAGGGAGTTCGTGAGCATCATCGACGGCACCGGCAGCACC
    AGCTACGCCGCCAGCGTGAAGGGCAGGTTCACCGCCAGCCAGGACAAGGGCAAGAAC
    ATCGCCTACCTGCAGATGAACACCCTGAAGCCCGAGGACACCGCCATGTACTACTGCA
    AGGCCAGCTGCGTGAGGGGCAGGGCCATCAGCGAGTACTGGGGCCAGGGCACCCAGGT
    GACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTG
    GTGCAGCCCGGCGGCAGCCTGAGGCTGAGCTGCACCGCCAGCGGCCTGACCTTCGACG
    ACAGCGTGATGGGCTGGTTCAGGCAGGCCCCCGGCAAGGGCAGGGAGGCCGTGAGCTG
    CATCAGCAGCAGCGGCGCCAACGCCTTCTACGCCGACAGCGTGAAGGGCAGGTTCACC
    ATCAGCAGGGACAACGCCAAGAACACCCTGTACCTGCAGATGAACAGCCTGAAGCCCG
    AGGACACCGCCACCTACTACTGCAAGAGGGGCCACGCCTGCGCCGGCTACTACCCCAT
    CCCCTACGACGACTACTGGGGCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCAC
    CACCACCACCACCACCAC
    181 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCAGGGCCAGCGGCAGCACCTACAGCAACTACTGCCTGGGCTGGTTCAGGC
    AGATCACCGGCAAGGAGAGGGAGGGCGTGGCCGTGATCAACTGGGTGGGCGGCATGCT
    GTACTTCGCCGACAGCGTGAAGGGCAGGTTCACCGTGAGCCAGGACCAGGCCAAGAAC
    ACCGTGTACCTGCAGATGAACAGCCTGAAGCCCGAGGACACCGCCATGTACTACTGCG
    CCGCCGAGAGCGTGAGCAGCTTCAGCTGCGGCGGCTGGCTGACCAGGCCCGACAGGGT
    GCCCTACTGGGGCCAGGGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTG
    CAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGGCTGAGC
    TGCACCGCCAGCGGCGCCATCGCCAGCGGCTACATCGACAGCAGGTGGTGCATGGCCT
    GGTTCAGGCAGGCCCCCGGCAAGGAGAGGGAGGGCGTGGCCGCCATCTGGCCCGGCGG
    CGGCCTGACCGTGTACGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACCAC
    GCCAAGAACACCCTGTACCTGCAGATGAACAACCTGAAGCCCGAGGACACCGCCATGT
    ACTACTGCGCCGCCGGCAGCCCCAGGATGTGCCCCAGCCTGGAGTTCGGCTTCGACTAC
    TGGGGCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCACCACCACCACCACCACC
    AC
    182 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCAGGGCCAGCGGCAGCACCTACAGCAACTACTGCCTGGGCTGGTTCAGGC
    AGATCACCGGCAAGGAGAGGGAGGGCGTGGCCGTGATCAACTGGGTGGGCGGCATGCT
    GTACTTCGCCGACAGCGTGAAGGGCAGGTTCACCGTGAGCCAGGACCAGGCCAAGAAC
    ACCGTGTACCTGCAGATGAACAGCCTGAAGCCCGAGGACACCGCCATGTACTACTGCG
    CCGCCGAGAGCGTGAGCAGCTTCAGCTGCGGCGGCTGGCTGACCAGGCCCGACAGGGT
    GCCCTACTGGGGCCAGGGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTG
    CAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGGCTGAGC
    TGCACCGCCCCCGGCTTCACCAGCAACAGCTGCGGCATGGACTGGTACAGGCAGGCCC
    CCGGCAAGGAGAGGGAGTTCGTGAGCAGCATCAGCACCGACGGCACCACCGGCTACGC
    CGACAGCGTGAAGGGCAGGTTCACCATCAGCAAGGACAAGGCCAAGGACACCGTGTAC
    CTGCAGATGAACAGCCTGAAGCCCGAGGACACCGGCATGTACAGCTGCAAGACCAAGG
    ACGGCACCATCGCCACCATGGAGCTGTGCGACTTCGGCTACTGGGGCCAGGGCACCCA
    GGTGACCGTGAGCGCTAGCCACCACCACCACCACCACCACCAC
    183 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCAGGGCCAGCGGCAGCACCTACAGCAACTACTGCCTGGGCTGGTTCAGGC
    AGATCACCGGCAAGGAGAGGGAGGGCGTGGCCGTGATCAACTGGGTGGGCGGCATGCT
    GTACTTCGCCGACAGCGTGAAGGGCAGGTTCACCGTGAGCCAGGACCAGGCCAAGAAC
    ACCGTGTACCTGCAGATGAACAGCCTGAAGCCCGAGGACACCGCCATGTACTACTGCG
    CCGCCGAGAGCGTGAGCAGCTTCAGCTGCGGCGGCTGGCTGACCAGGCCCGACAGGGT
    GCCCTACTGGGGCCAGGGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTG
    CAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGGCTGAGC
    TGCGCCGCCAGCGGCTACCCCTACAGCAACGGCTACATGGGCTGGTTCAGGCAGGCCC
    CCGGCAAGGAGAGGGAGGGCGTGGCCACCATCTACACCGGCGACGGCAGGACCTACTA
    CGCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAACACCGTG
    GACCTGCAGATGAGCAGCCTGAAGCCCGAGGACACCGCCATGTACTACTGCGCCGCCA
    GGGCCGCCCCCCTGTACAGCAGCGGCAGCCCCCTGACCAGGGCCAGGTACAACGTGTG
    GGGCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCACCACCACCACCACCACCAC
    184 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCAGGGCCAGCGGCAGCACCTACAGCAACTACTGCCTGGGCTGGTTCAGGC
    AGATCACCGGCAAGGAGAGGGAGGGCGTGGCCGTGATCAACTGGGTGGGCGGCATGCT
    GTACTTCGCCGACAGCGTGAAGGGCAGGTTCACCGTGAGCCAGGACCAGGCCAAGAAC
    ACCGTGTACCTGCAGATGAACAGCCTGAAGCCCGAGGACACCGCCATGTACTACTGCG
    CCGCCGAGAGCGTGAGCAGCTTCAGCTGCGGCGGCTGGCTGACCAGGCCCGACAGGGT
    GCCCTACTGGGGCCAGGGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTG
    CAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGGCTGAGC
    TGCGTGGCCAGCGCCAGCACCTACTGCACCTACGACATGCACTGGTACAGGCAGGCCC
    CCGGCAAGGGCAGGGAGTTCGTGAGCGCCATCGACAGCGACGGCACCACCAGGTACGC
    CGACAGCGTGAAGGGCAGGTTCACCATCAGCCAGGGCACCGCCAAGAACACCGTGTAC
    CTGCAGATGAACAGCCTGCAGCCCGAGGACACCGCCATGTACTACTGCAAGACCGTGT
    GCGTGGTGGGCAGCAGGTGGAGCGACTACTGGGGCCAGGGCACCCAGGTGACCGTGAG
    CGCTAGCCACCACCACCACCACCACCACCAC
    185 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCAGGGCCAGCGGCAGCACCTACAGCAACTACTGCCTGGGCTGGTTCAGGC
    AGATCACCGGCAAGGAGAGGGAGGGCGTGGCCGTGATCAACTGGGTGGGCGGCATGCT
    GTACTTCGCCGACAGCGTGAAGGGCAGGTTCACCGTGAGCCAGGACCAGGCCAAGAAC
    ACCGTGTACCTGCAGATGAACAGCCTGAAGCCCGAGGACACCGCCATGTACTACTGCG
    CCGCCGAGAGCGTGAGCAGCTTCAGCTGCGGCGGCTGGCTGACCAGGCCCGACAGGGT
    GCCCTACTGGGGCCAGGGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTG
    CAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGACCCTGAGCT
    GCGCCGCCAGCGAGTACGCCTACAGCACCTGCAACATGGGCTGGTACAGGCAGGCCCC
    CGGCAAGGAGAGGGAGCTGGTGAGCGCCTTCATCAGCGACGGCAGCACCTACTACGCC
    GACAGCGTGAAGGGCAGGTTCACCATCACCAGGGACAACGCCAAGAACACCGTGTACC
    TGCAGATGAACAGCCTGAAGCCCGAGGACACCGCCATCTACTACTGCAGCGCCAACTG
    CTACAGGAGGCTGAGGAACTACTGGGGCCAGGGCACCCAGGTGACCGTGAGCGCTAGC
    CACCACCACCACCACCACCACCAC
    186 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGG
    CTGAGCTGCAGGGCCAGCGGCAGCACCTACAGCAACTACTGCCTGGGCTGGTTCAGGC
    AGATCACCGGCAAGGAGAGGGAGGGCGTGGCCGTGATCAACTGGGTGGGCGGCATGCT
    GTACTTCGCCGACAGCGTGAAGGGCAGGTTCACCGTGAGCCAGGACCAGGCCAAGAAC
    ACCGTGTACCTGCAGATGAACAGCCTGAAGCCCGAGGACACCGCCATGTACTACTGCG
    CCGCCGAGAGCGTGAGCAGCTTCAGCTGCGGCGGCTGGCTGACCAGGCCCGACAGGGT
    GCCCTACTGGGGCCAGGGCACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTG
    CAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGCTGAGCT
    GCACCGCCAGCGGCCTGACCTTCGACGACAGCGTGATGGGCTGGTTCAGGCAGGCCCC
    CGGCAAGGGCAGGGAGGCCGTGAGCTGCATCAGCAGCAGCGGCGCCAACGCCTTCTAC
    GCCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAACACCCTGT
    ACCTGCAGATGAACAGCCTGAAGCCCGAGGACACCGCCACCTACTACTGCAAGAGGGG
    CCACGCCTGCGCCGGCTACTACCCCATCCCCTACGACGACTACTGGGGCCAGGGCACCC
    AGGTGACCGTGAGCGCTAGCCACCACCACCACCACCACCACCAC
    187 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGC
    TGAGCTGCGCCGCCAGCGGCTTCACCTTCAGCCTGAGCAGCATGAGCTGGGTGAGGCA
    GGCCCCCGGCAAGGGCCTGGAGTGGGTGAGCGCCATCAGCAGCGGCGGCGCCAGCACC
    TACTACACCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAACA
    TGCTGTACCTGCAGCTGAACAGCCTGAAGACCGAGGACACCGCCATGTACTACTGCGC
    CAAGGGCGGCAGCGGCTACGGCGACGCCAGCAGGATGACCAGCCCCGGCAGCCAGGG
    CACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGC
    GGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGGCTGAGCTGCACCGCCAGCGGCGCCA
    TCGCCAGCGGCTACATCGACAGCAGGTGGTGCATGGCCTGGTTCAGGCAGGCCCCCGG
    CAAGGAGAGGGAGGGCGTGGCCGCCATCTGGCCCGGCGGCGGCCTGACCGTGTACGCC
    GACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACCACGCCAAGAACACCCTGTACC
    TGCAGATGAACAACCTGAAGCCCGAGGACACCGCCATGTACTACTGCGCCGCCGGCAG
    CCCCAGGATGTGCCCCAGCCTGGAGTTCGGCTTCGACTACTGGGGCCAGGGCACCCAG
    GTGACCGTGAGCGCTAGCCACCACCACCACCACCACCACCAC
    188 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGC
    TGAGCTGCGCCGCCAGCGGCTTCACCTTCAGCCTGAGCAGCATGAGCTGGGTGAGGCA
    GGCCCCCGGCAAGGGCCTGGAGTGGGTGAGCGCCATCAGCAGCGGCGGCGCCAGCACC
    TACTACACCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAACA
    TGCTGTACCTGCAGCTGAACAGCCTGAAGACCGAGGACACCGCCATGTACTACTGCGC
    CAAGGGCGGCAGCGGCTACGGCGACGCCAGCAGGATGACCAGCCCCGGCAGCCAGGG
    CACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGC
    GGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGGCTGAGCTGCACCGCCCCCGGCTTCA
    CCAGCAACAGCTGCGGCATGGACTGGTACAGGCAGGCCCCCGGCAAGGAGAGGGAGTT
    CGTGAGCAGCATCAGCACCGACGGCACCACCGGCTACGCCGACAGCGTGAAGGGCAGG
    TTCACCATCAGCAAGGACAAGGCCAAGGACACCGTGTACCTGCAGATGAACAGCCTGA
    AGCCCGAGGACACCGGCATGTACAGCTGCAAGACCAAGGACGGCACCATCGCCACCAT
    GGAGCTGTGCGACTTCGGCTACTGGGGCCAGGGCACCCAGGTGACCGTGAGCGCTAGC
    CACCACCACCACCACCACCACCAC
    189 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGC
    TGAGCTGCGCCGCCAGCGGCTTCACCTTCAGCCTGAGCAGCATGAGCTGGGTGAGGCA
    GGCCCCCGGCAAGGGCCTGGAGTGGGTGAGCGCCATCAGCAGCGGCGGCGCCAGCACC
    TACTACACCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAACA
    TGCTGTACCTGCAGCTGAACAGCCTGAAGACCGAGGACACCGCCATGTACTACTGCGC
    CAAGGGCGGCAGCGGCTACGGCGACGCCAGCAGGATGACCAGCCCCGGCAGCCAGGG
    CACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGC
    GGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGGCTGAGCTGCGCCGCCAGCGGCTACC
    CCTACAGCAACGGCTACATGGGCTGGTTCAGGCAGGCCCCCGGCAAGGAGAGGGAGGG
    CGTGGCCACCATCTACACCGGCGACGGCAGGACCTACTACGCCGACAGCGTGAAGGGC
    AGGTTCACCATCAGCAGGGACAACGCCAAGAACACCGTGGACCTGCAGATGAGCAGCC
    TGAAGCCCGAGGACACCGCCATGTACTACTGCGCCGCCAGGGCCGCCCCCCTGTACAG
    CAGCGGCAGCCCCCTGACCAGGGCCAGGTACAACGTGTGGGGCCAGGGCACCCAGGTG
    ACCGTGAGCGCTAGCCACCACCACCACCACCACCACCAC
    190 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGC
    TGAGCTGCGCCGCCAGCGGCTTCACCTTCAGCCTGAGCAGCATGAGCTGGGTGAGGCA
    GGCCCCCGGCAAGGGCCTGGAGTGGGTGAGCGCCATCAGCAGCGGCGGCGCCAGCACC
    TACTACACCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAACA
    TGCTGTACCTGCAGCTGAACAGCCTGAAGACCGAGGACACCGCCATGTACTACTGCGC
    CAAGGGCGGCAGCGGCTACGGCGACGCCAGCAGGATGACCAGCCCCGGCAGCCAGGG
    CACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGC
    GGCGGCAGCGTGCAGGCCGGCGGCAGCCTGAGGCTGAGCTGCGTGGCCAGCGCCAGCA
    CCTACTGCACCTACGACATGCACTGGTACAGGCAGGCCCCCGGCAAGGGCAGGGAGTT
    CGTGAGCGCCATCGACAGCGACGGCACCACCAGGTACGCCGACAGCGTGAAGGGCAG
    GTTCACCATCAGCCAGGGCACCGCCAAGAACACCGTGTACCTGCAGATGAACAGCCTG
    CAGCCCGAGGACACCGCCATGTACTACTGCAAGACCGTGTGCGTGGTGGGCAGCAGGT
    GGAGCGACTACTGGGGCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCACCACCA
    CCACCACCACCAC
    191 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGC
    TGAGCTGCGCCGCCAGCGGCTTCACCTTCAGCCTGAGCAGCATGAGCTGGGTGAGGCA
    GGCCCCCGGCAAGGGCCTGGAGTGGGTGAGCGCCATCAGCAGCGGCGGCGCCAGCACC
    TACTACACCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAACA
    TGCTGTACCTGCAGCTGAACAGCCTGAAGACCGAGGACACCGCCATGTACTACTGCGC
    CAAGGGCGGCAGCGGCTACGGCGACGCCAGCAGGATGACCAGCCCCGGCAGCCAGGG
    CACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGC
    GGCGGCAGCGTGCAGGCCGGCGGCAGCCTGACCCTGAGCTGCGCCGCCAGCGAGTACG
    CCTACAGCACCTGCAACATGGGCTGGTACAGGCAGGCCCCCGGCAAGGAGAGGGAGCT
    GGTGAGCGCCTTCATCAGCGACGGCAGCACCTACTACGCCGACAGCGTGAAGGGCAGG
    TTCACCATCACCAGGGACAACGCCAAGAACACCGTGTACCTGCAGATGAACAGCCTGA
    AGCCCGAGGACACCGCCATCTACTACTGCAGCGCCAACTGCTACAGGAGGCTGAGGAA
    CTACTGGGGCCAGGGCACCCAGGTGACCGTGAGCGCTAGCCACCACCACCACCACCAC
    CACCAC
    192 CAGGTGCAGCTGCAGGAGAGCGGCGGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGC
    TGAGCTGCGCCGCCAGCGGCTTCACCTTCAGCCTGAGCAGCATGAGCTGGGTGAGGCA
    GGCCCCCGGCAAGGGCCTGGAGTGGGTGAGCGCCATCAGCAGCGGCGGCGCCAGCACC
    TACTACACCGACAGCGTGAAGGGCAGGTTCACCATCAGCAGGGACAACGCCAAGAACA
    TGCTGTACCTGCAGCTGAACAGCCTGAAGACCGAGGACACCGCCATGTACTACTGCGC
    CAAGGGCGGCAGCGGCTACGGCGACGCCAGCAGGATGACCAGCCCCGGCAGCCAGGG
    CACCCAGGTGACCGTCTCGAGTGGCGGCGGATCCCAGGTGCAGCTGCAGGAGAGCGGC
    GGCGGCCTGGTGCAGCCCGGCGGCAGCCTGAGGCTGAGCTGCACCGCCAGCGGCCTGA
    CCTTCGACGACAGCGTGATGGGCTGGTTCAGGCAGGCCCCCGGCAAGGGCAGGGAGGC
    CGTGAGCTGCATCAGCAGCAGCGGCGCCAACGCCTTCTACGCCGACAGCGTGAAGGGC
    AGGTTCACCATCAGCAGGGACAACGCCAAGAACACCCTGTACCTGCAGATGAACAGCC
    TGAAGCCCGAGGACACCGCCACCTACTACTGCAAGAGGGGCCACGCCTGCGCCGGCTA
    CTACCCCATCCCCTACGACGACTACTGGGGCCAGGGCACCCAGGTGACCGTGAGCGCT
    AGCCACCACCACCACCACCACCACCAC
  • Additional IL27R Binding Proteins
  • Further, additional IL27R binding proteins can include three CDR sequences as underlined in an anti-IL27Rα VHH antibody listed in Table 4 below, and three CDR sequences as underlined in an anti-gp130 VHH antibody of any one of SEQ ID NOS:232-237. Additional IL27R binding proteins can include an anti-IL27Rα VHH antibody (e.g., any one of the sequences listed in Table 4 below) and an anti-gp130 VHH antibody (e.g., any one of SEQ ID NOS:232-237. In some embodiments, the binding protein comprises the anti-IL27Rα VHH antibody at the N-terminus and the anti-gp130 VHH antibody at the C-terminus. In some embodiments, the binding protein comprises the anti-gp130 VHH antibody at the N-terminus and the anti-IL27Rα VHH antibody at the C-terminus. In some embodiments, the binding protein comprises a linker (e.g., any one of SEQ ID NOS:85-108 (e.g., SEQ ID NO:108)) between the anti-TL27Rα VHH antibody and the anti-gp130 VHH antibody. In certain embodiments, the binding protein comprises a purification tag, such as as a six-histidine peptide (His)6 (SEQ ID NO: 1531) (His-tag).
  • TABLE 4
    SEQ
    ID
    NO Sequence
    258 QVQLQESGGGSVQVGGSLRLSCAASGFTFSSYPMSWVRQAPGKGLEWISTISAGGDTTLY
    ADSVKGRFTSSRDNAKNTLYLQLNSLKTEDTAIYYCAKRIDCNSGYCYRRNYWGQGTQVT
    VSS
    259 QVQLQESGGGSVQAGGSLRLSCRASGSTYSNYCLGWFRQITGKEREGVAVINWVGGMLYF
    ADSVKGRFTVSQDQAKNTLYLQMNSLKPEDTAMYYCAAESVSSFSCGGWLTRPDRVPYW
    GQGTQVTVSS
    260 QVQLQESGGGSVQAGGSLRLSCVASGYVSCDYFLPSWYRQAPGKEREFVSIIDGTGSTSY
    AASVKGRFTASQDKGKNIAYLQMNSLKPEDTAMYYCKASCVRGRGISEYWGQGTQVTVSS
    261 QVQLQESGGGLVQPGGSLRLSCAASGFTFSHSGMSWVRQAPGKGLEWVSTINSGGASTYY
    TDSVKGRFTISRDNAKNMLYLQLNSLKTEDTAMYYCAKGGSGYGDASRMTSPGSQGTQV
    TVSS
    262 QVQLQESGGGLVQPGGSLRLSCAASGFTFSLSGMSWVRQAPGKGLEWVSAISSGGASTYY
    TDSVKGRFTISRDNAKNILYLQLNSLKTEDTAMYYCAKGGSGYGDASRMTSPGSQGTQVT
    VSS
    263 QVQLQESGGGSVQAGGSLRLSCVASGYVSCDYFLPSWYRQAPGKEREFVSIIDGTGSTSY
    AASVKGRFTASEDKGKNIAYLQMNSLKPEDTAMYYCKASCVRGRAVSEYWGQGTQVTVSS
    264 QVQLQESGGGSVQAGGSLRLSCTASGYVSCDYFLPSWYRQAPGKEREFVSVIDGTGSTSY
    AASVKGRFTASQDKGKNIAYLQMNSLKPEDTAMYYCKASCVRGRAISEYWGQGTQVTVSS
    265 QVQLQESGGGLVQPGGSLRLSCAASGFTFSSYPMSWVRQAPGKGLEWISTISAGGDTTLYA
    DSVKGRFTSSRDNAKNTLYLQLNSLKTEDTAIYYCAKRIDCNSGYCYRRNYWGQGTQVTV
    SS
    266 QVQLQESGGGSVQAGGSLRLSCRASGSTYSNYCLGWFRQSTGKEREGVAVINWVGGMLY
    FADSVKGRFTVSQDHAKNTVTLQMNSLKPEDTAMYYCAAESVSSFSCGGWLTRPGRVPY
    WGQGTQVTVSS
    267 QVQLQESGGGSVQAGESLRLSCRASGSTYSNYCLGWFRQITGKEREGVAVINWVGGMLYF
    ADSVKGRFTVSQDQAKNTVYLEMNSLKPEDTAMYYCATESVSSFSCGGWLTRPDRVPYW
    GQGTQVTVSS
    268 QVQLQESGGGSVQAGGSLRLSCVASGYVSCDYFLPSWYRQAPGKEREFVSIIDGTGSTSY
    AASVKGRFTASQDRGKNIAYLQMNSLKPEDTAMYYCKASCVRGRTISEYWGQGTQVTVSS
    269 QVQLQESGGGSVQAGGSLRLSCVASGYVSCDYFLPSWYRQAPGKEREFVSIIDGTGSTSY
    AASVKGRFTASQDKGKNIAYLQMNSLKPEDTAMYYCKASCVRGRAISEYWGQGTQVTVSS
    270 QVQLQESGGGSVQAGGSLRLSCRASGSTYSNYCLGWFRQITGKEREGVAVINWVGGMLYF
    ADSVKGRFTVSQDQAKNTVYLQMNSLKPEDTAMYYCAAESASSFSCGGWLTRPDRVPYW
    GQGTQVTVSS
    271 QVQLQESGGGLVQPGGSLRLSCAASGFTFSLSGMSWVRQAPGKGLEWVSAISSGGASTYY
    TDSVKGRFTISRDNAKNMLYLQLNSLKTEDTAMYYCAKGGSGYGDASRMTSPGSQGTQV
    TVSS
    272 QVQLQESGGGLVQPGGSLRLSCAASGFTFSSYPMSWVRQAPGKGLEWVSTISSGGDTTLY
    ADSVKGRFTSSRDNAKNTLYLQLNSLKTEDTAMYYCAKRIDCNSGYCYKRSYWGQGTQVT
    VSS
    273 QVQLQESGGGSVQAGGSLRLSCRASGSTYSNYCLGWFRQTTGKEREGVAVINWVGGMLY
    FADSVKGRFTVSQDQAKNTVYLQMNSLKPEDTAMYYCAAESVSSFSCGGWLTRPDRVPY
    WGQGTQVTVSS
    274 QVQLQESGGGSVQAGGSLRLSCRASRSPYGNYCLGWFRQSTGKEREGVAVINWVGGMLY
    FADSVKGRFTVSQDHAKNTVTLQMNSLKPEDTAMYYCAAESVSSFSCGGWLTRPDRVPY
    WGQGTQVTVSS
  • An IL27R binding protein can comprise three CDR sequences as underlined in an anti-IL27Rα VHH antibody and three CDR sequences as underlined in an anti-gp130 VHH antibody as described in each row of Table 5 below. In some embodiments, an L27R binding protein comprises an anti-IL27Rα VHH antibody and an anti-gp130 VHH antibody as described in each row of Table 5 below. In some embodiments, the binding protein comprises the anti-IL27Rα VHH antibody at the N-terminus and the anti-gp130 VHH antibody at the C-terminus. In some embodiments, the binding protein comprises the anti-gp130 VHH antibody at the N-terminus and the anti-IL27Rα VHH antibody at the C-terminus. In some embodiments, the binding protein comprises a linker (e.g., any one of SEQ ID NOS:85-108 (e.g., SEQ ID NO: 108)) between the anti-IL27Rα VHH antibody and the anti-gp130 VHH antibody. In certain embodiments, the binding protein comprises a purification tag, such as as a six-histidine peptide (His)6 (SEQ ID NO: 1531) (His-tag).
  • TABLE 5
    SEQ ID NO of Anti-IL27Rα SEQ ID NO of Anti-gp130
    VHH antibody VHH antibody
    258 232
    259 232
    260 232
    261 232
    262 232
    263 232
    264 232
    265 232
    266 232
    267 232
    268 232
    269 232
    270 232
    271 232
    272 232
    273 232
    274 232
    258 233
    259 233
    260 233
    261 233
    262 233
    263 233
    264 233
    265 233
    266 233
    267 233
    268 233
    269 233
    270 233
    271 233
    272 233
    273 233
    274 233
    258 234
    259 234
    260 234
    261 234
    262 234
    263 234
    264 234
    265 234
    266 234
    267 234
    268 234
    269 234
    270 234
    271 234
    272 234
    273 234
    274 234
    258 235
    259 235
    260 235
    261 235
    262 235
    263 235
    264 235
    265 235
    266 235
    267 235
    268 235
    269 235
    270 235
    271 235
    272 235
    273 235
    274 235
    258 236
    259 236
    260 236
    261 236
    262 236
    263 236
    264 236
    265 236
    266 236
    267 236
    268 236
    269 236
    270 236
    271 236
    272 236
    273 236
    274 236
    258 237
    259 237
    260 237
    261 237
    262 237
    263 237
    264 237
    265 237
    266 237
    267 237
    268 237
    269 237
    270 237
    271 237
    272 237
    273 237
    274 237
  • Further, an IL27R binding protein can comprise a mouse Anti IL27Rα VHH antibody and a mouse Anti gp130 VHH antibody. In some instances, due to sequence or structural similarities between the extracellular domains of receptors from various mammalian species, immunization with an antigen derived from a IL27Rα or gp130 of a first mammalian species may provide antibodies which specifically bind to receptors of one or more additional mammalian species. Such antibodies are termed “cross reactive.” For example, immunization of a camelid with a human derived antigen (e.g., the hIL27Rα-ECD) may generate antibodies that are cross-reactive the murine and human receptors. Evaluation of cross-reactivity of antibody with respect to the receptors derived from other mammalian species may be readily determined by the skilled artisan, for example using the methods relating to evaluation of binding affinity and/or specific binding described elsewhere herein such as flow cytometry or SPR. Consequently, the use of the term “human IL27Rα VHH” or “hIL27Rα VHH” merely denotes that the species of the IL27Rα antigen used for immunization of the camelid from which the VHH was derived was the human IL27Rα but should not be understood as limiting with respect to the specific binding affinity of the VHH for IL27Rα molecules of other mammalian species. Similarly, the use of the term “mouse IL27Rα VHH” or “mIL27Rα VHH” merely denotes that the species of the IL27Rα antigen used for immunization of the camelid from which the VHH was derived was the murine IL27Rα but should not be understood as limiting with respect to the specific binding affinity of the VHH for IL27Rα molecules of other mammalian species. In some embodiments, an IL27R binding protein can comprise three CDR sequences as underlined in a mouse anti-IL27Rα VHH antibody sequence listed below and three CDR sequences as underlined in a mouse anti-gp130 VHH antibody sequence listed below. In some embodiments, an IL27R binding protein comprises a mouse anti-IL27Rα VHH antibody listed below and a mouse anti-gp130 VHH antibody listed below. In some embodiments, the binding protein comprises the mouse anti-IL27Rα VHH antibody at the N-terminus and the mouse anti-gp130 VHH antibody at the C-terminus. In some embodiments, the binding protein comprises the mouse anti-gp130 VHH antibody at the N-terminus and the mouse anti-IL27Rα VHH antibody at the C-terminus. In some embodiments, the binding protein comprises a linker (e.g., any one of SEQ ID NOS:85-108 (e.g., SEQ ID NO:108)) between the mouse anti-IL27Rα VHH antibody and the mouse anti-gp130 VHH antibody. In certain embodiments, the binding protein comprises a purification tag, such as as a six-histidine peptide (His)6 (SEQ ID NO: 1531) (His-tag).
  • Examples of mouse anti-IL27Rα VHH antibody sequences:
  • >mouse anti-IL27Rα VHH antibody_SEQ ID NO: 275
    QVQLQESGGGSVQAGGSLRLSCAASKNSNFMGWFRQAPGKEREGVAAMMTKNNN
    TYYADSVKGRFTISHDNAKNTVYLQMDSLKPEDTAVYYCAAVYRTRRLRVLEAAN
    FDYWGQGTQVTVSS
    >mouse anti-IL27Rα VHH antibody_SEQ ID NO: 276
    QVQLQESGGGSVQAGGSLRLSCTASGYTSSRYCMGWFRQTPGKKREGVAAIYTGG
    GTTFYHGSVKGRFTISQDNTTNTVYLQMHNLKPEDTAMYYCAAGPVTRACDEYNY
    WGQGTQVTVSS
    >mouse anti-IL27Rα VHH antibody_SEQ ID NO: 277
    QVQLQESGGGSVQAGGSLRLSCAGSGYSLSNYCMGWFRQAPGQGREGVASLRFVS
    GATFYADSVKGRFTIAQDNAKNTLYLQMNSLKPEDTAMYYCGIKSRGICGGRLVDV
    DFGNWGQGTQVTVSS
    >mouse anti-IL27Rα VHH antibody_SEQ ID NO: 278
    QVQLQESGGGSVQAGGSLRLSCAASGYSINRMGWFRQAPGKEREGVAAISIGGGQT
    YYADSVKGRFTISQDNAKNTVDLQMNSLKPEDTAMYYCAAGLVYGEAWLDSRHY
    NKWGQGTQVTVSS
    >mouse anti-IL27Rα VHH antibody_SEQ ID NO: 279
    QVQLQESGGGSVQAGGSLRLSCAVSGDSTYSMGWFRQPPGKEREGVAAIAKDGITI
    HADSVKGRFTISKDNAKNTLYLQMNSLKPEDTAMYYCAAHRPYGPPLNPRWYTYW
    GQGTQVTVSS
    >mouse anti-IL27Rα VHH antibody_SEQ ID NO: 280
    QVQLQESGGGSVQAGGSLRLSCAASGYTYSSYCMAWFRQAPGKEREGVAAIDSDGS
    TSYADSVKGRFTISKDNAKNTLYLQMNSLKPEDTAMYYCAAASGRCLGPGIRSLIW
    GQGTQVTVSS
    >mouse anti-IL27Rα VHH antibody_SEQ ID NO: 281
    QVQLQESGGGSVQAGGSLRLSCAVSGDSTYSMGWFRQPPGKEREGVAAITKDITIHA
    DSVKGRFTISKDNAKNTLYLQMNSLKPEDTAMYYCAAHRPYGPPLNPRWYTYWGQ
    GTQVTVSS
    >mouse anti-IL27Rα VHH antibody_SEQ ID NO: 282
    QVQLQESGGGSVQAGGSLRLSCAVSGDSTYSMGWFRQPPGKEREGVAAIPTDGITIH
    ADSVKGRFTISKDNAKNTLYLQMNSLKPEDTAMYYCAAHRPYGPPLNPRWYTYWG
    QGTQVTVSS
    >mouse anti-IL27Rα VHH antibody_SEQ ID NO: 283
    QVQLQESGGGSVQAGGSLRLSCAVSGDSTYSMGWFRQPPGKEREGVAAIAKDGITI
    HADSVKGRFTISKDNAKNTLYLQMSSLKPEDTAMYYCAAHRPYGPPLNPRWYTYW
    GQGTQVTVSS
    >mouse anti-IL27Rα VHH antibody_SEQ ID NO: 284
    QVQLQESGGGSVQAGGSLRLSCAVSGDSTYSMGWFRQPPGKEREGVAAIGKDGITI
    HADSVKGRFTISKDNAKNTLYLQMNSLKPEDTAMYYCAAHRPYGPPLNPRWYTYW
    GQGTQVTVSS
    >mouse anti-IL27Rα VHH antibody_SEQ ID NO: 285
    QVQLQESGGGSVQAGGSLRLSCAVSGDSTYSMGWFRQPPGKEREGVAAITKDITIHA
    DSVKGRFTISKDNAKNTLYLQMNSLRPEDTAMYYCAAHRPYGPPLNPRWYTYWGQ
    GTQVTVSS
    >mouse anti-IL27Rα VHH antibody_SEQ ID NO: 286
    QVQLQESGGGSVQTGGSLRLSCAASGYSINRMAWFRQAPGKEREGVAAISIGGDRT
    YYADSVKGRFTISQDNAKHTVDLQMNSLKPEDTAMYYCAAGLVYGEAWLDSRHY
    NKWGQGTQVTVSS
    >mouse anti-IL27Rα VHH antibody_SEQ ID NO: 287
    QVQLQESGGGSVQAGGSLRLSCAASGYSINRMGWFRQAPGKEREGVAAISIGGGRT
    YYADSVKGRFTISQDNAKNTVDLQMNSLKPEDTAMYYCAAGLVYGEAWLDSRHY
    NKWGQGTQVTVSS
    >mouse anti-IL27Rα VHH antibody_SEQ ID NO: 288
    QVQLQESGGGSVQAGGSLRLSCAVSGDSTYSMGWFRQPPGKEREGVAAITKDGITIH
    ADSVKGRFTISGDNAKNTLYLQMNNLKPEDTAMYYCAAHRPYGPPLNPRWYTYWG
    QGTQVTVSS
  • Examples of mouse anti-gp130 VHH antibody sequences:
  • >mouse anti-gp130 VHH antibody_SEQ ID NO: 289
    QVQLQESGGGSVQAGGSLRLSCVISGFTYRQTFMGWFRQVLGKEREGVAAISTGGG
    STVYADSVKGRFTISQDSSKNTVYLEMNGLKLEDTGMYYCAASTVITSVSINRGLYQ
    YWGQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 290
    QVQLQESGGGSVQAGGSLRLSCAISGFTYRQTFMGWFRQVVGKEREGVAAISTGGG
    STVYADSVKGRFTISQDSSKDTVYLEMNGLKLEDTGMYYCAASTVITSESINRNLYQ
    YWGQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 291
    QVQLQESGGGLVQPGGSLRLSCAASGFTLSTYWIYWVRQAPGKGPEWVSTVSRSGG
    TTYYADSVNGRFTISRDNAKNTVYLQMNNLKPEDAAVYYCLASVSNLGWPPVRAPS
    PTGQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 292
    QVQLQESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAINSGGA
    GTYYTDSVKGRFTISRDNAKNTLYLQLNSLKTEDTAMYYCAKHVTGDYDPSLRHGY
    NVWSQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 293
    QVQLQESGGGSVQAGGSLRLSCVISGFTYRQTFMGWFRQVVGKEREGVAAISTGGG
    STIYADSVKGRFTISQDSSKDTVYLEMNGLKLEDTGMYYCAASTVITSESINRNLYQY
    WGQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 294
    QVQLQESGGGLVQPGGSLRLSCAASGFTLSTYWMYWVRQAPGKGPEWVSAVSRGG
    FNTYYADSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCMSSVSFYGWPPDRVP
    SPTGQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 295
    QVQLQESGGGLVQPGESLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAINSGGA
    GTYYTDSVKGRFTISRDNAKNTLYLQLNSLKTEDTAMYYCAKHVTGDYDPSLRYGY
    NVWSQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 296
    QVQLQESGGGSVQAGGSLRLSCVISGFTYRPTFMGWFRQVLGKEREGVAAITTGGG
    STVYADSVKGRFTISQDSSKNTVYLEMNGLKLEDTGMYYCAATTVITSVSINRNLYQ
    YWGQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 297
    QVQLQESGGGSVQAGGSLRLSCGISGFTYRPTFMGWFRQVLGKEREGVAAISTGGGS
    SVYADSVKGRFTVSQDSSKNTVYLEMNGLKLEDTGMYYCAASTVITSVSINRGLYQ
    YWGQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 298
    QVQLQESGGGLVQPGGSLRLSCTASGFTFRNYAMSWVRQAPGKGLEWVSAINSGG
    GSTYYADSVKGRFTISRDNAKNTLYLRLHSLKTEDTAMYYCAKHVTGDYDPSLRYE
    YNYWSQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 299
    QVQLQESGGGLVQPGGSLRLSCAASGFTFRNYAMSWVRQAPGKGLEWVSAINSGG
    GSTYYADSVKGRFTISRDNAKNTLYLQLNSLKTEDTAMYYCTKHVTGDYDPSLRYE
    YNYWSQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 300
    QVQLQESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAINSGGG
    STYYADSVKGRFTISRDNAKNTLYLQLNSLKTEDTAMYCCAKHVTGDYDPSLRYGY
    NCWGPGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 301
    QVQLQESGGGSVQPGGSLRLSCAASGFTFSTYDMSWVRQAPGKGLEWVSTINYSGS
    STYYVDSVLGRFTIARDNAKNTLYLQMNNLQTEDTAVYYCASVKERRSNGHPIVFG
    DRGQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 302
    QVQLQESGGGSVQAGGSLRLSCVISGFTYKQTFMGWFRQVPGKEREGVAAISTGGG
    STVYADSVKGRFTISQDSSKNTVYLEMNGLKLEDTGMYYCAASTVITSVSINRGLYQ
    YWGQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 303
    QVQLQESGGGSVQAGGSLRLSCVISGFTYRQTFMGWFRQVVGKEREGVAAISTGGG
    STVYADSVKGRFTISQDSSKDTVYLEMNGLKLEDTGMYYCAASTVITSESIYRNLYQ
    YWGQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 304
    QVQLQESGGGLVQPGGSLRLSCAASGFTFRNYAMSWVRQAPGKGLEWVSAINSGG
    GSTYYADSVKGRFTISRDNAKNTLYLQMNSLKPEDTAMYYCAKHVTGDYDPSLRY
    EYNYWSQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 305
    QVQLQESGGGLVQPGGSLRLSCAASGFTFRNYAMSWVRQAPGKGLEWVSAINSGG
    GSTYYADSVKGRFTISRDNAKNTLYLQLNSLKTEDTAMYYCAKHVTGDYDPSLRYE
    YAYWSQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 306
    QVQLQESGGGSVQAGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAINSGGG
    STYYADSVKARFTISRDNAKNTLYLQLNSLKTEDTAMYYCAKHVTGDYDPSLRYDY
    NYWGQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 307
    QVQLQESGGGSVQAGGSLRLSCGISGFTYRPTFMGWFRQVLGKEREGVAAISTGGGS
    SVYADSVKGRFTVSQDSSKNTVYLEMNGLKLEDTGMYYCAASTVITSVSINRALYQ
    YWGQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 308
    QVQLQESGGGLVQPGGSLRLSCAASGFTFSSYAVSWVRQAPGKGLEWVSTINSGGG
    STYYADSVKGRFTISRDNAKNTLYLQLNSLKTEDTAMYYCTKHVTGDYDPSLRYEY
    NVWSQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 309
    QVQLQESGGGSVQAGGSLRVSCQISGFTYRQTFMGWFRQVPGKEREGVAAISTGGG
    STVYADSVKGRFTISQDSSKNTVYLEMNGLKLEDTGMYYCAASTVITSPSINRNLYQ
    YWGQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 310
    QVQLQESGGGLVQPGGSLRLSCAVSGFTFSNYAMKWVRQAPGKGLEWVSSISGGG
    GATYYADSVKGRFTISRDNTKNTLYLQMNSLKTEDTAVYYCAAQNLDYRGQGTQV
    TVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 311
    QVQLQESGGGLVQPGGSLRLSCTASGFTFNSAHMKWERQPPGKGLEWVSFITPGGA
    STGYADSVKGRFTISRDNAKNTLYLQMNNLKTEDTAVYYCATGGLRGQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 312
    QVQLQESGGGSVQAGGSLRLSCVISGFTYRPTFMGWFRQVLGKEREGVAAITTGGG
    STLYADSVKGRFTISQDSSKNTVYLEMNGLKLEDTGMYYCAATTVITSVSINRNLY
    QYWGQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 313
    QVQLQESGGGSVQAGGSLRLSCVISGFTYKQTFMGWFRQVPGKEREGVAAISTGGG
    STVYADSVKGRFTISQDSSKNTVYLEMNGLKLEDTGMYYCAASTVITSVTINRGLYQ
    YWGQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 314
    QVQLQESGGGSVQAGGSLRLSCVISGFVYKQTFMGWFRQVPGKEREGVAAISTGGG
    STVYADSVKGRFTISQDSSKNTVYLEMNGLKLEDTGMYYCAASTVITSVSINRGLYQ
    YWGQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 315
    QVQLQESGGGSVQAGGSLRVSCVISGFTYRQTFMGWFRQVPGKEREGVAAISTGGG
    STVYADSVKGRFTISQDSSKNTVYLEMNGLKLEDTGMYYCAASTVITSVSINRGLYQ
    YWGQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 316
    QVQLQESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAINSGGG
    STYYADSVKGRFTISRDNAKSTLYLQLNSLKTEDTAMYYCTKHVTGDYDPSLRYEY
    NYWSQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 317
    QVQLQESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAINSGGA
    STYYADSVKGRFTISRDNAKNTLYLQLNSLKTEDTAMYCCAKHVTGDYDPSLRYEY
    NCWGPGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 318
    QVQLQESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAINSGGG
    STYYADSVKGRFTISRDNAKNTLYLQLNSLKTEDTAMYYCAKHVTGDYDPSLRYEY
    NYWSQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 319
    QVQLQESGGGSVQAGGSLRLSCVISGFTYRQTFMGWFRQVVGKEREGVAAISTGGG
    STVYADSVKGRFTISQDSSKDTVYLEMNGLKLEDTGMYYCAASTVITSESINRNLYQ
    YWGQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 320
    QVQLQESGGGSVQAGGSLRVSCVVSGFTYRQTFMGWFRQVPGKEREGVAAISTGG
    GSTVYADSVKGRFTISQDSSKNTVYLEMNGLKLEDTGMYYCAASTVITSVSINRNLY
    QYWGQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 321
    QVQLQESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAINSGGG
    STYYADSVKGRFTISRDNAKNTMYLQLNSLKTEDTAMYYCAKHVAGDYDPSLRYE
    WHVWGQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 322
    QVQLQESGGGLVQPGGSLRLSCAASGFTFRSYAMSWVRQAPGKGLEWVSAINSGGG
    STYYADSVKARFTISRDNAKNTLYLQLNSLKTEDTAMYYCAKHVTGDYDPSLRYEY
    NYWGQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 323
    QVQLQESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAINSGGG
    STYYADSVKGRFTISRDNAKNTLYLQLNSLKTEDTAMYYCAKHITGDYDPSLRYEY
    NYWGQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 324
    QVQLQESGGGSVQAGGSLRLSCVISGFTYRQTFMGWFRQVVGKEREGVAAISTGGG
    SMVYADSVKGRFTISQDSSKDTVYLEMNGLKLEDTGMYYCAASTVITSESINRNLYQ
    YWGQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 325
    QVQLQESGGGPVQAGGSLRLSCVISGFTYRQTFMGWFRQVPGKEREGVAAISTGGG
    STVYADSVKGRFTISQDSSKNTVYLEMNGLKLEDTGMYYCAASTVITSESINRGLYQ
    YWGQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 326
    QVQLQESGGGSVQAGGFLRLSCAFSGYTGCMGWFRQGPGQEREGVASINDGGSLTY
    ADSVKGRFTISKDNAKKTLDLQMNTLKPEDTAMYYCAASLSYCLNPTLRVDGYNY
    WGQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 327
    QVQLQESGGGSVQAGGSLRLSCVISGLTYKQTFMGWFRQVPGKEREGVAAISTGGG
    STVYADSVKGRFTISQDNSKNTVYLEMNGLKLEDTGMYYCAASTVITSVSINRYLYQ
    WWGQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 328
    QVQLQESGGGLVQPGGSLRLSCAASGFTFSNYAMSWVRQAPGKGVEWVSAINSGGS
    VFYADSVKGRFTISRDNAKNTLYLQLSSLKTEDTAMYYCAKHVTGDYDPSLRYGYN
    VWSQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 329
    QVQLQESGGGSVQAGGSLRLSCGISGFTYRPTFMGWFRQVLGKEREGVAAISTGGGS
    TVYADSVKGRFTISQDSSKDTVYLEMNGLKLEDTGMYYCAASTVITSESINRNLYQY
    WGQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 330
    QVQLQESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAINSGGG
    STYYADSVKGRFTISRDNAKNTLYLQLNSLKTEDTAMYYCAKHVTGDYDPSLRYGY
    NVWSQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 331
    QVQLQESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAINLGGD
    TTYYTDSVKGRFTISRDNAKNTLYLQLNSLKTEDTAMYYCAKHVTGDYDPSLRYEY
    GYWSQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 332
    QVQLQESGGGLVQPGGSLRLSCTASGFTFNSAHLKWERQPPGKGLEWVSFITNGGAS
    TGYADSVKGRFTISRDDAKNTLYLQMNNLKTEDTAVYYCATGGLRGQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 333
    QVQLQESGGGSVQAGGSLRVSCVISGFTYRQTFMGWFRQVPGKEREGVAAISTGGG
    STIYANSVKGRFTISQDSSKNTVYLEMNGLKLEDTGMYYCAASTVITSVSINRGLYQ
    YWGQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 334
    QVQLQESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAINSGGG
    STYYADSVKGRFTISRDNAKNTLYLQLNSLKTEDTAMYCCAKHITGDYDPSLRYEY
    NCWGQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 335
    QVQLQESGGGSVQAGGSLRLSCVISGFTYKQTFMGWFRQVPGKEREGVAAISTGGG
    NTVYADSVKGRFTISQDSSKNTVYLEMNGLKLEDTGMYYCAASTVITSVTVNRGLY
    QYWGQGTQVTVSS
    >mouse anti-gp130 VHH antibody_SEQ ID NO: 336
    QVQLQESGGALVQPGGSLRLSCAASGFTFSYYAMKWVRQAPGKGLEWVSSISGGG
    GATYYADSVKGRFTISRDNTNDTLYLQMNSLKTEDTAVYYCAAQNLDYRGQGTQV
    TVSS
    > mouse anti-gp130 VHH antibody _SEQ ID NO: 337
    QVQLQESGGGSVQAGGSLRLSCVISGFTYKQTFMGWFRQVPGKEREGVAAISTGGG
    STVYADSVKGRFTISQESSKNTVYLEMNGLKLEDTGMYYCAASTVITSVTINRGLYQ
    YWGQGTQVTVSS
  • In some embodiments, a VHH described herein can be humanized to contain human framework regions. Examples of human germlines that could be used to create humanized VHHs include, but are not limited to, VH3-23 (e.g., UniProt ID: P01764), VH3-74 (e.g., UniProt ID: A0A0B4J1X5), VH3-66 (e.g., UniProt ID: A0A0C4DH42), VH3-30 (e.g., UniProt ID: P01768), VH3-11 (e.g., UniProt ID: P01762), and VH3-9 (e.g., UniProt ID: P01782).
  • In some embodiments, the IL27R binding protein has a reduced Emax compared to the Emax caused by IL27. Emax reflects the maximum response level in a cell type that can be obtained by a ligand (e.g., a binding protein described herein or the native cytokine (e.g., IL27)). In some embodiments, the IL27R binding protein described herein has at least 1% (e.g., between 1% and 100%, between 10% and 100%, between 20% and 100%, between 30% and 100%, between 40% and 100%, between 50% and 100%, between 60% and 100%, between 70% and 100%, between 80% and 100%, between 90% and 100%, between 1% and 90%, between 1% and 80%, between 1% and 70%, between 1% and 60%, between 1% and 50%, between 10% and 40%, between 10% and 30%, between 10% and 20%, or between 10% and 10%) of the Emax caused by IL27. In other embodiments, the Emax of the IL27R binding protein described herein is greater (e.g., at least 1%, 5%, 10, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% greater) than the Emax of the natural ligand, IL27. In some embodiments, by varying the linker length of the IL27R binding protein, the Emax of the IL27R binding protein can be changed. The IL27R binding protein can cause Emax in the most desired cell types, and a reduced Emax in other cell types.
    • IV. Linkers
  • As previously described, the binding domains of the binding proteins of the present disclosure may be joined contiguously (e.g., the C-terminal amino acid of the first VHH in the binding protein to the N-terminal amino acid of the second VHH in the binding protein) or the binding domains of the binding protein may optionally be joined via a linker. A linker is a linkage between two elements, e.g., protein domains. In a bispecific VHH2 binding protein described herein, a linker is a linkage between the two VHHs in the binding protein. A linker can be a covalent bond or a peptide linker. In some embodiments, the two VHHs in a binding protein are joined directly (i.e., via a covalent bond). The length of the linker between two VHHs in a binding protein can be used to modulate the proximity of the two VHHs of the binding protein. By varying the length of the linker, the overall size and length of the binding protein can be tailored to bind to specific cell receptors or domains or subunits thereof. For example, if the binding protein is designed to bind to two receptors or domains or subunits thereof that are located close to each other on the same cell, then a short linker can be used. In another example, if the binding protein is designed to bind to two receptors or domains or subunits there of that are located on two different cells, then a long linker can be used.
  • In some embodiments, the linker is a peptide linker. A peptide linker can include between 1 and 50 amino acids (e.g., between 2 and 50, between 5 and 50, between 10 and 50, between 15 and 50, between 20 and 50, between 25 and 50, between 30 and 50, between 35 and 50, between 40 and 50, between 45 and 50, between 2 and 45, between 2 and 40, between 2 and 35, between 2 and 30, between 2 and 25, between 2 and 20, between 2 and 15, between 2 and 10, between 2 and 5 amino acids). A linker can also be a chemical linker, such as a synthetic polymer, e.g., a polyethylene glycol (PEG) polymer.
  • In some embodiments, a linker joins the C-terminus of the first VHH in the binding protein to the N-terminus of the second VHH in the binding protein. In other embodiments, a linker joins the C-terminus of the second VHH in the binding protein to the N-terminus of the first VHH in the binding protein.
  • Suitable peptide linkers are known in the art, and include, for example, peptide linkers containing flexible amino acid residues such as glycine and serine. In certain embodiments, a peptide linker can contain motifs, e.g., multiple or repeating motifs, of GS, GGS, GGGGS (SEQ ID NO:85), GGGGGS (SEQ ID NO:86), GGSG (SEQ ID NO:87), or SGGG (SEQ ID NO:88). In certain embodiments, a peptide linker can contain 2 to 12 amino acids including motifs of GS, e.g., GS, GSGS (SEQ ID NO:89), GSGSGS (SEQ ID NO:90), GSGSGSGS (SEQ ID NO:91), GSGSGSGSGS (SEQ ID NO:92), or GSGSGSGSGSGS (SEQ ID NO:93). In certain other embodiments, a peptide linker can contain 3 to 12 amino acids including motifs of GGS, e.g., GGS, GGSGGS (SEQ ID NO:94), GGSGGSGGS (SEQ ID NO:95), and GGSGGSGGSGGS (SEQ ID NO:96). In yet other embodiments, a peptide linker can contain 4 to 20 amino acids including motifs of GGSG (SEQ ID NO:87), e.g., GGSGGGSG (SEQ ID NO:97), GGSGGGSGGGSG (SEQ ID NO:98), GGSGGGSGGGSGGGSG (SEQ ID NO:99), or GGSGGGSGGGSGGGSGGGSG (SEQ ID NO:100). In other embodiments, a peptide linker can contain motifs of GGGGS (SEQ ID NO:85), e.g., GGGGSGGGGS (SEQ ID NO:101) or GGGGSGGGGSGGGGS (SEQ ID NO:102).
  • Examples of flexible linkers include glycine polymers (G)n, glycine-alanine polymers, alanine-serine polymers, glycine-serine polymers (for example, (GmSo)n (SEQ ID NO: 1535), (GSGGS)n (SEQ ID NO: 1536), (GmSoGm)n (SEQ ID NO: 1537), (GmSoGmSoGm)n (SEQ ID NO: 1538), (GSGGSm)n (SEQ ID NO: 1539), (GSGSmG)n (SEQ ID NO: 1540), (GGS)nG (SEQ ID NO: 1541) and (GGGSm)n (SEQ ID NO: 1542), and combinations thereof, where m, n, and o are each independently selected from an integer of at least 1 to 20, e.g., 1-18, 216, 3-14, 4-12, 5-10, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10), and other flexible linkers. Glycine and glycine-serine polymers are relatively unstructured, and therefore may serve as a neutral tether between components. Examples of flexible linkers include, but are not limited to GGSG (SEQ ID NO:87), GGSGG (SEQ ID NO:103), GSGSG (SEQ ID NO:104), GSGGG (SEQ ID NO: 105), GGGSG (SEQ ID NO: 106), and GSSSG (SEQ ID NO: 107).
  • Additional examples of flexible linkers include glycine polymers (G)n or glycine-serine polymers (e.g., (GS)n (SEQ ID NO: 1543), (GSGGS)n (SEQ ID NO: 1544), (GGGS)n (SEQ ID NO: 1545) and (GGGGS)n (SEQ ID NO: 1546), where n=1 to 50, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 10-20, 20-30, 30-50). Exemplary flexible linkers include, but are not limited to GGGS (SEQ ID NO:108), GGGGS (SEQ ID NO:85), GGSG (SEQ ID NO:87), GGSGG (SEQ ID NO:103), GSGSG (SEQ ID NO:104), GSGGG (SEQ ID NO:105), GGGSG (SEQ ID NO:106), and GSSSG (SEQ ID NO:107).
    • V. Modifications to Extend Duration of Action In Vivo
  • The binding proteins described herein can be modified to provide for an extended lifetime in vivo and/or extended duration of action in a subject. In some embodiments, the binding protein can be conjugated to carrier molecules to provide desired pharmacological properties such as an extended half-life. In some embodiments, the binding protein can be covalently linked to the Fc domain of IgG, albumin, or other molecules to extend its half-life, e.g., by pegylation, glycosylation, and the like as known in the art.
  • In some embodiments, the binding protein is conjugated to a functional domain of an Fc-fusion chimeric polypeptide molecule. Fc fusion conjugates have been shown to increase the systemic half-life of biopharmaceuticals, and thus the biopharmaceutical product can require less frequent administration. Fc binds to the neonatal Fc receptor (FcRn) in endothelial cells that line the blood vessels, and, upon binding, the Fc fusion molecule is protected from degradation and re-released into the circulation, keeping the molecule in circulation longer. This Fc binding is believed to be the mechanism by which endogenous IgG retains its long plasma half-life. More recent Fc-fusion technology links a single copy of a biopharmaceutical to the Fc region of an antibody to optimize the pharmacokinetic and pharmacodynamic properties of the biopharmaceutical as compared to traditional Fc-fusion conjugates. The “Fc region” useful in the preparation of Fc fusions can be a naturally occurring or synthetic polypeptide that is homologous to an IgG C-terminal domain produced by digestion of IgG with papain. IgG Fc has a molecular weight of approximately 50 kDa. The binding protein described herein can be conjugated to the entire Fc region, or a smaller portion that retains the ability to extend the circulating half-life of a chimeric polypeptide of which it is a part. In addition, full-length or fragmented Fc regions can be variants of the wild-type molecule. In a typical presentation, each monomer of the dimeric Fc can carry a heterologous polypeptide, the heterologous polypeptides being the same or different.
  • In some embodiments, when the binding protein described herein is to be administered in the format of an Fc fusion, particularly in those situations when the polypeptide chains conjugated to each subunit of the Fe dimer are different, the Fc fusion may be engineered to possess a “knob-into-hole modification.” The knob-into-hole modification is more fully described in Ridgway, et al. (1996) Protein Engineering 9(7):617-621 and U.S. Pat. No. 5,731,168, issued Mar. 24, 1998. The knob-into-hole modification refers to a modification at the interface between two immunoglobulin heavy chains in the CH3 domain, wherein: i) in a CH3 domain of a first heavy chain, an amino acid residue is replaced with an amino acid residue having a larger side chain (e.g., tyrosine or tryptophan) creating a projection from the surface (“knob”), and ii) in the CH3 domain of a second heavy chain, an amino acid residue is replaced with an amino acid residue having a smaller side chain (e.g., alanine or threonine), thereby generating a cavity (“hole”) at interface in the second CH3 domain within which the protruding side chain of the first CH3 domain (“knob”) is received by the cavity in the second CH3 domain. In one embodiment, the “knob-into-hole modification” comprises the amino acid substitution T366W and optionally the amino acid substitution S354C in one of the antibody heavy chains, and the amino acid substitutions T366S, L368A, Y407V and optionally Y349C in the other one of the antibody heavy chains. Furthermore, the Fe domains may be modified by the introduction of cysteine residues at positions S354 and Y349 which results in a stabilizing disulfide bridge between the two antibody heavy chains in the Fc region (Carter, et al. (2001) Immunol Methods 248, 7-15). The knob-into-hole format is used to facilitate the expression of a first polypeptide on a first Fc monomer with a “knob” modification and a second polypeptide on the second Fc monomer possessing a “hole” modification to facilitate the expression of heterodimeric polypeptide conjugates.
  • In some embodiments, the binding protein can be conjugated to one or more water-soluble polymers. Examples of water soluble polymers useful in the practice of the present disclosure include polyethylene glycol (PEG), poly-propylene glycol (PPG), polysaccharides (polyvinylpyrrolidone, copolymers of ethylene glycol and propylene glycol, poly(oxyethylated polyol), polyolefinic alcohol,), polysaccharides), poly-alpha-hydroxy acid), polyvinyl alcohol (PVA), polyphosphazene, polyoxazolines (POZ), poly(N-acryloylmorpholine), or a combination thereof.
  • In some embodiments, binding protein can be conjugated to one or more polyethylene glycol molecules or “PEGylated.” Although the method or site of PEG attachment to the binding protein may vary, in certain embodiments the PEGylation does not alter, or only minimally alters, the activity of the binding protein.
  • In some instances, when employing the VHH sequences describe herein in the preparation of th IL27 binding molecules of the present disclosure, the VHH possesses an N-terminal glutamine (“1Q”) residue. N-terminal glutamine residues have been observed to spontaneously cyclyize to form pyroglutamate (pE) at or near physiological conditions. (See e.g., Liu, et al (2011) J. Biol. Chem. 286(13): 11211-11217). In some embodiments, the formation of pyroglutamate complicates N-terminal PEG conjugation particularly when aldehyde chemistry is used for N-terminal PEGylation. Consequently, when PEGylating the IL27R binding molecules of the present disclosure, particularly when aldehyde chemistry is to be employed, the IL27Rα binding molecules possessing an amino acid at position 1 (e.g., 1Q) are substituted at position 1 with an alternative amino acid or are deleted at position 1 (e.g., des-1Q). In some embodiments, the IL27R binding molecules of the present disclosure comprise an amino acid substitution selected from the group Q1E and Q1D.
  • In some embodiments, selective PEGylation of the binding protein, for example, by the incorporation of non-natural amino acids having side chains to facilitate selective PEG conjugation, may be employed. Specific PEGylation sites can be chosen such that PEGylation of the binding protein does not affect its binding to the target receptors.
  • In certain embodiments, the increase in half-life is greater than any decrease in biological activity. PEGs suitable for conjugation to a polypeptide sequence are generally soluble in water at room temperature, and have the general formula R(O—CH2—CH2)nO—R, where R is hydrogen or a protective group such as an alkyl or an alkanol group, and where n is an integer from 1 to 1000. When R is a protective group, it generally has from 1 to 8 carbons.
  • The PEG conjugated to the polypeptide sequence can be linear or branched. Branched PEG derivatives, “star-PEGs” and multi-armed PEGs are contemplated by the present disclosure.
  • A molecular weight of the PEG used in the present disclosure is not restricted to any particular range. The PEG component of the binding protein can have a molecular mass greater than about 5 kDa, greater than about 10 kDa, greater than about 15 kDa, greater than about 20 kDa, greater than about 30 kDa, greater than about 40 kDa, or greater than about 50 kDa. In some embodiments, the molecular mass is from about 5 kDa to about 10 kDa, from about 5 kDa to about 15 kDa, from about 5 kDa to about 20 kDa, from about 10 kDa to about 15 kDa, from about 10 kDa to about 20 kDa, from about 10 kDa to about 25 kDa, or from about 10 kDa to about 30 kDa. Linear or branched PEG molecules having molecular weights from about 2,000 to about 80,000 daltons, alternatively about 2,000 to about 70,000 daltons, alternatively about 5,000 to about 50,000 daltons, alternatively about 10,000 to about 50,000 daltons, alternatively about 20,000 to about 50,000 daltons, alternatively about 30,000 to about 50,000 daltons, alternatively about 20,000 to about 40,000 daltons, or alternatively about 30,000 to about 40,000 daltons. In one embodiment of the disclosure, the PEG is a 40 kD branched PEG comprising two 20 kD arms.
  • The present disclosure also contemplates compositions of conjugates wherein the PEGs have different n values, and thus the various different PEGs are present in specific ratios. For example, some compositions comprise a mixture of conjugates where n=1, 2, 3 and 4. In some compositions, the percentage of conjugates where n=1 is 18-25%, the percentage of conjugates where n=2 is 50-66%, the percentage of conjugates where n=3 is 12-16%, and the percentage of conjugates where n=4 is up to 5%. Such compositions can be produced by reaction conditions and purification methods known in the art. Chromatography may be used to resolve conjugate fractions, and a fraction is then identified which contains the conjugate having, for example, the desired number of PEGs attached, purified free from unmodified protein sequences and from conjugates having other numbers of PEGs attached.
  • PEGs suitable for conjugation to a polypeptide sequence are generally soluble in water at room temperature, and have the general formula R(O—CH2—CH2)nO—R, where R is hydrogen or a protective group such as an alkyl or an alkanol group, and where n is an integer from 1 to 1000. When R is a protective group, it generally has from 1 to 8 carbons.
  • Two widely used first generation activated monomethoxy PEGs (mPEGs) are succinimdyl carbonate PEG (SC-PEG; see, e.g., Zalipsky, et al. (1992) Biotehnol. Appl. Biochem 15:100-114) and benzotriazole carbonate PEG (BTC-PEG; see, e.g., Dolence, et al. U.S. Pat. No. 5,650,234), which react preferentially with lysine residues to form a carbamate linkage but are also known to react with histidine and tyrosine residues. Use of a PEG-aldehyde linker targets a single site on the N-terminus of a polypeptide through reductive amination.
  • Pegylation most frequently occurs at the α-amino group at the N-terminus of the polypeptide, the epsilon amino group on the side chain of lysine residues, and the imidazole group on the side chain of histidine residues. Since most recombinant polypeptides possess a single alpha and a number of epsilon amino and imidazole groups, numerous positional isomers can be generated depending on the linker chemistry. General PEGylation strategies known in the art can be applied herein.
  • The PEG can be bound to a binding protein of the present disclosure via a terminal reactive group (a “spacer”) which mediates a bond between the free amino or carboxyl groups of one or more of the polypeptide sequences and polyethylene glycol. The PEG having the spacer which can be bound to the free amino group includes N-hydroxysuccinylimide polyethylene glycol, which can be prepared by activating succinic acid ester of polyethylene glycol with N-hydroxysuccinylimide.
  • In some embodiments, the PEGylation of the binding proteins is facilitated by the incorporation of non-natural amino acids bearing unique side chains to facilitate site specific PEGylation. The incorporation of non-natural amino acids into polypeptides to provide functional moieties to achieve site specific PEGylation of such polypeptides is known in the art. See e.g., Ptacin et al., PCT International Application No. PCT/US2018/045257 filed Aug. 3, 2018 and published Feb. 7, 2019 as International Publication Number WO 2019/028419A1.
  • The PEG conjugated to the polypeptide sequence can be linear or branched. Branched PEG derivatives, “star-PEGs” and multi-armed PEGs are contemplated by the present disclosure. Specific embodiments PEGs useful in the practice of the present disclosure include a 10 kDa linear PEG-aldehyde (e.g., Sunbright® ME-100AL, NOF America Corporation, One North Broadway, White Plains, NY 10601 USA), 10 kDa linear PEG-NHS ester (e.g., Sunbright® ME-100CS, Sunbright® ME-100AS, Sunbright® ME-100GS, Sunbright® ME-100HS, NOF), a 20 kDa linear PEG-aldehyde (e.g., Sunbright® ME-200AL, NOF), a 20 kDa linear PEG-NHS ester (e.g., Sunbright® ME-200CS, Sunbright® ME-200AS, Sunbright® ME-200GS, Sunbright® ME-200HS, NOF), a 20 kDa 2-arm branched PEG-aldehyde the 20 kDA PEG-aldehyde comprising two 10 kDA linear PEG molecules (e.g., Sunbright® GL2-200AL3, NOF), a 20 kDa 2-arm branched PEG-NHS ester the 20 kDA PEG-NHS ester comprising two 10 kDA linear PEG molecules (e.g., Sunbright® GL2-200TS, Sunbright® GL200GS2, NOF), a 40 kDa 2-arm branched PEG-aldehyde the 40 kDA PEG-aldehyde comprising two 20 kDA linear PEG molecules (e.g., Sunbright® GL2-400AL3), a 40 kDa 2-arm branched PEG-NHS ester the 40 kDA PEG-NHS ester comprising two 20 kDA linear PEG molecules (e.g., Sunbright® GL2-400AL3, Sunbright® GL2-400GS2, NOF), a linear 30 kDa PEG-aldehyde (e.g., Sunbright® ME-300AL) and a linear 30 kDa PEG-NHS ester.
  • In some embodiments, a linker can used to join the binding protein and the PEG molecule. Suitable linkers include “flexible linkers” which are generally of sufficient length to permit some movement between the modified polypeptide sequences and the linked components and molecules. The linker molecules are generally about 6-50 atoms long. The linker molecules may also be, for example, aryl acetylene, ethylene glycol oligomers containing 2-10 monomer units, diamines, diacids, amino acids, or combinations thereof. Suitable linkers can be readily selected and can be of any suitable length, such as 1 amino acid (e.g., Gly), 2, 3, 4, 5, 6, 7, 8, 9, 10, 10-20, 20-30, 30-50 or more than 50 amino acids. Examples of flexible linkers are described in Section IV. Further, a multimer (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 10-20, 20-30, or 30-50) of these linker sequences may be linked together to provide flexible linkers that may be used to conjugate two molecules. Alternative to a polypeptide linker, the linker can be a chemical linker, e.g., a PEG-aldehyde linker. In some embodiments, the binding protein is acetylated at the N-terminus by enzymatic reaction with N-terminal acetyltransferase and, for example, acetyl CoA. Alternatively, or in addition to N-terminal acetylation, the binding protein can be acetylated at one or more lysine residues, e.g., by enzymatic reaction with a lysine acetyltransferase. See, for example Choudhary et al. (2009) Science 325 (5942):834-840.
  • In other embodiments, the binding protein can be modified to include an additional polypeptide sequence that functions as an antigenic tag, such as a FLAG sequence. FLAG sequences are recognized by biotinylated, highly specific, anti-FLAG antibodies, as described herein (see e.g., Blanar et al. (1992) Science 256:1014 and LeClair, et al. (1992) PNAS-USA 89:8145). In some embodiments, the binding protein further comprises a C-terminal c-myc epitope tag.
  • In some embodiments, the binding protein is expressed as a fusion protein with an albumin molecule (e.g., human serum albumin) which is known in the art to facilitate extended exposure in vivo.
  • In some embodiment, the binding proteins (including fusion proteins of the binding proteins) of the present disclosure are expressed as a fusion protein with one or more transition metal chelating polypeptide sequences. The incorporation of such a transition metal chelating domain facilitates purification immobilized metal affinity chromatography (IMAC) as described in Smith, et al. U.S. Pat. No. 4,569,794 issued Feb. 11, 1986. Examples of transition metal chelating polypeptides useful in the practice of the present disclosure are described in Smith, et al. supra and Dobeli, et al. U.S. Pat. No. 5,320,663 issued May 10, 1995, the entire teachings of which are hereby incorporated by reference. Particular transition metal chelating polypeptides useful in the practice of the present disclosure are peptides comprising 3-6 contiguous histidine residues (SEQ ID NO: 1547) such as a six-histidine peptide (His)6 (SEQ ID NO: 1531) and are frequently referred to in the art as “His-tags.”
  • The foregoing fusion proteins may be readily produced by recombinant DNA methodology by techniques known in the art by constructing a recombinant vector comprising a nucleic acid sequence comprising a nucleic acid sequence encoding the binding protein in frame with a nucleic acid sequence encoding the fusion partner either at the N-terminus or C-terminus of the binding protein, the sequence optionally further comprising a nucleic acid sequence in frame encoding a linker or spacer polypeptide.
    • VI. Pharmaceutical Composition
  • The binding proteins of the present disclosure may be administered to a subject in a pharmaceutically acceptable dosage form. The preferred formulation depends on the intended mode of administration and therapeutic application. Pharmaceutical dosage forms of the binding proteins described herein comprise physiologically acceptable carriers that are inherently non-toxic and non-therapeutic. Examples of such carriers include ion exchangers, alumina, aluminum stearate, lecithin, serum proteins, such as human serum albumin, buffer substances such as phosphates, glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salts, or electrolytes such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinyl pyrrolidone, cellulose-based substances, and PEG. Carriers for topical or gel-based forms of polypeptides include polysaccharides such as sodium carboxymethylcellulose or methylcellulose, polyvinylpyrrolidone, polyacrylates, polyoxyethylene-polyoxypropylene-block polymers, PEG, polymeric amino acids, amino acid copolymers, and lipid aggregates (such as oil droplets or liposomes).
  • The pharmaceutical compositions may also comprise pharmaceutically-acceptable, non-toxic carriers, excipients, stabilizers, or diluents, which are defined as vehicles commonly used to formulate pharmaceutical compositions for animal or human administration. The diluent is selected so as not to affect the biological activity of the combination. Acceptable carriers, excipients, or stabilizers are non-toxic to recipients at the dosages and concentrations employed, and include buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid and methionine; preservatives (such as octadecyidimethylbenzyl ammonium chloride; hexamethonium chloride; benzalkonium chloride, benzethonium chloride; phenol, butyl or benzyl alcohol; alkyl parabens such as methyl or propyl paraben; catechol; resorcinol; cyclohexanol; 3-pentanol; and m-cresol); low molecular weight (less than about 10 residues) polypeptides; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arginine, or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugars such as sucrose, mannitol, trehalose or sorbitol; salt-forming counter-ions such as sodium; metal complexes (e.g., Zn-protein complexes); and/or non-ionic surfactants such as TWEEN™, PLURONICS™ or polyethylene glycol (PEG).
  • Formulations to be used for in vivo administration are typically sterile. Sterilization of the compositions of the present disclosure may readily accomplished by filtration through sterile filtration membranes.
  • Typically, compositions are prepared as injectables, either as liquid solutions or suspensions; solid forms suitable for solution in, or suspension in, liquid vehicles prior to injection can also be prepared. The preparation also can be emulsified or encapsulated in liposomes or micro particles such as polylactide, polyglycolide, or copolymer for enhanced adjuvant effect, as discussed above (Langer, Science 249: 1527, 1990 and Hanes, Advanced Drug Delivery Reviews 28: 97-119, 1997). The agents of this disclosure can be administered in the form of a depot injection or implant preparation which can be formulated in such a manner as to permit a sustained or pulsatile release of the active ingredient. The pharmaceutical compositions are generally formulated as sterile, substantially isotonic and in full compliance with all Good Manufacturing Practice (GMP) regulations of the U.S. Food and Drug Administration.
  • Administration of a binding protein described herein may be achieved through any of a variety of art recognized methods including but not limited to the topical, intravascular injection (including intravenous or intraarterial infusion), intradermal injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, intracranial injection, intratumoral injection, intranodal injection, transdermal, transmucosal, iontophoretic delivery, intralymphatic injection (Senti and Kundig (2009) Current Opinions in Allergy and Clinical Immunology 9(6):537-543), intragastric infusion, intraprostatic injection, intravesical infusion (e.g., bladder), respiratory inhalers including nebulizers, intraocular injection, intraabdominal injection, intralesional injection, intraovarian injection, intracerebral infusion or injection, intracerebroventricular injection (ICVI), and the like. In some embodiments, administration includes the administration of the binding protein itself (e.g., parenteral), as well as the administration of a recombinant vector (e.g., viral or non-viral vector) to cause the in situ expression of the binding protein in the subject. Alternatively, a cell, such as a cell isolated from the subject, could also be recombinantly modified to express the binding protein of the present disclosure.
  • The dosage of the pharmaceutical compositions depends on factors including the route of administration, the disease to be treated, and physical characteristics, e.g., age, weight, general health, of the subject. Typically, the amount of a binding protein contained within a single dose may be an amount that effectively prevents, delays, or treats the disease without inducing significant toxicity. A pharmaceutical composition of the disclosure may include a dosage of a binding protein described herein ranging from 0.01 to 500 mg/kg (e.g., from 0.01 to 450 mg, from 0.01 to 400 mg, from 0.01 to 350 mg, from 0.01 to 300 mg, from 0.01 to 250 mg, from 0.01 to 200 mg, from 0.01 to 150 mg, from 0.01 to 100 mg, from 0.01 to 50 mg, from 0.01 to 10 mg, from 0.01 to 1 mg, from 0.1 to 500 mg/kg, from 1 to 500 mg/kg, from 5 to 500 mg/kg, from 10 to 500 mg/kg, from 50 to 500 mg/kg, from 100 to 500 mg/kg, from 150 to 500 mg/kg, from 200 to 500 mg/kg, from 250 to 500 mg/kg, from 300 to 500 mg/kg, from 350 to 500 mg/kg, from 400 to 500 mg/kg, or from 450 to 500 mg/kg) and, in a more specific embodiment, about 1 to about 100 mg/kg (e.g., about 1 to about 90 mg/kg, about 1 to about 80 mg/kg, about 1 to about 70 mg/kg, about 1 to about 60 mg/kg, about 1 to about 50 mg/kg, about 1 to about 40 mg/kg, about 1 to about 30 mg/kg, about 1 to about 20 mg/kg, about 1 to about 10 mg/kg, about 10 to about 100 mg/kg, about 20 to about 100 mg/kg, about 30 to about 100 mg/kg, about 40 to about 100 mg/kg, about 50 to about 100 mg/kg, about 60 to about 100 mg/kg, about 70 to about 100 mg/kg, about 80 to about 100 mg/kg, or about 90 to about 100 mg/kg). In some embodiments, a pharmaceutical composition of the disclosure may include a dosage of a binding protein described herein ranging from 0.01 to 20 mg/kg (e.g., from 0.01 to 15 mg/kg, from 0.01 to 10 mg/kg, from 0.01 to 8 mg/kg, from 0.01 to 6 mg/kg, from 0.01 to 4 mg/kg, from 0.01 to 2 mg/kg, from 0.01 to 1 mg/kg, from 0.01 to 0.1 mg/kg, from 0.01 to 0.05 mg/kg, from 0.05 to 20 mg/kg, from 0.1 to 20 mg/kg, from 1 to 20 mg/kg, from 2 to 20 mg/kg, from 4 to 20 mg/kg, from 6 to 20 mg/kg, from 8 to 20 mg/kg, from 10 to 20 mg/kg, from 15 to 20 mg/kg). The dosage may be adapted by the physician in accordance with conventional factors such as the extent of the disease and different parameters of the subject.
  • A pharmaceutical composition containing a binding protein described herein can be administered to a subject in need thereof, for example, one or more times (e.g., 1-10 times or more) daily, weekly, monthly, biannually, annually, or as medically necessary. Dosages may be provided in either a single or multiple dosage regimens. The timing between administrations may decrease as the medical condition improves or increase as the health of the patient declines. A course of therapy may be a single dose or in multiple doses over a period of time. In some embodiments, a single dose is used. In some embodiments, two or more split doses administered over a period of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 21, 28, 30, 60, 90, 120 or 180 days are used. Each dose administered in such split dosing protocols may be the same in each administration or may be different. Multi-day dosing protocols over time periods may be provided by the skilled artisan (e.g., physician) monitoring the administration, taking into account the response of the subject to the treatment including adverse effects of the treatment and their modulation as discussed above.
    • VII. Indications
  • Immune Diseases
  • The present disclosure further provides methods of treating a subject suffering from a disease disorder or condition by the administration of a therapeutically effective amount of an IL27R binding protein (or nucleic acid encoding an IL27R binding protein including recombinant viruses encoding the IL27R binding protein) of the present disclosure. Disorders amenable to treatment with IL27R binding proteins (including pharmaceutically acceptable formulations comprising IL27R binding proteins and/or the nucleic acid molecules that encode them including recombinant viruses encoding such IL27R binding proteins) of the present disclosure include inflammatory or autoimmune diseases including but not limited to, viral infections (e.g., AIDS, influenza, chronic HCV, chronic viral hepatitis B, C or D), heliobacter pylori infection, HTLV, organ rejection, graft versus host disease, autoimmune thyroid disease, multiple sclerosis, allergy, asthma, neurodegenerative diseases including Alzheimer's disease, systemic lupus erythramatosis (SLE), autoinflammatory diseases, inflammatory bowel disease (IBD), Crohn's disease, diabetes including Type 1 or type 2 diabetes, inflammation, autoimmune disease, atopic diseases, paraneoplastic autoimmune diseases, cartilage inflammation, arthritis, rheumatoid arthritis, juvenile arthritis, juvenile rheumatoid arthritis, juvenile rheumatoid arthritis, polyarticular juvenile rheumatoid arthritis, systemic onset juvenile rheumatoid arthritis, juvenile ankylosing spondylitis, juvenile enteropathic arthritis, juvenile reactive arthritis, juvenile Reiter's Syndrome, SEA Syndrome (Seronegativity Enthesopathy Arthropathy Syndrome), juvenile dermatomyositis, juvenile psoriatic arthritis, juvenile scleroderma, juvenile systemic lupus erythematosus, juvenile vasculitis, pauciarticular rheumatoidarthritis, polyarticular rheumatoidarthritis, systemic onset rheumatoidarthritis, ankylosing spondylitis, enteropathic arthritis, reactive arthritis, Reiter's syndrome,SEA Syndrome(Seronegativity, Enthesopathy, Arthropathy Syndrome).
  • Other examples of proliferative and/or differentiative disorders amenable to treatment with IL27R binding proteins (including pharmaceutically acceptable formulations comprising IL27R binding proteins and/or the nucleic acid molecules that encode them including recombinant viruses encoding such IL27R binding proteins) of the present disclosure include, but are not limited to, skin disorders. The skin disorder may involve the aberrant activity of a cell or a group of cells or layers in the dermal, epidermal, or hypodermal layer, or an abnormality in the dermal-epidermal junction. For example, the skin disorder may involve aberrant activity of keratinocytes (e.g., hyperproliferative basal and immediately suprabasal keratinocytes), melanocytes, Langerhans cells, Merkel cells, immune cell, and other cells found in one or more of the epidermal layers, e.g., the stratum basale (stratum germinativum), stratum spinosum, stratum granulosum, stratum lucidum or stratum corneum. In other embodiments, the disorder may involve aberrant activity of a dermal cell, for example, a dermal endothelial, fibroblast, immune cell (e.g., mast cell or macrophage) found in a dermal layer, for example, the papillary layer or the reticular layer.
  • Examples of skin disorders include psoriasis, psoriatic arthritis, dermatitis (eczema), for example, exfoliative dermatitis or atopic dermatitis, pityriasis rubra pilaris, pityriasis rosacea, parapsoriasis, pityriasis lichenoiders, lichen planus, lichen nitidus, ichthyosiform dermatosis, keratodermas, dermatosis, alopecia areata, pyoderma gangrenosum, vitiligo, pemphigoid (e.g., ocular cicatricial pemphigoid or bullous pemphigoid), urticaria, prokeratosis, rheumatoid arthritis that involves hyperproliferation and inflammation of epithelial-related cells lining the joint capsule; dermatitises such as seborrheic dermatitis and solar dermatitis; keratoses such as seborrheic keratosis, senile keratosis, actinic keratosis, photo-induced keratosis, and keratosis follicularis; acne vulgaris; keloids and prophylaxis against keloid formation; nevi; warts including verruca, condyloma or condyloma acuminatum, and human papilloma viral (HPV) infections such as venereal warts; leukoplakia; lichen planus; and keratitis. The skin disorder can be dermatitis, e.g., atopic dermatitis or allergic dermatitis, or psoriasis.
  • The compositions of the present disclosure (including pharmaceutically acceptable formulations comprising IL27R binding proteins and/or the nucleic acid molecules that encode them including recombinant viruses encoding such IL27R binding proteins) can also be administered to a patient who is suffering from (or may suffer from) psoriasis or psoriatic disorders. The term “psoriasis” is intended to have its medical meaning, namely, a disease which afflicts primarily the skin and produces raised, thickened, scaling, nonscarring lesions. The lesions are usually sharply demarcated erythematous papules covered with overlapping shiny scales. The scales are typically silvery or slightly opalescent. Involvement of the nails frequently occurs resulting in pitting, separation of the nail, thickening and discoloration. Psoriasis is sometimes associated with arthritis, and it may be crippling. Hyperproliferation of keratinocytes is a key feature of psoriatic epidermal hyperplasia along with epidermal inflammation and reduced differentiation of keratinocytes. Multiple mechanisms have been invoked to explain the keratinocyte hyperproliferation that characterizes psoriasis. Disordered cellular immunity has also been implicated in the pathogenesis of psoriasis. Examples of psoriatic disorders include chronic stationary psoriasis, plaque psoriasis, moderate to severe plaque psoriasis, psoriasis vulgaris, eruptive psoriasis, psoriatic erythroderma, generalized pustular psoriasis, annular pustular psoriasis, or localized pustular psoriasis.
  • Combination of IL27R Binding Proteins with Additional Therapeutic Agents for Autoimmune Disease:
  • The present disclosure provides for the use of the IL27R binding proteins of the present disclosure in combination with one or more additional active agents (“supplementary agents”) in the treatment of autoimmune disease. As used herein, the term “supplementary agents” includes agents that can be administered or introduced separately, for example, formulated separately for separate administration (e.g., as may be provided in a kit) and/or therapies that can be administered or introduced in combination with the IL27R binding proteins.
  • As used herein, the term “in combination with” when used in reference to the administration of multiple agents to a subject refers to the administration of a first agent at least one additional (i.e., second, third, fourth, fifth, etc.) agent to a subject. For purposes of the present invention, one agent (e.g., IL27R binding protein) is considered to be administered in combination with a second agent (e.g. a therapeutic autoimmune antibody such as Humira®) if the biological effect resulting from the administration of the first agent persists in the subject at the time of administration of the second agent such that the therapeutic effects of the first agent and second agent overlap. For example, the therapeutic antibodies are sometimes administered by IV infusion every two weeks (e.g. adalimumab in the treatment of Crohn's disease) while the IL27R binding proteins of the present disclosure may be administered more frequently, e.g. daily, BID, or weekly. However, the administration of the first agent (e.g. entaercept) provides a therapeutic effect over an extended time and the administration of the second agent (e.g. an IL27R binding protein) provides its therapeutic effect while the therapeutic effect of the first agent remains ongoing such that the second agent is considered to be administered in combination with the first agent, even though the first agent may have been administered at a point in time significantly distant (e.g. days or weeks) from the time of administration of the second agent. In one embodiment, one agent is considered to be administered in combination with a second agent if the first and second agents are administered simultaneously (within 30 minutes of each other), contemporaneously or sequentially. In some embodiments, a first agent is deemed to be administered “contemporaneously” with a second agent if first and second agents are administered within about 24 hours of each another, preferably within about 12 hours of each other, preferably within about 6 hours of each other, preferably within about 2 hours of each other, or preferably within about 30 minutes of each other. The term “in combination with” shall also understood to apply to the situation where a first agent and a second agent are co-formulated in single pharmaceutically acceptable formulation and the co-formulation is administered to a subject. In certain embodiments, the IL27R binding protein and the supplementary agent(s) are administered or applied sequentially, e.g, where one agent is administered prior to one or more other agents. In other embodiments, the IL27R binding protein and the supplementary agent(s) are administered simultaneously, e.g., where two or more agents are administered at or about the same time; the two or more agents may be present in two or more separate formulations or combined into a single formulation (i.e., a co-formulation). Regardless of whether the agents are administered sequentially or simultaneously, they are considered to be administered in combination for purposes of the present disclosure.
  • In some embodiments, the supplementary agent is one or more agents selected from the group consisting of corticosteroids (including but not limited to prednisone, budesonide, prednilisone), Janus kinase inhibitors (including but not limited to tofacitinib (Xeljanz®), calcineurin inhibitors (including but not limited to cyclosporine and tacrolimus), mTor inhibitors (including but not limited to sirolimus and everolimus), IMDH inhibitors (including but not limited to azathioprine, leflunomide and mycophenolate), biologics such as abatcept (Orencia®) or etanercept (Enbrel®), and therapeutic antibodies. Examples of therapeutic antibodies that may be administered as supplementary agents in combination with the IL27R binding proteins of the present disclosure in the treatment of autoimmune disease include but are not limited to anti-CD25 antibodies (e.g. daclizumab and basiliximab), anti-VLA-4 antibodies (e.g. natalizumab), anti-CD52 antibodies (e.g. alemtuzumab), anti-CD20 antibodies (e.g. rituximab, ocrelizumab), anti-TNF antibodies (e.g. infliximab, and adalimumab), anti-IL6R antibodies (e.g. tocilizumab), anti-TNFα antibodies (e.g. adalimumab (Humira®), golimumab, and infliximab), anti-integrin-α4β7 antibodies (e.g. vedolizumab), anti-IL17a antibodies (e.g. brodalumab or secukinumab), anti-IL4Rα antibodies (e.g. dupilumab), anti-RANKL antibodies, IL6R antibodies, anti-IL1ß antibodies (e.g. canakinumab), anti-CD11a antibodies (e.g. efalizumab), anti-CD3 antibodies (e.g. muramonab), anti-IL5 antibodies (e.g. mepolizumab, reslizumab), anti-BLyS antibodies (e.g. belimumab); and anti-IL12/IL23 antibodies (e.g ustekinumab).
  • Many therapeutic antibodies have been approved for clinical use against autoimmune disease. Examples of antibodies approved by the United States Food and Drug Administration (FDA) for use in the treatment of autoimmune diseases in a subject suffering therefrom that may be administered as supplementary agents in combination with the IL27R binding proteins of the present disclosure (and optionally additional supplementary agents) for the treatment of the indicated autoimmune disease are provided in Table 4.
  • TABLE 4
    Name Target Indication
    belimumab BLyS Systemic lupus erythematosus
    efalizumab CD11a Psoriasis
    ocrelizumab CD20 Multiple sclerosis
    rituximab CD20 Multiple sclerosis
    basiliximab CD25 Transplantation rejection
    daclizumab CD25 Transplantation rejection
    muromonab CD3 Transplantation rejection
    alemtuzumab CD52 Multiple sclerosis
    omalizumab IgE Asthma
    ustekinumab IL12/IL23 Plaque psoriasis
    brodalumab IL17a Psoriasis, psoriatic arthritis, ankylosing spondylitis
    secukinumab IL17a Psoriasis, psoriatic arthritis, ankylosing spondylitis
    ixekizumab IL17a Psoriasis, psoriatic arthritis, ankylosing spondylitis
    canakinumab IL1ß Cryopyrin-associated periodic syndrome, tumor necrosis factor
    receptor associated periodic syndrome, hyperimmunoglobulin D
    syndrome, mevalonate kinase deficiency, familial Mediterranean fever,
    rheumatoid arthritis
    dupilumab IL4Rα Asthma, dermatitis
    mepolizumab IL5 Asthma
    reslizumab IL5 Asthma
    tocilizumab IL6R Rheumatoid arthritis
    vedolizumab Integrin-α4β7 Ulcerative colitis, Crohn's disease
    denosumab RANKL Osteoporosis
    certolizumab TNFa Chron's disease, rheumatoid arthritis
    golimumab TNFa Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis
    adalimumab TNFα Rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis,
    ankylosing spondylitis, Crohn's disease, plaque psoriasis
    infliximab TNFα Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing
    spondylitis, psoriatic arthritis, plaque psoriasis
    ranibizumab VEGF-A Neovascular age-related macular degeneration, macular edema
    natalizumab VLA-4 Multiple sclerosis, relapsing rultiple sclerosis, Crohn's disease
    • Treatment of Neoplastic Disease
  • The present disclosure provides methods of use of IL-27R binding molecules in the treatment of subjects suffering from a neoplastic disease disorder or condition by the administration of a therapeutically effective amount of a IL-27R binding molecule (or nucleic acid encoding a IL-27R binding molecule including recombinant vectors encoding IL-27R binding molecules, and eucaryotic and procaryotic cells modified to express a IL-27R binding molecule) as described herein.
  • Neoplasms Amenable to Treatment:
  • The compositions and methods of the present disclosure are useful in the treatment of subject suffering from a neoplastic disease characterized by the presence neoplasms, including benign and malignant neoplasms, and neoplastic disease.
  • Examples of benign neoplasms amenable to treatment using the compositions and methods of the present disclosure include but are not limited to adenomas, fibromas, hemangiomas, and lipomas. Examples of pre-malignant neoplasms amenable to treatment using the compositions and methods of the present disclosure include but are not limited to hyperplasia, atypia, metaplasia, and dysplasia. Examples of malignant neoplasms amenable to treatment using the compositions and methods of the present disclosure include but are not limited to carcinomas (cancers arising from epithelial tissues such as the skin or tissues that line internal organs), leukemias, lymphomas, and sarcomas typically derived from bone fat, muscle, blood vessels or connective tissues). Also included in the term neoplasms are viral induced neoplasms such as warts and EBV induced disease (i.e., infectious mononucleosis), scar formation, hyperproliferative vascular disease including intimal smooth muscle cell hyperplasia, restenosis, and vascular occlusion and the like.
  • The term “neoplastic disease” includes cancers characterized by solid tumors and non-solid tumors including but not limited to breast cancers; sarcomas (including but not limited to osteosarcomas and angiosarcomas and fibrosarcomas), leukemias, lymphomas, genitourinary cancers (including but not limited to ovarian, urethral, bladder, and prostate cancers); gastrointestinal cancers (including but not limited to colon esophageal and stomach cancers); lung cancers; myelomas; pancreatic cancers; liver cancers; kidney cancers; endocrine cancers; skin cancers; and brain or central and peripheral nervous (CNS) system tumors, malignant or benign, including gliomas and neuroblastomas, astrocytomas, myelodysplastic disorders; cervical carcinoma-in-situ; intestinal polyposes; oral leukoplakias; histiocytoses, hyperprofroliferative scars including keloid scars, hemangiomas; hyperproliferative arterial stenosis, psoriasis, inflammatory arthritis; hyperkeratoses and papulosquamous eruptions including arthritis.
  • The term neoplastic disease includes carcinomas. The term “carcinoma” refers to malignancies of epithelial or endocrine tissues including respiratory system carcinomas, gastrointestinal system carcinomas, genitourinary system carcinomas, testicular carcinomas, breast carcinomas, prostatic carcinomas, endocrine system carcinomas, and melanomas. The term neoplastic disease includes adenocarcinomas. An “adenocarcinoma” refers to a carcinoma derived from glandular tissue or in which the tumor cells form recognizable glandular structures.
  • As used herein, the term “hematopoietic neoplastic disorders” refers to neoplastic diseases involving hyperplastic/neoplastic cells of hematopoietic origin, e.g., arising from myeloid, lymphoid or erythroid lineages, or precursor cells thereof.
  • Myeloid neoplasms include, but are not limited to, myeloproliferative neoplasms, myeloid and lymphoid disorders with eosinophilia, myeloproliferative/myelodysplastic neoplasms, myelodysplastic syndromes, acute myeloid leukemia and related precursor neoplasms, and acute leukemia of ambiguous lineage. Exemplary myeloid disorders amenable to treatment in accordance with the present disclosure include, but are not limited to, acute promyeloid leukemia (APML), acute myelogenous leukemia (AML) and chronic myelogenous leukemia (CML).
  • Lymphoid neoplasms include, but are not limited to, precursor lymphoid neoplasms, mature B-cell neoplasms, mature T-cell neoplasms, Hodgkin's Lymphoma, and immunodeficiency-associated lymphoproliferative disorders. Exemplary lymphic disorders amenable to treatment in accordance with the present disclosure include, but are not limited to, acute lymphoblastic leukemia (ALL) which includes B-lineage ALL and T-lineage ALL, chronic lymphocytic leukemia (CLL), prolymphocytic leukemia (PLL), hairy cell leukemia (HLL) and Waldenstrom's macroglobulinemia (WM).
  • In some instances, the hematopoietic neoplastic disorder arises from poorly differentiated acute leukemias (e.g., erythroblastic leukemia and acute megakaryoblastic leukemia). As used herein, the term “hematopoietic neoplastic disorders” refers malignant lymphomas including, but are not limited to, non-Hodgkins lymphoma and variants thereof, peripheral T cell lymphomas, adult T-cell leukemia/lymphoma (ATL), cutaneous T cell lymphoma (CTCL), large granular lymphocytic leukemia (LGF), Hodgkin's disease and Reed-Stemberg disease.
  • The determination of whether a subject is “suffering from a neoplastic disease” refers to a determination made by a physician with respect to a subject based on the available information accepted in the field for the identification of a disease, disorder or condition including but not limited to X-ray, CT-scans, conventional laboratory diagnostic tests (e.g. blood count, etc.), genomic data, protein expression data, immunohistochemistry, that the subject requires or will benefit from treatment.
  • Assessing Anti-Neoplastic Efficacy:
  • The determination of efficacy of the methods of the present disclosure in the treatment of cancer is generally associated with the achievement of one or more art recognized parameters such as reduction in lesions particularly reduction of metastatic lesion, reduction in metastasis, reduction in tumor volume, improvement in ECOG score, and the like. Determining response to treatment can be assessed through the measurement of biomarker that can provide reproducible information useful in any aspect of IL-27R binding molecule therapy, including the existence and extent of a subject's response to such therapy and the existence and extent of untoward effects caused by such therapy. By way of example, but not limitation, biomarkers include enhancement of IFNγ, and upregulation of granzyme A, granzyme B, and perforin; increase in CD8+ T-cell number and function; enhancement of IFNγ, an increase in ICOS expression on CD8+ T-cells, enhancement of IL-10 expressing TReg cells. The response to treatment may be characterized by improvements in conventional measures of clinical efficacy may be employed such as Complete Response (CR), Partial Response (PR), Stable Disease (SD) and with respect to target lesions, Complete Response (CR),” Incomplete Response/Stable Disease (SD) as defined by RECIST as well as immune-related Complete Response (irCR), immune-related Partial Response (irPR), and immune-related Stable Disease (irSD) as defined Immune-Related Response Criteria (irRC) are considered by those of skill in the art as evidencing efficacy in the treatment of neoplastic disease in mammalian (e.g. human) subjects.
  • Maintenance of Serum Concentration:
  • In some embodiments of the invention the present disclosure provides methods and compositions for the treatment and/or prevention of neoplastic diseases, disorders or conditions by the administration of a therapeutically effective amount of an IL-27R binding molecules the serum concentration of the IL-27R binding molecule is maintained for a majority (i.e., greater than about 50% of the period of time, alternatively greater than about 60%, alternatively greater than about 70%, alternatively greater than about 80%, alternatively greater than about 90%) of a period of time (e.g. at least 24 hours, alternatively at least 48 hours, alternatively at least 72 hours, alternatively at least 96 hours, alternatively at least 120 hours, alternatively at least 144 hours, alternatively at least 7 days, alternatively at least 10 days, alternatively at least 12 days, alternatively at least 14 days, alternatively at least 28 days, alternatively at least 45 days, alternatively at least 60 days, or longer) at a serum concentration at or above the therapeutically effective concentration with respect to such IL-27R binding molecule.
  • Combination of IL-27R Binding Molecules with Supplementary Therapeutic Agents:
  • The present disclosure provides for the use of the IL-27R binding molecules of the present disclosure in combination with one or more additional active agents (“supplementary agents”). Such further combinations are referred to interchangeably as “supplementary combinations” or “supplementary combination therapy” and those therapeutic agents that are used in combination with IL-27R binding molecules of the present disclosure are referred to as “supplementary agents.” As used herein, the term “supplementary agents” includes agents that can be administered or introduced separately, for example, formulated separately for separate administration (e.g., as may be provided in a kit) and/or therapies that can be administered or introduced in combination with the IL-27R binding molecules.
  • Chemotherapeutic Agents:
  • In some embodiments, the supplementary agent is a chemotherapeutic agent. In some embodiments the supplementary agent is a “cocktail” of multiple chemotherapeutic agents. IN some embodiments the chemotherapeutic agent or cocktail is administered in combination with one or more physical methods (e.g. radiation therapy). The term “chemotherapeutic agents” includes but is not limited to alkylating agents such as thiotepa and cyclosphosphamide; alkyl sulfonates such as busulfan, improsulfan and piposulfan; aziridines such as benzodopa, carboquone, meturedopa, and uredopa; ethylenimines and methylamelamines including altretamine, triethylenemelamine, trietylenephosphoramide, triethylenethiophosphaoramide and trimethyl olomelamime; nitrogen mustards such as chiorambucil, chlomaphazine, cholophosphamide, estramustine, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, melphalan, novembichin, phenesterine, prednimustine, trofosfamide, uracil mustard; nitrosureas such as carmustine, chlorozotocin, fotemustine, lomustine, nimustine, ranimustine; antibiotics such as aclacinomysins, actinomycin, authramycin, azaserine, bleomycins such as bleomycin A2, cactinomycin, calicheamicin, carabicin, caminomycin, carzinophilin, chromomycins, dactinomycin, daunorubicin and derivaties such as demethoxy-daunomycin, 11-deoxydaunorubicin, 13-deoxydaunorubicin, detorubicin, 6-diazo-5-oxo-L-norleucine, doxorubicin, epirubicin, esorubicin, idarubicin, marcellomycin, mitomycins such as mitomycin C, N-methyl mitomycin C; mycophenolic acid, nogalamycin, olivomycins, peplomycin, potfiromycin, puromycin, quelamycin, rodorubicin, streptonigrin, streptozocin, tubercidin, ubenimex, zinostatin, zorubicin; anti-metabolites such as methotrexate and 5-fluorouracil (5-FU); folic acid analogues such as denopterin, methotrexate, pteropterin, trimetrexate, dideazatetrahydrofolic acid, and folinic acid; purine analogs such as fludarabine, 6-mercaptopurine, thiamiprine, thioguanine; pyrimidine analogs such as ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, dideoxyuridine, doxifluridine, enocitabine, floxuridine, 5-FU; androgens such as calusterone, dromostanolone propionate, epitiostanol, mepitiostane, testolactone; anti-adrenals such as aminoglutethimide, mitotane, trilostane; folic acid replenisher such as frolinic acid; aceglatone; aldophosphamide glycoside; aminolevulinic acid; amsacrine; best rabucil; bisantrene; edatraxate; defofamine; demecolcine; diaziquone; elformithine; elliptinium acetate; etoglucid; gallium nitrate; hydroxyurea; lentinan; lonidamine; mitoguazone; mitoxantrone; mopidamol; nitracrine; pentostatin; phenamet; pirarubicin; podophyllinic acid; 2-ethylhydrazide; procarbazine; razoxane; sizofiran; spirogermanium; tenuazonic acid; triaziquone; 2,2′,2″-trichlorotriethylamine; urethan; vindesine; dacarbazine; mannomustine; mitobronitol; mitolactol; pipobroman; gacytosine; arabinoside (Ara-C); cyclophosphamide; thiotepa; taxoids, e.g., paclitaxel, nab-paclitaxel and doxetaxel; chlorambucil; gemcitabine; 6-thioguanine; mercaptopurine; methotrexate; platinum and platinum coordination complexes such as cisplatin, oxaplatin and carboplatin; vinblastine; etoposide (VP-16); ifosfamide; mitomycin C; mitoxantrone; vincristine; vinorelbine; navelbine; novantrone; teniposide; daunomycin; aminopterin; xeloda; ibandronate; CPT11; topoisomerase inhibitors; difluoromethylornithine (DMFO); retinoic acid; esperamicins; capecitabine; taxanes such as paclitaxel, docetaxel, cabazitaxel; carminomycin, adriamycins such as 4′-epiadriamycin, 4-adriamycin-14-benzoate, adriamycin-14-octanoate, adriamycin-14-naphthaleneacetate; cholchicine and pharmaceutically acceptable salts, acids or derivatives of any of the above.
  • The term “chemotherapeutic agents” also includes anti-hormonal agents that act to regulate or inhibit hormone action on tumors such as anti-estrogens, including for example tamoxifen, raloxifene, aromatase inhibiting 4(5)-imidazoles, 4-hydroxytamoxifen, trioxifene, keoxifene, onapristone, and toremifene; and antiandrogens such as flutamide, nilutamide, bicalutamide, leuprolide, and goserelin; and pharmaceutically acceptable salts, acids or derivatives of any of the above.
  • In some embodiments, a supplementary agent isone or more chemical or biological agents identified in the art as useful in the treatment of neoplastic disease, including, but not limited to, a cytokines or cytokine antagonists such as IL-12, INFα, or anti-epidermal growth factor receptor, irinotecan; tetrahydrofolate antimetabolites such as pemetrexed; antibodies against tumor antigens, a complex of a monoclonal antibody and toxin, a T-cell adjuvant, bone marrow transplant, or antigen presenting cells (e.g., dendritic cell therapy), anti-tumor vaccines, replication competent viruses, signal transduction inhibitors (e.g., Gleevec® or Herceptin®) or an immunomodulator to achieve additive or synergistic suppression of tumor growth, non-steroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 (COX-2) inhibitors, steroids, TNF antagonists (e.g., Remicade® and Enbrel®), interferon-β1a (Avonex®), and interferon-β1b (Betaseron®) as well as combinations of one or more of the foreoing as practied in known chemotherapeutic treatment regimens including but not limited to TAC, FOLFOX, TPC, FEC, ADE, FOLFOX-6, EPOCH, CHOP, CMF, CVP, BEP, OFF, FLOX, CVD, TC, FOLFIRI, PCV, FOLFOXIRI, ICE-V, XELOX, and others that are readily appreciated by the skilled clinician in the art.
  • In some embodiments, the IL-27R binding molecule is administered in combination with BRAF/MEK inhibitors, kinase inhibitors such as sunitinib, PARP inhibitors such as olaparib, EGFR inhibitors such as osimertinib (Ahn, et al. (2016) J Thorac Oncol 11 S115), IDO inhibitors such as epacadostat, and oncolytic viruses such as talimogene laherparepvec (T-VEC).
  • Anti-Tumor Antigen Antibody Therapeutics as Supplementary Agents
  • In some embodiments, a “supplementary agent” is a therapeutic antibody (including bi-specific and tri-specific antibodies which bind to one or more tumor associated antigens including but not limited to bispecific T cell engagers (BITEs), dual affinity retargeting (DART) constructs, and trispecific killer engager (TriKE) constructs).
  • In some embodiments, the therapeutic antibody is an antibody that binds to at least one tumor antigen selected from the group consisting of HER2 (e.g. trastuzumab, pertuzumab, ado-trastuzumab emtansine), nectin-4 (e.g. enfortumab), CD79 (e.g. polatuzumab vedotin), CTLA4 (e.g. ipilumumab), CD22 (e.g. moxetumomab pasudotox), CCR4 (e.g. magamuizumab), IL23p19 (e.g. tildrakizumab), PDL1 (e.g. durvalumab, avelumab, atezolizumab), IL17a (e.g. ixekizumab), CD38 (e.g. daratumumab), SLAMF7 (e.g. elotuzumab), CD20 (e.g. rituximab, tositumomab, ibritumomab and ofatumumab), CD30 (e.g. brentuximab vedotin), CD33 (e.g. gemtuzumab ozogamicin), CD52 (e.g. alemtuzumab), EpCam, CEA, fpA33, TAG-72, CAIX, PSMA, PSA, folate binding protein, GD2 (e.g. dinuntuximab), GD3, IL6 (e.g. silutxumab) GM2, Ley, VEGF (e.g. bevacizumab), VEGFR, VEGFR2 (e.g. ramucirumab), PDGFRα (e.g. olartumumab), EGFR (e.g. cetuximab, panitumumab and necitumumab), ERBB2 (e.g. trastuzumab), ERBB3, MET, IGF1R, EPHA3, TRAIL R1, TRAIL R2, RANKL RAP, tenascin, integrin αVβ3, and integrin α4β1.
  • Examples of antibody therapeutics which are FDA approved and may be used as supplementary agents for use in the treatment of neoplastic disease include those provided in the Table below.
  • TABLE
    Approved Antineoplastic Disease Antibodies and Indications
    Name Tradename(s) Target; format Indication
    [fam]- Enhertu ™ HER2; Humanized IgG1 ADC HER2+ breast cancer
    trastuzumab deruxtecan
    Enfortumab vedotin Padcev ™ Nectin-4; Human IgG1 ADC Urothelial cancer
    Polatuzumab vedotin Polivy ™ CD79b; Humanized IgG1 ADC Diffuse large B-cell lymphoma
    Cemiplimab Libtayo ™ PD-1; Human mAb Cutaneous squamous cell
    carcinoma
    Moxetumomab pasudotox Lumoxiti ™ CD22; Murine Hairy cell leukemia
    IgG1 dsFv immunotoxin
    Mogamuizumab Poteligeo ™ CCR4; Humanized IgG1 Cutaneous T cell lymphoma
    Tildrakizumab Ilumya ™ IL23p19; Humanized IgG1 Plaque psoriasis
    Ibalizumab Trogarzo ™ CD4; Humanized IgG4 HIV infection
    Durvalumab IMFINZI ™ PD-L1; Human IgG1 Bladder cancer
    Inotuzumab BESPONSA ™ CD22; Humanized IgG4, ADC Hematological malignancy
    ozogamicin
    Avelumab Bavencio ™ PD-L1; Human IgG1 Merkel cell carcinoma
    Atezolizumab Tecentriq ™ PD-L1; Humanized IgG1 Bladder cancer
    Olaratumab Lartruvo ™ PDGRFα; Human IgG1 Soft tissue sarcoma
    Ixekizumab Taltz ™ IL-17a; Humanized IgG4 Psoriasis
    Daratumumab Darzalex ™ CD38; Human IgG1 Multiple myeloma
    Elotuzumab Empliciti ™ SLAMF7; Humanized IgG1 Multiple myeloma
    Necitumumab Portrazza ™ EGFR; Human IgG1 Non-small cell lung cancer
    Dinutuximab Unituxin ™ GD2; Chimeric IgG1 Neuroblastoma
    Nivolumab Opdivo ™ PD1; Human IgG4 Melanoma, non-small cell lung
    cancer
    Blinatumomab Blincyto ™ CD19, CD3; Murine bispecific Acute lymphoblastic leukemia
    tandem scFv
    Pembrolizumab Keytruda ™ PD1; Humanized IgG4 Melanoma
    Ramucirumab Cyramza ™ VEGFR2; Human IgG1 Gastric cancer
    Siltuximab Sylvant ™ IL-6; Chimeric IgG1 Castleman disease
    Obinutuzumab Gazyva ™ CD20; Humanized IgG1; Chronic lymphocytic leukemia
    Glycoengineered
    Ado-trastuzumab Kadcyla ™ HER2; Humanized IgG1, ADC Breast cancer
    emtansine
    Pertuzumab Perjeta ™ HER2; Humanized IgG1 Breast Cancer
    Brentuximab vedotin Adcetris ™ CD30; Chimeric IgG1, ADC Hodgkin lymphoma, systemic
    anaplastic large cell lymphoma
    Ipilimumab Yervoy ™ CTLA-4; Human IgG1 Metastatic melanoma
    Ofatumumab Arzerra ™ CD20; Human IgG1 Chronic lymphocytic leukemia
    Certolizumab pegol Cimzia ™ TNF; Humanized Fab, Crohn disease
    pegylated
    Catumaxomab Removab ™ EPCAM/CD3; Rat/mouse Malignant ascites
    bispecific mAb
    Panitumumab Vectibix ™ EGFR; Human IgG2 Colorectal cancer
    Bevacizumab Avastin ™ VEGF; Humanized IgG1 Colorectal cancer
    Cetuximab Erbitux ™ EGFR; Chimeric IgG1 Colorectal cancer
    Tositumomab-I131 Bexxar ™ CD20; Murine IgG2a Non-Hodgkin lymphoma
    Ibritumomab tiuxetan Zevalin ™ CD20; Murine IgG1 Non-Hodgkin lymphoma
    Gemtuzumab Mylotarg ™ CD33; Humanized IgG4, ADC Acute myeloid leukemia
    ozogamicin
    Trastuzumab Herceptin ™ HER2; Humanized IgG1 Breast cancer
    Infliximab Remicade ™ TNF; Chimeric IgG1 Crohn disease
    Rituximab MabThera ™, CD20; Chimeric IgG1 Non-Hodgkin lymphoma
    Rituxan ™
    Edrecolomab Panorex ™ EpCAM; Murine IgG2a Colorectal cancer
    • Physical Methods
  • In some embodiments, a supplementary agent is one or more non-pharmacological modalities (e.g., localized radiation therapy or total body radiation therapy or surgery). By way of example, the present disclosure contemplates treatment regimens wherein a radiation phase is preceded or followed by treatment with a treatment regimen comprising a IL-27R binding molecule and one or more supplementary agents. In some embodiments, the present disclosure further contemplates the use of a IL-27R binding molecule in combination with surgery (e.g. tumor resection). In some embodiments, the present disclosure further contemplates the use of a IL-27R binding molecule in combination with bone marrow transplantation, peripheral blood stem cell transplantation or other types of transplantation therapy.
  • Combination with Immune Checkpoint Modulators:
  • In some embodiments, a “supplementary agent” is an immune checkpoint modulator for the treatment and/or prevention neoplastic disease in a subject as well as diseases, disorders or conditions associated with neoplastic disease. The term “immune checkpoint pathway” refers to biological response that is triggered by the binding of a first molecule (e.g. a protein such as PD1) that is expressed on an antigen presenting cell (APC) to a second molecule (e.g. a protein such as PDL1) that is expressed on an immune cell (e.g. a T-cell) which modulates the immune response, either through stimulation (e.g. upregulation of T-cell activity) or inhibition (e.g. downregulation of T-cell activity) of the immune response. The molecules that are involved in the formation of the binding pair that modulate the immune response are commonly referred to as “immune checkpoints.” The biological responses modulated by such immune checkpoint pathways are mediated by intracellular signaling pathways that lead to downstream immune effector pathways, such as cell activation, cytokine production, cell migration, cytotoxic factor secretion, and antibody production. Immune checkpoint pathways are commonly triggered by the binding of a first cell surface expressed molecule to a second cell surface molecule associated with the immune checkpoint pathway (e.g. binding of PD1 to PDL1, CTLA4 to CD28, etc.). The activation of immune checkpoint pathways can lead to stimulation or inhibition of the immune response.
  • As used herein, the term “immune checkpoint pathway modulator” refers to a molecule that inhibits or stimulates the activity of an immune checkpoint pathway in a biological system including an immunocompetent mammal. An immune checkpoint pathway modulator may exert its effect by binding to an immune checkpoint protein (such as those immune checkpoint proteins expressed on the surface of an antigen presenting cell (APC) such as a cancer cell and/or immune T effector cell) or may exert its effect on upstream and/or downstream reactions in the immune checkpoint pathway. For example, an immune checkpoint pathway modulator may modulate the activity of SHP2, a tyrosine phosphatase that is involved in PD-1 and CTLA-4 signaling. The term “immune checkpoint pathway modulators” encompasses both immune checkpoint pathway modulator(s) capable of down-regulating at least partially the function of an inhibitory immune checkpoint (referred to herein as an “immune checkpoint pathway inhibitor” or “immune checkpoint pathway antagonist”) and immune checkpoint pathway modulator(s) capable of up-regulating at least partially the function of a stimulatory immune checkpoint (referred to herein as an “immune checkpoint pathway effector” or “immune checkpoint pathway agonist.”).
  • Immune checkpoint modulators include but are not limited to immune checkpoint antagonists (e.g. antagonist antibodies) that bind T-cell inhibitory receptors including but not limited to PD1 (also referred to as CD279), TIM3 (T-cell membrane protein 3; also known as HAVcr2), BTLA (B and T lymphocyte attenuator; also known as CD272), the VISTA (B7-H5) receptor, LAG3 (lymphocyte activation gene 3; also known as CD233) and CTLA4 (cytotoxic T-lymphocyte associated antigen 4; also known as CD152). In some embodiments, immune checkpoint modulators are agonists that trigger the checkpoint pathway resulting stimulation of the immune response. Examples of such agonist immune checkpoint modulators include, but is not limited to, agonist that modulate the binding of ICOSL to ICOS(CD278), B7-H6 to NKp30, CD155 to CD96, OX40L to OX40, CD70 to CD27, CD40 to CD40L, and GITRL to GITR. Examples of such positive immune checkpoint agonists include but are not limited to agonist antibodies that bind T-cell activating receptors such as ICOS (such as JTX-2011, Jounce Therapeutics), OX40 (such as MEDI6383, Medimmune), CD27 (such as varlilumab, Celldex Therapeutics), CD40 (such as dacetuzmumab CP-870,893, Roche, Chi Lob 7/4), HVEM, CD28, CD137 4-1BB, CD226, and GITR (such as MEDI1873, Medimmune; INCAGN1876, Agenus).
  • Exemplary negative immune checkpoint pathway inhibitors include but are not limited to programmed death-1 (PD1) pathway inhibitors, programed death ligand-1 (PDL1) pathway inhibitors, TIM3 pathway inhibitors and anti-cytotoxic T-lymphocyte antigen 4 (CTLA4) pathway inhibitors.
  • In one embodiment, the immune checkpoint pathway modulator is an antagonist of a negative immune checkpoint pathway that inhibits the binding of PD1 to PDL1 and/or PDL2 (“PD1 pathway inhibitor). The term PD1 pathway inhibitors includes monoclonal antibodies that interfere with the binding of PD1 to PDL1 and/or PDL2. Examples of commercially available PD1 pathway inhibitors useful as supplementary agents in the treatment of neoplastic disease include antibodies that interfere with the binding of PD1 to PDL1 and/or PDL2 including but not limited to nivolumab (Opdivo®, BMS-936558, MDX1106, commercially available from BristolMyers Squibb, Princeton NJ), pembrolizumab (Keytruda®MK-3475, lambrolizumab, commercially available from Merck and Company, Kenilworth NJ), and atezolizumab (Tecentriq®, Genentech/Roche, South San Francisco CA). Additional PD1 pathway inhibitors antibodies are in clinical development including but not limited to durvalumab (MEDI4736, Medimmune/AstraZeneca), pidilizumab (CT-011, CureTech), PDR001 (Novartis), BMS-936559 (MDX1105, BristolMyers Squibb), and avelumab (MSB0010718C, Merck Serono/Pfizer) and SHR-1210 (Incyte). Additional antibody PD1 pathway inhibitors are described in U.S. Pat. No. 8,217,149 (Genentech, Inc) issued Jul. 10, 2012; U.S. Pat. No. 8,168,757 (Merck Sharp and Dohme Corp.) issued May 1, 2012, U.S. Pat. No. 8,008,449 (Medarex) issued Aug. 30, 2011, U.S. Pat. No. 7,943,743 (Medarex, Inc) issued May 17, 2011.
  • The term PD1 pathway inhibitors are not limited to antagonist antibodies. Non-antibody biologic PD1 pathway inhibitors are also under clinical development including AMP-224, a PD-L2 IgG2a fusion protein, and AMP-514, a PDL2 fusion protein, are under clinical development by Amplimmune and Glaxo SmithKline), aptamers (Wang, et al. (2018) 145:125-130), peptide PD1 pathway inhibitors (Sasikumar, et al., U.S. Pat. No. 9,422,339 issued Aug. 23, 2016, and Sasilkumar, et al., U.S. Pat. No. 8,907,053 issued Dec. 9, 2014), small molecules (CA-170, AUPM-170, Aurigene/Curis; Sasikumar, et al., 1,2,4-oxadiazole and thiadiazole compounds as immunomodulators (PCT/IB2016/051266 filed Mar. 7, 2016, published as WO2016142833A1 Sep. 15, 2016) and Sasikumar, et al PCT/IB2016/051343 filed Mar. 9, 2016 and published as WO2016142886A2), BMS-1166 and Chupak LS and Zheng X. (2015) WO 2015/034820 A1, EP3041822 B1 granted Aug. 9, 2017; WO2015034820 A1; and Chupak, et al. 2015) WO 2015/160641 A2. WO 2015/160641 A2, Chupak, et al. Sharpe, et al. WO 2011082400 A2 published Jul. 7, 2011; U.S. Pat. No. 7,488,802 issued Feb. 10, 2009;
  • In some embodiments, the IL-27R binding molecule is administered in combination with an antagonist of a negative immune checkpoint pathway that inhibits the binding of CTLA4 to CD28 (“CTLA4 pathway inhibitor”). Examples of CTLA4 pathway inhibitors are well known in the art (See, e.g., U.S. Pat. No. 6,682,736 (Abgenix) issued Jan. 27, 2004; U.S. Pat. No. 6,984,720 (Medarex, Inc.) issued May 29, 2007; U.S. Pat. No. 7,605,238 (Medarex, Inc.) issued Oct. 20, 2009)
  • In some embodiments, the IL-27R binding molecule is administered in combination with an antagonist of a negative immune checkpoint pathway that inhibits the ability TIM3 to binding to TIM3-activating ligands (“TIM3 pathway inhibitor”). Examples of TIM3 pathway inhibitors are known in the art and with representative non-limiting examples described in PCT International Patent Publication No. WO 2016/144803 published Sep. 15, 2016; Lifke, et al. United States Patent Publication No. US 20160257749 A1 published Sep. 8, 2016 (F. Hoffman-LaRoche); Karunsky, U.S. Pat. No. 9,631,026 issued Apr. 27, 2017; Karunsky, Sabatos-Peyton, et al. U.S. Pat. No. 8,841,418 issued Sep. 23, 2014; U.S. Pat. No. 9,605,070; Takayanagi, et al., U.S. Pat. No. 8,552,156 issued Oct. 8, 2013.
  • In some embodiments, the IL-27R binding molecule is administered in combination with an inhibitor of both LAG3 and PD1 as the blockade of LAG3 and PD1 has been suggested to synergistically reverse anergy among tumor-specific CD8+ T-cells and virus-specific CD8+ T-cells in the setting of chronic infection. IMP321 (ImmuFact) is being evaluated in melanoma, breast cancer, and renal cell carcinoma. See generally Woo et al., (2012) Cancer Res 72:917-27; Goldberg et al., (2011) Curr. Top. Microbiol. Immunol. 344:269-78; Pardoll (2012) Nature Rev. Cancer 12:252-64; Grosso et al., (2007) J. Clin. Invest. 117:3383-392.
  • In some embodiments, the IL-27R binding molecule is administered in combination with an A2aR inhibitor. A2aR inhibits T-cell responses by stimulating CD4+ T-cells towards developing into TReg cells. A2aR is particularly important in tumor immunity because the rate of cell death in tumors from cell turnover is high, and dying cells release adenosine, which is the ligand for A2aR. In addition, deletion of A2aR has been associated with enhanced and sometimes pathological inflammatory responses to infection. Inhibition of A2aR can be effected by the administration of molecules such as antibodies that block adenosine binding or by adenosine analogs. Such agents may be used in combination with the IL-27R binding molecules for use in the treatment disorders such as cancer and Parkinson's disease.
  • In some embodiments, the IL-27R binding molecule is administered in combination with an inhibitor of IDO (Indoleamine 2,3-dioxygenase). IDO down-regulates the immune response mediated through oxidation of tryptophan resulting in in inhibition of T-cell activation and induction of T-cell apoptosis, creating an environment in which tumor-specific cytotoxic T lymphocytes are rendered functionally inactive or are no longer able to attack a subject's cancer cells. Indoximod (NewLink Genetics) is an IDO inhibitor being evaluated in metastatic breast cancer.
  • As previously described, the present invention provides for a method of treatment of neoplastic disease (e.g. cancer) in a mammalian subject by the administration of a IL-27R binding molecule in combination with an agent(s) that modulate at least one immune checkpoint pathway including immune checkpoint pathway modulators that modulate two, three or more immune checkpoint pathways.
  • In some embodiments the IL-27R binding molecule is administered in combination with an immune checkpoint modulator that modulates multiple immune checkpoint pathways. Multiple immune checkpoint pathways may be modulated by the administration of multi-functional molecules which act as modulators of multiple immune checkpoint pathways. Examples of such multiple immune checkpoint pathway modulators include but are not limited to bi-specific or poly-specific antibodies. Examples of poly-specific antibodies capable of acting as modulators or multiple immune checkpoint pathways are known in the art. For example, United States Patent Publication No. 2013/0156774 describes bispecific and multispecific agents (e.g., antibodies), and methods of their use, for targeting cells that co-express PD1 and TIM3. Moreover, dual blockade of BTLA and PD1 has been shown to enhance antitumor immunity (Pardoll, (April 2012) Nature Rev. Cancer 12:252-64). The present disclosure contemplates the use of IL-27R binding molecules in combination with immune checkpoint pathway modulators that target multiple immune checkpoint pathways, including but limited to bi-specific antibodies which bind to both PD1 and LAG3. Thus, antitumor immunity can be enhanced at multiple levels, and combinatorial strategies can be generated in view of various mechanistic considerations.
  • In some embodiments, the IL-27R binding molecule may be administered in combination with two, three, four or more checkpoint pathway modulators. Such combinations may be advantageous in that immune checkpoint pathways may have distinct mechanisms of action, which provides the opportunity to attack the underlying disease, disorder or conditions from multiple distinct therapeutic angles.
  • It should be noted that therapeutic responses to immune checkpoint pathway inhibitors often manifest themselves much later than responses to traditional chemotherapies such as tyrosine kinase inhibitors. In some instance, it can take six months or more after treatment initiation with immune checkpoint pathway inhibitors before objective indicia of a therapeutic response are observed. Therefore, a determination as to whether treatment with an immune checkpoint pathway inhibitors(s) in combination with a IL-27R binding molecule of the present disclosure must be made over a time-to-progression that is frequently longer than with conventional chemotherapies. The desired response can be any result deemed favorable under the circumstances. In some embodiments, the desired response is prevention of the progression of the disease, disorder or condition, while in other embodiments the desired response is a regression or stabilization of one or more characteristics of the disease, disorder or conditions (e.g., reduction in tumor size). In still other embodiments, the desired response is reduction or elimination of one or more adverse effects associated with one or more agents of the combination.
  • Cell Therapy Agents and Methods as Supplementary Agents:
  • In some embodiments, the methods of the disclosure may include the combination of the administration of a IL-27R binding molecules with supplementary agents in the form of cell therapies for the treatment of neoplastic, autoimmune or inflammatory diseases. Examples of cell therapies that are amenable to use in combination with the methods of the present disclosure include but are not limited to engineered T cell products comprising one or more activated CAR-T cells, engineered TCR cells, tumor infiltrating lymphocytes (TILs), engineered Treg cells. As engineered T-cell products are commonly activated ex vivo prior to their administration to the subject and therefore provide upregulated levels of CD25, cell products comprising such activated engineered T cells types are amenable to further support via the administration of an CD25 biased IL-27R binding molecule as described herein.
  • In some embodiments of the methods of the present disclosure, the supplementary agent is a “chimeric antigen receptor T-cell” and “CAR-T cell” are used interchangeably to refer to a T-cell that has been recombinantly modified to express a chimeric antigen receptor. As used herein, the terms As used herein, the terms “chimeric antigen receptor” and “CAR” are used interchangeably to refer to a chimeric polypeptide comprising multiple functional domains arranged from amino to carboxy terminus in the sequence: (a) an antigen binding domain (ABD), (b) a transmembrane domain (TD); and (c) one or more cytoplasmic signaling domains (CSDs) wherein the foregoing domains may optionally be linked by one or more spacer domains. The CAR may also further comprise a signal peptide sequence which is conventionally removed during post-translational processing and presentation of the CAR on the cell surface of a cell transformed with an expression vector comprising a nucleic acid sequence encoding the CAR. CARs useful in the practice of the present invention are prepared in accordance with principles well known in the art. See e.g., Eshhaar et al. U.S. Pat. No. 7,741,465 B1 issued Jun. 22, 2010; Sadelain, et al (2013) Cancer Discovery 3(4):388-398; Jensen and Riddell (2015) Current Opinions in Immunology 33:9-15; Gross, et al. (1989) PNAS(USA) 86(24):10024-10028; Curran, et al. (2012) J Gene Med 14(6):405-15. Examples of commercially available CAR-T cell products that may be modified to incorporate an orthogonal receptor of the present invention include axicabtagene ciloleucel (marketed as Yescarta® commercially available from Gilead Pharmaceuticals) and tisagenlecleucel (marketed as Kymriah® commercially available from Novartis). In some embodiments, the CAR-T possesses a CAR specifically binds to a cell surface molecule associated with a tumor cell is selected from the group consisting of GD2, BCMA, CD19, CD33, CD38, CD70, GD2, IL3Rα2, CD19, mesothelin, Her2, EpCam, Muc1, ROR1, CD133, CEA, EGRFRVIII, PSCA, GPC3, Pan-ErbB and FAP
    • Physical Methods:
  • In some embodiments, the supplementary agent is a anti-neoplastic physical methods including but not limited to radiotherapy, cryotherapy, hyperthermic therapy, surgery, laser ablation, and proton therapy.
  • Kits: The present disclosure also contemplates kits comprising pharmaceutical compositions IL-27R binding molecules and a pharmaceutical composition thereof. The kits are generally in the form of a physical structure housing various components, as described below, and can be utilized, for example, in practicing the methods described above. A kit may comprise a IL-27R binding molecule in the form of a pharmaceutical composition suitable for administration to a subject that is ready for use or in a form or requiring preparation for example, thawing, reconstitution or dilution prior to administration. When the IL-27R binding molecule is in a form that needs to be reconstituted by a user, the kit may also comprise a sterile container providing a reconstitution medium comprising buffers, pharmaceutically acceptable excipients, and the like. A kit of the present disclosure can be designed for conditions necessary to properly maintain the components housed therein (e.g., refrigeration or freezing). A kit may further contain a label or packaging insert including identifying information for the components therein and instructions for their use. Each component of the kit can be enclosed within an individual container, and all of the various containers can be within a single package. Labels or inserts can include manufacturer information such as lot numbers and expiration dates. The label or packaging insert can be, e.g., integrated into the physical structure housing the components, contained separately within the physical structure, or affixed to a component of the kit (e.g., an ampule, syringe or vial). Labels or inserts may be provided in a physical form or a computer readable medium. In some embodiments, the actual instructions are not present in the kit, but rather the kit provides a means for obtaining the instructions from a remote source, e.g., via an internet site, including by secure access by providing a password (or scannable code such as a barcode or QR code on the container of the IL-27R binding molecule or kit comprising) in compliance with governmental regulations (e.g., HIPAA) are provided.
  • It is intended that every maximum numerical limitation given throughout this specification includes every lower numerical limitation, as if such lower numerical limitations were expressly written herein. Every minimum numerical limitation given throughout this specification will include every higher numerical limitation, as if such higher numerical limitations were expressly written herein. Every numerical range given throughout this specification will include every narrower numerical range that falls within such broader numerical range, as if such narrower numerical ranges were all expressly written herein.
  • No admission is made that any reference cited herein constitutes prior art. The discussion of the references states what their authors assert, and the inventors reserve the right to challenge the accuracy and pertinence of the cited documents. It will be clearly understood that, although a number of information sources, including scientific journal articles, patent documents, and textbooks, are referred to herein; this reference does not constitute an admission that any of these documents forms part of the common general knowledge in the art.
  • The foregoing antibodies useful as supplementary agents in the practice of the methods of the present disclosure may be administered alone or in the form of any antibody drug conjugate (ADC) comprising the antibody, linker, and one or more drugs (e.g. 1, 2, 3, 4, 5, 6, 7, or 8 drugs) or in modified form (e.g. PEGylated).
  • In some embodiments the supplementary agent is a vaccine. The IL27R binding proteins of the present invention may be administered to a subject in combination with vaccines as an adjuvant to enhance the immune response to the vaccine in accordance with the teaching of Doyle, et al U.S. Pat. No. 5,800,819 issued Sep. 1, 1998. Examples of vaccines that may be combined with the IL27R binding proteins of the present invention include are HSV vaccines, Bordetella pertussis, Escherichia coli vaccines, pneumococcal vaccines including multivalent pneumococcal vaccines such as Prevnar® 13, diptheria, tetanus and pertussis vaccines (including combination vaccines such as Pediatrix®) and Pentacel®), varicella vaccines, Haemophilus influenzae type B vaccines, human papilloma virus vaccines such as Garasil®, polio vaccines, Leptospirosis vaccines, combination respiratory vaccine, Moraxella vaccines, and attenuated live or killed virus vaccine products such as bovine respiratory disease vaccine (RSV), multivalent human influenza vaccines such as Fluzone® and Quadravlent Fluzone®), feline leukemia vaccine, transmissible gastroenteritis vaccine, COVID-19 vaccine, and rabies vaccine.
  • For prophylactic applications, pharmaceutical compositions or medicaments are administered to a patient susceptible to, or otherwise at risk of disease in an amount sufficient to eliminate or reduce the risk, lessen the severity, or delay the outset of the disease, including biochemical, histologic and/or behavioral symptoms of the disease, its complications and intermediate pathological phenotypes presenting during development of the disease.
    • EXAMPLES Example 1
  • Camels were acclimated at research facility for at least 7 days before immunization. Antigen was diluted with 1×PBS (antigen total about 1 mg). The quality of the antigen was assessed by SDS-PAGE to ensure purity (e.g., >80%). For the first time, 10 mL CFA (then followed 6 times using IFA) was added into mortar, then 10 mL antigen in 1×PBS was slowly added into the mortar with the pestle grinding. The antigen and CFA/IFA were ground until the component showed milky white color and appeared hard to disperse. Camels were injected with antigen emulsified in CFA subcutaneously at at least six sites on the body, injecting about 2 mL at each site (total of 10 mL per camel). A stronger immune response was generated by injecting more sites and in larger volumes. The immunization was conducted every week (7 days), for 7 times. The needle was inserted into the subcutaneous space for 10 to 15 seconds after each injection to avoid leakage of the emulsion. Alternatively, a light pull on the syringe plunger also prevented leakage. The blood sample was collected three days later after 7th immunization.
  • 100 mL of blood was collected from the camel three days following the last injection in the immunization protocol. RNA was extracted from blood and transcribed to cDNA. The approximately 900 bp reverse transcribed sequences encoding the VH-CH1-hinge-CH2-CH3 constructs were isolated from the approximately desired 700 bp fragments encoding the VHH-hinge-CH2-CH3 species. The purified approximately 700 bp fragments were amplified by nested PCR. The amplified sequences were digested using Pst1 and Not1. The approximately 400 bp PST1/Not1 digested fragments were inserted into a Pst1/Not1 digested pMECS phagemid vector such that the sequence encoding the VHH was in frame with a DNA sequence encoding a HA/His sequence. The PCR generated sequences and the vector of pMECS phagemid were digested with Pst I and Not I, subsequently, ligated to pMECS/Nb recombinant. After ligation, the products were transformed into Escherichia coli (E. coli) TG1 cells by electroporation. The transformants were enriched in growth medium, followed by transfer to 2YT+2% glucose agar plates.
  • Bio-panning of the phage library was conducted to identify VHHs that bind IL27Rα. A 96-well plate was coated with IL27Rα and the phage library was incubated in each well to allow phage-expressing IL27Rα reactive VHH to bind to the IL27Rα on the plate. Non-specifically bound phage were washed off and the specifically bound phage isolated. After the selection, the enriched phage library expressing IL27Rα reactive VHH were amplified in TG1 cells. The aforementioned bio-panning process was repeated for 2-3 rounds to enrich the library for VHH selective for IL27Rα. Once biopanning was complete, three 96-well plates of individual phage clones were isolated in order to perform periplasmic extract ELISA PE-ELISA) on antigen coated plates to identify positive VHH binders. Briefly, A 96-well plate was coated with antigen and PBS under the same conditions. Next, wells were blocked at 37° C. for 1 h. Then, 100 μl of extracted antibodies was added to each well and incubated for 1 h. Subsequently, 100 μl of anti-tag polyclonal antibody conjugated to HRP was added to each well and incubated at 37° C. for 1 h. Plates were developed with TMB substrate. The reaction was stopped by the addition of H2SO4. Absorbance at 450 nm was read on a microtiter plate reader and antibodies with absorbance of the antigen-coated well at least threefold greater than PBS-coated control were specific binding molecules and subjected to sequence analysis.
    • Example 2—Recombinant Production and Purification
  • Codon optimized DNA inserts were cloned into modified pcDNA3.4 (Genewiz) for small scale expression in HEK293 cells in 24 well plates. The binding proteins were purified in substantial accordance with the following procedure. Using a Hamilton Star automated system, 96×4 mL of supernatants in 4×24-well blocks were re-arrayed into 4×96-well, 1 mL blocks. PhyNexus™ micropipette tips (Biotage, San Jose CA) holding 80 ptL of Ni-Excel IMAC resin (Cytiva) are equilibrated wash buffer: PBS pH 7.4, 30 mM imidazole. PhyNexus™ tips were dipped and cycled through 14 cycles of 1 mL pipetting across all 4×96-well blocks. PhyNexus™ tips were washed in 2×1 mL blocks holding wash buffer. PhyNexus™ tips were eluted in 3×0.36 mL blocks holding elution buffer: PBS pH 7.4, 400 mM imidazole. PhyNexus™ tips were regenerated in 3×1 mL blocks of 0.5 M sodium hydroxide.
  • The purified protein eluates were quantified using a Biacore® T200 as in substantial accordance with the following procedure. 10 uL of the first 96×0.36 mL eluates were transferred to a Biacore® 96-well microplate and diluted to 60 uL in HBS-EP+ buffer (10 mM Hepes pH 7.4, 150 mM NaCl, 1 mM EDTA, 0.05% Tween™ 20). Each of the 96 samples was injected on a CM5 series S chip previously functionalized with anti-histidine capture antibody (Cytiva): injection is performed for 18 seconds at 5 μL/min. Capture levels were recorded 60 seconds after buffer wash. A standard curve of known VHH concentrations (270, 90, 30, 10, 3.3, 1.1 μg/mL) was acquired in each of the 4 Biacore® chip flow cells to eliminate cell-to-cell surface variability. The 96 captures were interpolated against the standard curve using a non-linear model including specific and unspecific, one-site binding. Concentrations in the first elution block varied from 12 to 452 μg/mL corresponding to a 4-149 μg. SDS-PAGE analysis of 5 randomly picked samples was performed to ensure molecular weight of eluates corresponded to expected values (˜30 kDa).
  • The concentration of the proteins was normalized using the Hamilton Star automated system in substantial accordance with the following procedure. Concentration values are imported in an Excel spreadsheet where pipetting volumes were calculated to perform dilution to 50 μg/mL in 0.22 mL. The spreadsheet was imported in a Hamilton Star method dedicated to performing dilution pipetting using the first elution block and elution buffer as diluent. The final, normalized plate was sterile filtered using 0.22 μm filter plates (Corning).
    • Example 3
  • All experiments were conducted in 10 mM Hepes, 150 mMv NaCl, 0.05% (v/v) Polysorbate 20 (PS20) and 3 mMv EDTA (HBS-EP+ buffer) on a Biacore® T200 instrument equipped with a Protein A chip (Cytiva). Mono-Fc VHH ligands were flowed at 5 μl/min for variable time ranging from 18 to 300 seconds, reaching the capture loads listed in the tables below.
  • Following ligand capture, injections of a 2-fold dilution series of his-tagged cytokine receptors typically comprising at least five concentrations between 1 μM and 1 nM were performed in either high performance or single cycle kinetics mode. Surface regeneration was achieved by flowing 10 mMv glycine-HCl, pH 1.5 (60 seconds, 50 μL/min). Buffer-subtracted sensograms were processed with Biacore® T200 Evaluation Software and globally fit with a 1:1 Langmuir binding model (bulk shift set to zero) to extract kinetics and affinity constants (ka, kd, KD). RMAX<100 RU indicates surface density compatible with kinetics analysis. Calculated Rmax were generated using the equation Rmax=Load (RU)×valency of ligand×(Molecular weight of analyte/Molecular weight of ligand. Surface activity was defined as the ratio experimental/calculated Rmax. See tables below for sample information and experimental results.
  • Anti-hGP130 Mono-Fc VHHs (Ligand) Binding to hGP130-his (Sino Biological, Catalog #10974)
  • Calc.
    Affinity Rmax Load Rmax Surface
    Ligand kON (1/Ms) kOFF (1/s) (nM) (RU) (RU) (RU) Activity
    14-DR591 (SEQ ID NO. 5.9E+04 1.9E−03 33 52 84.6 252 21%
    232)
    15-DR592 (SEQ ID NO. 1.6E+05 5.9E−03 38 142.3 147 437 33%
    233)
    16-DR593 (SEQ ID NO. 2.5E+05 2.1E−02 82 64.2 110 326 20%
    234)
    17-DR594 (SEQ ID NO. 1.6E+05 9.5E−03 58 96.9 153 455 21%
    235)
    18-DR595 (SEQ ID NO. 1.8E+05 7.3E−03 41 127 128 379 33%
    236)
    19-DR596 (SEQ ID NO. 1.9E+05 8.2E−03 44 68.8 83.6 249 28%
    237)

    Anti-hIL27Rα Mono-Fc VHHs (Ligand) Binding to hIL27Ra-his (Origene, Catalog #TP307012)
  • Calc.
    Affinity Rmax Load Rmax Surface
    Ligand kON (1/Ms) kOFF (1/s) (nM) (RU) (RU) (RU) Activity
    20-DR597 (SEQ ID NO. 3.0E+04 5.7E−04 19.0 142* 1319 3564 4%
    245)
    24-DR601 (SEQ ID NO. 9.1E+04 4.1E−04 4.5 102 305 824 12%
    249)
    23-DR600 (SEQ ID NO. 5.9E+04 1.0E−03 17 79 232 627 13%
    248)
    25-DR602 (SEQ ID NO. 1.5E+05 7.6E−04 5.2 115* 210 568 20%
    250)
    26-DR603 (SEQ ID NO. 1.3E+05 7.7E−04 6.1 149* 305 823 18%
    251)
    *Both association and dissociation kinetics constants might be suppressed at Rmax > 100.
    If existing, this effect is likely cancelled in the kinetics ratio, i.e. affinity constant.
    • Example 4
  • Binding for all VHH was confirmed by ELISA. One representative VHH from each clonotype was selected for further analysis by surface plasmon resonance using Biacore® T200. See below.
  • hIL27 hgp1 kON kOFF Affinity kON kOFF Affinity
    Ra 30 (1/Ms) (1/s) (nM) (1/Ms) (1/s) (nM)
    Dimer arm arm hIL27Ra hIL27Ra hIL27Ra hgp130 hgp130 hgp130
    hIL27Ra_VH VHH1 DR591 3.00E+04 5.70E−04 19 5.90E+04 1.90E−03 33
    H1-DR591
    hIL27Ra_VH VHH4 DR591 — — — 5.90E+04 1.90E−03 33
    H4-DR591
    hIL27Ra_VH VHH6 DR591 — — — 5.90E+04 1.90E−03 33
    H6-DR591
    hIL27Ra_VH VHH9 DR591 9.10E+04 4.10E−04 4.5 5.90E+04 1.90E−03 33
    H9-DR591
    hIL27Ra_VH VHH15 DR591 5.90E+04 1.00E−03 17 5.90E+04 1.90E−03 33
    H15-DR591
    hIL27Ra_VH VHH19 DR591 1.50E+05 7.60E−04 5.2 5.90E+04 1.90E−03 33
    H19-DR591
    hIL27Ra_VH VHH21 DR591 1.30E+05 7.70E−04 6.1 5.90E+04 1.90E−03 33
    H21-DR591
    hIL27Ra_VH VHH1 DR592 3.00E+04 5.70E−04 19 1.60E+05 5.90E−03 38
    H1-DR592
    hIL27Ra_VH VHH4 DR592 — — — 1.60E+05 5.90E−03 38
    H4-DR592
    hIL27Ra_VH VHH6 DR592 — — — 1.60E+05 5.90E−03 38
    H6-DR592
    hIL27Ra_VH VHH9 DR592 9.10E+04 4.10E−04 4.5 1.60E+05 5.90E−03 38
    H9-DR592
    hIL27Ra_VH VHH15 DR592 5.90E+04 1.00E−03 17 1.60E+05 5.90E−03 38
    H15-DR592
    hIL27Ra_VH VHH19 DR592 1.50E+05 7.60E−04 5.2 1.60E+05 5.90E−03 38
    H19-DR592
    hIL27Ra_VH VHH21 DR592 1.30E+05 7.70E−04 6.1 1.60E+05 5.90E−03 38
    H21-DR592
    hIL27Ra_VH VHH1 DR593 3.00E+04 5.70E−04 19 2.50E+05 2.10E−02 82
    H1-DR593
    hIL27Ra_VH VHH4 DR593 — — — 2.50E+05 2.10E−02 82
    H4-DR593
    hIL27Ra_VH VHH6 DR593 — — — 2.50E+05 2.10E−02 82
    H6-DR593
    hIL27Ra_VH VHH9 DR593 9.10E+04 4.10E−04 4.5 2.50E+05 2.10E−02 82
    H9-DR593
    hIL27Ra_VH VHH15 DR593 5.90E+04 1.00E−03 17 2.50E+05 2.10E−02 82
    H15-DR593
    hIL27Ra_VH VHH19 DR593 1.50E+05 7.60E−04 5.2 2.50E+05 2.10E−02 82
    H19-DR593
    hIL27Ra_VH VHH21 DR593 1.30E+05 7.70E−04 6.1 2.50E+05 2.10E−02 82
    H21-DR593
    hIL27Ra_VH VHH1 DR594 3.00E+04 5.70E−04 19 1.60E+05 9.50E−03 58
    H1-DR594
    hIL27Ra_VH VHH4 DR594 — — — 1.60E+05 9.50E−03 58
    H4-DR594
    hIL27Ra_VH VHH6 DR594 — — — 1.60E+05 9.50E−03 58
    H6-DR594
    hIL27Ra_VH VHH9 DR594 9.10E+04 4.10E−04 4.5 1.60E+05 9.50E−03 58
    H9-DR594
    hIL27Ra_VH VHH15 DR594 5.90E+04 1.00E−03 17 1.60E+05 9.50E−03 58
    H15-DR594
    hIL27Ra_VH VHH19 DR594 1.50E+05 7.60E−04 5.2 1.60E+05 9.50E−03 58
    H19-DR594
    hIL27Ra_VH VHH21 DR594 1.30E+05 7.70E−04 6.1 1.60E+05 9.50E−03 58
    H21-DR594
    hIL27Ra_VH VHH1 DR595 3.00E+04 5.70E−04 19 1.80E+05 7.30E−03 41
    H1-DR595
    hIL27Ra_VH VHH4 DR595 — — — 1.80E+05 7.30E−03 41
    H4-DR595
    hIL27Ra_VH VHH6 DR595 — — — 1.80E+05 7.30E−03 41
    H6-DR595
    hIL27Ra_VH VHH9 DR595 9.10E+04 4.10E−04 4.5 1.80E+05 7.30E−03 41
    H9-DR595
    hIL27Ra_VH VHH15 DR595 5.90E+04 1.00E−03 17 1.80E+05 7.30E−03 41
    H15-DR595
    hIL27Ra_VH VHH19 DR595 1.50E+05 7.60E−04 5.2 1.80E+05 7.30E−03 41
    H19-DR595
    hIL27Ra_VH VHH21 DR595 1.30E+05 7.70E−04 6.1 1.80E+05 7.30E−03 41
    H21-DR595
    hIL27Ra_VH VHH1 DR596 3.00E+04 5.70E−04 19 1.90E+05 8.20E−03 44
    H1-DR596
    hIL27Ra_VH VHH4 DR596 — — — 1.90E+05 8.20E−03 44
    H4-DR596
    hIL27Ra_VH VHH6 DR596 — — — 1.90E+05 8.20E−03 44
    H6-DR596
    hIL27Ra_VH VHH9 DR596 9.10E+04 4.10E−04 4.5 1.90E+05 8.20E−03 44
    H9-DR596
    hIL27Ra_VH VHH15 DR596 5.90E+04 1.00E−03 17 1.90E+05 8.20E−03 44
    H15-DR596
    hIL27Ra_VH VHH19 DR596 1.50E+05 7.60E−04 5.2 1.90E+05 8.20E−03 44
    H19-DR596
    hIL27Ra_VH VHH21 DR596 1.30E+05 7.70E−04 6.1 1.90E+05 8.20E−03 44
    H21-DR596
  • LENGTHY TABLES
    The patent application contains a lengthy table section. A copy of the table is available in electronic form from the USPTO web site (https://seqdata.uspto.gov/?pageRequest=docDetail&DocID=US20240002542A1). An electronic copy of the table will also be available from the USPTO upon request and payment of the fee set forth in 37 CFR 1.19(b)(3).

Claims (7)

1. An IL27 receptor (IL27R) binding protein that specifically binds to IL27Rα subunit (IL27Rα) and glycoprotein 130 subunit (gp130),
wherein the binding protein causes the multimerization of IL27Rα and gp130 when bound to IL27Rα and gp130, and
wherein the binding protein comprises a single-domain antibody (sdAb) that specifically binds to IL27Rα (an anti-IL27Rα sdAb) and a sdAb that specifically binds to gp130 (an anti-gp130 sdAb) and wherein the anti-IL27Rα sdAb is an anti-IL27Rα VHH antibody and the anti-gp130 sdAb is an anti-gp130 VHH antibody and
wherein the anti-gp130 VHH antibody comprises a set of a CDR1, a CDR2, and a CDR3, wherein the set is selected from the group consisting of:
SEQ ID NO: 193, SEQ ID NO: 199, SEQ ID NO: 205, respectively;
SEQ ID NO: 194, SEQ ID NO: 200, SEQ ID NO: 206, respectively;
SEQ ID NO: 195, SEQ ID NO: 201, SEQ ID NO: 207, respectively;
SEQ ID NO: 196, SEQ ID NO: 202, SEQ ID NO: 208, respectively;
SEQ ID NO: 197, SEQ ID NO: 203, SEQ ID NO: 209, respectively; and
SEQ ID NO: 198, SEQ ID NO: 204, SEQ ID NO: 210, respectively; and
the anti-IL27Rα VHH antibody comprises a set of a CDR1, a CDR2, and a CDR3, wherein the set is selected from the group consisting of
SEQ ID NO: 211, SEQ ID NO: 218, SEQ ID NO: 225, respectively;
SEQ ID NO: 212, SEQ ID NO: 219, SEQ ID NO: 226, respectively;
SEQ ID NO: 213, SEQ ID NO: 220, SEQ ID NO: 227, respectively;
SEQ ID NO: 214, SEQ ID NO: 221, SEQ ID NO: 228, respectively;
SEQ ID NO: 215, SEQ ID NO: 222, SEQ ID NO: 229, respectively;
SEQ ID NO: 216, SEQ ID NO: 223, SEQ ID NO: 230, respectively; and
SEQ ID NO: 217, SEQ ID NO: 224, SEQ ID NO: 231, respectively.
2-30. (canceled)
31. The IL27R binding protein of claim 1, wherein the anti-gp130 VHH antibody comprises the set of CDR1, CDR2, and CDR3 comprising amino acid sequences of SEQ ID NO: 196, SEQ ID NO: 202, and SEQ ID NO: 208, respectively.
32. The IL27R binding protein of claim 31, wherein the anti-IL27Rα VHH antibody CDR1 comprises the set of CDR1, CDR2, and CDR3 comprising amino acid sequences of SEQ ID NO: 214, SEQ ID NO: 221, SEQ ID NO: 228, respectively.
33. The IL27R binding protein of claim 31, wherein the anti-IL27Rα VHH antibody CDR1 comprises the set of CDR1, CDR2, and CDR3 comprising amino acid sequences of SEQ ID NO: 216, SEQ ID NO: 223 and SEQ ID NO: 230, respectively.
34. An IL27 receptor (IL27R) binding protein that specifically binds to IL27Rα subunit (IL27Rα) and glycoprotein 130 subunit (gp130),
wherein the binding protein causes the multimerization of IL27Rα and gp130 when bound to IL27Rα and gp130, and
wherein the binding protein comprises a single-domain antibody (sdAb) that specifically binds to IL27Rα (an anti-IL27Rα sdAb) and a sdAb that specifically binds to gp130 (an anti-gp130 sdAb) and wherein the anti-IL27Rα sdAb is an anti-IL27Rα VHH antibody and the anti-gp130 sdAb is an anti-gp130 VHH antibody, and
wherein the IL27 receptor (IL27R) binding protein comprises an amino acid sequence of SEQ ID NO: 64.
35. An IL27 receptor (IL27R) binding protein that specifically binds to IL27Rα subunit (IL27Rα) and glycoprotein 130 subunit (gp130),
wherein the binding protein causes the multimerization of IL27Rα and gp130 when bound to IL27Rα and gp130, and
wherein the binding protein comprises a single-domain antibody (sdAb) that specifically binds to IL27Rα (an anti-IL27Rα sdAb) and a sdAb that specifically binds to gp130 (an anti-gp130 sdAb) and wherein the anti-IL27Rα sdAb is an anti-IL27Rα VHH antibody and the anti-gp130 sdAb is an anti-gp130 VHH antibody, and
wherein the IL27 receptor (IL27R) binding protein comprises an amino acid sequence of SEQ ID NO: 76.
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Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022031884A2 (en) * 2020-08-05 2022-02-10 Synthekine, Inc. Il2rg binding molecules and methods of use
KR20230065259A (en) * 2020-08-05 2023-05-11 신테카인, 인크. IL10 receptor binding molecules and methods of use
EP4192490A1 (en) * 2020-08-05 2023-06-14 Synthekine, Inc. IL27Ra BINDING MOLECULES AND METHODS OF USE
WO2023159162A2 (en) * 2022-02-18 2023-08-24 The Regents Of The University Of California Improved primary human nk cell expansion and function by chimeric cytokine receptor
US20240052047A1 (en) * 2022-08-03 2024-02-15 Pfizer Inc. Anti- il27r antibodies and methods of use thereof
WO2024040195A1 (en) 2022-08-17 2024-02-22 Capstan Therapeutics, Inc. Conditioning for in vivo immune cell engineering

Family Cites Families (71)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7198919B1 (en) 1983-04-25 2007-04-03 Genentech, Inc. Use of alpha factor sequences in yeast expression systems
US4569794A (en) 1984-12-05 1986-02-11 Eli Lilly And Company Process for purifying proteins and compounds useful in such process
US5013556A (en) 1989-10-20 1991-05-07 Liposome Technology, Inc. Liposomes with enhanced circulation time
US5279833A (en) 1990-04-04 1994-01-18 Yale University Liposomal transfection of nucleic acids into animal cells
US5439829A (en) 1991-01-30 1995-08-08 Eli Lilly And Company Immobilization of biologically active molecules by changing the Oxidation state of a chelated transition metal ion
WO1993002556A1 (en) 1991-07-26 1993-02-18 University Of Rochester Cancer therapy utilizing malignant cells
US5283185A (en) 1991-08-28 1994-02-01 University Of Tennessee Research Corporation Method for delivering nucleic acids into cells
IL104570A0 (en) 1992-03-18 1993-05-13 Yeda Res & Dev Chimeric genes and cells transformed therewith
US5320663A (en) 1992-07-02 1994-06-14 E. I. Du Pont De Nemours And Company Method of obtaining lead and organolead from contaminated media using metal accumulating plants
US5334761A (en) 1992-08-28 1994-08-02 Life Technologies, Inc. Cationic lipids
WO1995002698A1 (en) 1993-07-12 1995-01-26 Life Technologies, Inc. Composition and methods for transfecting eukaryotic cells
US5631236A (en) 1993-08-26 1997-05-20 Baylor College Of Medicine Gene therapy for solid tumors, using a DNA sequence encoding HSV-Tk or VZV-Tk
US5650234A (en) 1994-09-09 1997-07-22 Surface Engineering Technologies, Division Of Innerdyne, Inc. Electrophilic polyethylene oxides for the modification of polysaccharides, polypeptides (proteins) and surfaces
US5731168A (en) 1995-03-01 1998-03-24 Genentech, Inc. Method for making heteromultimeric polypeptides
WO2003066002A2 (en) * 2002-02-08 2003-08-14 University Of Medicine And Dentistry Of New Jersey IFN-a/b-INDEPENDENT MECHANISM OF ANTIVIRAL PROTECTION
US20060002935A1 (en) * 2002-06-28 2006-01-05 Domantis Limited Tumor Necrosis Factor Receptor 1 antagonists and methods of use therefor
CA2569240A1 (en) * 2004-06-01 2005-12-15 Domantis Limited Drug fusion comprising a polypeptide drug and an immunoglobulin heavy chain variable domain specific for serum albumin
AR049292A1 (en) 2004-06-04 2006-07-12 Genentech Inc METHOD TO TREAT LUPUS WITH A CD20 ANTIBODY
US7553932B1 (en) 2005-04-25 2009-06-30 La Jolla Institute For Allergy And Immunology Methods of treating viral infection with IL-10 receptor antagonists
LT2439273T (en) 2005-05-09 2019-05-10 Ono Pharmaceutical Co., Ltd. Human monoclonal antibodies to programmed death 1(PD-1) and methods for treating cancer using anti-PD-1 antibodies alone or in combination with other immunotherapeutics
CN105330741B (en) 2005-07-01 2023-01-31 E.R.施贵宝&圣斯有限责任公司 Human monoclonal antibodies to programmed death ligand 1 (PD-L1)
US7612181B2 (en) 2005-08-19 2009-11-03 Abbott Laboratories Dual variable domain immunoglobulin and uses thereof
AU2006284841B2 (en) 2005-09-01 2012-11-08 Merck Sharp & Dohme Corp. Use of IL-23 and IL-17 antagonists to treat autoimmune ocular inflammatory disease
ES2612383T3 (en) * 2006-07-19 2017-05-16 The Trustees Of The University Of Pennsylvania WSX-1 / IL-27 as a target for anti-inflammatory responses
EP2395025A1 (en) * 2007-02-28 2011-12-14 Schering Corporation Engineered Anti-IL-23R Antibodies
EP2650311A3 (en) 2007-11-27 2014-06-04 Ablynx N.V. Amino acid sequences directed against heterodimeric cytokines and/or their receptors and polypeptides comprising the same
EP2262837A4 (en) 2008-03-12 2011-04-06 Merck Sharp & Dohme Pd-1 binding proteins
WO2009154995A2 (en) 2008-05-27 2009-12-23 Kyowa Hakko Kirin Co., Ltd. Interleukin 10 receptor (il-10r) antibodies and methods of use
ATE497978T1 (en) * 2008-06-27 2011-02-15 Theranor Sprl PHARMACEUTICAL COMPOSITIONS OF ANTIBODIES FROM VIRUS DISEASES
SI2376535T1 (en) 2008-12-09 2017-07-31 F. Hoffmann-La Roche Ag Anti-pd-l1 antibodies and their use to enhance t-cell function
WO2010118243A2 (en) * 2009-04-08 2010-10-14 Genentech, Inc. Use of il-27 antagonists to treat lupus
WO2010142551A2 (en) * 2009-06-12 2010-12-16 Ablynx N.V. Single variable domain (vhh) antibodies to cytokines of the il-17 receptor family
GB201005063D0 (en) 2010-03-25 2010-05-12 Ucb Pharma Sa Biological products
WO2011051327A2 (en) * 2009-10-30 2011-05-05 Novartis Ag Small antibody-like single chain proteins
UY33492A (en) * 2010-07-09 2012-01-31 Abbott Lab IMMUNOGLOBULINS WITH DUAL VARIABLE DOMAIN AND USES OF THE SAME
US20120225081A1 (en) * 2010-09-03 2012-09-06 Boehringer Ingelheim International Gmbh Vegf-binding molecules
CN103154037A (en) * 2010-10-05 2013-06-12 诺瓦提斯公司 Anti-IL 12 Rbeta 1 antibodies and their use in treating autoimmune and inflammatory disorders
TR201802772T4 (en) * 2010-11-17 2018-03-21 Chugai Pharmaceutical Co Ltd Multi-specific antigen binding molecule with alternative function for the function of blood coagulation factor VIII.
UY33827A (en) 2010-12-22 2012-07-31 Abbott Lab MEDIUM-IMMUNOGLOBULIN UNION PROTEINS AND ITS USES
EP2663578A2 (en) * 2011-01-14 2013-11-20 Five Prime Therapeutics, Inc. Il-27 antagonists for treating inflammatory diseases
EP2714738B1 (en) * 2011-05-24 2018-10-10 Zyngenia, Inc. Multivalent and monovalent multispecific complexes and their uses
EP2729488A4 (en) * 2011-07-06 2015-01-14 Medimmune Llc Methods for making multimeric polypeptides
US8790651B2 (en) * 2011-07-21 2014-07-29 Zoetis Llc Interleukin-31 monoclonal antibody
WO2013059299A1 (en) 2011-10-17 2013-04-25 The Uab Research Foundation Antibodies for interferon subtypes and interferon/interferon receptor ternary complex and uses thereof
CN103396482B (en) * 2013-05-17 2016-08-10 东南大学 A kind of prealbumin nano antibody, its coded sequence and application
HRP20220553T1 (en) * 2013-07-25 2022-06-10 Cytomx Therapeutics Inc. Multispecific antibodies, multispecific activatable antibodies and methods of using the same
AU2014326674B2 (en) * 2013-09-26 2020-03-12 Ablynx Nv Bispecific nanobodies
EP3593812A3 (en) * 2014-03-15 2020-05-27 Novartis AG Treatment of cancer using chimeric antigen receptor
US10993990B2 (en) 2014-05-16 2021-05-04 Baylor Research Institute Methods and compositions for treating autoimmune and inflammatory conditions
JP6862343B2 (en) 2014-12-19 2021-04-21 アブリンクス エン．ヴェー． Cysteine-bonded nanobody dimer
ES2754427T3 (en) 2015-05-13 2020-04-17 Ablynx Nv T cell recruitment polypeptides based on TCR alpha / beta reactivity
IL293719B2 (en) 2015-05-21 2023-07-01 Harpoon Therapeutics Inc Trispecific binding proteins and methods of use
ES2841799T3 (en) 2015-08-06 2021-07-09 Agency Science Tech & Res Antibodies to IL2R-Beta / common gamma chain
CN106883297B (en) * 2015-12-16 2019-12-13 苏州康宁杰瑞生物科技有限公司 CH3 domain-based heterodimer molecule, preparation method and application thereof
CN107400166A (en) * 2016-05-19 2017-11-28 苏州康宁杰瑞生物科技有限公司 for CTLA4 single domain antibody and its derived protein
WO2018067991A1 (en) * 2016-10-07 2018-04-12 The Brigham And Women's Hospital, Inc. Modulation of novel immune checkpoint targets
ES2917000T3 (en) * 2016-10-24 2022-07-06 Orionis Biosciences BV Target mutant interferon-gamma and uses thereof
US11377497B2 (en) * 2017-01-23 2022-07-05 Suzhou Alphamab Co., Ltd. PD-L1 binding polypeptide or composite
CA3056600A1 (en) 2017-03-31 2018-10-04 Ignacio Moraga GONZALEZ Synthekine compositions and methods of use
EP3634465A4 (en) 2017-05-25 2021-01-20 The Broad Institute, Inc. Lymphocyte antigen cd5like (cd5l) monomer, homodimer, and interleukin 12b (p40) heterodimer antagonists and methods of use thereof
NZ761430A (en) 2017-08-03 2024-03-22 Synthorx Inc Cytokine conjugates for the treatment of proliferative and infectious diseases
MA51289A (en) * 2017-12-18 2021-03-24 Regeneron Pharma BISPECIFIC ANTIGEN BINDING MOLECULES BINDING TO THE LEPTIN RECEPTOR AND / OR GP130, AND THEIR METHODS OF USE
KR20200104333A (en) * 2017-12-28 2020-09-03 난징 레전드 바이오테크 씨오., 엘티디. Single-domain antibodies to TIGIT and variants thereof
WO2019241426A1 (en) * 2018-06-13 2019-12-19 Novartis Ag Bcma chimeric antigen receptors and uses thereof
SG11202008731XA (en) * 2018-06-19 2020-10-29 Nanjing Legend Biotech Co Ltd Engineered cells and uses thereof
EP3850013A4 (en) * 2018-09-10 2022-10-05 Nanjing Legend Biotech Co., Ltd. Single-domain antibodies against cll1 and constructs thereof
EP3908602A1 (en) 2019-01-07 2021-11-17 Bactolife ApS Pathogen binding proteins
GB201903767D0 (en) 2019-03-19 2019-05-01 Quadrucept Bio Ltd Multimers, tetramers & octamers
CN111018985B (en) 2019-12-06 2021-06-18 南京融捷康生物科技有限公司 Application of single-domain antibody aiming at bovine serum albumin BSA
IL296714A (en) * 2020-03-27 2022-11-01 Univ Indiana Trustees Immunotherapeutic targets in multiple myeloma and methods for their identification
EP4192490A1 (en) * 2020-08-05 2023-06-14 Synthekine, Inc. IL27Ra BINDING MOLECULES AND METHODS OF USE

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