EP3446120A1 - Neuer, in pankreatischen beta-zellen exprimierter biomarker, nützlich zur bildgebung oder zum targeting von beta-zellen - Google Patents
Neuer, in pankreatischen beta-zellen exprimierter biomarker, nützlich zur bildgebung oder zum targeting von beta-zellenInfo
- Publication number
- EP3446120A1 EP3446120A1 EP17721560.5A EP17721560A EP3446120A1 EP 3446120 A1 EP3446120 A1 EP 3446120A1 EP 17721560 A EP17721560 A EP 17721560A EP 3446120 A1 EP3446120 A1 EP 3446120A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- beta
- cells
- cell
- tmem132d
- variant
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
- G01N33/57407—Specifically defined cancers
- G01N33/57438—Specifically defined cancers of liver, pancreas or kidney
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/04—Endocrine or metabolic disorders
- G01N2800/042—Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism
Definitions
- approaches for clinical beta cell imaging should primarily rely on chemical resolution with high sensitivity (i.e., visualization of beta cells based on high specificity and biochemical/metabolic characteristics of a tracer molecule) by using tracers for positron emission tomography (PET) or single photon emission computed tomography (SPECT), techniques characterized by a very high sensitivity.
- PET positron emission tomography
- SPECT single photon emission computed tomography
- a method for detecting and/or visualising pancreatic beta-cells comprising the steps of:
- said measuring of the amount of beta-cell mass in the subject comprises the steps of:
- FIG. 2 Different splice variants of the TMEM132D gene. The boxes represent exons. TD indicates the transmembrane domain.
- Type 1 diabetes is an autoimmune disease in which the body's immune system attacks and kills its own insulin-producing beta cells and kills them.
- a key obstacle to early detection of T1 D, to understand the evolution of the disease and to assess the effectiveness of novel therapeutic interventions to prevent or cure the disease is the lack of direct, noninvasive technologies to visualize and measure beta cell mass.
- Type 2 diabetes is a long-term metabolic disorder that is characterized by high blood sugar caused by failure of the beta cells to compensate for insulin resistance, most commonly secondary to obesity.
- the lack of reliable methods to determine beta cell mass also limits follow up of pancreatic islet transplantation and of patients affected by type 2 diabetes (T2D), a disease where a progressive decrease of beta cell mass (albeit of less magnitude than T1 D) is also present.
- T2D type 2 diabetes
- T1 D type 2 diabetes
- TMEM132D transmembrane protein 132D, encoded by the TMEM132D gene, preferably the Human TMEM132D gene, such as the gene represented by NCBI reference sequence NM_133448.2 (SEQ ID NO: 15).
- the amino acid sequence of the human TMEM132D protein is preferably the one represented by NCBI reference sequence Q14C87-1 (SEQ ID NO: 1 ).
- variant 1 of TMEM132D "variant 2 of TMEM132D”
- variant 3 of TMEM132D are depicted in Figure 3.
- amino acid sequence in particular an antibody fragment, such as a V H H or functional fragments thereof, as disclosed herein is considered to be '(in) essentially isolated (form)' as used herein, when it has been extracted or purified from the host cell and/or medium in which it is produced.
- an amino acid sequence as disclosed herein when said amino acid sequence as disclosed herein is said to be 'specific for' a first target antigen of interest as opposed to a second target antigen of interest, it may specifically bind to (as defined herein) the first target antigen of interest, but not to the second target antigen of interest.
- methods for preparing a heavy chain variable domain sequence as disclosed herein comprise the steps of a) providing a set, collection or library of amino acid sequences of V H H domains; and b) screening said set, collection or library of V H H domains for amino acid sequences that can bind to and/or have affinity for variant 1 of TM EM 1 32D .
- Transformation or transfection of nucleic acids or vectors into host cells may be accomplished by a variety of means known to the person skilled in the art including calcium phosphate-DNA co-precipitation, DEAE-dextran-mediated transfection, polybrene- mediated transfection, electroporation, microinjection, liposome fusion, lipofection, protoplast fusion, retroviral infection, and biolistics.
- the introduction or linkage of such functional groups to a heavy chain variable domain can result in an increase in the solubility and/or the stability of the heavy chain variable domain, in a reduction of the toxicity of the heavy chain variable domain, or in the elimination or attenuation of any undesirable side effects of the heavy chain variable domain, and/or in other advantageous properties.
- the present invention provides hosts or host cells that express or are capable of expressing one or more amino acid sequences as disclosed herein. Suitable examples of hosts or host cells for expression of the V H H sequences, polypeptides of the invention will be clear to the skilled person.
- the present invention also provides polypeptides and pharmaceutical compositions comprising two or more identical or different V H H domains resulting in a bivalent (or multivalent) or a bispecific or (multispecific) polypeptide.
- biomarker of the invention can also be used in in-vitro methods for the analysis of the amount or characteristics of beta cells in a cell culture, either obtained from a biopsy or from a cell-line derived culture.
- Beta cell specific markers of the invention can further be used to characterize the differentiation state of cells such as modified stem cells, differentiated in vitro as beta cells.
- the determination of what action is to be taken, e.g., by a clinician, in view of said diagnosis, prediction and/or prognosis is performed by a (the) computer.
- a (the) computer reports (i.e., generates an electronic report of) the action to be taken, preferably substantially in real time.
- binding molecules that specifically bind with TMEM132D-variant-1 -positive cells were identified. Such molecules can be used as tracers for visualizing beta-cell mass.
- An approach to this is to utilize camelid single-domain antibody-fragment (“Nanobodies” (Ablynx NV), further referred to herein as "Nb(s)”) libraries, which could be screened for nanobodies that specifically bind to variant 1 of the TMEM132D protein.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP2016166582 | 2016-04-22 | ||
PCT/EP2017/059461 WO2017182605A1 (en) | 2016-04-22 | 2017-04-21 | A new biomarker expressed in pancreatic beta cells useful in imaging or targeting beta cells |
Publications (1)
Publication Number | Publication Date |
---|---|
EP3446120A1 true EP3446120A1 (de) | 2019-02-27 |
Family
ID=65030630
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP17721560.5A Withdrawn EP3446120A1 (de) | 2016-04-22 | 2017-04-21 | Neuer, in pankreatischen beta-zellen exprimierter biomarker, nützlich zur bildgebung oder zum targeting von beta-zellen |
Country Status (1)
Country | Link |
---|---|
EP (1) | EP3446120A1 (de) |
-
2017
- 2017-04-21 EP EP17721560.5A patent/EP3446120A1/de not_active Withdrawn
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