# US 2013/0156786 A1 · Peptide or peptide complex binding to 2 integrin and methods and uses involving the same

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- Number: US 2013/0156786 A1
- Document ID: US20130156786A1
- Status: Published application
- Kind: A1
- Application number: 13/819,620
- Filed: 2011-08-30
- Published: 2013-06-20
- Earliest claimed: 2010-08-31
- Assignees: Sanofi
- Inventors: Carsten Corvey; Horst Blum; Béatrice Cameron; Tarik Dabdoubi; Stephanie Decary; Nicolas Baurin; David Papin; Christian Lange
- Web page: https://patentgrep.com/patent/US20130156786A1

## CPC

- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- C07K 16/2842: {against integrin beta1-subunit-containing molecules, e.g. CD29, CD49}
- A61P 3/08: for glucose homeostasis (pancreatic hormones A61P5/48)
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 17/00: Drugs for dermatological disorders
- A61P 17/06: Antipsoriatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 27/02: Ophthalmic agents
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 31/04: Antibacterial agents
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 35/04: specific for metastasis
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/02: Immunomodulators
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/2839: {against the integrin superfamily}
- G01N 33/6857: {Antibody fragments}
- G01N 33/6872: {Intracellular protein regulatory factors and their receptors, e.g. including ion channels}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/55: Fab or Fab'
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/567: Framework region [FR]
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K 2317/94: Stability, e.g. half-life, pH, temperature or enzyme-resistance
- G01N 2333/70546: Integrin superfamily, e.g. VLAs, leuCAM, GPIIb/GPIIIa, LPAM
- G01N 2333/7055: Integrin beta1-subunit-containing molecules, e.g. CD29, CD49
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The present invention relates to a peptide or peptide complex binding to α2 integrin, to one or more nucleic acid(s) coding for the peptide or peptide complex, a recombinant cell producing the peptide or peptide complex, a method for producing the peptide or peptide complex, a pharmaceutical composition comprising the peptide or peptide complex or the nucleic acid(s) for use as a medicament, a method for detecting α2 integrin and a screening method.

## Claims

### Claim 1

Peptide or peptide complex, preferably isolated monoclonal antibody or antigen binding fragment thereof, wherein said peptide or peptide complex, antibody or fragment specifically binds to the I-domain of a human α2-integrin, said antibody or fragment comprising a heavy chain variable region (VH) domain and a light chain variable region (VL) domain, wherein said antibody or fragment cross-reacts with a non-human primate α2-integrin but does not cross-react with a non-primate α2-integrin.

### Claim 2

Peptide or peptide complex, preferably isolated monoclonal antibody or antigen binding fragment thereof, wherein said peptide or peptide complex, antibody or fragment specifically binds to the I-domain of a human α2-integrin, said antibody comprising a heavy chain variable region (VH) domain and a light chain variable region (VL) domain, wherein said antibody or fragment competes with a reference antibody for binding to the epitope of the reference antibody, said reference antibody comprising a light chain encoded by the plasmid as deposited with the DSMZ under accession No. DSM 23944 and a heavy chain encoded by either (i) the plasmid as deposited with the DSMZ under accession DSM 23946 or (ii) the plasmid as deposited with the DSMZ under accession No. DSM 23945.

### Claim 3

Peptide or peptide complex preferably isolated monoclonal antibody or antigen binding fragment thereof, comprising one or more of the following components a to f:
a) LCDR1, wherein LDR1 is RASESVESYGNSFIY (SEQ ID NO:6) or a functionally active variant thereof,
b) LCDR2, wherein LDR2 is LASNLAS (SEQ ID NO:7) or a functionally active variant thereof,
c) LCDR3, wherein LDR3 is QQNNEDPYT (SEQ ID NO:8) or a functional active variant thereof,
d) HCDR1, wherein HDR1 is (GYTFTSYWMN, SEQ ID NO:3) or a functionally active variant thereof,
e) HCDR2, wherein HDR2 is RIDPSDSETHYNQKFK (SEQ ID NO:4) or a functionally active variant thereof, and
f) HCDR3, wherein HDR3 is VGRGYFDY (SEQ ID NO:5) or a functional active variant thereof,
and wherein the one or more of the components a) to f) are arranged to allow for binding of the peptide or peptide complex to α2 integrin.

### Claim 4 (depends on 1, 2, 3)

Peptide or peptide complex according to one of the claims 1-3,
(i) wherein components a) to c) are comprised in a variable domain of a light chain (VL); and/or
(ii) wherein components d) to f) are comprised in a variable domain of a heavy chain (VH); and/or
(iii) wherein the peptide or peptide complex is an antibody; and/or
(iv) wherein the peptide or peptide complex is a monoclonal antibody, a chimeric antibody, a humanized antibody, a Fab, a Fab′, a F(ab′)2, a Fv, a disulfide linked Fv, a scFv, a (scFv)2, a single domain antibody, a diabody, a multispecific antibody, a dual specific antibody, a isotype antibody, a dual variable domain antibody and a bispecific antibody; and/or
(v) wherein the peptide or peptide complex comprises a heavy chain immunoglobulin constant domain selected from the group consisting of: a human IgM constant domain, a human IgG1 constant domain, a human IgG2 constant domain, a human IgG3 constant domain, domain, a human IgG4 constant domain, a human IgE constant domain, and a human IgA constant domain; and/or
(vi) wherein the functionally active variant is a functionally active fragment consisting of at least 90% sequence identity to any of the amino acid sequences of SEQ ID NOS: 3 to 8; and/or
(vii) wherein the functionally active variant is a functionally active variant having at least 70%, preferably at least 80%, more preferably at least 90% sequence identity to an amino acid sequence of any of SEQ ID NOS: 3 to 8, particularly wherein the functionally active variant is derived from the amino acid sequences of any of SEQ ID NOS: 3 to 8 one or more conservative amino acid substitution; and/or
(viii) comprising the amino acid sequence of
SEQ ID NO: 1, or a functionally active variant thereof, and/or
SEQ ID NO: 2, or a functionally active variant thereof, and/or
SEQ ID NO: 9, or a functionally active variant thereof, and/or
SEQ ID NO: 10, or a functionally active variant thereof, and/or
SEQ ID NO: 11, or a functionally active variant thereof, or
(ix) consisting of the amino acid sequence of
SEQ ID NO: 1, or a functionally active variant thereof, and
SEQ ID NO: 2, or a functionally active variant thereof, and
optionally 50 additional amino acid residue(s), preferably 1 to 40, more preferably 1 to 30, even more preferably at most 1 to 25, still more preferably at most 1 to 10, most preferably 1, 2, 3, 4 or 5 additional amino acids residue(s) or
(x) consisting of the amino acid sequence of
SEQ ID NO: 9, or a functionally active variant thereof, and
SEQ ID NO: 10, or a functionally active variant thereof, and
optionally 50 additional amino acid residue(s), preferably 1 to 40, more preferably 1 to 30, even more preferably at most 1 to 25, still more preferably at most 1 to 10, most preferably 1, 2, 3, 4 or 5 additional amino acids residue(s) or
(xi) consisting of the amino acid sequence of
SEQ ID NO: 9, or a functionally active variant thereof, and
SEQ ID NO: 11, or a functionally active variant thereof, and
optionally 50 additional amino acid residue(s), preferably 1 to 40, more preferably 1 to 30, even more preferably at most 1 to 25, still more preferably at most 1 to 10, most preferably 1, 2, 3, 4 or 5 additional amino acids residue(s).

### Claim 5 (depends on 1, 2, 3, 4)

Peptide or peptide complex according to one of the claims 1-4;
wherein the functionally active variant of LDR1 comprises the mutation at amino acid position 11, particularly 11Asn→Gln; and/or
wherein the functionally active variant of HDR2 comprises the mutation at amino acid position 6, particularly 6Asp→Glu; and/or
wherein the functionally active variant of SEQ ID NO: 1 comprises one or more mutations at amino acid positions 9, 12, 15, 22, 34, 46, 47, 80, 83, 85, 87 and/or 89, particularly selected from the group consisting of 9Ala→Ser, 12Ala→Ser, 15Leu→Val, 15Leu→Pro, 22Ser→Thr, 34Asn→Gln, 46Gln→Lys, 47Ala→Pro, 80Asp→Asn, 83Glu→Gln, 85Asp→Glu, 87Ala→Thr and 89Thr→Asn; and/or
wherein the functionally active variant of SEQ ID NO: 2 comprises one or more mutations at amino acids positions 5, 7, 11, 12, 17, 20, 38, 40, 43, 55, 61, 65, 66, 67, 76, 81, 82, 87, 91, 93, 112, 113 and/or 116, particularly selected from the group consisting of 5His→Val, 7Pro→Ser, 11Leu→Val, 12Val→Lys, 17Pro→Ser, 20Leu→Val, 38Lys→Arg, 40Arg→Ala, 43Arg→Gln, 55Asp→Glu, 61Asn→Ala, 65Lys→Gln, 66Asp→Gly, 67Lys→Arg, 76Ser→Thr, 81Ile→Met, 82Gln→Glu, 87Thr→Arg, 91Ser→Thr, 93Val→Lys, 112Thr→Leu, 113Leu→Val and 116Ser→Val.

### Claim 6 (depends on 1, 2, 3, 4, 5)

The Peptide or peptide complex according to any of the claims 1-5, wherein said antibody or fragment specifically binds to the I-domain of the human α2-integrin with nM binding affinity.

### Claim 7 (depends on 1, 2, 3, 4, 5, 6)

The Peptide or peptide complex according to any of the claims 1-6, wherein said peptide or peptide complex inhibits the interaction of the human α2-integrin with collagen in vitro, thereby inhibiting the activation of platelets due to adhesion of said platelets to said collagen.

### Claim 8

The Peptide or peptide complex according to any of the previous claims, said heavy chain variable region domain comprising the heavy chain HCDR3 of SEQ ID NO:5.

### Claim 9

The Peptide or peptide complex according to any of the previous claims, said heavy chain variable region domain comprising the heavy chain CDRs of SEQ ID NO:3 (HCDR1), SEQ ID NO:4 (HCDR2), and SEQ ID NO:5 (HCDR3), or functionally active variants thereof.

### Claim 10 (depends on 9)

The Peptide or peptide complex according to claim 9, wherein the functionally active variant of HCDR2 comprises the mutation Asp→Glu at amino acid position 6.

### Claim 11

The Peptide or peptide complex according to any one of the previous claims, said light chain variable region domain comprising the light chain LCDR3 of SEQ ID NO:8.

### Claim 12

The Peptide or peptide complex according to any one of the previous claims, said light chain variable region domain comprising the light chain CDRs of SEQ ID NO:6 (LCDR1), SEQ ID NO:7 (LCDR2), and SEQ ID NO:8 (LCDR3), or functionally active variants thereof.

### Claim 13 (depends on 12)

The Peptide or peptide complex according to claim 12, wherein the functionally active variant of LCDR1 comprises the mutation Asn→Gln at amino acid position 11.

### Claim 14

The Peptide or peptide complex according to any one of the previous claims, said heavy chain variable region (VH) domain having at least 90%, 95%, 97% or 99% sequence identity to the VH sequence of SEQ ID NO: 2.

### Claim 15 (depends on 14)

The Peptide or peptide complex according to claim 14, wherein said heavy chain variable region (VH) domain comprises the sequence of SEQ ID NO:2 or a functionally active variant thereof.

### Claim 16

The Peptide or peptide complex according to any one of the previous claims, said light chain variable region (VL) domain having at least 90%, 95%, 97% or 99% sequence identity to the VL sequence of SEQ ID NO: 1.

### Claim 17 (depends on 16)

The Peptide or peptide complex according to claim 16, wherein said light chain variable region (VL) domain comprises the sequence of SEQ ID NO:1 or a functionally active thereof.

### Claim 18

The Peptide or peptide complex according to any one of the previous claims, wherein said heavy chain variable region (VH) domain comprises one or more amino acid substitutions at positions selected from the group consisting of H5, H7, H11, H12, H17, H20, H38, H40, H43, H55, H61, H65, H66, H67, H76, H81, H82, H87, H91, H93, H112, H113 and H116.

### Claim 19 (depends on 18)

The Peptide or peptide complex according to claim 18, wherein the one or more amino acid substitutions are selected from the group consisting 5His→Val, 7Pro→Ser, 11Leu→Val, 12Val→Lys, 17Pro→Ser, 20Leu→Val, 38Lys→Arg, 40Arg→Ala, 43Arg→Gln, 55Asp→Glu, 61Asn→Ala, 65Lys→Gln, 66Asp→Gly, 67Lys→Arg, 76Ser→Thr, 81Ile→Met, 82Gln→Glu, 87Thr→Arg, 91Ser→Thr, 93Val→Lys, 112Thr→Leu, 113Leu→Val and 116Ser→Val.

### Claim 20

The Peptide or peptide complex according to any one of the previous claims, wherein said light chain variable region (VL) domain comprises one or more amino acid substitutions at positions selected from the group consisting of L9, L12, L15, L22, L34, L46, L47, L80, L83, L85, L87, and L89.

### Claim 21 (depends on 20)

The Peptide or peptide complex according to claim 20, wherein the one or more amino acid substitutions are selected from the group consisting of 9Ala→Ser, 12Ala→Ser, 15Leu→Val, 15Leu→Pro, 22Ser→Thr, 34Asn→Gln, 46Gln→Lys, 47Ala→Pro, 80Asp→Asn, 83Glu→Gln, 85Asp→Glu, 87Ala→Thr and 89Thr→Asn.

### Claim 22

The Peptide or peptide complex according to any one of the previous claims, said heavy chain variable region (VH) domain having at least 90%, 95%, 97% or 99% sequence identity to a VH sequence selected from the group consisting of SEQ ID NO: 38 (HC1), SEQ ID NO:39 (HC2), SEQ ID NO:40 (HC3), SEQ ID NO:41 (HC4), SEQ ID NO:42 (HC5), SEQ ID NO:43 (HC6), and SEQ ID NO:44 (HC7).

### Claim 23 (depends on 22)

The Peptide or peptide complex according to claim 22 said heavy chain variable region (VH) domain comprising a VH sequence selected from the group consisting of SEQ ID NO: 38 (HC1), SEQ ID NO:39 (HC2), SEQ ID NO:40 (HC3), SEQ ID NO:41 (HC4), SEQ ID NO:42 (HC5), SEQ ID NO:43 (HC6), and SEQ ID NO:44 (HC7).

### Claim 23

The Peptide or peptide complex according to any one of the previous claims, said light chain variable region (VL) domain having at least 90%, 95%, 97% or 99% sequence identity to a VL sequence selected from the group consisting of SEQ ID NO: 33 (LC1), SEQ ID NO:34 (LC2), SEQ ID NO:35 (LC3), SEQ ID NO:36 (LC4), and SEQ ID NO:37 (LC5).

### Claim 25 (depends on 24)

The Peptide or peptide complex according to claim 24, said light chain variable region (VL) domain comprising a VL sequence selected from the group consisting of SEQ ID NO: 33 (LC1), SEQ ID NO:34 (LC2), SEQ ID NO:35 (LC3), SEQ ID NO:36 (LC4), and SEQ ID NO:37 (LC5).

### Claim 26

The Peptide or peptide complex according to any one of the previous claims, wherein said antibody or binding portion is a chimeric antibody or humanized antibody.

### Claim 27

The Peptide or peptide complex according to any one of the previous claims, wherein the antigen binding portion is selected from the group consisting of a Fab, a Fab′, a F(ab′)2, a Fv, a disulfide linked Fv, a scFv, and a (scFv)2.

### Claim 28

The Peptide or peptide complex according to any one of the previous claims, which is selected from the group consisting of a multispecific antibody, a dual specific antibody, a isotype antibody, a dual variable domain antibody and a bispecific antibody.

### Claim 29

The Peptide or peptide complex according to any one of the previous claims, comprising a heavy chain immunoglobulin constant domain selected from the group consisting of: a human IgM constant domain, a human IgG1 constant domain, a human IgG2 constant domain, a human IgG3 constant domain, domain, a human IgG4 constant domain, a human IgE constant domain, and a human IgA constant domain.

### Claim 30

The Peptide or peptide complex according to any one of the previous claims, comprising a human IgG4 constant domain.

### Claim 31

The Peptide or peptide complex according to according to any of the previous claims, wherein the peptide or peptide complex comprises or consists of an isolated monoclonal antibody or antigen binding fragment thereof.

### Claim 32 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31)

One or more nucleic acid(s) coding for the peptide or peptide complex according to any of claims 1 to 31.

### Claim 33 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31)

Peptide or peptide complex according to one of the claims 1-31 for use in the treatment, prophylaxis or diagnosis of an α2-integrin-related disorder or disease.

### Claim 34 (depends on 32)

The nucleic(s) of claim 32, wherein the nucleic acid(s) is/are located in a vector.

### Claim 35 (depends on 32, 34)

A cell heterologously expressing one of the nucleic acids according to claim 32 or 34.

### Claim 36 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 35)

A method for producing a peptide or peptide complex according to any of claims 1 to 31 comprising culturing the cell according to claim 35 under conditions permitting expression of the peptide or peptide complex and optionally recovering the peptide or peptide complex from the host cell.

### Claim 37 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 34)

A pharmaceutical composition comprising at least one peptide or peptide complex according to any of claims 1 to 31 and/or at least one nucleic acid according to claim 32 or 34 for use as a medicament.

### Claim 38 (depends on 37)

The pharmaceutical composition of claim 37 for use in treating or preventing an α2 integrin-related disease or disorder, preferably selected from the group consisting of thrombosis, a vascular disease, cancer, including neo-angiogenesis and metastasis, inflammation, inflammatory disease, autoimmune disease and a disease characterized by abnormal or increase angiogenesis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, reactions to transplant, optical neuritis, spinal cord trauma, rheumatoid arthritis, systemic lupus erythematosus (SLE), multiple sclerosis, Reynaud's syndrome, experimental autoimmune encephalomyelitis, Sjorgen's syndrome, scleroderma, cardiovascular disease, psoriasis, and infections that induce an inflammatory response.

### Claim 39 (depends on 37)

The pharmaceutical composition of claim 37 for use in treating or preventing a vascular disease and/or thrombosis, particularly in the treatment of acute coronary syndrome, percutaneous coronary intervention, ischemic stroke, carotid artery stenosis or peripheral arterial occlusive disease.

### Claim 40 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31)

A method of diagnosing a disease associated with altered α2 integrin, the method comprising
a) contacting a sample comprising α2 integrin with the peptide or peptide complex of any of claims 1 to 31; and
b) detecting binding of α2 integrin to the peptide or peptide complex; and
c) comparing the binding of step b) with a reference,
wherein a altered α2 integrin binding in the sample relative to the reference is indicative of the disease.

### Claim 41 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 33, 36, 37, 38)

Article of manufacture comprising
a) a packaging material,
b) a peptide or peptide complex according to one of the claim 1-31 or 33 or a pharmaceutically acceptable salt thereof or comprising the pharmaceutical composition of one of the claims 36-38
c) a label or a package insert, the insert contained within said packaging material, indicating that said peptide or peptide complex is effective for treatment of a disease or disorder, especially an α2 integrin-related disease disorder.

### Claim 42 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31)

Diagnostic kit for the diagnosis of an α2-integrin related disorder or disease comprising a peptide or peptide complex according to one of the claims 1-31 and a suitable packaging, and possibly suitable instructions for using said peptide or peptide complex in the detection of a 2 integrin.

### Claim 43 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 34, 36, 37, 38)

Method of treatment or diagnosis of an α2 integrin-related disorder or disease using one or more peptide or peptide complex according to one of the claims 1-31 and/or one or more nucleic acids according to claim 32 or 34 or one of the pharmaceutical compositions according to one of claims 36-38.

### Claim 44 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31)

A method of diagnosing a disease associated with altered α2 integrin, the method comprising
a) contacting a taken sample of an individual with the peptide or peptide complex of any of claims 1 to 31; and
b) detecting binding of α2 integrin to the peptide or peptide complex; and
c) comparing the binding of step b) with the binding of α2 integrin to the peptide or peptide complex in one or more reference samples,
wherein an altered binding in the taken sample relative to the binding detected in the one or more reference samples is indicative of the disease.