# US 9,040,049 B2 · ADAM-15 antibodies and immunogenic peptides

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- Number: US 9,040,049 B2
- Document ID: US9040049B2
- Status: Granted
- Kind: B2
- Application number: 12/934,541
- Filed: 2009-03-24
- Published: 2011-05-19
- Granted: 2015-05-26
- Earliest claimed: 2008-03-24
- Assignees: Vasgen Limited
- Applicants: Salman Rahman; Yatin Patel; Holger Gerhardt; Andrea Emma Lundkvist
- Inventors: Salman Rahman; Yatin Patel; Holger Gerhardt; Andrea Emma Lundkvist
- Web page: https://patentgrep.com/patent/US9040049B2

## CPC

- C07K 16/40: against enzymes
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- C12N 15/1137: {against enzymes (viral enzymes C12N15/1131; receptors C12N15/1138)}
- A61K 2039/505: {comprising antibodies}
- C07K 2299/00: Coordinates from 3D structures of peptides, e.g. proteins or enzymes
- C07K 2317/14: Specific host cells or culture conditions, e.g. components, pH or temperature
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/75: Agonist effect on antigen
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2310/141: MicroRNAs, miRNAs
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

The present invention relates to antibodies and antigen-binding fragments thereof, immunogenic peptide(s), and siRNA molecules which are capable of inhibiting neovascularization and/or angiogenesis and endothelial cell proliferation. The invention relates to antibodies and antigen-binding fragments thereof with specificity towards the metalloprotease domain of ADAM 15 and to immunogenic peptide(s) that elicits such antibodies. The invention also relates to compositions and kits comprising the antibodies and immunogenic peptide(s) of the invention, as well as methods and uses of the antibodies and antigen-binding fragments thereof and immunogenic peptide(s), as well as siRNA molecules.

## Claims

### Claim 1

An isolated monoclonal antibody or antigen-binding fragment thereof that inhibits neovascularization, wherein the antibody or antigen-binding fragment thereof specifically binds to the catalytic cleft of the ADAM 15 metalloprotease domain and specifically inhibits ADAM 15 metalloprotease activity.

### Claim 2 (depends on 1)

The isolated antibody or antigen-binding fragment thereof of claim 1, wherein the antibody or antigen-binding fragment thereof specifically binds to a peptide having an amino acid sequence:
IAHELGHSLGLDHD
(SEQ ID NO: 3)
or a peptide with at least 90% sequence identity to SEQ ID NO: 3.

### Claim 3 (depends on 1)

The isolated antibody or antigen-binding fragment thereof of claim 1, wherein the antibody or antigen-binding fragment thereof specifically binds to an epitope on human ADAM 15 polypeptide, wherein the epitope comprises amino acids 346-359 of SEQ ID NO: 1.

### Claim 4 (depends on 1)

The isolated antibody or antigen-binding fragment thereof of claim 1, wherein the antibody or antigen-binding fragment thereof is a mouse, humanized, human, recombinant, chimeric, or synthetic antibody or antigen-binding fragment thereof.

### Claim 5 (depends on 1)

The isolated antibody or antigen-binding fragment thereof of claim 1, wherein the antibody or antigen-binding fragment thereof is capable of:
preventing proteolytic cleavage of the urokinase receptor (uPAR) by ADAM 15,
inhibiting the activation of the phosphoinositol 3 kinase (PI3 kinase) pathway including the Akt kinase (protein kinase B),
inhibiting the inactivation of glycogen synthase kinase 3 (GSK 3),
inhibiting cell survival, and/or
inhibiting endothelial cell proliferation.

### Claim 6 (depends on 1)

The isolated antibody or antigen-binding fragment of claim 1, wherein the antibody or antigen-binding fragment thereof comprises Fab, Fab1, F(ab′)2, scFv, Fv, dsFv, ds-scFv, Fd, dAbs, TandAbs dimers, minibodies, diabodies, multimers thereof, or a bispecific antibody fragment.

### Claim 7 (depends on 1)

The isolated antibody or antigen-binding fragment thereof of claim 1, wherein the antibody or antigen-binding fragment thereof specifically binds to an epitope on human ADAM 15 polypeptide,
wherein the epitope comprises amino acids His352, Ser353, Leu354, Gly355, Leu356, Asp357 and Asp359 of SEQ ID NO: 1; or
wherein the epitope comprises amino acids Leu354, Gly355, Leu356, Asp357, His358 and Asp359 of SEQ ID NO: 1.
