# US 10,501,533 B2 · Engineered antibody for inhibition of fibrosis

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- Number: US 10,501,533 B2
- Document ID: US10501533B2
- Status: Granted
- Kind: B2
- Application number: 15/699,083
- Filed: 2017-09-08
- Published: 2018-03-15
- Granted: 2019-12-10
- Earliest claimed: 2012-04-20
- Assignees: Thomas Jefferson University
- Applicants: Thomas Jefferson University
- Inventors: Andrzej Fertala; Andrzej Steplewski
- Web page: https://patentgrep.com/patent/US10501533B2

## CPC

- C07K 16/18: against material from animals or humans
- A61K 2039/505: {comprising antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/622: Single chain antibody (scFv)
- 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: 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)
- 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

A chimeric, humanized or single-chain antibody contains a light chain variable region containing the complementarity determining regions of SEQ ID NO:1, SEQ ID NO:2 and SEQ ID NO:3, and a heavy chain variable region containing the complementarity determining regions SEQ ID NO:5 and SEQ ID NO:6. The antibody or antibody fragment thereof is capable of binding the C-terminal telopeptide of the α2(I) chain of human collagen I, and is useful in the treatment of diseases or disorders associated with excessive collagen fibril.

## Claims

### Claim 1

A polynucleotide for expressing a chimeric antibody light chain, said polynucleotide comprising a first segment encoding an antibody light chain variable region having the amino acid sequence shown in SEQ ID NO:10 and a second segment encoding a human antibody light chain constant region.

### Claim 2 (depends on 1)

The polynucleotide according to claim 1, wherein the first segment comprises the nucleotide sequence shown in SEQ ID NO:22.

### Claim 3

A polynucleotide for expressing a chimeric antibody heavy chain, said polynucleotide comprising a first segment encoding an antibody heavy chain variable region having the amino acid sequence shown in SEQ ID NO:11 and a second segment encoding a human antibody heavy chain constant region.

### Claim 4 (depends on 3)

The polynucleotide according to claim 3, wherein the first segment comprises the nucleotide sequence shown in SEQ ID NO:23.

### Claim 5

A polynucleotide for expressing a single chain antibody comprising a first segment encoding an antibody light chain variable region having the amino acid sequence shown in SEQ ID NO:9, SEQ ID NO:10 or SEQ ID NO:26, and a second segment encoding an antibody heavy chain variable region comprising the amino acid sequence shown in SEQ ID NO:11.

### Claim 6 (depends on 5)

The polynucleotide of claim 5 comprising a linker segment between said first and second segments, said linker segment encoding a linker comprising one or more amino acids.

### Claim 7 (depends on 6)

The polynucleotide according to claim 6, wherein the linker segment encodes a linker comprising from two to twelve repeats of the amino acid sequence Gly-Gly-Ser, or from two to twelve repeats of the amino acid sequence Gly-Gly-Gly-Gly-Ser (SEQ ID NO:29).

### Claim 8 (depends on 7)

The polynucleotide according to claim 7 wherein the first DNA segment comprises the nucleotide sequence SEQ ID NO:22, SEQ ID NO:27 or SEQ ID NO:28, and the second DNA segment comprises the nucleotide sequence SEQ ID NO:23.

### Claim 9 (depends on 5)

The polynucleotide according to claim 5, encoding a single chain antibody comprising the amino acid sequence SEQ ID NO:12.

### Claim 10 (depends on 9)

The polynucleotide according to claim 9, comprising the nucleotide sequence SEQ ID NO:13.

### Claim 11 (depends on 5)

The polynucleotide according to claim 5, encoding a single chain antibody comprising the amino acid sequence SEQ ID NO:16.

### Claim 12 (depends on 11)

The polynucleotide according to claim 11, comprising the nucleotide sequence SEQ ID NO:17.