# US 10,865,238 B1 · Complement factor H antibodies

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- Number: US 10,865,238 B1
- Document ID: US10865238B1
- Status: Granted
- Kind: B1
- Application number: 15/973,345
- Filed: 2018-05-07
- Granted: 2020-12-15
- Earliest claimed: 2017-05-05
- Assignees: Duke University
- Applicants: Duke University
- Inventors: Edward F. Patz, Jr.; Michael J. Campa; Elizabeth Gottlin; Barton F. Haynes; Hua-Xin Liao; Michael Anthony Moody
- Web page: https://patentgrep.com/patent/US10865238B1

## CPC

- C07K 16/18: against material from animals or humans
- A61P 35/00: Antineoplastic agents
- C07K 16/2803: {against the immunoglobulin superfamily}
- C07K 16/2863: {against receptors for growth factors, growth regulators}
- C07K 16/2887: {against CD20}
- A61K 2039/507: {Comprising a combination of two or more separate antibodies}
- C07K 2317/21: from primates, e.g. man
- 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 2317/70: characterized by effect upon binding to a cell or to an antigen
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/734: Complement-dependent cytotoxicity [CDC]
- 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
- 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

Disclosed herein are Complement factor H (CFH) antibodies and methods of using the antibodies.

## Claims

### Claim 1

An isolated antibody or antibody fragment thereof which immunospecifically binds to Complement Factor H (CFH) protein, wherein the antibody comprises:
i. a variable heavy domain chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:11, a CDR2 comprising the amino acid sequence of SEQ ID NO:21, and a CDR comprising the amino acid sequence of SEQ ID NO:31, and a variable light domain chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:51, a CDR2 comprising the amino acid sequence of SEQ ID NO:61, and a CDR3 comprising the amino acid sequence of SEQ ID NO:71;
ii. a variable heavy domain chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:12, a CDR2 comprising the amino acid sequence of SEQ ID NO:22, and a CDR comprising the amino acid sequence of SEQ ID NO:32, and a variable light domain chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:52, a CDR2 comprising the amino acid sequence of SEQ ID NO:62, and a CDR3 comprising the amino acid sequence of SEQ ID NO:72;
iii. a variable heavy domain chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:13, a CDR2 comprising the amino acid sequence of SEQ ID NO:23, and a CDR comprising the amino acid sequence of SEQ ID NO:33, and a variable light domain chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:53, a CDR2 comprising the amino acid sequence of SEQ ID NO:63, and a CDR3 comprising the amino acid sequence of SEQ ID NO:73;
iv. a variable heavy domain chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:14, a CDR2 comprising the amino acid sequence of SEQ ID NO:24, and a CDR comprising the amino acid sequence of SEQ ID NO:34, and a variable light domain chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:54, a CDR2 comprising the amino acid sequence of SEQ ID NO:64, and a CDR3 comprising the amino acid sequence of SEQ ID NO:74;
v. a variable heavy domain chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:15, a CDR2 comprising the amino acid sequence of SEQ ID NO:25, and a CDR comprising the amino acid sequence of SEQ ID NO:35, and a variable light domain chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:55, a CDR2 comprising the amino acid sequence of SEQ ID NO:65, and a CDR3 comprising the amino acid sequence of SEQ ID NO:75;
vi. a variable heavy domain chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:16, a CDR2 comprising the amino acid sequence of SEQ ID NO:26, and a CDR comprising the amino acid sequence of SEQ ID NO:36, and a variable light domain chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:56, a CDR2 comprising the amino acid sequence of SEQ ID NO:66, and a CDR3 comprising the amino acid sequence of SEQ ID NO:76;
vii. a variable heavy domain chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:17, a CDR2 comprising the amino acid sequence of SEQ ID NO:27, and a CDR comprising the amino acid sequence of SEQ ID NO:37, and a variable light domain chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:57, a CDR2 comprising the amino acid sequence of SEQ ID NO:67, and a CDR3 comprising the amino acid sequence of SEQ ID NO:77;
viii. a variable heavy domain chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:18, a CDR2 comprising the amino acid sequence of SEQ ID NO:28, and a CDR comprising the amino acid sequence of SEQ ID NO:38, and a variable light domain chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:58, a CDR2 comprising the amino acid sequence of SEQ ID NO:68, and a CDR3 comprising the amino acid sequence of SEQ ID NO:78;
ix. a variable heavy domain chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:19, a CDR2 comprising the amino acid sequence of SEQ ID NO:29, and a CDR comprising the amino acid sequence of SEQ ID NO:39, and a variable light domain chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:59, a CDR2 comprising the amino acid sequence of SEQ ID NO:69, and a CDR3 comprising the amino acid sequence of SEQ ID NO:79; or
x. a variable heavy domain chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:20, a CDR2 comprising the amino acid sequence of SEQ ID NO:30, and a CDR comprising the amino acid sequence of SEQ ID NO: 40, and a variable light domain chain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO:60, a CDR2 comprising the amino acid sequence of SEQ ID NO:70, and a CDR3 comprising the amino acid sequence of SEQ ID NO:80.

### Claim 2 (depends on 1)

The isolated antibody or antibody fragment of claim 1, wherein the isolated antibody or antibody fragment thereof binds to an epitope within short consensus repeat (SCR) 19 of CFH protein and the epitope is a cryptic epitope that is exposed in a tumor-bound form of CFH.

### Claim 3 (depends on 2)

The isolated antibody or antibody fragment of claim 2, wherein the epitope comprises PIDNGDIT (SEQ ID NO: 3).

### Claim 4 (depends on 1)

The isolated antibody or antibody fragment of claim 1, wherein the antibody comprises:
a) a variable heavy domain comprising the amino acid sequence of SEQ ID NO:1 and a variable light domain region comprising the amino acid sequence of SEQ ID NO:41;
b) a variable heavy domain comprising the amino acid sequence of SEQ ID NO:2 and a variable light domain region comprising the amino acid sequence of SEQ ID NO:42;
c) a variable heavy domain comprising the amino acid sequence of SEQ ID NO:3 and a variable light domain region comprising the amino acid sequence of SEQ ID NO:43;
d) a variable heavy domain comprising the amino acid sequence of SEQ ID NO:4 and a variable light domain region comprising the amino acid sequence of SEQ ID NO:44;
e) a variable heavy domain comprising the amino acid sequence of SEQ ID NO:5 and a variable light domain region comprising the amino acid sequence of SEQ ID NO:45;
f) a variable heavy domain comprising the amino acid sequence of SEQ ID NO:6 and a variable light domain region comprising the amino acid sequence of SEQ ID NO:46;
g) a variable heavy domain comprising the amino acid sequence of SEQ ID NO:7 and a variable light domain region comprising the amino acid sequence of SEQ ID NO:47;
h) a variable heavy domain comprising the amino acid sequence of SEQ ID NO:8 and a variable light domain region comprising the amino acid sequence of SEQ ID NO:48;
i) a variable heavy domain comprising the amino acid sequence of SEQ ID NO:9 and a variable light domain region comprising the amino acid sequence of SEQ ID NO:49; or
j) a variable heavy domain comprising the amino acid sequence of SEQ ID NO:10 and a variable light domain region comprising the amino acid sequence of SEQ ID NO:50.

### Claim 5 (depends on 1)

The isolated antibody or antibody fragment of claim 1, wherein the isolated antibody or antibody fragment does not cross-react with at least one of systemic lupus erythematosus autoantigens SSA, SSB, sphingomyelin (Sm), ribonucleoprotein (RNP), sclerosis autoantigen (Scl-70), histidine-tRNA ligase (Jo-1), double-stranded DNA (dsDNA), centromere B (CentB), and histones.

### Claim 6 (depends on 1)

The isolated antibody or antibody fragment of claim 1, wherein the isolated antibody or antibody fragment is selected from the group consisting of a human antibody, an immunoglobulin molecule, a disulfide linked Fv, a monoclonal antibody, an affinity matured, a scFv, a chimeric antibody, a single domain antibody, a CDR-grafted antibody, a diabody, a humanized antibody, a multispecific antibody, a Fab, a dual specific antibody, a DVD, a TVD, a Fab′, a bispecific antibody, a F(ab′)2, and a Fv.

### Claim 7 (depends on 1)

The isolated antibody or antibody fragment of claim 1, wherein the isolated antibody or antibody fragment comprises a heavy chain immunoglobulin constant domain selected from the group consisting of a human IgM constant domain, a human IgG4 constant domain, a human IgG1 constant domain, a human IgE constant domain, a human IgG2 constant domain, a human igG3 constant domain, and a human IgA constant domain.

### Claim 8 (depends on 1)

A pharmaceutical composition comprising the isolated antibody or antibody fragment of claim 1.

### Claim 9 (depends on 1)

A method of inhibiting Complement Factor H (CFH) binding to C3b in a subject having cancer the method comprising administering to the subject the isolated antibody or antibody fragment of claim 1.

### Claim 10 (depends on 9)

The method of claim 9, wherein the cancer is lung cancer.

### Claim 11 (depends on 9)

The method of claim 9, further comprising administering an effective amount of at least one of Cetuximab, pertuzumab, or trastuzumab.

### Claim 12 (depends on 1)

A method of increasing complement dependent lysis of a cell, increasing C3b deposition on a cell, or inhibiting Complement Factor H (CFH) binding to C3b in a subject or a cell, the method comprising administering to the cell the isolated antibody or antibody fragment of claim 1.