# US 11,897,946 B2 · Methods of inhibiting complement factor H (CFH) comprising administering an antibody that binds CFH > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,897,946 B2 - Document ID: US11897946B2 - Status: Granted - Kind: B2 - Application number: 17/458,019 - Filed: 2021-08-26 - Published: 2021-12-23 - Granted: 2024-02-13 - Earliest claimed: 2013-06-07 - Assignees: Duke University - Applicants: Duke University - Inventors: Edward F. Patz, Jr.; Michael J. Campa; Elizabeth Gottlin; Barton F. Haynes; Hua-Xin Liao; M. Anthony Moody - Web page: https://patentgrep.com/patent/US11897946B2 ## CPC - C07K 16/18: against material from animals or humans - A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines} - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 35/00: Antineoplastic agents - C07K 14/4702: {Regulators; Modulating activity} - C07K 14/72: for hormones {(for neuromediators C07K14/70571)} - G01N 33/564: for pre-existing immune complex or autoimmune disease {, i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9} - G01N 33/6872: {Intracellular protein regulatory factors and their receptors, e.g. including ion channels} - G01N 33/6878: {in epitope analysis} - A61K 2039/505: {comprising antibodies} - A61K 2039/507: {Comprising a combination of two or more separate antibodies} - C07K 16/2863: {against receptors for growth factors, growth regulators} - C07K 2317/21: from primates, e.g. man - 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 2317/51: Complete heavy chain or Fd fragment, i.e. VH + CH1 - C07K 2317/565: Complementarity determining region [CDR] - C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation - C07K 2317/734: Complement-dependent cytotoxicity [CDC] - 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 - G01N 2333/4716: Complement proteins, e.g. anaphylatoxin, C3a, C5a - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - 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 Disclosed herein are Complement factor H (CFH) inhibitors, such as anti-CFH antibodies and small molecules, and methods of using said inhibitors. ## Claims ### Claim 1 A method for inhibiting complement factor H (CFH) protein in a subject by administering a therapeutically effective amount of an isolated antibody or antibody fragment thereof which immunospecifically binds to Complement Factor H (CFH) protein, wherein the isolated antibody or antibody fragment thereof binds to an epitope of PIDNGDIT (SEQ ID NO: 3) within short consensus repeat (SCR) 19 of CFH protein, wherein the antibody comprises: (a) a variable heavy domain comprising the amino acid sequence of SEQ ID NO: 73 and a variable light domain region comprising the amino acid sequence of SEQ ID NO: 84; (b) a variable heavy domain comprising the amino acid sequence of SEQ ID NO: 74 and a variable light domain region comprising the amino acid sequence of SEQ ID NO: 83; (c) a variable heavy domain comprising the amino acid sequence of SEQ ID NO: 75 and a variable light domain region comprising the amino acid sequence of SEQ ID NO: 85; (d) a variable heavy domain comprising the amino acid sequence of SEQ ID NO: 78 and a variable light domain region comprising the amino acid sequence of SEQ ID NO: 88; (e) a variable heavy domain comprising the amino acid sequence of SEQ ID NO: 79 and a variable light domain region comprising the amino acid sequence of SEQ ID NO: 89; (f) a variable heavy domain comprising the amino acid sequence of SEQ ID NO: 76 and a variable light domain region comprising the amino acid sequence of SEQ ID NO: 86; or (g) a variable heavy domain comprising the amino acid sequence of SEQ ID NO: 77 and a variable light domain region comprising the amino acid sequence of SEQ ID NO: 87. ### Claim 2 (depends on 1) The method of claim 1, wherein the isolated antibody or antibody fragment thereof comprises a variable heavy domain comprising the amino acid sequence of SEQ ID NO: 79 and a variable light domain region comprising the amino acid sequence of SEQ ID NO: 89. ### Claim 3 (depends on 1) The method of claim 1, wherein the isolated antibody or antibody fragment thereof 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 4 (depends on 1) The method of claim 1, wherein the isolated antibody or antibody fragment thereof 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 5 (depends on 1) The method of claim 1, wherein the subject has cancer. ### Claim 6 (depends on 1) The method of claim 1, wherein the subject has a cancer that uses CFH as a protective mechanism. ### Claim 7 (depends on 1) The method of claim 1, wherein the subject has lung cancer or breast cancer. ### Claim 8 (depends on 1) The method of claim 1, wherein the subject has non-small cell lung carcinoma. ### Claim 9 (depends on 1) The method of claim 1, wherein the method further comprises administering a therapeutically effective amount of one or more of doxorubicin, epirubicin, daunorubicin, capecitabine, carboplatin, cisplatin, cyclophosphamide, eribulin, fluorouracil, gemcitabine, ixabepilone, methotrexate, mitoxantrone, mitomycin, paclitaxel, docetaxel, thiotepa, vincristine, vinorelbine, lapatinib, onartuzumab, rilotumumab, ficlatuzumab, bevacizumab, rituximab, panatumamab, cetuximab, pertuzumab, or trastuzumab. ### Claim 10 A method for increasing complement dependent lysis of a cell, the method comprising administering to a cell a therapeutically effective amount of an isolated antibody or antibody fragment thereof which immunospecifically binds to Complement Factor H (CFH) protein, wherein the isolated antibody or antibody fragment thereof binds to an epitope of PIDNGDIT (SEQ ID NO: 3) within short consensus repeat (SCR) 19 of CFH protein, wherein the antibody comprises: (a) a variable heavy domain comprising the amino acid sequence of SEQ ID NO: 73 and a variable light domain region comprising the amino acid sequence of SEQ ID NO: 84; (b) a variable heavy domain comprising the amino acid sequence of SEQ ID NO: 74 and a variable light domain region comprising the amino acid sequence of SEQ ID NO: 83; (c) a variable heavy domain comprising the amino acid sequence of SEQ ID NO: 75 and a variable light domain region comprising the amino acid sequence of SEQ ID NO: 85; (d) a variable heavy domain comprising the amino acid sequence of SEQ ID NO: 78 and a variable light domain region comprising the amino acid sequence of SEQ ID NO: 88; (e) a variable heavy domain comprising the amino acid sequence of SEQ ID NO: 79 and a variable light domain region comprising the amino acid sequence of SEQ ID NO: 89; (f) a variable heavy domain comprising the amino acid sequence of SEQ ID NO: 76 and a variable light domain region comprising the amino acid sequence of SEQ ID NO: 86; or (g) a variable heavy domain comprising the amino acid sequence of SEQ ID NO: 77 and a variable light domain region comprising the amino acid sequence of SEQ ID NO: 87. ### Claim 11 (depends on 10) The method of claim 10, wherein the isolated antibody or antibody fragment thereof comprises a variable heavy domain comprising the amino acid sequence of SEQ ID NO: 79 and a variable light domain region comprising the amino acid sequence of SEQ ID NO: 89. ### Claim 12 (depends on 10) The method of claim 10, wherein the isolated antibody or antibody fragment thereof 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 13 (depends on 10) The method of claim 10, wherein the isolated antibody or antibody fragment thereof 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 14 (depends on 10) The method of claim 10, wherein the cell is a cancer cell. ### Claim 15 (depends on 10) The method of claim 10, wherein the cell is a cancer cell that uses CFH as a protective mechanism. ### Claim 16 (depends on 10) The method of claim 10, wherein the cell is a lung cancer cell or breast cancer cell. ### Claim 17 (depends on 10) The method of claim 10, wherein the cell is non-small cell lung carcinoma cell.