# US 2019/0169232 A1 · C1q AND HMGB1 FUSION PROTEINS AND USES THEREOF > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2019/0169232 A1 - Document ID: US20190169232A1 - Status: Published application - Kind: A1 - Application number: 16/263,389 - Filed: 2019-01-31 - Published: 2019-06-06 - Earliest claimed: 2016-08-03 - Assignees: The Feinstein Institute for Medical Research - Applicants: The Feinstein Institute for Medical Research - Inventors: Betty A. Diamond - Web page: https://patentgrep.com/patent/US20190169232A1 ## CPC - C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68) - A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection - C07K 14/4702: {Regulators; Modulating activity} - C07K 14/472: {Complement proteins, e.g. anaphylatoxin, C3a, C5a} - C07K 16/2803: {against the immunoglobulin superfamily} - C07K 16/46: Hybrid immunoglobulins (hybrids of an immunoglobulin with a peptide not being an immunoglobulin C07K19/00) - A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) - C07K 2317/31: multispecific - C07K 2317/72: Increased effector function due to an Fc-modification - C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC] - C07K 2317/94: Stability, e.g. half-life, pH, temperature or enzyme-resistance - C07K 2319/00: Fusion polypeptide - C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto - 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 Fusion proteins of C1q peptides and HMBG1 A-box or HMBG1 B-box, or C1q peptides and DWESY peptide are provided, and methods of use thereof. ## Claims ### Claim 1 A method of cross-linking LAIR-1 and RAGE comprising contacting the LAIR-1 and RAGE with a composition that binds to LAIR-1 and RAGE comprising a polypeptide. ### Claim 2 (depends on 1) The method of claim 1, wherein the LAIR-1 and RAGE are present on a monocyte, and wherein cross-linking LAIR-1 and RAGE mediates monocyte M2 differentiation. ### Claim 3 (depends on 1) The method of claim 1, wherein the polypeptide comprises (i) a C1q dodecamer peptide, or a C1q nonamer peptide wherein the nonamer peptide comprises KGEQGEPGA (SEQ ID NO:5), and (ii) a HMBG1 A-box peptide or a HMBG1 B-box peptide. ### Claim 4 (depends on 1) The method of claim 1, wherein the LAIR-1 and RAGE are present on a monocyte, and wherein cross-linking LAIR-1 and RAGE effects one or more of (i) dephosphorylation of RAGE, (ii) recruitment of SHP-1 to LAIR-1, and (iii) NF-κB signaling pathway inhibition. ### Claim 5 (depends on 3) The method of claim 3, wherein the polypeptide comprises SEQ ID NO:7. ### Claim 6 (depends on 3) The method of claim 3, wherein the polypeptide comprises SEQ ID NO:10. ### Claim 7 (depends on 1) The method of claim 1, wherein the polypeptide comprises (i) a C1q dodecamer peptide, or a C1q nonamer peptide wherein the nonamer peptide comprises KGEQGEPGA (SEQ ID NO:5), and (ii) a DWEYS peptide (SEQ ID NO:8). ### Claim 8 (depends on 7) The method of claim 7, wherein the polypeptide comprises SEQ ID NO:11. ### Claim 9 (depends on 1) The method of claim 1, wherein the composition comprises a bispecific antibody directed to LAIR-1 and RAGE. ### Claim 10 A polypeptide comprising (i) a C1q dodecamer peptide, or a C1q nonamer peptide wherein the nonamer peptide comprises KGEQGEPGA (SEQ ID NO:5), and (ii) a HMBG1 A-box peptide or a HMBG1 B-box peptide. ### Claim 11 (depends on 10) The polypeptide of claim 10, wherein the carboxy terminal amino acid or the amino terminal amino acid residue of the C1q dodecamer or nonamer is bound to the amino terminal amino acid or the carboxy terminal amino acid residue, respectively, of the HMBG1 A-box or HMBG1 B-box peptide. ### Claim 12 (depends on 10) The polypeptide of claim 10, wherein the C1q dodecamer or nonamer is bound directly by a peptide bond to the HMBG1 A-box or HMBG1 B-box peptide. ### Claim 13 (depends on 10) The polypeptide of claim 10, wherein the C1q dodecamer or nonamer is bound by a peptide bond to a linker peptide which is bound by a peptide bond to the HMBG1 A-box or HMBG1 B-box peptide. ### Claim at position 14 14-26. (canceled) ### Claim 27 (depends on 1) A method of treating an autoimmune inflammatory condition in a subject comprising administering an amount of the polypeptide or composition of claim 1 effective to treat an autoimmune inflammatory condition. ### Claim 28 (depends on 27) The method of claim 27, wherein the autoimmune inflammatory condition is systemic lupus erythematosus (SLE). ### Claim 29 (depends on 1) A method to quiesce a monocyte in a subject comprising administering an amount of the polypeptide of claim 1 effective to quiesce a monocyte in a subject. ### Claim at position 18 30-48. (canceled)