# US 10,870,698 B2 · Nucleic acids encoding lectin-like oxidized LDL receptor 1 antibodies > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,870,698 B2 - Document ID: US10870698B2 - Status: Granted - Kind: B2 - Application number: 15/971,250 - Filed: 2018-05-04 - Published: 2019-02-07 - Granted: 2020-12-22 - Earliest claimed: 2013-06-21 - Assignees: Novartis AG - Applicants: Novartis AG - Inventors: Kurt Alex Heldwein; Igor Splawski; Jennifer Brogdon; Joshua Goldstein; William Dole; John Trauger; Chonghui Zhang - Web page: https://patentgrep.com/patent/US10870698B2 ## CPC - C07K 16/28: against receptors, cell surface antigens or cell surface determinants - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - 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 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure - A61P 9/08: Vasodilators for multiple indications - A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis - A61P 9/12: Antihypertensives - C07K 16/2851: {against the lectin superfamily, e.g. CD23, CD72} - C12N 15/11: DNA or RNA fragments; Modified forms thereof (DNA or RNA not used in recombinant technology, C07H21/00); {Non-coding nucleic acids having a biological activity} - C12N 15/63: Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression - A61K 2039/505: {comprising antibodies} - C07K 14/4726: {Lectins} - C07K 14/705: Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)} - C07K 2317/21: from primates, e.g. man - C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered - 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 2317/565: Complementarity determining region [CDR] - 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) - 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) ## Abstract The present invention relates to monoclonal antibodies binding to human lectin-like oxidized LDL (low density lipoprotein) receptor 1 (hereinafter, sometimes referred to as “LOX-1”), and pharmaceutical compositions and methods of treatment comprising the same. ## Claims ### Claim 1 A nucleic acid encoding an antibody or antigen binding fragment thereof which specifically binds to human lectin-type oxidized low density lipoprotein receptor 1 (LOX-1), wherein said antibody or fragment comprises a heavy chain variable region (VH) comprising complementarity determining regions HCDR1, HCDR2, and HCDR3, and a light chain variable region (VL) comprising complementarity determining regions LCDR1, LCDR2, and LCDR3, and wherein the HCDR1 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 8, 28, 48, 68, and 88; the HCDR2 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 9, 29, 49, 69, and 89; the HCDR3 comprises an amino acid sequence selected from the group consisting of 10, 30, 50, 70, and 90; the LCDR1 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 18, 38, 58, 78, and 98; the LCDR2 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 19, 39, 59, 79, and 99; and the LCDR3 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 20, 40, 60, 80, and 100. ### Claim 2 (depends on 1) The nucleic acid of claim 1, wherein: (i) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 8, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 9, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 10; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 18, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 19, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 20; (ii) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 28, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 29, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 30; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 38, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 39, and LCDR3 comprises the amino acid sequence of SEQ ID NO: 40; (iii) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 48, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 49, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 50; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 58, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 59, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 60; (iv) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 68, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 69, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 70; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 78, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 79, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 80; or (v) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 88, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 89, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 90; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 98, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 99, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 100. ### Claim 3 (depends on 1) The nucleic acid of claim 1, wherein the antibody or antigen binding fragment thereof comprises (i) a VH selected from the group consisting of SEQ ID NO: 14, 34, 54, 74, or 94; and a VL selected from the group consisting of SEQ ID NO: 24, 44, 64, 84, or 104 or (ii) a VH and a VL comprising an amino acid sequence with 97-99% identity thereof. ### Claim 4 (depends on 1) The nucleic acid of claim 1, wherein the antibody or antigen binding fragment thereof comprises a variable heavy chain sequence selected from the group consisting of SEQ ID NO: 14, 34, 54, 74, or 94. ### Claim 5 (depends on 1) The nucleic acid of claim 1, wherein the antibody or antigen binding fragment thereof comprises a variable light chain sequence selected from the group consisting of SEQ ID NO: 24, 44, 64, 84, or 104. ### Claim 6 (depends on 1) The nucleic acid of claim 1, wherein the antibody or antigen binding fragment thereof comprises a variable heavy chain selected from the group consisting of SEQ ID NO: 14, 34, 54, 74, or 94; and a variable light chain selected from the group consisting of SEQ ID NO: 24, 44, 64, 84, or 104. ### Claim 7 (depends on 1) The nucleic acid of claim 1, wherein: (i) the VH comprises the amino acid sequence of SEQ ID NO: 14 and the VL comprises the amino acid sequence of SEQ ID NO: 24; (ii) the VH comprises the amino acid sequence of SEQ ID NO: 34 and the VL comprises the amino acid sequence of SEQ ID NO: 44; (iii) the VH comprises the amino acid sequence of SEQ ID NO: 54 and the VL comprises the amino acid sequence of SEQ ID NO: 64; (iv) the VH comprises the amino acid sequence of SEQ ID NO: 74 and the VL comprises the amino acid sequence of SEQ ID NO: 84; (v) the VH comprises the amino acid sequence of SEQ ID NO: 94 and the VL comprises the amino acid sequence of SEQ ID NO: 104; or (vi) the VH comprises the amino acid sequence of SEQ ID NO: 114 and the VL comprises the amino acid sequence of SEQ ID NO: 122. ### Claim 8 (depends on 1) The nucleic acid of claim 1, wherein the antibody or antigen binding fragment thereof comprises (i) a heavy chain selected from the group consisting of SEQ ID NO: 16, 36, 56, 76, or 96; and a light chain selected from the group consisting of SEQ ID NO: 26, 46, 66, 86, or 106 or (ii) a heavy chain and a light chain comprising an amino acid sequence with 97-99% identity thereof. ### Claim 9 (depends on 1) The nucleic acid of claim 1, wherein the antibody or antigen binding fragment thereof comprises a heavy chain sequence selected from the group consisting of SEQ ID NO: 16, 36, 56, 76, or 96. ### Claim 10 (depends on 1) The nucleic acid of claim 1, wherein the antibody or antigen binding fragment thereof comprises a light chain sequence selected from the group consisting of SEQ ID NO: 26, 46, 66, 86, or 106. ### Claim 11 (depends on 1) The nucleic acid of claim 1, wherein the antibody or antigen binding fragment thereof comprises a heavy chain selected from the group consisting of SEQ ID NO: 16, 36, 56, 76, or 96; and a light chain selected from the group consisting of SEQ ID NO: 26, 46, 66, 86, or 106. ### Claim 12 (depends on 1) The nucleic acid of claim 1, wherein the antibody or antigen binding fragment thereof comprises a heavy chain and a light chain, wherein: (i) the heavy chain comprises the amino acid sequence of SEQ ID NO: 16 and the light chain comprises the amino acid sequence of SEQ ID NO: 26; (ii) the heavy chain comprises the amino acid sequence of SEQ ID NO: 36 and the light chain comprises the amino acid sequence of SEQ ID NO: 46; (iii) the heavy chain comprises the amino acid sequence of SEQ ID NO: 56 and the light chain comprises the amino acid sequence of SEQ ID NO: 66; (iv) the heavy chain comprises the amino acid sequence of SEQ ID NO: 76 and the light chain comprises the amino acid sequence of SEQ ID NO: 86; or (v) the heavy chain comprises the amino acid sequence of SEQ ID NO: 96 and the light chain comprises the amino acid sequence of SEQ ID NO: 106. ### Claim 13 (depends on 1) A vector comprising the nucleic acid of claim 1. ### Claim 14 (depends on 13) A host cell comprising the vector of claim 13. ### Claim 15 (depends on 14) The host cell of claim 14, wherein the host cell is a mammalian cell. ### Claim 16 A nucleic acid encoding an antibody or antigen binding fragment thereof which specifically binds to human lectin-type oxidized low density lipoprotein receptor 1 (LOX-1), wherein said antibody or fragment comprises a heavy chain variable region comprising complementarity determining regions HCDR1, HCDR2, and HCDR3 and a light chain variable region comprising complementarity determining regions LCDR1, LCDR2, and LCDR3, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 8; the HCDR2 comprises the amino acid sequence of SEQ ID NO: 9; the HCDR3 comprises the amino acid sequence of SEQ ID NO: 10; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 18; the LCDR2 comprises the amino acid sequence of SEQ ID NO: 19; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 20. ### Claim 17 (depends on 16) The nucleic acid of claim 16, wherein said antibody or fragment comprises a VH comprising the amino acid sequence of SEQ ID NO: 14 and a VL comprising the amino acid sequence of SEQ ID NO: 24. ### Claim 18 (depends on 17) The nucleic acid of claim 17, which comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 16 and a light chain comprising the amino acid sequence of SEQ ID NO: 26. ### Claim 19 A nucleic acid encoding an antibody or antigen binding fragment thereof which specifically binds to human LOX-1, wherein said antibody or fragment comprises a VH comprising complementarity determining regions HCDR1, HCDR2, and HCDR3, and a VL comprising complementarity determining regions LCDR1, LCDR2, and LCDR3, and wherein the HCDR1 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 11, 31, 51, 71, and 91; the HCDR2 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 12, 32, 52, 72, and 92; the HCDR3 comprises an amino acid sequence selected from the group consisting of 13, 33, 53, 73, and 93; the LCDR1 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 21, 41, 61, 81, and 101; the LCDR2 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 22, 42, 62, 82, and 102; and the LCDR3 comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 23, 43, 63, 83, and 103. ### Claim 20 (depends on 19) The nucleic acid of claim 19, wherein: (i) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 11, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 12, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 13; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 21, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 22, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 23; (ii) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 31, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 32, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 33; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 41, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 42, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 43; (iii) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 51, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 52, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 53; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 61, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 62, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 63; (iv) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 71, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 72, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 73; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 81, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 82, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 83; or (v) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 91, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 92, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 93; the LCDR1 comprises the amino acid sequence of SEQ ID NO: 101, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 102, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 103. ### Claim 21 (depends on 20) The nucleic acid of claim 20, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 11, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 12, and the HCDR3 comprises the amino acid sequence of SEQ ID NO: 13; and the LCDR1 comprises the amino acid sequence of SEQ ID NO: 21, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 22, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 23. ### Claim 22 (depends on 19) A vector comprising the nucleic acid of claim 19. ### Claim 23 (depends on 22) A host cell comprising the vector of claim 22. ### Claim 24 (depends on 23) The host cell of claim 23, wherein the host cell is a mammalian cell.