# US 12,110,341 B2 · Composition comprising antibody that binds to domain II of HER2 and acidic variants thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,110,341 B2 - Document ID: US12110341B2 - Status: Granted - Kind: B2 - Application number: 18/640,824 - Filed: 2024-04-19 - Published: 2024-08-08 - Granted: 2024-10-08 - Earliest claimed: 2008-01-30 - Assignees: Genentech, Inc. - Applicants: Genentech, Inc. - Inventors: Reed J. Harris; Paul A. Motchnik - Web page: https://patentgrep.com/patent/US12110341B2 ## CPC - C07K 16/32: against translation products of oncogenes - A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants - A61P 11/00: Drugs for disorders of the respiratory system - A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives - A61P 35/00: Antineoplastic agents - C07K 1/18: Ion-exchange chromatography - C07K 16/065: {Purification, fragmentation} - C07K 16/2863: {against receptors for growth factors, growth regulators} - C07K 16/2896: {against molecules with a "CD"-designation, not provided for elsewhere} - A61K 2039/505: {comprising antibodies} - C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered - C07K 2317/41: Glycosylation, sialylation, or fucosylation - C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding - G01N 27/447: using electrophoresis - G01N 30/02: Column chromatography - G01N 2030/027: {Liquid chromatography} - 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) - 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 A composition comprising a main species HER2 antibody that binds to domain II of HER2 and acidic variants thereof is described. Pharmaceutical formulations comprising the composition, and therapeutic uses for the composition are also disclosed. ## Claims ### Claim 1 A method of treating HER2 positive cancer in a patient comprising administering a pharmaceutical formulation to the patient in an amount effective to treat the cancer, wherein the pharmaceutical formulation comprises: (i) a composition comprising: (a) a main species HER2 antibody comprising light chain and heavy chain amino acid sequences set forth in SEQ ID Nos. 15 and 16, respectively; and (b) acidic variants of the main species antibody, comprising a disulfide reduced variant, and: (ii) a pharmaceutically acceptable carrier. ### Claim 2 (depends on 1) The method of claim 1 wherein the percentage of acidic variants as compared to the main species antibody in the pharmaceutical formulation is no more than 25%. ### Claim 3 (depends on 1) The method of claim 1 wherein the disulfide reduced variant is detectable by non-reduced capillary electrophoresis with sodium dodecyl sulfate (CE-SDS). ### Claim 4 (depends on 1) The method of claim 1 wherein disulfide reduced variants in the pharmaceutical formulation comprise no more than 6% of the pharmaceutical formulation, when measured by non-reduced CE-SDS. ### Claim 5 (depends on 1) The method of claim 1 wherein disulfide reduced variants in the pharmaceutical formulation comprise 1% to 6% of the pharmaceutical formulation, when measured by non-reduced CE-SDS. ### Claim 6 (depends on 1) The method of claim 1 wherein the disulfide reduced variant is detectable by hydrophobic interaction chromatography. ### Claim 7 (depends on 1) The method of claim 1 wherein the acidic variants further comprise a glycated variant. ### Claim 8 (depends on 1) The method of claim 1 wherein the acidic variants further comprise a non-reducible variant. ### Claim 9 (depends on 1) The method of claim 1 wherein the acidic variants further comprise a sialylated variant. ### Claim 10 (depends on 1) The method of claim 1 wherein the acidic variants further comprise a deamidated variant. ### Claim 11 (depends on 1) The method of claim 1 wherein the acidic variants further comprise a glycated variant, a deamidated variant, a sialylated variant, and a non-reducible variant. ### Claim 12 (depends on 11) The method of claim 11 wherein the disulfide reduced variant, glycated variant, deamidated variant, sialylated variant, and non-reducible variant constitute at least 75 to 80% of the acidic variants in the pharmaceutical formulation. ### Claim 13 (depends on 1) The method of claim 1 wherein the composition further comprises a variant selected from the group consisting of: an amino acid-terminal leader extension of the main species antibody, wherein the amino acid-terminal leader extension comprises or consists of VHS-; an antibody comprising a C-terminal lysine residue on one or both heavy chains thereof; and an antibody with one or more oxidized methionine residues. ### Claim 14 (depends on 1) The method of claim 1 wherein the light and heavy chains are expressed by Chinese Hamster Ovary (CHO) cells and the composition is recovered from the CHO cells. ### Claim 15 (depends on 1) The method of claim 1 further comprising confirming the pharmaceutical formulation is effective for treating HER2 positive cancer in a patient comprising analyzing potency, monomer content, or pharmacokinetics of the pharmaceutical formulation. ### Claim 16 (depends on 1) The method of claim 1 further comprising confirming the pharmaceutical formulation is effective for treating HER2 positive cancer in a patient comprising analyzing potency and monomer content of the pharmaceutical formulation. ### Claim 17 A method of treating HER2 positive cancer in a patient comprising administering a pharmaceutical formulation to the patient in an amount effective to treat the cancer, wherein the pharmaceutical formulation comprises: (i) a composition comprising a main species HER2 antibody comprising light chain and heavy chain amino acid sequences set forth in SEQ ID Nos. 15 and 16, respectively, and acidic variants of the main species antibody, the acidic variants comprising a disulfide reduced variant; and (ii) a pharmaceutically acceptable carrier, wherein disulfide reduced variants in the pharmaceutical formulation comprise no more than 6% of the pharmaceutical formulation, when measured by non-reduced CE-SDS. ### Claim 18 (depends on 17) The method of claim 17 wherein the percentage of acidic variants as compared to the main species antibody in the pharmaceutical formulation is no more than 25%. ### Claim 19 (depends on 17) The method of claim 17 wherein disulfide reduced variants in the pharmaceutical formulation comprise 1% to 6% of the pharmaceutical formulation, when measured by non-reduced CE-SDS. ### Claim 20 (depends on 17) The method of claim 17 wherein the acidic variants further comprise a glycated variant. ### Claim 21 (depends on 17) The method of claim 17 wherein the acidic variants further comprise a non-reducible variant. ### Claim 22 (depends on 17) The method of claim 17 wherein the acidic variants further comprise a sialylated variant. ### Claim 23 (depends on 17) The method of claim 17 wherein the acidic variants further comprise a deamidated variant. ### Claim 24 (depends on 17) The method of claim 17 wherein the acidic variants further comprise a glycated variant, a deamidated variant, a sialylated variant, and a non-reducible variant. ### Claim 25 A method of treating HER2 positive cancer in a patient comprising administering pharmaceutical formulation to the patient in an amount effective to treat the cancer, wherein the pharmaceutical formulation comprises: (i) a composition comprising: (a) a main species HER2 antibody comprising light chain and heavy chain amino acid sequences set forth in SEQ ID Nos. 15 and 16, respectively; and (b) variants that elute earlier than the main species antibody upon separation by cation exchange chromatography, the variants comprising a disulfide reduced variant; and (ii) a pharmaceutically acceptable carrier. ### Claim 26 (depends on 25) The method of claim 25 wherein the percentage of acidic variants as compared to the main species antibody in the pharmaceutical formulation is no more than 25%. ### Claim 27 (depends on 25) The method of claim 25 wherein disulfide reduced variants in the pharmaceutical formulation comprise no more than 6% of the pharmaceutical formulation, when measured by non-reduced CE-SDS. ### Claim 28 A method of treating HER2 positive cancer in a patient comprising administering a pharmaceutical formulation to the patient in an amount effective to treat the cancer, wherein the pharmaceutical formulation comprises a main species HER2 antibody comprising light chain and heavy chain amino acid sequences set forth in SEQ ID Nos. 15 and 16, respectively, and variants that elute earlier than the main species antibody upon separation by cation exchange chromatography, the variants comprising disulfide reduced variant, glycated variant, deamidated variant, sialylated variant, and non-reducible variant constituting at least 75 to 80% of the acidic variants in the pharmaceutical formulation. ### Claim 29 (depends on 28) The method of claim 28 wherein the percentage of acidic variants as compared to the main species antibody in the pharmaceutical formulation is no more than 25%. ### Claim 30 (depends on 28) The method of claim 28 wherein disulfide reduced variants in the pharmaceutical formulation comprise no more than 6% of the pharmaceutical formulation, when measured by non-reduced CE-SDS.