# US 10,865,234 B2 · Monoclonal antibodies directed against trimeric forms of the HIV-1 envelope glycoprotein with broad and potent neutralizing activity > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,865,234 B2 - Document ID: US10865234B2 - Status: Granted - Kind: B2 - Application number: 16/513,859 - Filed: 2019-07-17 - Published: 2019-11-07 - Granted: 2020-12-15 - Earliest claimed: 2009-03-17 - Assignees: Theraclone Sciences, Inc.; International AIDS Vaccine Initiative; The Scripps Research Institute - Applicants: Theraclone Sciences, Inc.; International AIDS Vaccine Initiative; The Scripps Research Institute - Inventors: Po-Ying Chan-Hui; Steven Frey; Ole Olsen; Jennifer Mitcham; Matthew Moyle; Sanjay K. Phogat; Dennis R. Burton; Laura Marjorie Walker; Pascal Raymond Georges Poignard; Wayne Koff; Melissa Danielle De Jean De St. Marcel Simek-Lemos; Stephen Kaminsky - Web page: https://patentgrep.com/patent/US10865234B2 ## CPC - C07K 16/114: Lentivirus (G), e.g. human immunodeficiency virus [HIV], feline immunodeficiency virus [FIV] or simian immunodeficiency virus [SIV] - A61K 39/21: Retroviridae, e.g. equine infectious anemia virus - A61P 31/14: for RNA viruses - C07K 16/1145: {Env proteins, e.g. gp41, gp110/120, gp160, V3, principal neutralising domain [PND] or CD4-binding site} - A61K 2039/505: {comprising antibodies} - C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity - C07K 2317/56: variable (Fv) region, i.e. VH and/or VL - C07K 2317/565: Complementarity determining region [CDR] - C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding - 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 ## Abstract The invention provides a method for obtaining a broadly neutralizing antibody (bNab), including screening memory B cell cultures from a donor PBMC sample for neutralization activity against a plurality of HIV-1 species, cloning a memory B cell that exhibits broad neutralization activity; and rescuing a monoclonal antibody from that memory B cell culture. The resultant monoclonal antibodies are characterized by their ability to selectively bind epitopes from the Env proteins in native or monomeric form, as well as to inhibit infection of HIV-1 species from a plurality of clades. Compositions containing human monoclonal anti-HIV antibodies used for prophylaxis, diagnosis and treatment of HIV infection are provided. Methods for generating such antibodies by immunization using epitopes from conserved regions within the variable loops of gp120 are provided. Immunogens for generating anti-HIV1 bNAbs are also provided. Furthermore, methods for vaccination using suitable epitopes are provided. ## Claims ### Claim 1 A pharmaceutical composition comprising a non-naturally occurring anti-HIV-I PG9 monoclonal antibody or antigen binding portion thereof comprising: (a) a light chain variable region comprising three complementarity determining regions comprising the amino acid sequences of SEQ ID NOS: 126, 127, and 45; and (b) a heavy chain variable region comprising three complementarity determining regions comprising the amino acid sequences of SEQ ID NOS: 123, 124; and 7; and a pharmaceutically acceptable carrier, wherein the carrier is selected from the group consisting of a buffer, organic acid, antioxidant, preservative, alkyl paraben, oligopeptide, protein, amino acid, hydrophilic polymer, carbohydrate, chelating agent, tonicifier, sugar, and surfactant. ### Claim 2 (depends on 1) The composition of claim 1, wherein the antibody comprises: (a) a light chain variable region comprising the amino acid sequence of SEQ ID NO: 40; and (b) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 39. ### Claim 3 (depends on 1) The composition of claim 1, wherein the antibody comprises: (a) a light chain sequence comprising the amino acid sequence of SEQ ID NO: 30; and (b) a heavy chain sequence comprising the amino acid sequence of SEQ ID NO: 28. ### Claim 4 A pharmaceutical composition comprising a non-naturally occurring anti-HIV-1 PG16 monoclonal antibody or antigen binding portion thereof comprising: (a) a light chain variable region comprising three complementarity determining regions comprising the amino acid sequences of SEQ ID NOS: 92, 95, and 41, or SEQ ID NOS: 93, 95, and 41, or SEQ ID NOS: 97, 95, and 41; and (b) a heavy chain variable region comprising three complementarity determining regions comprising the amino acid sequences of SEQ ID NOS: 88, 89, and 6, or SEQ ID NOS: 88, 98, and 6; and a pharmaceutically acceptable carrier, wherein the carrier is selected from the group consisting of a buffer, organic acid, antioxidant, preservative, alkyl paraben, oligopeptide, protein, amino acid, hydrophilic polymer, carbohydrate, chelating agent, tonicifier, sugar, and surfactant. ### Claim 5 (depends on 4) The composition of claim 4, wherein the antibody comprises: (a) a light chain variable region comprising the amino acid sequence of SEQ ID NO: 32 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 31; or (b) a light chain variable region comprising the amino acid sequence of SEQ ID NO: 96 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 140; or (c) a light chain variable region comprising the amino acid sequence of SEQ ID NO: 51 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 48; or (d) a light chain variable region comprising the amino acid sequence of SEQ ID NO: 57 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 54; or (e) a light chain variable region comprising the amino acid sequence of SEQ ID NO: 32 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 60; or (f) a light chain variable region comprising the amino acid sequence of SEQ ID NO: 32 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 31. ### Claim 6 (depends on 4) The composition of claim 4, wherein the antibody comprises: (a) a light chain sequence comprising the amino acid sequence of SEQ ID NO: 14 and a heavy chain sequence comprising the amino acid sequence of SEQ ID NO: 12; or (b) a light chain sequence comprising the amino acid sequence of SEQ ID NO: 142 and a heavy chain sequence comprising the amino acid sequence of SEQ ID NO: 139; or (c) a light chain sequence comprising the amino acid sequence of SEQ ID NO: 50 and a heavy chain sequence comprising the amino acid sequence of SEQ ID NO: 47; or (d) a light chain sequence comprising the amino acid sequence of SEQ ID NO: 56 and a heavy chain sequence comprising the amino acid sequence of SEQ ID NO: 53; or (e) a light chain sequence comprising the amino acid sequence of SEQ ID NO: 14 and a heavy chain sequence comprising the amino acid sequence of SEQ ID NO: 59; or (f) a light chain sequence comprising the amino acid sequence of SEQ ID NO: 14 and a heavy chain sequence comprising the amino acid sequence of SEQ ID NO: 65. ### Claim 7 (depends on 1, 4) The composition according to claim 1 or 4, wherein the buffer is acetate, Tris, phosphate, or citrate.