# US 7,744,887 B2 · Human antibodies interacting with HIV gp41 > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 7,744,887 B2 - Document ID: US7744887B2 - Status: Granted - Kind: B2 - Application number: 11/628,164 - Filed: 2005-05-31 - Published: 2007-10-25 - Granted: 2010-06-29 - Earliest claimed: 2004-06-01 - Assignees: Merck & Co., Inc.; Whitehead Insitute of Biomedical Research; MedImmune, LLC; Istitute Di Ricerche Di Biologia Molecolare P. Angeletti S.P.A. - Inventors: John W. Shiver; Michael D. Miller; Romas Geleziunas; Daria J. Hazuda; Peter S. Kim; Debra M. Eckert; Michael J. Root; Simon N. Lennard; Elisabetta Bianchi - Web page: https://patentgrep.com/patent/US7744887B2 ## CPC - G01N 33/56988: {HIV or HTLV} - A61P 31/18: for HIV - C07K 16/1145: {Env proteins, e.g. gp41, gp110/120, gp160, V3, principal neutralising domain [PND] or CD4-binding site} - C07K 2317/21: from primates, e.g. man - C07K 2317/622: Single chain antibody (scFv) - C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding - G01N 2500/00: Screening for compounds of potential therapeutic value - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - 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) ## Abstract Human scFvs are disclosed which interact with a conformational epitope along the pre-hairpin, N-helix coiled coil structure within the heptad repeat 1 (HR1) region of gp41 of HIV. These antibodies, as well as IgG conversions, are shown to neutralize diverse HIV isolates. Isolated nucleic acid molecules are also disclosed which encode relevant portions of these antibodies, as well as the purified forms of the expressed antibodies or relevant antibody fragments, such as VH and VL chains. The antibody compositions disclosed within this specification may provide for a therapeutic treatment against HIV infection by reducing viral load levels within an infected individual, thus prolonging the asymptomatic phase of HIV infection. These antibodies will also be useful in assays to identify HIV antiviral compounds as well as allowing for the identification of candidate HIV vaccines, such as HIV peptide vaccines. ## Claims ### Claim 1 An isolated HIV monoclonal antibody comprising an antibody binding portion that interacts with a conformational epitope within a groove of adjacent coils of a trimeric pre-hairpin intermediate structure of the heptad repeat 1 (HR1) region of the ectodomain of gp41, wherein said conformational epitope comprises amino acids Leu568, Trp571 and Lys574 that occupy one or the other of the adjacent coils within the trimeric pre-hairpin structure and wherein said antibody inhibits HIV infection of a target cell in vitro, wherein said antibody comprises a heavy chain variable (VH) region and a light chain variable (VL) region, wherein said VH region and said VL region each comprise three complementarity determining regions (CDR) and four framework (FW) regions arranged from the NH2 terminus to the COOH terminus as follows: FW1, CDR1, FW2, CDR2, FW3, CDR3, FW4, and wherein: (a) said VH CDR1 comprises amino acids 31-35 of SEQ ID NO:4; (b) said VH CDR2 comprises amino acids 50-66 of SEQ ID NO:4; (c) said VH CDR3 comprises amino acids 99-108 of SEQ ID NO:4; (d) said VL CDR1 comprises amino acids 31-35 of SEQ ID NO:6; (e) said VL CDR2 comprises amino acids 50-56 of SEQ ID NO:6; and, (f) said VL CDR3 comprises amino acids 89-97 of SEQ ID NO:6. ### Claim 2 (depends on 1) The antibody of claim 1 comprising a heavy chain variable (VH) region which comprises SEQ ID NO:4 and a light chain variable (VL) region which comprises SEQ ID NO:6. ### Claim 3 (depends on 2) The antibody of claim 2 which is a scFv. ### Claim 4 (depends on 2) The antibody of claim 2 which is an immunoglobulin G (IgG). ### Claim 5 An isolated HIV monoclonal antibody comprising an antibody binding portion that interacts with a conformational epitope within a groove of adjacent coils of a trimeric pre-hairpin intermediate structure of the heptad repeat 1 (HR1) region of the ectodomain of gp41, wherein said conformational epitope comprises amino acids Leu568, Trp571 and Lys574 that occupy one or the other of the adjacent coils within the trimeric pre-hairpin structure and wherein said antibody inhibits HIV infection of a target cell in vitro, wherein said antibody comprises a heavy chain variable (VH) region and a light chain variable (VL) region, wherein said VH region and said VL region each comprise three complementarity determining regions (CDR) and four framework (FW) regions arranged from the NH2 terminus to the COOH terminus as follows: FW1, CDR1, FW2, CDR2, FW3, CDR3, FW4, and wherein: (a) said VH CDR1 comprises amino acids 31-35 of SEQ ID NO:10; (b) said VH CDR2 comprises amino acids 50-66 of SEQ ID NO:10; (c) said VH CDR3 comprises amino acids 99-108 of SEQ ID NO:10; (e) said VL CDR1 comprises amino acids 31-35 of SEQ ID NO:12; (e) said VL CDR2 comprises amino acids 50-56 of SEQ ID NO:12; and, (f) said VL CDR3 comprises amino acids 89-97 of SEQ ID NO:12. ### Claim 6 (depends on 5) The antibody of claim 5 comprising a heavy chain variable (VH) region which comprises SEQ ID NO:10 and a light chain variable (VL) region which comprises SEQ ID NO:12. ### Claim 7 (depends on 6) The antibody of claim 6 which is a scFv. ### Claim 8 (depends on 6) The antibody of claim 6 which is an immunoglobulin G (IgG). ### Claim 9 An isolated HIV monoclonal antibody comprising an antibody binding portion that interacts with a conformational epitope within a groove of adjacent coils of a trimeric pre-hairpin intermediate structure of the heptad repeat 1 (HR1) region of the ectodomain of gp41, wherein said conformational epitope comprises amino acids Leu568, Trp571 and Lys574 that occupy one or the other of the adjacent coils within the trimeric pre-hairpin structure and wherein said antibody inhibits HIV infection of a target cell in vitro, wherein said antibody comprises a heavy chain variable (VH) region and a light chain variable (VL) region, wherein the heavy chain variable (VH) region comprises SEQ ID NO:4 or SEQ ID NO:10. ### Claim 10 (depends on 9) The antibody of claim 9, wherein the heavy chain variable (VH) region comprises SEQ ID NO:4. ### Claim 11 (depends on 9) The antibody of claim 9, wherein the heavy chain variable (VH) region comprises SEQ ID NO:10.