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C07K 16/10 (2006.01) Foster City, California 94404 (US) ) ( (51) International Patent Classification: Craig S.; c/o Gilead Sciences, Inc., 333 Lakeside Drive, A61P31/18 (2006.01) C07K 16/10 (2006.01) Foster City, California 94404 (US). REHDER, Doug; c/o Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, Cal¬ (21) International Application Number: ifornia 94404 (US). SCHENAUER, Matthew Robert; c/ PCT/US20 19/040342 o Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, (22) International Filing Date: California 94404 (US). SERAFINI, Loredana; c/o Gilead 02 July 2019 (02.07.2019) Sciences, Inc., 333 Lakeside Drive, Foster City, Califor¬ nia 94404 (US). STEPHENSON, Heather Theresa; c/ (25) Filing Language: English o Gilead Sciences, Inc., 333 Lakeside Drive, Foster Ci¬ (26) Publication Language: English ty, California 94404 (US). THOMSEN, Nathan D.; c/o Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, Cal¬ (30) Priority Data: ifornia 94404 (US). YU, Helen; c/o Gilead Sciences, Inc., 62/693,642 03 July 2018 (03.07.2018) US 333 Lakeside Drive, Foster City, California 94404 (US). 62/810,191 25 February 2019 (25.02.2019) US ZHANG, Xue; c/o Gilead Sciences, Inc., 333 Lakeside Dri¬ (71) Applicant: GILEAD SCIENCES, INC. [US/US]; 333 ve, Foster City, California 94404 (US). Lakeside Drive, Foster City, California 94404 (US). (74) Agent: WAHLSTEN, Jennifer L. et al.; Gilead Sciences, (72) Inventors: BALAKRISHNAN, Mini; c/o Gilead Inc., 333 Lakeside Drive, Foster City, California 94404 Sciences, Inc., 333 Lakeside Drive, Foster City, Califor¬ (US). nia 94404 (US). CARR, Brian A.; c/o Gilead Sciences, (81) Designated States (unless otherwise indicated, for every Inc., 333 Lakeside Drive, Foster City, California 94404 kind of national protection av ailable) . AE, AG, AL, AM, (US). HUNG, Magdeleine S.; c/o Gilead Sciences, Inc., AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, 333 Lakeside Drive, Foster City, California 94404 (US). CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, KANWAR, Manu; c/o Gilead Sciences, Inc., 333 Lake¬ DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, side Drive, Foster City, California 94404 (US). PACE, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, (54) Title: ANTIBODIES THAT TARGET HIV GP120 AND METHODS OF USE (57) Abstract: Antibodies that bind to HIV gpl20 and neutralize HIV are disclosed. Also disclosed are methods of using such antibodies alone or in combination with other therapeutic agents to treat or prevent HIV infection. [Continued on next page] W O 2020/0 1 0 107 A1 11|||| |||| ||| ||||| ||||| III III 1III mil mil mil mil mil INI llll llll llll KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY,MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind of regional protection available) : ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, Cl, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Declarations under Rule 4.17: — as to applicant's entitlement to apply for and be granted a patent (Rule 4.17(H)) — as to the applicant's entitlement to claim the priority of the earlier application (Rule 4.17(iii)) Published: — with international search report (Art. 21(3)) — before the expiration of the time limit for amending the claims and to be republished in the event of receipt of amendments (Rule 48.2(h)) — with sequence listing part of description (Rule 5.2(a)) ANTIBODIES THAT TARGET HIV GP120 AND METHODS OF USE Cross Reference to Related Applications [0001] This application claims the benefit under 35 U.S.C. § 119(e) of U.S. provisional application no. 62/693,642, filed on July 3, 2018 and U.S. provisional application no. 62/810,191, filed on February 25, 2019, which are hereby incorporated herein by reference in their entireties for all purposes. Sequence Listing [0002] The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on June 10, 2019, is named l232_P2F_SL.txt and is 899,216 bytes in size. Field [0003] This disclosure relates to antibodies and antigen-binding fragments thereof for the treatment and/or prevention of human immunodeficiency virus (HIV) infection. Background [0004] Human immunodeficiency virus (HIV) infection and related diseases are a major public health problem worldwide. Most currently approved therapies for HIV infection target the viral reverse transcriptase, protease enzymes, and integrase. Yet resistance of HIV to these existing drugs, long-term toxicity, and lack of patient adherence to daily dosing regimens have been associated with these therapies. Therefore, it is important to discover and develop new anti-HIV antibodies with advantageous properties suitable for therapeutic uses. [0005] WO 2012/158948 describes human anti-HIV antibodies derived from memory B cells of HIV-infected donors, which are capable of inhibiting infection by HIV-l species from a plurality of clades. Anti-HIV antibodies are also disclosed e.g., in WO 2005/058963, WO 2013/090644, WO 2014/063059 and EP 0690132B1. The therapeutic use of the antibodies may be limited due to their intra-patient viral coverage, pharmacokinetics, polyspecificity, and other properties. Accordingly, there is a need for novel anti-HIV antibodies for therapeutic uses. Summary [0006] The present disclosure provides compositions for treating or preventing HIV. More specifically, provided herein are antibodies that bind human immunodeficiency virus (HIV) envelope (Env) glycoprotein gpl20 (gpl20). This disclosure provides anti- HIV antibodies and antigen-binding fragments thereof, including broadly neutralizing anti-HIV antibodies and antigen-binding fragments thereof, pharmaceutical compositions containing such antibodies and fragments thereof, and methods for using these antibodies and fragments thereof in the treatment and prevention of HIV infection. [0007] In one aspect, this disclosure provides an antibody or an antigen-binding fragment thereof that binds to human immunodeficiency virus- 1 (HIV-l) Envelope glycoprotein gpl20. The antibody or antigen-binding fragment thereof comprises a heavy chain variable region (VH) comprising VH complementary determining regions (CDRs) and a light chain variable region (VL) comprising VL CDRs. In some embodiments, the VH CDRs and VL CDRs have the sequences set forth in: SEQ ID NOs.: 137, 138, 139, 140, 141, and 142, respectively; SEQ ID NOs.: 159, 138, 139, 140, 141, and 142, respectively; SEQ ID NOs.: 137, 160, 139, 140, 141, and 142, respectively; SEQ ID NOs.: 137, 161, 139, 140, 141, and 142, respectively; SEQ ID NOs.: 137, 162, 139, 140, 141, and 142, respectively; SEQ ID NOs.: 137, 163, 139, 140, 141, and 142, respectively; SEQ ID NOs.: 137, 138, 164, 140, 141, and 142, respectively; SEQ ID NOs.: 159, 138, 164, 140, 141, and 142, respectively; SEQ ID NOs.: 137, 138, 139, 140, 165, and 142, respectively; SEQ ID NOs.: 137, 138, 139, 140, 166, and 142, respectively; SEQ ID NOs.: 137, 138, 139, 140, 167, and 142, respectively; SEQ ID NOs.: 137, 138, 139, 140, 168, and 142, respectively; SEQ ID NOs.: 137, 138, 154, 140, 141, and 142, respectively, or SEQ ID NOs.: 137, 138, 139, 570, 141, and 142, respectively. In some cases, the antibody or antigen-binding fragment thereof comprises in framework region 3 (FR3) of the VH at position corresponding to 74a, 74b, 74c, and 74d (Rabat numbering) the amino acid sequence set forth in SEQ ID NO: 453 or SEQ ID NO: 627. In some, the VH CDRs and VL CDRs have the sequences set forth in: SEQ ID NOs.: 137, 138, 139, 140, 141, and 142, respectively, wherein the antibody or antigen-binding fragment thereof comprises in framework region 3 (FR3) of the VH at position corresponding to 74a, 74b, 74c, and 74d (Rabat numbering) the amino acid sequence set forth in SEQ ID NO: 627. In some cases, the antibody or antigen-binding fragment thereof comprises a FR3 of the VH comprising the following amino acid sequence: RVSLTRHASWDFDTFSFYMDLRALRSDDTA VYF CAR (SEQ ID NO: 628) or RVSLTRHASFDFDTFSFYMDLRALRSDDTAVYFCAR (SEQ ID NO: 629). In certain embodiments, the antibody or antigen-binding fragment thereof comprises a FR3 of the VH comprising the following amino acid sequence: RVSLTRHASFDFDTFSFYMDLKALRSDDTAVYFCAR (SEQ ID NO: 629). In some, the VH CDRs and VL CDRs have the sequences set forth in: SEQ ID NOs.: 137, 138, 139, 140, 141, and 142, respectively, wherein the antibody or antigen-binding fragment thereof comprises a FR3 of the VH comprising the following amino acid sequence: RVSLTRHASFDFDTFSFYMDLKALRSDDTAVYF CAR (SEQ ID NO: 629). [0008] In another aspect, the VH CDRs and VL CDRs have the sequences set forth in: SEQ ID NOs.: 137, 138, 139, 140, 141, and 142, respectively; or SEQ ID NOs.: 153, 138, 139, 140, 141, and 142, respectively. In certain cases, the VH of this antibody has one or more of: histidine at position 3, serine at position 5, glutamine at position 72, tyrosine at position 76, valine at position 82c, isoleucine at position 89 (position numbering according to Rabat). In certain cases, the VL of this antibody has one or more of: arginine at position 14, alanine at position 60, valine at position 83, and isoleucine at position 98 (position numbering according to Rabat).
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