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CN-122005785-A - Method for identifying HIV patients susceptible to therapy with GP 120V 3 glycan-directed antibodies

CN122005785ACN 122005785 ACN122005785 ACN 122005785ACN-122005785-A

Abstract

The present invention provides methods for identifying a population of patients infected with HIV that can be targeted by antibodies that bind to the gl 20V 3 glycan region of HIV.

Inventors

  • B. Mordet
  • C S Perth

Assignees

  • 吉利德科学公司

Dates

Publication Date
20260512
Application Date
20200518
Priority Date
20190521

Claims (20)

  1. 1. Use of a reagent and an antibody or antigen binding fragment thereof for the preparation of a kit for performing a method of treating or preventing HIV-1 clade B in a human subject in need thereof, wherein the reagent identifies HIV-1 clade B species of gp120 having the viral genotype N332 glycan, D325 and L179 with amino acid position reference SEQ ID NO 4, The method comprises the following steps: a) Identifying a human subject infected with HIV-1 clade B or HIV-1 clade B population of gp120 having said viral genotype in a biological sample from said human subject using said reagent, and B) Administering to the human subject an effective amount of the antibody or antigen-binding fragment thereof comprising the VH and VL region amino acid sequences set forth below, respectively: SEQ ID NOs 400 and 401; SEQ ID NOs 402 and 404, or SEQ ID NOS 405 and 406.
  2. 2. The use of claim 1, the method comprising identifying a human subject infected with HIV-1 clade B or HIV-1 clade B population of gp120 having the following viral genotype: i. N332 glycans, D325, T63 and L179; N332 glycans, D325, L179 and T320; N332 glycans, D325, L179 and H330; iv, N332 glycans, D325, T63, L179 and T320; v, N332 glycans, D325, T63, L179 and H330; vi, N332 glycan, D325, L179, T320 and H330, or N332 glycans, D325, T63, L179, T320 and H330.
  3. 3. The use of claim 1, the method comprising identifying a human subject infected with HIV-1 clade B or HIV-1 clade B population of gp120 having the following viral genotype: i. N332 glycans, D325, T63 and L179; N332 glycans, D325, L179 and T320, or N332 glycans, D325, L179 and H330.
  4. 4. The use of claim 1, the method comprising identifying a human subject infected with HIV-1 clade B or HIV-1 clade B population of gp120 having the following viral genotype: i. N332 glycan, D325, T63, L179 and T320, or N332 glycans, D325, T63, L179 and H330.
  5. 5. The use of claim 1, the method comprising identifying a human subject infected with HIV-1 clade B or HIV-1 clade B population of gp120 having the following viral genotype: i. N332 glycan, D325, L179, T320 and H330, or N332 glycans, D325, T63, L179, T320 and H330.
  6. 6. The use of claim 1, wherein 90%,91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% of HIV-1 clade B species in the HIV-1 clade B population comprise the viral genotype.
  7. 7. The use of any one of claims 1 to 6, wherein the antibody comprises an Fc region comprising the following amino acids at specified positions numbered according to the EU index: i. tyrosine at position 252, threonine at position 254 and glutamic acid at position 256, or Leucine at position 428 and serine at position 434.
  8. 8. The use according to any one of claims 1 to 6, wherein the antibody comprises an Fc region comprising the amino acids aspartic acid at position 239 and glutamic acid at position 332 at specified positions numbered according to the EU index.
  9. 9. The use according to any one of claims 1 to 6, wherein the antibody comprises an Fc region comprising the amino acids aspartic acid at position 239, glutamic acid at position 332 and leucine at position 330 at specified positions numbered according to the EU index.
  10. 10. The use according to any one of claims 1 to 6, wherein the antibody comprises an Fc region comprising the amino acids aspartic acid at position 239, glutamic acid at position 332 and alanine at position 236 at specified positions numbered according to the EU index.
  11. 11. The use according to any one of claims 1 to 6, wherein the antibody comprises an Fc region comprising the amino acids aspartic acid at position 239, glutamic acid at position 332, alanine at position 236 and leucine at position 330 at specified positions numbered according to the EU index.
  12. 12. The use of any one of claims 1 to 6, the method comprising administering an antigen binding fragment.
  13. 13. The use according to claim 12, wherein the antigen binding fragment is selected from scFv, fab, fab ', F (ab') 2 and Fv.
  14. 14. The use of claim 12, wherein the antigen binding fragment is a diabody.
  15. 15. The use according to any one of claims 1 to 6, wherein the antibody is a multispecific antibody.
  16. 16. The use according to any one of claims 1 to 6, wherein the human subject is acutely infected with HIV-1 clade B.
  17. 17. The use of claim 16, wherein the antibody is administered to a human subject having a Fiebig stage IV or earlier HIV-1 clade B infection.
  18. 18. The use of claim 16, wherein the antibody is administered to a human subject that is not seroconverted.
  19. 19. The use of any one of claims 1 to 6, wherein the antibody is administered to a human subject suffering from HIV-1 clade B infection of Fiebig stage V or Fiebig stage VI.
  20. 20. The use of any one of claims 1 to 6, wherein the human subject is chronically infected with HIV-1 clade B.

Description

Method for identifying HIV patients susceptible to therapy with GP 120V 3 glycan-directed antibodies The present application is a divisional application of the application patent application of the application number 202080037770.7, day 18 of the year 2020, entitled "method of identifying HIV patients susceptible to therapy with GP 120V 3 glycan-directed antibodies". Cross Reference to Related Applications This patent application claims the benefit of U.S. provisional application 62/850,994 filed on 5/21 of 2019 in accordance with the regulations of clause 119 (e) of U.S. code 35, which provisional application is hereby incorporated by reference in its entirety for all purposes. Sequence listing This patent application contains a sequence listing submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. The ASCII copy was created on month 4, 27 of 2020, named 1289pf_sl.txt, and was 199,543 bytes in size. Background Human Immunodeficiency Virus (HIV) infection and related diseases are a major public health problem worldwide. Most currently approved therapies for HIV infection target viral reverse transcriptase, protease and integrase, but HIV resistance to these existing drugs, long-term toxicity, and lack of patient compliance with daily dosing regimens have proven to be problems associated with these therapies. Therefore, the discovery and development of new HIV drugs is very important. WO 2009/066702, WO 2012/030904, WO 2014/063059, WO 2016/149698, WO 2017/106346, WO 2018/075564 and WO 2018/125813, mccoy, retrovirology,2018, volume 15, page 70, sok and Burton, nat immunol, 2018, volume 19, 11, pages 1179-1188, possas et al, expert Opin tier Pat, month 2018, volume 28, 7, pages 551-560, and ph son and Barouch, curr HIV/AIDS Rep,2016, volume 13, pages 31-37 describe human anti-HIV antibodies derived from HIV infected donor memory B cells that target the V3 glycan region of gp120 and are capable of inhibiting infection by HIV-1 species from multiple clades. Therapeutic use of antibodies may be limited due to the need to identify patients infected with HIV-1 species that can be targeted by HIV gp 120V 3 glycan region antibodies. Disclosure of Invention The present invention provides methods for identifying patients most likely to benefit from therapy with antibodies targeting the V3 glycan region of HIV gp 120. Accordingly, in one aspect, the invention provides a method of treating or preventing HIV in a human subject in need thereof, comprising a) identifying a human subject infected with an HIV or HIV population expressing gp120 comprising glycosylated asparagine (N332 glycan) at a position corresponding to amino acid residue position 332, aspartic acid (D325) at a position corresponding to amino acid residue position 325, and one or more amino acid residues selected from the group consisting of threonine (T63) at a position corresponding to amino acid residue position 63, leucine (L179) at a position corresponding to amino acid residue position 179, Threonine (T320) at a position corresponding to amino acid residue position 320, and histidine (H330) at a position corresponding to amino acid residue position 330, wherein the amino acid position is referred to SEQ ID No. 4, and b) administering to the subject an effective amount of an antibody or antigen binding fragment thereof that competes with or comprises VH and VL regions that bind to an epitope of gp120 within a third variable loop (V3) and/or a high mannose patch comprising an N332 oligomannose glycan. In some embodiments, the method entails identifying a subject infected with HIV or a population of HIV expressing gp120 comprising amino acid residues i.N 332 glycans, D325 and T63, ii.N 332 glycans, D325 and L179, iii.N 332 glycans, D325 and T320, iv.N 332 glycans, D325 and H330, v.N 332 glycans, D325, T63 and L179, vi.N 332 glycans, D325, T63 and T320, vii.N 332 glycans, D325, T63 and H330, viii.N 332 glycans, D325, L179 and T320, ix N332 glycans, D325, L179 and H330, x N332 glycans, D325, T320 and H330, xi N332 glycans, D325, T63, T320 and H330, xii N332 glycans, D325, T63, L179 and T320, xii N332 glycans, D325, T63, L179 and H330, xiv N332 glycans, D325, L179, T320 and H330, or xv. N332 glycans, d325, T63, L179, T320 and H330, wherein the amino acid positions are referred to SEQ ID NO. 4. In some embodiments, the method entails identifying a subject infected with HIV or a population of HIV expressing gp120 comprising amino acid residues i.N 332 glycan, D325 and T63, ii.N 332 glycan, D325 and L179, iii.N 332 glycan, D325 and T320, or iv.N 332 glycan, D325 and H330, wherein the amino acid positions are referenced to SEQ ID NO. 4. In some embodiments, the method entails identifying a subject infected with HIV or a population of HIV expressing gp120 comprising i.N 332 glycan, D325, T63 and L179, ii.N 332 glycan, D325, T63 and T320, iii.N 332 glycan, D325, T63 and H330, iv.N 332 glycan, D325, L179 and