# US 10,870,683 B2 · N-glycan deleted HIV-1 envelope glycoprotein trimers > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,870,683 B2 - Document ID: US10870683B2 - Status: Granted - Kind: B2 - Application number: 16/130,531 - Filed: 2018-09-13 - Published: 2019-05-09 - Granted: 2020-12-22 - Earliest claimed: 2017-09-13 - Assignees: International AIDS Vaccine Initiative; The Scripps Research Institute - Applicants: International AIDS Vaccine Initiative; The Scripps Research Institute - Inventors: Viktoriya Dubrovskaya; Francisco Javier Guenaga; Richard Wyatt - Web page: https://patentgrep.com/patent/US10870683B2 ## CPC - C07K 14/005: from viruses - A61K 39/12: Viral antigens - A61K 2039/545: {characterised by the dose, timing or administration schedule} - A61K 2039/55555: {Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers} - A61K 2039/58: {raising an immune response against a target which is not the antigen used for immunisation} - C12N 2740/16122: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes - C12N 2740/16134: Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein - 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) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) ## Abstract The present application relates to novel HIV-1 envelope glycoproteins which may be utilized as an HIV-1 vaccine immunogens, antigens for crystallization and for the identification of broad neutralizing antibodies. The present invention encompasses the preparation and purification of immunogenic compositions which are formulated into the vaccines of the present invention. ## Claims ### Claim 1 An engineered or non-naturally occurring trimer, wherein the trimer is a flexibly linked NFL2P trimer, wherein the trimer comprises one or more trimer-derived mutations (“TD mutations”), wherein said TD mutations comprise one or more mutations at residue 569 wherein a numerical position of an amino acid residue of the trimer corresponds with a numerical position of an amino acid residue of a 16055 NFL Env protein upon direct alignment of the numerical positions of the amino acid residues of the trimer with the numerical positions of the amino acid residues of the 16055 NFL Env protein, whose sequence is based on a BG505 numbering system. ### Claim 2 (depends on 1) The trimer of claim 1, wherein the one or more mutations at residue 569 comprises G. ### Claim 3 (depends on 1) The trimer of claim 1, wherein the trimer is derived from an Indian subtype C HIV-I Env sequence. ### Claim 4 (depends on 1) The trimer of claim 1, wherein the trimer further comprises a disulfide linkage. ### Claim 5 (depends on 4) The trimer of claim 4, wherein the disulfide linkage is an engineered intra-protomer disulfide I201C-A433C (CC). ### Claim 6 (depends on 1) The trimer of claim 1, further comprising a 10 residue (G4S) flexible linker (SEQ ID NO: 34) between a REKR-deleted Env gp120 C-terminus (“REKR” disclosed as SEQ ID NO: 35) and the unmodified gp41 N-terminus. ### Claim 7 (depends on 1) The trimer of claim 1, further comprising substitutions E47D, K49E, V65K, E106T, 1165L, E429R, R432Q and/or A500R. ### Claim 8 (depends on 1) The trimer of claim 1, wherein the trimer further comprises, in addition to said mutations, a T569G substitution. ### Claim 9 (depends on 1) The trimer of claim 1, wherein the trimer further comprises substitutions at residues 197, 276, 234, 262, 301, 360, 463 or any combination thereof. ### Claim 10 (depends on 9) The trimer of claim 9, comprising substitutions N197Q, N276Q, N234Q, N262Q, N301Q, N360Q, N463Q or any combination thereof. ### Claim 11 (depends on 9) The trimer of claim 9, comprising the substitutions at residues 276, 301, 360, 463 or any combination thereof. ### Claim 12 (depends on 10) The trimer of claim 10, comprising substitutions N276Q, N301Q, N360Q, N463Q or any combination thereof. ### Claim 13 (depends on 1) The trimer of claim 1, further comprising a potential N-linked glycan (PNGS) introduced at residue 332 by a K334S mutation (“+N332 PT”), wherein an italicized N within the amino acid sequence refers to an N-glycan, not an asparagine residue. ### Claim 14 An engineered or non-naturally occurring trimer, wherein the trimer is a flexibly linked NFL2P trimer, wherein the trimer comprises a N276Q/N463Q glycan-deleted variant with or without N332 restored, a +N332 N276Q/N360Q/N463Q triple N-glycan-deleted variant or a +N332 N276Q/N360Q/N463Q/N301Q quadruple N-glycan-deleted variant wherein a numerical position of an amino acid residue of the trimer corresponds with a numerical position of an amino acid residue of a 16055 NFL Env protein upon direct alignment of the numerical positions of the amino acid residues of the trimer with the numerical positions of the amino acid residues of the 16055 NFL Env protein, whose sequence is based on a BG505 numbering system.