# US 2023/0265192 A1 · Anti-ctla-4 binding proteins and methods of use thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2023/0265192 A1 - Document ID: US20230265192A1 - Status: Published application - Kind: A1 - Application number: 18/003,076 - Filed: 2021-07-02 - Published: 2023-08-24 - Earliest claimed: 2020-07-02 - Assignees: GigaGen, Inc. - Applicants: GigaGen, Inc. - Inventors: David Scott JOHNSON; Adam Shultz ADLER; Rena Aviva MIZRAHI; Yoong Wearn LIM; Michael ASENSIO; Erica Lyn STONE - Web page: https://patentgrep.com/patent/US20230265192A1 ## CPC - C07K 16/2818: {against CD28 or CD152} - A61K 39/39591: {Stabilisation, fragmentation} - A61P 35/00: Antineoplastic agents - A61K 2039/505: {comprising antibodies} - A61K 2039/507: {Comprising a combination of two or more separate antibodies} - C07K 2317/14: Specific host cells or culture conditions, e.g. components, pH or temperature - C07K 2317/21: from primates, e.g. man - C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered - C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity - C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues - C07K 2317/41: Glycosylation, sialylation, or fucosylation - C07K 2317/52: Constant or Fc region; Isotype - C07K 2317/565: Complementarity determining region [CDR] - C07K 2317/622: Single chain antibody (scFv) - C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation - C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC] - C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding - C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value - 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 Provided herein are antigen-binding proteins (ABPs) that selectively bind to CTLA-4 and its isoforms and homologs, and compositions comprising the ABPs. Also provided are methods of using the ABPs, such as therapeutic and diagnostic methods. ## Claims ### Claim 1 An isolated antigen binding protein (ABP) that specifically binds a human cytotoxic T-lymphocyte associated protein 4 (CTLA-4), wherein the ABP contacts amino acids K130, Y139, L141, I143 but does not contact amino acid R70 of the CTLA-4; and/or the CTLA-4 can associate with CD80/CD86 when bound to the ABP; and/or an interaction between the ABP and amino acid L74A and/or E68 of the CTLA-4 is greater than an interaction between Ipilimumab and amino acid L74A of CTLA-4. ### Claim 2 (depends on 1) The ABP of claim 1, wherein the ABP comprises a CDR1-L consisting of SEQ ID NO:12078 or SEQ ID NO: 1014, a CDR2-L consisting of SEQ ID NO:12079 or SEQ ID NO: 2014, a CDR3-L consisting of SEQ ID NO:12080 or SEQ ID NO: 3014, a CDR1-H consisting of SEQ ID NO:12075 or SEQ ID NO: 4014, a CDR2-H consisting of SEQ ID NO:12076 or SEQ ID NO: 5014 and a CDR3-H consisting of SEQ ID NO:12077 or SEQ ID NO: 6014. ### Claim 3 (depends on 1) The ABP of claim 1, wherein the ABP comprises a CDR1-L consisting of SEQ ID NO: 12004, a CDR2-L consisting of SEQ ID NO: 12014, a CDR3-L consisting of SEQ ID NO: 12024, a CDR1-H consisting of SEQ ID NO: 12039, a CDR2-H consisting of SEQ ID NO: 12049, and a CDR3-H consisting of SEQ ID NO: 12059. ### Claim 4 (depends on 1) The ABP of claim 1, wherein the ABP comprises a CDR1-L consisting of SEQ ID NO: 12005, a CDR2-L consisting of SEQ ID NO: 12015, a CDR3-L consisting of SEQ ID NO: 12025, a CDR1-H consisting of SEQ ID NO: 12040, a CDR2-H consisting of SEQ ID NO: 12050, and a CDR3-H consisting of SEQ ID NO: 12060. ### Claim 5 (depends on 1) The ABP of claim 1, wherein the ABP comprises a CDR1-L consisting of SEQ ID NO: 12006, a CDR2-L consisting of SEQ ID NO: 12016, a CDR3-L consisting of SEQ ID NO: 12026, a CDR1-H consisting of SEQ ID NO: 12041, a CDR2-H consisting of SEQ ID NO: 12051, and a CDR3-H consisting of SEQ ID NO: 12061. ### Claim 6 (depends on 1) The ABP of claim 1, wherein the ABP comprises a CDR1-L consisting of SEQ ID NO: 12007, a CDR2-L consisting of SEQ ID NO: 12017, a CDR3-L consisting of SEQ ID NO: 12027, a CDR1-H consisting of SEQ ID NO: 12042, a CDR2-H consisting of SEQ ID NO: 12052, and a CDR3-H consisting of SEQ ID NO: 12062. ### Claim 7 (depends on 1) The ABP of claim 1, wherein the ABP comprises a CDR1-L consisting of SEQ ID NO: 12008, a CDR2-L consisting of SEQ ID NO: 12018, a CDR3-L consisting of SEQ ID NO: 12028, a CDR1-H consisting of SEQ ID NO: 12043, a CDR2-H consisting of SEQ ID NO: 12053, and a CDR3-H consisting of SEQ ID NO: 12063. ### Claim 8 (depends on 1, 2) The ABP of claim 1 or 2, wherein the ABP comprises a variable light chain (VL) comprising a sequence at least 97% identical to SEQ ID NO:14 and a variable heavy chain (VH) comprising a sequence at least 97% identical to SEQ ID NO:114. ### Claim 9 (depends on 1, 2, 3, 4, 5, 6, 7, 8) The ABP of any one of claims 1-8, wherein the ABP comprises an scFv or a full length monoclonal antibody. ### Claim 10 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9) The ABP of any one of claims 1-9, wherein the ABP comprises an immunoglobulin constant region. ### Claim 11 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10) The ABP of any one of claims 1-10, wherein the ABP binds human CTLA-4 with a KD of less than 500 nM, as measured by surface plasmon resonance; or the ABP binds human CTLA-4 with a KD of less than 200 nM, as measured by surface plasmon resonance; or the ABP binds human CTLA-4 with a KD of less than 25 nM, as measured by surface plasmon resonance; or the ABP binds to human CTLA-4 on a cell surface with a KD of less than 25 nM. ### Claim 12 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11) The ABP of any one of claims 1-11, wherein the ABP is a IgG1 ABP. ### Claim 13 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12) The ABP of any one of claims 1-12, wherein the ABP comprises an IGHG1*01 human heavy chain constant region gene segment. ### Claim 14 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13) The ABP of any one of claims 1-13, wherein the ABP comprises a lysine at amino acid position 97 (R97) according to IMGT exon numbering. ### Claim 15 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13) The ABP of any one of claims 1-13, wherein the ABP comprises a lysine at amino acid position 97 (R214) according to EU numbering. ### Claim 16 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15) The ABP of any one of claims 1-15, comprising an afucosylated Fc region. ### Claim 17 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16) The ABP of any one of claims 1-16, produced from a cell comprising a bacterial protein RMD (GDP-6-deoxy-D-lyxo-4-hexulose reductase) or a modification thereof. ### Claim 18 (depends on 13) The ABP of claim 13, wherein the cell is cultured in the absence of fucose. ### Claim 19 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18) The ABP of any one of claims 1-18, produced from a cell lacking or reduced expression of Fut8. ### Claim 20 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19) The ABP of any one of claims 1-19, produced from a cell cultured in the presence of a fucosylation inhibitor, 2-Fluorfucose (2FF). ### Claim 21 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20) The ABP of any one of claims 1-20, produced from a cell overexpressing glycosyltransferase (GnTIII). ### Claim 22 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21) The ABP of any one of claims 1-21, having been isolated based on its fucosylation status. ### Claim 23 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22) The ABP of any one of claims 1-22, comprising an Fc region lacking core fucosylation of the N-glycan of the Fc portion. ### Claim 24 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23) The ABP of any one of claims 1-23, wherein the ABP is an afucosylated monoclonal antibody. ### Claim 25 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24) A pharmaceutical composition comprising the ABP of any one of claims 1-24 and a pharmaceutically acceptable excipient. ### Claim 26 (depends on 25) The pharmaceutical composition of claim 25, wherein less than 50% of the ABP is fucosylated. ### Claim 27 (depends on 26) The pharmaceutical composition of claim 26, wherein less than 40% of the ABP is fucosylated. ### Claim 28 (depends on 27) The pharmaceutical composition of claim 27, wherein less than 30% of the ABP is fucosylated. ### Claim 29 (depends on 28) The pharmaceutical composition of claim 28, wherein less than 20% of the ABP is fucosylated. ### Claim 30 (depends on 29) The pharmaceutical composition of claim 29, wherein less than 10% of the ABP is fucosylated. ### Claim 31 (depends on 25) The pharmaceutical composition of claim 25, wherein more than 30% of the ABP is fucosylated. ### Claim 32 (depends on 31) The pharmaceutical composition of claim 31, wherein more than 40% of the ABP is fucosylated. ### Claim 33 (depends on 32) The pharmaceutical composition of claim 32, wherein more than 50% of the ABP is fucosylated. ### Claim 34 (depends on 33) The pharmaceutical composition of claim 33, wherein more than 60% of the ABP is fucosylated. ### Claim 35 (depends on 34) The pharmaceutical composition of claim 34, wherein more than 70% of the ABP is fucosylated. ### Claim 36 (depends on 35) The pharmaceutical composition of claim 35, wherein more than 80% of the ABP is fucosylated. ### Claim 37 (depends on 36) The pharmaceutical composition of claim 36, wherein more than 90% of the ABP is fucosylated. ### Claim 38 (depends on 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37) The pharmaceutical composition of any one of claims 25-37, having a pH from 5.0 to 6.5. ### Claim 39 (depends on 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38) The pharmaceutical composition of any one of claims 25-38, comprising 20 mM of histidine or citrate buffer. ### Claim 40 (depends on 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39) The pharmaceutical composition of any one of claims 25-39, comprising 50 mM of NaCl. ### Claim 41 (depends on 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40) The pharmaceutical composition of any one of claims 25-40, comprising sucrose at a concentration from 170 mM to 270 mM. ### Claim 42 (depends on 41) The pharmaceutical composition of claim 41, comprising 170 mM or 270 mM of sucrose. ### Claim 43 (depends on 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42) The pharmaceutical composition of any one of claims 25-42, comprising 5 mg/mL to 20 mg/mL of the ABP. ### Claim 44 (depends on 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43) The pharmaceutical composition of any one of claims 26-43, comprising 20 mg/mL of the ABP. ### Claim 45 (depends on 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44) The pharmaceutical composition of any one of claims 26-44, comprising 5 mg/mL of the ABP. ### Claim 46 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45) A method of treating a disease comprising the step of administering to a subject in need thereof an effective amount of the ABP of any of claims 1-24 or the pharmaceutical composition of any one of claims 25-45. ### Claim 47 (depends on 46) The method of claim 46, wherein the disease is selected from the group consisting of cancer, AIDS, Alzheimer's disease and viral or bacterial infection. ### Claim 48 (depends on 46, 47) The method of claim 46 or claim 47, further comprising the step of administering one or more additional therapeutic agents to the subject. ### Claim 49 (depends on 48) The method of claim 48, wherein the additional therapeutic agent is selected from an anti-PD-L1, an anti-PD1, a LAG-3 inhibitor, aCD47 inhibitor, a TIGIT inhibitor, a chemotherapy agent, an immune-stimulatory agent, radiation, a BRAF inhibitor, a MEK inhibitor, a PI3K inhibitor, a cytokine, a polynucleotide encoding a cytokine, an oncolytic virus encoding a cytokine, and a combination thereof. ### Claim 50 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24) An isolated polynucleotide encoding the ABP of any of claims 1-24. ### Claim 51 (depends on 50) A vector comprising the isolated polynucleotide of claim 50. ### Claim 52 (depends on 50, 51) A host cell comprising the isolated polynucleotide of claim 50 or the vector of claim 51. ### Claim 53 (depends on 52) The host cell of claim 52, wherein the host cell further comprises a bacterial protein RMD (GDP-6-deoxy-D-lyxo-4-hexulose reductase). ### Claim 54 (depends on 52, 53) The host cell of any one of claims 52-53, wherein the host cell is cultured in the absence of fucose. ### Claim 55 (depends on 52, 53, 54) The host cell of any one of claims 52-54, lacking or having reduced expression of Fut8. ### Claim 56 (depends on 52, 53, 54, 55) The host cell of any one of claims 52-55, cultured in the presence of a fucosylation inhibitor 2-Fluorfucose (2FF). ### Claim 57 (depends on 52, 53, 54, 55, 56) The host cell of any one of claims 52-56, overexpressing glycosyltransferase (GnTIII). ### Claim 58 (depends on 52, 53, 54, 55, 56, 57) A method of producing an isolated antigen binding protein (ABP) that specifically binds human CTLA-4, comprising inducing expression of the ABP in the host cell of any one of claims 52-57, and isolating the ABP. ### Claim 59 (depends on 58) The method of claim 58, further comprising the step of isolating the ABP based on its fucosylation status. ### Claim 60 (depends on 58, 59) The method of any one of claims 58-59, wherein the host cell is cultured in a cultured medium comprising a fucosylation inhibitor. ### Claim 61 (depends on 60) The method of claim 60, wherein the fucosylation inhibitor is 2-Fluorfucose (2FF). ### Claim 62 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45) A method of reducing CTLA-4HI Tregs in a subject with limited proliferation of remaining Tregs comprising administering an effective dose of the ABP of any one of claims 1-24 or the pharmaceutical composition of any one of claims 25-45 to the subject. ### Claim 63 (depends on 62) The method of claim 62, wherein the subject is a human subject, optionally, a human subject with RCC (renal cell cancer), NSCLC (non-small cell lung cancer), Merkel cell carcinoma, cSCC, mesothelioma, MSI colorectal cancer, ovarian cancer, or cervical cancer. ### Claim 64 (depends on 62, 63) The method of claim 62 or claim 63, further comprising the step of administering one or more additional therapeutic agents to the subject. ### Claim 65 (depends on 64) The method of claim 64, wherein the additional therapeutic agent is an anti-PD-L1 or an anti-PD1 or a combination thereof. ### Claim 66 An isolated antigen binding protein (ABP) that specifically binds a human cytotoxic T-lymphocyte associated protein 4 (CTLA-4), wherein the ABP comprises: (a) a CDR1-L consisting of SEQ ID NO:12078, a CDR2-L consisting of SEQ ID NO:12079, a CDR3-L consisting of SEQ ID NO: 12080, a CDR1-H consisting of SEQ ID NO:12075, a CDR2-H consisting of SEQ ID NO:12076 and a CDR3-H consisting of SEQ ID NO:12077; (b) a CDR1-L consisting of SEQ ID NO: 1014, a CDR2-L consisting of SEQ ID NO: 2014, a CDR3-L consisting of SEQ ID NO: 3014, a CDR1-H consisting of SEQ ID NO: 4014, a CDR2-H consisting of SEQ ID NO: 5014 and a CDR3-H consisting of SEQ ID NO: 6014; (c) a CDR1-L consisting of SEQ ID NO: 12004, a CDR2-L consisting of SEQ ID NO: 12014, a CDR3-L consisting of SEQ ID NO: 12024, a CDR1-H consisting of SEQ ID NO: 12039, a CDR2-H consisting of SEQ ID NO: 12049, and a CDR3-H consisting of SEQ ID NO: 12059; (d) a CDR1-L consisting of SEQ ID NO: 12005, a CDR2-L consisting of SEQ ID NO: 12015, a CDR3-L consisting of SEQ ID NO: 12025, a CDR1-H consisting of SEQ ID NO: 12040, a CDR2-H consisting of SEQ ID NO: 12050, and a CDR3-H consisting of SEQ ID NO: 12060; (e) a CDR1-L consisting of SEQ ID NO: 12006, a CDR2-L consisting of SEQ ID NO: 12016, a CDR3-L consisting of SEQ ID NO: 12026, a CDR1-H consisting of SEQ ID NO: 12041, a CDR2-H consisting of SEQ ID NO: 12051, and a CDR3-H consisting of SEQ ID NO: 12061; (f) a CDR1-L consisting of SEQ ID NO: 12007, a CDR2-L consisting of SEQ ID NO: 12017, a CDR3-L consisting of SEQ ID NO: 12027, a CDR1-H consisting of SEQ ID NO: 12042, a CDR2-H consisting of SEQ ID NO: 12052, and a CDR3-H consisting of SEQ ID NO: 12062; or (g) a CDR1-L consisting of SEQ ID NO: 12008, a CDR2-L consisting of SEQ ID NO: 12018, a CDR3-L consisting of SEQ ID NO: 12028, a CDR1-H consisting of SEQ ID NO: 12043, a CDR2-H consisting of SEQ ID NO: 12053, and a CDR3-H consisting of SEQ ID NO: 12063. ### Claim 67 (depends on 66) The ABP of claim 66, wherein the ABP comprises a variable light chain (VL) comprising a sequence at least 97% identical to SEQ ID NO:14 and a variable heavy chain (VH) comprising a sequence at least 97% identical to SEQ ID NO:114. ### Claim 68 (depends on 66, 67) The ABP of any one of claims 66-67, wherein the ABP comprises an scFv or a full length monoclonal antibody. ### Claim 69 (depends on 66, 67, 68) The ABP of any one of claims 66-68, wherein the ABP comprises an immunoglobulin constant region. ### Claim 70 (depends on 66, 67, 68, 69) The ABP of any one of claims 66-69, wherein the ABP binds human CTLA-4 with a KD of less than 500 nM, as measured by surface plasmon resonance; or the ABP binds human CTLA-4 with a KD of less than 200 nM, as measured by surface plasmon resonance; or the ABP binds human CTLA-4 with a KD of less than 25 nM, as measured by surface plasmon resonance; or the ABP binds to human CTLA-4 on a cell surface with a KD of less than 25 nM. ### Claim 71 (depends on 66, 67, 68, 69, 70) The ABP of any one of claims 66-70, wherein the ABP is a IgG1 ABP. ### Claim 72 (depends on 66, 67, 68, 69, 70, 71) The ABP of any one of claims 66-71, wherein the ABP comprises an IGHG1*01 human heavy chain constant region gene segment. ### Claim 73 (depends on 66, 67, 68, 69, 70, 71, 72) The ABP of any one of claims 66-72, wherein the ABP comprises a lysine at amino acid position 97 (R97) according to IMGT exon numbering. ### Claim 74 (depends on 66, 67, 68, 69, 70, 71, 72, 73) The ABP of any one of claims 66-73, wherein the ABP comprises a lysine at amino acid position 97 (R214) according to EU numbering. ### Claim 75 (depends on 66, 67, 68, 69, 70, 71, 72, 73, 74) The ABP of any one of claims 66-74, comprising an afucosylated Fc region. ### Claim 76 (depends on 66, 67, 68, 69, 70, 71, 72, 73, 74, 75) The ABP of any one of claims 66-75, produced from a cell comprising a bacterial protein RMD (GDP-6-deoxy-D-lyxo-4-hexulose reductase) or a modification thereof. ### Claim 77 (depends on 76) The ABP of claim 76, wherein the cell is cultured in the absence of fucose. ### Claim 78 (depends on 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77) The ABP of any one of claims 66-77, produced from a cell lacking or reduced expression of Fut8. ### Claim 79 (depends on 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78) The ABP of any one of claims 66-78, produced from a cell cultured in the presence of a fucosylation inhibitor, 2-Fluorfucose (2FF). ### Claim 80 (depends on 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79) The ABP of any one of claims 66-79, produced from a cell overexpressing glycosyltransferase (GnTIII). ### Claim 81 (depends on 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80) The ABP of any one of claims 66-80, having been isolated based on its fucosylation status. ### Claim 82 (depends on 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81) The ABP of any one of claims 58-81, comprising an Fc region lacking core fucosylation of the N-glycan of the Fc portion. ### Claim 83 (depends on 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82) The ABP of any one of claims 66-82, wherein the ABP is an afucosylated monoclonal antibody. ### Claim 84 (depends on 83) The ABP of claim 83, wherein the afucosylated Fc region has less than 30% fucosylation, and wherein less than 30% fucosylation enhances Fc Gamma Receptor IIIa (FcgRIIIa) signaling or a protein encoded by protein encoded by FcgR3a. ### Claim 85 (depends on 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84) A pharmaceutical composition comprising the ABP of any one of claims 66-84, and a pharmaceutically acceptable excipient. ### Claim 86 (depends on 85) The pharmaceutical composition of claim 85, wherein less than 50% of the ABP is fucosylated. ### Claim 87 (depends on 86) The pharmaceutical composition of claim 86, wherein less than 40% of the ABP is fucosylated. ### Claim 88 (depends on 87) The pharmaceutical composition of claim 87, wherein less than 30% of the ABP is fucosylated. ### Claim 89 (depends on 88) The pharmaceutical composition of claim 88, wherein less than 20% of the ABP is fucosylated. ### Claim 90 (depends on 89) The pharmaceutical composition of claim 89, wherein less than 10% of the ABP is fucosylated. ### Claim 91 (depends on 85) The pharmaceutical composition of claim 85, wherein more than 30% of the ABP is fucosylated. ### Claim 92 (depends on 91) The pharmaceutical composition of claim 91, wherein more than 40% of the ABP is fucosylated. ### Claim 93 (depends on 92) The pharmaceutical composition of claim 92, wherein more than 50% of the ABP is fucosylated. ### Claim 94 (depends on 93) The pharmaceutical composition of claim 93, wherein more than 60% of the ABP is fucosylated. ### Claim 95 (depends on 94) The pharmaceutical composition of claim 94, wherein more than 70% of the ABP is fucosylated. ### Claim 96 (depends on 95) The pharmaceutical composition of claim 95, wherein more than 80% of the ABP is fucosylated. ### Claim 97 (depends on 96) The pharmaceutical composition of claim 96, wherein more than 90% of the ABP is fucosylated. ### Claim 98 (depends on 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97) The pharmaceutical composition of any one of claims 85-97, having a pH from 5.0 to 6.5. ### Claim 99 (depends on 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98) The pharmaceutical composition of any one of claims 85-98, comprising 20 mM of histidine or citrate buffer. ### Claim 100 (depends on 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99) The pharmaceutical composition of any one of claims 85-99, comprising 50 mM of NaCl. ### Claim 101 (depends on 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100) The pharmaceutical composition of any one of claims 85-100, comprising sucrose at a concentration from 170 mM to 270 mM. ### Claim 102 (depends on 101) The pharmaceutical composition of claim 101, comprising 170 mM or 270 mM of sucrose. ### Claim 103 (depends on 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102) The pharmaceutical composition of any one of claims 85-102, comprising 20 mg/mL of the ABP. ### Claim 104 (depends on 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103) The pharmaceutical composition of any one of claims 85-103, comprising 5 mg/mL of the ABP. ### Claim 105 (depends on 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104) A method of treating cancer comprising the step of: administering to a subject in need thereof an effective amount of the ABP of any of claims 66-84 or the pharmaceutical composition of any one of claims 85-104. ### Claim 106 (depends on 105) The method of claim 105, wherein the subject has a malignant tumor. ### Claim 107 (depends on 105) The method of claim 105, wherein the ABP, when administered, comprises increased Fc receptor (FcR) signaling as compared to ipilimumab, and wherein said administering reduces the amount of CTLA-4HI Tregs in the subject. ### Claim 108 (depends on 107) The method of claim 107, wherein said administering reduces proliferation of peripheral Tregs in the subject as compared to ipilimumab. ### Claim 109 (depends on 105, 106, 107, 108) The method of any one of claims 105-108, further comprising the step of administering one or more additional therapeutic agents to the subject. ### Claim 110 (depends on 109) The method of claim 109, wherein the additional therapeutic agent is selected from an anti-PD-L1, an anti-PD1, a TIGIT inhibitor, a LAG-3 inhibitor, a CD47 inhibitor, a BRAF inhibitor, a MEK inhibitor, a PI3K inhibitor, a chemotherapy agent, an immune-stimulatory agent, radiation, a cytokine, a polynucleotide encoding a cytokine, an oncolytic virus encoding a cytokine, and a combination thereof. ### Claim 111 (depends on 105, 106, 107, 108, 109, 110) The method of any one of claims 105-110, wherein the ABP comprises an afucosylated Fc region that has less than 30% fucosylation, and wherein less than 30% fucosylation enhances Fc Gamma Receptor IIIa (FcgRIIIa) signaling or a protein encoded by protein encoded by FcgR3a. ### Claim 112 (depends on 105, 106, 107, 108, 109, 110) The method of any one of claims 105-110, wherein the ABP comprises a fucosylated Fc region that has more than 70% fucosylation. ### Claim 113 (depends on 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84) An isolated polynucleotide encoding the ABP of any of claims 66-84. ### Claim 114 (depends on 113) A vector comprising the isolated polynucleotide of claim 113. ### Claim 115 (depends on 113, 114) A host cell comprising the isolated polynucleotide of claim 113 or the vector of claim 114. ### Claim 116 (depends on 115) The host cell of claim 115, wherein the host cell is engineered to have reduced fucosylation as compared to a host cell that is not engineered. ### Claim 117 (depends on 116) The host cell of claim 116, wherein the host cell further comprises a bacterial protein RMD (GDP-6-deoxy-D-lyxo-4-hexulose reductase). ### Claim 118 (depends on 115, 116, 117) The host cell of any one of claims 115-117, wherein the host cell is cultured in the absence of fucose. ### Claim 119 (depends on 115, 116, 117, 118) The host cell of any one of claims 115-118, lacking or having reduced expression of Fut8. ### Claim 120 (depends on 115, 116, 117, 118, 119) The host cell of any one of claims 115-119, cultured in the presence of a fucosylation inhibitor 2-Fluorfucose (2FF). ### Claim 121 (depends on 115, 116, 117, 118, 119, 120) The host cell of any one of claims 115-120, overexpressing glycosyltransferase (GnTIII). ### Claim 122 (depends on 115, 116, 117, 118, 119, 120, 121) A method of producing an isolated antigen binding protein (ABP) that specifically binds human CTLA-4, comprising inducing expression of the ABP in the host cell of any one of claims 115-121, and isolating the ABP, wherein the ABP comprises an afucosylated Fc. ### Claim 123 (depends on 122) The method of claim 122, further comprising the step of isolating the ABP based on its fucosylation status. ### Claim 124 (depends on 115, 116, 117, 118, 119, 120, 121, 122, 123) The method of any one of claims 115-123, wherein the host cell is cultured in a cultured medium comprising a fucosylation inhibitor. ### Claim 125 (depends on 124) The method of claim 124, wherein the fucosylation inhibitor is 2-Fluorfucose (2FF). ### Claim 126 An isolated antigen binding protein (ABP) that specifically binds an antigen, comprising an IGHG1*01 human heavy chain constant region gene segment, optionally wherein the antigen is a human cytotoxic T-lymphocyte associated protein 4 (CTLA-4). ### Claim 127 (depends on 126) The ABP of claim 126, wherein the ABP comprises: (a) a CDR1-L consisting of SEQ ID NO:12078, a CDR2-L consisting of SEQ ID NO:12079, a CDR3-L consisting of SEQ ID NO: 12080, a CDR1-H consisting of SEQ ID NO:12075, a CDR2-H consisting of SEQ ID NO:12076 and a CDR3-H consisting of SEQ ID NO:12077; (b) a CDR1-L consisting of SEQ ID NO: 1014, a CDR2-L consisting of SEQ ID NO: 2014, a CDR3-L consisting of SEQ ID NO: 3014, a CDR1-H consisting of SEQ ID NO: 4014, a CDR2-H consisting of SEQ ID NO: 5014 and a CDR3-H consisting of SEQ ID NO: 6014; (c) a CDR1-L consisting of SEQ ID NO: 12004, a CDR2-L consisting of SEQ ID NO: 12014, a CDR3-L consisting of SEQ ID NO: 12024, a CDR1-H consisting of SEQ ID NO: 12039, a CDR2-H consisting of SEQ ID NO: 12049, and a CDR3-H consisting of SEQ ID NO: 12059; (d) a CDR1-L consisting of SEQ ID NO: 12005, a CDR2-L consisting of SEQ ID NO: 12015, a CDR3-L consisting of SEQ ID NO: 12025, a CDR1-H consisting of SEQ ID NO: 12040, a CDR2-H consisting of SEQ ID NO: 12050, and a CDR3-H consisting of SEQ ID NO: 12060; (e) a CDR1-L consisting of SEQ ID NO: 12006, a CDR2-L consisting of SEQ ID NO: 12016, a CDR3-L consisting of SEQ ID NO: 12026, a CDR1-H consisting of SEQ ID NO: 12041, a CDR2-H consisting of SEQ ID NO: 12051, and a CDR3-H consisting of SEQ ID NO: 12061; (f) a CDR1-L consisting of SEQ ID NO: 12007, a CDR2-L consisting of SEQ ID NO: 12017, a CDR3-L consisting of SEQ ID NO: 12027, a CDR1-H consisting of SEQ ID NO: 12042, a CDR2-H consisting of SEQ ID NO: 12052, and a CDR3-H consisting of SEQ ID NO: 12062; or (g) a CDR1-L consisting of SEQ ID NO: 12008, a CDR2-L consisting of SEQ ID NO: 12018, a CDR3-L consisting of SEQ ID NO: 12028, a CDR1-H consisting of SEQ ID NO: 12043, a CDR2-H consisting of SEQ ID NO: 12053, and a CDR3-H consisting of SEQ ID NO: 12063. ### Claim 128 (depends on 127) The ABP of claim 127, wherein the ABP comprises a variable light chain (VL) comprising a sequence at least 97% identical to SEQ ID NO:14 and a variable heavy chain (VH) comprising a sequence at least 97% identical to SEQ ID NO:114. ### Claim 129 (depends on 126) The ABP of claim 126, wherein the ABP comprises: (a) a CDR1-L consisting of any one of SEQ ID NOs:, a CDR2-L consisting of any one of SEQ ID NOs: 1001-1028, a CDR3-L consisting of any one of SEQ ID NOs: 2001-2028, a CDR1-H consisting of any one of SEQ ID NOs:, a CDR2-H consisting of consisting of any one of SEQ ID NOs: 3001-3028. ### Claim 130 (depends on 127) The ABP of claim 127, wherein the ABP comprises a variable light chain (VL) comprising a sequence at least 97% identical to any one of SEQ ID NOs:1-28 and a variable heavy chain (VH) comprising a sequence at least 97% identical to SEQ ID NO:1-128. ### Claim 131 (depends on 126) The ABP of claim 126, wherein the ABP comprises a lysine at amino acid position 97 (R97) according to IMGT exon numbering. ### Claim 132 (depends on 126) The ABP of claim 126, wherein the ABP comprises a lysine at amino acid position 97 (R214) according to EU numbering. ### Claim 133 (depends on 126, 127, 128, 129, 130, 131, 132) The ABP of any one of claims 126-132, comprising an afucosylated Fc region. ### Claim 134 (depends on 126, 127, 128, 129, 130, 131, 132, 133) The ABP of any one of claims 126-133, produced from a cell comprising a bacterial protein RMD (GDP-6-deoxy-D-lyxo-4-hexulose reductase) or a modification thereof. ### Claim 135 (depends on 134) The ABP of claim 134, wherein the cell is cultured in the absence of fucose. ### Claim 136 (depends on 126, 127, 128, 129, 130, 131, 132, 133, 134, 135) The ABP of any one of claims 126-135, produced from a cell lacking or reduced expression of Fut8. ### Claim 137 (depends on 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136) The ABP of any one of claims 126-136, produced from a cell cultured in the presence of a fucosylation inhibitor, 2-Fluorfucose (2FF). ### Claim 138 (depends on 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137) The ABP of any one of claims 126-137, produced from a cell overexpressing glycosyltransferase (GnTIII). ### Claim 139 (depends on 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138) The ABP of any one of claims 126-138, having been isolated based on its fucosylation status. ### Claim 140 (depends on 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139) The ABP of any one of claims 126-139, comprising an Fc region lacking core fucosylation of the N-glycan of the Fc portion. ### Claim 141 (depends on 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140) The ABP of any one of claims 126-140, wherein the ABP is an afucosylated monoclonal antibody. ### Claim 142 (depends on 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141) The ABP of any one of claims 131-141, wherein the ABP is selected from an anti-CTLA-4 antibody or antigen-binding fragment thereof, anti-PD-L1 antibody or antigen-binding fragment thereof, an anti-PD1 antibody or antigen-binding fragment thereof, a TIGIT antibody or antigen-binding fragment thereof, a LAG-3 antibody or antigen-binding fragment thereof, a CD47 antibody or antigen-binding fragment thereof, a BRAF antibody or antigen-binding fragment thereof, a MEK antibody or antigen-binding fragment thereof, and a PI3K antibody or antigen-binding fragment thereof. ### Claim 143 (depends on 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141) The ABP any one of claims 131-141, wherein the ABP comprises: (a) a CDR1-L consisting of SEQ ID NO:12078, a CDR2-L consisting of SEQ ID NO:12079, a CDR3-L consisting of SEQ ID NO:12080, a CDR1-H consisting of SEQ ID NO:12075, a CDR2-H consisting of SEQ ID NO:12076 and a CDR3-H consisting of SEQ ID NO:12077; (b) a CDR1-L consisting of SEQ ID NO: 1014, a CDR2-L consisting of SEQ ID NO: 2014, a CDR3-L consisting of SEQ ID NO: 3014, a CDR1-H consisting of SEQ ID NO: 4014, a CDR2-H consisting of SEQ ID NO: 5014 and a CDR3-H consisting of SEQ ID NO: 6014; (c) a CDR1-L consisting of SEQ ID NO: 12004, a CDR2-L consisting of SEQ ID NO: 12014, a CDR3-L consisting of SEQ ID NO: 12024, a CDR1-H consisting of SEQ ID NO: 12039, a CDR2-H consisting of SEQ ID NO: 12049, and a CDR3-H consisting of SEQ ID NO: 12059; (d) a CDR1-L consisting of SEQ ID NO: 12005, a CDR2-L consisting of SEQ ID NO: 12015, a CDR3-L consisting of SEQ ID NO: 12025, a CDR1-H consisting of SEQ ID NO: 12040, a CDR2-H consisting of SEQ ID NO: 12050, and a CDR3-H consisting of SEQ ID NO: 12060; (e) a CDR1-L consisting of SEQ ID NO: 12006, a CDR2-L consisting of SEQ ID NO: 12016, a CDR3-L consisting of SEQ ID NO: 12026, a CDR1-H consisting of SEQ ID NO: 12041, a CDR2-H consisting of SEQ ID NO: 12051, and a CDR3-H consisting of SEQ ID NO: 12061; (f) a CDR1-L consisting of SEQ ID NO: 12007, a CDR2-L consisting of SEQ ID NO: 12017, a CDR3-L consisting of SEQ ID NO: 12027, a CDR1-H consisting of SEQ ID NO: 12042, a CDR2-H consisting of SEQ ID NO: 12052, and a CDR3-H consisting of SEQ ID NO: 12062; or (g) a CDR1-L consisting of SEQ ID NO: 12008, a CDR2-L consisting of SEQ ID NO: 12018, a CDR3-L consisting of SEQ ID NO: 12028, a CDR1-H consisting of SEQ ID NO: 12043, a CDR2-H consisting of SEQ ID NO: 12053, and a CDR3-H consisting of SEQ ID NO: 12063. ### Claim 144 (depends on 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141) The ABP of any one of claims 131-141, wherein the ABP comprises a variable light chain (VL) comprising a sequence at least 97% identical to SEQ ID NO:14 and a variable heavy chain (VH) comprising a sequence at least 97% identical to SEQ ID NO:114. ### Claim 145 (depends on 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141) The ABP of any one of claims 131-141, wherein the ABP comprises: (a) a CDR1-L consisting of any one of SEQ ID NO: 12081: a CDR2-L consisting of SEQ ID NO: 12082, a CDR3-L consisting of SEQ ID NO: 12083, a CDR1-H consisting of SEQ ID NO: 12084, a CDR2-H consisting of consisting of SEQ ID NO: 12085, and a CDR3-H consisting of SEQ ID NO: 12086. ### Claim 146 (depends on 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141) The ABP of any one of claims 131-141, wherein the ABP comprises a variable light chain (VL) comprising a sequence at least 97% identical to SEQ ID NO: 12088 and a variable heavy chain (VH) comprising a sequence at least 97% identical to SEQ ID NO: 12087. ### Claim 147 (depends on 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146) A pharmaceutical composition comprising the ABP of any one of claims 126-146 and a pharmaceutically acceptable excipient. ### Claim 148 (depends on 147) The pharmaceutical composition of claim 147, wherein less than 50% of the ABP is fucosylated. ### Claim 149 (depends on 148) The pharmaceutical composition of claim 148, wherein less than 40% of the ABP is fucosylated. ### Claim 150 (depends on 149) The pharmaceutical composition of claim 149, wherein less than 30% of the ABP is fucosylated. ### Claim 151 (depends on 150) The pharmaceutical composition of claim 150, wherein less than 20% of the ABP is fucosylated. ### Claim 152 (depends on 151) The pharmaceutical composition of claim 151, wherein less than 10% of the ABP is fucosylated. ### Claim 153 (depends on 147) The pharmaceutical composition of claim 147, wherein more than 30% of the ABP is fucosylated. ### Claim 154 (depends on 153) The pharmaceutical composition of claim 153, wherein more than 40% of the ABP is fucosylated. ### Claim 155 (depends on 154) The pharmaceutical composition of claim 154, wherein more than 50% of the ABP is fucosylated. ### Claim 156 (depends on 155) The pharmaceutical composition of claim 155, wherein more than 60% of the ABP is fucosylated. ### Claim 157 (depends on 156) The pharmaceutical composition of claim 156, wherein more than 70% of the ABP is fucosylated. ### Claim 158 (depends on 157) The pharmaceutical composition of claim 157, wherein more than 80% of the ABP is fucosylated. ### Claim 159 (depends on 158) The pharmaceutical composition of claim 158, wherein more than 90% of the ABP is fucosylated. ### Claim 160 (depends on 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159) The pharmaceutical composition of any one of claims 147-159, having a pH from 5.0 to 6.5. ### Claim 161 (depends on 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160) The pharmaceutical composition of any one of claims 147-160, comprising 20 mM of histidine or citrate buffer. ### Claim 162 (depends on 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161) The pharmaceutical composition of any one of claims 147-161, comprising 50 mM of NaCl. ### Claim 163 (depends on 162) The pharmaceutical composition of any one of claims 162-162, comprising sucrose at a concentration from 170 mM to 270 mM. ### Claim 164 (depends on 163) The pharmaceutical composition of claim 163, comprising 170 mM or 270 mM of sucrose. ### Claim 165 (depends on 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164) The pharmaceutical composition of any one of claims 147-164, comprising 20 mg/mL of the ABP. ### Claim 166 (depends on 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165) A method of treating a disease comprising the step of administering to a subject in need thereof an effective amount of the ABP of any of claims 125-145 or the pharmaceutical composition of any one of claims 147-165. ### Claim 167 (depends on 166) The method of claim 166, wherein the disease is selected from the group consisting of cancer, AIDS, Alzheimer's disease and viral or bacterial infection. ### Claim 168 (depends on 166, 167) The method of claim 166 or claim 167, further comprising the step of administering one or more additional therapeutic agents to the subject. ### Claim 169 (depends on 168) The method of claim 168, wherein the additional therapeutic agent is selected from an anti-PD-L1, an anti-PD1, a TIGIT inhibitor, a LAG-3 inhibitor, a CD47 inhibitor, a BRAF inhibitor, a MEK inhibitor, a PI3K inhibitor, a chemotherapy agent, an immune-stimulatory agent, radiation, a cytokine, a polynucleotide encoding a cytokine, an oncolytic virus encoding a cytokine, and a combination thereof. ### Claim 170 (depends on 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146) An isolated polynucleotide encoding the ABP of any of claims 126-146. ### Claim 171 (depends on 170) A vector comprising the isolated polynucleotide of claim 170. ### Claim 172 (depends on 170) A host cell comprising the isolated polynucleotide of claim 170 or the vector of claim 170. ### Claim 173 (depends on 172) The host cell of claim 172, wherein the host cell further comprises a bacterial protein RMD (GDP-6-deoxy-D-lyxo-4-hexulose reductase). ### Claim 174 (depends on 172, 173) The host cell of any one of claims 172-173, wherein the host cell is cultured in the absence of fucose. ### Claim 175 (depends on 172, 173, 174) The host cell of any one of claims 172-174, lacking or having reduced expression of Fut8. ### Claim 176 (depends on 172, 173, 174, 175) The host cell of any one of claims 172-175, cultured in the presence of a fucosylation inhibitor 2-Fluorfucose (2FF). ### Claim 177 (depends on 172, 173, 174, 175, 176) The host cell of any one of claims 172-176, overexpressing glycosyltransferase (GnTIII). ### Claim 178 (depends on 171, 172, 173, 174, 175, 176, 177) A method of producing an isolated antigen binding protein (ABP) that specifically binds human CTLA-4, comprising inducing expression of the ABP in the host cell of any one of claims 171-177, and isolating the ABP. ### Claim 179 (depends on 178) The method of claim 178, further comprising the step of isolating the ABP based on its fucosylation status. ### Claim 180 (depends on 178, 179) The method of any one of claims 178-179, wherein the host cell is cultured in a cultured medium comprising a fucosylation inhibitor. ### Claim 181 (depends on 180) The method of claim 180, wherein the fucosylation inhibitor is 2-Fluorfucose (2FF). ### Claim 182 (depends on 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164) A method of reducing CTLA-4HI Tregs in a subject with limited proliferation of remaining Tregs comprising administering an effective dose of the ABP of any one of claims 126-146 or the pharmaceutical composition of any one of claims 141-164. ### Claim 183 (depends on 182) The method of claim 182, wherein the subject is a human subject, optionally, a human subject with melanoma, RCC (renal cell cancer), NSCLC (non-small cell lung cancer), Merkel cell carcinoma, cSCC, mesothelioma, MSI colorectal cancer, ovarian cancer, or cervical cancer. ### Claim 184 (depends on 182, 183) The method of claim 182 or claim 183, further comprising the step of administering one or more additional therapeutic agents to the subject. ### Claim 185 (depends on 184) The method of claim 184, wherein the additional therapeutic agent is an anti-PD-L1 or an anti-PD1 or a combination thereof. ### Claim 186 (depends on 182) The method of claim 182, wherein the subject has a tumor with high levels of Tregs, high levels of CTLA-4, high levels of NK cells, or high levels of activating FcRs. ### Claim 187 (depends on 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164) A method of reducing CTLA-4HI Tregs in a subject with limited proliferation of remaining Tregs comprising administering an effective dose of the ABP of any one of claims 126-146 or the pharmaceutical composition of any one of claims 146-164. ### Claim 188 (depends on 187) The method of claim 187, wherein the subject is a human subject, optionally, a human subject with melanoma, RCC (renal cell cancer), NSCLC (non-small cell lung cancer), Merkel cell carcinoma, cSCC, mesothelioma, MSI colorectal cancer, ovarian cancer, or cervical cancer. ### Claim 189 (depends on 187, 188) The method of claim 187 or claim 188, further comprising the step of administering one or more additional therapeutic agents to the subject. ### Claim 190 (depends on 187) The method of claim 187, wherein the subject has a tumor with high levels of Tregs, high levels of CTLA-4, high levels of NK cells, or high levels of activating FcRs. ### Claim 191 A method of reducing CTLA-4HI Tregs in a subject with limited proliferation of remaining Tregs comprising administering to the subject an effective dose of an antigen binding protein (ABP) that specifically binds a human cytotoxic T-lymphocyte associated protein 4 (CTLA-4). ### Claim 192 (depends on 191) The method of claim 191, wherein the subject is a human subject, optionally, a human subject with melanoma, RCC (renal cell cancer), NSCLC (non-small cell lung cancer), Merkel cell carcinoma, cSCC, mesothelioma, MSI colorectal cancer, ovarian cancer, or cervical cancer. ### Claim 193 (depends on 191, 192) The method of claim 191 or claim 192, further comprising the step of administering one or more additional therapeutic agents to the subject. ### Claim 194 (depends on 191) The ABP of claim 191, wherein the ABP comprises a variable light chain (VL) comprising a sequence at least 97% identical to SEQ ID NO:14 and a variable heavy chain (VH) comprising a sequence at least 97% identical to SEQ ID NO:114. ### Claim 195 (depends on 191) The ABP of claim 191, wherein the ABP comprises: (a) a CDR1-L consisting of any one of SEQ ID NOs:, a CDR2-L consisting of any one of SEQ ID NOs: 1001-1028, a CDR3-L consisting of any one of SEQ ID NOs: 3001-3028, a CDR1-H consisting of any one of SEQ ID NOs:, a CDR2-H consisting of consisting of any one of SEQ ID NOs: 3001-3028. ### Claim 196 (depends on 191) The ABP of claim 191, wherein the ABP comprises a variable light chain (VL) comprising a sequence at least 97% identical to any one of SEQ ID NOs:1-28 and a variable heavy chain (VH) comprising a sequence at least 97% identical to SEQ ID NO:101-128. ### Claim 197 (depends on 191) The ABP of claim 191, wherein the ABP comprises: (a) a CDR1-L consisting of any one of SEQ ID NO: 12081:, a CDR2-L consisting of SEQ ID NO: 12082, a CDR3-L consisting of SEQ ID NO: 12083, a CDR1-H consisting of SEQ ID NO: 12084, a CDR2-H consisting of consisting of SEQ ID NO: 12085, and a CDR3-H consisting of SEQ ID NO: 12086. ### Claim 198 (depends on 191) The ABP of claim 191, wherein the ABP comprises a variable light chain (VL) comprising a sequence at least 97% identical to SEQ ID NO: 12088 and a variable heavy chain (VH) comprising a sequence at least 97% identical to SEQ ID NO: 12087.