WO2022068919A1 - Peptide se liant à un anticorps anti-pd-1 et son application - Google Patents

Peptide se liant à un anticorps anti-pd-1 et son application Download PDF

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WO2022068919A1
WO2022068919A1 PCT/CN2021/122062 CN2021122062W WO2022068919A1 WO 2022068919 A1 WO2022068919 A1 WO 2022068919A1 CN 2021122062 W CN2021122062 W CN 2021122062W WO 2022068919 A1 WO2022068919 A1 WO 2022068919A1
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seq
amino acids
protein
fab
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夏瑜
王忠民
张鹏
李百勇
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CTTQ Akeso Shanghai Biomed Tech Co Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/715—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids

Definitions

  • the present invention belongs to the field of immunology. Specifically, it relates to peptides that bind to PD-1 antibodies and uses thereof.
  • Cell surface glycans play important roles in cancer, such as cell signaling and communication, tumor cell dissociation and invasion, cell-matrix interaction, tumor angiogenesis, immune regulation and metastasis formation, and immune surveillance (Varki A.( 2017). Glycobiology, 27, 3-49.). Glycosylation helps tumor cells escape immune surveillance (Okada M. et al. (2017). Cell Rep., 20, 1017-1028.) (Liu CY. et al. (2011). Proc. Natl. Acad. Sci. USA, 108, 11332-11337.) (Potapenko O.I. et al. (2010). Mol. Oncol., 4, 98-118.).
  • the core part of the glycan is composed of two N-acetylglucosamine (GlcNac, NAG) and one fucose (Fucose, FUC). Fucosylation is associated with cancer (Pinho, 2015), and depleted T cells in tumors tend to be highly core-fucosylated (Okada M. et al. (2017). Cell Rep., 20, 1017-1028 ). In some cancers, such as lung and breast cancer, overexpression of core fucosylation (FUT8) has been observed (Liu CY. et al. (2011). Proc. Natl. Acad. Sci. USA, 108, 11332- 11337) (Potapenko O.I. et al.
  • glycosyl groups on the surface of PD-1 may interact with anti-PD-1 antibodies, enhancing the binding activity of the two, which in turn leads to better clinical outcomes (Fessas H. et al. (2017). Semin. Oncol., 44, 136-140).
  • the present invention has been completed.
  • the present invention relates to the following aspects:
  • a peptide preferably binding an anti-PD-1 antibody or an antigen-binding fragment thereof, said peptide comprising building block 1 and building block 2, wherein building block 1 comprises a PD-1 protein fragment selected from the group consisting of: PD
  • building block 1 comprises a PD-1 protein fragment selected from the group consisting of: PD
  • Structural unit 2 comprises a PD-1 protein fragment selected from the group consisting of amino acids at positions 127-133 of PD-1 protein (as shown in SEQ ID NO: 18), amino acids at positions 127-132 (show in SEQ ID NO: 19), amino acids 128-133 (shown in SEQ ID NO: 20), and amino acids 128-132 (shown in SEQ ID NO: 21).
  • the peptide of claim 1, comprising structural unit 1 and structural unit 2, wherein structural unit 1 comprises amino acids at positions 29-85 of PD-1 protein (as shown in SEQ ID NO: 11) or Amino acids at positions 58-85 (as shown in SEQ ID NO: 15), and structural unit 2 comprises amino acids at positions 128-132 of PD-1 protein (as shown in SEQ ID NO: 21) or 130-132.
  • Amino acids (as shown in SEQ ID NO: 3) preferably structural unit 1 comprises amino acids at positions 58 to 85 of PD-1 protein (as shown in SEQ ID NO: 15), and structural unit 2 comprises 130 of PD-1 protein - amino acid at position 132 (as shown in SEQ ID NO: 3).
  • structural unit 1 comprises the sequence shown in any one of SEQ ID NO: 2 or SEQ ID NO: 10-17
  • structural unit 2 comprises SEQ ID NO: 3 or The sequence shown in any one of SEQ ID NOs: 18-21, preferably structural unit 1 comprises the sequence shown in SEQ ID NO: 2, and structural unit 2 comprises the sequence shown in SEQ ID NO: 3.
  • the antigen-binding fragment of the anti-PD-1 antibody is a Fab fragment, Fab', (Fab') 2 , Fab'-SH, Fab/c, Fv, Single chain antibodies (eg, scFv).
  • glycosylated side chain comprises mannose, N-acetylglucosamine; fucose and ⁇ -D-mannose.
  • D29, T59, E61, S62, K78, E84, D85, L128, P130, A132 or their combination of the PD-1 protein shown in SEQ ID NO: 1 is used for screening for antibodies or antigen-binding fragments thereof that bind to PD-1 use in.
  • antibody refers to an immunoglobulin molecule generally composed of two pairs of polypeptide chains, each pair having one "light” (L) chain and one "heavy” (H) chain .
  • Antibody light chains can be classified as kappa and lambda light chains.
  • Heavy chains can be classified as mu, delta, gamma, alpha, or epsilon, and define the antibody's isotype as IgM, IgD, IgG, IgA, and IgE, respectively.
  • the variable and constant regions are linked by a "J" region of about 12 or more amino acids, and the heavy chain also contains a "D" region of about 3 or more amino acids.
  • Each heavy chain consists of a heavy chain variable region (VH) and a heavy chain constant region (CH).
  • the heavy chain constant region consists of 3 domains (CH1, CH2 and CH3).
  • Each light chain consists of a light chain variable region (VL) and a light chain constant region (CL).
  • the light chain constant region consists of one domain, CL.
  • the constant regions of the antibodies mediate the binding of the immunoglobulin to host tissues or factors, including various cells of the immune system (eg, effector cells) and the first component (Clq) of the classical complement system.
  • the VH and VL regions can also be subdivided into regions of high variability called complementarity determining regions (CDRs) interspersed with more conserved regions called framework regions (FRs).
  • CDRs complementarity determining regions
  • Each VH and VL consists of 3 CDRs and 4 FRs arranged in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4 from amino terminus to carboxy terminus.
  • the assignment of amino acids to regions or domains follows the Kabat Sequences of Proteins of Immunological Interest (National Institutes of Health, Bethesda, Md. (1987 and 1991)), or Chothia & Lesk (1987) J. Mol. Biol. 196:901 -917; definition by Chothia et al. (1989) Nature 342:878-883.
  • antibody is not limited by any particular method of producing an antibody.
  • it includes, in particular, recombinant antibodies, monoclonal antibodies and polyclonal antibodies.
  • Antibodies can be of different isotypes, eg, IgG (eg, IgGl, IgG2, IgG3, or IgG4 subtype), IgAl, IgA2, IgD, IgE, or IgM antibodies.
  • the terms “monoclonal antibody” and “monoclonal antibody” refer to an antibody or a fragment of an antibody from a population of highly homologous antibody molecules, that is, excluding natural mutations that may arise spontaneously, A population of identical antibody molecules.
  • Monoclonal antibodies are highly specific for a single epitope on an antigen.
  • Polyclonal antibodies are relative to monoclonal antibodies, which generally comprise at least two or more different antibodies that generally recognize different epitopes on an antigen.
  • Monoclonal antibodies are typically obtained using the hybridoma technology first reported by Kohler et al. (Nature, 256:495, 1975), but can also be obtained using recombinant DNA technology (eg, see U.S. Patent 4,816,567).
  • humanized antibody refers to the replacement of all or part of the CDR regions of a human immunoglobulin (acceptor antibody) with the CDR regions of a non-human antibody (donor antibody)
  • the antibody or antibody fragment of which the donor antibody can be a non-human (eg, mouse, rat or rabbit) antibody with the desired specificity, affinity or reactivity.
  • some amino acid residues in the framework region (FR) of the acceptor antibody can also be replaced by amino acid residues of corresponding non-human antibodies, or by amino acid residues of other antibodies, to further improve or optimize the performance of the antibody.
  • antigen-binding fragments include, but are not limited to: Fab fragments, Fab', (Fab') 2 , Fab/c, Fv, Fab'-SH, single chain antibodies (eg, scFv).
  • Fab fragment consists of a light chain and the variable regions of CH1 and a heavy chain.
  • the heavy chain of a Fab molecule cannot form a disulfide bond with another heavy chain molecule.
  • Fab'fragment contains part of one light chain and one heavy chain (which contains the VH and CH1 domains and also the region between the CH1 and CH2 domains) part) so that an interchain disulfide bond can be formed between the two heavy chains of the two Fab' fragments to form an F(ab') 2 molecule.
  • F(ab') 2 fragment contains two light chains and two heavy chains containing part of the constant region between the CH1 and CH2 domains, so that the Interchain disulfide bonds are formed between the chains.
  • the F(ab') 2 fragment thus consists of two Fab' fragments held together by disulfide bonds between the two heavy chains.
  • Fv region includes variable regions from heavy and light chains, but lacks constant regions.
  • Fab'-SH is the designation herein for Fab' wherein one or more cysteine residues of the constant domains carry free thiol groups.
  • Figure 1 Overall structural model diagram of PD-1 protein complex with 14C12H1L1-Fab.
  • FAB-HC 14C12H1L1-Fab heavy chain portion;
  • FAB-LC 14C12H1L1-Fab light chain portion.
  • Figure 2 Schematic diagram of the interaction between PD-1 protein and 14C12H1L1-Fab heavy chain amino acids.
  • FAB-HC 14C12H1L1-Fab heavy chain portion.
  • Figure 3 Schematic diagram of the interaction between PD-1 protein and 14C12H1L1-Fab light chain amino acids.
  • FAB-LC 14C12H1L1-Fab light chain portion.
  • Figure 4 Schematic diagram of the interaction between the glycosylated side chain of PD-1 protein Asn58 and the heavy chain amino acids of 14C12H1L1-Fab.
  • MAN mannose, mannose
  • NAG N Acetyl Glucosamine, acetylglucosamine
  • FUC Fucose, fucose
  • BMA ⁇ -D-mannose, ⁇ -D-mannose.
  • FAB-HC 14C12H1L1-Fab heavy chain portion
  • FAB-LC 14C12H1L1-Fab light chain portion.
  • Figure 5 Binding surface of PD-1 to 14C12H1L1-Fab, Pembrolizumab or nivolumab.
  • the residues in contact with 14C12H1L1-Fab are E61, S62 amino acid residues
  • the residues in contact with nivolumab are V64, N66, Y68, Q75, T76, D77, K78, P83 amino acid residues
  • the overlapping residue bound by 14C12H1L1-Fab and nivolumab is the amino acid residue at position E84.
  • the residues in contact with pembrolizumab are L128, A129 amino acid residues, and the overlapping residues bound by 14C12H1L1-FAB and pembrolizumab are T59, P130, A131, K132 amino acid residues.
  • the amino acid residue at position D85 was not shown due to the occlusion of the steric structure.
  • Figure 6 The binding activity of anti-PD-1 antibody to human PD-1 protein mutant hPD1(D29A)-mFc and hPD1(E61A)-mFc was detected by combined ELISA method.
  • Figure 7 The binding activity of anti-PD-1 antibody to human PD-1 protein mutant hPD1(K78A)-mFc and hPD1(E84A)-mFc was detected by combined ELISA method.
  • Figure 8 Binding ELISA method to detect the binding activity of anti-PD-1 antibody to human PD-1 protein mutant hPD1(L128A)-mFc.
  • Figure 9 Detection results of kinetic parameters of the binding of anti-PD-1 antibody to human PD-1 protein hPD1-mFc.
  • Fig. 10 The detection results of kinetic parameters of the binding of anti-PD-1 antibody to human PD-1 protein mutant hPD1(D29A)-mFc.
  • Figure 11 The results of the kinetic parameters of the binding of anti-PD-1 antibody to human PD-1 protein mutant hPD1(E61A)-mFc.
  • Figure 12 The results of the kinetic characteristic parameters of the binding of anti-PD-1 antibody to human PD-1 protein mutant hPD1(K78A)-mFc.
  • Figure 13 The results of the kinetic parameter detection of anti-PD-1 antibody binding to human PD-1 protein mutant hPD1(E84A)-mFc.
  • Fig. 14 The detection results of kinetic parameters of the binding of anti-PD-1 antibody to human PD-1 protein mutant hPD1(L128A)-mFc.
  • hPD1-mFc produced by Kangfang Bio, batch number: 20181025 (Genbank ID of hPD-1: NP_005009, Genbank ID of mFc: P01863).
  • hPD1(D29A)-mFc produced by Kangfang Biotechnology, batch number 20191113.
  • hPD1(E61A)-mFc produced by Kangfang Biotechnology, batch number 20191113.
  • hPD1(K78A)-mFc produced by Kangfang Biotechnology, batch number 20191113.
  • hPD1(E84A)-mFc produced by Kangfang Biotechnology, batch number 20191113.
  • hPD1(L128A)-mFc produced by Kangfang Biotechnology, batch number 20191113.
  • the sequence of human PD-1 was searched through the NCBI protein database (PD-1 Genbank ID: NP_005009), and the amino acid sequence of the extracellular region of human PD-1 (amino acids 1-170) was combined with his purification tag sequence (SEQ ID NO: 6 ) for fusion design, and the fusion protein was abbreviated as "PD1-his” (SEQ ID NO: 7), also expressed as "hPD1-his”.
  • the cDNA sequence encoding the fusion protein was derived from the amino acid codon optimization and gene synthesis commissioned by Nanjing GenScript Biotechnology. Referring to the standard techniques introduced in "Molecular Cloning Experiment Guide (Second Edition)", PCR, enzyme digestion, gel recovery, Standard molecular cloning techniques such as ligation transformation, colony PCR or enzyme digestion identification are used to subclon the target gene into a mammalian cell expression vector, and the target gene of the recombinant expression vector is further sequenced and analyzed. After the sequencing was verified to be correct, the endotoxin-free expression plasmid was prepared in large quantities and the plasmid was transiently transfected into HEK293 cells for protein expression. After 7 days of culture, the cell culture medium was collected and affinity purified using MabSelect SuRe column (GE Healthcare).
  • the inventors based on the reported PD-1-nivolumab Fab (Tan SH, et al. (2017). Nat Commun., 8, 14369) and PD-1-Pembrolizumab Fab (Horita S et al. (2016). Sci Rep. ., 6, 35297) complex structure, using the method of X-ray crystal diffraction, to The Fab portion of antibody 14C12H1L1 (14C12H1L1-Fab) interacted with the PD-1 antigen at the resolution of 14C12H1L1 and compared the differences among the three.
  • amino acid sequence of the heavy chain portion of the antibody 14C12H1L1-Fab is as follows, the underlined portion is CH1, the bold bold is the CDR region, and the underlined bold italic is his-tag:
  • amino acid sequence of the light chain in the antibody 14C12H1L1-Fab is as follows, the underlined part is CL, and the bolded bold is the CDR region:
  • 14C12H1L1-Fab binds to PD-1 in a manner distinct from pembrolizumab and nivolumab. Although all three block the binding between PD-1 and PD-L1, according to literature reports, pembrolizumab and nivolumab bind to PD-1 in a glycosylation-independent manner (Tan SH, et al. (2017). ).Nat Commun., 8, 14369.) and PD-1-Pembrolizumab Fab (Horita S et al. (2016). Sci Rep., 6, 35297), 14C12H1L1-Fab showed on the BC loop of PD-1 Numerous interactions with sugar side chains linked at the N58 position.
  • PD1 protein such as PD-1-His
  • 14C12H1L1-Fab-his was mixed with 14C12H1L1-Fab-his at a molar ratio of 1:2, and incubated on ice for 2 hours.
  • the mixture was then purified by molecular sieves (Superdex 200 10/300 column, GE Healthcare) to obtain a complex of PD-1 protein and 14C12H1L1-Fab-his using buffer conditions of 20 mM HEPEs, pH 7.5, 100 mM NaCl, 5 mM DTT.
  • the complex peak was collected and concentrated by centrifugation (Millipore, MWCO 10 kDa), and the final complex concentration was about 10 mg/ml.
  • the concentrated complex was used for the primary screening of crystals and kept in a crystal room at 20°. Two weeks later, the crystal plate was observed under a microscope, and the crystallographic conditions were selected to repeat and optimize the crystallographic conditions.
  • the crystals were grown in PEG II suit F2 (0.1M MES, pH 6.5, 20% PEG4000, 0.6M sodium chloride) with 30% EG antifreeze. SDS-PAGE showed that the crystal contents were PD1-His+14C12H1L1-Fab-His complex. After acquiring available crystals, the resolution data was collected by using the Shanghai Synchrotron Radiation Light Source for diffraction to diffraction pattern.
  • the data analysis process is as follows: DIALS is used to index and integrate the data. Aimless was used to analyze and merge the processed data, and 5% of the data were randomly selected for Rfree estimation.
  • the Molrep molecular replacement procedure was used to find the phase solution in two steps. After sequence alignment, the sequence homology between 14C12H1L1-Fab and 6foe in the PDB database is as high as 85%, so use 6foe to find the solution of 14C12H1L1-Fab-his, then fix the position of 14C12H1L1-Fab-his, and use PD-1 monomer The structure of (PDB: 3rre) to find the solution of PD-1.
  • the analytical result is that an asymmetric unit contains a PD1-his monomer and a 14C12H1L1-Fab-his fragment.
  • the model is then revised in the reciprocal space using REFMAC5.
  • the protein model was corrected in real space using COOT.
  • the model is in good agreement with the electron density map, the crystallographic R-factor and Rfree are 0.21 and 0.27, respectively (Fig. 5), and the stereochemical parameters of the structural model are within a reasonable range.
  • 5 amino acid site mutations of human PD-1 protein were selected as 29 aspartic acid, 61 glutamic acid, 78 lysine, 84 glutamic acid and 128 leucine. is alanine [Lee, J.Y., et al., Structural basis of checkpoint blockade by monoclonal antibodies in cancer immunotherapy.
  • Dilute PD-1 antigen to 1 ⁇ g/mL with coating buffer add 50 ⁇ L per well to the ELISA plate, and incubate at 4°C overnight. After washing the plate with PBST, 300 ⁇ L of 1% BSA (PBS) was added to each well, and the plate was blocked at 37° C. for 2 h.
  • PBS 1% BSA
  • the anti-PD-1 antibody 14C12H1L1(hG1TM) was diluted with PBST to 0.3333 ⁇ g/mL as the starting concentration, and diluted 1:3 down to 0.1111 ⁇ g/mL, 0.0370 ⁇ g/mL on the ELISA plate , 0.0123 ⁇ g/mL, 0.0041 ⁇ g/mL, 0.0014 ⁇ g/mL, 0.0005 ⁇ g/mL, a total of 7 gradient concentrations, a blank control was set up, and 2 duplicate wells were made, each well 100 ⁇ L, mixed and incubated at 37°C 30min.
  • the detection results are shown in Table 1 and Figures 6-8.
  • the five human PD-1 protein mutants D29A, E61A, K78A, E84A, L128A bind to the anti-PD-1 antibody with EC50 of 0.021nM, 2.47 ⁇ 10 12 nM, 0.023nM, 0.022nM, 4.207nM.
  • the binding ability of E61A and L128A mutants to anti-PD-1 antibody was significantly reduced.
  • the anti-PD-1 antibody was diluted to 5 ⁇ g/mL with PBS (containing 0.02% Tween-20, 0.1% BSA, pH 7.4) and then immobilized on the surface of AHC sensor (Fortebio) for 120 s, and the sensor was equilibrated in the buffer
  • the anti-PD-1 antibody immobilized on the sensor binds to each PD1-mFc mutant at a concentration of 1.24-100nM (three-fold dilution) for 120s, and the protein dissociates in the buffer for 300s.
  • the detection temperature was 37° C.
  • the detection frequency was 0.3 Hz
  • the vibration rate of the sample plate was 1000 rpm. Data were analyzed with a 1:1 model fit to yield affinity constants.
  • the binding results of anti-PD-1 antibody and each PD-1 mutant are shown in Figure 9-14 and Table 2.
  • Five human PD-1 protein mutants D29A, E61A, K78A, E84A, L128A bind to anti-PD-1 antibody
  • the affinity constants were 4.25E-10M, 3.30E-08M, 1.31E-10M, 6.65E-10M, 7.68E-09M, respectively. Consistent with the binding ELISA results, the binding ability of the two mutants E61A and L128A to anti-PD-1 antibodies was significantly reduced.

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Abstract

L'invention concerne un peptide se liant à un anticorps anti-PD-1 ou à un fragment de liaison à l'antigène de celui-ci, comprenant des unités structurales 1 et 2, l'unité structurale 1 comprenant un acide aminé aux positions 58-85 d'une protéine PD-1, et l'unité structurale 2 comprenant un acide aminé aux positions 130-132 de la protéine PD-1.
PCT/CN2021/122062 2020-09-30 2021-09-30 Peptide se liant à un anticorps anti-pd-1 et son application Ceased WO2022068919A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP4538285A4 (fr) * 2022-06-06 2025-10-08 Chineo Medical Tech Co Ltd Variant de pd-1 et son utilisation

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107840887A (zh) * 2016-09-21 2018-03-27 基石药业（苏州）有限公司 一种新的pd‑1单克隆抗体
US20180118829A1 (en) * 2016-11-02 2018-05-03 Jounce Therapeutics, Inc. Antibodies to pd-1 and uses thereof
US20190077866A1 (en) * 2015-12-02 2019-03-14 Stcube, Inc. Antibodies specific to glycosylated pd-1 and methods of use thereof
US20190218297A1 (en) * 2016-07-20 2019-07-18 Stcube, Inc. Methods of cancer treatment and therapy using a combination of anitbodies that bind glycosylated pd-l1
US20190270815A1 (en) * 2015-08-11 2019-09-05 Wuxi Biologics (Cayman) Inc. Novel anti-pd-1 antibodies
US20190322749A1 (en) * 2017-01-06 2019-10-24 Crescendo Biologics Limited Single Domain Antibodies to Programmed Cell Death (PD-1)
US20200002420A1 (en) * 2016-09-21 2020-01-02 Cstone Pharmaceuticals The novel monoclonal antibodies to programmed death 1 (pd-1)

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20190270815A1 (en) * 2015-08-11 2019-09-05 Wuxi Biologics (Cayman) Inc. Novel anti-pd-1 antibodies
US20190077866A1 (en) * 2015-12-02 2019-03-14 Stcube, Inc. Antibodies specific to glycosylated pd-1 and methods of use thereof
US20190218297A1 (en) * 2016-07-20 2019-07-18 Stcube, Inc. Methods of cancer treatment and therapy using a combination of anitbodies that bind glycosylated pd-l1
CN107840887A (zh) * 2016-09-21 2018-03-27 基石药业（苏州）有限公司 一种新的pd‑1单克隆抗体
US20200002420A1 (en) * 2016-09-21 2020-01-02 Cstone Pharmaceuticals The novel monoclonal antibodies to programmed death 1 (pd-1)
US20180118829A1 (en) * 2016-11-02 2018-05-03 Jounce Therapeutics, Inc. Antibodies to pd-1 and uses thereof
US20190322749A1 (en) * 2017-01-06 2019-10-24 Crescendo Biologics Limited Single Domain Antibodies to Programmed Cell Death (PD-1)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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