WO2020010250A2 - Anti-tcr antibody molecules and uses thereof - Google Patents

Anti-tcr antibody molecules and uses thereof Download PDF

Info

Publication number
WO2020010250A2
WO2020010250A2 PCT/US2019/040592 US2019040592W WO2020010250A2 WO 2020010250 A2 WO2020010250 A2 WO 2020010250A2 US 2019040592 W US2019040592 W US 2019040592W WO 2020010250 A2 WO2020010250 A2 WO 2020010250A2
Authority
WO
WIPO (PCT)
Prior art keywords
tcrpv
tcrp
antibody molecule
molecule
seq
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2019/040592
Other languages
English (en)
French (fr)
Other versions
WO2020010250A3 (en
Inventor
Seng-Lai TAN
Brian Edward Vash
Jonathan Hsu
Dilini Charmain GUNASEKERA
Sangeetha Sagar PALAKURTHI
Andreas Loew
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Marengo Therapeutics Inc
Original Assignee
Elstar Therapeutics Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Elstar Therapeutics Inc filed Critical Elstar Therapeutics Inc
Priority to EP19745444.0A priority Critical patent/EP3818083A2/en
Priority to JP2021521940A priority patent/JP7554742B2/ja
Priority to US17/256,917 priority patent/US11845797B2/en
Priority to CN201980057685.4A priority patent/CN112955465A/zh
Priority to CA3105448A priority patent/CA3105448A1/en
Priority to AU2019297451A priority patent/AU2019297451A1/en
Publication of WO2020010250A2 publication Critical patent/WO2020010250A2/en
Publication of WO2020010250A3 publication Critical patent/WO2020010250A3/en
Anticipated expiration legal-status Critical
Priority to US17/529,017 priority patent/US20220064297A1/en
Priority to US17/820,634 priority patent/US20230025484A1/en
Priority to US17/820,806 priority patent/US20230034161A1/en
Priority to US17/820,818 priority patent/US20230031734A1/en
Priority to US17/820,811 priority patent/US20230142522A1/en
Priority to US17/820,800 priority patent/US20230127740A1/en
Priority to US17/820,805 priority patent/US12286477B2/en
Priority to US17/820,794 priority patent/US11965025B2/en
Priority to US18/472,920 priority patent/US12351632B2/en
Priority to US18/431,634 priority patent/US20240301060A1/en
Priority to JP2024154806A priority patent/JP2024170589A/ja
Priority to US19/080,243 priority patent/US20250215085A1/en
Priority to US19/214,564 priority patent/US20250340640A1/en
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • C07K16/2803—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2809—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against the T-cell receptor (TcR)-CD3 complex
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/14—Blood; Artificial blood
    • A61K35/17—Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/10—Cellular immunotherapy characterised by the cell type used
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/10—Cellular immunotherapy characterised by the cell type used
    • A61K40/11—T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
    • A61K40/41—Vertebrate antigens
    • A61K40/42—Cancer antigens
    • A61K40/4202—Receptors, cell surface antigens or cell surface determinants
    • A61K40/421—Immunoglobulin superfamily
    • A61K40/4211—CD19 or B4
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
    • A61K40/41—Vertebrate antigens
    • A61K40/42—Cancer antigens
    • A61K40/4202—Receptors, cell surface antigens or cell surface determinants
    • A61K40/4214—Receptors for cytokines
    • A61K40/4215—Receptors for tumor necrosis factors [TNF], e.g. lymphotoxin receptor [LTR], CD30
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • C07K16/2803—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • 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
    • C07K16/2803—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/283—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against Fc-receptors, e.g. CD16, CD32, CD64
    • 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
    • C07K16/2878—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0634—Cells from the blood or the immune system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
    • A61K2239/31—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterized by the route of administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
    • A61K2239/38—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterised by the dose, timing or administration schedule
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/55—Fab or Fab'
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622—Single chain antibody (scFv)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Definitions

  • the VH comprises a sequence having a consensus sequence of SEQ ID NO: 231 or 3290.
  • the anti-TCRpV antibody molecule comprises an antigen binding domain comprising a light chain variable region (VL) comprising one, two or all (e.g., three) of a LC CDR1, a LC CDR2 and a LC CDR3 of SEQ ID NO: 2, SEQ ID NO: 10 or SEQ ID NO: 11, or an amino acid sequence listed in Table 1.
  • VL light chain variable region
  • the anti-TCRpV antibody molecule comprises a framework region (FR) having at least 95% identity with all of: a FR1, a FR2, a FR3, and a FR4 of a humanized B- H HC of Table 2.
  • FR framework region
  • TEMRA cells have low or no expression of CCR7, e.g., CCR7- or CCR7 low. In some embodiments, expression of CCR7 on TEMRA cells cannot be detected by a method disclosed herein, e.g., flow cytometry.
  • TEMRA cells express CD95, e.g., CD95+.
  • expression of CD95 on TEMRA cells can be detected by a method disclosed herein, e.g., flow cytometry.
  • the proliferative capability of T cells can be detected by a method disclosed herein, e.g., a method described in Example 4.
  • cytokine expression of T cells can be detected by a method disclosed herein, e.g., a method described in Examples 10 and 21.
  • the expansion is at least about 1.1-10 fold expansion ( e.g ., at least about 1.1, 1.2, 1.3, 1.4, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10 fold expansion).
  • the expansion is compared to expansion of a similar population of cells with an antibody that binds to a CD3 molecule, e.g., CD3 epsilon (CD3e) molecule; or a TCR alpha (TCRa) molecule.
  • a CD3 molecule e.g., CD3 epsilon (CD3e) molecule; or a TCR alpha (TCRa) molecule.
  • a delay e.g., at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more hours delay, in increased level, e.g., expression level, and/or activity of IL-2;
  • (x) increased level, e.g., expression level, and/or activity of IL-15;
  • CD3 molecule e.g., CD3 epsilon (CD3e) molecule
  • TCRa TCR alpha
  • an anti-TCRpV antibody molecule disclosed herein does not comprise a viral peptide-MHC complex, e.g., as disclosed in Oncoimmunology. 2016; 5(1): el052930, herein incorporated by reference in its entirety.
  • a multispecific antibody molecule disclosed herein does not comprise a viral peptide-MHC complex, e.g., as disclosed in Oncoimmunology. 2016; 5(1): el052930, herein incorporated by reference in its entirety.
  • TCRP V10 subfamily comprising, e.g., one or more of TCRP Vl0-l*0l, TCRP V10- 1*02, TCRp Vl0-3*0l or TCRp Vl0-2*0l;
  • TCRP V19 subfamily comprising e.g., one or more of TCRP VI 9*01, or TCRP Vl9*02;
  • TCRp V10 e.g., one or more of TCRp Vl0-l*0l, TCRp Vl0-l*02, TCRp Vl0-3*0l or TCRp Vl0-2*0l;
  • a multispecific molecule e.g ., a bispecific molecule
  • a first moiety e.g., a first immune cell engager
  • TCRpV T cell receptor beta variable region
  • binding of the first moiety to the TCRpV region results in a cytokine profile, e.g., cytokine secretion profile, that differs from that of a T cell engager that binds to a receptor or molecule other than a TCRpV region (“a non-TCRpV-binding T cell engager”).
  • a cytokine profile e.g., cytokine secretion profile
  • the multispecific molecule further comprises: a tumor-targeting moiety, a cytokine molecule, an immune cell engager, e.g., a second immune cell engager, and/or a stromal modifying moiety.
  • a second moiety comprising one or more of: a tumor-targeting moiety; a second immune cell engager; a cytokine molecule or a stromal modifying moiety.
  • a multispecific molecule comprising an anti-TCRpV antibody molecule for use in the manufacture of a medicament for treating a disease, e.g., cancer, in a subject.
  • a method of treating a disease e.g., cancer, in a subject comprising administering to the subject an effective amount, e.g., a therapeutically effective amount, of an anti-TCRpV antibody molecule or a multispecific molecule comprising an anti- TCRpV antibody molecule disclosed herein, thereby treating the disease.
  • an effective amount e.g., a therapeutically effective amount, of an anti-TCRpV antibody molecule or a multispecific molecule comprising an anti- TCRpV antibody molecule disclosed herein, thereby treating the disease.
  • composition comprising an anti-TCRpV antibody molecule or a multispecific molecule comprising an anti-TCRpV antibody molecule disclosed herein, for use in the treatment of a disease, e.g., cancer, in a subject.
  • a disease e.g., cancer
  • the disease is a cancer, e.g. , a solid tumor or a hematological cancer, or a metastatic lesion.
  • (i) and (ii) are administered simultaneously or concurrently.
  • the disclosure provides, a method of targeting a T cell, e.g., in a subject having a disease, e.g., cancer, with an anti-TCRpV antibody disclosed herein or a multispecific molecule comprising an anti-TCRpV antibody disclosed herein.
  • the disclosure provides a method of treating, e.g., preventing or reducing, cytokine release syndrome (CRS) and/or neurotoxicity (NT) in a subject, e.g., CRS and/or NT associated with a treatment, e.g., a previously administered treatment, comprising administering to the subject an effective amount of an anti-TCRpV antibody disclosed herein or a multispecific molecule comprising an anti-TCRpV antibody disclosed herein, wherein, the subject has a disease, e.g., a cancer, thereby treating, e.g., preventing or reducing, CRS and/or NT in the subject.
  • CRS cytokine release syndrome
  • NT neurotoxicity
  • the biological sample comprising the population of immune effector cells is contacted with an anti- TCRpV antibody molecule that does not bind to the one or more TCRpV molecules (e.g., a different TCRpV molecule) identified as being higher, e.g., increased, in the biological sample.
  • an anti- TCRpV antibody molecule that does not bind to the one or more TCRpV molecules (e.g., a different TCRpV molecule) identified as being higher, e.g., increased, in the biological sample.
  • TCRP V19 subfamily comprising e.g., one or more of TCRP Vl9*0l, or TCRP Vl9*02;
  • the cancer is a solid tumor including but not limited to: melanoma, pancreatic (e.g., pancreatic adenocarcinoma) cancer, breast cancer, colorectal cancer (CRC), lung cancer (e.g., small or non- small cell lung cancer), skin cancer, ovarian cancer, or liver cancer.
  • pancreatic e.g., pancreatic adenocarcinoma
  • breast cancer colorectal cancer (CRC)
  • lung cancer e.g., small or non- small cell lung cancer
  • skin cancer e.g., ovarian cancer, or liver cancer.
  • myelodysplastic syndrome multiple myeloma, and acute lymphocytic leukemia.
  • a higher, e.g., increased, level or activity of one or more TCRpV molecules in a subject, e.g., in a sample from a subject, is indicative of a bias, e.g., a preferential expansion, e.g., clonal expansion, of T cells expressing said one or more TCRpV molecules in the subject.
  • a subject having B-CLL has a higher, e.g., increased, level or activity of a TCRP V3 subfamily comprising TCRP V3-l*0l.
  • the subject is administered an anti-TCRpV molecule (e.g., an agonistic anti- TCRpV molecule as described herein) that binds to one or more members of the TCRP V3 subfamily.
  • administration of the an anti-TCRpV molecule results in expansion of immune cells expressing one or more members of the TCRP V3 subfamily.
  • a subject having B-CLL has a higher, e.g., increased, level or activity of a TCRP V2 subfamily comprising TCRP V2*0l.
  • the subject is administered an anti-TCRpV molecule (e.g., an agonistic anti- TCRpV molecule as described herein) that binds to one or more members of the TCRP V2 subfamily.
  • administration of the an anti-TCRpV molecule results in expansion of immune cells expressing one or more members of the TCRP V2 subfamily.
  • a subject having B-CLL has a higher, e.g., increased, level or activity of a TCRP V19 subfamily comprising TCRP Vl9*0l, or TCRP Vl9*02.
  • the subject is administered an anti-TCRpV molecule (e.g., an agonistic anti- TCRBV molecule as described herein) that binds to one or more members of the TCRP V19 subfamily.
  • administration of the an anti-TCRpV molecule results in expansion of immune cells expressing one or more members of the TCRP V19 subfamily.
  • the subject has DLBCL.
  • a subject having melanoma has a higher, e.g., increased, level or activity of one or more TCRpV molecules, e.g., one or more TCRpV molecules comprising: (i) TCRP V13 subfamily comprising TCRP Vl3*0l; (ii) TCRP V3 subfamily comprising TCRP V3-l*0l; or (iii) TCRP V23 subfamily.
  • a subject having DLBCL has a higher, e.g., increased, level or activity of a TCRP V3 subfamily comprising TCRP V3-l*0l.
  • the subject is administered an anti-TCRpV molecule (e.g., an agonistic anti- TCRpV molecule as described herein) that binds to one or more members of the TCRP V3 subfamily.
  • administration of the an anti-TCRpV molecule results in expansion of immune cells expressing one or more members of the TCRP V3 subfamily.
  • TCRP V16 subfamily comprising TCRP Vl6*0l; or (iv) TCRP V21 subfamily.
  • a subject having CRC has a higher, e.g., increased, level or activity of a TCRP V19 subfamily comprising TCRP Vl9*0l, or TCRP Vl9*02.
  • the subject is administered an anti-TCRpV molecule (e.g., an agonistic anti- TCRpV molecule as described herein) that binds to one or more members of the TCRP V19 subfamily.
  • administration of the an anti-TCRpV molecule results in expansion of immune cells expressing one or more members of the TCRP V19 subfamily.
  • a subject having CRC has a higher, e.g., increased, level or activity of a TCRP V12 subfamily comprising TCRP Vl2-4*0l, TCRP Vl2-3*0l, or TCRP Vl2-5*0l.
  • the subject is administered an anti-TCRpV molecule (e.g., an agonistic anti- TCRpV molecule as described herein) that binds to one or more members of the TCRP V12 subfamily.
  • administration of the an anti-TCRpV molecule results in expansion of immune cells expressing one or more members of the TCRP V12 subfamily.
  • a subject having CRC has a higher, e.g., increased, level or activity of a TCRP V16 subfamily comprising TCRP Vl6*0l.
  • the subject is administered an anti-TCRpV molecule (e.g., an agonistic anti- TCRpV molecule as described herein) that binds to one or more members of the TCRP V16 subfamily.
  • administration of the an anti-TCRpV molecule results in expansion of immune cells expressing one or more members of the TCRP V16 subfamily.
  • an anti-TCRpV antibody molecule which:
  • (i) binds specifically to an epitope on TCRpV, e.g., the same or similar epitope as the epitope recognized by an anti-TCRpV antibody molecule as described herein, e.g., a second anti- TCRpV antibody molecule;
  • (ii) shows the same or similar binding affinity or specificity, or both, as an anti-TCRpV antibody molecule as described herein, e.g., a second anti-TCRpV antibody molecule;
  • the second anti-TCRpV antibody molecule comprises an antigen binding domain chosen from Table 1 or Table 2, or a sequence substantially identical thereto.
  • the second anti-TCRpV antibody molecule comprises an antigen binding domain, comprising:
  • HC CDR1 heavy chain complementarity determining region 1
  • HC CDR2 heavy chain complementarity determining region 2
  • HC CDR3 heavy chain complementarity determining region 3
  • LC CDR3 light chain complementarity determining region 1
  • LC CDR2 light chain complementarity determining region 2
  • LC CDR3 light chain complementarity determining region 3
  • HC CDR1 heavy chain complementarity determining region 1
  • HC CDR2 heavy chain complementarity determining region 2
  • HC CDR3 heavy chain complementarity determining region 3
  • LC CDR1 light chain complementarity determining region 1
  • LC CDR2 light chain complementarity determining region 2
  • LC CDR3 light chain complementarity determining region 3
  • the anti- TCRpV antibody molecule comprises an antigen binding domain comprising a light chain variable region (VL) comprising one, two or all ( e.g ., three) of a LC CDR1, a LC CDR2 and a LC CDR3 of SEQ ID NO: 2, SEQ ID NO: 10 or SEQ ID NO: 11.
  • VL light chain variable region
  • the anti- TCRpV antibody molecule comprises an antigen binding domain comprising a heavy chain variable region (VH) comprising one, two or all (e.g., three) of a HC CDR1, a HC CDR2 and a HC CDR3 of SEQ ID NO: 1 or SEQ ID NO: 9.
  • VH heavy chain variable region
  • the anti- TCRpV antibody molecule comprises an antigen binding domain comprising:
  • a VL comprising: a LC CDR1 amino acid sequence of SEQ ID NO: 6 (or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, e.g., substitutions, additions or deletions thereof), a LC CDR2 amino acid sequence of SEQ ID NO:7 (or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, e.g., substitutions, additions or deletions thereof), and/or a LC CDR3 amino acid sequence of SEQ ID NO:8 (or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, e.g., substitutions, additions or deletions thereof); and/or
  • a VH comprising: a HC CDR1 amino acid sequence of SEQ ID NO: 3 (or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, e.g., substitutions, additions or deletions thereof), a HC CDR2 amino acid sequence of SEQ ID NO:4 (or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, e.g., substitutions, additions or deletions thereof), and/or a HC CDR3 amino acid sequence of SEQ ID NO:5 (or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, e.g., substitutions, additions or deletions thereof).
  • the anti- TCRpV antibody molecule comprises an antigen binding domain comprising:
  • VH variable heavy chain
  • the anti- TCRpV antibody molecule comprises an antigen binding domain comprising the VH amino acid sequence of SEQ ID NO: 9 and the VL amino acid sequence of SEQ ID NO: 10.
  • the anti- TCRpV antibody molecule comprises a light chain comprising a framework region, e.g., framework region 2 (FR2), comprising one or both of: (i) a Histidine at position 36, e.g., a substitution at position 36 according to Kabat numbering, e.g., a Tyrosine to Histidine substitution; or (ii) an Alanine at position 46, e.g., a substitution at position 46 according to Kabat numbering, e.g., a Arginine to Alanine substitution.
  • the substitution is relative to a human germline light chain framework region sequence.
  • the anti- TCRpV antibody molecule binds to TCRp V6, e.g., TCRp V6-4*0l, TCRp V6-4*02, TCRp V6- 9*01, TCRp V6-8*0l, TCRp V6-5*0l, TCRp V6-6*02, TCRp V6-6*0l, TCRp V6-2*0l, TCRp V6-3*0l or TCRP V6-l*0l. In some embodiments the anti-TCRpV antibody molecule binds to TCRp V6-5*0l.
  • TCRp V6 e.g., TCRp V6-4*0l, TCRp V6-4*02, TCRp V6-9*0l, TCRp V6-8*0l, TCRp V6-5*0l, TCRp V6-6*02, TCRp V6-6*0l, TCRp V6-2*0l, TCRp V6- 3*01 or TCRP V6-l*0l, is recognized, e.g., bound, by SEQ ID NO: 1 and/or SEQ ID NO: 2.
  • TCRp V6 e.g., TCRp V6-4*0l, TCRp V6-4*02, TCRp V6-9*0l, TCRp V6-8*0l, TCRp V6-5*0l, TCRp V6-6*02, TCRp V6-6*0l, TCRp V6-2*0l, TCRp V6-3*0l or TCRP V6-l*0l, is recognized, e.g., bound, by SEQ ID NO: 9 and/or SEQ ID NO: 10.
  • the anti- TCRpV antibody molecule comprises an antigen binding domain comprising:
  • HC CDR1 heavy chain complementarity determining region
  • HC CDR2 heavy chain complementarity determining region
  • HC CDR3 of SEQ ID NO: 15, SEQ ID NO: 23, SEQ ID NO: 24 or SEQ IC NO: 25, or a sequence disclosed in Table 2;
  • LC CDR1 light chain complementarity determining region 1
  • LC CDR2 light chain complementarity determining region 1
  • LC CDR3 a light chain complementarity determining region 1 (LC CDR1), a LC CDR2, and/or a LC CDR3 of SEQ ID NO: 16, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29 or SEQ ID NO:30, or a sequence disclosed in Table 2.
  • the anti- TCRpV antibody molecule comprises an antigen binding domain comprising a light chain variable region (VL) comprising one, two or all of a LC CDR1, a LC CDR2 and a LC CDR3 of SEQ ID NO: 16, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29 or SEQ ID NO:30.
  • VL light chain variable region
  • VL variable light chain
  • Asparagine substitution or a Tyrosine to Asparagine substitution; or (iii) a Leucine at position 4, e.g., a substitution at position 4 according to Rabat numbering, e.g., a Methionine to Leucine substitution.
  • the substitution is relative to a human germline light chain framework region sequence.
  • the anti- TCRpV antibody molecule comprises a light chain comprising a framework region, e.g., framework region 3 (FR3), comprising one, two or all (e.g., three) of: (i) a Glycine as position 66, e.g., a substitution at position 66 according to Rabat numbering, e.g., a Lysine to Glycine substitution, or a Serine to Glycine substitution; or (ii) an Asparagine at position 69, e.g., a substitution at position 69 according to Rabat numbering, e.g., a Threonine to Asparagine substitution; or (iii) a Tyrosine at position 71, e.g., a substitution at position 71 according to Rabat numbering, e.g., a Phenylalanine to Tyrosine substitution, or an Alanine to Tyrosine substitution.
  • FR3 framework region 3
  • the anti- TCRpV antibody molecule binds to TCRp V12, e.g., TCRp Vl2-4*0l, TCRp Vl2-3*0l, or TCRP Vl2-5*0l. In some embodiments the anti-TCRpV antibody molecule binds to TCRP V12- 4*01 or TCRp Vl2-3*0l.
  • TCRp V12 e.g., TCRp Vl2-4*0l, TCRp Vl2-3*0l, or TCRp Vl2-5*0l
  • TCRp V12 is recognized, e.g., bound, by any one of SEQ ID NOs 23-25, and/or any one of SEQ ID NO: 26- 30, or an amino acid sequence having at least about 75%, 80%, 85%, 90%, 95%, or 99% sequence identity thereto.
  • TCRP Vl2-4*0l is recognized, e.g., bound, by any one of SEQ ID NOs 23-25, and/or any one of SEQ ID NO: 26-30, or an amino acid sequence having at least about 75%, 80%, 85%, 90%, 95%, or 99% sequence identity thereto.
  • TCRP Vl2-3*0l is recognized, e.g., bound, by any one of SEQ ID NOs 23-25, and/or any one of SEQ ID NO: 26-30, or an amino acid sequence having at least about 75%,
  • the anti- TCRpV antibody molecule comprises the anti-TCRpV antibody molecule comprises an antigen binding domain comprising a single chain Fv (scFv) or a Fab. In some embodiments of any of the compositions or methods disclosed herein, the anti- TCRpV antibody molecule comprises binds to a conformational or a linear epitope on the T cell.
  • the anti- TCRpV antibody molecule is a full antibody (e.g., an antibody that includes at least one, and preferably two, complete heavy chains, and at least one, and preferably two, complete light chains), or an antigen-binding fragment (e.g., a Fab, F(ab')2, Fv, a single chain Fv fragment, a single domain antibody, a diabody (dAb), a bivalent antibody, or bispecific antibody or fragment thereof, a single domain variant thereof, a camelid antibody, or a rat-derived VH.
  • an antigen-binding fragment e.g., a Fab, F(ab')2, Fv, a single chain Fv fragment, a single domain antibody, a diabody (dAb), a bivalent antibody, or bispecific antibody or fragment thereof, a single domain variant thereof, a camelid antibody, or a rat-derived VH.
  • the anti- TCRpV antibody molecule comprises a heavy chain constant region of an IgJ or a fragment thereof, optionally wherein the IgJ heavy chain constant region comprises the sequence of SEQ ID NO: 76 or a sequence with at least 85%, 90%, 95%, or 99% sequence identity thereto.
  • the anti- TCRpV antibody molecule comprises a heavy chain constant region of an IgGA2, or a fragment thereof, optionally wherein the IgGA2 heavy chain constant region comprises a sequence listed in Table 3, e.g., SEQ ID NO: 75, or a sequence with at least 85%, 90%, 95%, or 99% sequence identity thereto.
  • (xii) expansion e.g., at least about 1.1-10 fold expansion (e.g., at least about 1.1, 1.2, 1.3, 1.4, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10 fold expansion), of a population of memory T cells, e.g., wherein (ix)-(xii) are relative to the non-TCRpV-binding T cell engager.
  • the anti-TCRbV antibody molecule in a multispecific molecule disclosed herein is a first immune cell engager moiety.
  • the anti-TCRbV antibody molecule does not bind to ⁇ b V12, or binds to TCRb V12 with an affinity and/or binding specificity that is less than (e.g., less than about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or about 2-, 5-, or 10- fold) the affinity and/or binding specificity of the 16G8 murine antibody or a humanized version thereof as described in US Patent 5,861,155.
  • the anti- TCRpV antibody molecule binds to a TCRpV region other than TCRP V5-5*0l or TCRP V5- 1*01 (e.g., TCRpV region as described herein, e.g., TCRP V6 subfamily (e.g., TCRP V6-5*0l) with an affinity and/or binding specificity that is greater than (e.g., greater than about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or about 2-, 5-, or 10- fold) the affinity and/or binding specificity of the TM23 murine antibody or a humanized version thereof as described in US Patent 5,861,155.
  • the anti-TCRpV antibody molecule does not comprise the CDRs of the TM23 murine antibody.
  • the second immune cell engager comprises a T cell engager which binds to CD3, TCRa, TCRy, TCR , ICOS, CD28, CD27, HVEM, LIGHT, CD40, 4-1BB, 0X40, DR3, GITR, CD30, TIM1, SLAM, CD2, or CD226.
  • a multispecific molecule disclosed herein comprises a tumor targeting moiety.
  • the tumor-targeting moiety comprises an antibody molecule (e.g ., Fab or scFv), a receptor molecule (e.g., a receptor, a receptor fragment or functional variant thereof), or a ligand molecule (e.g., a ligand, a ligand fragment or functional variant thereof), or a combination thereof, that binds to a cancer antigen.
  • the tumor-targeting moiety binds to a cancer antigen present on a cancer, e.g., a hematological cancer, a solid tumor, a metastatic cancer, soft tissue tumor, metastatic lesion, or a combination thereof.
  • the tumor-targeting moiety binds to a cancer antigen, e.g.,
  • the tumor-targeting antibody molecule binds to a conformational or a linear epitope on the tumor antigen.
  • the BCMA antigen can be present on a tumor, e.g., a tumor of a class typified by having one or more of: limited tumor perfusion, compressed blood vessels, or fibrotic tumor interstitium.
  • the tumor targeting moiety comprising a BCMA targeting moiety comprises an anti-BCMA antibody or antigen-binding fragment thereof described in US8920776, US9243058, US9340621, US8846042, US7083785, US9545086, US7276241, US9034324, US7799902, US9387237, US8821883, US861745, US20130273055, US20160176973, US20150368351, US20150376287, US20170022284, US20160015749, US20140242077, US20170037128, US20170051068, US20160368988, US20160311915, US20160131654, US20120213768, US20110177093, US20160297885,
  • EP3137500 EP2699259, EP2982694, EP3029068, EP3023437, W02016090327,
  • the FcRH5 antigen can be present on a tumor, e.g., a tumor of a class typified by having one or more of: limited tumor perfusion, compressed blood vessels, or fibrotic tumor interstitium.
  • the tumor targeting moiety comprising a FcRH5 targeting moiety comprises an anti- FcRH5 antibody or antigen-binding fragment thereof described in US Patent 7,999,077 the entire contents of which are incorporated herein by reference.
  • the cancer is a hematological cancer including, but not limited to: a B-cell or T cell malignancy, e.g., Hodgkin’s lymphoma, Non-Hodgkin’s lymphoma (e.g., B cell lymphoma, diffuse large B cell lymphoma, follicular lymphoma, chronic lymphocytic leukemia, mantle cell lymphoma, marginal zone B-cell lymphoma, Burkitt lymphoma, lymphoplasmacytic lymphoma, hairy cell leukemia), acute myeloid leukemia (AML), chronic myeloid leukemia, myelodysplastic syndrome, multiple myeloma, and acute lymphocytic leukemia.
  • the hematological cancer is multiple myeloma.
  • a multispecific molecule disclosed herein further comprises a cytokine molecule, e.g., one or two cytokine molecules.
  • the cytokine molecule is chosen from interleukin-2 (IL-2), interleukin-7 (IL-7), interleukin- 12 (IL-12), interleukin- 15 (IL-15), interleukin- 18 (IL-18), interleukin -21 (IL-21), or interferon gamma, or a fragment, variant or combination thereof.
  • IL-2 interleukin-2
  • IL-7 interleukin-7
  • IL-12 interleukin- 12
  • IL-15 interleukin- 15
  • IL-18 interleukin- 18
  • interleukin -21 interferon gamma
  • the cytokine molecule further comprises a receptor dimerizing domain, e.g., an ILl5Ralpha dimerizing domain.
  • a tumor-targeting antibody molecule e.g., an antibody molecule that binds to a hematological antigen as described herein, e.g., chosen from one or more of BCMA, FcRH5, CD19, CD22, CD33, CD123, FcRH5, CDl79a, or CLEC12.
  • the dimerization of the immunoglobulin chain constant region is enhanced by providing an Fc interface of a first and a second Fc region with one or more of: a paired cavity-protuberance (“knob-in-a hole”), an electrostatic interaction, or a strand- exchange, such that a greater ratio of heteromultimenhomomultimer forms, e.g., relative to a non-engineered interface.
  • Fc region a paired cavity-protuberance
  • electrostatic interaction e.g., electrostatic interaction
  • strand- exchange e.g., strand- exchange
  • a multispecific molecule disclosed herein further comprises a linker, e.g., a linker described herein, optionally wherein the linker is selected from: a cleavable linker, a non-cleavable linker, a peptide linker, a flexible linker, a rigid linker, a helical linker, or a non-helical linker.
  • a linker e.g., a linker described herein, optionally wherein the linker is selected from: a cleavable linker, a non-cleavable linker, a peptide linker, a flexible linker, a rigid linker, a helical linker, or a non-helical linker.
  • the dimerization module comprises an immunoglobulin constant domain, e.g., a heavy chain constant domain (e.g., a homodimeric or heterodimeric heavy chain constant region, e.g., an Fc region), or a constant domain of an immunoglobulin variable region (e.g., a Fab region); and
  • an immunoglobulin constant domain e.g., a heavy chain constant domain (e.g., a homodimeric or heterodimeric heavy chain constant region, e.g., an Fc region), or a constant domain of an immunoglobulin variable region (e.g., a Fab region); and
  • At least one, two, or three of A, B, C, and D comprises an antigen binding domain that preferentially binds to a TCRpV region disclosed herein, and
  • any of the remaining A, B, C, and D is absent or comprises one of a tumor targeting moiety, a second immune cell engager, a cytokine molecule, or a stromal modifying moiety.
  • the dimerization module comprises one or more immunoglobulin chain constant regions (e.g ., Fc regions) comprising one or more of: a paired cavity-protuberance (“knob-in-a hole”), an electrostatic interaction, or a strand-exchange.
  • the one or more immunoglobulin chain constant regions e.g., Fc regions
  • the one or more immunoglobulin chain constant regions comprise an amino acid substitution at a position chosen from one or more of 347, 349, 350, 351, 366, 368, 370, 392,
  • the disease is a cancer chosen from: a hematological cancer, a solid tumor, a metastatic cancer, soft tissue tumor, metastatic lesion, or a combination thereof.
  • FIGs. 1A-1B shows the alignment of the Antibody A source mouse VH and VL framework 1, CDR 1, framework 2, CDR 2, framework 3, CDR3, and framework 4 regions with their respective humanized sequences. Rabat CDRs are shown in bold, Chothia CDRs are shown in italics, and combined CDRs are shown in boxes. The framework positions that were back mutated are double underlined.
  • FIG. 1A shows VH sequences for murine Antibody A (SEQ ID NO: 1) and humanized Antibody A-H (SEQ ID NO: 9).
  • FIG. IB shows VL sequences for murine Antibody A (SEQ ID NO: 2) and humanized Antibody A-H (SEQ ID NO: 10 and SEQ ID NO: 11).
  • FIG. 3 depicts the phylogenetic tree of TCRBV gene family and subfamilies with corresponding antibodies mapped. Subfamily identities are as follows: Subfamily A: TCRP V6; Subfamily B: TCRP V10; Subfamily C: TCRP V12; Subfamily D: TCRP V5; Subfamily E:
  • Subfamily T TCRP V24; Subfamily U: TCRP V20; Subfamily V: TCRP V25; and Subfamily W:TCRP V29 subfamily. Subfamily members are described in detail herein in the Section titled “TCR beta V (TCRpV)”.
  • FIGs. 6A-6B show IFNg production by human PBMCs activated with the indicated antibodies.
  • Human PBMCs were isolated from whole blood from the indicated number of donors, followed by solid-phase (plate-coated) stimulation with the indicated antibodies at lOONm. Supernatant was collected on Days 1, 2, 3, 5, or 6.
  • FIG. 6A is a graph comparing the production of IFNg in human PBMCs activated with the antibodies indicated activated with anti- TCR nb13.1 antibodies (A-H.l or A-H.2) or anti-CD3e antibodies (OKT3 or SP34-2) on Day 1, 2, 3, 5, or 6 post-activation.
  • FIG. 6B shows IFNg production in human PBMCs activated with the antibodies indicated activated with the indicated anti-TCR nb13.1 antibodies or anti-CD3e antibody (OKT3) on Day 1, 2, 3, 5, or 6 post-activation.
  • FIGs. 7A-7B show IL-2 production by human PBMCs activated with the indicated antibodies. A similar experimental setup as described for FIGs 6A-6B was used.
  • FIGs. 8A- 8B show IL-6 production by human PBMCs activated with the indicated antibodies. A similar experimental setup as described for FIGs 6A-6B was used.
  • FIGs. 9A- 9B show TNF-alpha production by human PBMCs activated with the indicated antibodies. A similar experimental setup as described for FIGs 6A-6B was used.
  • FIGs. 10A- 10B show IL-lbeta production by human PBMCs activated with the indicated antibodies. A similar experimental setup as described for FIGs 6A-6B was used.
  • FIG. 12 depicts increased CD8+ TSCM and Temra T cell subsets in human PBMCs activated by anti-TCR nb13.1 antibodies (A-H.l or A-H.2) compared to PBMCs activated by anti-CD3e antibodies (OKT3 or SP34-2).
  • FIG. 13C is a graph showing IFN-g secretion by PBMCs stimulated with an anti-TCRVb antibody, or anti-CD3 antibodies.
  • FIG. 13D shows target cell lysis by T cells stimulated with an anti-TCRVb antibody, or anti-CD3 antibodies. Cells were stimulated for 4 days followed by 2 days incubation with multiple myeloma target cells for assessment of cell killing.
  • FIGS. 15A-15C show secretion of cytokines in PBMCs stimulated with an anti-TCRVb antibody, or anti-CD3 antibodies.
  • FIGs 16A-16B show killing of MM cells by dual targeting BCMA-TCRvb antibody molecules.
  • FIG.16A shows in vitro killing by one of the following dual-targeting antibody molecules: BCMA-TCRVb (Molecule I), BCMA-CD3, or Control-TCRVb; or an isotype control.
  • FIG. 16B shows in vivo killing of MM cells by a dual-targeting BCM-TCRVb antibody (Molecule I).
  • FIGs 18A-18B demonstrate cytokine production from human PBMCs activated by anti- TCR Vp8a antibodies (B-H. l) when compared to those activated by anti-CD3e antibodies (OKT3 or SP34-2).
  • FIG. 18A shows that human PBMCs activated by anti-TCR Vp8a antibodies (B-H. l) produce similar or reduced levels of IFNy.
  • FIGs 19A-19C demonstrate cytokine production from human PBMCs activated by anti- TCR Vp8a antibodies (B-H.l).
  • Human PBMCs activated by anti-TCR Vp8a antibodies (B-H.l) do not significantly produce IL-6 (FIG. 19A), ILlb (FIG. 19B), and less TNFa (FIG. 19C), when compared to PBMCs activated by anti-CD3e antibodies (OKT3 or SP34-2).
  • FIGs. 20A-20E demonstrate cytokine production from human PBMCs activated by anti- TCRpV Antibody D antibody compared to control anti-CD3e antibody (OKT3).
  • FIG. 20A shows that human PBMCs activated by anti-TCRpV Antibody D antibody produce similar or reduced levels of IFNy.
  • FIG. 20B shows human PBMCs activated by anti-TCRpV Antibody D antibody produce higher levels of IL-2 when compared to those activated by anti-CD3e antibodies (OKT3).
  • FIGs. 21A-21B demonstrate cytokine production from human PBMCs activated by anti- TCR nb5 antibody (Antibody E).
  • FIG. 21A shows that human PBMCs activated by anti-TCR nb5 antibody produce similar or reduced levels of IFNy compared to PBMCS activated by anti- CD3e antibodies (OKT3 or SP34-2).
  • FIGs. 23A-23E demonstrate cytokine production from human PBMCs activated by a dual targeting (bispecific molecule) comprising an anti-TCRbV binding moiety and a BCMA binding moiety.
  • FIG. 23A shows that human PBMCs activated by the bispecific molecule produce similar or reduced levels of IFNy as PBMCS activated by anti-CD3e antibodies (OKT3).
  • FIG. 23B shows human PBMCs activated by the bispecific molecule produce higher levels of IL-2 when compared to PBMCs activated by anti-CD3e antibodies (OKT3).
  • FIG. 28 is a graph depicting mean tumor volume in N O D/S C I D/ 1 L- 2 Ry null (NSG) mice engrafted with Raji-luc cells at days 10 to 28.
  • the Star denotes PBMC implantation.
  • Open triangles denote antibody treatment with the indicated antibodies.
  • FIGs. 29A-B depicting Mean tumor burden (Total Flux) in N O D/S C I D/ 1 L- 2 Ry null (NSG) mice engrafted with cancer cells and treated with the indicated antibody.
  • NSG mice were implanted with PBMCs on Day 1 followed by injection with cancer cells on Day 7 (Raji-luc in FIG. 29A; K562-Luc control in FIG. 29B).
  • Antibody treatment with the indicated antibodies began on Day 16.
  • FIG. 29A shows mean tumor burden at days 16 to 37 in NOD/SCID/IL- 2Rynull (NSG) mice engrafted with Raji-luc cells.
  • FIG. 29B shows mean tumor burden (Total Flux) at days 16 to 30 in animals engrafted with K562-luc cells.
  • FIG. 30 is a graph depicting Mean tumor burden (Total Flux) mean tumor volume in NOD/SCID/IL-2Rynull (NSG) mice engrafted with RPMI-8226 cells.
  • the RPMI-8226 cells were engrafted on Day 1.
  • PBMCs were implanted into the mice and antibody treatment began on Day 17.
  • FIG.31A shows data generated using anti-TCR Vpi 3.1/anti-CD19 (Molecule F), anti-CD3/anti-CDl9, and anti-TCR nb13.1 (A-H.l).
  • FIG. 31B shows data generated using anti-TCR Vpl3.l/anti-BCMA (Molecule G), anti-CD3/anti-BCMA, and anti-TCR Vpl3.l (A- H.l).
  • FIGs. 32A-32F are graphs showing cytokine secretion stimulated by anti-TCR nb/anti- BCMA (Molecule H) or anti-CD3 (OKT3) at Days 1, 2, 3, and 5. Cytokines examined include: IFNy, IL-2, IL- I b, IL-6, IL-10, and TNFa (FIGs. 32A-32F, respectively).
  • FIGs. 33A-33F are graphs showing cytokine secretion stimulated by anti-TRBCl (Antibody F) or anti-CD3 (OKT3) at Days 2 and 5. Cytokines examined include: IFNy, IL-2,
  • IL- 1 b IL-6, IL-10, and TNFa (FIGs. 33A-33F, respectively).
  • cytokine release syndrome (CRS) (Shimabukuro-Vomhagen et ah, J Immunother Cancer. 2018 Jun l5;6(l):56, herein incorporated by reference in its entirety).
  • CRS cytokine release syndrome
  • This invention features molecules targeting the TCRpV chain of TCR and methods thereof. Without wishing to be bound by theory, such molecules are capable of binding, activating, and/or expanding only a subset of T cells, avoiding or reducing CRS and/or NT and minimizing potential immunosuppressive effects of anti-CD3 mAbs.
  • TCR is a disulfide-linked membrane- anchored heterodimeric protein normally consisting of the highly variable alpha (a) and beta (b) chains expressed as part of a complex with the invariant CD3 chain molecules.
  • TCR on ab T cells is formed by a heterodimer of one alpha chain and one beta chain.
  • Each alpha or beta chain consists of a constant domain and a highly variable domain classified as the Immunoglobulin superfamily (IgSF) fold.
  • the ⁇ bn chains can be further classified into 30 subfamilies (TRBV1-30). Despite their high structural and functional homology, the amino acid sequence homology in the TRBV genes is very low.
  • TCRs formed between alpha and beta chains of highly diverse sequences show a remarkable structural homology (FIGs. 24A and 24B) and elicit a similar function, e.g., activation of T cells.
  • the anti-TCRpV antibody molecules disclosed herein bind to an outward facing epitope of a TCRpV protein when it is in a complex with a TCRalpha protein, e.g., as denoted by the circled area in FIG. 24A.
  • the anti-TCRpV antibody molecules disclosed herein recognize (e.g., bind to), a domain (e.g., an epitope) on the TCRpV protein that is: (1) structurally conserved among different TCRpV subfamilies; and (2) has minimal sequence identity among the different TCRpV subfamilies.
  • TCRpV proteins from the different TCRBV subfamilies share minimal sequence similarity.
  • FIG. 24A-B TCRpV proteins which have minimal sequence similarity, share a similar 3D
  • the anti-TCRpV antibody molecules disclosed herein do not recognize, e.g., bind to, a constant region of a TCRpV protein. In some embodiments, the anti-TCRpV antibody molecules disclosed herein do not recognize, e.g., bind to, one or more (e.g., all) of a complementarity determining region (e.g., CDR1, CDR2 and/or CDR3) of a TCRpV protein.
  • a complementarity determining region e.g., CDR1, CDR2 and/or CDR3
  • TCRpV beta subunit of TCR
  • the anti- TCRpV antibody molecules disclosed herein result in lesser or no production of cytokines associated with CRS, e.g., IL-6, IL-lbeta, IL-10 and TNF alpha; and enhanced and/or delayed production of IL-2 and IFNg.
  • the anti-TCRpV antibodies disclosed herein have a cytokine profile, e.g., as described herein, which differs from a cytokine profile of a T cell engager that binds to a receptor or molecule other than a TCRpV region (“a non-TCRpV-binding T cell engager”).
  • the anti-TCRpV antibodies disclosed herein result in expansion of TCRpV+ T cells, e.g., a subset of memory effector T cells known as TEMRA.
  • compositions comprising anti-TCRpV antibody molecules of the present disclosure can be used, e.g., to: (1) activate and redirect T cells to promote tumor cell lysis for cancer immunotherapy; and/or (2) expand TCRpV+ T cells.
  • compositions comprising anti-TCRpV antibody molecules as disclosed herein limit the harmful side-effects of CRS and/or NT, e.g., CRS and/or NT associated with anti-CD3e targeting.
  • the anti-TCRpV antibody molecule does not bind to TCRP V12, or binds to TCRP V12 with an affinity and/or binding specificity that is less than (e.g., less than about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or about 2-, 5-, or 10- fold) the affinity and/or binding specificity of the 16G8 murine antibody or a humanized version thereof as described in US Patent 5,861,155.
  • the anti-TCRpV antibody molecule binds to TCRP V12 with an affinity and/or binding specificity that is greater than (e.g., greater than about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or about 2-, 5-, or 10- fold) the affinity and/or binding specificity of the 16G8 murine antibody or a humanized version thereof as described in US Patent 5,861,155.
  • the anti-TCRpV antibody molecule does not bind to TCRP V5- 5*01 or TCRP V5-l*0l, or binds to TCRP V5-5*0l or TCRP V5-l*0l with an affinity and/or binding specificity that is less than (e.g., less than about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or about 2-, 5-, or 10- fold) the affinity and/or binding specificity of the TM23 murine antibody or a humanized version thereof as described in US Patent 5,861,155.
  • the anti-TCRpV antibody molecule binds to a TCRpV region other than TCRP V5-5*0l or TCRP V5-l*0l (e.g ., TCRpV region as described herein, e.g., TCRP V6 subfamily (e.g., TCRP V6-5*0l) with an affinity and/or binding specificity that is greater than (e.g., greater than about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or about 2-, 5-, or 10- fold) the affinity and/or binding specificity of the TM23 murine antibody or a humanized version thereof as described in US Patent 5,861,155.
  • TCRpV region e.g ., TCRpV region as described herein, e.g., TCRP V6 subfamily (e.g., TCRP V6-5*0l) with an affinity and/or binding specificity that is greater than (e.g., greater than about 10%, 20%, 30%, 40%
  • the anti-TCRpV antibody molecule does not comprise the CDRs of the TM23 murine antibody.
  • “a” and“an” refers to one or to more than one (i.e., to at least one) of the grammatical object of the article.
  • “an element” means one element or more than one element.
  • Directly acquiring a physical entity includes performing a process that includes a physical change in a physical substance, e.g., a starting material.
  • Directly acquiring a value includes performing a process that includes a physical change in a sample or another substance, e.g., performing an analytical process which includes a physical change in a substance, e.g., a sample.
  • human-like antibody molecule refers to a humanized antibody molecule, human antibody molecule or an antibody molecule having at least 95% identity with a non-murine germline framework region, e.g., FR1, FR2, FR3 and/or FR4.
  • the human-like antibody molecule comprises a framework region having at least 95% identity to a human germline framework region, e.g., a FR1, FR2, FR3 and/or FR4 of a human germline framework region.
  • the human-like antibody molecule is a recombinant antibody.
  • the human-like antibody molecule is a humanized antibody molecule.
  • cytokine profile refers to the level and/or activity of on one or more cytokines or chemokines, e.g., as described herein.
  • a cytokine profile comprises the level and/or activity of a naturally occurring cytokine, a fragment or a variant thereof.
  • a cytokine profile comprises the level and/or activity of one or more cytokines and/or one or more chemokines (e.g., as described herein).
  • a cytokine profile comprises the level and/or activity of one or more of: IL-2 (e.g., full length, a variant, or a fragment thereof); IL-lbeta (e.g., full length, a variant, or a fragment thereof); IL-6 (e.g., full length, a variant, or a fragment thereof); TNFa (e.g., full length, a variant, or a fragment thereof); IFNg (e.g., full length, a variant, or a fragment thereof) IL-10 (e.g., full length, a variant, or a fragment thereof); IL-4 (e.g., full length, a variant, or a fragment thereof); TNF alpha (e.g., full length, a variant, or a fragment thereof) ;IL-l2p70 (e.g., full length, a variant, or a fragment thereof); IL-13 (e.g., full length, a variant, or a fragment thereof);
  • a cytokine in a cytokine profile can be modulated, e.g., increased or decreased, by an anti-TCRBV antibody molecule described herein.
  • the cytokine profile includes cytokines associated with a cytokine storm or cytokine release syndrome (CRS), e.g., IL-6, IL-lbeta, TNFalpha and IL-10.
  • CRS cytokine storm or cytokine release syndrome
  • variant refers to a polypeptide that has a substantially identical amino acid sequence to the naturally-occurring sequence, or are encoded by a substantially identical nucleotide sequence.
  • the variant is a functional variant.
  • a TCRpV variant can bind to TCRa and form a TCR a:b complex.
  • “functional variant” refers to a polypeptide that has a substantially identical amino acid sequence to the naturally-occurring sequence, or are encoded by a substantially identical nucleotide sequence, and are capable of having one or more activities of the naturally- occurring sequence.
  • a“multifunctional” or a“multispecific” molecule refers to molecule, e.g., a polypeptide, that has two or more functionalities, e.g., two or more binding specificities.
  • the functionalities can include one or more immune cell engagers, one or more tumor binding molecules, one or more cytokine molecules, one or more stromal modifiers, and other moieties described herein.
  • the multispecific molecule is a multispecific antibody molecule, e.g., a bispecific antibody molecule.
  • the multispecific molecule includes an anti-TCRVb antibody molecule as described herein.
  • the multifunctional molecule includes an immune cell engager.
  • An immune cell engager refers to one or more binding specificities that bind and/or activate an immune cell, e.g., a cell involved in an immune response.
  • the immune cell is chosen from a T cell, an NK cell, a B cell, a dendritic cell, and/or the macrophage cell.
  • the immune cell engager when it is an antibody molecule, it binds to an immune cell antigen (e.g., a T cell antigen, an NK cell antigen, a B cell antigen, a dendritic cell antigen, and/or a macrophage cell antigen) with a dissociation constant of less than about 10 nM.
  • an immune cell antigen e.g., a T cell antigen, an NK cell antigen, a B cell antigen, a dendritic cell antigen, and/or a macrophage cell antigen
  • the multifunctional molecule includes a cytokine molecule.
  • a“cytokine molecule” refers to full length, a fragment or a variant of a cytokine; a cytokine further comprising a receptor domain, e.g., a cytokine receptor dimerizing domain; or an agonist of a cytokine receptor, e.g., an antibody molecule (e.g., an agonistic antibody) to a cytokine receptor, that elicits at least one activity of a naturally-occurring cytokine.
  • the cytokine molecule is chosen from interleukin-2 (IL-2), interleukin-7 (IL-7), interleukin- 12 (IL-12), interleukin- 10 (IL-10), interleukin- 15 (IL-15), interleukin- 18 (IL-18), interleukin-21 (IL-21), or interferon gamma, or a fragment or variant thereof, or a combination of any of the aforesaid cytokines.
  • the cytokine molecule can be a monomer or a dimer.
  • the cytokine molecule can further include a cytokine receptor dimerizing domain.
  • the cytokine molecule is an agonist of a cytokine receptor, e.g., an antibody molecule ( e.g ., an agonistic antibody) to a cytokine receptor chosen from an IL-l5Ra or IL-21R.
  • a cytokine receptor e.g., an antibody molecule ( e.g ., an agonistic antibody) to a cytokine receptor chosen from an IL-l5Ra or IL-21R.
  • the multifunctional molecule includes a stromal modifying moiety.
  • A“stromal modifying moiety,” as used herein refers to an agent, e.g., a protein (e.g., an enzyme), that is capable of altering, e.g., degrading a component of, the stroma.
  • a protein e.g., an enzyme
  • the articles“a” and“an” refer to one or more than one, e.g., to at least one, of the grammatical object of the article.
  • the use of the words “a” or “an” when used in conjunction with the term “comprising” herein may mean “one,” but it is also consistent with the meaning of "one or more,” “at least one,” and “one or more than one.”
  • “about” and“approximately” generally mean an acceptable degree of error for the quantity measured given the nature or precision of the measurements. Exemplary degrees of error are within 20 percent (%), typically, within 10%, and more typically, within 5% of a given range of values.
  • antibody fragment or“functional fragment” also include isolated fragments consisting of the variable regions, such as the“Fv” fragments consisting of the variable regions of the heavy and light chains or recombinant single chain polypeptide molecules in which light and heavy variable regions are connected by a peptide linker (“scFv proteins”).
  • an antibody fragment does not include portions of antibodies without antigen binding activity, such as Fc fragments or single amino acid residues.
  • Exemplary antibody molecules include full length antibodies and antibody fragments, e.g., dAb (domain antibody), single chain, Fab, Fab’, and F(ab’) 2 fragments, and single chain variable fragments (scFvs).
  • the antibody molecule is an antibody mimetic.
  • an“immunoglobulin variable domain sequence” refers to an amino acid sequence which can form the structure of an immunoglobulin variable domain.
  • the sequence may include all or part of the amino acid sequence of a naturally-occurring variable domain.
  • the sequence may or may not include one, two, or more N- or C-terminal amino acids, or may include other alterations that are compatible with formation of the protein structure.
  • an antibody molecule is monospecific, e.g., it comprises binding specificity for a single epitope.
  • an antibody molecule is multispecific, e.g., it comprises a plurality of immunoglobulin variable domain sequences, where a first immunoglobulin variable domain sequence has binding specificity for a first epitope and a second immunoglobulin variable domain sequence has binding specificity for a second epitope.
  • an antibody molecule is a bispecific antibody molecule.“Bispecific antibody molecule” as used herein refers to an antibody molecule that has specificity for more than one ( e.g ., two, three, four, or more) epitope and/or antigen.
  • an antigen can be synthesized or can be derived from a biological sample, e.g., a tissue sample, a tumor sample, a cell, or a fluid with other biological components.
  • a“tumor antigen” or interchangeably, a“cancer antigen” includes any molecule present on, or associated with, a cancer, e.g., a cancer cell or a tumor microenvironment that can provoke an immune response.
  • an“immune cell antigen” includes any molecule present on, or associated with, an immune cell that can provoke an immune response.
  • the three hypervariable regions of a light chain and the three hypervariable regions of a heavy chain are disposed relative to each other in three dimensional space to form an antigen-binding surface, which is complementary to the three-dimensional surface of a bound antigen.
  • the three hypervariable regions of each of the heavy and light chains are referred to as“complementarity-determining regions,” or“CDRs.”
  • cancer includes relapsed and/or resistant cancer.
  • cancer includes relapsed and/or resistant cancer.
  • the terms“cancer” and“tumor” can be used interchangeably. For example, both terms encompass solid and liquid tumors.
  • the term“cancer” or“tumor” includes premalignant, as well as malignant cancers and tumors.
  • an“immune cell” refers to any of various cells that function in the immune system, e.g., to protect against agents of infection and foreign matter.
  • this term includes leukocytes, e.g., neutrophils, eosinophils, basophils, lymphocytes, and monocytes.
  • leukocytes include phagocytes (e.g., macrophages, neutrophils, and dendritic cells), mast cells, eosinophils, basophils, and natural killer cells.
  • phagocytes e.g., macrophages, neutrophils, and dendritic cells
  • mast cells e.g., eosinophils, basophils, and natural killer cells.
  • Innate leukocytes identify and eliminate pathogens, either by attacking larger pathogens through contact or by engulfing and then killing microorganisms, and are mediators in the activation of an adaptive immune response.
  • lymphocytes The cells of the adaptive immune system are special types of leukocytes, called lymphocytes.
  • B cells and T cells are important types of lymphocytes and are derived from hematopoietic stem cells in the bone marrow. B cells are involved in the humoral immune response, whereas T cells are involved in cell-mediated immune response.
  • the term“immune cell” includes immune effector cells.
  • Immuno effector cell refers to a cell that is involved in an immune response, e.g., in the promotion of an immune effector response.
  • immune effector cells include, but are not limited to, T cells, e.g., alpha/beta T cells and gamma/delta T cells, B cells, natural killer (NK) cells, natural killer T (NK T) cells, and mast cells.
  • effector function or“effector response” refers to a specialized function of a cell. Effector function of a T cell, for example, may be cytolytic activity or helper activity including the secretion of cytokines.
  • nucleotide sequence in the context of nucleotide sequence, the term "substantially identical" is used herein to refer to a first nucleic acid sequence that contains a sufficient or minimum number of nucleotides that are identical to aligned nucleotides in a second nucleic acid sequence such that the first and second nucleotide sequences encode a polypeptide having common functional activity, or encode a common structural polypeptide domain or a common functional polypeptide activity.
  • variant refers to a polypeptide that has a substantially identical amino acid sequence to a reference amino acid sequence, or is encoded by a substantially identical nucleotide sequence. In some embodiments, the variant is a functional variant.
  • the term“functional variant” refers to a polypeptide that has a substantially identical amino acid sequence to a reference amino acid sequence, or is encoded by a substantially identical nucleotide sequence, and is capable of having one or more activities of the reference amino acid sequence.
  • the sequences are aligned for optimal comparison purposes (e.g., gaps can be introduced in one or both of a first and a second amino acid or nucleic acid sequence for optimal alignment and non-homologous sequences can be disregarded for comparison purposes).
  • the length of a reference sequence aligned for comparison purposes is at least 30%, preferably at least 40%, more preferably at least 50%, 60%, and even more preferably at least 70%, 80%, 90%, 100% of the length of the reference sequence.
  • the amino acid residues or nucleotides at corresponding amino acid positions or nucleotide positions are then compared.
  • amino acid or nucleic acid “identity” is equivalent to amino acid or nucleic acid “homology”
  • the comparison of sequences and determination of percent identity between two sequences can be accomplished using a mathematical algorithm.
  • the percent identity between two amino acid sequences is determined using the Needleman and Wunsch ((1970) J. Mol. Biol. 48:444-453 ) algorithm which has been incorporated into the GAP program in the GCG software package (available at http://www.gcg.com), using either a Blossum 62 matrix or a PAM250 matrix, and a gap weight of 16, 14, 12, 10, 8, 6, or 4 and a length weight of 1, 2, 3, 4, 5, or 6.
  • the percent identity between two nucleotide sequences is determined using the GAP program in the GCG software package (available at http://www.gcg.com), using a NWSgapdna.CMP matrix and a gap weight of 40, 50, 60, 70, or 80 and a length weight of 1, 2, 3, 4, 5, or 6.
  • a particularly preferred set of parameters are a Blossum 62 scoring matrix with a gap penalty of 12, a gap extend penalty of 4, and a frameshift gap penalty of 5.
  • the percent identity between two amino acid or nucleotide sequences can be determined using the algorithm of E. Meyers and W. Miller ((1989) CABIOS, 4:11-17) which has been incorporated into the ALIGN program (version 2.0), using a PAM120 weight residue table, a gap length penalty of 12 and a gap penalty of 4.
  • nucleic acid and protein sequences described herein can be used as a "query sequence" to perform a search against public databases to, for example, identify other family members or related sequences. Such searches can be performed using the NBLAST and
  • Gapped BLAST can be utilized as described in Altschul et al, (1997) Nucleic Acids Res. 25:3389-3402.
  • NBLAST NBLAST
  • a “conservative amino acid substitution” is one in which the amino acid residue is replaced with an amino acid residue having a similar side chain.
  • Families of amino acid residues having similar side chains have been defined in the art. These families include amino acids with basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine).
  • polymers of amino acids of any length may be linear or branched, it may comprise modified amino acids, and it may be interrupted by non amino acids.
  • the terms also encompass an amino acid polymer that has been modified; for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation, such as conjugation with a labeling component.
  • the polypeptide can be isolated from natural sources, can be a produced by recombinant techniques from a eukaryotic or prokaryotic host, or can be a product of synthetic procedures.
  • nucleic acid refers to a polymeric form of nucleotides of any length, either deoxyribonucleotides or ribonucleotides, or analogs thereof.
  • the polynucleotide may be either single- stranded or double-stranded, and if single-stranded may be the coding strand or non-coding (antisense) strand.
  • a polynucleotide may comprise modified nucleotides, such as methylated nucleotides and nucleotide analogs.
  • the sequence of nucleotides may be interrupted by non-nucleotide components.
  • a polynucleotide may be further modified after polymerization, such as by conjugation with a labeling component.
  • the nucleic acid may be a recombinant polynucleotide, or a polynucleotide of genomic, cDNA, semisynthetic, or synthetic origin which either does not occur in nature or is linked to another polynucleotide in a non-natural arrangement.
  • isolated refers to material that is removed from its original or native environment (e.g ., the natural environment if it is naturally occurring).
  • a naturally-occurring polynucleotide or polypeptide present in a living animal is not isolated, but the same polynucleotide or polypeptide, separated by human intervention from some or all of the co-existing materials in the natural system, is isolated.
  • Such polynucleotides could be part of a vector and/or such polynucleotides or polypeptides could be part of a composition, and still be isolated in that such vector or composition is not part of the environment in which it is found in nature.
  • TCR Human T cell receptor
  • TCR alpha chain consists of V, J and C regions.
  • the rearrangement of the T-cell receptor (TCR) through somatic recombination of V (variable), D (diversity), J (joining), and C (constant) regions is a defining event in the development and maturation of a T cell. TCR gene rearrangement takes place in the thymus.
  • TCR beta V TCRflV
  • the TCR V beta repertoire varies between individuals and populations because of, e.g., 7 frequently occurring inactivating polymorphisms in functional gene segments and a large insertion/deletion-related polymorphism encompassing 2 V beta gene segments.
  • a TCRBV gene family comprises one or more subfamilies, e.g., as described herein, e.g., in FIG. 3, Table 8A or Table 8B.
  • the TCRpV gene family comprises: a TCRP V6 subfamily, a TCRP V10 subfamily, a TCRP V12 subfamily, a TCRP V5 subfamily, a TCRP V7 subfamily, a TCRP VI 1 subfamily, a TCRP V14 subfamily, a TCRP V16 subfamily, a TCRp VI 8 subfamily, a TCRp V9 subfamily, a TCRp V13 subfamily, a TCRp V4 subfamily, a TCRP V3 subfamily, a TCRP V2 subfamily, a TCRP V15 subfamily, a TCRP V30 subfamily, a TCRp V19 subfamily, a TCRp V27 subfamily, a TCRp V28 subfamily, a TCR
  • TCRP V6 subfamily is also known as TCRP V13.1.
  • the TCRP V6 subfamily comprises: TCRP V6-4*0l, TCRP V6-4*02, TCRP V6- 9*01, TCRp V6-8*0l, TCRp V6-5*0l, TCRp V6-6*02, TCRp V6-6*0l, TCRp V6-2*0l, TCRp V6-3*0l or TCRP V6-l*0l, or a variant thereof.
  • TCRP V6 comprises TCRP V6-4*0l, or a variant thereof.
  • TCRP V6 comprises TCRP V6- 4*02, or a variant thereof.
  • TCRP V6 comprises TCRP V6-9*0l, or a variant thereof. In some embodiments, TCRP V6 comprises TCRP V6-8*0l, or a variant thereof. In some embodiments, TCRP V6 comprises TCRP V6-5*0l, or a variant thereof. In some embodiments, TCRP V6 comprises TCRP V6-6*02, or a variant thereof. In some embodiments, TCRP V6 comprises TCRP V6-6*0l, or a variant thereof. In some embodiments, TCRP V6 comprises TCRP V6-2*0l, or a variant thereof. In some embodiments, TCRP V6 comprises TCRP V6-3*0l, or a variant thereof. In some embodiments, TCRP V6 comprises TCRP V6- 1*01, or a variant thereof.
  • TCRP V6 comprises TCRP V6-5*0l, or a variant thereof.
  • TCRP V6, e.g., TCRP V6-5*0l is recognized, e.g., bound, by SEQ ID NO: 1 and/or SEQ ID NO: 2.
  • TCRP V6, e.g., TCRP V6-5*0l is recognized, e.g., bound, by SEQ ID NO: 9 and/or SEQ ID NO: 10.
  • TCRP V6 is recognized, e.g., bound, by SEQ ID NO: 9 and/or SEQ ID NO: 11.
  • TCRP V12 subfamily is also known as TCRP V8.1.
  • the TCRP V12 subfamily comprises: TCRP Vl2-4*0l, TCRP Vl2-3*0l, or TCRP Vl2-5*0l, or a variant thereof.
  • TCRP V12 is recognized, e.g., bound, by SEQ ID NO: 15 and/or SEQ ID NO: 16.
  • TCRP V12 is recognized, e.g., bound, by any one of SEQ ID NOs 23-25, and/or any one of SEQ ID NO: 26-30:
  • the TCRP V5 subfamily is chosen from: TCRP V5-5*0l, TCRP V5-6*0l, TCRp V5-4*0l, TCRp V5-8*0l, TCRp V5-l*0l, or a variant thereof.
  • the TCRP V7 subfamily comprises TCRP V7-7*0l, TCRP V7- 6*01, TCRp V7 -8*02, TCRp V7 -4*01, TCRp V7-2*02, TCRp V7-2*03, TCRp V7-2*0l,
  • the TCRP VI 1 subfamily comprises: TCRP VI 1-1*01, TCRP VI 1-2*01 or TCRP VI 1-3*01, or a variant thereof.
  • the TCRP V14 subfamily comprises TCRP Vl4*0l, or a variant thereof.
  • the TCRP V16 subfamily comprises TCRP Vl6*0l, or a variant thereof.
  • the TCRP V18 subfamily comprises TCRP Vl8*0l, or a variant thereof.
  • the TCRP V9 subfamily comprises TCRP V9*0l or TCRP V9*02, or a variant thereof.
  • the TCRP V13 subfamily comprises TCRP Vl3*0l, or a variant thereof.
  • the TCRP V4 subfamily comprises TCRP V4-2*0l, TCRP V4- 3*01, or TCRP V4-l*0l, or a variant thereof.
  • the TCRP V3 subfamily comprises TCRP V3-l*0l, or a variant thereof.
  • the TCRP V2 subfamily comprises TCRP V2*0l, or a variant thereof.
  • the TCRP V15 subfamily comprises TCRP Vl5*0l, or a variant thereof.
  • the TCRP V30 subfamily comprises TCRP V30*0l, or TCRP V30*02, or a variant thereof.
  • the TCRP V19 subfamily comprises TCRP Vl9*0l, or TCRP VI 9*02, or a variant thereof.
  • the TCRP V27 subfamily comprises TCRP V27*0l, or a variant thereof.
  • the TCR3 V28 subfamily comprises TCR3 V28*0l, or a variant thereof.
  • V20-l*02 or a variant thereof.
  • the TCR3 V25 subfamily comprises TCR3 V25-l*0l, or a variant thereof.
  • the TCR3 V29 subfamily comprises TCR3 V29-l*0l, or a variant thereof.
  • Table 8A List of TCRpV subfamilies and subfamily members
  • TCRBV amino acid sequences in Table 9 underscores the diversity of TCR sequences.
  • TRBV sequences from different subfamilies are considerably different from each other.
  • the anti-TCRpV antibody molecules disclosed herein do not recognize, e.g., bind to, an interface of a TCRpV:TCRalpha complex.
  • the anti-TCRpV antibody molecules disclosed herein do not recognize, e.g., bind to, a constant region of a TCRpV protein.
  • An exemplary antibody that binds to a constant region of a TCRBV region is JOVI.l as described in Viney el al., (Hybridoma.
  • the anti-TCRpV antibody molecules disclosed herein do not recognize, e.g., bind to, one or more (e.g., all) of a complementarity determining region (e.g., CDR1, CDR2 and/or CDR3) of a TCRpV protein. In some embodiments, the anti-TCRpV antibody molecules disclosed herein binds (e.g., specifically binds) to a TCRpV region.
  • a complementarity determining region e.g., CDR1, CDR2 and/or CDR3
  • binding of anti-TCRpV antibody molecules disclosed herein results in a cytokine profile that differs from a cytokine profile of a T cell engager that binds to a receptor or molecule other than a TCRpV region (“a non-TCRpV- binding T cell engager”).
  • the non-TCRpV-binding T cell engager comprises an antibody that binds to a CD3 molecule ( e.g ., CD3 epsilon (CD3e) molecule); or a TCR alpha (TCRa) molecule.
  • the non-TCRpV-binding T cell engager is an OKT3 antibody or an SP34-2 antibody.
  • the disclosure provides an anti-TCRpV antibody molecule that binds to human TCRpV, e.g., a TCRpV gene family, e.g., one or more of a TCRpV subfamily, e.g., as described herein, e.g., in FIG. 3, Table 8A, or Table 8B.
  • a TCRpV gene family e.g., one or more of a TCRpV subfamily, e.g., as described herein, e.g., in FIG. 3, Table 8A, or Table 8B.
  • the anti-TCRpV antibody molecule binds to a TCRP V6 subfamily comprising: TCRp V6-4*0l, TCRp V6-4*02, TCRp V6-9*0l, TCRp V6-8*0l, TCRp V6-5*0l, TCRp V6-6*02, TCRp V6-6*0l, TCRp V6-2*0l, TCRp V6-3*0l or TCRp V6-l*0l, or a variant thereof.
  • the TCRP V6 subfamily comprises TCRP V6-5*0l, or a variant thereof.
  • TCRP V6 comprises TCRP V6-4*0l, or a variant thereof.
  • TCRP V6 comprises TCRP V6-4*02, or a variant thereof. In some embodiments, TCRP V6 comprises TCRP V6-9*0l, or a variant thereof. In some embodiments, TCRP V6 comprises TCRP V6-8*0l, or a variant thereof. In some embodiments, TCRP V6 comprises TCRP V6-5*0l, or a variant thereof. In some embodiments, TCRP V6 comprises TCRP V6-6*02, or a variant thereof. In some embodiments, TCRP V6 comprises TCRP V6-6*0l, or a variant thereof. In some embodiments, TCRP V6 comprises TCRP V6- 2*01, or a variant thereof. In some embodiments, TCRP V6 comprises TCRP V6-3*0l, or a variant thereof. In some embodiments, TCRP V6 comprises TCRP V6- 1*01, or a variant thereof.
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule, may include any CDR described herein.
  • substantially identical e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical
  • substantially identical e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical
  • amino acid alteration but not more than two, three or four alterations (e.g., substitutions, deletions, or insertions, e.g., conservative substitutions) relative to one, two, three, four, five, or six CDRs according to Kabat et al. shown in Table 1.
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule, includes at least one, two, three, four, five, or six CDRs according to Chothia et al.
  • a combined CDR as set out in Table 1 is a CDR that comprises a Rabat CDR and a Chothia CDR.
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule, molecule includes a combination of CDRs or hypervariable loops identified as combined CDRs in Table 1.
  • the anti- TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule, can contain any combination of CDRs or hypervariable loops according the“combined” CDRs are described in Table 1.
  • LC CDR3 complementarity determining region 3
  • HC CDR3 complementarity determining region 3
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti- TCRp V6-5*0l) antibody molecule comprises a LC CDR1, LC CDR2, and LC CDR3 of SEQ ID NO: 10, and a HC CDR1, HC CDR2, and HC CDR3 of SEQ ID NO: 9.
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti- TCRP V6-5*0l) antibody molecule comprises:
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule comprises:
  • VL light chain variable region
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti- TCRP V6-5*0l) antibody molecule comprises:
  • VL light chain variable region
  • VH heavy chain variable region
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti- TCRP V6-5*0l) antibody molecule comprises:
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule comprises:
  • VL light chain variable region
  • the light or the heavy chain variable framework (e.g., the region encompassing at least FR1, FR2, FR3, and optionally FR4) of the anti-TCRpV antibody molecule, e.g., anti-TCRP V6 (e.g ., anti-TCRP V6-5*0l) antibody molecule can be chosen from: (a) a light or heavy chain variable framework including at least 80%, 85%, 87% 90%, 92%, 93%, 95%, 97%, 98%, or 100% of the amino acid residues from a human light or heavy chain variable framework, e.g., a light or heavy chain variable framework residue from a human mature antibody, a human germline sequence, or a human consensus sequence; (b) a light or heavy chain variable framework including from 20% to 80%, 40% to 60%, 60% to 90%, or 70% to 95% of the amino acid residues from a human light or heavy chain variable framework, e.g., a light or heavy chain variable framework residue from a human mature antibody,
  • the light or heavy chain variable framework region (particularly FR1, FR2 and/or FR3) includes a light or heavy chain variable framework sequence at least 70, 75, 80, 85, 87, 88, 90, 92, 94, 95, 96, 97, 98, 99% identical or identical to the frameworks of a VL or VH segment of a human germline gene.
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule, comprises the light chain framework region 1 of A-H.l or A-H.2, e.g., as shown in FIG. IB.
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule, comprises the light chain framework region 2 of A-H.l or A-H.2, e.g., as shown in FIG. IB.
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule, comprises the light chain framework region 3 of A-H.l or A-H.2, e.g., as shown in FIG. IB.
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule, comprises the light chain framework region 4 of A-H.l or A-H.2, e.g., as shown in FIG. IB.
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule
  • the FR1 comprises a Phenylalanine at position 10, e.g., a Serine to Phenyalanine substitution.
  • the substitution is relative to a human germline light chain framework region sequence.
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule
  • FR2 comprises a Histidine at position 36, e.g., a substitution at position 36 according to Rabat numbering, e.g., a Tyrosine to Histidine substitution.
  • FR2 comprises an Alanine at position 46, e.g., a substitution at position 46 according to Rabat numbering, e.g., an Arginine to Alanine substitution.
  • the substitution is relative to a human germline light chain framework region sequence.
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule, comprises a light chain variable domain comprising a framework region, e.g., framework region 3 (FR3), comprising a change, e.g., a substitution (e.g., a conservative substitution) at a position disclosed herein according to Rabat numbering.
  • FR3 framework region 3
  • FR3 comprises a Phenyalanine at position 87, e.g., a substitution at position 87 according to Rabat numbering, e.g., a Tyrosine to Phenyalanine substitution.
  • the substitution is relative to a human germline light chain framework region sequence.
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule
  • Phenyalanine substitution e.g., as shown in the amino acid sequence of SEQ ID NO: 10.
  • the substitution is relative to a human germline light chain framework region sequence.
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule, comprises the heavy chain framework region 1 of A- H.l or A-H.2, e.g., as shown in FIG. 1A.
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule, comprises the heavy chain framework region 2 of A- H.l or A-H.2, e.g., as shown in FIG. 1A
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule, comprises the heavy chain framework region 4 of A- H.l or A-H.2, e.g., as shown in FIG. 1A.
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule
  • FR3 comprises a Threonine at position 73, e.g., a substitution at position 73 according to Rabat numbering, e.g., a Glutamic Acid to Threonine substitution.
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule
  • FR3 framework region 3
  • Threonine at position 73 e.g., a substitution at position 73 according to Kabat numbering, e.g., a Glutamic Acid to Threonine substitution
  • a Glycine at position 94 e.g.,
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule, comprises the heavy chain framework regions 1-4 of A- H.l or A-H.2, e.g., SEQ ID NO: 9, or as shown in FIGs. 1A and IB.
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule, comprises the light chain framework regions 1-4 of A- H.l, e.g., SEQ ID NO: 10, or as shown in FIGs. 1A and IB.
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule, comprises the light chain framework regions 1-4 of A- H.2, e.g., SEQ ID NO: 11, or as shown in FIGs. 1A and IB.
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule
  • the anti-TCRpV antibody molecule comprises the heavy chain framework regions 1-4 of A- H.l, e.g., SEQ ID NO: 9; and the light chain framework regions 1-4 of A-H.l, e.g., SEQ ID NO:
  • FIGs. 1A and IB are numbered 10, or as shown in FIGs. 1A and IB.
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule
  • the anti-TCRpV antibody molecule comprises the heavy chain framework regions 1-4 of A- H.2, e.g., SEQ ID NO: 9; and the light chain framework regions 1-4 of A-H.2, e.g., SEQ ID NO:
  • FIGs. 1A and IB are identical to FIGs. 1A and IB.
  • the heavy or light chain variable domain, or both, of the anti- TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule
  • the anti- TCRpV antibody molecule includes an amino acid sequence, which is substantially identical to an amino acid disclosed herein, e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical to a variable region of an antibody described herein, e.g., an antibody chosen from A-H.l or A-H.2, or as described in Table 1, or encoded by the nucleotide sequence in Table 1; or which differs at least 1 or 5 residues, but less than 40, 30, 20, or 10 residues, from a variable region of an antibody described herein.
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule includes a VH and/or VL domain encoded by a nucleic acid having a nucleotide sequence as set forth in Table 1, or a sequence substantially identical thereto (e.g., a sequence at least about 85%, 90%, 95%, 99% or more identical thereto, or which differs by no more than 3, 6, 15, 30, or 45 nucleotides from the sequences shown in Table 1.
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule, comprises:
  • VH domain comprising the amino acid sequence of SEQ ID NO: 9, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence of SEQ ID NO: 9, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 9; and/or
  • VL domain comprising the amino acid sequence of SEQ ID NO: 10, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence of SEQ ID NO: 10, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 10.
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule, comprises:
  • VL domain comprising the amino acid sequence of SEQ ID NO: 11, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence of SEQ ID NO: 11, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 11.
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule is a full antibody or fragment thereof (e.g., a Fab,
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule is a monoclonal antibody or an antibody with single specificity.
  • the anti-TCRpV antibody molecule, e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule can also be a humanized, chimeric, camelid, shark, or an in vitro- generated antibody molecule.
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6- 5*01) antibody molecule
  • the heavy and light chains of the anti-TCRpV antibody molecule can be full-length (e.g., an antibody can include at least one, and preferably two, complete heavy chains, and at least one, and preferably two, complete light chains) or can include an antigen-binding fragment (e.g., a Fab, F(ab')2, Fv, a single chain Fv fragment, a single domain antibody, a diabody (dAb), a bivalent antibody, or bispecific antibody or fragment thereof, a single domain variant thereof, or a camelid antibody).
  • an antibody can include at least one, and preferably two, complete heavy chains, and at least one, and preferably two, complete light chains
  • an antigen-binding fragment e.g., a Fab, F(ab')2, Fv, a single chain Fv fragment,
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule
  • the Fc region is chosen from the heavy chain constant regions of IgGl, IgG2, IgG3, and IgG4.
  • the Fc region is chosen from the heavy chain constant region of IgGl or IgG2 (e.g., human IgGl, or IgG2).
  • the heavy chain constant region is human IgGl.
  • the constant region is altered, e.g., mutated, to modify the properties of the anti- TCRpV antibody molecule, e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule (e.g., to increase or decrease one or more of: Fc receptor binding, antibody glycosylation, the number of cysteine residues, effector cell function, or complement function).
  • anti-TCRP V6 e.g., anti-TCRP V6-5*0l
  • Fc receptor binding e.g., anti-TCRP V6-5*0l
  • the constant region is mutated at positions 296 (M to Y), 298 (S to T), 300 (T to E), 477 (H to K) and 478 (N to F) to alter Fc receptor binding (e.g., the mutated positions correspond to positions 132 (M to Y), 134 (S to T), 136 (T to E), 313 (H to K) and 314 (N to F) of SEQ ID NOs: 212 or 214; or positions 135 (M to Y), 137 (S to T), 139 (T to E), 316 (H to K) and 317 (N to F) of SEQ ID NOs: 215, 216, 217 or 218), e.g., relative to human IgGl.
  • the mutated positions correspond to positions 132 (M to Y), 134 (S to T), 136 (T to E), 313 (H to K) and 314 (N to F) of SEQ ID NOs: 212 or 214; or positions 135 (M to
  • Antibody A-H.l comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 3278 and a light chain comprising the amino acid sequence of SEQ ID NO: 72.
  • Antibody A-H.2 comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 3278 and a light chain comprising the amino acid sequence of SEQ ID NO: 3279.
  • Table 1 Amino acid and nucleotide sequences for murine, chimeric and humanized antibody molecules.
  • the antibody molecules include murine mAb Antibody A, and humanized mAb Antibody A-H Clones A-H.l and A-H.2.
  • the amino acid the heavy and light chain CDRs, and the amino acid and nucleotide sequences of the heavy and light chain variable regions, and the heavy and light chains are shown.
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule comprises a VH and/or a VL of an antibody described in Table 1, or a sequence with at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more identity thereto.
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*0l) antibody molecule comprises a VH and a VL of an antibody described in Table 1, or a sequence with at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more identity thereto.
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V12 antibody molecule
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V12 antibody molecule
  • the anti-TCRpV antibody molecule includes a kappa light chain constant region, e.g., a human kappa light chain constant region.
  • the light chain constant region comprises an amino sequence set forth in Table 3, or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) thereto.
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V12 antibody molecule includes at least one, two, three, four, five, or six CDRs according to Rabat et al. (e.g., at least one, two, three, four, five, or six CDRs according to the Rabat definition as set out in Table 2) from the heavy and light chain variable regions of an antibody described herein, e.g., an antibody as described in Table 2, or encoded by the nucleotide sequence in Table 2; or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences; or which have at least one amino acid alteration, but not more than two, three or four alterations (e.g., substitutions, deletions, or insertions, e.g., conservative substitutions) relative to one, two, three, four, five, or six CDRs
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V12 antibody molecule includes at least one, two, or three CDRs according to Chothia et al. (e.g., at least one, two, or three CDRs according to the Chothia definition as set out in Table 2) from a light chain variable region of an antibody described herein, e.g., an antibody as described in Table 2, or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences; or which have at least one amino acid alteration, but not more than two, three or four alterations (e.g., substitutions, deletions, or insertions, e.g., conservative substitutions) relative to one, two, or three CDRs according to Chothia et al. shown in Table 2.
  • alterations e.g., substitutions, deletions, or insertions, e
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V12 antibody molecule includes at least one, two, three, four, five, or six CDRs according to Chothia et al.
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V12 antibody molecule includes all six CDRs according to Chothia et al. (e.g., all six CDRs according to the Chothia definition as set out in Table 2) from the heavy and light chain variable regions of an antibody described herein, e.g., an antibody as described in Table 2, or encoded by the nucleotide sequence in Table 2; or encoded by the nucleotide sequence in Table 2; or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences; or which have at least one amino acid alteration, but not more than two, three or four alterations (e.g., substitutions, deletions, or insertions, e.g., conservative substitutions) relative to all six CDRs according to Chothia et al.
  • alterations e.g., substitutions
  • the anti-TCRpV antibody molecule e.g., anti-TCRP V12 antibody molecule includes at least one, two, three, four, five, or six CDRs according to a combined CDR. (e.g., at least one, two, three, four, five, or six CDRs according to the combined CDR definition as set out in Table 2) from the heavy and light chain variable regions of an antibody described herein, e.g., an antibody as described in Table 2, or encoded by the nucleotide sequence in Table 2; or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%,

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Biochemistry (AREA)
  • Biomedical Technology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Biotechnology (AREA)
  • Zoology (AREA)
  • Cell Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Hematology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Microbiology (AREA)
  • General Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Virology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
PCT/US2019/040592 2018-07-03 2019-07-03 Anti-tcr antibody molecules and uses thereof Ceased WO2020010250A2 (en)

Priority Applications (19)

Application Number Priority Date Filing Date Title
EP19745444.0A EP3818083A2 (en) 2018-07-03 2019-07-03 Anti-tcr antibody molecules and uses thereof
JP2021521940A JP7554742B2 (ja) 2018-07-03 2019-07-03 抗ｔｃｒ抗体分子およびその使用
US17/256,917 US11845797B2 (en) 2018-07-03 2019-07-03 Anti-TCR antibody molecules and uses thereof
CN201980057685.4A CN112955465A (zh) 2018-07-03 2019-07-03 抗tcr抗体分子及其用途
CA3105448A CA3105448A1 (en) 2018-07-03 2019-07-03 Anti-tcr antibody molecules and uses thereof
AU2019297451A AU2019297451A1 (en) 2018-07-03 2019-07-03 Anti-TCR antibody molecules and uses thereof
US17/529,017 US20220064297A1 (en) 2018-07-03 2021-11-17 Anti-tcr antibody molecules and uses thereof
US17/820,794 US11965025B2 (en) 2018-07-03 2022-08-18 Method of treating solid cancers with bispecific interleukin-anti-TCRß molecules
US17/820,805 US12286477B2 (en) 2018-07-03 2022-08-18 Anti-TCR antibody molecules and uses thereof
US17/820,800 US20230127740A1 (en) 2018-07-03 2022-08-18 Anti-tcr antibody molecules and uses thereof
US17/820,806 US20230034161A1 (en) 2018-07-03 2022-08-18 Anti-tcr antibody molecules and uses thereof
US17/820,634 US20230025484A1 (en) 2018-07-03 2022-08-18 Anti-tcr antibody molecules and uses thereof
US17/820,818 US20230031734A1 (en) 2018-07-03 2022-08-18 Anti-tcr antibody molecules and uses thereof
US17/820,811 US20230142522A1 (en) 2018-07-03 2022-08-18 Anti-tcr antibody molecules and uses thereof
US18/472,920 US12351632B2 (en) 2018-07-03 2023-09-22 Anti-TCR antibody molecules and uses thereof
US18/431,634 US20240301060A1 (en) 2018-07-03 2024-02-02 Anti-tcr antibody molecules and uses thereof
JP2024154806A JP2024170589A (ja) 2018-07-03 2024-09-09 抗ｔｃｒ抗体分子およびその使用
US19/080,243 US20250215085A1 (en) 2018-07-03 2025-03-14 Anti-tcr antibody molecules and uses thereof
US19/214,564 US20250340640A1 (en) 2018-07-03 2025-05-21 Anti-tcr antibody molecules and uses thereof

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
US201862693653P 2018-07-03 2018-07-03
US62/693,653 2018-07-03
US201862737829P 2018-09-27 2018-09-27
US62/737,829 2018-09-27
US201962788674P 2019-01-04 2019-01-04
US62/788,674 2019-01-04
US201962808700P 2019-02-21 2019-02-21
US62/808,700 2019-02-21

Related Child Applications (10)

Application Number Title Priority Date Filing Date
US17/256,917 A-371-Of-International US11845797B2 (en) 2018-07-03 2019-07-03 Anti-TCR antibody molecules and uses thereof
US17/529,017 Continuation US20220064297A1 (en) 2018-07-03 2021-11-17 Anti-tcr antibody molecules and uses thereof
US17/820,818 Continuation US20230031734A1 (en) 2018-07-03 2022-08-18 Anti-tcr antibody molecules and uses thereof
US17/820,811 Continuation US20230142522A1 (en) 2018-07-03 2022-08-18 Anti-tcr antibody molecules and uses thereof
US17/820,634 Continuation US20230025484A1 (en) 2018-07-03 2022-08-18 Anti-tcr antibody molecules and uses thereof
US17/820,794 Continuation US11965025B2 (en) 2018-07-03 2022-08-18 Method of treating solid cancers with bispecific interleukin-anti-TCRß molecules
US17/820,800 Continuation US20230127740A1 (en) 2018-07-03 2022-08-18 Anti-tcr antibody molecules and uses thereof
US17/820,805 Continuation US12286477B2 (en) 2018-07-03 2022-08-18 Anti-TCR antibody molecules and uses thereof
US17/820,806 Continuation US20230034161A1 (en) 2018-07-03 2022-08-18 Anti-tcr antibody molecules and uses thereof
US18/472,920 Continuation US12351632B2 (en) 2018-07-03 2023-09-22 Anti-TCR antibody molecules and uses thereof

Publications (2)

Publication Number Publication Date
WO2020010250A2 true WO2020010250A2 (en) 2020-01-09
WO2020010250A3 WO2020010250A3 (en) 2020-02-06

Family

ID=67441685

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2019/040592 Ceased WO2020010250A2 (en) 2018-07-03 2019-07-03 Anti-tcr antibody molecules and uses thereof

Country Status (8)

Country Link
US (13) US11845797B2 (https=)
EP (1) EP3818083A2 (https=)
JP (2) JP7554742B2 (https=)
CN (1) CN112955465A (https=)
AU (1) AU2019297451A1 (https=)
CA (1) CA3105448A1 (https=)
DE (1) DE202019005887U1 (https=)
WO (1) WO2020010250A2 (https=)

Cited By (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2020142672A3 (en) * 2019-01-04 2020-08-20 Elstar Therapeutics, Inc. Anti-tcr antibody molecules and uses thereof
WO2020172596A1 (en) * 2019-02-21 2020-08-27 Elstar Therapeutics, Inc. Anti-tcr antibody molecules and thereof
CN112552404A (zh) * 2020-07-20 2021-03-26 北京鼎成肽源生物技术有限公司 一种靶向c-Met的单链抗体、嵌合抗原受体、重组载体、CAR-T细胞及应用
WO2021155112A1 (en) * 2020-01-29 2021-08-05 The Trustees Of The University Of Pennsylvania Compositions and methods of t cell receptor vb family member targeting for the treatment of t cell associated disease
WO2022056199A1 (en) * 2020-09-11 2022-03-17 Janssen Biotech, Inc. Multi-specific immune targeting molecules and uses thereof
WO2022046920A3 (en) * 2020-08-26 2022-04-07 Marengo Therapeutics, Inc. Multifunctional molecules that bind to calreticulin and uses thereof
US20220119479A1 (en) * 2019-01-30 2022-04-21 Immunocore Limited Half-life extended immtac binding cd3 and a hla-a*02 restricted peptide
WO2022119955A1 (en) * 2020-12-01 2022-06-09 The Johns Hopkins University Methods and materials for treating t cell cancers
RU2774031C1 (ru) * 2021-12-02 2022-06-14 Федеральное государственное бюджетное учреждение "Национальный медицинский исследовательский центр радиологии" Министерства здравоохранения Российской Федерации (ФГБУ "НМИЦ радиологии" Минздрава России) Способ подавления индуцирующего действия высокомолекулярной гиалуроновой кислоты на стволовые клетки рака молочной железы
WO2022194042A1 (zh) * 2021-03-15 2022-09-22 成都益安博生物技术有限公司 一种急性髓细胞性白血病的外周血tcr标志物及其检测试剂盒和应用
US20230087378A1 (en) * 2019-12-20 2023-03-23 UCB Biopharma SRL Multi-specific antibody with binding specificity for human il-13 and il-17
US20230102344A1 (en) * 2020-01-03 2023-03-30 Marengo Therapeutics, Inc. Multifunctional molecules that bind to cd33 and uses thereof
US11845797B2 (en) 2018-07-03 2023-12-19 Marengo Therapeutics, Inc. Anti-TCR antibody molecules and uses thereof
US11859009B2 (en) 2021-05-05 2024-01-02 Immatics Biotechnologies Gmbh Antigen binding proteins specifically binding PRAME
WO2023235772A3 (en) * 2022-05-31 2024-01-04 Fred Hutchinson Cancer Center Humanized anti-cd45 antibodies and uses thereof
JP2024515591A (ja) * 2021-04-08 2024-04-10 マレンゴ・セラピューティクス，インコーポレーテッド Ｔｃｒに結合する多機能性分子およびその使用
US11965024B2 (en) 2020-09-11 2024-04-23 Janssen Biotech, Inc. Methods and compositions for modulating beta chain mediated immunity
EP4084823A4 (en) * 2020-01-03 2024-05-15 Marengo Therapeutics, Inc. ANTI-TCR ANTIBODY MOLECULES AND THEIR USES
US12077586B2 (en) 2018-09-19 2024-09-03 LAVA Therapeutics N.V. Bispecific antibodies for use in the treatment of hematological malignancies
US12110328B2 (en) 2015-01-27 2024-10-08 LAVA Therapeutics N.V. Single domain antibodies targeting CD1d
US12152073B2 (en) 2018-03-14 2024-11-26 Marengo Therapeutics, Inc. Multifunctional molecules that bind to calreticulin and uses thereof
WO2024254611A3 (en) * 2023-06-09 2025-03-06 Marengo Therapeutics, Inc. Multispecific molecules binding to tcr and uses thereof
US12247060B2 (en) 2018-01-09 2025-03-11 Marengo Therapeutics, Inc. Calreticulin binding constructs and engineered T cells for the treatment of diseases
US12264197B2 (en) 2019-03-11 2025-04-01 Janssen Biotech, Inc. Anti-Vβ17/anti-CD123 bispecific antibodies
US12312400B2 (en) 2020-02-16 2025-05-27 Aulos Bioscience, Inc. Engineered anti-il-2 antibodies
US12358982B2 (en) 2019-02-21 2025-07-15 Marengo Therapeutics, Inc. Multifunctional molecules that bind to T cell related cancer cells and uses thereof
US12384842B2 (en) 2019-02-21 2025-08-12 Marengo Therapeutics, Inc. Antibody molecules that bind to NKP30 and uses thereof
US12428493B2 (en) 2020-07-08 2025-09-30 LAVA Therapeutics N.V. Antibodies that bind PSMA and gamma-delta T cell receptors
US12448449B2 (en) 2020-09-11 2025-10-21 Janssen Biotech, Inc. Immune targeting molecules and uses thereof
US12492226B2 (en) 2020-08-10 2025-12-09 Janssen Biotech, Inc. Materials and methods for producing bioengineered virus specific lymphocytes
EP4426321A4 (en) * 2021-11-05 2025-12-10 Marengo Therapeutics Inc IMMUNE CELL POPULATIONS AND THEIR USES

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP7590430B2 (ja) * 2019-11-14 2024-11-26 マレンゴ・セラピューティクス，インコーポレーテッド 抗ｔｃｒ抗体分子およびその使用
CN119233999A (zh) * 2022-05-25 2024-12-31 羿尊生物医药（浙江）有限公司 靶向细胞膜受体蛋白的融合蛋白及其应用
AU2023361491A1 (en) * 2022-10-12 2025-05-08 Marengo Therapeutics, Inc. Multifunctional molecules binding to tcr and uses thereof
AU2024240821A1 (en) 2023-03-23 2025-11-06 Bodhi Bio Llc Compositions and methods for antigen-specific therapy
WO2025049771A1 (en) * 2023-08-30 2025-03-06 Marengo Therapeutics, Inc. Multifunctional molecules binding to tcr and uses thereof
WO2025085862A2 (en) * 2023-10-20 2025-04-24 BioNTech SE Multispecific t cell engagers compositions and methods of use thereof
CN117442721B (zh) * 2023-12-20 2024-03-15 苏州艾凯利元生物科技有限公司 一种包括nk细胞和nk细胞接合器分子的组合物
WO2025222063A2 (en) * 2024-04-17 2025-10-23 Marengo Therapeutics, Inc. Multifunctional molecules binding to tcr and uses thereof
WO2025245071A1 (en) * 2024-05-21 2025-11-27 Marengo Therapeutics, Inc. Multifunctional molecules binding to tcr and uses thereof
WO2025247325A1 (en) * 2024-05-30 2025-12-04 Hanx Biopharmaceuticals, (Wuhan) Ltd. Antibody-drug conjugates targeting trbv12 and uses thereof
WO2026019667A1 (en) * 2024-07-17 2026-01-22 Jn Biosciences Llc Trispecific antibodies for activation of immune cells

Citations (220)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US861745A (en) 1906-11-21 1907-07-30 Jefferson D Maxwell Hydraulic dredging apparatus.
EP0125023A1 (en) 1983-04-08 1984-11-14 Genentech, Inc. Recombinant immunoglobulin preparations, methods for their preparation, DNA sequences, expression vectors and recombinant host cells therefor
EP0171496A2 (en) 1984-08-15 1986-02-19 Research Development Corporation of Japan Process for the production of a chimera monoclonal antibody
EP0173494A2 (en) 1984-08-27 1986-03-05 The Board Of Trustees Of The Leland Stanford Junior University Chimeric receptors by DNA splicing and expression
WO1986001533A1 (en) 1984-09-03 1986-03-13 Celltech Limited Production of chimeric antibodies
EP0184187A2 (en) 1984-12-04 1986-06-11 Teijin Limited Mouse-human chimaeric immunoglobulin heavy chain, and chimaeric DNA encoding it
GB2188638A (en) 1986-03-27 1987-10-07 Gregory Paul Winter Chimeric antibodies
WO1990002809A1 (en) 1988-09-02 1990-03-22 Protein Engineering Corporation Generation and selection of recombinant varied binding proteins
EP0368684A1 (en) 1988-11-11 1990-05-16 Medical Research Council Cloning immunoglobulin variable domain sequences.
EP0388151A1 (en) 1989-03-13 1990-09-19 Celltech Limited Modified antibodies
WO1991000906A1 (en) 1989-07-12 1991-01-24 Genetics Institute, Inc. Chimeric and transgenic animals capable of producing human antibodies
WO1991010741A1 (en) 1990-01-12 1991-07-25 Cell Genesys, Inc. Generation of xenogeneic antibodies
WO1991017271A1 (en) 1990-05-01 1991-11-14 Affymax Technologies N.V. Recombinant library screening methods
WO1992001047A1 (en) 1990-07-10 1992-01-23 Cambridge Antibody Technology Limited Methods for producing members of specific binding pairs
WO1992003917A1 (en) 1990-08-29 1992-03-19 Genpharm International Homologous recombination in mammalian cells
WO1992003918A1 (en) 1990-08-29 1992-03-19 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
WO1992009690A2 (en) 1990-12-03 1992-06-11 Genentech, Inc. Enrichment method for variant proteins with altered binding properties
WO1992015679A1 (en) 1991-03-01 1992-09-17 Protein Engineering Corporation Improved epitode displaying phage
WO1992018619A1 (en) 1991-04-10 1992-10-29 The Scripps Research Institute Heterodimeric receptor libraries using phagemids
WO1992020791A1 (en) 1990-07-10 1992-11-26 Cambridge Antibody Technology Limited Methods for producing members of specific binding pairs
EP0519596A1 (en) 1991-05-17 1992-12-23 Merck & Co. Inc. A method for reducing the immunogenicity of antibody variable domains
WO1993001288A1 (de) 1991-07-08 1993-01-21 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Phagemid zum screenen von antikörpern
US5223409A (en) 1988-09-02 1993-06-29 Protein Engineering Corp. Directed evolution of novel binding proteins
US5225539A (en) 1986-03-27 1993-07-06 Medical Research Council Recombinant altered antibodies and methods of making altered antibodies
WO1994004678A1 (en) 1992-08-21 1994-03-03 Casterman Cecile Immunoglobulins devoid of light chains
JPH06153947A (ja) 1992-06-26 1994-06-03 Seikagaku Kogyo Co Ltd コンドロイチナーゼａｂｃ、その製造法及び医薬組成物
EP0616640A1 (en) 1991-12-02 1994-09-28 Medical Research Council Production of anti-self antibodies from antibody segment repertoires and displayed on phage
WO1995009917A1 (en) 1993-10-07 1995-04-13 The Regents Of The University Of California Genetically engineered bispecific tetravalent antibodies
US5585089A (en) 1988-12-28 1996-12-17 Protein Design Labs, Inc. Humanized immunoglobulins
US5624821A (en) 1987-03-18 1997-04-29 Scotgen Biopharmaceuticals Incorporated Antibodies with altered effector functions
US5731116A (en) 1989-05-17 1998-03-24 Dai Nippon Printing Co., Ltd. Electrostatic information recording medium and electrostatic information recording and reproducing method
US5811097A (en) 1995-07-25 1998-09-22 The Regents Of The University Of California Blockade of T lymphocyte down-regulation associated with CTLA-4 signaling
US5831012A (en) 1994-01-14 1998-11-03 Pharmacia & Upjohn Aktiebolag Bacterial receptor structures
WO1998056915A2 (en) 1997-06-12 1998-12-17 Research Corporation Technologies, Inc. Artificial antibody polypeptides
US5861155A (en) 1993-12-08 1999-01-19 Astra Ab Humanized antibodies and uses thereof
WO1999016873A1 (de) 1997-09-26 1999-04-08 Arne Skerra Anticaline
WO1999045110A1 (en) 1998-03-06 1999-09-10 Diatech Pty. Ltd. V-like domain binding molecules
WO2000034784A1 (en) 1998-12-10 2000-06-15 Phylos, Inc. Protein scaffolds for antibody mimics and other binding proteins
WO2000060070A1 (en) 1999-04-01 2000-10-12 Innogenetics N.V. A polypeptide structure for use as a scaffold
US6172197B1 (en) 1991-07-10 2001-01-09 Medical Research Council Methods for producing members of specific binding pairs
WO2001004144A2 (de) 1999-07-13 2001-01-18 Scil Proteins Gmbh Design von beta-faltblatt-proteinen mit spezifischen bindungseigenschaften
WO2001064942A1 (en) 2000-02-29 2001-09-07 Phylos, Inc. Protein scaffolds for antibody mimics and other binding proteins
US6291158B1 (en) 1989-05-16 2001-09-18 Scripps Research Institute Method for tapping the immunological repertoire
US6352694B1 (en) 1994-06-03 2002-03-05 Genetics Institute, Inc. Methods for inducing a population of T cells to proliferate using agents which recognize TCR/CD3 and ligands which stimulate an accessory molecule on the surface of the T cells
WO2003002609A2 (en) 2001-06-28 2003-01-09 Domantis Limited Dual-specific ligand and its use
US6534055B1 (en) 1988-11-23 2003-03-18 Genetics Institute, Inc. Methods for selectively stimulating proliferation of T cells
US6582915B1 (en) 1991-12-02 2003-06-24 Medical Research Council Production of anti-self bodies from antibody segment repertories and displayed on phage
WO2004003019A2 (en) 2002-06-28 2004-01-08 Domantis Limited Immunoglobin single variant antigen-binding domains and dual-specific constructs
US20040009530A1 (en) 2002-01-16 2004-01-15 Wilson David S. Engineered binding proteins
US6696245B2 (en) 1997-10-20 2004-02-24 Domantis Limited Methods for selecting functional polypeptides
WO2004058821A2 (en) 2002-12-27 2004-07-15 Domantis Limited Dual specific single domain antibodies specific for a ligand and for the receptor of the ligand
US6765087B1 (en) 1992-08-21 2004-07-20 Vrije Universiteit Brussel Immunoglobulins devoid of light chains
US20040175756A1 (en) 2001-04-26 2004-09-09 Avidia Research Institute Methods for using combinatorial libraries of monomer domains
WO2004081026A2 (en) 2003-06-30 2004-09-23 Domantis Limited Polypeptides
WO2004101790A1 (en) 2003-05-14 2004-11-25 Domantis Limited A process for recovering polypeptides that unfold reversibly from a polypeptide repertoire
WO2004106368A1 (de) 2003-05-28 2004-12-09 Scil Proteins Gmbh Generierung künstlicher bindungsproteine auf der grundlage von ubiquitin-proteinen
US6838254B1 (en) 1993-04-29 2005-01-04 Conopco, Inc. Production of antibodies or (functionalized) fragments thereof derived from heavy chain immunoglobulins of camelidae
US20050048512A1 (en) 2001-04-26 2005-03-03 Avidia Research Institute Combinatorial libraries of monomer domains
US20050053973A1 (en) 2001-04-26 2005-03-10 Avidia Research Institute Novel proteins with targeted binding
US6905680B2 (en) 1988-11-23 2005-06-14 Genetics Institute, Inc. Methods of treating HIV infected subjects
US20060008844A1 (en) 2004-06-17 2006-01-12 Avidia Research Institute c-Met kinase binding proteins
US7083785B2 (en) 1999-08-17 2006-08-01 Biogen Idcc MA Inc. Methods of treatment by administering an anti-BCMA antibody
WO2006079372A1 (en) 2005-01-31 2006-08-03 Ablynx N.V. Method for generating variable domain sequences of heavy chain antibodies
US7105149B1 (en) 1999-11-29 2006-09-12 The Trustees Of Columbia University In The City Of New York Isolation of five novel genes coding for new Fc receptors-type melanoma involved in the pathogenesis of lymphoma/myeloma
WO2006121168A1 (en) 2005-05-09 2006-11-16 Ono Pharmaceutical Co., Ltd. Human monoclonal antibodies to programmed death 1(pd-1) and methods for treating cancer using anti-pd-1 antibodies alone or in combination with other immunotherapeutics
WO2007005874A2 (en) 2005-07-01 2007-01-11 Medarex, Inc. Human monoclonal antibodies to programmed death ligand 1 (pd-l1)
US7183076B2 (en) 1997-05-02 2007-02-27 Genentech, Inc. Method for making multispecific antibodies having heteromultimeric and common components
WO2007059782A1 (en) 2005-11-28 2007-05-31 Genmab A/S Recombinant monovalent antibodies and methods for production thereof
US7276241B2 (en) 1999-10-06 2007-10-02 Biogen Idec Ma Inc. Methods of treating a tumor that expresses APRIL by administering BCMA
EP1870459A1 (en) 2005-03-31 2007-12-26 Chugai Seiyaku Kabushiki Kaisha Methods for producing polypeptides by regulating polypeptide association
US20080069820A1 (en) 2006-08-30 2008-03-20 Genentech, Inc. Multispecific antibodies
US7431380B1 (en) 2005-02-24 2008-10-07 Theodore Allen Buresh Louver kit
US20080247944A1 (en) 2005-01-12 2008-10-09 Robert Graziano Irta-2 Antibodies and Their Uses
US7476724B2 (en) 2004-08-05 2009-01-13 Genentech, Inc. Humanized anti-cmet antibodies
US7501121B2 (en) 2004-06-17 2009-03-10 Wyeth IL-13 binding agents
WO2009089004A1 (en) 2008-01-07 2009-07-16 Amgen Inc. Method for making antibody fc-heterodimeric molecules using electrostatic steering effects
WO2009101611A1 (en) 2008-02-11 2009-08-20 Curetech Ltd. Monoclonal antibodies for tumor treatment
WO2009114335A2 (en) 2008-03-12 2009-09-17 Merck & Co., Inc. Pd-1 binding proteins
US7642228B2 (en) 1995-03-01 2010-01-05 Genentech, Inc. Method for making heteromultimeric polypeptides
US20100028330A1 (en) 2002-12-23 2010-02-04 Medimmune Limited Methods of upmodulating adaptive immune response using anti-pd1 antibodies
WO2010019570A2 (en) 2008-08-11 2010-02-18 Medarex, Inc. Human antibodies that bind lymphocyte activation gene-3 (lag-3), and uses thereof
WO2010027827A2 (en) 2008-08-25 2010-03-11 Amplimmune, Inc. Targeted costimulatory polypeptides and methods of use to treat cancer
US7741446B2 (en) 2006-08-18 2010-06-22 Armagen Technologies, Inc. Fusion antibodies that cross the blood-brain barrier in both directions
US7750128B2 (en) 2004-09-24 2010-07-06 Amgen Inc. Modified Fc molecules
WO2010077634A1 (en) 2008-12-09 2010-07-08 Genentech, Inc. Anti-pd-l1 antibodies and their use to enhance t-cell function
US7767429B2 (en) 2003-03-05 2010-08-03 Halozyme, Inc. Soluble hyaluronidase glycoprotein (sHASEGP), process for preparing the same, uses and pharmaceutical compositions comprising thereof
US7799902B2 (en) 2004-03-23 2010-09-21 Biogen Idec Ma Inc. Receptor coupling agents and compositions thereof
US20100316645A1 (en) 2009-06-16 2010-12-16 Sabine Imhof-Jung Bispecific Antigen Binding Proteins
US7855275B2 (en) 2004-09-23 2010-12-21 Genentech, Inc. Cysteine engineered antibodies and conjugates
US20110054151A1 (en) 2009-09-02 2011-03-03 Xencor, Inc. Compositions and methods for simultaneous bivalent and monovalent co-engagement of antigens
US7919257B2 (en) 2003-05-30 2011-04-05 Merus Biopharmaceuticals, B.V.I.O. Method for selecting a single cell expressing a heterogeneous combination of antibodies
WO2011066342A2 (en) 2009-11-24 2011-06-03 Amplimmune, Inc. Simultaneous inhibition of pd-l1/pd-l2
US20110177073A1 (en) 2002-07-18 2011-07-21 Merus B.V. Recombinant production of mixtures of antibodies
US20110177093A1 (en) 2002-02-21 2011-07-21 Biogen, Inc. Use of bcma as an immunoregulatory agent
US7999077B2 (en) 2004-09-30 2011-08-16 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services IRTA2 antibodies and methods of use
US8003774B2 (en) 2003-01-09 2011-08-23 Macrogenics, Inc. Identification and engineering of antibodies with variant Fc regions and methods of using same
US20110293613A1 (en) 2010-03-26 2011-12-01 Ulrich Brinkmann Bispecific antibodies
WO2011155607A1 (ja) 2010-06-11 2011-12-15 協和発酵キリン株式会社 抗ｔｉｍ－３抗体
US20120039906A1 (en) 2009-02-09 2012-02-16 INSER (Institut National de la Recherche Medicale) PD-1 Antibodies and PD-L1 Antibodies and Uses Thereof
US20120114649A1 (en) 2008-08-25 2012-05-10 Amplimmune, Inc. Delaware Compositions of pd-1 antagonists and methods of use
US20120149876A1 (en) 2010-11-05 2012-06-14 Zymeworks Inc. Stable Heterodimeric Antibody Design with Mutations in the Fc Domain
US20120184716A1 (en) 2010-08-16 2012-07-19 Novlmmune S.A. Methods for the Generation of Multispecific and Multivalent Antibodies
US8227577B2 (en) 2007-12-21 2012-07-24 Hoffman-La Roche Inc. Bivalent, bispecific antibodies
US20120201746A1 (en) 2010-12-22 2012-08-09 Abbott Laboratories Half immunoglobulin binding proteins and uses thereof
US20120213768A1 (en) 2011-02-19 2012-08-23 Baylor Research Institute Diagnostic and Therapeutic Uses for B Cell Maturation Antigen
US8354509B2 (en) 2007-06-18 2013-01-15 Msd Oss B.V. Antibodies to human programmed death receptor PD-1
US20130017200A1 (en) 2009-12-04 2013-01-17 Genentech, Inc. Multispecific antibodies, antibody analogs, compositions, and methods
US20130022601A1 (en) 2009-04-07 2013-01-24 Ulrich Brinkmann Trivalent, bispecific antibodies
US8362213B2 (en) 2009-04-01 2013-01-29 Genentech, Inc. Anti-FcRH5 antibodies and immunoconjugates and methods of use
US20130078249A1 (en) 2011-08-23 2013-03-28 Oliver Ast Bispecific t cell activating antigen binding molecules
WO2013079174A1 (en) 2011-11-28 2013-06-06 Merck Patent Gmbh Anti-pd-l1 antibodies and uses thereof
US8466260B2 (en) 2009-04-01 2013-06-18 Genentech, Inc. Anti-FcRH5 antibodies and immunoconjugates and methods of use
US20130165638A1 (en) 2011-12-27 2013-06-27 Development Center For Biotechnology Light chain-bridged bispecific antibody
US20130178605A1 (en) 2011-03-25 2013-07-11 Stanislas Blein Hetero-Dimeric Immunoglobulins
US20130195849A1 (en) 2011-11-04 2013-08-01 Zymeworks Inc. Stable Heterodimeric Antibody Design with Mutations in the Fc Domain
US20130243775A1 (en) 2012-03-14 2013-09-19 Regeneron Pharmaceuticals, Inc. Multispecific antigen-binding molecules and uses thereof
US20130266568A1 (en) 2010-08-24 2013-10-10 Roche Glycart Ag Activatable bispecific antibodies
US20130267686A1 (en) 2010-08-24 2013-10-10 Hoffmann-La Roche Inc. Bispecific antibodies comprising a disulfide stabilized - fv fragment
US20130273055A1 (en) 2010-11-16 2013-10-17 Eric Borges Agents and methods for treating diseases that correlate with bcma expression
US8580252B2 (en) 2004-03-05 2013-11-12 Halozyme, Inc. Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminoglycanases
US20130303396A1 (en) 2008-04-11 2013-11-14 Chugai Seiyaku Kabushiki Kaisha Antigen-binding molecule capable of binding to two or more antigen molecules repeatedly
US8586713B2 (en) 2009-06-26 2013-11-19 Regeneron Pharmaceuticals, Inc. Readily isolated bispecific antibodies with native immunoglobulin format
US20130317200A1 (en) 2011-10-19 2013-11-28 Novlmmune S.A. Methods of Purifying Antibodies
US8602269B2 (en) 2009-09-14 2013-12-10 Guala Dispensing S.P.A. Trigger sprayer
WO2014008218A1 (en) 2012-07-02 2014-01-09 Bristol-Myers Squibb Company Optimization of antibodies that bind lymphocyte activation gene-3 (lag-3), and uses thereof
US20140037621A1 (en) 2012-08-02 2014-02-06 Jn Biosciences Llc Antibodies or fusion proteins multimerized via cysteine mutation and a mu tailpiece
US20140051833A1 (en) 2012-03-13 2014-02-20 Novlmmune S.A. Readily Isolated Bispecific Antibodies with Native Immunoglobulin Format
US20140051835A1 (en) 2012-06-25 2014-02-20 Zymeworks Inc. Process and Methods for Efficient Manufacturing of Highly Pure Asymmetric Antibodies in Mammalian Cells
EP2699259A1 (en) 2011-04-21 2014-02-26 Boehringer Ingelheim International GmbH Bcma-based stratification and therapy for multiple myeloma patients
US20140072581A1 (en) 2012-07-23 2014-03-13 Zymeworks Inc. Immunoglobulin Constructs Comprising Selective Pairing of the Light and Heavy Chains
US20140079689A1 (en) 2011-02-04 2014-03-20 Genentech, Inc. Fc VARIANTS AND METHODS FOR THEIR PRODUCTION
US8703132B2 (en) 2009-06-18 2014-04-22 Hoffmann-La Roche, Inc. Bispecific, tetravalent antigen binding proteins
US20140154254A1 (en) 2012-11-21 2014-06-05 Amgen Inc. Heterodimeric immunoglobulins
US20140199294A1 (en) 2011-06-30 2014-07-17 Chugai Seiyaku Kabushiki Kaisha Heterodimerized polypeptide
US20140200331A1 (en) 2012-11-28 2014-07-17 Zymeworks Inc. Engineered Immunoglobulin Heavy Chain-Light Chain Pairs And Uses Thereof
US20140242077A1 (en) 2013-01-23 2014-08-28 Abbvie, Inc. Methods and compositions for modulating an immune response
US20140242075A1 (en) 2011-05-30 2014-08-28 Genmab B.V. Antibody variants and uses thereof
US8821883B2 (en) 2003-03-28 2014-09-02 Biogen Idec Ma Inc. Method of treating B cell cancers by administering truncated BAFF receptors
US8846042B2 (en) 2011-05-16 2014-09-30 Fabion Pharmaceuticals, Inc. Multi-specific FAB fusion proteins and methods of use
US20140308285A1 (en) 2013-03-15 2014-10-16 Amgen Inc. Heterodimeric bispecific antibodies
US8871912B2 (en) 2006-03-24 2014-10-28 Merck Patent Gmbh Engineered heterodimeric protein domains
US20140322221A1 (en) 2000-04-11 2014-10-30 Genentech, Inc. Multivalent antibodies and uses therefor
US20140348839A1 (en) 2011-12-20 2014-11-27 Medimmune, Llc Modified polypeptides for bispecific antibody scaffolds
US20140363426A1 (en) 2013-03-15 2014-12-11 Gregory Moore Heterodimeric proteins
US20140377269A1 (en) 2012-12-19 2014-12-25 Adimab, Llc Multivalent antibody analogs, and methods of their preparation and use
US8920776B2 (en) 2002-01-22 2014-12-30 Corixa Corporation Compositions and methods for the detection diagnosis and therapy of hematological malignancies
US20150018529A1 (en) 2012-02-22 2015-01-15 Ucb Pharma S.A. Sequence Symmetric Modified IgG4 Bispecific Antibodies
US20150017187A1 (en) 2013-07-10 2015-01-15 Sutro Biopharma, Inc. Antibodies comprising multiple site-specific non-natural amino acid residues, methods of their preparation and methods of their use
EP2847231A1 (en) 2012-05-10 2015-03-18 Bioatla LLC Multi-specific monoclonal antibodies
US9000130B2 (en) 2010-06-08 2015-04-07 Genentech, Inc. Cysteine engineered antibodies and conjugates
US20150098900A1 (en) 2013-06-24 2015-04-09 Genentech, Inc. Anti-fcrh5 antibodies
US20150133638A1 (en) 2012-02-10 2015-05-14 Genentech, Inc. Single-chain antibodies and other heteromultimers
US9034324B2 (en) 2009-03-10 2015-05-19 Biogen Idec Ma Inc. Anti-BCMA antibodies
US20150166670A1 (en) 2012-05-24 2015-06-18 Hoffmann-La Roche Inc. Multispecific antibodies
US20150166661A1 (en) 2013-12-17 2015-06-18 Genentech, Inc. Anti-cd3 antibodies and methods of use
US20150175707A1 (en) 2012-07-06 2015-06-25 Genmab B.V. Dimeric protein with triple mutations
US20150203591A1 (en) 2012-08-02 2015-07-23 Regeneron Pharmaceuticals, Inc. Mutivalent antigen-binding proteins
WO2015107026A1 (en) 2014-01-15 2015-07-23 F. Hoffmann-La Roche Ag Fc-region variants with modified fcrn- and maintained protein a-binding properties
WO2015107015A1 (en) 2014-01-15 2015-07-23 F. Hoffmann-La Roche Ag Fc-region variants with improved protein a-binding
WO2015107025A1 (en) 2014-01-15 2015-07-23 F. Hoffmann-La Roche Ag Fc-region variants with modified fcrn-binding properties
US20150211001A1 (en) 2012-10-03 2015-07-30 Jason Baardsnes Methods of quantitating heavy and light chain polypeptide pairs
US20150232560A1 (en) 2012-06-27 2015-08-20 Hoffmann-La Roche Inc. Method for the selection and production of tailor-made, selective and multi-specific therapeutic molecules comprising at least two different targeting entities and uses thereof
WO2015127158A1 (en) 2014-02-21 2015-08-27 Regeneron Pharmaceuticals, Inc. Methods, compositions and kits for cell specific modulation of target antigens
US9145588B2 (en) 2011-09-26 2015-09-29 Merus Biopharmaceuticals B.V. Generation of binding molecules
US20150315296A1 (en) 2014-04-02 2015-11-05 Hoffmann-La Roche Inc. Multispecific antibodies
US9200060B2 (en) 2009-11-23 2015-12-01 Amgen Inc. Monomeric antibody Fc
WO2015181805A1 (en) 2014-05-28 2015-12-03 Zymeworks Inc. Modified antigen binding polypeptide constructs and uses thereof
US20150344570A1 (en) 2012-12-27 2015-12-03 Chugai Seiyaku Kabushiki Kaisha Heterodimerized polypeptide
US20150353636A1 (en) 2013-01-10 2015-12-10 Genmab B.V. Human igg1 fc region variants and uses thereof
US20150368352A1 (en) 2013-02-08 2015-12-24 Stemcentrx, Inc. Novel multispecific constructs
US20150368351A1 (en) 2013-02-05 2015-12-24 Engmab Ag Method for the selection of antibodies against bcma
WO2015197582A1 (en) 2014-06-27 2015-12-30 Innate Pharma Monomeric multispecific antigen binding proteins
WO2015197598A2 (en) 2014-06-27 2015-12-30 Innate Pharma Multispecific antigen binding proteins
US20160015749A1 (en) 2013-03-05 2016-01-21 Baylor College Of Medicine Engager cells for immunotherapy
US9243058B2 (en) 2012-12-07 2016-01-26 Amgen, Inc. BCMA antigen binding proteins
WO2016016299A1 (en) 2014-07-29 2016-02-04 F. Hoffmann-La Roche Ag Multispecific antibodies
EP2982694A1 (en) 2014-08-04 2016-02-10 EngMab AG Bispecific antibodies against cd3epsilon and bcma
US20160039947A1 (en) 2013-03-15 2016-02-11 Eli Lilly And Company Methods for producing fabs and bi-specific antibodies
WO2016026943A1 (en) 2014-08-20 2016-02-25 Argen-X N.V Asymmetric multispecific antibodies
US20160075785A1 (en) 2014-08-04 2016-03-17 Hoffmann-La Roche Inc. Bispecific t cell activating antigen binding molecules
US9309311B2 (en) 2009-04-27 2016-04-12 Oncomed Pharmaceuticals, Inc. Method for making Heteromultimeric molecules
US20160102135A1 (en) 2013-05-31 2016-04-14 Zymeworks Inc. Heteromultimers with reduced or silenced effector function
US20160114057A1 (en) 2013-05-24 2016-04-28 Zyeworks Inc. Modular protein drug conjugate therapeutic
US20160130347A1 (en) 2012-10-08 2016-05-12 Roche Glycart Ag Fc-free antibodies comprising two Fab-fragments and methods of use
WO2016071376A2 (en) 2014-11-06 2016-05-12 F. Hoffmann-La Roche Ag Fc-region variants with modified fcrn-binding and methods of use
US20160131654A1 (en) 2013-02-08 2016-05-12 Institute For Myeloma & Bone Cancer Research Diagnostic, prognostic, and monitoring methods for multiple myeloma, chronic lymphocytic leukemia, and b-cell non-hodgkin lymphoma
WO2016071377A1 (en) 2014-11-06 2016-05-12 F. Hoffmann-La Roche Ag Fc-region variants with modified fcrn- and protein a-binding properties
US9340621B2 (en) 2011-11-15 2016-05-17 Boehringer Ingelheim International Gmbh Binding molecules for BCMA and CD3
EP3023437A1 (en) 2014-11-20 2016-05-25 EngMab AG Bispecific antibodies against CD3epsilon and BCMA
WO2016079081A1 (en) 2014-11-20 2016-05-26 F. Hoffmann-La Roche Ag Common light chains and methods of use
US20160145340A1 (en) 2013-03-15 2016-05-26 Amegen Inc. Bispecific-fc molecules
US9359437B2 (en) 2013-02-01 2016-06-07 Regeneron Pharmaceuticals, Inc. Antibodies comprising chimeric constant domains
US9358286B2 (en) 2012-04-20 2016-06-07 Merus B.V. Methods and means for the production of IG-like molecules
EP3029068A1 (en) 2014-12-03 2016-06-08 EngMab AG Bispecific antibodies against CD3epsilon and BCMA for use in the treatment of diseases
WO2016090327A2 (en) 2014-12-05 2016-06-09 Memorial Sloan-Kettering Cancer Center Antibodies targeting b-cell maturation antigen and methods of use
WO2016087416A1 (en) 2014-12-03 2016-06-09 F. Hoffmann-La Roche Ag Multispecific antibodies
WO2016087650A1 (en) 2014-12-05 2016-06-09 Merck Patent Gmbh Domain-exchanged antibody
US20160176973A1 (en) 2013-03-15 2016-06-23 Amgen Research (Munich) Gmbh Binding molecules for bcma and cd3
US9382323B2 (en) 2009-04-02 2016-07-05 Roche Glycart Ag Multispecific antibodies comprising full length antibodies and single chain fab fragments
US20160194389A1 (en) 2013-04-29 2016-07-07 Hoffmann-La Roche Inc. Fc-receptor binding modified asymmetric antibodies and methods of use
US9387237B2 (en) 2003-10-20 2016-07-12 Biogen Ma Inc. Methods of treating a patient having an autoimmune disorder by administering a soluble BCMA
WO2016110584A1 (en) 2015-01-08 2016-07-14 Biontech Ag Agonistic tnf receptor binding agents
WO2016115274A1 (en) 2015-01-14 2016-07-21 Compass Therapeutics Llc Multispecific immunomodulatory antigen-binding constructs
WO2016118641A1 (en) 2015-01-20 2016-07-28 Igm Biosciences, Inc. Tumor necrosis factor (tnf) superfamily receptor binding molecules and uses thereof
US20160229915A1 (en) 2013-09-27 2016-08-11 Chugai Seiyaku Kabushiki Kaisha Method for producing polypeptide heteromultimer
EP3055329A1 (en) 2013-10-11 2016-08-17 F. Hoffmann-La Roche AG Multispecific domain exchanged common variable light chain antibodies
US20160257763A1 (en) 2012-05-10 2016-09-08 Zymeworks Inc. Heteromultimer constructs of immunoglobulin heavy chains with mutations in the fc domain
US20160264685A1 (en) 2015-03-13 2016-09-15 Novimmune Sa Methods of purifying bispecific antibodies
US20160297885A1 (en) 2015-04-13 2016-10-13 Pfizer Inc. Therapeutic antibodies and their uses
WO2016168149A1 (en) 2015-04-13 2016-10-20 Five Prime Therapeutics, Inc. Combination therapy for cancer
US20160311915A1 (en) 2013-10-10 2016-10-27 Ucl Business Plc Molecule
US20160368988A1 (en) 2015-07-10 2016-12-22 Merus N.V. Human cd3 binding antibody
US20160368985A1 (en) 2015-06-16 2016-12-22 Genentech, Inc. HUMANIZED AND AFFINITY MATURED ANTIBODIES TO FcRH5 AND METHODS OF USE
US9545086B2 (en) 1999-01-25 2017-01-17 Biogen Ma Inc. BAFF, inhibitors thereof and their use in the modulation of B-cell response and treatment of autoimmune disorders
US20170022284A1 (en) 2015-07-23 2017-01-26 Inhibrx Lp Multivalent and multispecific gitr-binding fusion proteins
US20170037128A1 (en) 2014-04-13 2017-02-09 Affimed Gmbh Trifunctional antigen-binding molecule
WO2017021450A1 (en) 2015-08-03 2017-02-09 Engmab Ag Monoclonal antibodies against bcma
US20170051068A1 (en) 2015-08-17 2017-02-23 Janssen Pharmaceutica Nv Anti-BCMA Antibodies, Bispecific Antigen Binding Molecules that Bind BCMA and CD3, and Uses Thereof
EP3137500A1 (en) 2014-04-30 2017-03-08 Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft Humanized antibodies against cd269 (bcma)
WO2018057955A1 (en) 2016-09-23 2018-03-29 Elstar Therapeutics, Inc. Multispecific antibody molecules comprising lambda and kappa light chains

Family Cites Families (437)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4475196A (en) 1981-03-06 1984-10-02 Zor Clair G Instrument for locating faults in aircraft passenger reading light and attendant call control system
US4447233A (en) 1981-04-10 1984-05-08 Parker-Hannifin Corporation Medication infusion pump
US4433059A (en) 1981-09-08 1984-02-21 Ortho Diagnostic Systems Inc. Double antibody conjugate
US4444878A (en) 1981-12-21 1984-04-24 Boston Biomedical Research Institute, Inc. Bispecific antibody determinants
US4439196A (en) 1982-03-18 1984-03-27 Merck & Co., Inc. Osmotic drug delivery system
US4522811A (en) 1982-07-08 1985-06-11 Syntex (U.S.A.) Inc. Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides
US4447224A (en) 1982-09-20 1984-05-08 Infusaid Corporation Variable flow implantable infusion apparatus
US4487603A (en) 1982-11-26 1984-12-11 Cordis Corporation Implantable microinfusion pump system
US4486194A (en) 1983-06-08 1984-12-04 James Ferrara Therapeutic device for administering medicaments through the skin
WO1985000817A1 (en) 1983-08-10 1985-02-28 Amgen Microbial expression of interleukin ii
JPH0334065Y2 (https=) 1984-09-13 1991-07-18
US4596556A (en) 1985-03-25 1986-06-24 Bioject, Inc. Hypodermic injection apparatus
US4737456A (en) 1985-05-09 1988-04-12 Syntex (U.S.A.) Inc. Reducing interference in ligand-receptor binding assays
US5374548A (en) 1986-05-02 1994-12-20 Genentech, Inc. Methods and compositions for the attachment of proteins to liposomes using a glycophospholipid anchor
MX9203291A (es) 1985-06-26 1992-08-01 Liposome Co Inc Metodo para acoplamiento de liposomas.
US4676980A (en) 1985-09-23 1987-06-30 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Target specific cross-linked heteroantibodies
JPS63501765A (ja) 1985-11-01 1988-07-21 インタ−ナショナル、ジェネティック、エンジニアリング　インコ−ポレ−テッド 抗体遺伝子のモジュ−ル組立体、それにより産生された抗体及び用途
US6548640B1 (en) 1986-03-27 2003-04-15 Btg International Limited Altered antibodies
US5869620A (en) 1986-09-02 1999-02-09 Enzon, Inc. Multivalent antigen-binding proteins
IL85035A0 (en) 1987-01-08 1988-06-30 Int Genetic Eng Polynucleotide molecule,a chimeric antibody with specificity for human b cell surface antigen,a process for the preparation and methods utilizing the same
US4941880A (en) 1987-06-19 1990-07-17 Bioject, Inc. Pre-filled ampule and non-invasive hypodermic injection device assembly
US4790824A (en) 1987-06-19 1988-12-13 Bioject, Inc. Non-invasive hypodermic injection device
US5606040A (en) 1987-10-30 1997-02-25 American Cyanamid Company Antitumor and antibacterial substituted disulfide derivatives prepared from compounds possessing a methyl-trithio group
US5770701A (en) 1987-10-30 1998-06-23 American Cyanamid Company Process for preparing targeted forms of methyltrithio antitumor agents
US5057423A (en) 1987-12-18 1991-10-15 University Of Pittsburgh Method for the preparation of pure LAK-active lymphocytes
JPH021556A (ja) 1988-06-09 1990-01-05 Snow Brand Milk Prod Co Ltd ハイブリッド抗体及びその作製方法
US5766947A (en) 1988-12-14 1998-06-16 Astra Ab Monoclonal antibodies reactive with an epitope of a Vβ3.1 variable region of a T cell receptor
US5116615A (en) 1989-01-27 1992-05-26 Immunolytics, Inc. Method for treating benign prostatic hypertrophy
US5108921A (en) 1989-04-03 1992-04-28 Purdue Research Foundation Method for enhanced transmembrane transport of exogenous molecules
CA2018248A1 (en) 1989-06-07 1990-12-07 Clyde W. Shearman Monoclonal antibodies against the human alpha/beta t-cell receptor, their production and use
DE3920358A1 (de) 1989-06-22 1991-01-17 Behringwerke Ag Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung
AU6290090A (en) 1989-08-29 1991-04-08 University Of Southampton Bi-or trispecific (fab)3 or (fab)4 conjugates
US5208020A (en) 1989-10-25 1993-05-04 Immunogen Inc. Cytotoxic agents comprising maytansinoids and their therapeutic use
CA2026147C (en) 1989-10-25 2006-02-07 Ravi J. Chari Cytotoxic agents comprising maytansinoids and their therapeutic use
US5959177A (en) 1989-10-27 1999-09-28 The Scripps Research Institute Transgenic plants expressing assembled secretory antibodies
US5312335A (en) 1989-11-09 1994-05-17 Bioject Inc. Needleless hypodermic injection device
US5064413A (en) 1989-11-09 1991-11-12 Bioject, Inc. Needleless hypodermic injection device
US6075181A (en) 1990-01-12 2000-06-13 Abgenix, Inc. Human antibodies derived from immunized xenomice
US6150584A (en) 1990-01-12 2000-11-21 Abgenix, Inc. Human antibodies derived from immunized xenomice
US5273743A (en) 1990-03-09 1993-12-28 Hybritech Incorporated Trifunctional antibody-like compounds as a combined diagnostic and therapeutic agent
GB9012995D0 (en) 1990-06-11 1990-08-01 Celltech Ltd Multivalent antigen-binding proteins
US5770429A (en) 1990-08-29 1998-06-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
GB9022788D0 (en) 1990-10-19 1990-12-05 Cortecs Ltd Pharmaceutical formulations
US5582996A (en) 1990-12-04 1996-12-10 The Wistar Institute Of Anatomy & Biology Bifunctional antibodies and method of preparing same
US5571894A (en) 1991-02-05 1996-11-05 Ciba-Geigy Corporation Recombinant antibodies specific for a growth factor receptor
DE4118120A1 (de) 1991-06-03 1992-12-10 Behringwerke Ag Tetravalente bispezifische rezeptoren, ihre herstellung und verwendung
US6511663B1 (en) 1991-06-11 2003-01-28 Celltech R&D Limited Tri- and tetra-valent monospecific antigen-binding proteins
EP1400536A1 (en) 1991-06-14 2004-03-24 Genentech Inc. Method for making humanized antibodies
US5637481A (en) 1993-02-01 1997-06-10 Bristol-Myers Squibb Company Expression vectors encoding bispecific fusion proteins and methods of producing biologically active bispecific fusion proteins in a mammalian cell
GB9114948D0 (en) 1991-07-11 1991-08-28 Pfizer Ltd Process for preparing sertraline intermediates
US5747036A (en) 1991-08-28 1998-05-05 Brigham & Women's Hospital Methods and compositions for detecting and treating a subset of human patients having an autoimmune disease
WO1993006217A1 (en) 1991-09-19 1993-04-01 Genentech, Inc. EXPRESSION IN E. COLI OF ANTIBODY FRAGMENTS HAVING AT LEAST A CYSTEINE PRESENT AS A FREE THIOL, USE FOR THE PRODUCTION OF BIFUNCTIONAL F(ab')2 ANTIBODIES
FI941572L (fi) 1991-10-07 1994-05-27 Oncologix Inc Anti-erbB-2-monoklonaalisten vasta-aineiden yhdistelmä ja käyttömenetelmä
WO1993008829A1 (en) 1991-11-04 1993-05-13 The Regents Of The University Of California Compositions that mediate killing of hiv-infected cells
DE69232137T2 (de) 1991-11-25 2002-05-29 Enzon Inc Multivalente antigen-bindende proteine
US5932448A (en) 1991-11-29 1999-08-03 Protein Design Labs., Inc. Bispecific antibody heterodimers
GB9125768D0 (en) 1991-12-04 1992-02-05 Hale Geoffrey Therapeutic method
HU215180B (hu) 1992-01-23 1998-10-28 Merck Patent Gmbh. Eljárás monomer és dimer antitest-fragment fúziós fehérjék előállítására
AU675929B2 (en) 1992-02-06 1997-02-27 Curis, Inc. Biosynthetic binding protein for cancer marker
AU675223B2 (en) 1992-05-08 1997-01-30 Creative Biomolecules, Inc. Chimeric multivalent protein analogues and methods of use thereof
US5383851A (en) 1992-07-24 1995-01-24 Bioject Inc. Needleless hypodermic injection device
US6005079A (en) 1992-08-21 1999-12-21 Vrije Universiteit Brussels Immunoglobulins devoid of light chains
EP0669987B1 (en) 1992-09-25 2008-08-13 Aventis Pharma S.A. Adenovirus vectors for the transfer of foreign genes into cells of the central nervous system, particularly in brain
SG41929A1 (en) 1992-09-25 1997-08-15 Commw Scient Ind Res Org Target binding polypeptide
GB9221657D0 (en) 1992-10-15 1992-11-25 Scotgen Ltd Recombinant bispecific antibodies
US5837821A (en) 1992-11-04 1998-11-17 City Of Hope Antibody construct
MD1367C2 (ro) 1992-11-13 2000-11-30 Idec Pharmaceuticals Corporation Metode de tratament al limfomului celulelor B, anticorpi anti-CD20, hibridom.
GB9323648D0 (en) 1992-11-23 1994-01-05 Zeneca Ltd Proteins
US5635483A (en) 1992-12-03 1997-06-03 Arizona Board Of Regents Acting On Behalf Of Arizona State University Tumor inhibiting tetrapeptide bearing modified phenethyl amides
ATE199392T1 (de) 1992-12-04 2001-03-15 Medical Res Council Multivalente und multispezifische bindungsproteine, deren herstellung und verwendung
US5780588A (en) 1993-01-26 1998-07-14 Arizona Board Of Regents Elucidation and synthesis of selected pentapeptides
JPH0787994A (ja) 1993-04-30 1995-04-04 Sumitomo Electric Ind Ltd Ｔ細胞抗原受容体Ｖβ２２に対するモノクローナル抗体及びその製造方法
AU691811B2 (en) 1993-06-16 1998-05-28 Celltech Therapeutics Limited Antibodies
US6476198B1 (en) 1993-07-13 2002-11-05 The Scripps Research Institute Multispecific and multivalent antigen-binding polypeptide molecules
DE69420024T2 (de) 1993-08-10 2000-02-24 W.L. Gore & Associates, Inc. Zelleinkapselungsvorrichtung
US5635602A (en) 1993-08-13 1997-06-03 The Regents Of The University Of California Design and synthesis of bispecific DNA-antibody conjugates
US5773001A (en) 1994-06-03 1998-06-30 American Cyanamid Company Conjugates of methyltrithio antitumor agents and intermediates for their synthesis
US5968753A (en) 1994-06-14 1999-10-19 Nexell Therapeutics, Inc. Positive and positive/negative cell selection mediated by peptide release
JP3659261B2 (ja) 1994-10-20 2005-06-15 モルフォシス・アクチェンゲゼルシャフト 組換体タンパク質の多機能性複合体への標的化ヘテロ結合
US5789199A (en) 1994-11-03 1998-08-04 Genentech, Inc. Process for bacterial production of polypeptides
FR2727867B1 (fr) 1994-12-13 1997-01-31 Rhone Poulenc Rorer Sa Transfert de genes dans les motoneurones medullaires au moyen de vecteurs adenoviraux
AU712441B2 (en) 1994-12-14 1999-11-04 Scripps Research Institute, The In vivo activation of tumor-specific cytotoxic T cells
US5840523A (en) 1995-03-01 1998-11-24 Genetech, Inc. Methods and compositions for secretion of heterologous polypeptides
US5641870A (en) 1995-04-20 1997-06-24 Genentech, Inc. Low pH hydrophobic interaction chromatography for antibody purification
US5869046A (en) 1995-04-14 1999-02-09 Genentech, Inc. Altered polypeptides with increased half-life
CA2222055A1 (en) 1995-05-23 1996-11-28 Morphosys Gesellschaft Fur Proteinoptimierung Mbh Multimeric proteins
WO1996039993A1 (en) 1995-06-07 1996-12-19 Gore Hybrid Technologies, Inc. An implantable containment apparatus for a therapeutical device and method for loading and reloading the device therein
US5712374A (en) 1995-06-07 1998-01-27 American Cyanamid Company Method for the preparation of substantiallly monomeric calicheamicin derivative/carrier conjugates
US5714586A (en) 1995-06-07 1998-02-03 American Cyanamid Company Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates
US5626561A (en) 1995-06-07 1997-05-06 Gore Hybrid Technologies, Inc. Implantable containment apparatus for a therapeutical device and method for loading and reloading the device therein
US6267958B1 (en) 1995-07-27 2001-07-31 Genentech, Inc. Protein formulation
AU6854696A (en) 1995-09-22 1997-04-09 Gore Hybrid Technologies, Inc. Improved cell encapsulation device
US5989830A (en) 1995-10-16 1999-11-23 Unilever Patent Holdings Bv Bifunctional or bivalent antibody fragment analogue
GB9603256D0 (en) 1996-02-16 1996-04-17 Wellcome Found Antibodies
US5849589A (en) 1996-03-11 1998-12-15 Duke University Culturing monocytes with IL-4, TNF-α and GM-CSF TO induce differentiation to dendric cells
ES2225961T3 (es) 1996-04-04 2005-03-16 Unilever N.V. Proteina de union a antigeno multivalente y multiespecifica.
WO1998014206A1 (en) 1996-10-04 1998-04-09 Thomas Jefferson University T cells mediating an immune response and methods of use
EP0981548A4 (en) 1997-04-30 2005-11-23 Enzon Inc GLYCOSYLATABLE SINGLE CHAIN ANTIGEN-BINDING PROTEINS, MANUFACTURE AND USE THEREOF
US20030207346A1 (en) 1997-05-02 2003-11-06 William R. Arathoon Method for making multispecific antibodies having heteromultimeric and common components
AU736707B2 (en) 1997-06-11 2001-08-02 Anaphore, Inc. Trimerising module
US6171586B1 (en) 1997-06-13 2001-01-09 Genentech, Inc. Antibody formulation
ATE296315T1 (de) 1997-06-24 2005-06-15 Genentech Inc Galactosylierte glykoproteine enthaltende zusammensetzungen und verfahren zur deren herstellung
DE69837706T2 (de) 1997-07-21 2008-01-10 Active Biotech Ab Zytolyse der geeigneten zielzellen mit superantigen konjugate mittels der induktion von t-zell aktivierung
US6040498A (en) 1998-08-11 2000-03-21 North Caroline State University Genetically engineered duckweed
BR9813276A (pt) 1997-10-27 2000-08-22 Unilever Nv Proteìna multivalente de ligação de antìgeno, sequências de nucleotìdeos, vetor de expressão, célula hospedeira, processo para preparação de proteìna multivalente de ligação de antìgeno, e, uso da mesma
WO1999022764A1 (en) 1997-10-31 1999-05-14 Genentech, Inc. Methods and compositions comprising glycoprotein glycoforms
US6610833B1 (en) 1997-11-24 2003-08-26 The Institute For Human Genetics And Biochemistry Monoclonal human natural antibodies
ES2375931T3 (es) 1997-12-05 2012-03-07 The Scripps Research Institute Humanización de anticuerpo murino.
ES2234241T3 (es) 1998-01-23 2005-06-16 Vlaams Interuniversitair Instituut Voor Biotechnologie Derivados de anticuerpo de multiples fines.
US6194551B1 (en) 1998-04-02 2001-02-27 Genentech, Inc. Polypeptide variants
ES2292236T3 (es) 1998-04-02 2008-03-01 Genentech, Inc. Variantes de anticuerpos y sus fragmentos.
HUP9900956A2 (hu) 1998-04-09 2002-04-29 Aventis Pharma Deutschland Gmbh. Egyláncú, több antigéntkötőhely kialakítására képes molekulák, előállításuk és alkalmazásuk
ES2434961T5 (es) 1998-04-20 2018-01-18 Roche Glycart Ag Ingeniería de glicosilación de anticuerpos para mejorar la citotoxicidad celular dependiente del anticuerpo
DE19819846B4 (de) 1998-05-05 2016-11-24 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Multivalente Antikörper-Konstrukte
GB9812545D0 (en) 1998-06-10 1998-08-05 Celltech Therapeutics Ltd Biological products
EP1100830B1 (en) 1998-07-28 2003-10-01 Micromet AG Heterominibodies
US6333396B1 (en) 1998-10-20 2001-12-25 Enzon, Inc. Method for targeted delivery of nucleic acids
US6737056B1 (en) 1999-01-15 2004-05-18 Genentech, Inc. Polypeptide variants with altered effector function
HU230769B1 (hu) 1999-01-15 2018-03-28 Genentech Inc. Módosított effektor-funkciójú polipeptid-változatok
EP1176195B1 (en) 1999-04-09 2013-05-22 Kyowa Hakko Kirin Co., Ltd. Method for controlling the activity of immunologically functional molecule
US7527787B2 (en) 2005-10-19 2009-05-05 Ibc Pharmaceuticals, Inc. Multivalent immunoglobulin-based bioactive assemblies
US7534866B2 (en) 2005-10-19 2009-05-19 Ibc Pharmaceuticals, Inc. Methods and compositions for generating bioactive assemblies of increased complexity and uses
US7125978B1 (en) 1999-10-04 2006-10-24 Medicago Inc. Promoter for regulating expression of foreign genes
CN100427603C (zh) 1999-10-04 2008-10-22 麦迪卡格公司 调控外源基因转录的方法
CA2388245C (en) 1999-10-19 2012-01-10 Kyowa Kirin Co., Ltd. The use of serum-free adapted rat cells for producing heterologous polypeptides
ATE423848T1 (de) 1999-11-15 2009-03-15 Innate Pharma Auslösender rezeptor der an der natürlichen cytotoxizität der menschlichen natürlichen killerzellen (natural killer cells) beteiligt ist und antikörper die diesen rezeptor identifizieren
US6979546B2 (en) 1999-11-15 2005-12-27 Universita Di Genova Triggering receptor involved in natural cytotoxicity mediated by human natural killer cells and antibodies that identify the same
AU784983B2 (en) 1999-12-15 2006-08-17 Genentech Inc. Shotgun scanning, a combinatorial method for mapping functional protein epitopes
ATE344801T1 (de) 1999-12-29 2006-11-15 Immunogen Inc Doxorubicin- und daunorubicin-enthaltende, zytotoxische mittel und deren therapeutische anwendung
AU2001227966A1 (en) 2000-01-20 2001-07-31 Chiron Corporation Methods for treating tumors
EP1299419A2 (en) 2000-05-24 2003-04-09 Imclone Systems, Inc. Bispecific immunoglobulin-like antigen binding proteins and method of production
DK2336187T3 (en) 2000-06-19 2016-08-22 Beth Israel Deaconess Medical Ct Inc Compositions and Methods of monoclonal and polyclonal antibodies which are specific for T-cell subpopulations
CA2410551A1 (en) 2000-06-30 2002-01-10 Vlaams Interuniversitair Instituut Voor Biotechnologie Vzw (Vib) Heterodimeric fusion proteins
IL137419A0 (en) 2000-07-20 2001-07-24 Yissum Res Dev Co Nk cells activating receptors and their therapeutic and diagnostic uses
JP2004523205A (ja) 2000-07-25 2004-08-05 イムノメディクス， インコーポレイテッド 多価標的結合タンパク質
US6946292B2 (en) 2000-10-06 2005-09-20 Kyowa Hakko Kogyo Co., Ltd. Cells producing antibody compositions with increased antibody dependent cytotoxic activity
ES2639222T5 (es) 2000-10-06 2023-11-24 Kyowa Kirin Co Ltd Células que producen unas composiciones de anticuerpo
US7064191B2 (en) 2000-10-06 2006-06-20 Kyowa Hakko Kogyo Co., Ltd. Process for purifying antibody
EP2351838A1 (en) 2000-10-20 2011-08-03 Chugai Seiyaku Kabushiki Kaisha Crosslinking agonistic antibodies
US6596541B2 (en) 2000-10-31 2003-07-22 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
CN1487996B (zh) 2000-11-30 2010-06-16 米德列斯公司 用于生产人类抗体的转基因转染色体啮齿动物
US7829084B2 (en) 2001-01-17 2010-11-09 Trubion Pharmaceuticals, Inc. Binding constructs and methods for use thereof
ES2365602T3 (es) 2001-03-05 2011-10-07 Yissum Research Development Company Of The Hebrew University Of Jerusalem Proteínas oligoméricas tipo chaperona, estables a desnaturalizantes y/o resistentes a proteasa, polinucleótidos que codifican las mismas y sus usos.
WO2002072635A2 (en) 2001-03-13 2002-09-19 University College London Specific binding members
ES2437875T3 (es) 2001-04-30 2014-01-14 Eli Lilly And Company Anticuerpos humanizados que reconocen el péptido beta-amiloide
US6833441B2 (en) 2001-08-01 2004-12-21 Abmaxis, Inc. Compositions and methods for generating chimeric heteromultimers
EP2180044A1 (en) 2001-08-03 2010-04-28 GlycArt Biotechnology AG Antibody glycosylation variants having increased anti-body-dependent cellular cytotoxicity
CA2763913C (en) 2001-08-10 2014-10-28 Aberdeen University Antigen binding domains
DE60124912T2 (de) 2001-09-14 2007-06-14 Affimed Therapeutics Ag Multimerische, einzelkettige, Tandem-Fv-Antikörper
HUP0600342A3 (en) 2001-10-25 2011-03-28 Genentech Inc Glycoprotein compositions
PT1454138E (pt) 2001-12-04 2012-03-28 Merck Patent Gmbh Imunocitoquinas com seletividade modulada
US20030211078A1 (en) 2001-12-07 2003-11-13 Heavner George A. Pseudo-antibody constructs
US20040093621A1 (en) 2001-12-25 2004-05-13 Kyowa Hakko Kogyo Co., Ltd Antibody composition which specifically binds to CD20
JP4820055B2 (ja) 2001-12-27 2011-11-24 グライコフィ， インコーポレイテッド 哺乳動物型糖質構造を操作するための方法
CA2478011C (en) 2002-03-01 2013-05-21 Immunomedics, Inc. Bispecific antibody point mutations for enhancing rate of clearance
EA200401325A1 (ru) 2002-04-09 2005-04-28 Киова Хакко Когио Ко., Лтд. Клетки с модифицированным геномом
CA2481920A1 (en) 2002-04-09 2003-10-16 Kyowa Hakko Kogyo Co., Ltd. Antibody composition-containing medicament
US20040132140A1 (en) 2002-04-09 2004-07-08 Kyowa Hakko Kogyo Co., Ltd. Production process for antibody composition
ATE503829T1 (de) 2002-04-09 2011-04-15 Kyowa Hakko Kirin Co Ltd Zelle mit erniedrigter oder deletierter aktivität eines am gdp-fucosetransport beteiligten proteins
JP4832719B2 (ja) 2002-04-09 2011-12-07 協和発酵キリン株式会社 ＦｃγＲＩＩＩａ多型患者に適応する抗体組成物含有医薬
US20040259150A1 (en) 2002-04-09 2004-12-23 Kyowa Hakko Kogyo Co., Ltd. Method of enhancing of binding activity of antibody composition to Fcgamma receptor IIIa
EP1500665B1 (en) 2002-04-15 2011-06-15 Chugai Seiyaku Kabushiki Kaisha METHODS FOR CONSTRUCTING scDb LIBRARIES
JP2006506954A (ja) 2002-04-29 2006-03-02 ゲンパト７７ ファーマコジェネティクス エージー Ｔｃｒ及びｔｉｒｃ７に結合する新規な抗体、並びに治療及び診断におけるその使用
US7829289B2 (en) 2002-05-14 2010-11-09 Institut National De La Sante Et De Recherche Medicale T cell subpopulation regulating gut immunity
EP1513879B1 (en) 2002-06-03 2018-08-22 Genentech, Inc. Synthetic antibody phage libraries
US7906118B2 (en) 2005-04-06 2011-03-15 Ibc Pharmaceuticals, Inc. Modular method to prepare tetrameric cytokines with improved pharmacokinetics by the dock-and-lock (DNL) technology
DE60333201D1 (de) 2002-09-12 2010-08-12 Greenovation Biotech Gmbh Verfahren zur herstellung von proteinen
AU2003271904B2 (en) 2002-10-09 2009-03-05 Adaptimmune Limited Single chain recombinant T cell receptors
US7361740B2 (en) 2002-10-15 2008-04-22 Pdl Biopharma, Inc. Alteration of FcRn binding affinities or serum half-lives of antibodies by mutagenesis
WO2004053054A2 (en) 2002-12-09 2004-06-24 Natspears Ltd. Nk cell receptor conjugates for treating malignancies
EP3263596A1 (en) 2002-12-16 2018-01-03 Genentech, Inc. Immunoglobulin variants and uses thereof
US7781197B2 (en) 2002-12-20 2010-08-24 Greenovation Biotech Gmbh Transformed bryophyte cell having disrupted endogenous alpha 1,3-fucosyl and beta 1,2-xylosyl transferase encoding nucleotide sequences for the production of heterologous glycosylated proteins
DE10261223A1 (de) 2002-12-20 2004-07-08 MedInnova Gesellschaft für medizinische Innovationen aus akademischer Forschung mbH Steigerung der Immunantwort durch Substanzen, welche die Funktion von Natürlichen Killerzellen beeinflussen
WO2004056392A1 (en) 2002-12-23 2004-07-08 Innate Pharma Pharmaceutical compositions having an effect on the proliferation of nk cells and a method using the same
GB0230203D0 (en) 2002-12-27 2003-02-05 Domantis Ltd Fc fusion
CA2510003A1 (en) 2003-01-16 2004-08-05 Genentech, Inc. Synthetic antibody phage libraries
CN103540600B (zh) 2003-01-22 2017-12-01 罗氏格黎卡特股份公司 融合构建体及其用来生产Fc受体结合亲和性和效应子功能提高的抗体的用途
US20060104968A1 (en) 2003-03-05 2006-05-18 Halozyme, Inc. Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminogly ycanases
GB0305702D0 (en) 2003-03-12 2003-04-16 Univ Birmingham Bispecific antibodies
US20050003403A1 (en) 2003-04-22 2005-01-06 Rossi Edmund A. Polyvalent protein complex
CA2525251C (en) 2003-05-09 2015-10-27 Duke University Cd20-specific antibodies and methods employing same
WO2005028517A2 (en) 2003-05-09 2005-03-31 The General Hospital Corporation SOLUBLE TGF-β TYPE III RECEPTOR FUSION PROTEINS
US20070105105A1 (en) 2003-05-23 2007-05-10 Mount Sinai School Of Medicine Of New York University Surrogate cell gene expression signatures for evaluating the physical state of a subject
CA2529945A1 (en) 2003-06-27 2005-01-06 Biogen Idec Ma Inc. Use of hydrophobic-interaction-chromatography or hinge-region modifications for the production of homogeneous antibody-solutions
KR20060041205A (ko) 2003-07-01 2006-05-11 이뮤노메딕스, 인코오포레이티드 양특이성 항체들의 다가 담체들
US7803376B2 (en) 2003-07-24 2010-09-28 Innate Pharma S.A. Methods and compositions for increasing the efficiency of therapeutic antibodies using NK cell potentiating compounds
US7696322B2 (en) 2003-07-28 2010-04-13 Catalent Pharma Solutions, Inc. Fusion antibodies
US20080241884A1 (en) 2003-10-08 2008-10-02 Kenya Shitara Fused Protein Composition
JPWO2005035778A1 (ja) 2003-10-09 2006-12-21 協和醗酵工業株式会社 α１，６−フコシルトランスフェラーゼの機能を抑制するＲＮＡを用いた抗体組成物の製造法
ES2672640T3 (es) 2003-11-05 2018-06-15 Roche Glycart Ag Moléculas de unión a antígeno con afinidad de unión a receptores Fc y función efectora incrementadas
US7498298B2 (en) 2003-11-06 2009-03-03 Seattle Genetics, Inc. Monomethylvaline compounds capable of conjugation to ligands
WO2005053742A1 (ja) 2003-12-04 2005-06-16 Kyowa Hakko Kogyo Co., Ltd. 抗体組成物を含有する医薬
US20050136051A1 (en) 2003-12-22 2005-06-23 Bernard Scallon Methods for generating multimeric molecules
GB0329825D0 (en) 2003-12-23 2004-01-28 Celltech R&D Ltd Biological products
US20050266425A1 (en) 2003-12-31 2005-12-01 Vaccinex, Inc. Methods for producing and identifying multispecific antibodies
US8383575B2 (en) 2004-01-30 2013-02-26 Paul Scherrer Institut (DI)barnase-barstar complexes
CN1961003B (zh) 2004-03-31 2013-03-27 健泰科生物技术公司 人源化抗TGF-β抗体
US7785903B2 (en) 2004-04-09 2010-08-31 Genentech, Inc. Variable domain library and uses
KR100891620B1 (ko) 2004-04-13 2009-04-02 에프. 호프만-라 로슈 아게 항-ｐ-셀렉틴 항체
WO2005105849A1 (en) 2004-04-30 2005-11-10 Innate Pharma Compositions and methods for treating proliferative disorders such as nk-type ldgl
WO2005105848A1 (en) 2004-04-30 2005-11-10 Innate Pharma Compositions and methods for enhancing nk cell activity
US8361794B2 (en) 2004-06-29 2013-01-29 Immunocore Limited Cells expressing a modified T cell receptor
JP2008512352A (ja) 2004-07-17 2008-04-24 イムクローン システムズ インコーポレイティド 新規な四価の二重特異性抗体
EP1789446A2 (en) 2004-09-02 2007-05-30 Genentech, Inc. Heteromultimeric molecules
TWI309240B (en) 2004-09-17 2009-05-01 Hoffmann La Roche Anti-ox40l antibodies
JO3000B1 (ar) 2004-10-20 2016-09-05 Genentech Inc مركبات أجسام مضادة .
CN101072793B (zh) 2004-12-09 2012-06-20 默克专利有限公司 具有降低的免疫原性的il-7变体
AU2006207987B2 (en) 2005-01-27 2011-09-15 Novartis Vaccines And Diagnostics Inc. Methods for treating renal cell carcinoma
EP1874824A4 (en) 2005-04-06 2009-12-30 Ibc Pharmaceuticals Inc METHODS OF GENERATING STABLE COMPOUND RELATED COMPLEXES OF HOMODIMERS, HOMOTRATEERS OR DIMER SIZES AND USES THEREOF
EP3479844B1 (en) 2005-04-15 2023-11-22 MacroGenics, Inc. Covalent diabodies and uses thereof
AU2006237329B2 (en) 2005-04-18 2012-04-12 Novo Nordisk A/S IL-21 variants
US20060263367A1 (en) 2005-05-23 2006-11-23 Fey Georg H Bispecific antibody devoid of Fc region and method of treatment using same
WO2006135886A2 (en) 2005-06-13 2006-12-21 The Regents Of The University Of Michigan Compositions and methods for treating and diagnosing cancer
JP2006345852A (ja) 2005-06-16 2006-12-28 Virxsys Corp 抗体複合体
CN103145839A (zh) * 2005-06-30 2013-06-12 Abbvie公司 Il-12/p40结合蛋白
ES2401706T3 (es) 2005-07-27 2013-04-23 Eli Lilly And Company Un método de tratar células cancerosas para crear una célula cancerosa modificada que provoca una respuesta inmunogénica
US7612181B2 (en) 2005-08-19 2009-11-03 Abbott Laboratories Dual variable domain immunoglobulin and uses thereof
ATE452913T1 (de) 2005-08-26 2010-01-15 Pls Design Gmbh Bivalente igy antikörperkonstrukte für diagnostische und therapeutische anwendungen
EP3190125A1 (en) * 2005-08-31 2017-07-12 Merck Sharp & Dohme Corp. Engineered anti-il-23 antibodies
EP1929302A2 (en) 2005-09-23 2008-06-11 Novo Nordisk A/S Methods of identifying antibodies to ligands of orphan receptors
WO2007044887A2 (en) 2005-10-11 2007-04-19 Transtarget, Inc. Method for producing a population of homogenous tetravalent bispecific antibodies
WO2007042809A2 (en) 2005-10-11 2007-04-19 Domantis Limited Antibody polypeptide library screening and selected antibody polypeptides
WO2007047335A2 (en) 2005-10-13 2007-04-26 Biogen Idec Ma Inc. Methods for use with baff antagonists
AU2006301163B2 (en) 2005-10-14 2012-02-23 Innate Pharma Compositions and methods for treating proliferative disorders
WO2007048849A1 (en) 2005-10-28 2007-05-03 Novo Nordisk A/S Fusion proteins that bind effector lymphocytes and target cells
EP1957531B1 (en) 2005-11-07 2016-04-13 Genentech, Inc. Binding polypeptides with diversified and consensus vh/vl hypervariable sequences
WO2007062466A1 (en) 2005-11-29 2007-06-07 The University Of Sydney Demibodies: dimerisation-activated therapeutic agents
WO2007064919A2 (en) 2005-12-02 2007-06-07 Genentech, Inc. Binding polypeptides with restricted diversity sequences
WO2007095338A2 (en) 2006-02-15 2007-08-23 Imclone Systems Incorporated Functional antibodies
EP1991679A2 (fr) 2006-03-08 2008-11-19 Biomethodes Variants de l'interferon- gamma humain (ifngamma)
KR101516823B1 (ko) 2006-03-17 2015-05-07 바이오겐 아이덱 엠에이 인코포레이티드 안정화된 폴리펩티드 조성물
US8946391B2 (en) 2006-03-24 2015-02-03 The Regents Of The University Of California Construction of a multivalent scFv through alkyne-azide 1,3-dipolar cycloaddition
US9670269B2 (en) 2006-03-31 2017-06-06 Chugai Seiyaku Kabushiki Kaisha Methods of modifying antibodies for purification of bispecific antibodies
JP2009536527A (ja) 2006-05-09 2009-10-15 ジェネンテック・インコーポレーテッド 最適化されたスキャフォールドを備えた結合ポリペプチド
JP5189082B2 (ja) 2006-05-25 2013-04-24 バイエル・ファルマ・アクチェンゲゼルシャフト 二量体分子複合体
US20070274985A1 (en) 2006-05-26 2007-11-29 Stefan Dubel Antibody
WO2007146968A2 (en) 2006-06-12 2007-12-21 Trubion Pharmaceuticals, Inc. Single-chain multivalent binding proteins with effector function
WO2008017859A2 (en) 2006-08-10 2008-02-14 Isis Innovation Limited Ligand for the g6b receptor on blood platelets
WO2008073160A2 (en) 2006-08-17 2008-06-19 The Trustees Of Columbia University In The City Of New York Methods for converting or inducing protective immunity
ES2566502T3 (es) 2006-09-13 2016-04-13 The Trustees Of Columbia University In The City Of New York Agentes y métodos para provocar una respuesta inmune antitumoral
CA2668208C (en) 2006-11-02 2017-09-12 Daniel J. Capon Hybrid immunoglobulins with moving parts
US20080226635A1 (en) 2006-12-22 2008-09-18 Hans Koll Antibodies against insulin-like growth factor I receptor and uses thereof
WO2008087219A1 (en) 2007-01-19 2008-07-24 INSERM (Institut National de la Santé et de la Recherche Médicale) Compositions and methods for regulating t cell activity
WO2008119353A1 (en) 2007-03-29 2008-10-09 Genmab A/S Bispecific antibodies and methods for production thereof
EP2144930A1 (en) 2007-04-18 2010-01-20 ZymoGenetics, Inc. Single chain fc, methods of making and methods of treatment
DK2160401T3 (da) 2007-05-11 2014-10-20 Altor Bioscience Corp Fusionsmolekyler og il-15-varianter
TW201531484A (zh) 2007-05-21 2015-08-16 Alder Biopharmaceuticals Inc 抗ＴＮＦ-α之抗體及其用途
CN100592373C (zh) 2007-05-25 2010-02-24 群康科技(深圳)有限公司 液晶显示面板驱动装置及其驱动方法
EP2014680A1 (en) 2007-07-10 2009-01-14 Friedrich-Alexander-Universität Erlangen-Nürnberg Recombinant, single-chain, trivalent tri-specific or bi-specific antibody derivatives
KR20100058509A (ko) 2007-07-31 2010-06-03 메디뮨 엘엘씨 다중특이적 에피토프 결합 단백질 및 이의 용도
WO2009021754A2 (en) 2007-08-15 2009-02-19 Bayer Schering Pharma Aktiengesellschaft Monospecific and multispecific antibodies and method of use
AU2008304748C1 (en) 2007-09-26 2014-06-12 Chugai Seiyaku Kabushiki Kaisha Modified antibody constant region
KR101662622B1 (ko) 2007-10-04 2016-10-05 지모제넥틱스, 인코포레이티드 Ｂ7 패밀리 구성원 ｚＢ7Ｈ6 및 관련된 조성물 및 방법
UA104132C2 (en) 2007-11-13 2014-01-10 Тева Биофармасьютикалз Юесей, Инк. Humanized antibodies against tl1a
EP2220120A2 (en) 2007-11-27 2010-08-25 Ablynx N.V. Amino acid sequences directed against heterodimeric cytokines and/or their receptors and polypeptides comprising the same
AU2008328726B2 (en) 2007-11-30 2014-06-12 Glaxo Group Limited Antigen-binding constructs
RU2570559C2 (ru) 2007-12-17 2015-12-10 Пфайзер Лимитед Лечение интерстициального цистита
US20090162359A1 (en) 2007-12-21 2009-06-25 Christian Klein Bivalent, bispecific antibodies
US8242247B2 (en) 2007-12-21 2012-08-14 Hoffmann-La Roche Inc. Bivalent, bispecific antibodies
US9266967B2 (en) 2007-12-21 2016-02-23 Hoffmann-La Roche, Inc. Bivalent, bispecific antibodies
CA2712474A1 (en) 2008-02-21 2009-08-27 Baxter Healthcare S.A. Procedure for the generation of a high producer cell line for the expression of a recombinant anti-cd34 antibody
US9593376B2 (en) 2008-06-02 2017-03-14 Institut Gustave Roussy Natural killer p30 (NKp30) dysfunction and the biological applications thereof
AU2009288354A1 (en) 2008-08-26 2010-03-11 Macrogenics Inc. T-cell receptor antibodies and methods of use thereof
TWI516501B (zh) 2008-09-12 2016-01-11 禮納特神經系統科學公司 Ｐｃｓｋ９拮抗劑類
EP2326670A4 (en) 2008-09-17 2014-04-16 Nat Res Council Canada HETERO MULTIVALENT BINDING AGENT FOR ELEMENTS OF THE TGF-BETA SUPERFAMILY
US8580267B2 (en) 2008-12-19 2013-11-12 Philogen S.P.A. Immunocytokines for tumour therapy with chemotherapeutic agents
US8497071B2 (en) 2009-06-29 2013-07-30 California Institute Of Technology Isolation of unknown rearranged T-cell receptors from single cells
ES2534085T3 (es) 2009-08-17 2015-04-17 Roche Glycart Ag Inmunoconjugados dirigidos
KR20120060877A (ko) 2009-09-01 2012-06-12 아보트 러보러터리즈 이원 가변 도메인 면역글로불린 및 이의 용도
EP2510011B2 (en) 2009-12-09 2021-03-31 Institut National de la Santé et de la Recherche Médicale Monoclonal antibodies that bind b7h6 and uses thereof
US20130129723A1 (en) 2009-12-29 2013-05-23 Emergent Product Development Seattle, Llc Heterodimer Binding Proteins and Uses Thereof
CN102958942A (zh) 2009-12-29 2013-03-06 新兴产品开发西雅图有限公司 异二聚体结合蛋白及其应用
WO2011085178A1 (en) 2010-01-11 2011-07-14 Trustees Of Dartmouth College Monomeric bi-specific fusion protein
EP3907242A1 (en) 2010-01-29 2021-11-10 Chugai Seiyaku Kabushiki Kaisha Anti-dll3 antibody
CA3083324A1 (en) 2010-03-05 2011-09-09 The Johns Hopkins University Compositions and methods for targeted immunomodulatory antibodies and fusion proteins
DK2560993T3 (da) 2010-04-20 2024-10-14 Genmab As Heterodimeric antibody fc-containing proteins and methods for production thereof
US9018006B2 (en) 2010-07-23 2015-04-28 The University Of Toledo Stable Tregs and related materials and methods
CN101985476B (zh) 2010-10-29 2012-11-21 中国科学技术大学 抗人NKp30单克隆抗体的制备、鉴定及应用
PH12013501201A1 (en) 2010-12-09 2013-07-29 Univ Pennsylvania Use of chimeric antigen receptor-modified t cells to treat cancer
WO2012088309A1 (en) 2010-12-21 2012-06-28 The Board Of Trustees Of The Leland Stanford Junior University Therapeutic and diagnostic methods for manipulating phagocytosis through calreticulin and low density lipoprotein-related receptor
HUE029139T2 (hu) 2011-02-10 2017-02-28 Roche Glycart Ag Mutáns interleukin-2 polipeptidek
EP2681242B1 (en) 2011-03-01 2018-01-24 Amgen Inc. Sclerostin and dkk-1 bispecific binding agents
EP2694549B1 (en) 2011-04-08 2018-08-15 The United States of America, as represented by The Secretary, Department of Health and Human Services Anti-epidermal growth factor receptor variant iii chimeric antigen receptors and use of same for the treatment of cancer
EA201892619A1 (ru) 2011-04-29 2019-04-30 Роше Гликарт Аг Иммуноконъюгаты, содержащие мутантные полипептиды интерлейкина-2
JP2014520123A (ja) 2011-06-17 2014-08-21 アムジエン・インコーポレーテツド Ｃｌｅｃ−２を使用して代謝性障害を治療または改善させる方法
EP2723380B1 (en) 2011-06-24 2019-08-21 Stephen D. Gillies Light chain immunoglobulin fusion proteins and methods of use thereof
EP3549611B1 (en) 2011-07-29 2021-06-30 The Trustees of the University of Pennsylvania Switch costimulatory receptors
US9833476B2 (en) 2011-08-31 2017-12-05 The Trustees Of Dartmouth College NKP30 receptor targeted therapeutics
UY34317A (es) 2011-09-12 2013-02-28 Genzyme Corp Anticuerpo antireceptor de célula T (alfa)/ß
SG10201604104PA (en) 2011-10-25 2016-07-28 Prothena Therapeutics Ltd Antibody formulations and methods
US10344050B2 (en) 2011-10-27 2019-07-09 Genmab A/S Production of heterodimeric proteins
US20130273089A1 (en) 2011-11-03 2013-10-17 Tolera Therapeutics, Inc. Antibody and methods for selective inhibition of t-cell responses
LT2794658T (lt) 2011-12-19 2017-05-10 Synimmune Gmbh Bispecifinė antikūno molekulė
JP6153947B2 (ja) 2012-01-05 2017-06-28 ヴィザ インターナショナル サーヴィス アソシエイション 取引映像キャプチャ装置、方法およびシステム
PE20190658A1 (es) 2012-02-24 2019-05-08 Abbvie Stemcentrx Llc Moduladores y metodos de empleo novedosos
AR092044A1 (es) 2012-08-07 2015-03-18 Roche Glycart Ag Inmunoterapia mejorada
US20140044675A1 (en) 2012-08-10 2014-02-13 Roche Glycart Ag Interleukin-2 fusion proteins and uses thereof
US9682143B2 (en) 2012-08-14 2017-06-20 Ibc Pharmaceuticals, Inc. Combination therapy for inducing immune response to disease
CN104769103B (zh) 2012-09-04 2018-06-08 塞勒克提斯公司 多链嵌合抗原受体和其用途
US20140079691A1 (en) 2012-09-20 2014-03-20 Anaptysbio, Inc. Thermostable antibody framework regions
AU2013204922B2 (en) 2012-12-20 2015-05-14 Celgene Corporation Chimeric antigen receptors
MX2015008117A (es) 2012-12-21 2016-03-31 Amplimmune Inc Anticuerpos anti-h7cr.
US9989524B2 (en) 2013-02-05 2018-06-05 Sanofi Immuno imaging agent for use with antibody-drug conjugate therapy
GB201302447D0 (en) 2013-02-12 2013-03-27 Oxford Biotherapeutics Ltd Therapeutic and diagnostic target
TW201446794A (zh) 2013-02-20 2014-12-16 Novartis Ag 利用抗－ｃｄ１２３嵌合抗原受體工程化ｔ細胞之初級人類白血病有效靶向
BR112015019909A2 (pt) 2013-02-22 2017-08-29 Abbvie Stemcentrx Llc Conjugados anticorpo-fármaco, composição farmacêutica, usos dos mesmos, e kit
CN105143270B (zh) 2013-02-26 2019-11-12 罗切格利卡特公司 双特异性t细胞活化抗原结合分子
JP6676521B2 (ja) 2013-03-14 2020-04-08 マクロジェニクス，インコーポレーテッド 二重特異性分子、薬学的組成物及びそれらの使用
NZ710929A (en) 2013-03-15 2018-02-23 Novartis Ag Antibody drug conjugates
CA2921805C (en) 2013-08-22 2023-03-07 Acceleron Pharma, Inc. Tgf-beta receptor type ii variants and uses thereof
PT2808338E (pt) 2013-09-16 2016-06-15 Cemm - Forschungszentrum Für Molekulare Medizin Gmbh Calreticulina mutante para o diagnóstico de malignidades mieloides
SG11201603193PA (en) 2013-10-30 2016-05-30 Genzyme Corp Methods for enhancing immunosuppressive therapy by multiple administration of alpha beta tcr-binding polypeptide
EP3082853A2 (en) 2013-12-20 2016-10-26 The Broad Institute, Inc. Combination therapy with neoantigen vaccine
KR102042246B1 (ko) 2014-02-06 2019-11-28 에프. 호프만-라 로슈 아게 인터류킨-2 융합 단백질 및 이의 용도
US9676863B2 (en) 2014-02-10 2017-06-13 Merck Patent Gmbh Targeted TGFβ inhibitors
DK3105252T3 (da) 2014-02-12 2019-10-14 Michael Uhlin Bispecifikke antistoffer til anvendelse ved stamcelletransplantation
PE20161209A1 (es) 2014-02-21 2016-11-10 Abbvie Stemcentrx Llc Conjugados de anticuerpos anti-drosophila similar a delta 3 (anti-dll3) y medicamentos para usarse en el tratamiento contra melanoma
US11385233B2 (en) 2015-03-05 2022-07-12 Autolus Limited Methods of depleting malignant T-cells
CN112094347A (zh) 2014-03-05 2020-12-18 奥托路斯有限公司 具有针对T细胞受体beta恒定区的抗原结合域的嵌合抗原受体(CAR)
MX373460B (es) 2014-03-11 2020-04-07 Cellectis Metodo para generar celulas t compatibles para el trasplante alogenico.
EP3593812A3 (en) 2014-03-15 2020-05-27 Novartis AG Treatment of cancer using chimeric antigen receptor
EP3122779B1 (en) 2014-03-24 2019-05-22 Cancer Research Technology Limited Modified antibodies containing modified igg2 domains which elicit agonist or antagonistic properties and use thereof
WO2015164815A1 (en) 2014-04-24 2015-10-29 The Board Of Trustees Of The Leland Stanford Junior University Superagonists, partial agonists and antagonists of interleukin-2
IL290655B2 (en) 2014-05-29 2024-05-01 Us Health Anti-human papillomavirus 16 E7 T-cell chelates
EP3152235B1 (en) 2014-05-29 2021-08-25 MacroGenics, Inc. Tri-specific binding molecules and methods of use thereof
JP6822849B2 (ja) 2014-06-27 2021-01-27 イナート・ファルマ・ソシエテ・アノニムＩｎｎａｔｅ Ｐｈａｒｍａ Ｐｈａｒｍａ Ｓ．Ａ． 多重特異的ＮＫｐ４６結合タンパク質
WO2016019969A1 (en) 2014-08-08 2016-02-11 Ludwig-Maximilians-Universität München Subcutaneously administered bispecific antibodies for use in the treatment of cancer
HRP20190881T1 (hr) 2014-08-28 2019-07-12 Halozyme, Inc. Kombinacijska terapija s hijaluronan-razgrađujućim enzimom i inhibitorom imunološke kontrolne točke
BR112017004270B1 (pt) 2014-09-04 2023-03-07 Stemcell Technologies Inc Método de ativação de células t ou células nk
MA40764A (fr) 2014-09-26 2017-08-01 Chugai Pharmaceutical Co Ltd Agent thérapeutique induisant une cytotoxicité
WO2016051205A1 (en) 2014-10-03 2016-04-07 Isis Innovation Limited Analysis of t-cell monotypia
WO2016069282A1 (en) 2014-10-31 2016-05-06 The Trustees Of The University Of Pennsylvania Altering gene expression in modified t cells and uses thereof
US20170269092A1 (en) 2014-12-02 2017-09-21 Cemm - Forschungszentrum Fuer Molekulare Medizin Gmbh Anti-mutant calreticulin antibodies and their use in the diagnosis and therapy of myeloid malignancies
WO2016090337A1 (en) 2014-12-05 2016-06-09 Memorial Sloan-Kettering Cancer Center Chimeric antigen receptors targeting fc receptor-like 5 and uses thereof
US9767555B2 (en) 2015-01-05 2017-09-19 Case Western Reserve University Disease characterization from fused pathology and radiology data
US20170151281A1 (en) 2015-02-19 2017-06-01 Batu Biologics, Inc. Chimeric antigen receptor dendritic cell (car-dc) for treatment of cancer
WO2016176756A1 (en) 2015-05-05 2016-11-10 University Health Network Nk cells and antibodies for cancer treatment
PT3294768T (pt) 2015-05-13 2019-11-05 Ablynx Nv Polipétidos de recrutamento de células t com base na reatividade do tcr alfa/beta
WO2016193301A1 (en) 2015-06-01 2016-12-08 Medigene Immunotherapies Gmbh T-cell receptor specific antibodies
WO2016193300A1 (en) 2015-06-01 2016-12-08 Medigene Immunotherapies Gmbh Method for generating antibodies against t cell receptor
TWI793062B (zh) 2015-07-31 2023-02-21 德商安美基研究（慕尼黑）公司 Ｄｌｌ３及ｃｄ３抗體構築體
EA039859B1 (ru) 2015-07-31 2022-03-21 Эмджен Рисерч (Мюник) Гмбх Биспецифические конструкты антител, связывающие egfrviii и cd3
US20200231652A1 (en) 2015-08-31 2020-07-23 National Research Council Of Canada Tgf-b-receptor ectodomain fusion molecules and uses thereof
JP6905163B2 (ja) 2015-09-03 2021-07-21 ザ トラスティーズ オブ ザ ユニバーシティ オブ ペンシルバニア サイトカイン放出症候群を予測するバイオマーカー
US20170096485A1 (en) 2015-10-02 2017-04-06 Hoffmann-La Roche Inc. Bispecific t cell activating antigen binding molecules
MX389194B (es) 2015-10-06 2025-03-20 Univ Minnesota Compuestos terapéuticos y métodos.
AU2016334063B2 (en) 2015-10-08 2023-05-25 Zymeworks Bc Inc. Antigen-binding polypeptide constructs comprising kappa and lambda light chains and uses thereof
US11702477B2 (en) 2015-11-06 2023-07-18 Orionis Biosciences BV Bi-functional chimeric proteins and uses thereof
WO2017165464A1 (en) 2016-03-21 2017-09-28 Elstar Therapeutics, Inc. Multispecific and multifunctional molecules and uses thereof
WO2017167350A1 (en) 2016-03-30 2017-10-05 Horst Lindhofer Multispecific antibodies for use in the treatment of a neoplasm of the urinary tract
IL262241B2 (en) 2016-04-13 2024-05-01 Sanofi Sa Trispecific and/or trivalent binding proteins with a crossover dual variable domain arm and a traditional antibody fab arm, pharmaceutical composition comprising said binding proteins and their uses in preventing and/or treating cancer or inflammatory diseases
CA2937157A1 (en) 2016-07-25 2018-01-25 Ucl Business Ltd Protein-based t-cell receptor knockdown
US11851491B2 (en) 2016-11-22 2023-12-26 TCR2 Therapeutics Inc. Compositions and methods for TCR reprogramming using fusion proteins
CA3051866A1 (en) 2017-02-01 2018-08-09 Nant Holdings Ip, Llc Calreticulin-mediated cancer treatment
WO2018151820A1 (en) 2017-02-16 2018-08-23 Elstar Therapeutics, Inc. Multifunctional molecules comprising a trimeric ligand and uses thereof
US12134654B2 (en) 2017-04-19 2024-11-05 Marengo Therapeutics, Inc. Multispecific molecules and uses thereof
WO2018193103A1 (en) 2017-04-20 2018-10-25 Adc Therapeutics Sa Combination therapy with an anti-psma antibody-drug conjugate
CA3059769A1 (en) 2017-04-28 2018-11-01 Elstar Therapeutics, Inc. Multispecific molecules comprising a non-immunoglobulin heterodimerization domain and uses thereof
JP2020521452A (ja) 2017-05-24 2020-07-27 パンディオン・セラピューティクス・インコーポレイテッド 標的化免疫寛容
JP2020522254A (ja) 2017-05-31 2020-07-30 エルスター セラピューティクス， インコーポレイテッド 骨髄増殖性白血病（ｍｐｌ）タンパク質に結合する多特異性分子およびその使用
GB201709203D0 (en) 2017-06-09 2017-07-26 Autolus Ltd Antigen-binding domain
US12195529B2 (en) 2017-06-21 2025-01-14 Gsbio, Llc Heterodimeric bispecific antibodies
TWI828625B (zh) 2017-06-25 2024-01-11 美商西雅圖免疫公司 引導及導航控制蛋白質以及彼之製造及使用方法
US20210017247A1 (en) 2017-07-03 2021-01-21 Torque Therapeutics, Inc. Fusion Molecules Targeting Immune Regulatory Cells and Uses Thereof
EP3654991A1 (en) 2017-07-19 2020-05-27 Rubius Therapeutics, Inc. Compositions and methods related to multimodal therapeutic cell systems for infectious disease
IL316357A (en) 2017-07-31 2024-12-01 Trishula Therapeutics Inc Anti-cd39 antibodies, compositions comprising anti-cd39 antibodies and methods of using anti-cd39 antibodies
WO2019028419A1 (en) 2017-08-03 2019-02-07 Synthorx, Inc. CYTOKINE CONJUGATES FOR THE TREATMENT OF PROLIFERATIVE AND INFECTIOUS DISEASES
WO2019035938A1 (en) 2017-08-16 2019-02-21 Elstar Therapeutics, Inc. MULTISPECIFIC MOLECULES BINDING TO BCMA AND USES THEREOF
US10578740B2 (en) 2017-08-23 2020-03-03 Mezmeriz Inc. Coherent optical distance measurement apparatus and method
EP3672990A1 (en) 2017-08-25 2020-07-01 Five Prime Therapeutics, Inc. B7-h4 antibodies and methods of use thereof
SG11202002298PA (en) 2017-09-14 2020-04-29 Dragonfly Therapeutics Inc Proteins binding nkg2d, cd16, and c-type lectin-like molecule-1 (cll-1)
MX2020004185A (es) 2017-09-27 2021-01-08 Univ Southern California Nuevas plataformas para coestimulacion, nuevos diseños car y otras mejoras para terapia celular adoptiva.
GB201718088D0 (en) 2017-11-01 2017-12-13 Autolus Ltd Vectors
AU2018371114A1 (en) 2017-11-21 2020-05-07 Innate Pharma Multispecific antigen binding proteins
US20200299349A1 (en) 2017-11-21 2020-09-24 The Board Of Trustees Of The Leland Stanford Junior University Partial agonists of interleukin-2
JP7348899B2 (ja) 2017-12-08 2023-09-21 マレンゴ・セラピューティクス，インコーポレーテッド 多重特異性分子及びその使用
RU2694412C9 (ru) 2017-12-25 2019-09-18 Федеральное государственное бюджетное образовательное учреждение высшего образования "Российский национальный исследовательский медицинский университет им. Н.И. Пирогова" Министерства здравоохранения Российской Федерации (ФГБОУ ВО РНИМУ им. Н.И. Пирогова Минздрава России) Моноклональные антитела и способы их применения
CN111527109B (zh) 2017-12-26 2024-11-01 南京金斯瑞生物科技有限公司 以抗体Fc区为骨架的融合蛋白二聚体及其应用
US11667713B2 (en) 2017-12-28 2023-06-06 Chugai Seiyaku Kabushiki Kaisha Cytotoxicity-inducing therapeutic agent
EP3737692A4 (en) 2018-01-09 2021-09-29 Elstar Therapeutics, Inc. CALRETICULIN AND MODIFIED T-LYMPHOCYTES BINDING CONSTRUCTIONS FOR THE TREATMENT OF DISEASES
GB201800298D0 (en) 2018-01-09 2018-02-21 Autolus Ltd Method
WO2019158764A1 (en) 2018-02-16 2019-08-22 Iltoo Pharma Use of interleukin 2 for treating sjögren's syndrome
US12152073B2 (en) 2018-03-14 2024-11-26 Marengo Therapeutics, Inc. Multifunctional molecules that bind to calreticulin and uses thereof
WO2019178364A2 (en) 2018-03-14 2019-09-19 Elstar Therapeutics, Inc. Multifunctional molecules and uses thereof
US20210024631A1 (en) 2018-03-28 2021-01-28 Orionis Biosciences, Inc. Bi-functional proteins and construction thereof
CA3099308A1 (en) 2018-05-21 2019-11-28 Compass Therapeutics Llc Compositions and methods for enhancing the killing of target cells by nk cells
EA202091977A1 (ru) 2018-05-28 2021-02-09 Драгонфлай Терапьютикс, Инк. Мультиспецифические связывающие белки, которые связывают cd33, nkg2d и cd16, и способы применения
EP3810640A1 (en) 2018-06-25 2021-04-28 University of Washington De novo design of potent and selective interleukin mimetics
EP3818083A2 (en) 2018-07-03 2021-05-12 Elstar Therapeutics, Inc. Anti-tcr antibody molecules and uses thereof
US20210277120A1 (en) 2018-07-18 2021-09-09 The General Hospital Corporation Compositions and methods for treatment of t cell malignancies
CN108949698B (zh) 2018-07-31 2019-05-31 广东和信健康科技有限公司 杂交瘤细胞株c11-6f7及其产生的hcmv单克隆抗体和应用
JOP20210022A1 (ar) 2018-08-03 2021-01-28 Amgen Inc بنيات جسم مضاد لـ cldn18.2وcd3
GB201812650D0 (en) 2018-08-03 2018-09-19 Autolus Ltd Molecular assessment of TRBC usage
EA202091888A1 (ru) 2018-08-08 2020-10-23 Драгонфлай Терапьютикс, Инк. Вариабельные домены антител, нацеленные на рецептор nkg2d
WO2020057646A1 (zh) 2018-09-21 2020-03-26 信达生物制药(苏州)有限公司 新型白介素2及其用途
SG11202103022WA (en) 2018-09-25 2021-04-29 Harpoon Therapeutics Inc Dll3 binding proteins and methods of use
JP2022502443A (ja) 2018-09-28 2022-01-11 ピエール、ファーブル、メディカマン 癌の処置のための新規な免疫サイトカイン
CN113194984A (zh) 2018-10-18 2021-07-30 金德雷德生物科学股份有限公司 兽用的与新生儿Fc受体(FcRn)结合改变的Fc变体
GB201817172D0 (en) 2018-10-22 2018-12-05 Autolus Ltd Antibody
AU2019366956B2 (en) 2018-10-23 2025-10-30 Dragonfly Therapeutics, Inc. Heterodimeric Fc-fused proteins
US12378295B2 (en) 2018-10-29 2025-08-05 1Globe Biomedical Co., Ltd. Rationally designed protein compositions
GB201817822D0 (en) 2018-10-31 2018-12-19 Autolus Ltd Binding domain
EP3883956A1 (en) 2018-11-20 2021-09-29 University of Washington Split interleukin mimetics and their use
RU2712251C1 (ru) 2018-12-25 2020-01-27 Федеральное государственное автономное образовательное учреждение высшего образования "Российский национальный исследовательский медицинский университет имени Н.И. Пирогова" Министерства здравоохранения Российской Федерации (ФГАОУ ВО РНИМУ им. Н.И. Пирогова Минздрава России) Гуманизированные антитела против участка бета цепи 9-го семейства TRBV9 TKP человека, и способы их применения
AR117735A1 (es) 2018-12-25 2021-08-25 Joint Stock Company “Biocad” ANTICUERPOS MONOCLONALES QUE SE UNEN ESPECÍFICAMENTE A LA REGIÓN b DE LA FAMILIA TRBV-9 DEL RECEPTOR DE CÉLULAS T HUMANO, Y LOS MÉTODOS PARA SU USO
GB2595980B (en) 2019-01-04 2023-06-14 Marengo Therapeutics Inc Anti-TCR antibody molecules and uses thereof
WO2020154032A1 (en) 2019-01-23 2020-07-30 Massachusetts Institute Of Technology Combination immunotherapy dosing regimen for immune checkpoint blockade
AU2020224681A1 (en) 2019-02-21 2021-09-16 Marengo Therapeutics, Inc. Antibody molecules that bind to NKp30 and uses thereof
WO2020172601A1 (en) 2019-02-21 2020-08-27 Elstar Therapeutics, Inc. Multifunctional molecules that bind to calreticulin and uses thereof
EP3927745A1 (en) 2019-02-21 2021-12-29 Marengo Therapeutics, Inc. Multifunctional molecules that bind to t cells and uses thereof to treat autoimmune disorders
AU2020226904B2 (en) 2019-02-21 2025-05-01 Marengo Therapeutics, Inc. Anti-TCR antibody molecules and uses thereof
JP7710373B2 (ja) 2019-02-21 2025-07-18 マレンゴ・セラピューティクス，インコーポレーテッド Ｔ細胞関連のがん細胞に結合する多機能性分子およびその使用
WO2020180591A1 (en) 2019-03-01 2020-09-10 Allogene Therapeutics, Inc. Dll3 targeting chimeric antigen receptors and binding agents
JP7566766B2 (ja) 2019-03-11 2024-10-15 ヤンセン バイオテツク，インコーポレーテツド 抗Ｖβ１７／抗ＣＤ１２３二重特異性抗体
WO2020249757A1 (en) 2019-06-14 2020-12-17 Philogen S.P.A Immunoconjugates comprising a single chain diabody and interleukin-15 or interleukin-15 and a sushi domain of interleukin-15 receptor alpha
EP4054633A1 (en) 2019-11-05 2022-09-14 Merck Patent GmbH Combined inhibition of pd-1, tgfb and tigit for the treatment of cancer
JP7590430B2 (ja) 2019-11-14 2024-11-26 マレンゴ・セラピューティクス，インコーポレーテッド 抗ｔｃｒ抗体分子およびその使用
WO2021138407A2 (en) 2020-01-03 2021-07-08 Marengo Therapeutics, Inc. Multifunctional molecules that bind to cd33 and uses thereof
CN116234829A (zh) 2020-01-03 2023-06-06 马伦戈治疗公司 抗tcr抗体分子及其用途
KR20220147583A (ko) 2020-01-09 2022-11-03 바이오뮤넥스 파마슈티컬스 Mait 및 종양 세포 둘 모두에 결합하는 다중특이적 항체
WO2021188454A1 (en) 2020-03-16 2021-09-23 Marengo Therapeutics, Inc. Engineered cell compositions and methods of use thereof
GB2612450A (en) 2020-04-24 2023-05-03 Marengo Therapeutics Inc Multifunctional molecules that bind to T cell related cancer cells and uses thereof
KR20230074487A (ko) 2020-08-26 2023-05-30 마렝고 테라퓨틱스, 인크. Trbc1 또는 trbc2를 검출하는 방법
CA3190755A1 (en) 2020-08-26 2022-03-03 Andreas Loew Multifunctional molecules that bind to calreticulin and uses thereof
AU2021331076A1 (en) 2020-08-26 2023-04-06 Marengo Therapeutics, Inc. Antibody molecules that bind to NKp30 and uses thereof
WO2022179580A1 (zh) 2021-02-26 2022-09-01 盛禾(中国)生物制药有限公司 一种抗NKp30抗体及其应用
CA3214757A1 (en) 2021-04-08 2022-10-13 Andreas Loew Multifuntional molecules binding to tcr and uses thereof
US20240317856A1 (en) 2021-05-10 2024-09-26 Amgen Inc. Dosing regimen for combination therapy targeting dll3 and pd-1
WO2023081412A2 (en) 2021-11-05 2023-05-11 Marengo Therapeutics, Inc. Immune cell populations and uses thereof
CN118786150A (zh) 2021-12-22 2024-10-15 马伦戈治疗公司 与tcr结合的多功能分子及其用途
EP4466019A4 (en) 2022-01-21 2026-01-07 Marengo Therapeutics Inc MULTIFUNCTIONAL MOLECULES COMPRISING A G6B BINDER AND/OR A CD34 BINDER AND THEIR USES
AU2023361491A1 (en) 2022-10-12 2025-05-08 Marengo Therapeutics, Inc. Multifunctional molecules binding to tcr and uses thereof
EP4601747A1 (en) 2022-10-12 2025-08-20 Marengo Therapeutics, Inc. Multifunctional molecules binding to tcr and uses thereof
WO2024197082A2 (en) 2023-03-21 2024-09-26 Marengo Therapeutics, Inc. Tcr targeting molecules and uses thereof
WO2024226532A2 (en) 2023-04-24 2024-10-31 Marengo Therapeutics, Inc. Multifunctional molecules binding to tcr and uses thereof
AU2024264260A1 (en) 2023-04-27 2025-11-13 Marengo Therapeutics, Inc. Combination therapies using molecules binding to tcr
EP4724500A2 (en) 2023-06-09 2026-04-15 Marengo Therapeutics, Inc. Multispecific molecules binding to tcr and uses thereof

Patent Citations (243)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US861745A (en) 1906-11-21 1907-07-30 Jefferson D Maxwell Hydraulic dredging apparatus.
EP0125023A1 (en) 1983-04-08 1984-11-14 Genentech, Inc. Recombinant immunoglobulin preparations, methods for their preparation, DNA sequences, expression vectors and recombinant host cells therefor
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
EP0171496A2 (en) 1984-08-15 1986-02-19 Research Development Corporation of Japan Process for the production of a chimera monoclonal antibody
EP0173494A2 (en) 1984-08-27 1986-03-05 The Board Of Trustees Of The Leland Stanford Junior University Chimeric receptors by DNA splicing and expression
WO1986001533A1 (en) 1984-09-03 1986-03-13 Celltech Limited Production of chimeric antibodies
EP0184187A2 (en) 1984-12-04 1986-06-11 Teijin Limited Mouse-human chimaeric immunoglobulin heavy chain, and chimaeric DNA encoding it
GB2188638A (en) 1986-03-27 1987-10-07 Gregory Paul Winter Chimeric antibodies
US5225539A (en) 1986-03-27 1993-07-06 Medical Research Council Recombinant altered antibodies and methods of making altered antibodies
US5624821A (en) 1987-03-18 1997-04-29 Scotgen Biopharmaceuticals Incorporated Antibodies with altered effector functions
US5648260A (en) 1987-03-18 1997-07-15 Scotgen Biopharmaceuticals Incorporated DNA encoding antibodies with altered effector functions
WO1990002809A1 (en) 1988-09-02 1990-03-22 Protein Engineering Corporation Generation and selection of recombinant varied binding proteins
US5223409A (en) 1988-09-02 1993-06-29 Protein Engineering Corp. Directed evolution of novel binding proteins
EP0368684A1 (en) 1988-11-11 1990-05-16 Medical Research Council Cloning immunoglobulin variable domain sequences.
US6905680B2 (en) 1988-11-23 2005-06-14 Genetics Institute, Inc. Methods of treating HIV infected subjects
US6534055B1 (en) 1988-11-23 2003-03-18 Genetics Institute, Inc. Methods for selectively stimulating proliferation of T cells
US5693762A (en) 1988-12-28 1997-12-02 Protein Design Labs, Inc. Humanized immunoglobulins
US5585089A (en) 1988-12-28 1996-12-17 Protein Design Labs, Inc. Humanized immunoglobulins
US5693761A (en) 1988-12-28 1997-12-02 Protein Design Labs, Inc. Polynucleotides encoding improved humanized immunoglobulins
EP0388151A1 (en) 1989-03-13 1990-09-19 Celltech Limited Modified antibodies
US6291158B1 (en) 1989-05-16 2001-09-18 Scripps Research Institute Method for tapping the immunological repertoire
US5731116A (en) 1989-05-17 1998-03-24 Dai Nippon Printing Co., Ltd. Electrostatic information recording medium and electrostatic information recording and reproducing method
WO1991000906A1 (en) 1989-07-12 1991-01-24 Genetics Institute, Inc. Chimeric and transgenic animals capable of producing human antibodies
WO1991010741A1 (en) 1990-01-12 1991-07-25 Cell Genesys, Inc. Generation of xenogeneic antibodies
WO1991017271A1 (en) 1990-05-01 1991-11-14 Affymax Technologies N.V. Recombinant library screening methods
WO1992020791A1 (en) 1990-07-10 1992-11-26 Cambridge Antibody Technology Limited Methods for producing members of specific binding pairs
WO1992001047A1 (en) 1990-07-10 1992-01-23 Cambridge Antibody Technology Limited Methods for producing members of specific binding pairs
WO1992003918A1 (en) 1990-08-29 1992-03-19 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
WO1992003917A1 (en) 1990-08-29 1992-03-19 Genpharm International Homologous recombination in mammalian cells
WO1992009690A2 (en) 1990-12-03 1992-06-11 Genentech, Inc. Enrichment method for variant proteins with altered binding properties
WO1992015679A1 (en) 1991-03-01 1992-09-17 Protein Engineering Corporation Improved epitode displaying phage
WO1992018619A1 (en) 1991-04-10 1992-10-29 The Scripps Research Institute Heterodimeric receptor libraries using phagemids
EP0519596A1 (en) 1991-05-17 1992-12-23 Merck & Co. Inc. A method for reducing the immunogenicity of antibody variable domains
WO1993001288A1 (de) 1991-07-08 1993-01-21 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Phagemid zum screenen von antikörpern
US6172197B1 (en) 1991-07-10 2001-01-09 Medical Research Council Methods for producing members of specific binding pairs
US6593081B1 (en) 1991-12-02 2003-07-15 Medical Research Council Production of anti-self antibodies from antibody segment repertoires and displayed on phage
US6582915B1 (en) 1991-12-02 2003-06-24 Medical Research Council Production of anti-self bodies from antibody segment repertories and displayed on phage
EP0616640A1 (en) 1991-12-02 1994-09-28 Medical Research Council Production of anti-self antibodies from antibody segment repertoires and displayed on phage
JPH06153947A (ja) 1992-06-26 1994-06-03 Seikagaku Kogyo Co Ltd コンドロイチナーゼａｂｃ、その製造法及び医薬組成物
US6765087B1 (en) 1992-08-21 2004-07-20 Vrije Universiteit Brussel Immunoglobulins devoid of light chains
WO1994004678A1 (en) 1992-08-21 1994-03-03 Casterman Cecile Immunoglobulins devoid of light chains
US6838254B1 (en) 1993-04-29 2005-01-04 Conopco, Inc. Production of antibodies or (functionalized) fragments thereof derived from heavy chain immunoglobulins of camelidae
WO1995009917A1 (en) 1993-10-07 1995-04-13 The Regents Of The University Of California Genetically engineered bispecific tetravalent antibodies
US5861155A (en) 1993-12-08 1999-01-19 Astra Ab Humanized antibodies and uses thereof
US5831012A (en) 1994-01-14 1998-11-03 Pharmacia & Upjohn Aktiebolag Bacterial receptor structures
US6352694B1 (en) 1994-06-03 2002-03-05 Genetics Institute, Inc. Methods for inducing a population of T cells to proliferate using agents which recognize TCR/CD3 and ligands which stimulate an accessory molecule on the surface of the T cells
US7642228B2 (en) 1995-03-01 2010-01-05 Genentech, Inc. Method for making heteromultimeric polypeptides
US5811097A (en) 1995-07-25 1998-09-22 The Regents Of The University Of California Blockade of T lymphocyte down-regulation associated with CTLA-4 signaling
US7183076B2 (en) 1997-05-02 2007-02-27 Genentech, Inc. Method for making multispecific antibodies having heteromultimeric and common components
WO1998056915A2 (en) 1997-06-12 1998-12-17 Research Corporation Technologies, Inc. Artificial antibody polypeptides
WO1999016873A1 (de) 1997-09-26 1999-04-08 Arne Skerra Anticaline
US6696245B2 (en) 1997-10-20 2004-02-24 Domantis Limited Methods for selecting functional polypeptides
WO1999045110A1 (en) 1998-03-06 1999-09-10 Diatech Pty. Ltd. V-like domain binding molecules
US6818418B1 (en) 1998-12-10 2004-11-16 Compound Therapeutics, Inc. Protein scaffolds for antibody mimics and other binding proteins
WO2000034784A1 (en) 1998-12-10 2000-06-15 Phylos, Inc. Protein scaffolds for antibody mimics and other binding proteins
US9545086B2 (en) 1999-01-25 2017-01-17 Biogen Ma Inc. BAFF, inhibitors thereof and their use in the modulation of B-cell response and treatment of autoimmune disorders
WO2000060070A1 (en) 1999-04-01 2000-10-12 Innogenetics N.V. A polypeptide structure for use as a scaffold
WO2001004144A2 (de) 1999-07-13 2001-01-18 Scil Proteins Gmbh Design von beta-faltblatt-proteinen mit spezifischen bindungseigenschaften
US7083785B2 (en) 1999-08-17 2006-08-01 Biogen Idcc MA Inc. Methods of treatment by administering an anti-BCMA antibody
US7276241B2 (en) 1999-10-06 2007-10-02 Biogen Idec Ma Inc. Methods of treating a tumor that expresses APRIL by administering BCMA
US7105149B1 (en) 1999-11-29 2006-09-12 The Trustees Of Columbia University In The City Of New York Isolation of five novel genes coding for new Fc receptors-type melanoma involved in the pathogenesis of lymphoma/myeloma
US8299220B2 (en) 1999-11-29 2012-10-30 Trustees Of Columbia University In The City Of New York Isolation of five novel genes coding for new Fc receptors-type melanoma involved in the pathogenesis of lymphoma/melanoma
WO2001064942A1 (en) 2000-02-29 2001-09-07 Phylos, Inc. Protein scaffolds for antibody mimics and other binding proteins
US20140322221A1 (en) 2000-04-11 2014-10-30 Genentech, Inc. Multivalent antibodies and uses therefor
US20050048512A1 (en) 2001-04-26 2005-03-03 Avidia Research Institute Combinatorial libraries of monomer domains
US20050053973A1 (en) 2001-04-26 2005-03-10 Avidia Research Institute Novel proteins with targeted binding
US20040175756A1 (en) 2001-04-26 2004-09-09 Avidia Research Institute Methods for using combinatorial libraries of monomer domains
WO2003002609A2 (en) 2001-06-28 2003-01-09 Domantis Limited Dual-specific ligand and its use
US20040009530A1 (en) 2002-01-16 2004-01-15 Wilson David S. Engineered binding proteins
US8920776B2 (en) 2002-01-22 2014-12-30 Corixa Corporation Compositions and methods for the detection diagnosis and therapy of hematological malignancies
US20110177093A1 (en) 2002-02-21 2011-07-21 Biogen, Inc. Use of bcma as an immunoregulatory agent
WO2004003019A2 (en) 2002-06-28 2004-01-08 Domantis Limited Immunoglobin single variant antigen-binding domains and dual-specific constructs
US20110177073A1 (en) 2002-07-18 2011-07-21 Merus B.V. Recombinant production of mixtures of antibodies
US20100028330A1 (en) 2002-12-23 2010-02-04 Medimmune Limited Methods of upmodulating adaptive immune response using anti-pd1 antibodies
WO2004058821A2 (en) 2002-12-27 2004-07-15 Domantis Limited Dual specific single domain antibodies specific for a ligand and for the receptor of the ligand
US8003774B2 (en) 2003-01-09 2011-08-23 Macrogenics, Inc. Identification and engineering of antibodies with variant Fc regions and methods of using same
US7767429B2 (en) 2003-03-05 2010-08-03 Halozyme, Inc. Soluble hyaluronidase glycoprotein (sHASEGP), process for preparing the same, uses and pharmaceutical compositions comprising thereof
US8772246B2 (en) 2003-03-05 2014-07-08 Halozyme, Inc. Soluble hyaluronidase glycoprotein (sHASEGP), process for preparing the same, uses and pharmaceutical compositions comprising thereof
US8202517B2 (en) 2003-03-05 2012-06-19 Halozyme, Inc. Soluble hyaluronidase glycoprotein (sHASEGP), process for preparing the same, uses and pharmaceutical compositions comprising thereof
US8450470B2 (en) 2003-03-05 2013-05-28 Halozyme, Inc. Soluble hyaluronidase glycoprotein (sHASEGP), process for preparing the same, uses and pharmaceutical compositions comprising thereof
US8821883B2 (en) 2003-03-28 2014-09-02 Biogen Idec Ma Inc. Method of treating B cell cancers by administering truncated BAFF receptors
WO2004101790A1 (en) 2003-05-14 2004-11-25 Domantis Limited A process for recovering polypeptides that unfold reversibly from a polypeptide repertoire
WO2004106368A1 (de) 2003-05-28 2004-12-09 Scil Proteins Gmbh Generierung künstlicher bindungsproteine auf der grundlage von ubiquitin-proteinen
US7919257B2 (en) 2003-05-30 2011-04-05 Merus Biopharmaceuticals, B.V.I.O. Method for selecting a single cell expressing a heterogeneous combination of antibodies
WO2004081026A2 (en) 2003-06-30 2004-09-23 Domantis Limited Polypeptides
WO2005035572A2 (en) 2003-10-08 2005-04-21 Domantis Limited Antibody compositions and methods
US9387237B2 (en) 2003-10-20 2016-07-12 Biogen Ma Inc. Methods of treating a patient having an autoimmune disorder by administering a soluble BCMA
US8580252B2 (en) 2004-03-05 2013-11-12 Halozyme, Inc. Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminoglycanases
US7799902B2 (en) 2004-03-23 2010-09-21 Biogen Idec Ma Inc. Receptor coupling agents and compositions thereof
US7501121B2 (en) 2004-06-17 2009-03-10 Wyeth IL-13 binding agents
US20060008844A1 (en) 2004-06-17 2006-01-12 Avidia Research Institute c-Met kinase binding proteins
US7476724B2 (en) 2004-08-05 2009-01-13 Genentech, Inc. Humanized anti-cmet antibodies
US7855275B2 (en) 2004-09-23 2010-12-21 Genentech, Inc. Cysteine engineered antibodies and conjugates
US7750128B2 (en) 2004-09-24 2010-07-06 Amgen Inc. Modified Fc molecules
US7999077B2 (en) 2004-09-30 2011-08-16 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services IRTA2 antibodies and methods of use
US20080247944A1 (en) 2005-01-12 2008-10-09 Robert Graziano Irta-2 Antibodies and Their Uses
WO2006079372A1 (en) 2005-01-31 2006-08-03 Ablynx N.V. Method for generating variable domain sequences of heavy chain antibodies
US7431380B1 (en) 2005-02-24 2008-10-07 Theodore Allen Buresh Louver kit
US20100015133A1 (en) 2005-03-31 2010-01-21 Chugai Seiyaku Kabushiki Kaisha Methods for Producing Polypeptides by Regulating Polypeptide Association
EP1870459A1 (en) 2005-03-31 2007-12-26 Chugai Seiyaku Kabushiki Kaisha Methods for producing polypeptides by regulating polypeptide association
WO2006121168A1 (en) 2005-05-09 2006-11-16 Ono Pharmaceutical Co., Ltd. Human monoclonal antibodies to programmed death 1(pd-1) and methods for treating cancer using anti-pd-1 antibodies alone or in combination with other immunotherapeutics
US8008449B2 (en) 2005-05-09 2011-08-30 Medarex, Inc. Human monoclonal antibodies to programmed death 1 (PD-1) and methods for treating cancer using anti-PD-1 antibodies alone or in combination with other immunotherapeutics
WO2007005874A2 (en) 2005-07-01 2007-01-11 Medarex, Inc. Human monoclonal antibodies to programmed death ligand 1 (pd-l1)
US7943743B2 (en) 2005-07-01 2011-05-17 Medarex, Inc. Human monoclonal antibodies to programmed death ligand 1 (PD-L1)
WO2007059782A1 (en) 2005-11-28 2007-05-31 Genmab A/S Recombinant monovalent antibodies and methods for production thereof
US8871912B2 (en) 2006-03-24 2014-10-28 Merck Patent Gmbh Engineered heterodimeric protein domains
US7741446B2 (en) 2006-08-18 2010-06-22 Armagen Technologies, Inc. Fusion antibodies that cross the blood-brain barrier in both directions
US20080069820A1 (en) 2006-08-30 2008-03-20 Genentech, Inc. Multispecific antibodies
US8354509B2 (en) 2007-06-18 2013-01-15 Msd Oss B.V. Antibodies to human programmed death receptor PD-1
US8227577B2 (en) 2007-12-21 2012-07-24 Hoffman-La Roche Inc. Bivalent, bispecific antibodies
US8592562B2 (en) 2008-01-07 2013-11-26 Amgen Inc. Method for making antibody Fc-heterodimeric molecules using electrostatic steering effects
WO2009089004A1 (en) 2008-01-07 2009-07-16 Amgen Inc. Method for making antibody fc-heterodimeric molecules using electrostatic steering effects
WO2009101611A1 (en) 2008-02-11 2009-08-20 Curetech Ltd. Monoclonal antibodies for tumor treatment
WO2009114335A2 (en) 2008-03-12 2009-09-17 Merck & Co., Inc. Pd-1 binding proteins
US20130303396A1 (en) 2008-04-11 2013-11-14 Chugai Seiyaku Kabushiki Kaisha Antigen-binding molecule capable of binding to two or more antigen molecules repeatedly
WO2010019570A2 (en) 2008-08-11 2010-02-18 Medarex, Inc. Human antibodies that bind lymphocyte activation gene-3 (lag-3), and uses thereof
US20110150892A1 (en) 2008-08-11 2011-06-23 Medarex, Inc. Human antibodies that bind lymphocyte activation gene-3 (lag-3) and uses thereof
WO2010027827A2 (en) 2008-08-25 2010-03-11 Amplimmune, Inc. Targeted costimulatory polypeptides and methods of use to treat cancer
US8609089B2 (en) 2008-08-25 2013-12-17 Amplimmune, Inc. Compositions of PD-1 antagonists and methods of use
US20120114649A1 (en) 2008-08-25 2012-05-10 Amplimmune, Inc. Delaware Compositions of pd-1 antagonists and methods of use
WO2010077634A1 (en) 2008-12-09 2010-07-08 Genentech, Inc. Anti-pd-l1 antibodies and their use to enhance t-cell function
US20120039906A1 (en) 2009-02-09 2012-02-16 INSER (Institut National de la Recherche Medicale) PD-1 Antibodies and PD-L1 Antibodies and Uses Thereof
US9034324B2 (en) 2009-03-10 2015-05-19 Biogen Idec Ma Inc. Anti-BCMA antibodies
US8617559B2 (en) 2009-04-01 2013-12-31 Genetech, Inc. Anti-FcRH5 antibodies and immunoconjugates and methods of use
US8362213B2 (en) 2009-04-01 2013-01-29 Genentech, Inc. Anti-FcRH5 antibodies and immunoconjugates and methods of use
US8466260B2 (en) 2009-04-01 2013-06-18 Genentech, Inc. Anti-FcRH5 antibodies and immunoconjugates and methods of use
US9382323B2 (en) 2009-04-02 2016-07-05 Roche Glycart Ag Multispecific antibodies comprising full length antibodies and single chain fab fragments
US20130022601A1 (en) 2009-04-07 2013-01-24 Ulrich Brinkmann Trivalent, bispecific antibodies
US9309311B2 (en) 2009-04-27 2016-04-12 Oncomed Pharmaceuticals, Inc. Method for making Heteromultimeric molecules
US20100316645A1 (en) 2009-06-16 2010-12-16 Sabine Imhof-Jung Bispecific Antigen Binding Proteins
US8703132B2 (en) 2009-06-18 2014-04-22 Hoffmann-La Roche, Inc. Bispecific, tetravalent antigen binding proteins
US8586713B2 (en) 2009-06-26 2013-11-19 Regeneron Pharmaceuticals, Inc. Readily isolated bispecific antibodies with native immunoglobulin format
US20110054151A1 (en) 2009-09-02 2011-03-03 Xencor, Inc. Compositions and methods for simultaneous bivalent and monovalent co-engagement of antigens
US8602269B2 (en) 2009-09-14 2013-12-10 Guala Dispensing S.P.A. Trigger sprayer
US9200060B2 (en) 2009-11-23 2015-12-01 Amgen Inc. Monomeric antibody Fc
WO2011066342A2 (en) 2009-11-24 2011-06-03 Amplimmune, Inc. Simultaneous inhibition of pd-l1/pd-l2
US20130017200A1 (en) 2009-12-04 2013-01-17 Genentech, Inc. Multispecific antibodies, antibody analogs, compositions, and methods
US20110293613A1 (en) 2010-03-26 2011-12-01 Ulrich Brinkmann Bispecific antibodies
US9000130B2 (en) 2010-06-08 2015-04-07 Genentech, Inc. Cysteine engineered antibodies and conjugates
EP2581113A1 (en) 2010-06-11 2013-04-17 Kyowa Hakko Kirin Co., Ltd. Anti-tim-3 antibody
US20140044728A1 (en) 2010-06-11 2014-02-13 Kyushu University, National University Corporation Anti-tim-3 antibody
US8552156B2 (en) 2010-06-11 2013-10-08 Kyowa Hakko Kirin Co., Ltd Anti-TIM-3 antibody
WO2011155607A1 (ja) 2010-06-11 2011-12-15 協和発酵キリン株式会社 抗ｔｉｍ－３抗体
US20120184716A1 (en) 2010-08-16 2012-07-19 Novlmmune S.A. Methods for the Generation of Multispecific and Multivalent Antibodies
US20130267686A1 (en) 2010-08-24 2013-10-10 Hoffmann-La Roche Inc. Bispecific antibodies comprising a disulfide stabilized - fv fragment
US20130266568A1 (en) 2010-08-24 2013-10-10 Roche Glycart Ag Activatable bispecific antibodies
US20120149876A1 (en) 2010-11-05 2012-06-14 Zymeworks Inc. Stable Heterodimeric Antibody Design with Mutations in the Fc Domain
US20130273055A1 (en) 2010-11-16 2013-10-17 Eric Borges Agents and methods for treating diseases that correlate with bcma expression
US20120201746A1 (en) 2010-12-22 2012-08-09 Abbott Laboratories Half immunoglobulin binding proteins and uses thereof
US20140079689A1 (en) 2011-02-04 2014-03-20 Genentech, Inc. Fc VARIANTS AND METHODS FOR THEIR PRODUCTION
US20120213768A1 (en) 2011-02-19 2012-08-23 Baylor Research Institute Diagnostic and Therapeutic Uses for B Cell Maturation Antigen
US20130178605A1 (en) 2011-03-25 2013-07-11 Stanislas Blein Hetero-Dimeric Immunoglobulins
EP2699259A1 (en) 2011-04-21 2014-02-26 Boehringer Ingelheim International GmbH Bcma-based stratification and therapy for multiple myeloma patients
US8846042B2 (en) 2011-05-16 2014-09-30 Fabion Pharmaceuticals, Inc. Multi-specific FAB fusion proteins and methods of use
US20140242075A1 (en) 2011-05-30 2014-08-28 Genmab B.V. Antibody variants and uses thereof
US20140199294A1 (en) 2011-06-30 2014-07-17 Chugai Seiyaku Kabushiki Kaisha Heterodimerized polypeptide
US20130078249A1 (en) 2011-08-23 2013-03-28 Oliver Ast Bispecific t cell activating antigen binding molecules
US9145588B2 (en) 2011-09-26 2015-09-29 Merus Biopharmaceuticals B.V. Generation of binding molecules
US20130317200A1 (en) 2011-10-19 2013-11-28 Novlmmune S.A. Methods of Purifying Antibodies
US20130195849A1 (en) 2011-11-04 2013-08-01 Zymeworks Inc. Stable Heterodimeric Antibody Design with Mutations in the Fc Domain
US9340621B2 (en) 2011-11-15 2016-05-17 Boehringer Ingelheim International Gmbh Binding molecules for BCMA and CD3
WO2013079174A1 (en) 2011-11-28 2013-06-06 Merck Patent Gmbh Anti-pd-l1 antibodies and uses thereof
US20140348839A1 (en) 2011-12-20 2014-11-27 Medimmune, Llc Modified polypeptides for bispecific antibody scaffolds
US20130165638A1 (en) 2011-12-27 2013-06-27 Development Center For Biotechnology Light chain-bridged bispecific antibody
US20150133638A1 (en) 2012-02-10 2015-05-14 Genentech, Inc. Single-chain antibodies and other heteromultimers
US20150018529A1 (en) 2012-02-22 2015-01-15 Ucb Pharma S.A. Sequence Symmetric Modified IgG4 Bispecific Antibodies
US20140051833A1 (en) 2012-03-13 2014-02-20 Novlmmune S.A. Readily Isolated Bispecific Antibodies with Native Immunoglobulin Format
US20130243775A1 (en) 2012-03-14 2013-09-19 Regeneron Pharmaceuticals, Inc. Multispecific antigen-binding molecules and uses thereof
US9358286B2 (en) 2012-04-20 2016-06-07 Merus B.V. Methods and means for the production of IG-like molecules
EP2847231A1 (en) 2012-05-10 2015-03-18 Bioatla LLC Multi-specific monoclonal antibodies
US20160257763A1 (en) 2012-05-10 2016-09-08 Zymeworks Inc. Heteromultimer constructs of immunoglobulin heavy chains with mutations in the fc domain
US20150166670A1 (en) 2012-05-24 2015-06-18 Hoffmann-La Roche Inc. Multispecific antibodies
US20140051835A1 (en) 2012-06-25 2014-02-20 Zymeworks Inc. Process and Methods for Efficient Manufacturing of Highly Pure Asymmetric Antibodies in Mammalian Cells
US20150232560A1 (en) 2012-06-27 2015-08-20 Hoffmann-La Roche Inc. Method for the selection and production of tailor-made, selective and multi-specific therapeutic molecules comprising at least two different targeting entities and uses thereof
WO2014008218A1 (en) 2012-07-02 2014-01-09 Bristol-Myers Squibb Company Optimization of antibodies that bind lymphocyte activation gene-3 (lag-3), and uses thereof
US20150175707A1 (en) 2012-07-06 2015-06-25 Genmab B.V. Dimeric protein with triple mutations
US20140072581A1 (en) 2012-07-23 2014-03-13 Zymeworks Inc. Immunoglobulin Constructs Comprising Selective Pairing of the Light and Heavy Chains
US20150203591A1 (en) 2012-08-02 2015-07-23 Regeneron Pharmaceuticals, Inc. Mutivalent antigen-binding proteins
US20140037621A1 (en) 2012-08-02 2014-02-06 Jn Biosciences Llc Antibodies or fusion proteins multimerized via cysteine mutation and a mu tailpiece
US20150211001A1 (en) 2012-10-03 2015-07-30 Jason Baardsnes Methods of quantitating heavy and light chain polypeptide pairs
US20160130347A1 (en) 2012-10-08 2016-05-12 Roche Glycart Ag Fc-free antibodies comprising two Fab-fragments and methods of use
US20140154254A1 (en) 2012-11-21 2014-06-05 Amgen Inc. Heterodimeric immunoglobulins
US20140200331A1 (en) 2012-11-28 2014-07-17 Zymeworks Inc. Engineered Immunoglobulin Heavy Chain-Light Chain Pairs And Uses Thereof
US9243058B2 (en) 2012-12-07 2016-01-26 Amgen, Inc. BCMA antigen binding proteins
US20140377269A1 (en) 2012-12-19 2014-12-25 Adimab, Llc Multivalent antibody analogs, and methods of their preparation and use
US20150344570A1 (en) 2012-12-27 2015-12-03 Chugai Seiyaku Kabushiki Kaisha Heterodimerized polypeptide
US20150353636A1 (en) 2013-01-10 2015-12-10 Genmab B.V. Human igg1 fc region variants and uses thereof
US20150337049A1 (en) 2013-01-10 2015-11-26 Genmab B.V. Inert format
US20140242077A1 (en) 2013-01-23 2014-08-28 Abbvie, Inc. Methods and compositions for modulating an immune response
US9359437B2 (en) 2013-02-01 2016-06-07 Regeneron Pharmaceuticals, Inc. Antibodies comprising chimeric constant domains
US20150376287A1 (en) 2013-02-05 2015-12-31 Engmab Ag Bispecific antibodies against cd3 and bcma
US20150368351A1 (en) 2013-02-05 2015-12-24 Engmab Ag Method for the selection of antibodies against bcma
US20160131654A1 (en) 2013-02-08 2016-05-12 Institute For Myeloma & Bone Cancer Research Diagnostic, prognostic, and monitoring methods for multiple myeloma, chronic lymphocytic leukemia, and b-cell non-hodgkin lymphoma
US20150368352A1 (en) 2013-02-08 2015-12-24 Stemcentrx, Inc. Novel multispecific constructs
US20160015749A1 (en) 2013-03-05 2016-01-21 Baylor College Of Medicine Engager cells for immunotherapy
US20160039947A1 (en) 2013-03-15 2016-02-11 Eli Lilly And Company Methods for producing fabs and bi-specific antibodies
US20140363426A1 (en) 2013-03-15 2014-12-11 Gregory Moore Heterodimeric proteins
US20160176973A1 (en) 2013-03-15 2016-06-23 Amgen Research (Munich) Gmbh Binding molecules for bcma and cd3
US20140308285A1 (en) 2013-03-15 2014-10-16 Amgen Inc. Heterodimeric bispecific antibodies
US20160145340A1 (en) 2013-03-15 2016-05-26 Amegen Inc. Bispecific-fc molecules
US20160194389A1 (en) 2013-04-29 2016-07-07 Hoffmann-La Roche Inc. Fc-receptor binding modified asymmetric antibodies and methods of use
US20160114057A1 (en) 2013-05-24 2016-04-28 Zyeworks Inc. Modular protein drug conjugate therapeutic
US20160102135A1 (en) 2013-05-31 2016-04-14 Zymeworks Inc. Heteromultimers with reduced or silenced effector function
US20150098900A1 (en) 2013-06-24 2015-04-09 Genentech, Inc. Anti-fcrh5 antibodies
US20150017187A1 (en) 2013-07-10 2015-01-15 Sutro Biopharma, Inc. Antibodies comprising multiple site-specific non-natural amino acid residues, methods of their preparation and methods of their use
US20160229915A1 (en) 2013-09-27 2016-08-11 Chugai Seiyaku Kabushiki Kaisha Method for producing polypeptide heteromultimer
US20160311915A1 (en) 2013-10-10 2016-10-27 Ucl Business Plc Molecule
EP3055329A1 (en) 2013-10-11 2016-08-17 F. Hoffmann-La Roche AG Multispecific domain exchanged common variable light chain antibodies
US20150166661A1 (en) 2013-12-17 2015-06-18 Genentech, Inc. Anti-cd3 antibodies and methods of use
WO2015107025A1 (en) 2014-01-15 2015-07-23 F. Hoffmann-La Roche Ag Fc-region variants with modified fcrn-binding properties
WO2015107015A1 (en) 2014-01-15 2015-07-23 F. Hoffmann-La Roche Ag Fc-region variants with improved protein a-binding
WO2015107026A1 (en) 2014-01-15 2015-07-23 F. Hoffmann-La Roche Ag Fc-region variants with modified fcrn- and maintained protein a-binding properties
WO2015127158A1 (en) 2014-02-21 2015-08-27 Regeneron Pharmaceuticals, Inc. Methods, compositions and kits for cell specific modulation of target antigens
US20150315296A1 (en) 2014-04-02 2015-11-05 Hoffmann-La Roche Inc. Multispecific antibodies
US20170037128A1 (en) 2014-04-13 2017-02-09 Affimed Gmbh Trifunctional antigen-binding molecule
EP3137500A1 (en) 2014-04-30 2017-03-08 Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft Humanized antibodies against cd269 (bcma)
WO2015181805A1 (en) 2014-05-28 2015-12-03 Zymeworks Inc. Modified antigen binding polypeptide constructs and uses thereof
WO2015197582A1 (en) 2014-06-27 2015-12-30 Innate Pharma Monomeric multispecific antigen binding proteins
WO2015197598A2 (en) 2014-06-27 2015-12-30 Innate Pharma Multispecific antigen binding proteins
WO2016016299A1 (en) 2014-07-29 2016-02-04 F. Hoffmann-La Roche Ag Multispecific antibodies
EP2982694A1 (en) 2014-08-04 2016-02-10 EngMab AG Bispecific antibodies against cd3epsilon and bcma
US20160075785A1 (en) 2014-08-04 2016-03-17 Hoffmann-La Roche Inc. Bispecific t cell activating antigen binding molecules
WO2016026943A1 (en) 2014-08-20 2016-02-25 Argen-X N.V Asymmetric multispecific antibodies
WO2016071376A2 (en) 2014-11-06 2016-05-12 F. Hoffmann-La Roche Ag Fc-region variants with modified fcrn-binding and methods of use
WO2016071377A1 (en) 2014-11-06 2016-05-12 F. Hoffmann-La Roche Ag Fc-region variants with modified fcrn- and protein a-binding properties
EP3023437A1 (en) 2014-11-20 2016-05-25 EngMab AG Bispecific antibodies against CD3epsilon and BCMA
WO2016079081A1 (en) 2014-11-20 2016-05-26 F. Hoffmann-La Roche Ag Common light chains and methods of use
WO2016087416A1 (en) 2014-12-03 2016-06-09 F. Hoffmann-La Roche Ag Multispecific antibodies
EP3029068A1 (en) 2014-12-03 2016-06-08 EngMab AG Bispecific antibodies against CD3epsilon and BCMA for use in the treatment of diseases
WO2016087650A1 (en) 2014-12-05 2016-06-09 Merck Patent Gmbh Domain-exchanged antibody
WO2016090327A2 (en) 2014-12-05 2016-06-09 Memorial Sloan-Kettering Cancer Center Antibodies targeting b-cell maturation antigen and methods of use
WO2016110584A1 (en) 2015-01-08 2016-07-14 Biontech Ag Agonistic tnf receptor binding agents
WO2016115274A1 (en) 2015-01-14 2016-07-21 Compass Therapeutics Llc Multispecific immunomodulatory antigen-binding constructs
WO2016118641A1 (en) 2015-01-20 2016-07-28 Igm Biosciences, Inc. Tumor necrosis factor (tnf) superfamily receptor binding molecules and uses thereof
US20160264685A1 (en) 2015-03-13 2016-09-15 Novimmune Sa Methods of purifying bispecific antibodies
WO2016168149A1 (en) 2015-04-13 2016-10-20 Five Prime Therapeutics, Inc. Combination therapy for cancer
US20160297885A1 (en) 2015-04-13 2016-10-13 Pfizer Inc. Therapeutic antibodies and their uses
US20160368985A1 (en) 2015-06-16 2016-12-22 Genentech, Inc. HUMANIZED AND AFFINITY MATURED ANTIBODIES TO FcRH5 AND METHODS OF USE
US20160368988A1 (en) 2015-07-10 2016-12-22 Merus N.V. Human cd3 binding antibody
US20170022284A1 (en) 2015-07-23 2017-01-26 Inhibrx Lp Multivalent and multispecific gitr-binding fusion proteins
WO2017021450A1 (en) 2015-08-03 2017-02-09 Engmab Ag Monoclonal antibodies against bcma
US20170051068A1 (en) 2015-08-17 2017-02-23 Janssen Pharmaceutica Nv Anti-BCMA Antibodies, Bispecific Antigen Binding Molecules that Bind BCMA and CD3, and Uses Thereof
WO2018057955A1 (en) 2016-09-23 2018-03-29 Elstar Therapeutics, Inc. Multispecific antibody molecules comprising lambda and kappa light chains

Non-Patent Citations (99)

* Cited by examiner, † Cited by third party
Title
"Antibody Engineering Lab Manual", SPRINGER-VERLAG, article "Protein Sequence and Structure Analysis of Antibody Variable Domains"
"Recognition of haemagglutinins on virus-infected cells by NKp46 activates lysis by human NK cells", NATURE, vol. 409, no. 6823, 22 February 2001 (2001-02-22), pages 1055 - 60
"Recognition of viral hemagglutinins by NKp44 but not by NKp30", EUR J IMMUNOL., vol. 31, no. 9, September 2001 (2001-09-01), pages 2680 - 9
AGOSTINIS, P. ET AL., CA CANCER J. CLIN., vol. 61, 2011, pages 250 - 281
ALA-AHO R ET AL.: "Collagenases in cancer", BIOCHIMIE, vol. 87, no. 3-4, March 2005 (2005-03-01), pages 273 - 86, XP004803222, doi:10.1016/j.biochi.2004.12.009
AL-LAZIKANI ET AL., JMB, vol. 273, 1997, pages 927 - 948
ALTSCHUL ET AL., J. MOL. BIOL., vol. 215, 1990, pages 403 - 10
ALTSCHUL ET AL., NUCLEIC ACIDS RES., vol. 25, 1997, pages 3389 - 3402
BARBAS ET AL., PNAS, vol. 88, 1991, pages 7978 - 7982
BEIDLER ET AL., J. IMMUNOL., vol. 141, 1988, pages 4053 - 4060
BERG ET AL., TRANSPLANT PROC., vol. 30, no. 8, 1998, pages 3975 - 3977
BLOOD, vol. 118, no. 11, 15 September 2011 (2011-09-15)
BRUGGEMAN ET AL., EUR J IMMUNOL, vol. 21, 1991, pages 1323 - 1326
BRUGGEMAN ET AL., YEAR IMMUNOL, vol. 7, 1993, pages 33 - 40
CHAO ET AL., NATURE PROTOCOLS, vol. 1, no. 2, 2006, pages 755 - 68
CHEMICAL ABSTRACTS, Columbus, Ohio, US; abstract no. 477202-00-9
CHOTHIA, C. ET AL., J. MOL. BIOL., vol. 196, 1987, pages 901 - 917
CLACKSON ET AL., NATURE, vol. 352, 1991, pages 624 - 628
COLCHER, D. ET AL., ANN N Y ACAD SCI, vol. 880, 1999, pages 263 - 80
COLOMA, J. ET AL., NATURE BIOTECH, vol. 15, 1997, pages 159
CONNOLLY JL ET AL.: "Tumor Structure and Tumor Stroma Generation", 2003, HOLLAND-FREI
COSTA-MATTIOLI M.SONENBERG N.: "RAPping production of type I interferon in pDCs through mTOR", NATURE IMMUNOL., vol. 9, 2008, pages 1097 - 1099
DAVIS JH ET AL.: "SEEDbodies: fusion proteins based on strand exchange engineered domain (SEED) CH3 heterodimers in an Fc analogue platform for asymmetric binders or immunofusions and bispecific antibodies", PROTEIN ENG DES SEL, vol. 23, 2010, pages 195 - 202, XP055018770, doi:10.1093/protein/gzp094
DOYLE S. ET AL.: "IRF3 mediates a TLR3/TLR4-specific antiviral gene program", IMMUNITY, vol. 17, no. 3, 2002, pages 251 - 63
E. MEYERSW. MILLER, CABIOS, vol. 4, 1989, pages 11 - 17
ERJA KERKELA ET AL., JOURNAL OF INVESTIGATIVE DERMATOLOGY, vol. 114, 2000, pages 1113 - 1119
FRONT IMMUNOL., vol. 4, 2013, pages 76
FROSTSTERN: "A Microtiter-Based Assay for Hyaluronidase Activity Not Requiring Specialized Reagents", ANALYTICAL BIOCHEMISTRY, vol. 251, 1997, pages 263 - 269, XP002276368, doi:10.1006/abio.1997.2262
GARLAND ET AL., J. IMMUNOL METH., vol. 227, no. 1-2, 1999, pages 53 - 63
GARRAD ET AL., BIOLTECHNOLOGY, vol. 9, 1991, pages 1373 - 1377
GRAM ET AL., PNAS, vol. 89, 1992, pages 3576 - 3580
GREEN, L.L. ET AL., NATURE GENET., vol. 7, 1994, pages 13 - 21
GRIFFTHS ET AL., EMBO J, vol. 12, 1993, pages 725 - 734
HAANEN ET AL., J. EXP. MED., vol. 190, no. 9, 1999, pages 13191328
HALL ET AL., JOURNAL FOR IMMUNOTHERAPY OF CANCER, vol. 4, 2016, pages 61
HAMID, O. ET AL., NEW ENGLAND JOURNAL OF MEDICINE, vol. 369, no. 2, 2013, pages 134 - 44
HAWKINS ET AL., JMOL BIOL, vol. 226, 1992, pages 889 - 896
HAY ET AL., HUM ANTIBOD HYBRIDOMAS, vol. 3, 1992, pages 81 - 85
HIROFUMI MIYAZONO ET AL., SEIKAGAKU, vol. 61, 1939, pages 1023
HIROFUMI MIYAZONO ET AL., SEIKAGAKU, vol. 61, 1989, pages 1023
HOOGENBOOM ET AL., NUC ACID RES, vol. 19, 1991, pages 4133 - 4137
HUSE ET AL., SCIENCE, vol. 246, 1989, pages 1275 - 1281
HUSTON ET AL., PROC. NATL. ACAD. SCI. USA, vol. 85, 1988, pages 5879 - 5883
J EXP MED., vol. 169, no. 1, 1 January 1989 (1989-01-01), pages 73 - 86
J IMMUNOL., vol. 150, no. 6, 15 March 1993 (1993-03-15), pages 2305 - 15
JONES ET AL., NATURE, vol. 321, 1986, pages 552 - 525
K. HIYAMAS. OKADA, J. BIOCHEM. (TOKYO, vol. 80, 1976, pages 1201
K. HIYAMAS. OKADA, J. BIOL. CHEM., vol. 250, 1975, pages 1824
KENICHI MAEYAMA ET AL., SEIKAGAKU, vol. 57, 1985, pages 1189
KLEIN ET AL., MABS, vol. 4, no. 6, November 2012 (2012-11-01), pages 653 - 663
LABRIJN ET AL., NATURE PROTOCOLS, vol. 9, no. 10, 2014, pages 2450 - 63
LABRIJN ET AL., PNAS, vol. 110, no. 13, 2013, pages 5145 - 5150
LI ET AL., BIOPOLYMERS, vol. 87, 2007, pages 225 - 230
LI HANCHEN ET AL.: "Tumor Microenvironment: The Role of the Tumor Stroma in Cancer", J OF CELLULAR BIOCHEMISTRY, vol. 101, 2007, pages 805 - 815
LIU ET AL., BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 17, 2007, pages 617 - 620
LIU ET AL., J. IMMUNOL., vol. 139, 1987, pages 3521 - 3526
LOBUGLIO ET AL., HYBRIDOMA, vol. 5, 1986, pages 5117 - 5123
LONBERG, N. ET AL., NATURE, vol. 368, 1994, pages 856 - 859
MARTENS T ET AL.: "A novel one-armed antic- Met antibody inhibits glioblastoma growth in vivo", CLIN CANCER RES, vol. 12, 2006, pages 6144 - 52, XP002618391, doi:10.1158/1078-0432.CCR-05-1418
MARTIN ET AL., EMBO J., vol. 13, 1994, pages 5303 - 5309
MAYER G.NYLAND J.: "Microbiology and Immunology on-line", 2010, UNIVERSITY OF SOUTH CAROLINA SCHOOL OF MEDICINE, article "Major Histocompatibility Complex and T-cell Receptors-Role in Immune Responses"
MCCONNELLHOESS, J MOL. BIOL., vol. 250, 1995, pages 460
MOORE GL ET AL.: "A novel bispecific antibody format enables simultaneous bivalent and monovalent co-engagement of distinct target antigens", MABS, vol. 3, 2011, pages 546 - 57, XP055030488, doi:10.4161/mabs.3.6.18123
MORRISON, S. L., SCIENCE, vol. 229, 1985, pages 1202 - 1207
MORRISON, S.L. ET AL., PROC. NATL. ACAD. SCI. USA, vol. 81, 1994, pages 6851 - 6855
NEEDLEMANWUNSCH, J. MOL. BIOL., 1970, pages 444 - 453
NISHIMURA ET AL., CANC. RES., vol. 47, 1987, pages 999 - 1005
OI ET AL., BIOTECHNIQUES, vol. 4, 1986, pages 214
ONCOIMMUNOLOGY, vol. 5, no. 1, 2016, pages e1052930
PARDOLL. NAT. REV. CANCER, vol. 12.4, 2012, pages 252 - 64
PROC NATL ACAD SCI USA., vol. 102, no. 21, 24 May 2005 (2005-05-24), pages 7641 - 7646
RAKOFF-NAHOUM S.MEDZHITOV R.: "Toll-like receptors and cancer", NAT REVS CANCER, vol. 9, 2009, pages 57 - 63
REITER, Y., CLIN CANCER RES, vol. 2, 1996, pages 245 - 52
RIDGWAY, J. ET AL., PROT. ENGINEERING, vol. 9, no. 7, 1996, pages 617 - 621
ROSENBERG ET AL., NEW ENG. J. OF MED., vol. 319, 1988, pages 1676
SALEH ET AL., J. CANCER IMMUNOL. IMMUNOTHER., vol. 32, 1990, pages 180 - 190
SCODELLER P: "Hyaluronidase and other Extracellular Matrix Degrading Enzymes for Cancer Therapy: New Uses and Nano- Formulations", J CARCINOG MUTAGE, vol. 5, 2014, pages 178, XP055222389, doi:10.4172/2157-2518.1000178
See also references of EP3818083A2
SHAW ET AL., J. NATL CANCER INST., vol. 80, 1988, pages 1553 - 1559
SHIMABUKURO-VORNHAGEN ET AL., J IMMUNOTHER CANCER, vol. 6, no. 1, 15 June 2018 (2018-06-15), pages 56
SPEISS ET AL., MOLECULAR IMMUNOLOGY, vol. 67, 2015, pages 95 - 106
SPIESS C ET AL.: "Alternative molecular formats and therapeutic applications for bispecific antibodies", MOLECULAR IMMUNOLOGY, vol. 67, 2015, pages 95 - 106, XP029246892, doi:10.1016/j.molimm.2015.01.003
SPIESS ET AL., MOL. IMMUNOL., vol. 67, 2015, pages 95 - 106
SUN ET AL., PNAS, vol. 84, 1987, pages 3439 - 3443
T. YAMAGATA ET AL., J. BIOL. CHEM., vol. 243, 1968, pages 1543
THORPE, P.E., CLIN. CANCER RES., vol. 10, 2004, pages 415 - 427
TOMLINSON ET AL., J. MOL. BIOL., vol. 227, 1992, pages 776 - 798
TRAMONTANO ET AL., J MOL. RECOGNIT., vol. 7, 1994, pages 9
TUAILLON ET AL., PNAS, vol. 90, 1993, pages 3720 - 3724
VERHOEYAN ET AL., SCIENCE, vol. 239, 1988, pages 1534 - 1043
VINEY ET AL., HYBRIDOMA, vol. ll, no. 6, December 1992 (1992-12-01), pages 701 - 13
WANG CY ET AL., INT J ONCOL., vol. 48, no. 6, 2016, pages 2247 - 56
WEI S.CONCANNON P., HUMAN IMMUNOLOGY, vol. 41, no. 3, 1994, pages 201 - 206
WEIDLE U ET AL.: "The Intriguing Options of Multispecific Antibody Formats for Treatment of Cancer", CANCER GENOMICS & PROTEOMICS, vol. 10, 2013, pages 1 - 18, XP002728008
WINNAKER: "From Genes to Clones", 1987, VERLAGSGESELLSCHAFT
WOOD ET AL., NATURE, vol. 314, 1985, pages 446 - 449
Y. M. MICHELACCIC. P. DIETRICH, BIOCHEM. BIOPHYS. RES. COMMUN., vol. 56, 1974, pages 973
Y. M. MICHELACCIC. P. DIETRICH, BIOCHEM. J., vol. 151, 1975, pages 121
YASSAI ET AL., IMMUNOGENETICS, vol. 61, no. 7, 2009, pages 493 - 502

Cited By (46)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12110328B2 (en) 2015-01-27 2024-10-08 LAVA Therapeutics N.V. Single domain antibodies targeting CD1d
US12247060B2 (en) 2018-01-09 2025-03-11 Marengo Therapeutics, Inc. Calreticulin binding constructs and engineered T cells for the treatment of diseases
US12152073B2 (en) 2018-03-14 2024-11-26 Marengo Therapeutics, Inc. Multifunctional molecules that bind to calreticulin and uses thereof
US11965025B2 (en) 2018-07-03 2024-04-23 Marengo Therapeutics, Inc. Method of treating solid cancers with bispecific interleukin-anti-TCRß molecules
US12286477B2 (en) 2018-07-03 2025-04-29 Marengo Therapeutics, Inc. Anti-TCR antibody molecules and uses thereof
US12351632B2 (en) 2018-07-03 2025-07-08 Marengo Therapeutics, Inc. Anti-TCR antibody molecules and uses thereof
US11845797B2 (en) 2018-07-03 2023-12-19 Marengo Therapeutics, Inc. Anti-TCR antibody molecules and uses thereof
US12077586B2 (en) 2018-09-19 2024-09-03 LAVA Therapeutics N.V. Bispecific antibodies for use in the treatment of hematological malignancies
GB2595980B (en) * 2019-01-04 2023-06-14 Marengo Therapeutics Inc Anti-TCR antibody molecules and uses thereof
GB2595980A (en) * 2019-01-04 2021-12-15 Marengo Therapeutics Inc Anti-TCR antibody molecules and uses thereof
WO2020142672A3 (en) * 2019-01-04 2020-08-20 Elstar Therapeutics, Inc. Anti-tcr antibody molecules and uses thereof
IL284891B1 (en) * 2019-01-30 2026-01-01 Immunocore Ltd HLA-A 02 and CD3 restricted peptide binds IMMTAC with extended half-life
US20220119479A1 (en) * 2019-01-30 2022-04-21 Immunocore Limited Half-life extended immtac binding cd3 and a hla-a*02 restricted peptide
GB2598218B (en) * 2019-02-21 2024-05-08 Marengo Therapeutics Inc Anti-TCR antibody molecules and uses thereof
US12384842B2 (en) 2019-02-21 2025-08-12 Marengo Therapeutics, Inc. Antibody molecules that bind to NKP30 and uses thereof
US12358982B2 (en) 2019-02-21 2025-07-15 Marengo Therapeutics, Inc. Multifunctional molecules that bind to T cell related cancer cells and uses thereof
WO2020172596A1 (en) * 2019-02-21 2020-08-27 Elstar Therapeutics, Inc. Anti-tcr antibody molecules and thereof
GB2598218A (en) * 2019-02-21 2022-02-23 Marengo Therapeutics Inc Anti-TCR antibody molecules and uses thereof
US12264197B2 (en) 2019-03-11 2025-04-01 Janssen Biotech, Inc. Anti-Vβ17/anti-CD123 bispecific antibodies
US20230087378A1 (en) * 2019-12-20 2023-03-23 UCB Biopharma SRL Multi-specific antibody with binding specificity for human il-13 and il-17
US12570738B2 (en) * 2019-12-20 2026-03-10 UCB Biopharma SRL Multi-specific antibody with binding specificity for human IL-13 and IL-17
EP4084823A4 (en) * 2020-01-03 2024-05-15 Marengo Therapeutics, Inc. ANTI-TCR ANTIBODY MOLECULES AND THEIR USES
US12486326B2 (en) 2020-01-03 2025-12-02 Marengo Therapeutics, Inc. Anti-TCR antibody molecules and uses thereof
US20230102344A1 (en) * 2020-01-03 2023-03-30 Marengo Therapeutics, Inc. Multifunctional molecules that bind to cd33 and uses thereof
WO2021155112A1 (en) * 2020-01-29 2021-08-05 The Trustees Of The University Of Pennsylvania Compositions and methods of t cell receptor vb family member targeting for the treatment of t cell associated disease
US12312400B2 (en) 2020-02-16 2025-05-27 Aulos Bioscience, Inc. Engineered anti-il-2 antibodies
US12428493B2 (en) 2020-07-08 2025-09-30 LAVA Therapeutics N.V. Antibodies that bind PSMA and gamma-delta T cell receptors
CN112552404A (zh) * 2020-07-20 2021-03-26 北京鼎成肽源生物技术有限公司 一种靶向c-Met的单链抗体、嵌合抗原受体、重组载体、CAR-T细胞及应用
US12492226B2 (en) 2020-08-10 2025-12-09 Janssen Biotech, Inc. Materials and methods for producing bioengineered virus specific lymphocytes
WO2022046920A3 (en) * 2020-08-26 2022-04-07 Marengo Therapeutics, Inc. Multifunctional molecules that bind to calreticulin and uses thereof
US11965024B2 (en) 2020-09-11 2024-04-23 Janssen Biotech, Inc. Methods and compositions for modulating beta chain mediated immunity
US12448449B2 (en) 2020-09-11 2025-10-21 Janssen Biotech, Inc. Immune targeting molecules and uses thereof
WO2022056199A1 (en) * 2020-09-11 2022-03-17 Janssen Biotech, Inc. Multi-specific immune targeting molecules and uses thereof
US20220089737A1 (en) * 2020-09-11 2022-03-24 Janssen Biotech, Inc. Multi-specific immune targeting molecules and uses thereof
US12492256B2 (en) 2020-09-11 2025-12-09 Janssen Biotech, Inc. Methods and compositions for modulating beta chain mediated immunity
JP2023540799A (ja) * 2020-09-11 2023-09-26 ヤンセン バイオテツク，インコーポレーテツド 多重特異性免疫標的化分子及びその使用
JP2023551535A (ja) * 2020-12-01 2023-12-08 ザ・ジョンズ・ホプキンス・ユニバーシティー Ｔ細胞がんを治療するための方法および材料
WO2022119955A1 (en) * 2020-12-01 2022-06-09 The Johns Hopkins University Methods and materials for treating t cell cancers
WO2022194042A1 (zh) * 2021-03-15 2022-09-22 成都益安博生物技术有限公司 一种急性髓细胞性白血病的外周血tcr标志物及其检测试剂盒和应用
JP2024515591A (ja) * 2021-04-08 2024-04-10 マレンゴ・セラピューティクス，インコーポレーテッド Ｔｃｒに結合する多機能性分子およびその使用
US11859009B2 (en) 2021-05-05 2024-01-02 Immatics Biotechnologies Gmbh Antigen binding proteins specifically binding PRAME
US12570760B2 (en) 2021-05-05 2026-03-10 Immatics Biotechnologies Gmbh Antigen binding proteins specifically binding PRAME
EP4426321A4 (en) * 2021-11-05 2025-12-10 Marengo Therapeutics Inc IMMUNE CELL POPULATIONS AND THEIR USES
RU2774031C1 (ru) * 2021-12-02 2022-06-14 Федеральное государственное бюджетное учреждение "Национальный медицинский исследовательский центр радиологии" Министерства здравоохранения Российской Федерации (ФГБУ "НМИЦ радиологии" Минздрава России) Способ подавления индуцирующего действия высокомолекулярной гиалуроновой кислоты на стволовые клетки рака молочной железы
WO2023235772A3 (en) * 2022-05-31 2024-01-04 Fred Hutchinson Cancer Center Humanized anti-cd45 antibodies and uses thereof
WO2024254611A3 (en) * 2023-06-09 2025-03-06 Marengo Therapeutics, Inc. Multispecific molecules binding to tcr and uses thereof

Also Published As

Publication number Publication date
US20230025484A1 (en) 2023-01-26
US20250215085A1 (en) 2025-07-03
JP2021530246A (ja) 2021-11-11
US20220064297A1 (en) 2022-03-03
US20230031734A1 (en) 2023-02-02
DE202019005887U1 (de) 2023-06-14
EP3818083A2 (en) 2021-05-12
CA3105448A1 (en) 2020-01-09
US12286477B2 (en) 2025-04-29
US11965025B2 (en) 2024-04-23
CN112955465A (zh) 2021-06-11
AU2019297451A1 (en) 2021-01-28
WO2020010250A3 (en) 2020-02-06
US20230272074A1 (en) 2023-08-31
US20230174650A1 (en) 2023-06-08
US20230127740A1 (en) 2023-04-27
JP2024170589A (ja) 2024-12-10
JP7554742B2 (ja) 2024-09-20
US20230034161A1 (en) 2023-02-02
US20250340640A1 (en) 2025-11-06
US20240076377A1 (en) 2024-03-07
US20240301060A1 (en) 2024-09-12
US20210277119A1 (en) 2021-09-09
US11845797B2 (en) 2023-12-19
US20230142522A1 (en) 2023-05-11
US12351632B2 (en) 2025-07-08

Similar Documents

Publication Publication Date Title
US12351632B2 (en) Anti-TCR antibody molecules and uses thereof
US12486326B2 (en) Anti-TCR antibody molecules and uses thereof
US20250099579A1 (en) Multispecific molecules binding to tcr and uses thereof
AU2020224154A1 (en) Multifunctional molecules that bind to calreticulin and uses thereof
US20240409636A1 (en) Multifunctional molecules binding to tcr and uses thereof
AU2021331075A1 (en) Multifunctional molecules that bind to calreticulin and uses thereof
US20250297007A1 (en) Multifunctional molecules binding to tcr and uses thereof
US20240400990A1 (en) Immune cell populations and uses thereof
WO2024226532A2 (en) Multifunctional molecules binding to tcr and uses thereof
WO2025222066A1 (en) Multifunctional molecules binding to tcr and uses thereof

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 19745444

Country of ref document: EP

Kind code of ref document: A2

ENP Entry into the national phase

Ref document number: 3105448

Country of ref document: CA

ENP Entry into the national phase

Ref document number: 2021521940

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2019297451

Country of ref document: AU

Date of ref document: 20190703

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 2019745444

Country of ref document: EP

Effective date: 20210203