IL297412A - Precursor tri-specific antibody constructs and methods of use thereof - Google Patents

Precursor tri-specific antibody constructs and methods of use thereof

Info

Publication number
IL297412A
IL297412A IL297412A IL29741222A IL297412A IL 297412 A IL297412 A IL 297412A IL 297412 A IL297412 A IL 297412A IL 29741222 A IL29741222 A IL 29741222A IL 297412 A IL297412 A IL 297412A
Authority
IL
Israel
Prior art keywords
seq
domain
polypeptide
nos
binding domain
Prior art date
Application number
IL297412A
Other languages
English (en)
Hebrew (he)
Original Assignee
Immunorizon Ltd
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 Immunorizon Ltd filed Critical Immunorizon Ltd
Publication of IL297412A publication Critical patent/IL297412A/en

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
    • 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
    • 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
    • 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
    • C07K16/2851—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 lectin superfamily, e.g. CD23, CD72
    • 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
    • C07K16/2863—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C07K16/3069—Reproductive system, e.g. ovaria, uterus, testes, prostate
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • C07K16/468—Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
    • 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
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • 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
    • 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
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/35—Valency
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/51—Complete heavy chain or Fd fragment, i.e. VH + CH1
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/515—Complete light chain, i.e. VL + CL
    • 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
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
    • 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
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/50—Fusion polypeptide containing protease site

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Medicinal Chemistry (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Cell Biology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • General Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Gynecology & Obstetrics (AREA)
  • Pregnancy & Childbirth (AREA)
  • Reproductive Health (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
IL297412A 2020-05-04 2021-05-04 Precursor tri-specific antibody constructs and methods of use thereof IL297412A (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US202063019443P 2020-05-04 2020-05-04
US202063026143P 2020-05-18 2020-05-18
PCT/IL2021/050506 WO2021224913A1 (en) 2020-05-04 2021-05-04 Precursor tri-specific antibody constructs and methods of use thereof

Publications (1)

Publication Number Publication Date
IL297412A true IL297412A (en) 2022-12-01

Family

ID=76076399

Family Applications (1)

Application Number Title Priority Date Filing Date
IL297412A IL297412A (en) 2020-05-04 2021-05-04 Precursor tri-specific antibody constructs and methods of use thereof

Country Status (11)

Country Link
US (1) US20230312753A1 (https=)
EP (1) EP4146695A1 (https=)
JP (1) JP2023525695A (https=)
KR (1) KR20230005952A (https=)
CN (1) CN116096754A (https=)
AU (1) AU2021267953A1 (https=)
BR (1) BR112022022369A2 (https=)
CA (1) CA3181963A1 (https=)
IL (1) IL297412A (https=)
MX (1) MX2022013876A (https=)
WO (1) WO2021224913A1 (https=)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3966250A4 (en) * 2019-05-07 2022-11-23 Immunorizon Ltd. PRECURSOR TRI-SPECIFIC ANTIBODY CONSTRUCTIONS AND METHODS OF USE THEREOF
US11912771B2 (en) 2021-03-09 2024-02-27 Cdr-Life Ag MAGE-A4 peptide-MHC antigen binding proteins
EP4304725A1 (en) 2021-03-09 2024-01-17 CDR-Life AG Rabbit-derived antigen binding protein nucleic acid libraries
US20240228626A1 (en) * 2021-05-04 2024-07-11 Immunorizon Ltd. Anti-nkg2d antibodies and uses thereof
CA3217716A1 (en) * 2021-05-04 2022-11-10 Oren Bogin Anti-5t4 antibodies and uses thereof
US12162940B2 (en) 2021-05-05 2024-12-10 Immatics Biotechnologies Gmbh BMA031 antigen binding polypeptides
JP2025500845A (ja) * 2021-12-14 2025-01-15 ユニバーシティ オブ ピッツバーグ －オブ ザ コモンウェルス システム オブ ハイヤー エデュケイション Ｃｄ９４／ｎｋｇ２ａヘテロ二量体ポリペプチドに結合する分子
KR20250067130A (ko) 2022-09-14 2025-05-14 씨디알-라이프 아게 Mage-a4 펩티드 이중 t 세포 연결체
TW202540188A (zh) * 2023-12-01 2025-10-16 比利時商艾伯霖克斯公司 精準活化的多肽

Family Cites Families (47)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4237224A (en) 1974-11-04 1980-12-02 Board Of Trustees Of The Leland Stanford Jr. University Process for producing biologically functional molecular chimeras
US4751180A (en) 1985-03-28 1988-06-14 Chiron Corporation Expression using fused genes providing for protein product
US4935233A (en) 1985-12-02 1990-06-19 G. D. Searle And Company Covalently linked polypeptide cell modulators
US6291158B1 (en) 1989-05-16 2001-09-18 Scripps Research Institute Method for tapping the immunological repertoire
US6291161B1 (en) 1989-05-16 2001-09-18 Scripps Research Institute Method for tapping the immunological repertiore
US5283173A (en) 1990-01-24 1994-02-01 The Research Foundation Of State University Of New York System to detect protein-protein interactions
US5151510A (en) 1990-04-20 1992-09-29 Applied Biosystems, Inc. Method of synethesizing sulfurized oligonucleotide analogs
US6005079A (en) 1992-08-21 1999-12-21 Vrije Universiteit Brussels Immunoglobulins devoid of light chains
AU701578B2 (en) 1992-08-21 1999-02-04 Vrije Universiteit Brussel Immunoglobulins devoid of light chains
WO1994025591A1 (en) 1993-04-29 1994-11-10 Unilever N.V. PRODUCTION OF ANTIBODIES OR (FUNCTIONALIZED) FRAGMENTS THEREOF DERIVED FROM HEAVY CHAIN IMMUNOGLOBULINS OF $i(CAMELIDAE)
ES2229236T3 (es) 1994-01-11 2005-04-16 Dyax Corporation Inhibidores de la plasmina humana derivados de los dominios de kunitz.
US5837458A (en) 1994-02-17 1998-11-17 Maxygen, Inc. Methods and compositions for cellular and metabolic engineering
AUPP221098A0 (en) 1998-03-06 1998-04-02 Diatech Pty Ltd V-like domain binding molecules
SI1629011T1 (sl) 2003-05-31 2010-05-31 Micromet Ag Humane molekule za vezavo anti hu cd
CN103555733A (zh) 2005-01-05 2014-02-05 F-星生物技术研究与开发有限公司 分子中互补决定区以外的区域中工程改造了的具有结合特性的合成免疫球蛋白结构域
GB0504767D0 (en) 2005-03-08 2005-04-13 Ares Trading Sa Lipocalin protein
AU2006301492B2 (en) 2005-10-11 2011-06-09 Amgen Research (Munich) Gmbh Compositions comprising cross-species-specific antibodies and uses thereof
EP1829895A1 (en) 2006-03-03 2007-09-05 f-star Biotechnologische Forschungs- und Entwicklungsges.m.b.H. Bispecific molecule binding TLR9 and CD32 and comprising a T cell epitope for treatment of allergies
CN101484471B (zh) * 2006-06-30 2013-11-06 诺沃-诺迪斯克有限公司 抗-nkg2a抗体及其用途
WO2008119565A2 (en) 2007-04-03 2008-10-09 Micromet Ag Cross-species-specific binding domain
RS53008B2 (sr) 2007-04-03 2022-12-30 Amgen Res Munich Gmbh Interspecijski specifičan cd3-epsilon vezujući domen
CN101319011B (zh) * 2007-06-04 2010-11-10 中国人民解放军军事医学科学院基础医学研究所 多型别hcv-e1表位复合免疫原及其编码基因与应用
CA2738568C (en) 2008-10-01 2024-02-20 Micromet Ag Cross-species-specific single domain bispecific single chain antibody
PT2403935T (pt) 2009-03-04 2017-09-22 Univ Pennsylvania Composições compreendendo fatores angiogénicos e metedos para a sua utilização
JP5593641B2 (ja) 2009-06-26 2014-09-24 味の素株式会社 減塩飲食品用組成物
WO2012158818A2 (en) 2011-05-16 2012-11-22 Fabion Pharmaceuticals, Inc. Multi-specific fab fusion proteins and methods of use
DK2714733T3 (da) 2011-05-21 2019-05-06 Macrogenics Inc Cd3-bindende molekyler, der er i stand til at binde til human og ikke-human cd3
KR102047248B1 (ko) * 2011-06-17 2019-11-21 노보 노르디스크 에이/에스 침식성 세포의 선택적 제거
GB201203442D0 (en) 2012-02-28 2012-04-11 Univ Birmingham Immunotherapeutic molecules and uses
WO2014012085A2 (en) * 2012-07-13 2014-01-16 Zymeworks Inc. Bispecific asymmetric heterodimers comprising anti-cd3 constructs
CN110627907B (zh) 2013-11-04 2024-03-29 艾科诺斯科技股份有限公司 重靶向t细胞的异源二聚免疫球蛋白的产生
IL270562B (en) 2014-01-31 2022-08-01 Cytomx Therapeutics Inc Polypeptide substrates that activate matriptase and u-plasminogen and other cleavable groups, preparations containing them and their uses
JP7020909B2 (ja) * 2014-07-25 2022-02-16 シトムクス セラピューティクス，インコーポレイティド 抗－ｃｄ３抗体、活性化可能抗－ｃｄ３抗体、多重特異的抗－ｃｄ３抗体、多重特異的活性化可能抗－ｃｄ３抗体、及びそれらの使用方法
EP2985294A1 (en) * 2014-08-14 2016-02-17 Deutsches Krebsforschungszentrum Recombinant antibody molecule and its use for target cell restricted T cell activation
CA2959463A1 (en) * 2014-09-16 2016-03-24 Innate Pharma Treatment regimens using anti-nkg2a antibodies
AU2015323313B2 (en) 2014-09-25 2021-04-01 Amgen Inc. Protease-activatable bispecific proteins
CA3011374A1 (en) * 2016-02-05 2017-08-10 Washington University Compositions and methods for targeted cytokine delivery
CN109476756B (zh) * 2016-03-15 2022-05-31 埃泰美德(香港)有限公司 一种多特异性Fab融合蛋白及其用途
CR20180453A (es) 2016-03-22 2018-12-05 Hoffmann La Roche Moleculas biespecíficas de células t activadas por proteasas
SG11202007572VA (en) * 2018-02-15 2020-09-29 Macrogenics Inc Variant cd3-binding domains and their use in combination therapies for the treatment of disease
WO2019164930A1 (en) * 2018-02-20 2019-08-29 Dragonfly Therapeutics, Inc. Multi-specific binding proteins that bind cd33, nkg2d, and cd16, and methods of use
US20210269530A1 (en) * 2018-05-14 2021-09-02 Harpoon Therapeutics, Inc. Conditionally activated binding protein comprising a sterically occluded target binding domain
EP3793607A1 (en) * 2018-05-15 2021-03-24 MedImmune Limited Treatment of cancer
EA202091977A1 (ru) * 2018-05-28 2021-02-09 Драгонфлай Терапьютикс, Инк. Мультиспецифические связывающие белки, которые связывают cd33, nkg2d и cd16, и способы применения
WO2020023553A1 (en) * 2018-07-24 2020-01-30 Inhibrx, Inc. Multispecific polypeptide constructs containing a constrained cd3 binding domain and a receptor binding region and methods of using the same
EA202091888A1 (ru) * 2018-08-08 2020-10-23 Драгонфлай Терапьютикс, Инк. Вариабельные домены антител, нацеленные на рецептор nkg2d
WO2020084608A1 (en) * 2018-10-22 2020-04-30 Explore Bio 1 Ltd Precursor bispecific antibody constructs and methods of use thereof

Also Published As

Publication number Publication date
CN116096754A (zh) 2023-05-09
EP4146695A1 (en) 2023-03-15
MX2022013876A (es) 2023-02-09
US20230312753A1 (en) 2023-10-05
WO2021224913A1 (en) 2021-11-11
AU2021267953A1 (en) 2022-11-17
BR112022022369A2 (pt) 2023-03-14
CA3181963A1 (en) 2021-11-11
KR20230005952A (ko) 2023-01-10
JP2023525695A (ja) 2023-06-19

Similar Documents

Publication Publication Date Title
IL297412A (en) Precursor tri-specific antibody constructs and methods of use thereof
US20220195041A1 (en) Precursor tri-specific antibody constructs and methods of use thereof
US20210393776A1 (en) Bispecific fab fusion proteins comprising a cd3-binding fab fragment with n-terminal fusion to a binding domain and methods of use
JP6669800B2 (ja) Ｍａｓｐ−２依存性の補体活性化を阻害するための組成物
RU2725811C1 (ru) Антитела против 4-1bb человека и их применение
IL298111A (en) Antibodies to tigit
KR20220012256A (ko) Il-2 조성물 및 이의 사용 방법
IL258394A (en) Anti-tigit antigen-binding proteins and methods of their use
IL259162A (en) Fgfr2 inhibitors alone or in combination with vaccine stimulants in cancer treatment
IL255577A (en) Coupling-tigit materials and their uses
WO2020084608A1 (en) Precursor bispecific antibody constructs and methods of use thereof
JP2016529882A (ja) ヒト化またはキメラｃｄ３抗体
KR20200041835A (ko) 재조합 이중특이적 항체
JP2022507253A (ja) チェックポイント分子に対する多重特異性結合性構築物およびその使用
IL298867A (en) Bispecific immune cell engagers with binding specificity for hla-g and another antigen
IL295413A (en) Antibodies conjugated with fatty acid molecules and their uses
IL303295A (en) Multi-specific antibodies and antibody combinations
IL317834A (en) Fusion protein containing anti-CD73 antibody and IL2 and use thereof
HK1198540B (en) Multi-specific fab fusion proteins and methods of use
HK40030237A (en) Anti-sirp-alpha antibodies and related methods