WO2013001065A1 - Antikörper gegen das prostata-spezifische stammzellantigen und dessen verwendung - Google Patents

Antikörper gegen das prostata-spezifische stammzellantigen und dessen verwendung Download PDF

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Publication number
WO2013001065A1
WO2013001065A1 PCT/EP2012/062716 EP2012062716W WO2013001065A1 WO 2013001065 A1 WO2013001065 A1 WO 2013001065A1 EP 2012062716 W EP2012062716 W EP 2012062716W WO 2013001065 A1 WO2013001065 A1 WO 2013001065A1
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WO
WIPO (PCT)
Prior art keywords
antibody
psca
seq
antibodies
binding
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/EP2012/062716
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German (de)
English (en)
French (fr)
Inventor
Michael Bachmann
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.)
Technische Universitaet Dresden
Original Assignee
Technische Universitaet Dresden
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
Priority to DK12729996.4T priority Critical patent/DK2726507T3/en
Priority to EP12729996.4A priority patent/EP2726507B1/de
Priority to AU2012277784A priority patent/AU2012277784B2/en
Priority to EP18207370.0A priority patent/EP3505536B1/de
Priority to LTEP12729996.4T priority patent/LT2726507T/lt
Priority to RS20190218A priority patent/RS58448B1/sr
Priority to HRP20190289TT priority patent/HRP20190289T1/hr
Priority to US14/129,933 priority patent/US9200078B2/en
Priority to JP2014517736A priority patent/JP2014528696A/ja
Application filed by Technische Universitaet Dresden filed Critical Technische Universitaet Dresden
Priority to ES12729996T priority patent/ES2711978T3/es
Priority to SI201231523T priority patent/SI2726507T1/sl
Priority to SM20190085T priority patent/SMT201900085T1/it
Priority to PL12729996T priority patent/PL2726507T3/pl
Publication of WO2013001065A1 publication Critical patent/WO2013001065A1/de
Anticipated expiration legal-status Critical
Priority to CY20191100176T priority patent/CY1121249T1/el
Ceased legal-status Critical Current

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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
    • C07K16/30—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
    • 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
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
    • 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
    • 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
    • C07K16/30—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
    • 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
    • C07K2317/60—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

  • CDR of heavy chain variable region CDR1 SEQ ID NO. 4, CDR2 SEQ ID NO. 5, CDR3 SEQ ID NO. 6th
  • antibody includes any antibody or antibody fragment capable of binding specifically to an antigen, recombinant antibodies being antibodies produced by genetically engineered organisms includes both the complete monoclonal antibodies and their epitope-binding fragments, where the epitope-binding fragments (also referred to herein as antibody fragments) comprise those parts of the antibody capable of binding to the antigen.
  • a pharmaceutical composition according to the invention preferably contains at least two different (preferably recombinant) antibodies, wherein at least one anti-PSCA antibody according to the invention is contained and at least one further recombinant antibody, which forms a specific binding with the anti-PSCA antibody according to the invention.
  • Preferred combinations thereof are a bispecific anti-PSCA antibody containing the 5B9 paratope and another recombinant antibody containing a peptide having an amino acid sequence identity of at least 90%, preferably at least 95%, more preferably at least 99% to any of the amino acid sequences of SEQ ID no. 75 or a bispecific anti-PSCA antibody containing the 7B6 paratope and another recombinant antibody comprising a peptide having an amino acid sequence identity of at least 90%, preferably at least 95%, more preferably at least 99% to one of the amino acid sequences of SEQ ID No. 76 contains.
  • nucleic acids within the meaning of the invention, in addition to deoxyribonucleic acids (DNA) and ribonucleic acids (RNA) also includes all other linear polymers in which the bases adenine (A), cytosine (C), guanine (G) and thymine (T) or uracil
  • the invention also encompasses the corresponding RNA sequences (in which thymine is replaced by uracil), complementary sequences and sequences with modified nucleic acid backbone or 3 'or 5' terminus
  • Altered backbone nucleic acid sequences encompasses all other linear polymers in which the bases adenine (A), cytosine (C), guanine (G) and thymine (T) or uracil (U) are arranged in a corresponding sequence, such as.
  • oligonucleotides according to SEQ ID no. 138 to 142 stored together. Subsequently, the humanized nucleic acid sequence of the heavy chain variable region of the 5B9 antibody (with a G 4 S linker peptide, SEQ ID No. 132) was amplified by means of the primer pair according to SEQ ID no. 143 and 144 amplified. For the humanization of the light chain variable region of the 5B9 antibody, oligonucleotides according to SEQ ID no. 145 to 149 together. The humanized nucleic acid sequence of the 5B9 light chain variable region was amplified with the primer pair of SEQ ID NO. 150 and 151 amplified.
  • a mouse anti-c-myc IgG-FITC detection antibody (AbD Serotec, Dusseldorf, Germany) was used, which after completion of the first staining step for 30 min at 4 ° C with the anti-PSCA antibody-labeled PSCA-positive cells was incubated.
  • a negative control a sample was carried in which PSCA-positive cells were stained only with the detection antibody mouse anti-c-myc IgG-FITC.
  • the cells were analyzed on a BD FACS Calibur Flow Cytometer (BD Biosciences Pharmingen, Heidelberg, Germany) and the data were evaluated using the WinMDI 2.8 software (Joseph Trotter, La Jolla, CA USA).
  • the determined MFI values (mean fluorescence intensity values) were plotted against the antibody concentrations tested and in each case a trend line of the polynomial regression type of the second order was calculated.
  • a polynomial regression type trend line type was calculated and inserted.
  • the resulting binding curve served as the basis for the calculation of the affinity constant K D , which is defined as the concentration which is reached at the 50% value of the maximum MFI value and thus at half maximum saturation of the binding.
  • K D the affinity constant
  • the first derivative of the bond curve which follows a quadratic function, was first formed. In order to determine the maximum of the function on the basis of this equation, the first derivative "zero" was set and resolved to x.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Cell Biology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Gynecology & Obstetrics (AREA)
  • Engineering & Computer Science (AREA)
  • Reproductive Health (AREA)
  • Pregnancy & Childbirth (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Biomedical Technology (AREA)
  • Mycology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Microbiology (AREA)
  • Epidemiology (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)
  • Investigating Or Analysing Biological Materials (AREA)
PCT/EP2012/062716 2011-06-30 2012-06-29 Antikörper gegen das prostata-spezifische stammzellantigen und dessen verwendung Ceased WO2013001065A1 (de)

Priority Applications (14)

Application Number Priority Date Filing Date Title
JP2014517736A JP2014528696A (ja) 2011-06-30 2012-06-29 前立腺特異幹細胞抗原に対する抗体およびその使用
AU2012277784A AU2012277784B2 (en) 2011-06-30 2012-06-29 Antibodies against prostate-specific stem cell antigen and use thereof
EP18207370.0A EP3505536B1 (de) 2011-06-30 2012-06-29 Antikörper gegen das prostata-spezifische stammzellantigen und dessen verwendung
LTEP12729996.4T LT2726507T (lt) 2011-06-30 2012-06-29 Antikūnai, atpažįstantys prostatai specifinį kamieninių ląstelių antigeną, ir jų panaudojimas
RS20190218A RS58448B1 (sr) 2011-06-30 2012-06-29 Antitela protiv antigena matičnih ćelija specifičan za prostatu i njihova upotreba
HRP20190289TT HRP20190289T1 (hr) 2011-06-30 2012-06-29 Protutijela protiv antigena specifičnog za matične stanice prostate i njihova upotreba
US14/129,933 US9200078B2 (en) 2011-06-30 2012-06-29 Antibodies against prostate-specific stem cell antigen and use thereof
DK12729996.4T DK2726507T3 (en) 2011-06-30 2012-06-29 ANTIBODY AGAINST THE PROSTATE-SPECIFIC STEM CELL ANTIGEN AND ITS USE
ES12729996T ES2711978T3 (es) 2011-06-30 2012-06-29 Anticuerpos contra el antígeno de células madre específico de la próstata y su uso
EP12729996.4A EP2726507B1 (de) 2011-06-30 2012-06-29 Antikörper gegen das prostata-spezifische stammzellantigen und dessen verwendung
SI201231523T SI2726507T1 (sl) 2011-06-30 2012-06-29 Protitelesa proti antigenu prostatno specifičnih matičnih celic in njihova uporaba
SM20190085T SMT201900085T1 (it) 2011-06-30 2012-06-29 Anticorpi contro l'antigene delle cellule staminali prostatiche e suo uso
PL12729996T PL2726507T3 (pl) 2011-06-30 2012-06-29 Przeciwciała przeciwko antygenowi komórek macierzystych swoistemu dla gruczołu krokowego i ich zastosowanie
CY20191100176T CY1121249T1 (el) 2011-06-30 2019-02-11 Αντισωμα εναντι του ειδικου προστατικου αντιγονου βλαστικου κυτταρου και χρησεις αυτου

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102011118022.6A DE102011118022B4 (de) 2011-06-30 2011-06-30 Antikörper gegen das Prostata-spezifische Stammzellenantigen und dessen Verwendung
DE102011118022.6 2011-06-30

Related Child Applications (1)

Application Number Title Priority Date Filing Date
EP18207370.0A Previously-Filed-Application EP3505536B1 (de) 2011-06-30 2012-06-29 Antikörper gegen das prostata-spezifische stammzellantigen und dessen verwendung

Publications (1)

Publication Number Publication Date
WO2013001065A1 true WO2013001065A1 (de) 2013-01-03

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PCT/EP2012/062716 Ceased WO2013001065A1 (de) 2011-06-30 2012-06-29 Antikörper gegen das prostata-spezifische stammzellantigen und dessen verwendung

Country Status (18)

Country Link
US (1) US9200078B2 (enExample)
EP (2) EP2726507B1 (enExample)
JP (4) JP2014528696A (enExample)
AU (1) AU2012277784B2 (enExample)
CY (1) CY1121249T1 (enExample)
DE (1) DE102011118022B4 (enExample)
DK (1) DK2726507T3 (enExample)
ES (2) ES2989975T3 (enExample)
HR (1) HRP20190289T1 (enExample)
HU (1) HUE042008T2 (enExample)
LT (1) LT2726507T (enExample)
PL (1) PL2726507T3 (enExample)
PT (1) PT2726507T (enExample)
RS (1) RS58448B1 (enExample)
SI (1) SI2726507T1 (enExample)
SM (1) SMT201900085T1 (enExample)
TR (1) TR201901991T4 (enExample)
WO (1) WO2013001065A1 (enExample)

Cited By (2)

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Publication number Priority date Publication date Assignee Title
US10611814B2 (en) 2014-08-29 2020-04-07 Gemoab Monoclonals Gmbh Universal chimeric antigen expressing immune cells for targeting of diverse multiple antigens and method of manufacturing the same and use of the same for treatment of cancer, infections and autoimmune disorders
WO2025179294A2 (en) 2024-02-22 2025-08-28 Capstan Therapeutics, Inc. Immune engineering amplification

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DE102011118022B4 (de) * 2011-06-30 2018-01-18 Gemoab Monoclonals Gmbh Antikörper gegen das Prostata-spezifische Stammzellenantigen und dessen Verwendung
EP4491234A3 (en) 2017-02-08 2025-04-09 Dragonfly Therapeutics, Inc. Multi-specific binding proteins for activation of natural killer cells and therapeutic uses thereof to treat cancer
BR112019017197A2 (pt) 2017-02-20 2020-04-14 Dragonfly Therapeutics, Inc. proteínas que se ligam a her2, nkg2d e cd16
WO2019066093A1 (ko) * 2017-09-26 2019-04-04 주식회사 와이바이오로직스 Scf 특이적 항체
AU2019218125B2 (en) 2018-02-08 2025-03-13 Dragonfly Therapeutics, Inc. Combination therapy of cancer involving multi-specific binding proteins that activate natural killer cells
PE20220278A1 (es) 2018-02-08 2022-02-25 Dragonfly Therapeutics Inc Dominios variables de anticuerpos que se dirigen al receptor nkg2d
TW201942134A (zh) 2018-02-20 2019-11-01 美商蜻蜓醫療公司 結合cd33、nkg2d及cd16之多特異性結合蛋白及使用方法
EA202190468A1 (ru) 2018-08-08 2021-07-06 Драгонфлай Терапьютикс, Инк. Мультиспецифические связывающие белки, которые связывают bcma, nkg2d и cd16, и способы их применения
KR20250112921A (ko) 2018-08-08 2025-07-24 드래곤플라이 쎄라퓨틱스, 인크. Nkg2d, cd16 및 종양 관련 항원에 결합하는 단백질
EA202091888A1 (ru) 2018-08-08 2020-10-23 Драгонфлай Терапьютикс, Инк. Вариабельные домены антител, нацеленные на рецептор nkg2d
EP4146271A4 (en) 2020-05-06 2024-09-04 Dragonfly Therapeutics, Inc. PROTEINS THAT BIND NKG2D, CD16 AND CLEC12A
AU2021276327A1 (en) * 2020-05-19 2022-12-01 City Of Hope Engineered anti-prostate stem cell antigen fusion proteins and uses thereof
US12377144B2 (en) 2021-03-03 2025-08-05 Dragonfly Therapeutics, Inc. Methods of treating cancer using multi-specific binding proteins that bind NKG2D, CD16 and a tumor-associated antigen
WO2024233662A2 (en) * 2023-05-09 2024-11-14 University Of Pittsburgh - Of The Commonwealth System Of Higher Education Molecules that bind to psca polypeptides

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US10611814B2 (en) 2014-08-29 2020-04-07 Gemoab Monoclonals Gmbh Universal chimeric antigen expressing immune cells for targeting of diverse multiple antigens and method of manufacturing the same and use of the same for treatment of cancer, infections and autoimmune disorders
US10766943B2 (en) 2014-08-29 2020-09-08 Gemoab Monoclonals Gmbh Universal chimeric antigen expressing immune cells for targeting of diverse multiple antigens and method of manufacturing the same and use of the same for treatment of cancer, infections and autoimmune disorders
WO2025179294A2 (en) 2024-02-22 2025-08-28 Capstan Therapeutics, Inc. Immune engineering amplification

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