WO2009056631A2 - Molecules and methods for modulating complement component - Google Patents
Molecules and methods for modulating complement component Download PDFInfo
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- WO2009056631A2 WO2009056631A2 PCT/EP2008/064809 EP2008064809W WO2009056631A2 WO 2009056631 A2 WO2009056631 A2 WO 2009056631A2 EP 2008064809 W EP2008064809 W EP 2008064809W WO 2009056631 A2 WO2009056631 A2 WO 2009056631A2
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- binding molecule
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- 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
- C07K2317/90—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
- complement pathways indicates either or both the alternative complement pathway or the classical complement pathway.
- the complement component proteins whose level is to be modulated are anaphylotoxins, Factor H, Factor P, Factor B, C3 or C5 convertase; C3 cleavage products such as C3a, C3b, iC3b and C3d, C5 cleavage products C5a and C5b; MAC, and MAC-dependent production of complement by-products.
- C3b binding molecules also include molecules in which the binding portion is not derived from an antibody, e.g., C3b binding molecules derived from polypeptides that have an immunoglobulin-like fold, and in which the antigen binding portion is engineered to bind C3b neo- epitopes through randomization, selection, and affinity maturation.
- Preferred C3b binding molecules include antibodies, fragments thereof or artificial constructs comprising antibodies or fragments thereof or artificial constructs designed to mimic the binding of antibodies or fragments thereof.
- the invention also features C3b binding molecules which are not antibodies.
- Binding kinetics also can be assessed by standard assays known in the art, such as by Biacore ® analysis. Assays to evaluate the effects of C3b binding molecules on functional properties of C3b are described in further detail below.
- the antibody encoded by the altered antibody sequence(s) is one that retains one, some or all of the functional properties of the anti-C3b antibody from which it is derived, which functional properties include, but are not limited to, specifically binding to C3b, inhibiting formation of C3b complexes, inhibiting C3 convertase activation, inhibiting C5 convertase activation, inhibiting formation of MAC.
- the functional properties of the altered antibodies can be assessed using standard assays available in the art and/or described herein (e.g., ELISAs).
- Scaffold proteins suitable for deriving antigen binding molecules include fibronectin or a fibronectin dimer, tenascin, N-cadherin, E-cadherin, ICAM, titin, GCSF-receptor, cytokine receptor, glycosidase inhibitor, antibiotic chromoprotein, myelin membrane adhesion molecule PO, CD8, CD4, CD2, class I MHC, T-cell antigen receptor, CD1 , C2 and l-set domains of VCAM-1 , l-set immunoglobulin domain of myosin-binding protein C, l-set immunoglobulin domain of myosin-binding protein H, l-set immunoglobulin domain of telokin, NCAM, twitchin, neuroglian, growth hormone receptor, erythropoietin receptor, prolactin receptor, interferon-gamma receptor, D-galactosidase/glucuronidase, G- glucuronidase
- transgenic animal systems expressing human immunoglobulin genes are available in the art and can be used to raise anti-C3b antibodies of the invention.
- an alternative transgenic system referred to as the Xenomouse ® (Abgenix, Inc.) can be used.
- Such mice are described in, e.g., U.S. Pat. Nos. 5,939,598; 6,075,181 ; 6,114,598; 6, 150,584 and 6,162,963 to Kucherlapati et al.
- the HCo12 strain carries the HCo12 human heavy chain transgene as described in Example 2 of WO 01/09187.
- the HCo17 stain carries the HCo17 human heavy chain transgene.
- the KNM strain contains the SC20 transchromosome as described in WO 02/43478. To generate fully human monoclonal antibodies to C3b neo-epitopes,
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Ophthalmology & Optometry (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
Description
Claims
Priority Applications (11)
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JP2010532555A JP2011503024A (en) | 2007-11-02 | 2008-10-31 | Molecules and methods for modulating complement components |
EA201000717A EA201000717A1 (en) | 2007-11-02 | 2008-10-31 | MOLECULES AND METHODS INTENDED FOR MODULATING COMPONENT OF COMPLEMENT SYSTEM |
CA2703911A CA2703911A1 (en) | 2007-11-02 | 2008-10-31 | Molecules and methods for modulating complement component |
EP08844727A EP2207807A2 (en) | 2007-11-02 | 2008-10-31 | Molecules and methods for modulating complement component |
CN200880114277A CN101848937A (en) | 2007-11-02 | 2008-10-31 | Molecules and methods for modulating complement component |
MX2010004833A MX2010004833A (en) | 2007-11-02 | 2008-10-31 | Molecules and methods for modulating complement component. |
AU2008320820A AU2008320820A1 (en) | 2007-11-02 | 2008-10-31 | Molecules and methods for modulating complement component |
IL204722A IL204722A0 (en) | 2007-11-02 | 2010-03-25 | Molecules and methods for modulating complement component |
ZA2010/02335A ZA201002335B (en) | 2007-11-02 | 2010-04-01 | Molecules and methods for modulating complement component |
TN2010000169A TN2010000169A1 (en) | 2007-11-02 | 2010-04-16 | Molecules and methods for modulating complement component |
MA32801A MA31795B1 (en) | 2007-11-02 | 2010-04-30 | Particles and methods of modification of the supplement component |
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IL (1) | IL204722A0 (en) |
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SV (1) | SV2010003556A (en) |
TN (1) | TN2010000169A1 (en) |
TW (1) | TW200924795A (en) |
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ZA (1) | ZA201002335B (en) |
Cited By (13)
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JP2012525829A (en) * | 2009-05-06 | 2012-10-25 | ノバルティス アーゲー | Compositions and methods of antibodies targeting complement protein C3b |
US8758754B2 (en) | 2007-11-02 | 2014-06-24 | Novartis Ag | Nogo-A binding molecules and pharmaceutical use thereof |
US9066925B2 (en) | 2009-07-02 | 2015-06-30 | Musc Foundation For Research Development | Methods of stimulating liver regeneration |
US9212212B2 (en) | 2006-06-21 | 2015-12-15 | The Regents Of The University Of Colorado, A Body Corporate | Targeting complement factor H for treatment of diseases |
US9259488B2 (en) | 2012-08-17 | 2016-02-16 | The Regents Of The University Of Colorado, A Body Corporate | Anti-C3d antibody conjugates and methods of detecting complement activation |
US9494601B2 (en) | 2013-08-07 | 2016-11-15 | Alexion Pharmaceuticals, Inc. | Atypical hemolytic uremic syndrome (AHUS) biomarker proteins |
US20160333082A1 (en) * | 2014-01-08 | 2016-11-17 | The United States Of America, As Represented By The Secretary, Dept. Of Health And Human Services | ANTIBODY TARGETING CELL SURFACE DEPOSITED COMPLEMENT PROTEIN C3d AND USE THEREOF |
US9650447B2 (en) | 2010-05-14 | 2017-05-16 | The Regents Of The University Of Colorado, A Body Corporate | Complement receptor 2 (CR2) targeting groups |
US9815890B2 (en) | 2010-06-22 | 2017-11-14 | The Regents Of The University Of Colorado, A Body Corporate | Antibodies to the C3d fragment of complement component 3 |
US10239937B2 (en) | 2009-11-05 | 2019-03-26 | Alexion Pharmaceuticals, Inc. | Treatment of paroxysmal nocturnal hemoglobinuria, hemolytic anemias and disease states involving intravascular and extravascular hemolysis |
US11007254B2 (en) | 2016-10-17 | 2021-05-18 | Musc Foundation For Research Development | Compositions and methods for treating central nervous system injury |
US11053306B2 (en) | 2018-12-11 | 2021-07-06 | Q32 Bio Inc. | Fusion protein constructs comprising anti-C3d antibody and factor H |
US11191851B2 (en) | 2012-08-17 | 2021-12-07 | Musc Foundation For Research Development | Anti-C3d antibody conjugates and methods of detecting complement activation |
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US8680019B2 (en) * | 2007-08-10 | 2014-03-25 | Protelica, Inc. | Universal fibronectin Type III binding-domain libraries |
AU2008287426B2 (en) * | 2007-08-10 | 2014-06-26 | Protelica, Inc. | Universal fibronectin type III binding-domain libraries |
US8470966B2 (en) | 2007-08-10 | 2013-06-25 | Protelica, Inc. | Universal fibronectin type III binding-domain libraries |
EP2646821A4 (en) | 2010-11-29 | 2015-09-23 | Novelmed Therapeutics Inc | Neoantibodies for diagnosing tissue injury |
US10568568B2 (en) * | 2014-08-27 | 2020-02-25 | Capnia, Inc. | Methods for immune globulin administration |
CN108699121B (en) | 2015-12-23 | 2023-07-04 | 艾丽法有限责任公司 | Polypeptides for inhibiting complement activation |
UA124734C2 (en) | 2016-06-14 | 2021-11-10 | Рідженерон Фармасьютікалз, Інк. | Anti-c5 antibodies and uses thereof |
EP3724226A1 (en) | 2017-12-13 | 2020-10-21 | Regeneron Pharmaceuticals, Inc. | Anti-c5 antibody combinations and uses thereof |
GB201800620D0 (en) * | 2018-01-15 | 2018-02-28 | Univ Manchester | C3b Binding Polypeptide |
CN111171147B (en) * | 2020-02-11 | 2021-07-20 | 北京康普美特创新医药科技有限责任公司 | Fully human monoclonal antibody of anti-complement C3 molecule and application |
US20240228652A9 (en) * | 2022-09-20 | 2024-07-11 | Visterra, Inc. | Treatment of complement mediated diseases and disorders with c3b antibodies |
Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1987006344A1 (en) * | 1986-04-11 | 1987-10-22 | Nilsson Ulf R | Antibody preparation directed against neoantigens in human c3 (complement factor 3) and the use and manufacture thereof |
WO1997001578A1 (en) * | 1995-06-29 | 1997-01-16 | Medical Biology Institute | Method for identifying peptides that affect protein-protein interactions and complement-modulating peptides |
US5968512A (en) * | 1991-05-03 | 1999-10-19 | The Rockefeller University | Antibody recognizing endothelial cell ligand for leukocyte CR3 |
WO2002088750A2 (en) * | 2001-05-02 | 2002-11-07 | Oxford Glycosciences (Uk) Ltd | Proteins, genes and their use for diagnosis and treatment of breast cancer |
WO2006012621A2 (en) * | 2004-07-23 | 2006-02-02 | University Of Virginia Patent Foundation | Compositions and methods for regulating the alternative pathway of complement |
WO2006042252A2 (en) * | 2004-10-08 | 2006-04-20 | Potentia Pharmeceuticals, Inc. | Viral complement control proteins for eye disorders |
WO2007047796A2 (en) * | 2005-10-17 | 2007-04-26 | Institute For Systems Biology | Tissue-and serum-derived glycoproteins and methods of their use |
WO2008154251A2 (en) * | 2007-06-07 | 2008-12-18 | Genentech, Inc. | C3b antibodies and methods for the prevention and treatment of complement- associated disorders |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7042716B2 (en) * | 2003-08-25 | 2006-05-09 | Simon John Edward Shearman | Ergonomic pull-out computer housing |
US7327547B1 (en) * | 2006-01-20 | 2008-02-05 | Epstein Barry M | Circuit element and use thereof |
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Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1987006344A1 (en) * | 1986-04-11 | 1987-10-22 | Nilsson Ulf R | Antibody preparation directed against neoantigens in human c3 (complement factor 3) and the use and manufacture thereof |
US5968512A (en) * | 1991-05-03 | 1999-10-19 | The Rockefeller University | Antibody recognizing endothelial cell ligand for leukocyte CR3 |
WO1997001578A1 (en) * | 1995-06-29 | 1997-01-16 | Medical Biology Institute | Method for identifying peptides that affect protein-protein interactions and complement-modulating peptides |
WO2002088750A2 (en) * | 2001-05-02 | 2002-11-07 | Oxford Glycosciences (Uk) Ltd | Proteins, genes and their use for diagnosis and treatment of breast cancer |
WO2006012621A2 (en) * | 2004-07-23 | 2006-02-02 | University Of Virginia Patent Foundation | Compositions and methods for regulating the alternative pathway of complement |
WO2006042252A2 (en) * | 2004-10-08 | 2006-04-20 | Potentia Pharmeceuticals, Inc. | Viral complement control proteins for eye disorders |
WO2007047796A2 (en) * | 2005-10-17 | 2007-04-26 | Institute For Systems Biology | Tissue-and serum-derived glycoproteins and methods of their use |
WO2008154251A2 (en) * | 2007-06-07 | 2008-12-18 | Genentech, Inc. | C3b antibodies and methods for the prevention and treatment of complement- associated disorders |
Non-Patent Citations (8)
Title |
---|
BECHERER J D ET AL: "Segment Spanning Residues 727-768 of the Complement C3 Sequence Contains a Neoantigenic Site and Accomodates the Binding of CR1, Factor H and Factor B" BIOCHEMISTRY, AMERICAN CHEMICAL SOCIETY, EASTON, PA.; US, vol. 31, no. 6, 1 January 1992 (1992-01-01), pages 1787-1794, XP002484977 ISSN: 0006-2960 * |
DILILLO D J ET AL: "Selective and efficient inhibition of the alternative pathway of complement by a mAb that recognizes C3b/iC3b" MOLECULAR IMMUNOLOGY, PERGAMON, GB, vol. 43, no. 7, 1 March 2006 (2006-03-01), pages 1010-1019, XP025037212 ISSN: 0161-5890 [retrieved on 2006-03-01] * |
FEARON D T ET AL: "Complement ligand-receptor interactions that mediate biological responses." ANNUAL REVIEW OF IMMUNOLOGY 1983, vol. 1, 1983, pages 243-271, XP002515685 ISSN: 0732-0582 * |
JOHNSON L V ET AL: "Complement activation and inflammatory processes in drusen formation and age related macular degeneration" EXPERIMENTAL EYE RESEARCH, ACADEMIC PRESS LTD., LONDON, vol. 73, no. 6, 1 December 2001 (2001-12-01), pages 887-896, XP002386744 ISSN: 0014-4835 cited in the application * |
KENNEDY A D ET AL: "An anti-C3b(i) mAb enhances complement activation, C3b(i) deposition, and killing of CD20+ cells by rituximab" BLOOD, AMERICAN SOCIETY OF HEMATOLOGY, US, vol. 101, no. 3, 1 February 2003 (2003-02-01), pages 1071-1079, XP002994576 ISSN: 0006-4971 * |
LACHMANN P J ET AL: "Three rat monoclonal antibodies to human C3." IMMUNOLOGY NOV 1980, vol. 41, no. 3, November 1980 (1980-11), pages 503-515, XP002515684 ISSN: 0019-2805 * |
SOKOLOFF M H ET AL: "Targeting of cancer cells with monoclonal antibodies specific for C3b(i)" CANCER IMMUNOLOGY AND IMMUNOTHERAPY, SPRINGER-VERLAG, BERLIN, DE, vol. 49, no. 10, 1 December 2000 (2000-12-01), pages 551-562, XP000999171 ISSN: 0340-7004 * |
TOSIC L ET AL: "Preparation of monoclonal antibodies to C3b by immunization with C3b(i)-Sepharose" JOURNAL OF IMMUNOLOGICAL METHODS, ELSEVIER SCIENCE PUBLISHERS B.V.,AMSTERDAM, NL, vol. 120, no. 2, 21 June 1989 (1989-06-21), pages 241-249, XP023975210 ISSN: 0022-1759 [retrieved on 1989-06-21] * |
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Also Published As
Publication number | Publication date |
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CN101848937A (en) | 2010-09-29 |
EP2207807A2 (en) | 2010-07-21 |
MX2010004833A (en) | 2010-05-27 |
TN2010000169A1 (en) | 2011-11-11 |
IL204722A0 (en) | 2010-11-30 |
US20090175875A1 (en) | 2009-07-09 |
PE20091388A1 (en) | 2009-09-24 |
CL2008003241A1 (en) | 2009-07-31 |
ZA201002335B (en) | 2011-02-23 |
CR11361A (en) | 2010-06-01 |
WO2009056631A3 (en) | 2009-08-20 |
KR20100067681A (en) | 2010-06-21 |
SV2010003556A (en) | 2011-03-23 |
EA201000717A1 (en) | 2010-12-30 |
AU2008320820A1 (en) | 2009-05-07 |
MA31795B1 (en) | 2010-10-01 |
TW200924795A (en) | 2009-06-16 |
JP2011503024A (en) | 2011-01-27 |
AR069130A1 (en) | 2009-12-30 |
CO6270341A2 (en) | 2011-04-20 |
CA2703911A1 (en) | 2009-05-07 |
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