WO2005085288A2 - Natural igm antibodies and inhibitors thereof - Google Patents

Natural igm antibodies and inhibitors thereof Download PDF

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Publication number
WO2005085288A2
WO2005085288A2 PCT/US2005/006276 US2005006276W WO2005085288A2 WO 2005085288 A2 WO2005085288 A2 WO 2005085288A2 US 2005006276 W US2005006276 W US 2005006276W WO 2005085288 A2 WO2005085288 A2 WO 2005085288A2
Authority
WO
WIPO (PCT)
Prior art keywords
seq
nucleic acid
antibody
igm
peptide
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/US2005/006276
Other languages
English (en)
French (fr)
Other versions
WO2005085288A3 (en
Inventor
Michael C. Carroll
Jr. Francis D. Moore
Herbert B. Hechtman
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.)
Brigham and Womens Hospital Inc
CBR Institute for Biomedical Research Inc
Harvard University
Original Assignee
Brigham and Womens Hospital Inc
CBR Institute for Biomedical Research Inc
Harvard University
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 AU2005219839A priority Critical patent/AU2005219839B9/en
Priority to DE602005026260T priority patent/DE602005026260D1/de
Priority to CN200580012909.8A priority patent/CN1977043B/zh
Priority to CA002560066A priority patent/CA2560066A1/en
Priority to AT05723931T priority patent/ATE498010T1/de
Priority to EP05723931A priority patent/EP1725659B1/en
Application filed by Brigham and Womens Hospital Inc, CBR Institute for Biomedical Research Inc, Harvard University filed Critical Brigham and Womens Hospital Inc
Priority to JP2007501869A priority patent/JP5557982B2/ja
Publication of WO2005085288A2 publication Critical patent/WO2005085288A2/en
Publication of WO2005085288A3 publication Critical patent/WO2005085288A3/en
Priority to IL177825A priority patent/IL177825A/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • 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
    • 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
    • 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
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/57—Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • 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
    • 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
    • C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype

Definitions

  • Figure 7C is a series of photomicrographs showing the absence of IgM and complement C3 or C4 within the microvilli of P8-treated animals.
  • Representative cryosections of intestinal tissues were harvested following intestinal RL
  • Panels i-viii are IgM CM"22 reconstituted RAG-l " mice without pretreatment with P S (panels i-iv) or with P8 (panels v-viii).
  • Panels represent cryosections from the intestines of WT without P8 (panels ix - xii) or pretreated with P8 (panels xiii - xvi).
  • Figure 14 shows the (A) nucleic acid sequence (SEQ ID NO: 53; Genbank Accession no. NM_005964) and (B) amino acid sequence (SEQ ID NO: 54; Genbank Accession no. NP_005955) of human non-muscle myosin heavy chain II-B (hNMHC-IIB).
  • Figure 15 shows the (A) nucleic acid sequence (SEQ ID NO: 55; Genbank
  • the coding sequences need not be contiguous to one another so long as the expressed sequences ultimately process to produce the desired protein.
  • An expression control sequence operatively linked to a coding sequence is ligated such that expression of the coding sequence is achieved under conditions compatible with the expression control sequences.
  • expression control sequences refers to nucleic acid sequences that regulate the expression of a nucleic acid sequence to which it is operatively linked. Expression control sequences are operatively linked to a nucleic acid sequence when the expression control sequences control and regulate the transcription and, as appropriate, translation of the nucleic acid sequence.
  • an isolated nucleic acid can comprise an IgM CM"22 (or 22A5 IgM) heavy chain variable region nucleotide sequence having a nucleotide sequence as shown in Figure 1 A (SEQ ID NO: 1), or a sequence, which is at least 80%, 90%, 95%, 96%, 97%, 98%o, or 99% identical to SEQ ID NO: 1.
  • a nucleic acid molecule may comprise the heavy chain CDR1 nucleotide sequence of SEQ ID NO: 3, or a portion thereof. Further, the nucleic acid molecule may comprise the heavy chain CDR2 nucleotide sequence of SEQ ID NO: 5, or a portion thereof.
  • the nucleic acid molecule comprises a light chain CDRl nucleotide sequence of SEQ ID NO: 9, or portion thereof, and a light chain CDR2 nucleotide sequence of SEQ ID NO: 11 , or portion thereof.
  • the nucleic acid molecules of the present invention may comprise light chain sequences, e.g. SEQ ID NOs: 7, 9 or 11, or combinations thereof, or encompass nucleotides having at least 80%, 90%, 95%, 96%, 97 %, 98%, and 99% sequence identity to SEQ ID NOs: 7, 9 or 11.
  • Further nucleic acid molecules may comprise light chain sequences, which hybridize under stringent conditions, e.g.
  • Chimeric antibodies e.g. mouse-human monoclonal antibodies
  • Chimeric antibodies can be produced by recombinant DNA techniques known in the art. For example, a gene encoding the Fc constant region of a murine (or other species) monoclonal antibody molecule is digested with restriction enzymes to remove the region encoding the murine Fc, and the equivalent portion of a gene encoding a human Fc constant region is substituted, (see Robinson et al., International Patent Publication PCT/US86/02269; Akira, et al., European Patent Application 184,187; Taniguchi, M., European Patent Application 171,496; Mo ⁇ ison et al., European Patent Application 173,494; Neuberger et al., International Application WO 86/01533; Cabilly et al.
  • the method includes: altering the sequence, e.g., by substitution or deletion of one or more residues, of a pathogenic immunoglobulin, e.g., altering the sequence of a non-conserved region, or a domain or residue described herein, and testing the altered polypeptide for the desired activity.
  • the modified natural immunoglobulin may have a reduced ability to activate complement. For example, one or more of the amino acid residues involved in complement binding and/or activation are mutated.
  • a change e.g., decrease in the level of binding between the natural IgM antibody and the antigen or the component of the complement pathway in the presence of the test compound relative to that detected in the absence of the test compound indicates that the test compound is an inhibitor of the interaction between the natural IgM antibody and the antigen or the component of the complement pathway.
  • the method can further include pre-treating the natural IgM antibodies with one or more test compounds.
  • the pre-treated natural IgM antibodies can then be injected into mice deficient in natural immunoglobulins.
  • the methods is perfo ⁇ ried in vitro.
  • the contacting step is effected in vivo.
  • the antigen is myosin.
  • the aliquots of derivatized beads are then washed, "pooled” (i.e., recombined), and the pool of beads is again divided, with each aliquot being placed in a separate reaction vessel.
  • Another activated amino acid is then added to each aliquot of beads. The cycle of synthesis is repeated until a desired peptide length is obtained.
  • Activated cells are hybridized with fusion partner myeloma cells in the presence of PEG and grown in HAT-selective medium.
  • Hybridomas are screened for IgM secreting clones by ELISA , and positive wells are expanded for purification of IgM.
  • Twenty-two IgM-secreting hybridoma clones were analyzed by pooling an equal amount of IgM product from each of the clones.
  • Treatment of antibody-deficient mice with the pooled IgM restored injury similar to that seen with pooled IgM from serum. This finding confirmed that the pathogenic IgM was among the twenty-two hybridomas produced.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Immunology (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Vascular Medicine (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Urology & Nephrology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (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)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
PCT/US2005/006276 2004-03-01 2005-03-01 Natural igm antibodies and inhibitors thereof Ceased WO2005085288A2 (en)

Priority Applications (8)

Application Number Priority Date Filing Date Title
DE602005026260T DE602005026260D1 (de) 2004-03-01 2005-03-01 Natürliche igm-antikörper und inhibitoren davon
CN200580012909.8A CN1977043B (zh) 2004-03-01 2005-03-01 天然IgM抗体及其抑制剂
CA002560066A CA2560066A1 (en) 2004-03-01 2005-03-01 Natural igm antibodies and inhibitors thereof
AT05723931T ATE498010T1 (de) 2004-03-01 2005-03-01 Natürliche igm-antikörper und inhibitoren davon
EP05723931A EP1725659B1 (en) 2004-03-01 2005-03-01 Natural igm antibodies and inhibitors thereof
AU2005219839A AU2005219839B9 (en) 2004-03-01 2005-03-01 Natural IgM antibodies and inhibitors thereof
JP2007501869A JP5557982B2 (ja) 2004-03-01 2005-03-01 天然ＩｇＭ抗体およびその阻害剤
IL177825A IL177825A (en) 2004-03-01 2006-08-31 PEPTIDE INHIBITOR OF AN IgM MOLECULE, NUCLEIC ACID ENCODING THE SAME, VECTOR COMPRISING THE NUCLEIC ACID, HOST CELL COMPRISING THE VECTOR, COMPOSITION COMPRISING THE INHIBITOR AND USE OF THE COMPOSITION

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US54912304P 2004-03-01 2004-03-01
US60/549,123 2004-03-01
US58864804P 2004-07-16 2004-07-16
US60/588,648 2004-07-16

Publications (2)

Publication Number Publication Date
WO2005085288A2 true WO2005085288A2 (en) 2005-09-15
WO2005085288A3 WO2005085288A3 (en) 2006-08-03

Family

ID=34922704

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2005/006276 Ceased WO2005085288A2 (en) 2004-03-01 2005-03-01 Natural igm antibodies and inhibitors thereof

Country Status (9)

Country Link
US (5) US7442783B2 (https=)
EP (2) EP2290077B1 (https=)
JP (3) JP5557982B2 (https=)
AT (1) ATE498010T1 (https=)
AU (1) AU2005219839B9 (https=)
CA (1) CA2560066A1 (https=)
DE (1) DE602005026260D1 (https=)
IL (1) IL177825A (https=)
WO (1) WO2005085288A2 (https=)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8324352B2 (en) 2009-12-07 2012-12-04 Decimmune Therapeutics, Inc. Anti-inflammatory antibodies and uses therefor
US9243059B2 (en) 2013-03-12 2016-01-26 Decimmune Therapeutics, Inc. Humanized anti-N2 antibodies and methods of treating ischemia-reperfusion injury

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US20100136684A1 (en) * 2004-03-01 2010-06-03 Carroll Michael C Natural IgM Antibodies
ATE498010T1 (de) 2004-03-01 2011-02-15 Immune Disease Inst Inc Natürliche igm-antikörper und inhibitoren davon
KR20130108104A (ko) * 2010-06-03 2013-10-02 아브락시스 바이오사이언스, 엘엘씨 말초혈 ｓｐａｒｃ 결합 항체와 이들의 용도
WO2014055392A2 (en) * 2012-10-01 2014-04-10 Decimmune Therapeutics, Inc. Method of protecting cardiac function
JP6551825B2 (ja) * 2014-02-10 2019-07-31 公立大学法人首都大学東京 クロマチン構造制御剤

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8324352B2 (en) 2009-12-07 2012-12-04 Decimmune Therapeutics, Inc. Anti-inflammatory antibodies and uses therefor
EP2510000A4 (en) * 2009-12-07 2013-07-24 Decimmune Therapeutics Inc Anti-inflammatory antibodies and applications thereof
US9243059B2 (en) 2013-03-12 2016-01-26 Decimmune Therapeutics, Inc. Humanized anti-N2 antibodies and methods of treating ischemia-reperfusion injury
US9409977B2 (en) 2013-03-12 2016-08-09 Decimmune Therapeutics, Inc. Humanized, anti-N2 antibodies

Also Published As

Publication number Publication date
WO2005085288A3 (en) 2006-08-03
IL177825A0 (en) 2006-12-31
JP5557982B2 (ja) 2014-07-23
CA2560066A1 (en) 2005-09-15
US7442783B2 (en) 2008-10-28
EP2290077B1 (en) 2016-01-27
US20050276811A1 (en) 2005-12-15
IL177825A (en) 2013-02-28
US20170342109A1 (en) 2017-11-30
EP1725659A2 (en) 2006-11-29
DE602005026260D1 (de) 2011-03-24
US20160280740A1 (en) 2016-09-29
EP1725659B1 (en) 2011-02-09
HK1154904A1 (en) 2012-05-04
ATE498010T1 (de) 2011-02-15
AU2005219839B9 (en) 2011-12-22
US9657060B2 (en) 2017-05-23
JP5618852B2 (ja) 2014-11-05
EP2290077A3 (en) 2011-05-18
US9914751B2 (en) 2018-03-13
US20090176966A1 (en) 2009-07-09
JP2008504807A (ja) 2008-02-21
JP2014155497A (ja) 2014-08-28
AU2005219839A1 (en) 2005-09-15
JP2011139704A (ja) 2011-07-21
US20140127214A1 (en) 2014-05-08
AU2005219839B2 (en) 2011-11-24
EP2290077A2 (en) 2011-03-02

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