DK2470671T3 - Antikin- antistoffer, der binder til flere cc-chemokiner - Google Patents

Antikin- antistoffer, der binder til flere cc-chemokiner Download PDF

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DK2470671T3
DK2470671T3 DK10812667T DK10812667T DK2470671T3 DK 2470671 T3 DK2470671 T3 DK 2470671T3 DK 10812667 T DK10812667 T DK 10812667T DK 10812667 T DK10812667 T DK 10812667T DK 2470671 T3 DK2470671 T3 DK 2470671T3
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antibody
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Carol Raport
Dan Allison
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Regeneron Pharma
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    • 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
    • C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • 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
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2863—Immunoglobulins [IGs], 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
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • 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
    • 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
    • C07K16/28—Immunoglobulins [IGs], 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 [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IGs], 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 [IGs], 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/564—Immunoassay; Biospecific binding assay; Materials therefor for pre-existing immune complex or autoimmune disease, i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
    • 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
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
    • 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
    • C07K2317/54—F(ab')2
    • 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
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/52—Assays involving cytokines
    • G01N2333/521—Chemokines
    • G01N2333/523—Beta-chemokines, e.g. RANTES, I-309/TCA-3, MIP-1alpha, MIP-1beta/ACT-2/LD78/SCIF, MCP-1/MCAF, MCP-2, MCP-3, LDCF-1or LDCF-2

Claims (29)

1. Monoklonalt antistof eller antigenbindende fragment deraf, der binder til mindst tre forskellige CC-chemokiner, hvor mindst et CC-chemokin er CCL3/MIP-1a, CCL4/MIP-1 β eller CCL5/RANTES, hvor antistoffet eller det antigenbindende fragment deraf: (a) har et HCVR/LCVR-aminosyresekvenspar, udvalgt fra gruppen bestående af SEQ ID NR: 2/7, 12/17, 22/27, 32/37, 42/47, 52/57 og 62/67; eller (b) konkurrerer med et antistof, der har et HCVR/LCVR-aminosyresekvenspar, udvalgt fra gruppen bestående af SEQ ID NR: 2/7, 12/17, 22/27, 32/37, 42/47, 52/57 og 62/67, om specifik binding til CCL3/MIP-1a, CCL4/MIP-1 β eller CCL5/RANTES.
2. Monoklonalt antistof eller antigenbindende fragment deraf ifølge krav 1, der ikke binder til MCP-1, MCP-2 eller MCP-3.
3. Monoklonalt antistof eller antigenbindende fragment deraf ifølge krav 1, der binder til mindst tre forskellige CC-chemokiner, udvalgt fra gruppen bestående af CCL2/MCP-1, CCL3/MIP-1 a, CCL4/MIP-^, CCL5/RANTES, CCL14/HCC-1, CCL15/HCC-2, CCL18/PARC og CCL23/MPIF-1.
4. Monoklonalt antistof eller antigenbindende fragment ifølge krav 1, der binder til mindst én determinant af CCL2/MCP-1, CCL3/MIP-1a, CCL4/MIP-1 β, CCL5/RANTES, CCL14/HCC-1, CCL15/HCC-2, CCL18/PARC og CCL23/MPIF-1, hvilken determinant er placeret mellem CC-resterne af CC-chemokinet og den sidste C-rest af chemokinet.
5. Monoklonalt antistof eller antigenbindende fragment ifølge krav 1, der binder til mindst én determinant af CCL2/MCP-1, CCL3/MIP-1a, CCL4/MIP-1 β, CCL5/RANTES, CCL14/HCC-1, CCL15/HCC-2, CCL18/PARC og CCL23/MPIF-1, som er placeret i N-loopet, 30’s-loopet eller 40’s-loopet af CC-chemokinet.
6. Monoklonalt antistof eller antigenbindende fragment ifølge krav 1, der binder til mindst én determinant i CC-receptorbindingsresterne af et CC-chemokin.
7. Monoklonalt antistof eller antigenbindende fragment ifølge krav 1, der neutraliserer den kemotaktiske aktivitet af et CC-chemokin, hvortil det binder.
8. Monoklonalt antistof eller antigenbindende fragment deraf ifølge krav 1, der produceres af hybridomcellelinje 3C12F, 7D1G, 7D12A, 18V4F eller 18P7E, eller som kompetitivt blokerer binding af et antistof produceret af hybridomcellelinje 3C12F, 7D1G, 7D12A, 18V4F eller 18P7E , hvor - hybridomcellelinje 3C12F blev deponeret den 12. august 2010 hos American Type Culture Collection (ATCC) under accesionsnummer PTA-11261, - hybridomcellelinje 7D1G blev deponeret den 12. august 2010 hos ATCC under accesionsnummer PTA-11257, - hybridomcellelinje 7D12A blev deponeret den 12. august 2010 hos ATCC under accesionsnummer PTA-11259, - hybridomcellelinje 18V4F blev deponeret den 12. august 2010 hos ATCC under accesionsnummer PTA-11260, og - hybridomcellelinje 18P7E blev deponeret den 12. august 2010 hos ATCC under accesionsnummer PTA-11258.
9. Monoklonalt antistof eller antigenbindende fragment deraf ifølge krav 1, der binder til mindst fem CC-chemokiner, udvalgt fra gruppen bestående af CCL3/MIP-1 a, CCL4/MIP-1p, CCL5/RANTES, CCL15/HCC-2 og CCL23/MPIF-1, og som ikke binder til CCL2/MCP-1.
10. Monoklonalt antistof eller antigenbindende fragment deraf ifølge krav 1, der binder til mindst fem CC-chemokiner, udvalgt fra gruppen bestående af CCL3/MIP-1 a, CCL4/MIP-1p, CCL5/RANTES, CCL15/HCC-2 og CCL23/MPIF-1, og som ikke binder til CCL2/MCP-1 omfattende CDR-sekvenskombinationer af tung og let kæde (HCDR1/HCDR2/HCDR3/LCDR1/LCDR2/LCDR3), udvalgt fra gruppen bestående af SEQ ID NR: 3/4/5/8/9/10 og 53/54/55/58/59/60, eller som konkurrerer om binding til mindst fem CC-chemokiner, udvalgt fra CCL3/MIP-1a, CCL-4/ΜΙΡ-Ιβ, CCL5/RANTES, CCL15/HCC-2 og CCL23/MPIF-1, med et antistof eller et antigenbindende fragment omfattende CDR-sekvenskombinationer af tung og let kæde, udvalgt fra gruppen bestående af SEQ ID NR: 3/4/5/8/9/10 og 53/54/55/58/59/60.
11. Monoklonalt antistof eller antigenbindende fragment ifølge krav 9, der produceres af den hybridomcellelinje, der producerer MAb 3C12F, eller en subkultur deraf; eller som kompetitivt blokerer binding af et antistof produceret af hybridomcellelinje 3C12F, hvor hybridomcellelinje 3C12F blev deponeret den 12. august 2010 hos ATCC under accesionsnummer PTA-11261.
12. Monoklonalt antistof eller antigenbindende fragment deraf ifølge krav 1, der binder til mindst fire CC-chemokiner, udvalgt fra gruppen bestående af CCL3/MIP-1a, 0Ο_4/ΜΙΡ-1β, CCL5/RANTES, CCL14/HCC-1 og CCL18/PARC, og som ikke binder til CCL2/MCP-1.
13. Monoklonalt antistof eller antigenbindende fragment deraf ifølge krav 1, der binder til mindst fire CC-chemokiner, udvalgt fra gruppen bestående af CCL3/MIP-1a, CCL4/MIP-1p, CCL5/RANTES, CCL14/HCC-1 og CCL18/PARC, og som ikke binder til CCL2/MCP-1, der omfatter en CDR-sekvenskombination af tung og let kæde (HCDR1/HCDR2/HCDR3/LCDR1/LCDR2/LCDR3) af SEQ ID NR: 23/24/25/28/29/30, eller som konkurrerer om binding til mindst fire CC-chemokiner, udvalgt fra gruppen bestående af CCL3/MIP-1a, CCI-4/ΜΙΡ-Ιβ, CCL5/RANTES, CCL4/FICC-1 og CCL18/PARC, med et antistof eller antigenbindende fragment omfattende en CDR-sekvenskombination af tung og let kæde af SEQ ID NR: 23/24/25/28/29/30.
14. Monoklonalt antistof eller antigenbindende fragment ifølge krav 12, der produceres af den hybridomcellelinje, der producerer MAb 7D1G, eller af en subkultur deraf; eller som kompetitivt blokerer binding af et antistof produceret af hybridomcellelinje 7D1 G, hvor hybridomcellelinje 7D1G blev deponeret 12. august 2010 hos ATCC under accesionsnummer PTA-11257.
15. Monoklonalt antistof eller antigenbindende fragment deraf ifølge krav 1, der binder til mindst fire CC-chemokiner, udvalgt fra gruppen bestående af CCL3/MIP-1a, CCL-4/ΜΙΡ-Ιβ, CCL5/RANTES og CCL23/MPIF-1, og som ikke binder til CCL2/MCP-1.
16. Monoklonalt antistof eller antigenbindende fragment deraf ifølge krav 1, der binder til mindst fire CC-chemokiner, udvalgt fra gruppen bestående af CCL3/MIP-1 a, CCL-4/ΜΙΡ-Ιβ, CCL5/RANTES og CCL23/MPIF-1, og som ikke binder til CCL2/MCP-1 omfattende en CDR-sekvenskombination af tung og let kæde (HCDR1/HCDR2/HCDR3/LCDR1/LCDR2/LCDR3) af SEQ ID NR: 13/14/15/18/19/20, eller som konkurrerer om binding til mindst fire CC-chemokiner, udvalgt fra CCL3/MIP-1a, CCL4/MIP-1 β, CCL5/RANTES og CCL23/MPIF-1, med et antistof eller antigenbindende fragment omfattende en CDR- sekvenskombination af tung og let kæde af SEQ ID NOS: 13/14/15/18/19/20.
17. Monoklonalt antistof eller antigenbindende fragment ifølge krav 15, der produceres af den hybridomcellelinje, der producerer MAb 7D12A, eller af en subkultur deraf; eller som kompetitivt blokerer binding af et antistof produceret af hybridomcellelinje 7D12A, hvor hybridomcellelinje 7D12A blev deponeret den 12. august 2010 hos ATCC under accesionsnummer PTA-11259.
18. Monoklonalt antistof eller antigenbindende fragment deraf ifølge krav 1, der binder til tre CC-chemokiner, udvalgt fra gruppen bestående af CCL3/MIP-1a, CCI-4/ΜΙΡ-Ιβ og CCL5/RANTES, og som ikke binder til CCL2/MCP 1.
19. Monoklonalt antistof eller antigenbindende fragment deraf ifølge krav 1, der binder til CCL3/MIP-1a, CCI-4/ΜΙΡ-Ιβ og CCL5/RANTES, og som ikke binder til CCL2/MCP-1 omfattende en CDR-sekvenskombination af tung og let kæde (HCDR1/HCDR2/HCDR3/LCDR1/LCDR2/LCDR3), udvalgt fra gruppen bestående af SEQ ID NR: 33/34/35/38/39/40 og 63/64/65/68/69/70, eller som konkurrerer om binding til CCL3/MIP-1a, CCI-4/ΜΙΡ-Ιβ og CCL5/RANTES med et antistof eller antigenbindende fragment omfatter en CDR-sekvenskombination af tung og let kæde, udvalgt fra gruppen bestående af SEQ ID NR: 33/34/35/38/39/40 og 63/64/65/68/69/70.
20. Monoklonalt antistof eller antigenbindende fragment ifølge krav 18, der produceres af den hybridomcellelinje, der producerer MAb 18V4F, eller af en subkultur deraf; eller som kompetitivt blokerer binding af et antistof produceret af hybridomcellelinje 18V4F, hvor hybridomcellelinje 18V4F blev deponeret den 12. august 2010 hos ATCC under accesionsnummer PTA-11260.
21. Monoklonalt antistof eller antigenbindende fragment deraf ifølge krav 1, der binder til mindst tre CC-chemokiner, udvalgt fra gruppen bestående af CCL3/MIP-1a, CCI-4/ΜΙΡ-Ιβ og CCL5/RANTES, og som ikke binder til CCL2/MCP-1.
22. Monoklonalt antistof eller antigenbindende fragment deraf ifølge et hvilket som helst af kravene 9, 12, 15, 18 og 21, der binder til en determinant i N-loopet, 30’s-loopet eller 40’s-loopet af mindst ét af CC-chemokinerne.
23. Monoklonalt antistof eller antigenbindende fragment ifølge et hvilket som helst af kravene 9, 12, 15,18 og 21, der binder til mindst én antigendeterminant af CCL3/MIP-1a placeret inde i resterne 11-15 (CCFSY), resterne 17-24 (SRQIPQNF), resterne 34-35 (QC) eller resterne 57-67 (EWVQKYVSDLE) af SEQ ID NR: 71; der binder til mindst én antigendeterminant af CCI-4/ΜΙΡ-Ιβ placeret inde i resterne 11-15 (CCFSY), resterne 17-24 (ARKLPHNF), resterne 34-35 (LC) eller resterne 57-67 (SWVQEYVYDLE) af SEQ ID NR: 72; der binder til mindst én antigendeterminant af CCL5/RANTES placeret inde i resterne 10-14 (CCFAY), resterne 16-23 (ARPLPRAH), resterne 33-34 (Kc) eller resterne 56-66 (KWVREYINSLE) af SEQ ID NO: 73.
24. Monoklonalt antistof eller antigenbindende fragment deraf ifølge krav 1, der binder til mindst tre chemokiner, udvalgt fra gruppen bestående af CCL3/MIP-1a, CCI-4/ΜΙΡ-Ιβ og CCL5/RANTES, og som ikke binder til CCL2/MCP-1 omfattende en CDR-sekvenskombination af tung og let kæde (HCDR1/HCDR2/HCDR3/LCDR1/LCDR2/LCDR3) af SEQ ID NR: 43/44/45/48/49/50, eller der konkurrerer om binding til CCL3/MIP-1a, CCI-4/ΜΙΡ-Ιβ og CCL5/RANTES med et antistof eller antigenbindende fragment omfattende en CDR-sekvenskombination af tung og let kæde af SEQ ID NR: 43/44/45/48/49/50.
25. Monoklonalt antistof eller antigenbindende fragment ifølge krav 21, der produceres af den hybridomcellelinje, der producerer MAb 18P7E, eller af en subkultur deraf; eller som kompetitivt blokerer binding af et antistof produceret af hybridomcellelinje 18P7E, hvor hybridomcellelinje 18P7E blev deponeret den 12. august 2010 hos ATCC under accesionsnummer PTA-11258.
26. Monoklonalt antistof eller antigenbindende fragment deraf ifølge et hvilket som helst af kravene 1,9, 12, 15, 18 og 21, som er et humant antistof, et humaniseret antistof eller et kimært human-murint antistof eller et antigenbindende fragment deraf.
27. Hybridomcellelinje, der producerer et monoklonalt antistof ifølge krav 1.
28. Sammensætning, omfattende mindst ét monoklonalt antistof eller antigenbindende fragment deraf ifølge krav 1 i kombination med en bærer, excipiens eller buffer.
29. Monoklonalt antistof ifølge krav 1 eller et antigenbindende fragment deraf til anvendelse ved behandling af en sygdom, forstyrrelse eller tilstand, som medieres af ét eller flere CC-chemokiner, hvor sygdommen, forstyrrelsen eller tilstanden er udvalgt fra gruppen bestående af rheumatoid arthritis, dissemineret sklerose, fibrotisk sygdom, arteriosklerose, astma, onkogene sygdomme, inflammatoriske tarmsygdomme, atopisk dermatitis, psoriasis, slagtilfælde, organtransplantation, COPD, glomerulonephritis, lupus nephritis, sklerodermi, cirrhose, Alzheimers sygdom, CHF-iskæmi, koronar restenose, diabetisk neuropati/neuropati/retinopati, osteoarthritis, periodontitis, gær- og virusinfektioner og svangerskabsforstyrrelser.
DK10812667T 2009-08-28 2010-08-27 Antikin- antistoffer, der binder til flere cc-chemokiner DK2470671T3 (da)

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PCT/US2010/047004 WO2011025962A1 (en) 2009-08-28 2010-08-27 Antikine antibodies that bind to multiple cc chemokines

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JP (2) JP6109571B2 (da)
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