US2006147446A1PendingUtilityA1
Humanized antibodies to human GP39, compositions, and therapeutic uses thereof
Est. expiryNov 7, 2015(expired)· nominal 20-yr term from priority
A61P 37/08A61P 37/00A61P 3/10A61P 35/02A61P 37/04A61P 35/00A61P 29/00A61P 3/00A61P 27/00C07K 2317/92A61P 11/00C07K 2317/24G01N 2800/24A61P 17/00C07K 2317/56C07K 2317/73G01N 2333/70578A61K 2039/505A61P 1/00A61K 38/00A61P 11/06A61P 1/04C07K 16/467C07K 16/2875C07K 2317/76A61P 17/06A61K 39/395C07K 16/46C07K 16/00C07K 16/28
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Claims
Abstract
The present invention is directed to humanized antibodies which bind human gp39 and their use as therapeutic agents. These humanized antibodies are especially useful for treatment of autoimmune diseases.
Claims
exact text as granted — not AI-modified1 . A humanized antibody which is capable of competing with the murine 24-31 antibody for inhibiting CD40 binding to gp39.
2 . The antibody of claim 1 which contains the complementarity determining regions of the 24-31 antibody as set forth in FIGS. 4-8 or variants and equivalents which contain one or more conservative amino acid substitutions.
3 . A humanized antibody derived from murine monoclonal antibody 24-31.
4 - 6 . (canceled)
7 . The humanized antibody of claim 1 , wherein said antibody contains a humanized variable light sequence selected from the following group.
(1)
DIVMTQSPSFLSASVGDRVTITC KASQNVITAVA WYQQK
PGKSPKLLIY SASNRYT GVPDRFSGSGSGTDFTLTISSL
QPEDFADYFC QQYNSYPYT FGGGTKLEIK;
(2)
DIVMTQSPDSLAVSLGERATINC KASQNVITAVA WYQQK
PGQSPKLLIY SASNRYT GVPDRFSGSGSGTDFTLTISSL
QAEDVADYFC QQYNSYPYT FGGGTKLEIK;
(3)
DIVMTQSPSFMSTSVGDRVTITC KASQNVITAVA WYQQK
PGKSPKLLIY SASNRYT GVPDRFSGSGSGTDFTLTISSM
QPEDFADYFC QQYNSYPYT FGGGTKLEIK;
(4)
DIVMTQSPDSMATSLGERVTINC KASQNVITAVA WYQQK
PGQSPKLLIY SASNRYT GVPDRFSGSGSGTDFTLTISSM
QAEDVADYFC QQYNSYPYT FGGGTKLEIK,
and variants and equivalents thereof which contain one or more conservative amino acid substitutions which do not substantially affect the ability of the resultant humanized antibody to bind the gp39 antigen.
8 . The humanized antibody of claim 1 , wherein said antibody contains a humanized variable heavy sequence selected from the group consisting of:
(1)
EVQLQESGPGLVKPSETLSLTCTVSGDSIT NGFWI
WIRKPPGNKLEYMG YISYSGSTYYNPSLKS RISISRDTSK
NQFSLKLSSVTAADTGVYYCAC RSYGRTPYYFDF WGQGTT
LTVSS;
(2)
EVQLQESGPGLVKPSQTLSLTCTVSGDSIT NGFWI WIRKH
PGNKLEYMG YISYSGSTYYNPSLKS RISISRDTSKNQFSL
KLSSVTAADTGVYYCAC RSYGRTPYYFDF
WGQGTTLTVSS;
(3)
EVQLQESGPGLVKPSQTLSLTCAVSGDSIT NGFWI WIRKH
PGNKLEYMG YISYSGSTYYNPSLKS RISISRDTSNNQFSL
NLNSVTRADTGVYYCAC RSYGRTPYYFDF
WGQGTTLTVSS;
(4)
EVQLQESGPGLVKPSETLSLTCAVYGDSIT NGFWI WIRKP
PGNKLEYMG YISYSGSTYYNPSLKS RISISRDTSKNQFYL
KLSSVTAADTGVYYCAC RSYGRTPYYFDF
WGQGTTLTVSS.
and variants and equivalents thereof which contain one or more conservative amino acid substitutions which do not substantially affect the ability of the resultant humanized antibody to bind the gp39 antigen.
9 . The humanized antibody of claim 1 , which contains a humanized variable light sequence selected from the group consisting of the following group:
(1)
DIVMTQSPSFLSASVGDRVTITC KASQNVITAVA WYQQKPGKSP
KLLIY SASNRYT GVPDRFSGSGSGTDFTLTISSLQPEDFADYFC
QQYNSYPYT FGGGTKLEIK;
(2)
DIVMTQSPDSLAVSLGERATINC KASQNVITAVA WYQQKPGQSP
KLLIY SASNRYT GVPDRFSGSGSGTDFTLTISSLQAEDVADYFC
QQYNSYPYT FGGGTKLEIK;
(3)
DIVMTQSPSFMSTSVGDRVTITC KASQNVITAVA WYQQKPGKSP
KLLIY SASNRYT GVPDRFSGSGSGTDFTLTISSMQPEDFADYFC
QQYNSYPYT FGGGTKLEIK;.
(4)
DIVMTQSPDSMATSLGERVTINC KASQNVITAVA WYQQKPGQSP
KLLIY SASNRYT GVPDRFSGSGSGTDFTLTISSMQAEDVADYFC
QQYNSYPYT FGGGTKLEIK
and a humanized variable heavy sequence selected from the following group:
(1)
EVQLQESGPGLVKPSETLSLTCTVSGDSIT NGFWI WIRKP
PGNKLEYMG YISYSGSTYYNPSLKS RISISRDTSKNQFSL
KLSSVTAADTGVYYCAC RSYGRTPYYFDF
WGQGTTLTVSS;
(2)
EVQLQESGPGLVKPSQTLSLTCTVSGDSIT NGFWI WIRKH
PGNKLEYMG YISYSGSTYYNPSLKS RISISRDTSKNQFSL
KLSSVTAADTGVYYCAC RSYGRTPYYFDF
WGQGTTLTVSS;
(3)
EVQLQESGPGLVKPSQTLSLTCAVSGDSIT NGFWI WIRKH
PGNKLEYMG YISYSGSTYYNPSLKS RISISRDTSNNQFSL
NLNSVTRADTGVYYCAC RSYGRTPYYFDF
WGQGTTLTVSS;
(4)
EVQLQESGPGLVKPSETLSLTCAVYGDSIT NGFWI WIRKP
PGNKLEYMG YISYSGSTYYNPSLKS RISISRDTSKNQFYL
KLSSVTAADTGVYYCAC RSYGRTPYYFDF
WGQGTTLTVSS,
and
and variants and equivalents thereof which contain one or more conservative amino acid substitutions which do not substantially affect the ability of the resultant humanized antibody to bind the gp39 antigen.
10 . The humanized antibody of claim 9 , which contains humanized variable light sequence (I) and humanized variable heavy sequence (1).
11 . The humanized antibody of claim 9 , which contains humanized variable light sequence (2) and humanized variable heavy sequence (1).
12 - 13 . (canceled)
14 . The humanized antibody of claim 1 , which contains the human kappa or lambda light chain constant region and either the human gamma 1 or gamma 4 heavy chain constant region.
15 - 16 . (canceled)
17 . A pharmaceutical composition which contains a humanized antibody derived from murine monoclonal antibody 24-31.
18 . The pharmaceutical composition of claim 17 , wherein said humanized antibody contains a humanized variable light sequence selected from the following group:
(1)
DIVMTQSPSFLSASVGDRVTITC KASQNVITAVA WYQQKPGKSPK
LLIY SASNRYT GVPDRFSGSGSGTDFTLTISSLQPEDFADYFC Q
QYNSYPYT FGGGTKLEIK;
(2)
DIVMTQSPDSLAVSLGERATINC KASQNVITAVA WYQQKPGQSPK
LLIY SASNRYT GVPDRFSGSGSGTDFTLTISSLQAEDVADYFC Q
QYNSYPYT FGGGTKLEIK;
(3)
DIVMTQSPSFMSTSVGDRVTITC KASQNVITAVA WYQQKPGKSPK
LLIY SASNRYT GVPDRFSGSGSGTDFTLTISSMQPEDFADYFC Q
QYNSYPYT FGGGTKLEIK;
(4)
DIVMTQSPDSMATSLGERVTINC KASQNVITAVA WYQQKPGQSPK
LLIY SASNRYT GVPDRFSGSGSGTDFTLTISSMQAEDVADYFC Q
QYNSYPYT FGGGTKLEIK.
and variants and equivalents thereof which contain one or more conservative amino acid substitutions which do not substantially affect the ability of the resultant humanized antibody to bind the gp39 antigen.
19 . The pharmaceutical composition of claim 18 , wherein said humanized antibody contains a humanized variable heavy sequence selected from the following group:
(1)
EVQLQESGPGLVKPSETLSLTCTVSGDSIT NGFWI
WIRKPPGNKLEYMG YISYSGSTYYNPSLKS
RISISRDTSKNQFSLKLSSVTAADTGVYYCAC
RSYGRTPYYFDF WGQGTTLTVSS;
(2)
EVQLQESGPGLVKPSQTLSLTCTVSGDSIT NGFWI
WIRKHPGNKLEYMG YISYSGSTYYNPSLKS
RISISRDTSKNQFSLKLSSVTAADTGVYYCAC
RSYGRTPYYFDF WGQGTITLTVSS;
(3)
EVQLQESGPGLVKPSQTLSLTCAVSGDSIT NGFWI
WIRKHPGNKLEYMG YISYSGSTYYNPSLKS
RISISRDTSNNQFSLNLNSVTRADTGVYYCAC
RSYGRTPYYFDF WGQGTTLTVSS;
(4)
EVQLQESGPGLVKPSETLSLTCAVYGDSIT NGFWI
WIRKPPGNKLEYMG YISYSGSTYYNPSLKS
RISISRDTSKNQFYLKLSSVTAADTGVYYCAC
RSYGRTPYYFDF WGQGTTLTVSS,
and variants and equivalents thereof which contain one or more conservative amino acid substitutions which do not substantially affect the ability of the resultant humanized antibody to bind the gp39 antigen.
20 . The pharmaceutical composition of claim 17 , wherein said humanized antibody contains a humanized variable light sequence selected from the following group:
(1)
DIVMTQSPSFLSASVGDRVTITC KASQNVITAVA
WYQQKPGKSPKLLIY SASNRYT
GVPDRFSGSGSGTDFTLTISSLQPEDFADYFC QQYNSYPYT
FGGGTKLEIK;
(2)
DIVMTQSPDSLAVSLGERATINC KASQNVITAVA
WYQQKPGQSPKLLIY SASNRYT
GVPDRFSGSGSGTDFTLTISSLQAEDVADYFC QQYNSYPYT
FGGGTKLEIK;
(3)
DIVMTQSPSFMSTSVGDRVTITC KASQNVITAVA
WYQQKPGKSPKLLIY SASNRYT
GVPDRFSGSGSGTDFTLTISSMQPEDFADYFC QQYNSYPYT
FGGGTKLEIK;
(4)
DIVMTQSPDSMATSLGERVTINC KASQNVITAVA
WYQQKPGQSPKLLIY SASNRYT
GVPDRFSGSGSGTDFTLTISSMQAEDVADYFC QQYNSYPYT
FGGGTKLEIK
and a humanized variable heavy sequence selected from the following group:
(1)
EVQLQESGPGLVKPSETLSLTCTVSGDSIT NGFWI
WIRKPPGNKLEYMG YISYSGSTYYNPSLKS
RISISRDTSKNQFSLKLSSVTAADTGVYYCAC
RSYGRTPYYFDF WGQGTTLTVSS;
(2)
EVQLQESGPGLVKPSQTLSLTCTVSGDSIT NGFWI
WIRKHPGNKLEYMG YISYSGSTYYNPSLKS
RISISRDTSKNQFSLKLSSVTAADTGVYYCAC
RSYGRTPYYFDF WGQGTTLTVSS;
(3)
EVQLQESGPGLVKPSQTLSLTCAVSGDSIT NGFWI
WIRKHPGNKLEYMG YISYSGSTYYNPSLKS
RISISRDTSNNQFSLNLNSVTRADTGVYYCAC
RSYGRTPYYFDF WGQGTTLTVSS;
(4)
EVQLQESGPGLVKPSETLSLTCAVYGDSIT NGFWI
WLRKPPGNKLEYMG YISYSGSTYYNPSLKS
RISISRDTSKNQFYLKLSSVTAADTGVYYCAC
RSYGRTPYYFDF WGQGTTLTVSS,
and variants and equivalents thereof which contain one or more conservative amino acid substitutions which do not substantially affect the ability of the resultant humanized antibody to bind the gp39 antigen.
21 . The pharmaceutical composition of claim 20 , wherein the humanized antibody contains humanized variable light sequence (1) and humanized variable heavy sequence (1).
22 . The pharmaceutical composition of claim 20 , wherein the antibody contains humanized variable light sequence (2) and humanized variable heavy sequence (1).
23 - 24 . (canceled)
25 . A method of treatment of a disease treatable by modulating gp39 expression or inhibiting the gp39/CD40 interaction which comprises administering a therapeutically effective amount of a humanized antibody according to claim 1 .
26 . The method of claim 25 , wherein said disease is an autoimmune disorder.
27 . The method of claim 26 , wherein said autoimmune disorder is selected from the group consisting of rheumatoid arthritis, psoriasis, multiple sclerosis, diabetes, systemic lupus erythematosus and ITP.
28 . The method of claim 25 , wherein the disease is a non-autoimmune disorder.
29 . The method of claim 26 , wherein the disease is graft-versus-host disease or graft rejection.Cited by (0)
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