Humanized anti-cd20 antibodies and methods of use
OwnerDavid G. Williamsinventor
Life of this patent
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Abstract
Humanized anti-CD20 antibodies are provided that may be used for the treatment of diseases and conditions associated with CD20-expressing cells. Also provided are nucleic acids enoding such antibodies, methods of making such antibodies, and compositions comprising such antibodies.
Claims51
A humanized antibody comprising:
- (a) a light chain comprising a light chain variable region comprising an amino acid sequence selected from the group consisting of:
- (SEQ ID NO:
- 1)
- (1) Glu Ile Val Leu Thr Gln Ser Pro Ser Ser Leu
- Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys
- Arg Ala Ser Ser Ser Leu Ser Phe Met His Trp Tyr
- Gln Gln Lys Pro Gly Lys Ala Pro Lys Xaa45 Xaa46
- Ile Tyr Ala Thr Ser Asn Leu Ala Ser Gly Val Pro
- Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Xaa70
- Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe
- Ala Thr Tyr Xaa86 Cys His Gln Trp Ser Ser Asn Pro
- Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
- wherein
- Xaa45 is Pro or Leu;
- Xaa46 is Trp or Leu;
- Xaa70 is Tyr or Phe;
- and
- Xaa86 is Tyr or Phe;
- and
- (SEQ ID NO:
- 2)
- (2) Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu
- Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys
- Arg Ala Ser Ser Ser Leu Ser Phe Met His Trp Tyr
- Gln Gln Lys Pro Gly Gln Ala Pro Arg Xaa45 Xaa46
- Ile Tyr Ala Thr Ser Asn Leu Ala Ser Gly Ile Pro
- Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Xaa70
- Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe
- Ala Val Tyr Phe Cys His Gln Trp Ser Ser Asn Pro
- Leu Thr Phe Gly Gln Gly Thr Lys Val Glu Leu Lys
- wherein
- Xaa45 is Pro or Leu;
- Xaa46 is Trp or Leu;
- and
- Xaa70 is Tyr or Phe;
- and
- (b) a heavy chain comprising a heavy chain variable region comprising the following amino acid sequence:
- (SEQ ID NO:
- 3)
- Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys
- Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala
- Ser Gly Tyr Thr Phe Thr Ser Tyr Asn Met His Trp
- Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Ile
- Gly Ala Ile Tyr Pro Gly Asn Gly Asp Thr Ser Tyr
- Asn Gln Lys Phe Lys Gly Arg Xaa68 Thr Xaa70
- Thr Xaa72 Asp Xaa74 Ser Ala Asn Thr Ala Tyr Met
- Glu Leu Ser Ser Leu Lys Ser Glu Asp Thr Ala Val
- Tyr Tyr Cys Ala Arg Ser His Tyr Gly Ser Asn Tyr
- Val Asp Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Leu
- Val Thr Val Ser Ser
- wherein
- Xaa68 is Val or Ala;
- Xaa70 is Val or Leu;
- Xaa72 is Arg or Ala;
- and
- Xaa74 is Thr or Lys;
- wherein the humanized antibody binds to human CD-20.
A pharmaceutical composition comprising the humanized antibody of any of the preceding claims and a pharmaceutically acceptable excipient.
A humanized antibody comprising a light chain comprising a light chain variable region comprising the following amino acid sequence:
- (SEQ ID NO:
- 1)
- Glu Ile Val Leu Thr Gln Ser Pro Ser Ser Leu Ser
- Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg
- Ala Ser Ser Ser Leu Ser Phe Met His Trp Tyr Gln
- Gln Lys Pro Gly Lys Ala Pro Lys Xaa45 Xaa46
- Ile Tyr Ala Thr Ser Asn Leu Ala Ser Gly Val Pro
- Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Xaa70
- Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe
- Ala Thr Tyr Xaa86 Cys His Gln Trp Ser Ser
- Asn Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu
- Ile Lys
- wherein
- Xaa45 is Pro or Leu;
- Xaa46 is Trp or Leu;
- Xaa70 is Tyr or Phe;
- and
- Xaa86 is Tyr or Phe;
- wherein the humanized antibody binds to human CD-20.
A humanized antibody comprising a light chain comprising a light chain variable region comprising the following amino acid sequence:
- (SEQ ID NO:
- 2)
- Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser
- Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg
- Ala Ser Ser Ser Leu Ser Phe Met His Trp Tyr Gln
- Gln Lys Pro Gly Gln Ala Pro Arg Xaa45 Xaa46
- Ile Tyr Ala Thr Ser Asn Leu Ala Ser Gly Ile Pro
- Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Xaa70
- Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe
- Ala Val Tyr Phe Cys His Gln Trp Ser Ser Asn Pro
- Leu Thr Phe Gly Gln Gly Thr Lys Val Glu Leu Lys
- wherein
- Xaa45 is Pro or Leu;
- Xaa46 is Trp or Leu;
- and
- Xaa70 is Tyr or Phe;
- wherein the humanized antibody binds to human CD-20.
A humanized antibody comprising a heavy chain comprising a heavy chain variable region comprising the following amino acid sequence:
- (SEQ ID NO:
- 3)
- Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys
- Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala
- Ser Gly Tyr Thr Phe Thr Ser Tyr Asn Met His Trp
- Val Arg Gln Ala Pro Gly Gln Arg Leu Glu Trp Ile
- Gly Ala Ile Tyr Pro Gly Asn Gly Asp Thr Ser Tyr
- Asn Gln Lys Phe Lys Gly Arg Xaa68 Thr Xaa70 Thr
- Xaa72 Asp Xaa74 Ser Ala Asn Thr Ala Tyr Met Glu
- Leu Ser Ser Leu Lys Ser Glu Asp Thr Ala Val Tyr
- Tyr Cys Ala Arg Ser His Tyr Gly Ser Asn Tyr Val
- Asp Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val
- Thr Val Ser Ser
- wherein
- Xaa68 is Val or Ala;
- Xaa70 is Val or Leu;
- Xaa72 is Arg or Ala;
- and
- Xaa74 is Thr or Lys;
- wherein the humanized antibody is capable of binding to human CD-20.
Dependencies are inferred from the claim text.