Antibodies
AssigneeGenmab A/S
InventorsDavid SATIJN, Esther C. W. BREIJ, Bart E. C. G. DE GOEIJ, Kristel KEMPER, Patrick ENGELBERTS, Edward N. VAN DEN BRINK, Rik RADEMAKER, Dennis VERZIJL, Sjeng HORBACH, Paul PARREN
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Abstract
The present invention relates to antibodies binding to 5T4, including bispecific antibodies binding to 5T4 and CD3. The invention further provides pharmaceutical compositions comprising the antibodies and use of the antibodies for therapeutic and diagnostic procedures, in particular in cancer therapy.
Claims31
1-133. (canceled)
A bispecific antibody comprising a first heavy chain and a first light chain comprising a first antigen-binding region which binds to human 5T4, and a second heavy chain and a second light chain comprising a second antigen-binding region which binds to human CD3, wherein
- (a) the first antigen-binding region comprises a variable heavy chain (VH) region comprising the complementarity determining regions (CDRs) and the framework regions (FRs) within the amino acid sequence set forth in SEQ ID NO:
- 40 and a variable light chain (VL) region comprising the CDRs and FRs within the amino acid sequence set forth in SEQ ID NO:
- 44, and
- (b) the second antigen-binding region comprises a VH region comprising the CDRs and FRs within the amino acid sequence set forth in SEQ ID NO.:
- 68 and a VL region comprising the CDRs and FRs within the amino acid sequence set forth in SEQ ID NO:
- 60, and
- wherein in each of the VH and VL regions, the CDRs and FRs are arranged from amino-terminus to carboxy-terminus in the following order:
- FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4.
A bispecific antibody comprising a first heavy chain and a first light chain comprising a first antigen-binding region which binds to human 5T4, and a second heavy chain and a second light chain comprising a second antigen-binding region which binds to human CD3, wherein
- (a) the first antigen-binding region comprises a variable heavy chain (VH) region comprising the complementarity determining regions (CDRs) and the framework regions (FRs) within the amino acid sequence set forth in SEQ ID NO.:
- 40 and a variable light chain (VL) region comprising the CDRs and FRs within the amino acid sequence set forth in SEQ ID NO:
- 44, and
- (b) the second antigen-binding region comprises a VH region comprising the CDRs and FRs within the amino acid sequence set forth in SEQ ID NO.:
- 68 and a VL region comprising the CDRs and FRs within the amino acid sequence set forth in SEQ ID NO:
- 60,
- wherein in each of the VH and VL regions, the CDRs and FRs are arranged from amino-terminus to carboxy-terminus in the following order:
- FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4,
- wherein the bispecific antibody comprises a human IgG1 Fc region, and wherein the first heavy chain comprises a constant region wherein the amino acid residues corresponding to L234, L235, D265, and K409 in a human IgG1 heavy chain according to EU numbering are F, E, A and R, respectively, and the second heavy chain comprises a constant region wherein the amino acid residues corresponding to L234, L235, D265, and F405 in a human IgG1 heavy chain according to EU numbering are F, E, A, and L, respectively, and
- wherein the first light chain and second light chain comprise light chain constant regions consisting of the amino acid sequences set forth in SEQ ID NOs:
- 95 and 96, respectively.
A bispecific antibody comprising a first heavy chain and a first light chain comprising a first antigen-binding region which binds to human 5T4, and a second heavy chain and a second light chain comprising a second antigen-binding region which binds to human CD3, wherein
- (a) the first antigen-binding region comprises a variable heavy chain (VH) region consisting of the amino acid sequence set forth in SEQ ID NO.:
- 40 and a variable light chain (VL) region consisting of the amino acid sequence set forth in SEQ ID NO:
- 44, and
- (b) the second antigen-binding region comprises a VH region consisting of the amino acid sequence set forth in SEQ ID NO.:
- 68 and a VL region consisting of the amino acid sequence set forth in SEQ ID NO:
- 60.
A bispecific antibody comprising a first heavy chain and a first light chain comprising a first antigen-binding region which binds to human 5T4, and a second heavy chain and a second light chain comprising a second antigen-binding region which binds to human CD3, wherein
- (a) the first antigen-binding region comprises a variable heavy chain (VH) region consisting of the amino acid sequence set forth in SEQ ID NO:
- 40 and a variable light chain (VL) region consisting of the amino acid sequence set forth in SEQ ID NO:
- 44, and
- (b) the second antigen-binding region comprises a VH region consisting of the amino acid sequence set forth in SEQ ID NO:
- 68 and a VL region consisting of the amino acid sequence set forth in SEQ ID NO:
- 60,
- wherein the bispecific antibody comprises a human IgG1 Fc region, and wherein the first heavy chain comprises a constant region wherein the amino acid residues corresponding to L234, L235, D265, and K409 in a human IgG1 heavy chain according to EU numbering are F, E, A, and R, respectively, and the second heavy chain comprises a constant region wherein the amino acid residues corresponding to L234, L235, D265, and F405 in a human IgG1 heavy chain according to EU numbering are F, E, A, and L, respectively, and
- wherein the first light chain and second light chain comprise light chain constant regions consisting of the amino acid sequences set forth in SEQ ID NOs:
- 95 and 96, respectively.
Dependencies are inferred from the claim text.