Dual FC antigen binding proteins

• US 9,982,036 B2
• Filed: 02/27/2012
• Issued: 05/29/2018
• Est. Priority Date: 02/28/2011
• Status: Active Grant

• Current Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Original Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Inventors: Bossenmaier, Birgit, Kettenberger, Hubert, Klein, Christian, Kuenkele, Klaus-Peter, Regula, Joerg-Thomas, Schaefer, Wolfgang, Schwaiger, Manfred, Sustmann, Claudio
• Primary Examiner(s): ALLEN, MICHAEL D
• Application Number:
  US13/406,411
• Publication Number:
  US 20120237506A1
• Time in Patent Office: 2,283 Days
• Field of Search: None
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 16/00 Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies antibodies with enzymatic activity, e.g. abzymes C12N9/0002
• CPC Class Codes: C07K 16/2863 against receptors for growth factors, growth regulators
• CPC Class Codes: C07K 16/32 against translation products of oncogenes
• CPC Class Codes: C07K 2317/41 Glycosylation, sialylation, or fucosylation
• CPC Class Codes: C07K 2317/64 comprising a combination of variable region and constant region components
• CPC Class Codes: C07K 2317/66 comprising a swap of domains, e.g. CH3-CH2, VH-CL or VL-CH1
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/77 Internalization into the cell
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C07K 2317/94 Stability, e.g. half-life, pH, temperature or enzyme-resistance
• CPC Class Codes: C12N 15/85 for animal cells
• CPC Class Codes: G01N 21/553 and using surface plasmons fluorescence excitation G01N21/648; enhanced Raman G01N21/658

Abstract

The present invention relates to antigen binding proteins comprising two Fc parts, methods for their production, pharmaceutical compositions containing said antigen binding proteins, and uses thereof.

Claims

1. An isolated antigen binding protein comprising

a) two modified heavy chains of an antibody which specifically binds to an antigen, wherein VH of each heavy chain is replaced by the VL of said antibody, said modified heavy chains being associated with each other via their CH3 domains of the Fc part;

and

b) two modified heavy chains of said antibody wherein CH1 of each heavy chain is replaced by CL of said antibody, said modified heavy chains being associated with each other via their CH3 domains of the Fc part;

wherein the VL domains of the heavy chains of a) are associated with the VH domains of the heavy chains of b), and the CH1 domains of the heavy chains of a) are associated with the CL domains of the heavy chains of b);

wherein the antigen-binding protein does not comprise an antibody light chain;

wherein the CH2 and CH3 domains of the Fc part of the modified heavy chains of a) and the CH2 and CH3 domains of the Fc part of the modified heavy chains of b) are of the human IgG1 isotype; and

wherein either the two modified heavy chains of a), or the two modified heavy chains of b), are further modified by the amino acid substitutions S364G, L368F, D399K and K409 D, wherein the amino acid positions are numbered according to the EU Index of Kabat, and wherein the other two modified heavy chains comprise wild type CH3 amino acid sequences.

2. The isolated antigen binding protein according to claim 1, characterized in comprising

I, a) two modified heavy chains comprising the amino acid sequence of SEQ ID NO:

1; and

b) two modified heavy chains comprising the amino acid sequence of SEQ ID NO;

2;

wherein either the two modified heavy chains of a) or the two modified heavy chains of b) are further modified by the amino acid substitutions S364G, L368F, D399K and K409D, wherein the amino acid positions are numbered according to the EU Index of Kabat;

II, a) two modified heavy chains comprising the amino acid sequence of SEQ ID NO;

3; and

b) two modified heavy chains comprising the amino acid sequence of SEQ ID NO;

4;

wherein either the two modified heavy chains of a) or the two modified heavy chains of b) are further modified by the amino acid substitutions S364G, L368F, D399K and K409D, wherein the amino acid positions are numbered according to the EU Index of Kabat;

or

III, a) two modified heavy chains comprising the amino acid sequence of SEQ ID NO;

5; and

b) two modified heavy chains comprising the amino acid sequence of SEQ ID NO;

6;

wherein either the two modified heavy chains of a) or the two modified heavy chains of b) are further modified by the amino acid substitutions S364G, L368F, D399K and K409D, wherein the amino acid positions are numbered according to the EU Index of Kabat.

3. A pharmaceutical composition comprising an isolated antigen binding protein according to claim 1 and a pharmaceutical carrier.