Human antigen binding proteins that bind to a complex comprising β-Klotho and an FGF receptor
The present invention provides compositions and methods relating to or derived from antigen binding proteins capable of inducing B-Klotho, and or FGF21-like mediated signaling.
1. An isolated antigen binding protein that induces FGF21-mediated signaling, wherein the antigen binding protein comprises a light chain CDR1 comprising the sequence of SEQ ID NO: 821, a light chain CDR2 comprising the sequence of SEQ ID NO: 900, a light chain CDR3 comprising the sequence of SEQ ID NO: 954, a heavy chain CDR1 comprising the sequence of SEQ ID NO: 611, a heavy chain CDR2 comprising the sequence of SEQ ID NO: 664, and a heavy chain CDR3 comprising the sequence of SEQ ID NO: 741.
2. The antigen binding protein of claim 1 , comprising one or more of:
(a) a light chain variable domain sequence comprising V L 47 of Table 2A (SEQ ID NO. 263);
(b) a heavy chain variable domain sequence comprising V H 46 of Table 2B (SEQ ID NO: 361); or
(c) a combination comprising a light chain variable domain of (a) and a heavy chain variable domain of (b).
3. The antigen binding protein of claim 2 , wherein the light chain variable domain and the heavy chain variable domain comprise V L 47 and V H 46.
4. The antigen binding protein of claim 3 , further comprising:
(a) the kappa light chain constant sequence of SEQ ID NO: 12
(b) the lambda light chain constant sequence of SEQ ID NO: 13
(c) the heavy chain constant sequence of SEQ ID NO: 11; or
(d) (i) the kappa light chain constant sequence of SEQ ID NO: 12 or
the lambda light chain constant sequence of SEQ ID NO: 13, and
(ii) the heavy chain constant sequence of SEQ ID NO: 11.
5. The antigen binding protein of claim 1 , wherein the antigen binding protein is a human antibody, a humanized antibody, chimeric antibody, a monoclonal antibody, a polyclonal antibody, a recombinant antibody, an antigen-binding antibody fragment, a single chain antibody, a diabody, a triabody, a tetrabody, a Fab fragment, an F(fab′) 2 fragment, an IgD antibody, an IgE antibody, an IgM antibody, an IgG1 antibody, an IgG2 antibody, an IgG3 antibody, an IgG4 antibody, or an IgG4 antibody having at least one mutation in the hinge region.
6. A pharmaceutical composition comprising one or more antigen binding proteins of claim 1 , 2 , 3 , 4 or 5 in admixture with a pharmaceutically acceptable carrier thereof.
7. The antigen binding protein of claim 1 , wherein the antigen binding protein comprises one or more non-naturally occurring or encoded amino acids.
8. A method of treating a condition in a subject in need of such treatment comprising administering a therapeutically effective amount of the composition of claim 6 to the subject, wherein the condition is treatable by lowering one or more of blood glucose, insulin or serum lipid levels.
9. The method of claim 8 , wherein the condition is type 2 diabetes, obesity, dyslipidemia, NASH, cardiovascular disease or metabolic syndrome.
10. An isolated nucleic acid comprising a polynucleotide sequence encoding the light chain variable domain amino acid sequence, the heavy chain variable domain amino acid sequence, or both amino add sequences, of an antigen binding protein that induces FGF21-mediated signaling, wherein the antigen binding protein comprises a light chain CDR1 comprising the sequence of SEQ ID NO: 821, a light chain CDR2 comprising the sequence of SEQ ID NO: 900, a light chain CDR3 comprising the sequence of SEQ ID NO: 954, a heavy chain CDR1 comprising the sequence of SEQ ID NO: 611, a heavy chain CDR2 comprising the sequence of SEQ ID NO: 664, and a heavy chain CDR3 comprising the sequence of SEQ ID NO: 741.
11. An expression vector comprising the nucleic acid of claim 10 .
12. An isolated cell comprising the nucleic acid of claim 11 .
13. An isolated cell comprising the expression vector of claim 12 .
14. A method of producing an antigen binding protein comprising incubating the host cell of claim 13 under conditions that allow it to express the antigen binding protein.