Plasma kallikrein binding proteins
View Patent ↗Plasma kallikrein binding proteins and methods of using such proteins are described.
1. A method of treating edema in a subject, the method comprising:
administering an antibody that binds to the active form of human plasma kallikrein to a subject in need thereof, wherein the antibody comprises:
(i) a heavy chain variable region comprising a complementary determining region (CDR) 1 set forth as HYIMM (SEQ ID NO: 166), a CDR2 set forth as GIYSSGGITVYADSVKG (SEQ ID NO: 167), and a CDR3 set forth as RRIGVPRRDEFDI (SEQ ID NO: 1171) or RRTGVPRWDDFDI (SEQ ID NO: 1177); and
(ii) a light chain variable region comprising a CDR1 set forth as RASQSISSWLA (SEQ ID NO: 1172), a CDR2 set forth as KASTLES (SEQ ID NO: 1173), and a CDR3 set forth as QQYNTYWT (SEQ ID NO: 1174).
2. The method of claim 1 , wherein
the heavy chain variable region of the antibody comprises the amino acid sequence of EVQLLESGGGLVQPGGSLRLSCAASGFTFSHYIMMWVRQAPGKGLEWVSGIYSSGGITVY ADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAYRRIGVPRRDEFDIWGQGTMVTV SS (SEQ ID NO: 2410) or EVQLLESGGGLVQPGGSLRLSCAASGFTFSHYIMMWVRQAPGK GLEWVSGIYSSGGITVYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAFRRTGVP RWDDFDIWGQGTMVTVSSASTKGPSVFPLAPSSKS (SEQ ID NO: 1801), and
the light chain variable region of the antibody comprises the amino acid sequence of DIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYKASTLESGVPSRF SGSGSGTEFTLTISSLQPDDFATYYCQQYNTYWTFGQGTKVEIK (SEQ ID NO: 2394).
3. The method of claim 1 , wherein
the heavy chain variable region of the antibody comprises the amino acid sequence of EVQLLESGGGLVQPGGSLRLSCAASGFTFSHYIMMWVRQAPGKGLEWVSGIYSSGGITVY ADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAYRRIGVPRRDEFDIWGQGTMVTV SS (SEQ ID NO: 2410) or EVQLLESGGGLVQPGGSLRLSCAASGFTFSHYIMMWVRQAPGK GLEWVSGIYSSGGITVYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAFRRTGVP RWDDFDIWGQGTMVTVSSASTKGPSVFPLAPSSKS (SEQ ID NO: 1801), and
the light chain variable region of the antibody comprises the amino acid sequence of DIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYKASTLESGVPSRF SGSGSGTEFTLTISSLQPDDFATYYCQQYNTYWTFGQGTKVEI (SEQ ID NO: 2395).
4. The method of claim 1 , wherein the antibody is a full-length antibody.
5. The method of claim 4 , wherein the antibody is an IgG molecule.
6. The method of claim 1 , wherein the antibody is an antigen-binding fragment of a full-length antibody.
7. The method of claim 1 , wherein the subject is a human patient having or at risk for edema.
8. The method of claim 1 , wherein the edema is hereditary angioedema.
9. The method of claim 7 , wherein the edema is hereditary angioedema.