I have now studied the PCSK9 patents by REGN and AMGN, and I have a preliminary view of the litigation as reported in the press. I do not have a copy of the court filing, so if anyone has that or knows how to find it I will be appreciative. Also, I may have missed patent(s) though I think my key word search at the USPTO database has been appropriate. I will post my view on the litigation validity as soon as I read the court filing on the litigation. So, I am parking the below the PSCK9 patent summaries, and the claims of what I think seem to be the key patents.
Regeneron and Amgen PCSK9 Patents
REGN
1. United States Patent
| 8,062,640
| Sleeman , et al.
| November 22, 2011
| High affinity human antibodies to PCSK9
Abstract
An human antibody or antigen-binding fragment of a human antibody that specifically binds and inhibits human proprotein convertase subtilisin/kexin type 9 (hPCSK9) characterized by the ability to reduce serum LDL cholesterol by 40-80% over a 24, 60 or 90 day period relative to predose levels, with little or no reduction in serum HDL cholesterol and/or with little or no measurable effect on liver function, as determined by ALT and AST measurements.
We claim:
1. An antibody or antigen-binding fragment thereof which specifically binds hPCSK9, wherein the antibody or antigen-binding fragment comprises the heavy and light chain CDRs of a HCVR/LCVR amino acid sequence pair having SEQ ID NOs:218/226.
2. The antibody or antigen-binding fragment of claim 1 comprising heavy and light chain CDR amino acid sequences having SEQ ID NOs:220, 222, 224, 228, 230 and 232.
3. The antibody or antigen-binding fragment of claim 2 comprising an HCVR having the amino acid sequence of SEQ ID NO:218 and an LCVR having the amino acid sequence of SEQ ID NO:226.
2. United States Patent
| 8,501,184
| Sleeman , et al.
| August 6, 2013
| High affinity human antibodies to PCSK9
Abstract
An human antibody or antigen-binding fragment of a human antibody that specifically binds and inhibits human proprotein convertase subtilisin/kexin type 9 (hPCSK9) characterized by the ability to reduce serum LDL cholesterol by 40-80% over a 24, 60 or 90 day period relative to predose levels, with little or no reduction in serum HDL cholesterol and/or with little or no measurable effect on liver function, as determined by ALT and AST measurements.
3. United States Patent
| 8,795,669
| Walsh , et al.
| August 5, 2014
| Stabilized formulations containing anti-PCSK9 antibodies
Abstract
The present invention provides pharmaceutical formulations comprising a human antibody that specifically binds to human proprotein convertase subtilisin/kexin type 9 (PCSK9). The formulations may contain, in addition to an anti-PCSK9 antibody, at least one amino acid, at least one sugar, or at least one non-ionic surfactant. The pharmaceutical formulations of the present invention exhibit a substantial degree of antibody stability after storage for several months.
AMGN
1. United States Patent
| 8,030,457
| Jackson , et al.
| October 4, 2011
| Antigen binding proteins to proprotein convertase subtilisin kexin type 9 (PCSK9)
Abstract
Antigen binding proteins that interact with Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) are described. Methods of treating hypercholesterolemia and other disorders by administering a pharmaceutically effective amount of an antigen binding protein to PCSK9 are described. Methods of detecting the amount of PCSK9 in a sample using an antigen binding protein to PCSK9 are described.
What is claimed is:
1. An isolated neutralizing antigen binding protein that binds to a PCSK9 protein comprising the amino acid sequence of SEQ ID NO: 1, wherein the neutralizing antigen binding protein comprises: a heavy chain polypeptide comprising the following complementarity determining regions (CDRs): a heavy chain CDR1 that is a CDR1 in SEQ ID NO: 49; a heavy chain CDR2 that is a CDR2 in SEQ ID NO: 49; a heavy chain CDR3 that is a CDR3 in SEQ ID NO: 49 and a light chain polypeptide comprising the following CDRs: a light chain CDR1 that is a CDR1 in SEQ ID NO: 23; a light chain CDR2 that a CDR2 in SEQ ID NO: 23; and a light chain CDR3 that is a CDR3 in SEQ ID NO: 23.
2. The isolated neutralizing antigen binding protein of claim 1, wherein the antigen binding protein is a LDLR competitive neutralizing antigen binding protein.
3. A pharmaceutical composition comprising at least one antigen binding protein according to claim 1, and a pharmaceutically acceptable excipient.
4. The isolated neutralizing antigen binding protein of claim 1, wherein the heavy chain polypeptide comprises all three of the following amino acid sequences: SEQ ID NO: 308, SEQ IDNO: 175, and SEQ ID NO: 180.
5. The isolated neutralizing antigen binding protein of claim 1, wherein the heavy chain polypeptide comprises all three of the following amino acid sequences: SEQ ID NO: 368, SEQ ID NO: 175, and SEQ ID NO: 180.
6. The isolated neutralizing antigen binding protein of claim 1, wherein the light chain polypeptide comprises all three of the following amino acid sequences: SEQ ID NO: 158, SEQ ID NO: 162, and SEQ ID NO: 395.
7. The isolated neutralizing antigen binding protein of claim 6, wherein the heavy chain polypeptide comprises all three of the following amino acid sequences: SEQ ID NO: 308, SEQ ID NO: 175, and SEQ ID NO: 180.
8. The isolated neutralizing antigen binding protein of claim 6, wherein the heavy chain polypeptide comprises all three of the following amino acid sequences: SEQ ID NO: 368, SEQ ID NO: 175, and SEQ ID NO: 180.
9. The isolated neutralizing antigen binding protein of claim 1, wherein the light chain polypeptide comprises: a CDR1 comprising SEQ ID NO: 158, a CDR2 comprising SEQ ID NO: 162, and a CDR3 comprising SEQ ID NO: 395.
10. The isolated neutralizing antigen binding protein of claim 1, wherein the heavy chain polypeptide comprises: a CDR1 comprising SEQ ID NO: 308, a CDR2 comprising SEQ ID NO: 175, and a CDR3 comprising SEQ ID NO: 180.
11. The isolated neutralizing antigen binding protein of claim 1, wherein the heavy chain polypeptide comprises: a CDR1 comprising SEQ ID NO: 368, a CDR2 comprising SEQ ID NO: 175, and a CDR3 comprising SEQ ID NO: 180.
12. The isolated neutralizing antigen binding protein of claim 10, wherein the light chain polypeptide comprises: a CDR1 comprising SEQ ID NO: 158, a CDR2 comprising SEQ ID NO: 162, and a CDR3 comprising SEQ ID NO: 395.
13. The isolated neutralizing antigen binding protein of claim 11, wherein the light chain polypeptide comprises: a CDR1 comprising SEQ ID NO: 158, a CDR2 comprising SEQ ID NO: 162, and a CDR3 comprising SEQ ID NO: 395.
14. The isolated neutralizing antigen binding protein of claim 1, wherein the heavy chain polypeptide comprises SEQ ID NO: 49 and the light chain polypeptide comprises SEQ ID NO: 23.
15. The isolated neutralizing antigen binding protein of claim 1, wherein each CDR is defined in accordance with the Kabat definition, the Chothia definition, the combination of the Kabat definition and the Chothia definition, the AbM definition, or the contact definition of CDR.
16. The isolated neutralizing antigen binding protein of claim 15, wherein each CDR is defined in accordance with the CDR definition of Kabat.
17. The isolated neutralizing antigen binding protein of claim 15, wherein each CDR is defined in accordance with the CDR definition of Chothia.
18. The isolated neutralizing antigen binding protein of claim 15, wherein each CDR is defined in accordance with the combination of the Kabat definition and the Chothia definition.
19. An isolated neutralizing human monoclonal antibody that binds to a PCSK9 protein comprising: a heavy chain polypeptide comprising the following complementarity determining regions (CDRs): a heavy chain CDR1 that is a CDR1 in SEQ ID NO: 49; a heavy chain CDR2 that is a CDR2 in SEQ ID NO: 49; a heavy chain CDR3 that is a CDR3 in SEQ ID NO: 49; and a light chain polypeptide comprising the following CDRs: a light chain CDR1 that is a CDR1 in SEQ ID NO: 23; a light chain CDR2 that a CDR2 in SEQ ID NO: 23; and a light chain CDR3 that is a CDR3 in SEQ ID NO: 23, wherein each CDR is defined in accordance with the CDR definition of Kabat.
20. The isolated neutralizing human monoclonal antibody of claim 19, wherein the heavy chain polypeptide comprises all three of the following amino acid sequences: SEQ ID NO: 308, SEQ ID NO: 175, and SEQ ID NO: 180.
21. The isolated neutralizing human monoclonal antibody of claim 19, wherein the heavy chain polypeptide comprises all three of the following amino acid sequences: SEQ ID NO: 368, SEQ ID NO: 175, and SEQ ID NO: 180.
22. The isolated neutralizing human monoclonal antibody of claim 20, wherein the light chain polypeptide comprises all three of the following sequences: SEQ ID NO: 158, SEQ ID NO: 162, and SEQ ID NO: 395.
23. The isolated neutralizing human monoclonal antibody of claim 21, wherein the light chain polypeptide comprises all three of the following sequences: SEQ ID NO: 158, SEQ ID NO: 162, and SEQ ID NO: 395.
24. The isolated neutralizing human monoclonal antibody of claim 19, wherein the heavy chain polypeptide comprises SEQ ID NO: 49 and the light chain polypeptide comprises SEQ ID NO: 23.
25. An isolated neutralizing human monoclonal antibody that binds to a PCSK9 protein comprising: a heavy chain polypeptide comprising: the amino acid sequence of SEQ ID NO: 180; the amino acid sequence of SEQ ID NO: 175; and the amino acid sequence of SEQ ID NO: 308; and a light chain polypeptide comprising: the amino acid sequence of SEQ ID NO: 395; the amino acid sequence of SEQ ID NO: 162; and the amino acid sequence of SEQ ID NO: 158.
26. An isolated neutralizing human monoclonal antibody that binds to a PCSK9 protein comprising: a heavy chain polypeptide comprising the following complementarity determining regions (CDRs): a heavy chain CDR1 that is a CDR1 in SEQ ID NO: 308 or a CDR1 in SEQ ID NO:368; a heavy chain CDR2 that is a CDR2 in SEQ ID NO: 175; a heavy chain CDR3 that is a CDR3 in SEQ ID NO: 180; and a light chain polypeptide comprising the following CDRs: a light chain CDR1 that is a CDR1 in SEQ ID NO: 158; a light chain CDR2 that is a CDR2 in SEQ ID NO: 162; and a light chain CDR3 that is a CDR3 in SEQ ID NO: 395.
27. An isolated neutralizing human monoclonal antibody that binds to a PCSK9 protein comprising: a heavy chain polypeptide comprising the following complementarity determining regions (CDRs): a heavy chain CDR1 that is a CDR1in SEQ ID NO: 49; a heavy chain CDR2 that is a CDR2 in SEQ ID NO: 49; a heavy chain CDR3 that is a CDR3 in SEQ ID NO: 49, wherein the heavy chain polypeptide comprises: the amino acid sequence of SEQ ID NO: 180; the amino acid sequence of SEQ ID NO: 175; and the amino acid sequence of SEQ ID NO: 308; and a light chain polypeptide comprising the following CDRs: a light chain CDR1 that is a CDR1 in SEQ ID NO: 23; a light chain CDR2 that a CDR2 in SEQ ID NO: 23; and a light chain CDR3 that is a CDR3 in SEQ ID NO: 23, wherein the light chain polypeptide comprises: the amino acid sequence of SEQ ID NO: 395; the amino acid sequence of SEQ ID NO: 162; and the amino acid sequence of SEQ ID NO: 158.
2. United States Patent
| 8,168,762
| Jackson , et al.
| May 1, 2012
| Antigen binding proteins to proprotein convertase subtilisin kexin type 9 (PCSK9)
Abstract
Antigen binding proteins that interact with Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) are described. Methods of treating hypercholesterolemia and other disorders by administering a pharmaceutically effective amount of an antigen binding protein to PCSK9 are described. Methods of detecting the amount of PCSK9 in a sample using an antigen binding protein to PCSK9 are described.
3. United States Patent
| 8,563,698
| Jackson , et al.
| October 22, 2013
| Antigen binding proteins to proprotein convertase subtilisin kexin type 9 (PCSK9)
Abstract
Antigen binding proteins that interact with Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) are described. Methods of treating hypercholesterolemia and other disorders by administering a pharmaceutically effective amount of an antigen binding protein to PCSK9 are described. Methods of detecting the amount of PCSK9 in a sample using an antigen binding protein to PCSK9 are described.
Filed:
| May 28, 2009
| 4. United States Patent
| 8,829,165
| Jackson , et al.
| September 9, 2014
| Antigen binding proteins to proprotein convertase subtilisin kexin type 9 (PCSK9)
Abstract
Antigen binding proteins that interact with Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) are described. Methods of treating hypercholesterolemia and other disorders by administering a pharmaceutically effective amount of an antigen binding protein to PCSK9 are described. Methods of detecting the amount of PCSK9 in a sample using an antigen binding protein to PCSK9 are described.
United States Patent
| 8,859,741
| Jackson , et al.
| October 14, 2014
| Antigen binding proteins to proprotein convertase subtilisin kexin type 9 (PCSK9)
Abstract
Antigen binding proteins that interact with Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) are described. Methods of treating hypercholesterolemia and other disorders by administering a pharmaceutically effective amount of an antigen binding protein to PCSK9 are described. Methods of detecting the amount of PCSK9 in a sample using an antigen binding protein to PCSK9 are described.
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