DETAILED ACTION
Status of Application, Amendments and/or Claims
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 18-35 are pending.
Election/Restrictions
The elections of (1) non-response to statin and PCSK9 inhibitor as the species of patient non-response, and (2) familial hypercholesterolemia as the species of co-morbidity in reply filed 3/11/26 are acknowledged. In view of the prior art identified below the species of non-response to statin, ezetimibe and PCSK9 inhibitor is rejoined and also examined. Claims 19, 22, 24, and 28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Claims 18, 20-21, 23, 25-27 and 29-35 are under consideration, as they read upon the elected species.
Specification
The disclosure is objected to because of the following informalities:
The title of the invention is not descriptive because (1) it is directed to a compound whereas the pending claims are directed to a method of treatment; and (2) it is generic to any treatment of atherosclerotic cardiovascular disease, whereas the claims are limited to treatment by administering a gp130-Fc dimer. A new title is required that is clearly indicative of the invention to which the claims are directed. The following title is suggested: “Method for Treating Atherosclerotic Cardiovascular Disease with a gp130-Fc Dimer”.
Appropriate correction is required.
Claim Objections
Claim 20 is objected to because of the following informalities:
In claim 20, the recitation of:
“wherein the monomers comprise the gp130 D6 domain comprising the amino acids at positions 585-595 of SEQ ID NO: 1, an Fc domain hinge region comprising the amino acids at positions 609-612 of SEQ ID NO: 1, and the monomers do not comprise a linker between the gp130 part and the Fc part”
Should read (underlining adding for emphasis:
“wherein the monomers comprise the gp130 D6 domain comprising the amino acids at positions 585-595 of SEQ ID NO: 1, and an Fc domain hinge region comprising the amino acids at positions 609-612 of SEQ ID NO: 1; and wherein the monomers do not comprise a linker between the gp130 part and the Fc part.
Appropriate correction is required.
Note on Prior Art Rejection(s)
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were effectively filed absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned at the time a later invention was effectively filed in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 18, 20-21, 23, 25-27 and 29-35 are rejected under 35 U.S.C. 103(a) as being unpatentable over Cottingham et al, U.S. Patent Application Publication 20170320932, published 11/9/17 (cited on the 6/21/23 IDS), and further in view of Santos et al (2016. Lancet Diabetes-Endocrinol. 4: 850-861). The earliest date to which the instant application claims priority is 6/10/20.
Claim 18 encompasses a method for treating atherosclerotic cardiovascular disease (AVSCD) in a human patient, comprising administering to a patient in need thereof a therapeutically effective amount of a polypeptide dimer comprising two gp130-Fc monomers, each monomer having at least 90% sequence identity to SEQ ID NO: 1, wherein said patient is a non-responder to a statin, ezetimibe and a PCSK9 inhibitor. The term “non-responders” is defined in the specification as “human patients who show a partial or complete lack of the expected response to an appropriate therapy at an appropriate dose according to current guidelines, whether alone or in combination with other therapies” (¶ 20). This embodiment also reads on dependent claims 21, 23 and 25.
Cottingham teaches:
“A method for the treatment of an inflammatory disease or an IL-6-mediated
condition in a human comprising administering to a human in need thereof 0.5 mg to 5 g of a polypeptide dimer, wherein the polypeptide dimer comprises two monomers, each monomer having at least 90% sequence identity to SEQ ID NO: 1, wherein the monomers comprise the gp130 D6 domain corresponding to the amino acids at positions 585-595 of SEQ ID NO:1, an Fc domain hinge region comprising the amino acids at positions 609-612 of SEQ ID NO:1, and the monomers do not comprise a linker between the gp130 D6 domain and the Fc domain hinge region” (independent claim 24).
SEQ ID NO: 1 as taught by Cottingham is described as “gp130-Fc fusion monomer” (see Sequence Listing), and is a 822 amino acid sequence that is 100% identical to instant SEQ ID NO: 1. Cottingham further teaches that the inflammatory disease is atherosclerosis; see dependent claim 41. Atherosclerosis is encompassed by AVSCD as recited in claim 1. As such, Cottingham teaches a method for treating AVSCD in a human patient comprising administering a therapeutically effective amount of a polypeptide dimer comprising two gp130-Fc monomers, each monomer having at least 90% sequence identity to SEQ ID NO: 1. Cottingham does not further teach that the subject is a non-responder to a statin, ezetimibe and a PCSK9 inhibitor.
Santos teaches that “[f]amilial hypercholesterolaemia is an autosomal co-dominant disorder characterised by raised concentrations of LDL cholesterol in blood and an average 3–13 times greater risk of premature atherosclerotic cardiovascular disease, compared with individuals with normal blood concentrations of LDL cholesterol” (page 850). Santos teaches “Most guidelines endorse a minimum reduction in LDL cholesterol of 50% for patients with familial hypercholesterolaemia … Specific absolute targets are sometimes recommended—eg, LDL cholesterol concentrations less than 2·5 mmol/L (100 mg/dL), or 1·8 mmol/L (70 mg/dL) in individuals presenting with clinical atherosclerotic cardiovascular disease” (page 852). Santos teaches that if a patient has “presence of clinical atherosclerotic disease”, a “realistic goal is to reduce LDL cholesterol by ≥50%; the ideal goal is to achieve LDL cholesterol <1.8 mmol/L (70 mg/dL)” (page 855). Santos further teaches a “[t]reatment algorithm for severe familial hypercholesterolaemia” that includes consideration of “four-drug therapy” when “LDL cholesterol is still not at ideal goal” after trying the “triple-drug therapy” of high-intensity statin at maximum tolerated dose plus ezetimibe and a PCSK9 inhibitor; Figure 2 on page 856. LDL not reaching the ideal goal indicates a partial response, which is encompassed by the term “non-responder” as defined by the instant specification.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to take the method of treatment of atherosclerosis by administering to a patient in need thereof a gp130-Fc monomer as taught by Cottingham and to modify said method to apply it to such a patient that has atherosclerosis and is also a non-responder to a statin, ezetimibe, and a PCSK9 inhibitor as taught by Santos. The person of ordinary skill in the art would have been motivated to make such a change in order to lower the LDL of the provide a fourth therapy to a patient with familial hypercholesterolaemia (FH) that has not achieved an LDL cholesterol at a target goal as taught by Santos. The person of ordinary skill in the art would have had a reasonable expectation of success because Santos teaches other fourth therapies that can be combined with the triple-drug therapy. This rationale supports a prima facie conclusion of obviousness in accord with KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (2007). The modified method obvious over the teachings of Cottingham in view of Santos meets the limitations of claims 18, 21, 23 and 25.
Claim 20 encompasses a method of claim 18 wherein the monomers comprise wherein the monomers comprise the gp130 D6 domain comprising the amino acids at positions 585-595 of SEQ ID NO: 1, an Fc domain hinge region comprising the amino acids at positions 609-612 of SEQ ID NO: 1, and the monomers do not comprise a linker between the gp130 part and the Fc part. These further limitations are also present in the teachings of Cottingham set forth above; see claim 24 of Cottingham.
Claims 26 and 27 encompass a method of claim 18 wherein the human patient is classified as a non-responder based upon detection of a biomarker for non-response (claim 26) that is plasma levels of LDL cholesterol (claim 27). In the teachings of Santos described above, the patient is considered not responsive to the three-drug therapy based on LDL levels. As such, the modified method obvious over the teachings of Cottingham in view of Santos also meets the limitations of claims 26 and 27.
In claim 29, the further wherein clause has been fully considered in context of the entire claim, but does not render the claimed method patentably distinct from a method taught by the prior art because it simply expresses the intended result of a process step positively recited. See MPEP 2111.04, which states that a "whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited" (Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), quoting Minton v. Nat ’l Ass ’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)). Specifically, in claim29, the wherein clause simply express the intended result (reduction of plaque size, intima media thickness and arterial wall inflammation) of a process step positively recited (administering a gp130-Fc dimer). As such, the method obvious over the teachings of Cottingham in view of Santos also meets the limitations of claim 29.
Claim 30 encompasses a method of claim 18 wherein the ASCVD is inflammatory ASCVD. In the teachings of Cottingham set forth above, the atherosclerosis is a form of inflammatory disease. As such, the method obvious over the teachings of Cottingham in view of Santos also meets the limitations of claim 30.
Claim 31 encompasses a method of claim 18 wherein the patient is suffering from familial hypercholesterolemia (FH). In the teachings of Santos set forth above, the patient has FH. As such, the method obvious over the teachings of Cottingham in view of Santos also meets the limitations of claim 30.
Claims 32 and 33 encompass a method of claim 18 further comprising administering 60 mg to 1 g of the dimer (claim 32) or 150 mg to 600 mg of the dimer. Cottingham further teaches doses in the range of “60 mg to 1 g” (¶ 31), as well as doses of 600 mg (e.g., ¶ 33, 37, 38).
Claims 34 and 35 encompass a method of claim 18 wherein the dimer is administered once every 1 to 4 weeks (claim 34) or further where this is once every 1 to 2 weeks (claim 35). Cottingham further teaches that the dose can be “biweekly (i.e., every other week)” (¶ 6), which is encompassed by once every 2 weeks.
Double Patenting
The nonstatutory double (NSDP) patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A NSDP rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer (TD) in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on NSDP provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A TD must be signed in compliance with 37 CFR 1.321(b).
The filing of a TD by itself is not a complete reply to a NSDP rejection. A complete reply requires that the TD be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains TD forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer (eTD) may be filled out completely online using web-screens. An eTD that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTDs, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 18, 20-21, 23, 25-27 and 29-35 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 and 13-17 of U.S. Patent No. 11,198,721, issued 12/14/21 (cited on the 6/21/23 IDS), and which shares the same applicant with the instant application, and further in view of Santos et al (2016. Lancet Diabetes-Endocrinol. 4: 850-861). Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons.
The ’721 patent issued from application 15/532,092, which was also published as Cottingham et al, U.S. Patent Application Publication 20170320932 (cited above).
The scope of the claims is as set forth above in the section, “Claim Rejections 35 U.S.C. 103(a)”.
Claim 1 of the ‘721 patent is directed to:
A method for the treatment of an inflammatory disease or an IL-6- mediated condition in a human, said method comprising administering to a human in need thereof an effective amount of a polypeptide dimer that inhibits IL-6 trans-signaling, wherein the polypeptide dimer comprises two monomers, each monomer comprises an amino acid sequence having at least 95% sequence identity to SEQ ID NO: 1, and comprises the gp130 D6 domain corresponding to the amino acids at positions 585-595 of SEQ ID NO: 1, and an Fc domain hinge region comprising the amino acids at positions 609-612 of SEQ ID NO: 1, and each monomer does not comprise a linker between the gp130 D6 domain and the Fc domain hinge region; wherein the effective amount is 60 mg to 750 mg of the polypeptide dimer; and wherein the polypeptide dimer is administered every 7-60 days.
Dependent claim 14 further limits the inflammatory disease to atherosclerosis.
As such, the claims of ‘721 meet all of the limitations of instant claim 1, except that the claims of ‘721 do not include that the subject is a non-responder to a statin and a PCSK9 inhibitor.
The teachings of Santos are set forth above in the section, “Claim Rejections 35 U.S.C. 103(a)”.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to take the method of treatment of atherosclerosis by administering to a patient in need thereof a gp130-Fc monomer as claimed by ‘721 and to modify said method to apply it to such a patient that is also a non-responder to a statin, ezetimibe, and a PCSK9 inhibitor as taught by Santos, for the same reasons as set forth above in the section, “Claim Rejections 35 U.S.C. 103(a)”.
The modified method obvious over the claims of ‘721 in view of the teachings of Santos meets the limitations of claims 18, 21, 23 and 25. As such, the two sets of claims are not patentably distinct.
The further limitations of claim 20 are also present in claim 1 of ‘721; as such claim 20 is not patentably distinct from the claims of ‘721 in view of Santos for the same reasons as parent claim 18.
Claims 26 and 27 encompass a method of claim 18 wherein the human patient is classified as a non-responder based upon detection of a biomarker for non-response (claim 26) that is plasma levels of LDL cholesterol (claim 27). In the teachings of Santos described above, the patient is considered not responsive to the three-drug therapy based on LDL levels. As such, the modified method obvious over the teachings of the claims of ‘721 in view of Santos also meets the limitations of claims 26 and 27.
As set forth above the further wherein clause of claim 29 does not render the claimed method patentably distinct from a method taught by the prior art because it simply expresses the intended result of a process step positively recited. As such, the method obvious over the claims of the claims of ‘721 in view of Santos also meets the limitations of claim 29.
Claim 30 encompasses a method of claim 18 wherein the ASCVD is inflammatory ASCVD. In the claims of ‘721, the atherosclerosis is a form of inflammatory disease. As such, the method obvious over the teachings of the claims of ‘721 in view of Santos also meets the limitations of claim 30.
Claim 31 encompasses a method of claim 18 wherein the patient is suffering from familial hypercholesterolemia (FH). In the teachings of Santos set forth above, the patient has FH. As such, the method obvious over the claims of ‘721 in view of Santos also meets the limitations of claim 30.
Claims 32 and 33 encompass a method of claim 18 further comprising administering 60 mg to 1 g of the dimer (claim 32) or 150 mg to 600 mg of the dimer. This further limitation corresponds to that of dependent claim 3 of ‘721, which includes a dosage of 600 mg. As such, claims 32 and 33 are also not patentably distinct from the claims of ‘721 in view of the teachings of Santos.
Claims 34 and 35 encompass a method of claim 18 wherein the dimer is administered once every 1 to 4 weeks (claim 34) or further where this is once every 1 to 2 weeks (claim 35). This further limitation corresponds to that of dependent claim 8 of ‘721, which includes administration every 14 days (i.e., 2 weeks). As such, claims 34 and 35 are also not patentably distinct from the claims of ‘721 in view of the teachings of Santos.
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZACHARY Cottingham HOWARD whose telephone number is (571)272-2877. The examiner can normally be reached on Monday to Friday from 9 AM to 5 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford, can be reached at telephone number (571) 272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ZACHARY C HOWARD/Primary Examiner, Art Unit 1674
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