Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Please note the change in Examiner to Jerica Wilson. Updated contact information can be found in the conclusion.
DETAILED ACTION
Claims 1-21, 23, and 25 are pending in the instant application.
Claims 1-21, 23, and 25 are examined herein.
Priority
The instant application claims benefit of foreign priority to PCTCN2020272748, filed on 17 January 2020 and the benefit of priority to PCT/CN2021/071745, filed on 14 January 2021. The claims to the benefit of priority are acknowledged. As such, the effective filing date of the claims is 17 January 2020.
Information Disclosure Statement
The information disclosure statements (IDS), submitted on 30 September 2022, 12 MARCH 2024, 01 December 2025, are acknowledged and considered. The submissions are in compliance with the provisions of 37 CFR 1.97.
Response to Election/Restrictions
Applicant’s election of Group I, with traverse, in the reply filed on 17 March 2025 is acknowledged. The traversal is on the grounds that Groups I and II share a single inventive concept with a special technical feature. The Examiner agrees with the Applicant and the requirement for restriction is withdrawn. Pending claims 1-21, 23, and 25, of Groups I and II, will be examined as a whole.
As such election of a species is not required and all species of Formula (I) are examined herein.
Claim Interpretation
Claims 23 and 25 are drawn to a method of preventing a PCSK-9 mediated disease. PCSK9 inhibitors can reduce LDL cholesterol levels which can lead to cardiovascular disease. Prevention of cardiovascular disease is known in the art (Grzesk et al. Biomedicine & Pharmacotherapy.2022;156:113957) and therefore the specification is enabled.
Improper Markush
Claims 1-12, 14-16, 18, 21, 23, and 25, are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of Y, B, and A are improper because the alternatives defined by the Markush grouping do not share both a single structural similarity, as there is no common core, and a common use, as the specification fails to use a combination of these variables for the use as PCSK9 inhibitors.
The possible substitution patterns set forth in claim 1 create a genus of compounds that spans classifications. Without a representative number of structures, expressing the range of variability, disclosed in the specification or shown in the prior art, the instant application does not show all the possible structure subtypes to be functionally equivalent and have a common use. The specification sets forth 86 embodiments. Of these Y is O in all embodiments; B is either an indole, benzofuran, furan, oxazole, or pyrrole; and A is either phenyl, indene, or cyclopentane. Y is defined in the claims as O, S, NH, or CH2, exclusion of three of the four possible substitution patterns set forth is not an adequate representation of the Markush grouping. B is defined as C3-7 cycloalkyl, 3- to 7-membered heterocyclyl, C6-10 aryl, or 5- to 10-membered heteroaryl and A is defined as C3-7 cycloalkyl, 3- to 7-membered heterocyclyl, C6-10 aryl; with the possible substitution patterns in heterocyclic structures both A and B span a large group of diverse structures and the representation in the specification is not an adequate depiction of the structural diversity. With an inadequate representation of the possible structural variety one skilled in the art is unable to deem the claimed substitution patterns as functionally equivalent.
Claim 13, depicts a proper Markush grouping most closely resembling the species of the instant genus. Incorporation of the B moiety from Formula (II-1) into the Formulas of claim 13 would result in a Formula representative of all the instant species, as the current Formulas of claim 13 do add the flouro substituent limitation which is not seen in all embodiments.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-21, 23, and 25 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 recites a compound of Formula (I), or a pharmaceutically acceptable salt, an enantiomer, a diastereomer, a racemate, a solvate, a hydrate, a polymorph, a prodrug, or an isotope variant thereof. The applicant provides no examples of a polymorph or prodrug.
Regarding a polymorph, Harris (Journal of Pharmacy and Pharmacology. 2007; 59: 225-239) emphasizes the importance of distinguishing and documenting all polymorphs of a possible pharmaceutical compound. The Applicant has not documented any polymorphs in the specification. No documentation of a polymorphic structure also means function for the polymorphic structure(s) is unknown, as it/they may not be equivalent. The lack of an example provided in the instant application suggests the applicant is not in possession of any polymorphs of a compound of Formula I.
Regarding prodrugs, one of ordinary skill in the art would not be able to determined the scope of a functional prodrug of a compound of Formula (I). The specification defines a prodrug’s function, but does not depict a structure nor relate a prodrug’s function to its structure. Formulation of a prodrug would require the applicant to possess the knowledge of which structural moieties would lead to a functional drug, and which would not. Strickley et al. (Formulation Challenges of Prodrugs. Prodrugs. 2007. Chapter 4.1.2. 383-410) discuss several formulation challenges presented with prodrugs, namely; chemical stability, reactive by-products, solubility, and polymorphism. Experimentation is required to make a successful prodrug. The specification does not provide any structure-function correlation to support the bounds of a functional prodrug of Formula I; nor are any examples presented in the instant specification, which suggests the applicant is not in possession of a prodrug of a compound of Formula I.
In conclusion, there is no structure-function correlation between what is and what is not a functional polymorph nor a functional prodrug in the specification. Based on the work of Harris and Strickley, polymorphs and prodrugs are unpredictable, without the correlation between structure and function or an adequate representation of species functioning as a polymorph or prodrug, the instant invention fails to comply with the written description requirement.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 10 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 10 recites the broad recitation of possible ring structures for the B substituent and the claim also recites “preferably, wherein Ring B is…” and recites a narrower range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Double Patenting
The nonstatutory double 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 nonstatutory double patenting 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 in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting 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 terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer 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 terminal disclaimer 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 may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-5, 7-8, 10-11, 23, and 25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-3, 5-8, 10-11, 22, and 25 of co-pending Application No. 18/577,388 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 1, the reference application recites a compound of Formula (I) (pictured below) which overlaps with the instant Formula(I) when R is -C(Rx)(Ry)(Rz), wherein Rz is H and Rx and Ry form a C3-4 cycloalkyl or 3- to 7-membered heteroaryl group (claim 1).
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Regarding claim 2, the reference application recites a compound f Formula(I) where R2 is H (claim 2).
Regarding claim 3, the reference application recites a compound of Formula(I) where R1 is a group other than H (claim 3).
Regarding claim 4, the reference application recites a compound of Formula(I) where q=1, 2, 3, 4, or 5 and at leat one of Rs4 is selected from halogen or C1-6 haloalkyl (claim 5).
Regarding claim 5, the reference application recites a compound of Formula (I) where m=0, 1, 2, or 3, and Rs1 is selected from H, halogen, -CN, -NO2, -ORa, -SRa, -NRbRc, -C(O)Ra, -C(O)ORa, -C(O)NRbRc, C1-6 alkyl, or C1-6 haloalkyl (claim 6).
Regarding claim 7, the reference application recites a compound of Formula (I) where Y is O (claim 7).
Regarding claim 8, the reference application recites a compound of Formula (I) where L2 is -C(O)- (claim 8).
Regarding claim 10, the reference application recites a compound of Formula (I) where Ring B is selected from one of the following (claim 10):
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Regarding claim 11, the reference application recites a compound of Formula (I) where the compound belongs to one of the following formulae which overlaps with the instant genus when R is -C(Rx)(Ry)(Rz), wherein Rz is H and Rx and Ry form a C3-4 cycloalkyl or 3- to 7-membered heteroaryl group (claim 11).
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Regarding claim 21, the reference application recites a composition comprising a compound of (claim 20).
Regarding claim 23, the reference application recites a method of treating and/or preventing a PCSK9-mediated disease comprising administering a compound of Formula (I)(claim 22).
Regarding claim 25, the reference application recites a method of wherein the disease is atherosclerosis, dyslipidemia, hypertriglyceridemia, hypertension, heart failure, cardiac arrhythmias, low HDL levels, high LDL levels, sudden death, stable angina, coronary heart disease, acute myocardial infarction, secondary prevention of myocardial infarction, cardiomyopathy, endocarditis, type 2 diabetes, insulin resistance, impaired glucose tolerance, hypercholesterolemia (including heterozygous and homozygous familial hypercholesterolemia), stroke, hyperlipidemia, hyperlipoproteinemia, chronic kidney disease, intermittent claudication, hyperphosphatemia, carotid atherosclerosis, peripheral arterial disease, diabetic nephropathy, hypercholesterolemia in HIV infection, acute coronary syndrome (ACS), non-alcoholic fatty liver disease, arterial occlusive diseases, cerebral arteriosclerosis, cerebrovascular disorders, myocardial ischemia, nonalcoholic fatty liver disease (NLLD), nonalcoholic steatohepatitis (NASH), and diabetic autonomic neuropathy (claim 25).
Conclusion
Claims 1-21, 23, and 25 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jerica K Wilson whose telephone number is (703)756-4690. The examiner can normally be reached Monday-Friday 9:00-5:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton Brooks can be reached at (571)270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/J.K.W./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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