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 .
DETAILED ACTION
This Office action is responsive to Applicant's preliminary amendment, filed 4/11/2024. As filed, Claims 62-81 are pending. Claims 1-61 are cancelled.
Information Disclosure Statement
Applicants' information disclosure statements (IDS) filed have been considered except where lined through. Please refer to Applicants' copy of the 1449 submitted herewith.
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 62-81 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.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail such that the Artisan can reasonably conclude that the inventor(s) had possession of the claimed invention. Such possession may be demonstrated by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and/or formulae that fully set forth the claimed invention. Possession may be shown by an actual reduction to practice, showing that the invention was “ready for patenting”, or by describing distinguishing identifying characteristics sufficient to show that Applicant was in possession of the claimed invention (January 5, 2001 Fed. Reg., Vol. 66, No. 4, pp. 1099-11).
In Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc) (“Ariad”), the Federal Circuit stated that “the hallmark of written description is disclosure.” A specification adequately describes an invention when it “reasonably conveys to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date.” Id. at 1351. “A ‘mere wish or plan’ for obtaining the claimed invention is not adequate written description.” Centocor Ortho Biotech, Inc. v. Abbott Labs, 636 F.3d 1341, 1348 (Fed. Cir. 2011).
What is required to meet the written description requirement “varies with the nature and scope of the invention at issue, and with the scientific and technologic knowledge already in existence.” Capon v. Eshhar, 418 F.3d 1349, 1357 (Fed. Cir. 2005). The Federal Circuit explained what is required to meet the written description requirement in Ariad Pharm., Inc. v. Eli Lilly & Co.:
This inquiry, as we have long held, is a question of fact. Ralston Purina, 772 F.2d at 575. Thus, we have recognized that determining whether a patent complies with the written description requirement will necessarily vary depending on the context. Capon v. Eshhar, 418 F.3d 1349, 1357-58 (Fed. Cir. 2005). Specifically, the level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology. Id. For generic claims, we have set forth a number of factors for evaluating the adequacy of the disclosure, including “the existing knowledge in the particular field, the extent and content of the prior art, the maturity of the science or technology, [and] the predictability of the aspect at issue.” Id. at 1359.
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Nature and scope of the instant claims in view of the specification: Instant claims are drawn to a method of preventing myocardial infarction in a human by administering a therapeutically effective amount of a pharmaceutical material comprising the compound of formula (V) (bempedoic acid ) in amount greater than 85% or 98% by weight and the pharmaceutical material comprises a compound of formula (VI) in amount 0.001 % to 0.15%; claims 69, 74, 81 further recite a second therapeutic agent in composition which is ezetimibe.
By contrast, the nature and scope of the invention described in the Specification includes a process for preparing a pharmaceutical material comprising a purified
amount of the Compound of Formula (V) and the amount
of the dial impurity of formula (VI) in the pharmaceutical material. While discussion example sod diseases treatable by bempedoic acid on [0405], there is no method of preventing or treatment myocardial infarction by the claimed compositions shown anywhere in the Specification.
The extent and content of the prior art: Applicant has provided several patent application documents (see IDS referenced). For example, WO 2018/218147 which teaches a method for treating or reducing the risk of cardiovascular disease in a subject in need thereof, the method comprising administering: ETC-1002 (bempedoic acid); ezetimibe; and one or more pharmaceutical excipients or carriers to the subject
The predictability of the aspect at issue: the pharmaceutical art is generally recognized as unpredictable. In re Fisher, 427 F.2d 833, 839 (CCPA 1970) (“In cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved (emphasis added.”).
Conclusion: Claims 62-81 are rejected because the disclosure does not provide support for the claimed method of preventing myocardial infarction in a human by administering a pharmaceutical material comprising the compound of formula (V) in amount greater than 85% or 98% by weight and the diol impurity compound of formula (VI) in amount 0.001 % to 0.15% and optionally with ezetimibe. A person having ordinary skill in the art, in view of the Specification, would conclude that Applicant was in possession of the method as claimed.
As stated in MPEP 2163 II: If the application as filed does not disclose the method of the claimed invention as a whole, determine whether the specification discloses other relevant identifying characteristics sufficient to describe the claimed invention in such full, clear, concise, and exact terms that a skilled artisan would recognize applicant was in possession of the claimed invention. The instant specification is devoid of a description for the method of preventing myocardial infarction in a human by administering a therapeutically effective amount of a pharmaceutical
material comprising the compound of formula (V) in amount greater than 85% or 98% by weight and the pharmaceutical material comprises a compound of formula (VI) in amount 0.001 % to 0.15% and ezetimibe. Consequently, it is concluded that the written description requirement is not satisfied.
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 62-81 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2018/218147 (cited by Applicants in IDS).
Instant claims are drawn to a method of preventing myocardial infarction in a human by administering a therapeutically effective amount of a pharmaceutical material comprising the compound of formula (V) (bempedoic acid ) in amount greater than 85% or 98% by weight and the pharmaceutical material comprises a compound of formula (VI) in amount 0.001 % to 0.15%; claims 69, 74, 81 further recite a second therapeutic agent in composition which is ezetimibe.
The ‘197 publication teaches a pharmaceutical composition and a therapeutic combination comprising a novel cholesteryl ester transfer protein (CETP) inhibitor and an adenosine triphosphate citrate lyase (ACL) inhibitor/ adenosine monophosphate-activated protein kinase (AMPK) activator, which may be used in the treatment of subjects suffering from or having an increased risk for cardiovascular diseases such as myocardial infarction (page 8 lines 1-5).
The ‘197 publication teaches that an intensively studied representative investigational ACL inhibitor / AMPK activator drug compound is the small molecule ETC-1002,or bempedoic acid
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– which corresponds to claimed formula V; ETC-1002 is under development in the clinic for the treatment of dyslipidemia and coronary artery disease, and other cardiometabolic risk factors. The pharmaceutical composition according to the present invention comprises besides Compound A and the at least one ACL inhibitor / AMPK activators also a pharmaceutically acceptable excipient, i.e. a pharmaceutically acceptable ingredient, which is commonly used in the pharmaceutical technology for preparing granulate, solid or liquid oral dosage formulations (page 13; instant claims 62-68, 70-73, 75-80).
The ‘197 publication teaches that: the pharmaceutical composition comprises about 60 to 180 mg of the at least one ACL inhibitor / AMPK activator, e.g. ETC-1002, and further comprises about 1 to 30 mg of a cholesterol absorption inhibitor, e.g. ezetimibe, preferably about 10 mg ezetimibe.” (page 13-14; instant claims 69, 74, 81).
The difference between the instant claims and the teachings of the ’197 publication is that prior art does not expressly teach the composition comprising the compound of formula VI; the prior art does not specify the crystalline form of bempedoic acid.
Regarding the presence of the compound of formula VI in the composition containing bempedoic acid of formula (V), the diol of formula (VI) is an impurity resulted in the process of producing bempedoic acid.
MPEP 2144.04:” Factors to be considered in determining whether a purified form of an old product is obvious over the prior art include whether the claimed chemical compound or composition has the same utility as closely related materials in the prior art, and whether the prior art suggests the particular form or structure of the claimed material or suitable methods of obtaining that form or structure. In re Cofer, 354 F.2d 664, 148 USPQ 268 (CCPA 1966) (Claims to the free-flowing crystalline form of a compound were held unobvious over references disclosing the viscous liquid form of the same compound because the prior art of record did not suggest the claimed compound in crystalline form or how to obtain such crystals.). However, in the case of product-by-process claims, if a first prior art process is improved to enhance the purity of the product produced by the process, and if the purified product has no structural or functional difference from the products produced by other prior art processes, then the improvement in the first process that improves the purity of the product does not give rise to patentability. See Purdue Pharma v. Epic Pharma, 811 F.3d 1345, 117 USPQ2d 1733 (Fed. Cir. 2016)”
In the instant case, the prior art by ‘197 publication specifically teach pharmaceutical composition comprising bempedoic acid, the same compound as claimed and further comprises a cholesterol absorption inhibitor, e.g. ezetimibe as pharmacotherapies in treating cardiovascular conditions including myocardial infarction. As such, one of ordinary skills in the art would expect such compounds of purity suitable for using said compounds and compositions in the treatment of myocardial infarction.
Furthermore, only in those cases where the purified product is as a result of the purification so different in properties and uses as to be in effect a new compound has such a purified product been considered patentable. The instant case does not come under this exception. Instant disclosure does not present experimental data shown the criticality of diol component, compound (VI) in the composition containing bempedoic acid, compound of formula V in the treatment and prevention of myocardial infarction.
Regarding the limitation of claims 63-66, 72, 76, 77 about crystalline compound , the compound of the prior art has the same structure and chemical formula as compound of instant claims, formula (V), bempedoic acid and is disclosed as solid, in compositions for treating/ preventing cardiovascular conditions including myocardial infarction.
Regarding the crystalline form of a compound, it is noted that a novel or unobvious chemical product is identified first by its "chemical nature, i.e. elemental content and their ratios, i.e. the chemical identity. Solid compounds exhibit polymorphism which is defined as the ability of a substance to exist as two or more crystalline phases that have different arrangements and/or conformations of the molecules in the crystal lattice. Thus, in the strictest sense polymorphs are different crystalline forms of the same pure substance in which the molecules have different arrangements and/or different conformations of the molecules.
Additionally, for a known compound with defined chemical structure to be patentable for a new form, it must have a patentability basis of an advantage in terms of stability, formulation, solubility, bioavailability, hydroscopicity, etc.
Even if the product of the instant application and the prior art differ in X-ray diffraction, differential scanning calorimetry or "crystalline" the mere difference in physical parameter such as X-ray diffraction pattern, differential scanning calorimetry does not offer any unexpected advantage of prior art product with the same chemical property and biological property i.e. a mere variation in physical property which flows naturally with the changing form.
MPEP 2112.V states that, “once a reference teaching product appearing to be substantially identical is made the basis of a rejection, and the Examiner presents evidence or reasoning tending to show inherency, the burden shifts to the Applicant to show an unobvious difference." See also Ex parte Anderson, 21 USPQ 2nd 1241 and 1251 "There is ample precedent for shifting burden to an Applicant to reproduce a prior art product whose final structure or properties are, at least, in part determined by the precise process used in its manufacture.”
In the instant case, given that the prior art teach the compound with the same structure and chemical formula as compound of instant claims, namely bempedoic acid, one of ordinary skills in the art can conclude that the compound disclosed in the prior art and the instantly claimed compound (V) in a form of crystal appear to be identical and therefore the compound of prior art would have identical inherent properties.
The office does not have the facilities and resources to provide the factual evidence needed in order to establish that the compound of the prior art does not possess the same material, structural and functional characteristics of the claimed compound. In the absence of evidence to the contrary, the burden is on the applicant to prove that the claimed compound is of crystal form those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989).
The prior art is silent as to some characteristics such as crystal form of compound but the absence of such data does not necessarily mean that the prior art compound were of different physical form and characteristics and potency in the method of treatment and prevention of cardiovascular conditions including myocardial infarction
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention because, as suggested by the ‘917 publication regarding methods of treating/ preventing myocardial infarction by composition comprising bempedoic acid.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
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.
1.Claim 62-68, 70-73, 75-80 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No 11613511.
Although the claims at issue are not identical, they are not patentably distinct from each other because there is significant overlap between the two applications.
The instant claims are drawn to a method of preventing myocardial infarction in a human by administering a therapeutically effective amount of a pharmaceutical material comprising the compound of formula (V) and the pharmaceutical material comprises a compound of formula (VI). The ‘511 is drawn to a pharmaceutical material comprising the compound of formula (V) and the pharmaceutical material comprises a compound of formula (VI) as claimed in the instant application and teach that such compositions can be used in treating cardiovascular conditions such as myocardial infarction. Thus, since the ‘511 patent suggests the method of treatment using this said compositions, it would have been obvious for one of ordinary skill to claim so.
2 Claim 62-68, 70-73, 75-80 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No 11760714.The instant claims are drawn to a method of preventing myocardial infarction in a human by administering a therapeutically effective amount of a pharmaceutical material comprising the compound of formula (V) and the pharmaceutical material comprises a compound of formula (VI). The ‘714 patent is drawn to a pharmaceutical material comprising the compound of formula (V) and the pharmaceutical material comprises a compound of formula (VI) as claimed in the instant application and teach that such compositions can be used in treating cardiovascular conditions such as myocardial infarction. Thus, since the ‘714 patent suggests the method of treatment using this said compositions, it would have been obvious for one of ordinary skill to claim so.
3. Claim 62-68, 70-73, 75-80 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No 12398087.
The instant claims are drawn to a method of preventing myocardial infarction in a human by administering a therapeutically effective amount of a pharmaceutical material comprising the compound of formula (V) and the pharmaceutical material comprises a compound of formula (VI). The ‘087 patent is drawn to a pharmaceutical material comprising the compound of formula (V) and the pharmaceutical material comprises a compound of formula (VI) as claimed in the instant application and teach that such compositions can be used in treating cardiovascular conditions such as myocardial infarction. Thus, since the ‘087 patent suggests the method of treatment using this said compositions, it would have been obvious for one of ordinary skill to claim so.
Conclusion
Claims 62-81 are rejected.
Telephone Inquiry
Any inquiry concerning this communication or earlier communications from the
examiner should be directed to
Ana Muresan
(571) 270-7587 (phone)
(571)270-8587 (fax)
Ana.Muresan@uspto.gov
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/ANA Z MURESAN/Primary Examiner, Art Unit 1692