DETAILED ACTION
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 .
Election/Restrictions
Applicant's election with traverse of group II, claims 13-15, in the reply filed on 01/1 is acknowledged. The traversal is on the ground(s) that the inventions identified, and that examining the claims together would not impose an undue burden. This is not found persuasive because the inventions have.
The requirement is still deemed proper and is therefore made FINAL.
Applicant has elected the compound having the structure depicted below, which the Examiner herein denotes as Compound A for shorthand. This is found as Example I in the specification (see bottom of p. 50). For the disease to be treated with Compound A, Applicant has elected a cardiovascular disease or disorder.
PNG
media_image1.png
182
343
media_image1.png
Greyscale
Above: Compound A
Status of the Claims
Claims 13-17 are under examination. In the reply filed on 01/14/2026, claims 1-12 were canceled, claims 13-15 were amended, and claims 16-17 were added.
Priority
This application claims priority to Chinese patent application No. PCT/CN2023/097282, filed 05/30/2023, and to U.S. Provisional Application No. 63/370,300, filed 08/03/2023.
Information Disclosure Statement
The information disclosure statement filed 03/08/2024 fails to comply with 37 CFR 1.98(a)(3)(i) because it does not include a concise explanation of the relevance, as it is presently understood by the individual designated in 37 CFR 1.56(c) most knowledgeable about the content of the information, of each reference listed that is not in the English language. It has been placed in the application file, but the information referred to therein has not been considered. The reference Nasonov et al., “The role of interleukin 1 in the development of human diseases” does not have a copy provided in English.
Claim Objections
Claim 13 is objected to because the limitation “in which the NLRP3 signaling contributes to the pathology, and/or symptoms, and/or progression, of said disease or disorder” has an extra comma between “progression” and “of said disease or disorder”. The phrase “and/or” before “symptoms” is also unnecessary. The limitation should read: “in which the NLRP3 signaling contributes to the pathology, progression of said disease or disorder”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
112(b)
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 16 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.
Regarding claim 16, the instances of the phrase “including” render the claim indefinite because it is unclear whether the diseases or disorders following each instance of the phrase “including” are part of the claimed group of diseases or merely a representative example. Furthermore, it is not clear what items are meant to be grouped in each “including” clause. For example, regarding the limitation “heart failure including congestive heart failure and heart failure with preserved ejection fraction, embolism, aneurysms including abdominal aortic aneurysm…”, it is not clear whether embolism and aneurysms are construed to be examples of heart failure or as groups of diseases separate from heart failure. In the interest of compact prosecution, these will be considered as separate embodiments for the purposes of applying prior art.
112(a)
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 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of inhibiting in vitro comprising administering Compound A, does not reasonably provide enablement for inhibiting NLRP3 inflammasome in a subject by administering Compound A, nor for treating any disease or any cardiovascular disease or disorder in which NLRP3 activity is implicated. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. This is a scope of enablement rejection.
To be enabling, the specification of the patent application must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fd. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996). As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is "undue", not "experimentation".
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors:
1- the quantity of experimentation necessary,
2- the amount of direction or guidance provided,
3- the presence or absence of working examples,
4- the nature of the invention,
5- the state of the prior art,
6- the relative skill of those in the art,
7- the predictability of the art, and
8- the breadth of the claims
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
1. The nature of the invention, state and predictability of the art, and relative skill of those in the art
The invention relates to a method of treating a cardiovascular disease or disorder in which NLRP3 inflammasome activity is implicated, comprising administering a therapeutically effective amount of Compound A or a pharmaceutically acceptable salt thereof.
The relative skill of those in the art is high, generally that of an M.D. or Ph.D. The artisan using Applicant’s invention would generally be a physician with a M.D. degree and several years of experience.
The high level of skill is outweighed, however, by the unpredictable nature of the art. It is well established that “the scope of enablement varies with the degree of unpredictability of the factors involved” and physiological activity is considered to be an unpredictable factor. See In re Fisher, 166 USPQ 18, at 24 (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); Nationwide Chemical Corporation, et. al. v. Wright, et. al., 192 USPQ 95 (one skilled in chemical and biological arts cannot always reasonably predict how different chemical compounds and elements might behave under varying circumstances); Ex parte Sudilovsky 21 USPQ2d 1702 (Applicant’s invention concerns pharmaceutical activity. Because there is no evidence of record of analogous activity for similar compounds, the art is relatively unpredictable); In re Wright 27 USPQ2d 1510 (the physiological activity of RNA viruses was sufficiently unpredictable that success in developing specific avian vaccine was uncertain).
As illustrative of the state of the art of treating cardiovascular disease, the Examiner cites Ohlstein (“The Grand Challenges in Cardiovascular Drug Discovery and Development”) and Hong (“The grand challenge of discovering new cardiovascular drugs”). As Ohlstein notes, “Sometimes an obvious therapeutic target with excellent preclinical data does not translate into a safe and effective medicine. The recent example of the failure of the CETP inhibitor Torcetrapib illustrates this problem. It was widely accepted that increasing HDL produces a beneficial therapeutic effect and decrease atherosclerosis. People were stunned when Torcetrapib failed to translate the biochemistry and pharmacology into a clinical benefit. Although the hypothesis that inhibition of CETP to increase HDL is still viable and compounds are still being developed, it cast doubt on the sole reliance of established biomarkers for the efficacy of potential new drugs” (pg. 1). Even when mechanisms of action are known in vivo, these results often do not translate to clinical efficacy, let alone when only in vitro results are known.
As of 2022, beyond the effective filing date of the instant application, the state of the art has not improved. As Hong notes, “the cost of developing new molecular entities (NMEs) into approved therapies is extremely high, with costs often ranging over $3 billion per launched NME. A major reason for this is that only 5–10% of candidate NMEs are eventually approved. For those in the cardiovascular drug development field, which often relies on large, expensive clinical trials to demonstrate efficacy, the stakes could not be higher” (pg. 02).
As the articles by Ohlstein and Hong demonstrate, the state of the art for the development of drugs for cardiovascular diseases is unpredictable and underdeveloped.
2. The breadth of the claims
Claims 13-17 are very broad in that they claim administering Compound A to
treat in a subject any disease in which NLRP3 inflammasome activity is implicated, including the treatment of any cardiovascular disease or disorder. These diseases include those with opposing mechanisms and pathologies, such as hypotension and hypertension or tachycardia and bradycardia. In addition, claims 16-17 claim the administration of Compound A for cardiovascular risk reduction, further broadening the scope to include prevention of disease.
3. The amount of direction or guidance provided and the presence or absence of working examples
The specification provides data for Compound A to inhibit NLRP3 activity in vitro by demonstrating the decreased production of IL-1β and TNF-α in vitro (pp. 67-68, noting that Example 1 is Compound A). However, in vitro assays are insufficient to support enablement for inhibiting NLRP3 activity in a subject, nor for treating in a subject the full scope of diseases or disorders implicated by NLRP3 activity, including cardiovascular diseases in particular.
4. The quantity of experimentation necessary
Because of the known unpredictability of the art (as discussed supra) and in the absence of experimental evidence commensurate in scope with the claims, the skilled artisan would not accept that Compound A could be predictably used to treat all diseases encompassed by diseases or disorders in which NLRP3 activity is implicated or all cardiovascular diseases in which NLRP3 activity is implicated, nor to reliably inhibit NLRP3 activity in a subject. Genentech Inc. vs. Nova Nordisk states, "[A] patent is not a hunting license. It is not a reward for a search but a compensation for its successful conclusion and 'patent protection' is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable" (42 USPQ 2d 1001, Fed. Circuit 1997).
As noted above, the specification provides no experimental support for the treatment of any disease or disorder in which NLRP3 activity is implicated. A review of the state of the art fails to reveal that Compound A is useful for the treatment of any cardiovascular disease within the scope of the instant claims, nor that it can inhibit NLRP3 activity in a subject. Determining if the claimed compound would treat any particular cardiovascular disease state or would inhibit NLRP3 activity in vivo would require synthesis of the compound, formulation into a suitable dosage form, and subjecting it to clinical trials or to testing in an assay known to correlate to clinical efficacy of such treatment. This is undue experimentation given the limited guidance and direction provided by Applicant. As noted supra, even in vitro and in vivo assays do not always correlate to efficacy in humans and are not generally predictive of clinical efficacy.
Accordingly, claims 13-17 do not comply with the enablement requirement of 35 U.S.C. 112(a), since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OLIVER D. HEES whose telephone number is (571)272-9840. The examiner can normally be reached Monday - Friday 8:00 am - 5:00 pm.
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, AMY L. CLARK can be reached at (571) 272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/OLIVER D HEES/Examiner, Art Unit 1628
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628