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 in reply to Applicant remarks filed 23 March 2026 for application 18/283,487 filed 22 September 2023, 371 of PCT/GB2022/050726 filed 23 March 2022, claiming foreign priority to GB2104038.1 filed 23 March 2021. Claims 10 and 12-13 are canceled. Currently, claims 1-9, 11 and 14-21 are pending.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 10 January 2024, 24 January 2024, and 21 January 2026 was filed after the mailing date of the application on 22 September 2023. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Election/Restrictions
Applicant’s election of Group I in the reply filed on 23 March 2026 is acknowledged.
Applicant’s election of 1-[[3-[3-fluoro-4-[(2-methylimidazol-1-yl)methyl]phenyl]-5-isobutyl-2-thienyl]sulfonyl]-3-(2-hydroxyethyl)urea, illustrated below, in the reply filed on 23 March 2026 is acknowledged:
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The elected species, per the Applicant’s Remarks, reads upon claims 1-9 and 11. As such, claims 14-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention or species, there being no allowable generic or linking claim. Election was made in the reply filed on 23 March 2026.
The elected species was searched and found to be free of the prior art.
The search was expanded to the full scope of the claims. The closest match are structures detailed by Wu et al. (Selective angiotensin II AT2 receptor agonists: arylbenzylimidazole structure-activity relationships, J. Med. Chem. 2006, 49, 7160-7168). Wu discloses structure 13 illustrated below (pg. 7161 – scheme 1):
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While structure 13 encompasses a large portion of the core structures, it does not read fully on claim 1, where R1 represents C1-4 alkyl, optionally substituted by one or more fluorine atoms and/or with OR7; R7 representing H or methyl optionally substituted by one or more fluorine atoms. Similar, though ones that generally do not read as well on formula (I), are also taught by Wannberg et al. (A convenient transesterification method for synthesis of AT2 receptor ligands with improved stability in human liver microsomes, Bioorg. Med. Chem. Lett. 2018, 28, 519-522; entered into the IDS on 10 January 2024).
Claims 1-9 and 11 are directed to an allowable product. Pursuant to the procedures set forth in MPEP § 821.04(B), claims 14-21, directed to the process of making or using an allowable product, previously withdrawn from consideration as a result of a restriction requirement, are hereby rejoined and fully examined for patentability under 37 CFR 1.104.
Because all claims previously withdrawn from consideration under 37 CFR 1.142 have been rejoined, the restriction requirement as set forth in the Office action mailed on 26 January 2026 is hereby withdrawn. In view of the withdrawal of the restriction requirement as to the rejoined inventions, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(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 14-20 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.
A review of the rejected claim language indicates that these claims are drawn toward “a method of treatment of an autoimmune disease, a viral respiratory tract infection and/or pneumonia as a consequence thereof, a fibrotic disease, a chronic kidney disease, pulmonary hypertension, heart failure and/or myocardial infarction” in the case of claim 14, the disease of “interstitial lung disease” in the case of claim 15, the disease of “idiopathic pulmonary fibrosis or sarcoidosis” in the case of claim 16, the disease of “rheumatoid arthritis or systemic sclerosis” in the case of claim 17, the disease of “diabetic nephropathy” in the case of claim 18, the condition of “pulmonary arterial hypertension” in the case of claim 19, or the condition “wherein the heart failure is with preserved ejection fraction” as in the case of claim 20. A description of the term “a method of treating or preventing a disease or disorder…” may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or of a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus. Regents of the University of California v. Eli Lilly & Co., 119 F3d 1559, 1569, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). In Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412), the court held that a generic statement which defines a genus of nucleic acids by only their functional activity does not provide an adequate written description of the genus. The court indicated that, while applicants are not required to disclose every species encompassed by a genus, the description of the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. At section B (1), the court states “An adequate written description of a DNA ... requires a precise definition, such as by structure, formula, chemical name, or physical properties, not a mere wish or plan for obtaining the claimed chemical invention”. Hence, an adequate written description of the components requires more than a mere statement that it is part of the invention. The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ Application/Control Number: 18/335,687 369, 372-73 (Fed. Cir. 1984).
In Applicant’s originally filed specification, angiotensin II (Ang II) is an octa-peptide that is a component of the renin angiotension system (RAS), expressed in most organs and is responsible for most pathological effects of Ang II. These include involvement in apoptosis and inhibition of cell proliferation, with Ang II receptor agonists correlated with treatment of disorders of the alimentary tract and multiple organ failure or other damaged tissues, and demonstrates reparative properties. However, the applicant only demonstrates application of the claimed structures in terms of binding to human recombinant Ang II receptor and Ang I receptors through a radiometric scintillation assay. Applicant does not demonstrate that the product is capable of the claimed method of treatment of the various diseases and conditions part of the claim limitations to the breadth and scope of which broadest reasonable interpretation requires. The limited biochemical data leads one to conclude that the applicant was not in possession of a method of treating any of the diseases or conditions listed. Sheervalilou et al. (COVID-19 under spotlight: a close look at the origin, transmission, diagnosis, and treatment of the 2019-nCoV disease, J. Cell. Physiol. 2020, 235, 8873-8924) teaches that SARS-CoV-2 virus has diverse pathogenesis, expressing specific sequences that are advantageous to adaption after successful insertion to human cells that exhibit receptors for the virus spike protein (pg 2- pathogenesis). However, the pathological outcomes vary, even considering the organ and tissue type that have been infected, including conditions such as septic shock in the respiratory system, an inflammatory cytokine storm, and abnormal liver function (pgs. 8875-8876 - respiratory system, immune system, liver damage). These idiopathic factors for just the case of SARS-CoV-2 infections alone, undermine the concept that biochemical results are prophetic to the final therapeutic application of the invention to all the various diseases and conditions claimed. Whether the specification shows that the inventor was in possession of the claimed invention is not a single, simple determination, but rather a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structures, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. In contrast, for inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predicable which are known to one of ordinary skill in the art, more evidence is required to show possession. One of skill in the art would not recognize from the disclosure that the applicant was in possession of a “method of treatment” for the diseases and conditions as claimed.
Additionally, it is known that there are significant challenges translating biochemical, in vitro, and in vivo studies to a clinical setting, and that not all biochemical, in vitro, and in vivo studies can be directly translated to the clinical setting. Indeed, J. M. McKim (Building a tiered approach to in vitro predictive toxicity screening: a focus on assays with in vivo resistance, Combo. Chem. & High Throughput Scr. 2010, 13, 188-206) emphasizes a truism of the pharmaceutical industry that persists to this day, is the failure of over 90% of promising new drug candidates due to unanticipated adverse effects or a lack of efficacy in humans, contrary to anticipated results based on prior biochemical, cell, or animal models (introduction). As the specification discloses working examples only performed biochemically, one of skill in the art would not recognize that the Applicant was in possession of “a method of treatment” of the various diseases and conditions claimed in an in vivo, much less a clinical, setting.
Claims 14-20 are 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 binding to the AT1 and AT2 receptors, does not reasonably provide enablement for treating an autoimmune disease, a viral respiratory tract infection and/or pneumonia as a consequence thereof, a fibrotic disease, a chronic kidney disease, pulmonary hypertension, heart failure, myocardial infarction, interstitial lung disease, idiopathic pulmonary fibrosis or sarcoidosis, rheumatoid arthritis or systemic sclerosis, diabetic nephropathy, the condition of pulmonary arterial hypertension, or the condition wherein the heart failure is with preserved ejection fraction. 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.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue”. These factors include, but are not limited to: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. See MPEP § 2164.01(a).
Upon consideration of the factors discussed below, the examiner concludes that one skilled in the art could not practice the invention without being burdened with undue experimentation based on the information provided by the applicant. A discussion of these factors as they relate to the pending claims is as follows:
(A) Breadth of claims & (B) Nature of invention –
The applicant’s claims are broad. For example, claim 14 is directed to “a method of treating an autoimmune disease, a viral respiratory tract infection and/or pneumonia as a consequence thereof, a fibrotic disease, a chronic kidney disease, pulmonary hypertension, heart failure and/or myocardial infarction, which comprises administering an effective amount of a compound as defined in claim 1 or a pharmaceutically acceptable salt thereof, to a patient in need of such treatment”. Not only are the diseases and conditions varied as different genus, with disparate etiologies, patient populations, and numerous other relevant factors, the term patient is extremely broad as it includes not only humans but any creature of whom this treatment may be relevant for, including mammals of which there are far too many examples to list here. As the specification discloses working examples only performed in biochemical assays, one of ordinary skill in the art would not recognize that the evidence provided by the Applicant in the instant specification is “a method of treatment” for any disease or condition claimed considering the possible breadth of what are individually diverse diseases and conditions that can arise from multiple factors and pathways, never mind considering the aggregate.
(C) The state of the prior art –
The state of the prior art provides evidence for the degree of predictability in the art and is related to the amount of direction or guidance needed in the specification as filed to meet the enablement requirement. The state of the prior art is also related to the need for working examples in the specification. See MPEP § 2164.05(a). As taught by Sheervalilou, infection by the SARS-CoV-2 virus is commonly associated with respiratory tract infections but has a wide variety of pathological outcomes and has varying etiologies among patients. This is but one of the diseases and conditions claimed. Therefore, it is reasonable to conclude that the current state of the art is highly unpredictable, indicating that more details, working examples, and guidance would be required to practice the invention as disclosed for the treatment of the diseases and conditions claimed.
(D) The level of one of ordinary skill in the art –
MPEP 2141.03 states (in part), “A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton.” KSR International Co. v. Teleflex Inc., 127 S.Ct. 1727, 167 LEd2d 705, 82 USPQ2d 1385, 1397 (2007). “[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle.” Id. Office personnel may also take into account “the inferences and creative steps that a person of ordinary skill in the art would employ.” Id. At 1396, 82 USPQ2d at 1396. The “hypothetical person having ordinary skill in the art' to which the claimed subject matter pertains would, of necessity, have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988) disagreeing with the examiner' s definition of one of ordinary skill in the art (i.e. a doctorate level engineer or scientist working at least 40 hours per week in semiconductor research or development), and finding that the hypothetical person is not definable by way of credentials, and that the evidence in the application did not support the conclusion that such a person would require a doctorate or equivalent knowledge in science or engineering).
These hurdles render application of “a method of treatment” of the diseases and conditions claimed to a very high level of unpredictability. The lack of significant guidance from the present specification makes practicing the claimed invention unpredictable. Where the predictability in the art is low, the Applicant is required to provide greater disclosure and guidance to comply with the enablement requirement. MPEP § 2164.03.
(E) Existence of working examples & (F) Amount of direction or guidance by the inventor –
As previously established by Sheervalilou, infection by SARS-CoV-2 is a complex and sophisticated process. Conversely, the specification does not demonstrate, also as previously established, a means to treat respiratory tract infection by SARS-CoV-2, or any other source, nor any of the other diseases and conditions listed. Instead, the instant specification only provides results of biochemical binding to AT1 and AT2. Therefore, the applicant has not provided sufficient guidance to enable one of skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims.
(G) Quantity of experimentation needed to make or use the invention –
Taken together, the prior art demonstrates that the diseases and conditions arise from multiple factors and etiologies. This covers a breadth and scope of material that is far from adequately addressed in the instant specification. While the specification demonstrates binding to the target proteins, it does not demonstrate how “a compound” would be able to matriculate into a preclinical candidate, much less a new investigational drug with a reasonable chance of success to reach the status as a demonstrative drug containing therapeutically efficacious properties. Even if the compound was not being considered for human treatment, there are, as established by McKim, numerous hurdles that must be overcome for use in the broad category of a patient including the most basic of demonstrating efficacy in vitro and in vivo, which is not a guaranteed, linear progression. This constitutes undue experimentation. Therefore, the lack of working examples commensurate in scope to the claimed invention and the unpredictability in successful application as described by claims 14-20, and as described in the specification, as filed, does not provide enablement for the claimed method of use.
In conclusion, the claimed invention does not provide enablement for the application in the method of use in treating the diseases and conditions claimed. Thus, for the reasons outlined above, the specification is not considered to be enabling for one skilled in the art to make and use the claimed invention as the amount of experimentation is undue, due to the broad scope of the claim, the lack of guidance and working examples provided in the specification. Therefore, the specification is not representative of the instant claims and the specification is not fully enabled for the instant claims. In view of the above, one of ordinary skill in the art would be forced into undue experimentation to practice the claimed invention.
Allowable Subject Matter
Claims 1-9, 11, and 21 are allowed.
Reasons For Allowance
The following is an examiner’s statement of reasons for allowance: the following is a statement of reason for the indication of allowable subject matter: the structure as defined by the elected species 1-[[3-[3-fluoro-4-[(2-methylimidazol-1-yl)methyl]phenyl]-5-isobutyl-2-thienyl]sulfonyl]-3-(2-hydroxyethyl)urea and other analogous structures in claim 9 were not taught in the prior art in a 100% embodiment. The closest match are structures detailed by Wu et al. (Selective angiotensin II AT2 receptor agonists: arylbenzylimidazole structure-activity relationships, J. Med. Chem. 2006, 49, 7160-7168). Wu discloses structure 13 illustrated below (pg. 7161 – scheme 1):
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While structure 13 encompasses a large portion of the core structures, it does not read fully on claim 1, where R1 represents C1-4 alkyl, optionally substituted by one or more fluorine atoms and/or with OR7; R7 representing H or methyl optionally substituted by one or more fluorine atoms. Nor does it encompass the alkyl/cycloalkyl hydroxy moieties found in the distal end attached to the urea or the inclusion of an aryl fluorine in the connecting phenyl in the structures listed in claim 9.
Therefore, the prior art neither anticipates nor reasonably makes obvious the claimed invention and therefore, the claimed invention is deemed novel and unobvious over the prior art.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee. Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.”
Summary
Claims 1-9, 11 and 21 are allowable. Claims 14-20 are rejected under 35 U.S.C. 112(a).
Conclusion
Claims 1-9, 11 and 21 are allowed. Claims 14-20 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Allen Chao whose telephone number is (571)272-7001. The examiner can normally be reached Monday - Friday 0700-1300.
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, James H Alstrum-Acevedo can be reached at 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALLEN CHAO/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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