DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
The instant application is a 35 USC 371 National Stage filing of PCT/US2022/046595, filed October 13, 2022, which claims the benefit of an effective US filing date under 35 USC 119(e) from US Provisional Application 63/262,514.
Information Disclosure Statement
The information disclosure statements (IDS) dated November 18, 2024 and July 13, 2026 were in compliance with the provisions of 37 CFR 1.97 and 1.98. Accordingly, the IDS documents were considered and signed copies of the 1449 forms are attached.
Election/Restrictions
Applicant’s election without traverse of the invention of Group II (claims 110 and 122, drawn to a method of using a compound of Group I) in the reply filed June 9, 2026 is acknowledged. Further, Applicant’s election without traverse of the species of Example 1 in the same reply is also acknowledged. Claims 13-15, 17, 20, 40, 55, 56, 64, 107 and 122, as amended, read on the elected invention and species.
In accordance with the MPEP, if upon examination of the elected species, no prior art is found that would anticipate or render obvious the instant invention based on the elected species and the claims drawn to the elected species are allowable, the search of the Markush-type claim will be extended (see MPEP 803.02). If prior art is then found that anticipates or renders obvious the non-elected species, the Markush-type claim will be rejected. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be reexamined. Id. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. Id. In the event prior art is found during reexamination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final. Id.
As indicated above, the Examiner searched the claimed invention based on the elected species above, wherein: the claims drawn to the elected species were not found to be allowable. Since this scope was not found to be allowable, the scope of the search and examination was not extended further.
Status of Claims
Currently, claims 1, 5, 13-15, 17, 20, 24, 26-27, 36, 38, 40, 55-56, 64, 89, 101, 106-110 and 122 pending in the instant application. Presently, claims 1, 5, 24, 26-27, 36, 38, 89, 101, 106 and 108-110 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a non-elected invention there being no allowable generic or linking claim.
Claims 13-15, 17, 20, 40, 55, 56, 64, 107 and 122 read on an elected invention and species and are therefore under consideration in the instant application to the extent that they read on the elected embodiment described herein.
Claim Rejections - 35 USC § 112
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 13-15, 17, 20, 40, 55, 56, 64, 107 and 122 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. In particular, the specification, while being enabling for treatment of particular conditions recited in the instant claims in patients already having said conditions,, does not reasonably provide enablement for the full scope of “treating” which includes prophylactic treatment per the definition in the specification, nor does the specification enable the treatment of the full scope of diseases encompassed by the claimed scope.
As a general rule, enablement must be commensurate with the scope of claim language. MPEP 2164.08 states, “The Federal Circuit has repeatedly held that “the specification 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, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)” (emphasis added). The “make and use the full scope of the invention without undue experimentation” language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: “A lack of enablement for the full scope of a claim, however, is a legitimate rejection.” The principle was explicitly affirmed most recently in Liebel-Flarsheim Co. v. Medrad, Inc. 481 F.3d 1371, 82 USPQ2d 1113; Auto. Tech. Int’l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008).
The factors to be considered in determining whether a disclosure meets the enablement requirements of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 858 F.2d 731, 8 USPQ2d 1400 (Fed. Cir., 1988). The court in Wands states, “Enablement is not precluded by the necessity for some experimentation, such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is ‘undue’, not ‘experimentation’” (Wands, 8 USPQ2sd 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations” (Wands, 8 USPQ2d 1404). Among these factors are: (1) the nature of the invention; (2) the breadth of the claims; (3) the state of the prior art; (4) the predictability or unpredictability of the art; (5) the relative skill of those in the art; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
While all of these factors are considered, a sufficient amount for a prima facie case is discussed below.
(1) The nature of the invention and (2) the breadth of the claims:
The claims are drawn to methods of treating and preventing families of diseases and disorders, comprising administering to a patient a therapeutically effective amount of an incredibly broad group of compounds of Formula II. The claims are broad in scope, reciting the treatment or prevention of a very broad range of disease and disorders comprising administering any compound within the claimed scope, including all diseases “mediated by” reactive oxygen species, inflammatory cells, Th2, Th17, Th1, IL-1 or T regulatory cell/T-helper cell imbalance.
Thus, the claims taken together with the specification imply that an effective amount of any compound of the claimed formula will treat or prevent any of the literally hundreds of diseases or disorders encompassed by the claims, or more. According to the specification, a non-exclusive list of these compounds includes such diseases as rheumatoid arthritis, multiple sclerosis, multiple types of cancer, and many more.
(3) The state of the prior art and (4) the predictability or unpredictability of the art:
It is well established that "the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity relating to the treatment or prevention of any single disease or disorder is generally considered to be an unpredictable factor. Unpredictability in treating and preventing specific diseases that fall within the scope of the instant claims is established by the following references:
1) Das, U.N. (Journal of Inflammation Research, 2010:3, pages 143 –170) reviews strategies for the treatment and management of lupus, a chronic inflammatory condition, based on molecular signatures of acute and chronic inflammation (Title, abstract). Das discloses that the current strategy of management includes administration of nonsteroidal anti-inflammatory drugs and immunosuppressive drugs such as corticosteroids (Abstract). Das discloses (page 144, right column, 1st paragraph)
“the response of patients with lupus and rheumatoid arthritis is variable. Some respond, others may not respond, and some may show only a partial response to the same therapeutic measures. This type of differential response is at times baffling and suggest the involvement of various organs and tissues due to the underlying inflammatory process is varied, and the degree of involvement may differ in both time and extent and, more importantly, is unpredictable. It is also possible that continued inflammatory events seen in lupus, rheumatoid arthritis (RA) and other rheumatological conditions, could be due to failure of the resolution of inflammation. Thus, the balance between inflammation and resolution is disturbed more in favor of proinflammatory events and/or failure of resolution molecules to be produces at the most appropriate time, leading to non-resolution of inflammation. In other words even after the inciting agent responsible for the initiation of inflammation is removed, inappropriate inflammation continues simply because resolution failed to occur. This leads to delay in the healing/repair process and so tissue/organ damage continues. This may explain why target organ damage continues even when these patients are continuing to take antiinflammatory and immunosuppressive medicines. In view of this, it is imperative that administration of proresolution-inducing agents is needed to obtain full remission and restore normal physiological function of the target tissues/organs in these diseases.
Das discloses lipoxins as an example of one of several pro-resolution-inducing molecules and states:
“Hence, understanding the interactions(s) between proinflammatory and anti-inflammatory and pro-resolution molecules is important to devise newer therapeutic strategies in several inflammatory conditions.”
Das concludes by stating (page 165, 1st and 2nd paragraphs)
“Although there have been significant advances in the management of autoimmune diseases by the use of these drugs, especially biologics, their actions are often unpredictable: Not all patients respond adequately to these therapeutic approaches…Hence….newer therapeutic approaches are needed.
It is possible that GIK, EP, lipid-enriched albumin, VNS, PUFA’s and their products LXs, resolvins, protectins and ghrelin altogether may not be able to produce adequate immunosuppression and anti-inflammatory actions that lead to amelioration of the disease process in lupus, RA and other autoimmune diseases.
It is recommended that some of these suggested approaches could be performed in combination with the currently available therapeutic drugs. For example, GIK regimen, ethylpyruvate, lipid-enriched albumin, VNS, LXs, resolvins, protectins and their synthetic analogs, and ghrelin could be tried in combination with nonsteroidal anti-inflammatory compounds, chloroquine (hydroxychloroquine), corticosteroids (oral or parenteral), d-penicillamine, sulfasalazine, methotrexate, anti-TNF antibodies, and immunosuppressive drugs (such as cyclosporine, cyclophosphamide, and azathioprine).
Another option that could be investigated is the use of anti-TNF-α and other biologics in combination (as a complex or separately) with EP, ghrelin, PUFAs, LXs, resolvins and protectins, and insulin and be used as parenteral infusion.
All these permutations and combinations need to be tried both in the animal models of various autoimmune diseases and other inflammatory conditions and in the clinic before knowing which therapeutic approach is of significant benefit to these patients. With such an approach, one can measure various plasma tissue factors, as shown in Table 1, to determine the effectiveness of the therapeutic approach employed”.
Accordingly, the disclosure of Das casts doubt on whether administration of any single anti-inflammatory agent, or any combination of potential anti-inflammatory agents will predictably be effective in treating diseases characterized by chronic inflammation or an autoimmune response. As noted above, Das cautions that, in view of said unpredictability in the art, all permutations and combinations of potential therapeutic agents need to be tried both in the animal models of various autoimmune diseases and other inflammatory conditions and in the clinic before knowing which therapeutic approach is of significant benefit to these patients.
In summary, the state of the art, as discussed by Das, would predict that the instantly claimed method of administering an anti-inflammatory compound would demonstrate some level of anti-inflammatory activity. As discussed in the specification, certain AHR modulating compounds are known to exhibit anti-inflammatory response in some models of disease.
However, because Das teaches that compounds known to have ant-inflammatory activity may not be able to produce adequate immunosuppression and anti-inflammatory actions that lead to amelioration of the disease process in lupus, RA and other autoimmune diseases, the state of the art is such that the ability of the compounds of the claimed formula to effectively treat or prevent the diseases, would have been highly unpredictable.
Therefore, absent specific evidence demonstrating that compounds of formula (II) are effective in treating any specific autoimmune disease or inflammatory condition, the state of the art suggests that merely demonstrating anti-inflammatory activity is insufficient to predictably expect amelioration of a disease process such as RA, multi-inflammatory syndrome and other autoimmune diseases. In view of said unpredictability, one of skill in the art would need to try each of the specific compounds of formula (II) alone and in combination with all other potential therapeutic agents, in each animal model of various autoimmune diseases and other inflammatory conditions and in the clinic before knowing which anti-inflammatory compound or combination of anti-inflammatory compounds and in what amounts, are sufficient to provide a significant benefit (i.e. treatment) to these patients. However, there is no evidence that this activity would be able to prevent the initial onset of any disease state, especially for diseases which are known in the art not to be preventable (RA, multiple sclerosis, type 1 diabetes, etc., for example).
(5) The relative skill of those in the art:
The relative skill of those in the art of treating and preventing diseases and modulating immune responses is high, generally that of a Ph.D. scientist or an M.D. That factor is outweighed, however, by the nature of the art which, as noted by Das above, is unpredictable and even compounds that are known to have some anti-inflammatory activity may not be able to produce adequate immunosuppression and anti-inflammatory actions that lead to amelioration of the disease process in RA and other claimed diseases, or the prevention or delay of those diseases.
(6) The amount of direction or guidance presented and (7) the presence or absence of working examples:
As noted above, the specification provides a list of compounds where are considered to be AHR modulating capable of the claimed activity. The specification provides statements that the compounds of the invention will have an effect on AHR but discloses only a single example of one compound of the incredibly broad formula as having anti-inflammatory activity. As such, the specification does not provide guidance as to whether any of the compounds of the claimed formula are effective preventing or delaying any disease or for effectively treating any diseases. It is noted that it is well-understood in the art the in vitro activity does not always correlate to in vivo results. Therefore, claiming a method wherein an entire class of compounds is claimed based on their in vitro activity as AHR modulators would not be expected to reasonably correlate to the use of the entirety of the broad classification of compounds for the treatment or prevention of the entirety of claimed conditions. This is especially true since the claimed chemical formula can differ significantly from the single tested example at both of the two ring systems in the chemical formula. It is suggested that Applicants amend the claimed scope of compounds and diseases to reasonably correlate with the data and evidence provided.
(8) The quantity of experimentation necessary:
As set forth in Rasmusson v. SmithKline Beecham Corp., 75 USPQ2d 1297,1302 (CAFC 2005), enablement cannot be established unless one skilled in the art "would accept without question" an Applicant's statements regarding an invention, particularly in the absence of evidence regarding the effect of a claimed invention. Specifically: "As we have explained, we have required a greater measure of proof, and for good reason. If mere plausibility were the test for enablement under section 112, applicants could obtain patent rights to "inventions" consisting of little more than respectable guesses as to the likelihood of their success. When one of the guesses later proved true, the "inventor" would be rewarded the spoils instead of the party who demonstrated that the method actually worked. That scenario is not consistent with the statutory requirement that the inventor enable an invention rather than merely proposing an unproved hypothesis.”
In the present case, practicing the claimed invention would require testing all permutations and combinations of potential therapeutic agents in animal models of various autoimmune diseases and other inflammatory conditions and in the clinic before knowing which therapeutic approach is of significant benefit to these patients. Further, the person of ordinary skill in the art would be tasked with preventing diseases which heretofore are known not to be preventable. Such a need equates to a burden of undue experimentation to practice the invention commensurate with the full scope of the claims.
It is further noted that as currently drafted the claims recite a method for “preventing or treating…the modulation of immune responses” such that the claims actually recite the prevention of the intended effect. This is believed to be a typographical error and should be corrected upon response.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Alicia L. Otton whose telephone number is (571)270-7683. The examiner can normally be reached on Monday - Thursday, 8:00-6:00.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Mr. Fereydoun Sajjadi can be reached on 571-272-3311. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALICIA L OTTON/Primary Examiner, Art Unit 1699
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