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 .
Status of Claims
Claims 1-2 and 5-27 are pending in the instant application. Claims 1 and 5-22 are amended, claims 3-4 are cancelled and claims 23-27 are added via the amendment filed April 15th, 2026.
Priority
This is a 35 U.S.C. 371 National Stage filing of Application No. PCT/US2021/057628 filed November 1st, 2021, which is a continuation of Application No. 63108054, filed October 30th, 2020.
Withdrawn Rejections
Applicant’s arguments, filed April 15th, 2026, with respect to double patenting rejection of claims 1-3, 6-9 and 11-18 as being unpatentable over Application No. 19/203,874 have been fully considered and are persuasive. The double patenting rejection of claims 1-3, 6-9 and 11-18 has been withdrawn.
This rejection has been overcome as copending Application No. 19/203,874 has been abandoned.
Maintained Rejections
Applicant's arguments filed April 15th, 2026, with respect to the Improper Markush rejection of claims 1-3, 6-9, 11 and 16-21 have been fully considered but they are not persuasive.
See response to remarks.
Applicant's arguments filed April 15th, 2026, with respect to the 35 U.S.C. 103 rejection of claims 1-3, 6-9 and 11-21 have been fully considered but they are not persuasive.
See response to remarks.
Response to Remarks
Applicant’s arguments regarding the double patenting rejection are moot as the rejection has been overcome. The double patenting rejection is withdrawn as the copending application has been abandoned.
Applicant’s arguments and amendments regarding the improper Markush rejection have been fully considered but are not persuasive for the reasons explained below.
On p. 19 of the remarks, Applicant argues that as claim 1 has been amended to include that Z is -C(O)- and X is selected from the group consisting of -N derivatives that the Markush grouping of claim 1 is now proper.
However, the various permutations of variables X, Y, rings A and B result in compounds that only require a structure of a tricyclic structure in common, which is not a significant structural similarity. Applicant’s alleged amendment only places limitations of variable Z, but still does not produce group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use. As stated in the previous Office action, defining the X, Y and Z variables would appear to be a minimum requirement since the options for X, Y and Z to be the multiple options listed in instant claim 1 results in numerous dissimilar ring permutations.
Further, although Applicant alleges that the amendment to claim 1 requires that Z is -C(O)-, there is no definition for the Z variable in the amendment of claim 1, filed April 15th, 2026.
Thus, the improper Markush rejection is maintained.
Applicant’s arguments and amendments regarding the 35 U.S.C. 103 rejection have been fully considered but are not persuasive for the reasons explained below.
On p. 20 of the remarks, Applicant argues that the removal of “stroke” from claim 1 overcomes the rejection. Applicant further argues that Schinazi does not report or suggest treating pancreatitis, sarcopenia, glioblastoma or traumatic brain injury.
In response, the teachings of Schinazi are still applicable to amended claim 1, as the claims embrace the prevention of pancreatitis, sarcopenia, glioblastoma or traumatic brain injury. As such, the claims encompass the administration of a compound of formula A to a subject in need to prevention of pancreatitis, sarcopenia, glioblastoma or traumatic brain injury, which reads on the administration of a compound of instant formula A to any subject.
Further, as stated in the previous Office action, Schinazi teaches a method for treatment or prophylaxis of a disease affected by Retinoic Acid Receptor-like Orphan Receptor (ROR) modulators, comprising administering an effective treatment amount of a pharmaceutical composition comprising a compound of any of a general formula (A) to a patient in need of treatment thereof (claim 27). Schinazi further teaches that the disorder is brain cancers (claim 33). Glioblastoma is the most common malignant primary brain tumor making up 54% of all gliomas and 16% of all primary brain tumors, as evidenced by Tamimi et al (Codon Publications; 2017 Sep 27. Chapter 8).
In view of the above, the 35 U.S.C. rejection is maintained and altered below, as necessitated by Applicant’s amendment.
Response to Restriction/Election Requirement
Applicant’s election with traverse of the following compound,
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, to prosecute Group I, in the reply filed on November 3rd, 2025, is acknowledged. The transversal is on the grounds that examination of all of the claims does not create an undue search burden on the examiner. This is not found persuasive in view of the art below.
Applicant states that Claims 1-9 and 11-21 encompass the elected species. However, claims 4, 5 and 10 do not read on the elected species. Regarding claims 5, in the elected species Z is -C(O)- and X is -NH, these claims do not allow for this. Further, regarding claim 10, in the elected species R2 is H and R1 is C(O)R3, wherein R3 is heterocycloalkyl, substituted with R4, wherein R4 is aryl, claim 10 does not allow for this. As such, claims 5 and 10 are also withdrawn as being drawn to a nonelected species.
As per MPEP 803.02, the examiner will determine whether the entire scope of the claims is patentable. Applicants' elected species is not allowable. Therefore, according to MPEP 803.02:
Following election, the Markush claim will be examined fully with respect to the elected species and further to the extent necessary to determine patentability.
If the Markush claim is not allowable, the provisional election will be given effect and examination will be limited to the Markush claim and claims to the elected species, with claims drawn to species patentably distinct from the elected species held withdrawn from further consideration.
If on examination the elected species is found to be anticipated or rendered obvious by prior art, the Markush claim and claims to the elected species will be rejected, and claims to the nonelected species will be held withdrawn from further consideration.
As the elected species has been found not allowable, the Markush-type claims have been rejected and claims to the nonelected invention held withdrawn from further consideration. Claims 1-2,6-9, 11-21 and 23-27 have been examined to the extent that they are readable on the elected compound above. Since the elected species is not allowable, subject matter not embraced by the elected embodiment is therefore withdrawn from further consideration, claims 5, 10 and 22 are withdrawn as being drawn to a nonelected group. Any additional issues below that address subject matter outside the scope of the search and examination discussed above are presented in the interest of compact prosecution since they were discovered incidental to said search and examination.
New Claim Rejections - 35 USC § 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 1-2, 6-9, 11-19 and 23-27 is 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 methods of treating pancreatitis and glioblastoma comprising administering a compound according to claim 1, the specification does not reasonably provide enablement for the prevention of pancreatitis and glioblastoma and treatment or prevention of sarcopenia and traumatic brain injury. 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:
5A. The nature of the invention, state and predictability of the art, and relative skill of those in the art
The invention relates to methods for treating, preventing, reducing the susceptibility to, reducing the severity of, or delaying the progression of a disorder selected from the group consisting of pancreatitis, sarcopenia, stroke and traumatic brain injury.
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 factor 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.); 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, the examiner cites the art below, wherein the compounds for the invention are known to treat brain cancers.
This art plainly demonstrate that the art of developing and testing compounds for the prevention of treatment of sarcopenia and traumatic brain injury, and prevention of pancreatitis and glioblastoma, particularly for use in humans, is extremely unpredictable, particularly in the case of a single compound or genus of compounds being used.
5B. The breadth of the claims
Claim(s) 1-2, 6-9, 11-19 and 23-27 are very broad: the treating, preventing, reducing the susceptibility to, reducing the severity of, or delaying the progression of a disorder selected from the group consisting of pancreatitis, sarcopenia, stroke and traumatic brain injury with a compound of formula (A).
5C. The amount of direction or guidance provided and the presence or absence of working examples
The specification provides data merely for the production of compositions with compounds of formula A and experimental data with Huh-7 cells, HCC-derived cells and pancreatitis treatment data. The specification provides no particular direction or guidance for determining the particular administration regimens (e.g., timing, administration routes, etc.) necessary to prevent and treat the diseases encompassed by the claims, particularly in humans. There is no experimentation or mechanism of action presented or discussed in the specification regarding the prevention of pancreatitis and glioblastoma and treatment or prevention of sarcopenia and traumatic brain injury.
5D. 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 any compound of formula A could be predictably used as the prevention of pancreatitis and glioblastoma and treatment or prevention of sarcopenia and traumatic brain injury.
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, none of the experimentation provided is drawn to the prevention of pancreatitis and glioblastoma and treatment or prevention of sarcopenia and traumatic brain injury. A review of the state of the art fails to reveal that compounds of formula A can find prevention of pancreatitis and glioblastoma and treatment or prevention of sarcopenia and traumatic brain injury. Determining if any particular claimed compound would allow the prevention of pancreatitis and glioblastoma and treatment or prevention of sarcopenia and traumatic brain injury 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 Applicants. 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, the instant claims 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.
Claim Rejections - 35 USC § 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.
Claims 1-2, 5, 7-9, 11-12 and 14-21 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.
Claim 1 recites formula A, wherein variable Z is present. However, the claim fails to define variable Z. As such, the metes and bounds of the claim are unclear.
For the purposes of examination, Examiner has interpreted Z to be -C(O)-. Claims 2, 5, 7-9, 11-12 and 14-21 ultimately depend from claim 1 and do not define variable Z and thus, as such, the claims are also rejected as being indefinite.
Maintained Improper Markush Grouping
Claims 1-2, 6-9, 11 and 16-21 stand rejected on the basis that they contain 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 Formula (A) is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: the various permutations of variables X, Y and Z and rings A and B result in compounds that only require a structure of a tricyclic structure in common, which is not a significant structural similarity. The varying permutations are not recognized to belong to the same physical or chemical class or to the same art-recognized class. 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. The scope of formula A (inclusive of the elected species) that would form a proper Markush grouping would be where X is -C(O) and X and Y are -NH. There would appear to be several different ways in which a proper Markush grouping could be derived from the scope instantly claimed; however, defining the X, Y and Z variables would appear to be a minimum requirement since the options for X, Y and Z to be the multiple options listed in instant claim 1 results in numerous dissimilar ring permutations.
Maintained 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-2, 6-9, 11-21 and 23-27 stand rejected under 35 U.S.C. 103 as being unpatentable over Schinazi et al (WO 2019/213584 A1, as cited on the IDS dated 08/14/2023), as evidenced by Tamimi et al (Codon Publications; 2017 Sep 27. Chapter 8).
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Schinazi teaches a method for treatment or prophylaxis of a disease affected by Retinoic Acid Receptor-like Orphan Receptor (ROR) modulators, comprising administering an effective treatment amount of a pharmaceutical composition comprising a compound of any of a general formula (A) to a patient in need of treatment thereof (claim 27).
Schinazi further teaches that the disorder is brain cancers (claim 33). ). Glioblastoma is the most common malignant primary brain tumor making up 54% of all gliomas and 16% of all primary brain tumors, as evidenced by Tamimi et al (Codon Publications; 2017 Sep 27. Chapter 8).
Schinazi teaches compounds of formula (A) that includes the following (claim 13):
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This compound is embraced by instant formula A, wherein Z is -C(O)-, X is -NH-, Y is -NH, A and B are phenyl, R2 is H, and R1 is C(O)R3, wherein R3 is heterocycloalkyl, substituted with R4, wherein R4 is aryl.
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
Schinazi does not teach an explicit embodiment where the compound above was administered to a patient.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
Regarding claim 1, while the prior art does not explicitly teach an embodiment where the compound above was administered to a patient, Schinazi teaches compounds of instantly claimed formula B and their utility in treating a subject suffering from brain cancers A person having ordinary skill in the art would have been motivated to screen the example compounds of the prior art in the particular utilities to determine which would provide optimum treatment outcomes.
Regarding claim 2, Schinazi teaches that the compound is an ROR alpha agonist (claim 36).
Regarding claims 3 and 6, X is -C(O) and Z is -NH-.
Regarding claim 7, Y is -NH.
Regarding claims 8-9, R2 is H.
Regarding claim 11, R2 is
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Regarding claim 12, R2 is -C(O)-heterocyclyl-alkylaryl.
Regarding claim 13, the compound above is the first compound of the instant claim.
Regarding claim 14, the compound above is embraced by the formula of the instant claim.
Regarding claim 15, Schinazi teaches that the pharmaceutical composition comprises a pharmaceutically acceptable carrier or excipient (claim 15).
Regarding claim 16, Schinazi teaches that the pharmaceutical composition is a transdermal composition or a nanoparticulate composition (claim 16).
Regarding claim 17, Schinazi teaches that the pharmaceutical composition further comprises a second Retinoic Acid Receptor-like Orphan Receptor (ROR) modulator from formula (A).
Regarding claims 18-19, Schinazi teaches that the pharmaceutical composition further comprises aspirin (claim 24).
Regarding claim 20, the claim recites “wherein the pancreatitis is…”, however, the method of the prior art is a method of treating brain cancers. Claim 1, the claim from which claims 7 depends, recites that the disorder can be pancreatitis, sarcopenia, glioblastoma and traumatic brain injury. As the limitations of claim 20 is to pancreatitis, the method of the prior art above reads on the claim. Regarding claim 21, the claim is also concerned with pancreatitis as the claim recites “associated with an increased risk of pancreatitis”.
Regarding claims 23-27, the compound above is of formula (B), wherein u is 0 and n is 0.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Anna Grace Kuckla whose telephone number is (703)756-5610. The examiner can normally be reached Monday-Friday 7:30-5.
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/A.G.K./Examiner, Art Unit 1626
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699
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