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 the Claims
Claims 1, 4-8, 13-14, 30-33, 38, and 71 are pending.
Claims 32-33, 38, and 71 are withdrawn.
Claims 2-3, 9-12, 15-29, 34-37, and 39-70 are cancelled.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 08/07/2026 has been entered.
Priority
Applicant’s claim for benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. This application is a national stage entry of and claims priority to Application Serial No. PCT/US21/63360, filed 12/14/2021; and further claims priority to provisional application 63/231,582 and 63/125,175, filed 08/10/2021 and 12/14/2020, respectively.
Information Disclosure Statement
All references from IDS(s) received 06/10/2024 and 3/13/2026 have been considered unless marked with a strikethrough.
Response to Arguments
Applicant's arguments filed 8/07/2026 have been fully considered and have been found not persuasive.
In a final dated 05/08/2025, Claims 1, 4-8, 13-14, 30-31 were examined upon their merits.
In a final dated 05/08/2025, Claims 1, 4-8, 13-14, 30-31 were rejected 35 U.S.C. 103. The Applicant amended claims 1 and 30 as follows:
Applicant amended claim 1 to strike through all structures of B except for:
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Applicant amended claim 30 to strikethrough the following compound:
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In response to the 103 rejection, the Applicant argues that both the primary reference provided by the Examiner (“Riether”) and secondary reference (“Xiang”) fail to teach compounds with the newly amended instant ring B. The Examiner agrees that Riether fails to teach an example where the core structure would have a -N- in the ring bound to instant -L1. Riether only teaches where instant Ring B would have a -N- in the ring bound to instant -R1. All four structural limitations in instant claim 1 require a -N- in the ring bound to instant L1. The Examiner agrees that Xiang fails to teach an example where the core structure has a -H in the position ortho to instant -N-R1. Xiang only teaches where this position would have a -N or an -O. Xiang also fails to teach where the core ring structure is a saturated ring, as required by newly amended claim 1, and rather only teaches it as an aromatic ring. Therefore, the Examiner agrees that Riether and Xiang fail to teach compounds with the newly amended instant ring B. The Examiner previously argued that because Riether and Xiang both teach the compounds as CB2 agonists, it would be obvious to arrive at the instant invention of the core ring because of bio isosteric replacement. The Examiner now believes that with the amendments, the current invention is too far from both the teachings of Riether and Xiang to reasonably combine them to arrive at the instant invention. A person skilled in the art would have to add an additional -N- in the ring or change the position of the -N- in the ring of that taught by Riether, but to be motivated by Xiang would require a person to make two more adjustments in ring structure to use the teachings of Riether and Xiang to arrive at the instant invention. Furthermore, as the Applicant points out, Xiang teaches the compounds as CB2 antagonists rather than agonists. Therefore, the Examiner believes a person skilled in the art would move away from the teachings of Xiang to modify Riether. This 103 rejection is moot and withdrawn.
However, the Examiner has found new art based on the broad genus structure. See new 102 and 103 rejections below.
NEW REJECTIONS
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1 and 6-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wei, Y. et al. (Org. Lett. (2010) 12 (19): 4220–4223; “Wei”).
This rejection applies to an expanded species where Ring A is pyridyl, R4 is H, Ring B is pyrrolidine, R1 is H, L1-L2 are direct bonds, Q is O, and R2-R3 and Ra are H. The Examiner has provided a structure for reference below:
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Wei teaches a genus structure overlapping with the instant claims.
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(Wei, Table 2)
Wei teaches where R1 can be 2-pyridyl (Table 2, compound 3j), as required by the expanded species.
Therefore, the limitations of claims 1 and 6-8 are anticipated by Wei.
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.
Claims 1, 4, 6-8, and 31 are rejected under 35 U.S.C. 103 as being unpatentable over Wei, Y. et al. (Org. Lett. (2010) 12 (19): 4220–4223; “Wei”) in further view of Meanwell, N. (J. Med. Chem. (2011) 54 (8): 2529–2591; “Meanwell”).
This rejection applies to an expanded species where Ring A is pyridyl, R4 is alkyl, Ring B is pyrrolidine, R1 is H, L1-L2 are direct bonds, Q is O, and R2-R3 and Ra are H. The Examiner has provided a structure for reference below:
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Wei teaches a genus structure overlapping with the instant claims.
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(Wei, Table 2)
Wei teaches where R1 can be 2-pyridyl (Table 2, compound 3j).
Wei fails to teach where instant -R4 can is an alkyl, aryl, or heteroaryl when R1 is a pyridine as required by the expanded species and instant claim 4.
However, Wei teaches an example where R1 is -PhMe (Table 2, Claims 3d-3e).
Pyridine and phenyl groups are known bioisosteres. Substitution of a phenyl for a pyridine group is a well-known way to improve solubility and ADME properties in the field of medicinal chemistry, as taught by Meanwell (Section 3.3, “N Substitution for CH in Benzene Rings”). Therefore, it would be obvious to a person skilled in the art to extract the structures of Wei where -R1 is -PhMe and substitute the -Ph for a pyridyl group.
With respect to claim 31, Wei fails to explicitly teach pharmaceutical composition of the compounds discussed. However, Wei teaches derivatives of the compounds are used in pharmaceutical treatments (Introduction). Therefore, it would be obvious to a person skilled in the art that these derivatives/analogs could also be used in pharmaceutical compositions.
The Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham.
Examples of rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Applying KSR example rationale (B), it would have been prima facie obvious to extract the structures of Wei where -R1 is -PhMe and substitute the -Ph for a pyridyl group. A person skilled in the art would be motivated to do so because Pyridine and phenyl groups are known bioisosteres. Substitution of a phenyl for a pyridine group is a well-known way to improve solubility and ADME properties in the field of medicinal chemistry, as taught by Meanwell.
Therefore, claims 1, 4, 6-8, and 31 would have been obvious to a person skilled in the art at the time.
Allowable Subject Matter/Claim Objections
Claims 5 and 13-14 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim 30 is considered allowable. Examiners reasons for allowance are below:
Although a 103 rejection was previously made over claims 1, 4-8, 13-14, 30-31 over Riether, D. et al. (Bioorg. Med. Chem. Lett. 25 (2015) 581–586; cited in the IDS filed 6/10/2024; “Riether”) in view of Xiang, J. et al. (US6100259A; cited in the IDS filed 6/10/2024; “Xiang”), it was withdrawn for the following reasons:
Riether teaches a genus structure that falls within the genus structure of the instant claims.
Riether fails to teach where the core ring having two heteroatoms that are nitrogen, such as a pyrazolidine. However, Xiang teaches an overlapping genus structure for a similar use as a CB2 agonist that has a pyrazolidine ring. The Examiner previously argued that because the structures are considered isosteres of each other and Xiang provides an example where the structure is also a CB2 agonist, it would be obvious to a person skilled in the art to extract the structure taught by Riether and add a second heteroatom, such as a N in the core ring structure. However, the Examiner now believes that with the amendments, the current invention is too far from both the teachings of Riether and Xiang to reasonably combine them to arrive at the instant invention. A person skilled in the art would have to add an additional -N- in the ring or change the position of the -N- in the ring of that taught by Riether, but to be motivated by Xiang would require a person to make two more adjustments in ring structure to use the teachings of Riether and Xiang to arrive at the instant invention. Furthermore, as the Applicant points out, Xiang teaches the compounds as CB2 antagonists rather than agonists. Therefore, the Examiner believes a person skilled in the art would move away from the teachings of Xiang to modify Riether. Therefore, the 103 rejection was withdrawn.
The following is the closest other prior art and why it was not used in a rejection:
WO2010077836A2; The ‘836 publication teaches an overlapping genus structure with the instant claims. However, the ‘836 publication fails to teach the core structure would have a -N- in the ring bound to instant -L1, rather only teaches where instant Ring B would have a -N- in the ring bound to instant -R1. Therefore, for the same reasons as above, the ‘836 publication was not used in a 103 rejection.
Bartolozzi, A. et al. (Bioorg. Med. Chem. Lett. 25 (2015) 587–592); Bartolozzi teaches an overlapping genus structure with the instant claims. However, Bartolozzi fails to teach the core structure would have a -N- in the ring bound to instant -L1, rather only teaches where instant Ring B would have a -N- in the ring bound to instant -R1. Therefore, for the same reasons as above, Bartolozzi was not used in a 103 rejection.
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.”
Conclusion
Claims 1, 4, 6-8, and 31 are rejected.
Claims 5 and 13-14 are objected to and considered allowable subject matter.
Claim 30 is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NICOLA MARIA BAUER whose telephone number is (703)756-1269. The examiner can normally be reached Monday-Friday 7:30-5 EST.
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/N.M.B./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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