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
The present office action is in responsive to November 22, 2023 Remarks and Comments and corresponding miscellaneous documents.
Claims 1-14 are pending and currently amended in the above-identified application.
Priority
U.S. Pat. Appln. Ser. No.: 18/563,554, Filed: November 22, 2023, is 371 Nat.’l Stage Entry of (i.e., PCT/EP2022/063870, Intern.’l Filing Date: May 23, 2022 ; Intern.’l Pub. Date: December 1, 2022), which claims foreign priority to EP 21382471.7, Filed: May 24, 2021
Information Disclosure Statement
An Information Disclosure Statement (IDS) submitted on January 24, 2024 is in compliance with the provisions of 37 CFR 1.97.
Accordingly, Information Disclosure Statements have been considered by the Examiner.
Claim Objections
Claim 11 is objected to because of the following informalities: Claim 11 recites “wherein the compound of formula (I) is claims, which is…” The words “is claims, which” appear to be redundant. Appropriate correction is required.
.Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conc lude 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.
Claims 12 and 14 are 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.
[1] Claim 12 recites a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instance, claim 12 recites the broad recitation "LGMD R1 calpain- \3 related and the claim also recites the following terms in the parentheses (LGMDR1 or calpainopathy) which is the narrower statement of the range/limitation; i.e., the scope of the phrase before the terms defined inside the parentheses appear to be mismatched those the phrase set forth before it
The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is:
merely exemplary of the remainder of the claim, and therefore not required, or
(b) a required feature of the claims.
Appropriate correction is requested accordingly.
[2] Claim 14 is rejected for lack of clarity and for being vague, ambiguous and indefinite such that the metes and bound of the scope of the claimed invention is indeterminate, because :
Claim 14 recites unclear language “used in combination with” and indefinite language “may” in the phrase:
“. . . the compound of formula (I) is used in combination with one or more active ingredients to provide a combination therapy, wherein the other active ingredients may form part of the same composition, or be provided as a separate composition for administration”;
where that:
statement fails to particularly point out exactly what constitutes the active step and what Applicants regards as their claimed invention; and
use of the indefinite term “may” in any claim causes ambiguity as it is indeterminate as to when the formation of “part of the same composition for administration” occurs “at the same time” or “at different time”.
To obviate this rejection, claim amendments are required to overcome each of the above-identified rejections accordingly.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
The Claimed Invention
The present invention relates to:
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Mechanism of action : inhibition of glycogen synthase kinase 3 β (GSK-3b) activity
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(i.e., specification at p. 4, lines 21-26)
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(i.e., specification at p. 3, lines 24-26)
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(i.e. specification at p. 4, lines 12-16)
Claims 1-14 are rejected under 35 U.S.C. 103 as being unpatentable over Palomo et al., J. Med. Chem. 2017, 60, 4983−5001, alone, in combination with and/or further in view of Jones et al., J Clin Invest. 2012 Dec;122(12):4461-72, doi: 10.1172/JCI64081 and Yalvac et. al., Skeletal Muscle (2017) 7:27, DOI 10.1186/s13395-017-0146-6.
The Palomo reference:
teaches 3-carboxamide quinoline derivative compounds which are identified as allosteric glycogen synthase kinase 3 β (GSK-3b) activity modulators generally associated therapeutic use for chronic treatment of neurological and neuromuscular diseases and other chronic diseases where GSK-3β inhibition exhibits therapeutic effects (i.e., see Abstract at page 4983 and page 4990, col. 1, lines 9-12; diseases taught therein inc. some types of muscular dystrophies delayed myogenesis in Congenital Myotonic Dystrophy type 1 (CDM1) and protective effects in Spinal Muscular Atrophy (SMA)); and
further teaches that allosteric inhibitors of GSK-3β regulate muscle homeostasis and cellular pathways (i.e., such as Wnt/b-catenin and mTOR signaling pathways) associated with various neuromuscular/inflammatory/other chronic diseases.
In particular, Palomo discloses compounds that read on the claimed invention as indicated below:
Compound 1: quinoline-3-carbohydrazide 1 (VP0.7, i.e., which is disclosed in the present invention) and corresponding compounds with the chemical scaffold shown in Figure 2 below:
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; and
Compounds of Formula 26-62 (see Table 1 therein),
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In general, Palomo teaches:
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with congenital myotonic dystrophy type 1 (CDM1) and spinal muscular atrophy (SMA) patients. We found that compound 53 improves delayed myogenesis in CDM1 myoblasts, while compounds 1 and 53 have neuroprotective properties in SMA-derived cells. These findings suggest that the allosteric modulators of GSK-3β may be used for future development of drugs for DM1, SMA, and other chronic diseases where GSK-3β inhibition exhibits therapeutic effects.
(i.e., Palomo, see page 4983)
While Palomo teaches 3-carboxamide quinoline derivative compounds are allosteric glycogen synthase kinase 3 β (GSK-3b) activity modulators where GSK-3β inhibition exhibits therapeutic effects associated therapeutic use for chronic treatment of neurological and neuromuscular diseases and other chronic diseases; (i.e., see Abstract at page 4983 and page 4990, col. 1, lines 9-12), it does not teach treatment of specific neuromuscular diseases,
such as muscular dystrophies (i.e., which includes Limb-Girdle Muscular Dystrophy (LGMD) and more specifically limb girdle muscular dystrophy R1 calpain 3-related “LGMDR1), with quinoline compounds such as those taught by Palomo and the present invention.
However, the conventional art teaches that there is a nexus between GSK-3β activity, which regulates muscle homeostasis and interrelated cellular pathways (i.e., such as Wnt/b-catenin and mTOR signaling pathways) and neuromuscular diseases, such as muscular dystrophies, including Limb Girdle Muscular Dystrophy, such as Limb-girdle muscular dystrophy R1 calpain 3-related (i.e., LGMDR1, calpainopathy or LGMD2A under updated classification system).
This is exemplified by:
Jones generally teaches that complex neuromuscular diseases, in particular, myotonic dystrophy type 1 (i.e., characterized by skeletal muscle wasting, weakness and myotonia), operates by increased GSK3β activity, which mediates muscle pathology, inhibits and corrects muscle degenerative pathways as associated with muscle weakness, myotonia, and corrects molecular abnormalities via a GSK-3β modulation mechanism; i.e., directed to suppressing the same Wnt/mTOR pathway, that inhibits GSK-3β activity is a valid therapeutic strategy for correcting muscle degenerative pathways (i.e., see Jones generally, Abstract at page 4461 and 4469, col 2, lines 4-5); and
Yalvac which specifically teaches that CAPN3 deficiency and Limb-girdle muscular dystrophy R1 calpain 3-related, LGMD2A (i.e., equivalent to LGMDR1, calpainopathy), which is directly linked to impaired regeneration via the Akt/mTOR pathway, such that GSK3b activity is interrelated by the same MOA associated with the nTOR pathway neuromuscular diseases include LGMD and LGMDRI (i.e., see Yalvac generally, Abstract summary at page 1)
Based on the foregoing and the teachings of the art, the ordinary artisan in preparing and/or using the quinoline allosteric modulators or pharmaceutically acceptable salts thereof or corresponding pharmaceutical compositions to treat LGMD diseases would meet with a reasonable expectation of success, because:
comparative data of quinoline compound derivatives of VP0.7 demonstrated enhanced biological allosteric GSK-3b inhibitory activity based on structure activity relationships, chemical and physical properties, activities and efficacies in preclinical models for neurological and neuromuscular degenerative diseases;
substantial data exists in understanding of the mechanism of action due to GSK-3β modulation inhibition mechanism;
i.e., directed to suppressing the sane Wnt/mTOR pathway, which also includes inhibiting GSK-3β activity is a valid therapeutic strategy for correcting muscle degenerative pathways.; and
where discussed and demonstrated research results identified by literature compounds demonstrating positive and/or desired results, would encourage one of ordinary skill in the art would have:
“good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely that product [was] not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under § 103.”KSR, 550 U.S. at 421, 82 USPQ2d at 1397. If any of these findings cannot be made, then this rationale cannot be used to support a conclusion that the claim would have been obvious to one of ordinary skill in the art (i.e., see MPEP 2143: Section E “Obvious To Try”.; and
One of ordinary skill in the art would have been motivated to administer VP0.7 and its derivative compounds of Palomo, because there is an unmet need to find new ways to treat muscular dystrophy disease (i.e., including limb girdle muscular dystrophy, and more particularly limb girdle muscular dystrophy R1 calpain 3-related (LGMDR1)) as indicated in Applicants specification, especially demonstrated structure activity and allosteric biological activity and mechanistic nexus shown by GSK-3β inhibition activity between signaling pathways, such as Wnt and mTOR, of LGMDR1patient's muscles, and to look for new therapeutic agents to treat this disease.
Based on the foregoing, claimed invention is rendered obvious over Palomo. alone, in view of or in combination with Jones and/or Yalvac.
CONCLUSION
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to GRACE C HSU whose telephone number is (571) 270-1689.
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If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, KORTNEY L. KLINKEL can be reached on 571-270-5239. 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.
/G.C.H./
Examiner, Art Unit 1624
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627