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
Election/Restriction
Acknowledgement is made of Applicant’s election of Group I, subgenus of Formula I wherein R3 is C2-6 alkyl substituted with at least one of amino, C1-6 alkyl-amino, etc.,and compound species, Example 10 having following structure, in the reply filed on 01/08/2026,
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Applicant elected the species with traverse. Applicant argues claim 1 has been amended to require R3 to be C2-6 alkyl substituted with at least one of amino, C1-6 alkyl-amino, etc. and compounds 210 and 211 by Slaugenhaupt ( US2018/0118748 A1) do not teach instantly claimed R3. Please note the Restriction/Election requirement is NOT full examination. Slaugenhaupt’s 748 teaches the core structure of pyrrolopyrimidine that reads on instant claimed compounds. Thus, the shared common structure of instant claimed compound of Formula I is not novel in view of Slaugenhaupt’s 748. The Restriction/Election requirement is deemed proper and made final.
The elected species is a compound of Formula I wherein
R1 is furanyl;
R2 is fluoro;
R3 is C2-6 alkyl substituted with amino;
R4 is H;
R5 is chloro.
Claims 1-4, 6-12 read on the elected species. Claim 5 directing to R-configuration is also considered/examined since isomers are construed as exhibiting similar activity in the absence of evidence to the contrary.
The elected species, Example 10 (CAS# 2477799-01-0, entered STN database on 09/11/2020) is disclosed by WO2020167624 A1(hereafter “Wang’624) which is prior art under 102(a)(2) based upon the earlier effectively filed date.
The examiner has expanded the search to non-elected species, wherein R1 is phenyl or heteroaryl (e.g. furanyl), R2 is H or C1-6 alkyl, R3 is C1-6 alkyl substituted with C1-6 alkyl-amino; R4 is H, C1-6 alkyl, R5 is H or halogen( e.g. chloro). The non-elected species are rejected under the 103 rejections shown below. Other non-elected species are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species. The absence of other citations of prior art should not be interpreted as an indication that other subgenera within Formula I are free of prior art. 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 reconsidered. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. In the event prior art is found during reconsideration that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final.
Status of Claims
Claims 1-12 are pending and currently under examination.
Priority
This instant application 18/264,183 filed 08/03/2023, is a 371 of PCT/US2022/014929 filed 02/02/2022, which claims benefit of US provisional application 63/146,139 filed on 02/05/2021.
Information Disclosure Statement
The information disclosure statements are in compliance with the provisions of 37 CFR 1.97. Accordingly, the reference listed in IDS are being considered by the Examiner. Reference written in foreign language is considered to the degree of English abstract or patent family of foreign patent by Examiner.
Claim Objections
Claims 1-12 are objected to because of the following informalities: Claims 1-9 recite compound of Formula I and species and a form thereof, wherein the form of the compound is selected from the group consisting of a salt ,hydrate, solvate, and tautomer form thereof. The form of the compound and tautomer form are repetitive.
Claims 10-12 recite the compound or the form thereof or the compound salt or the form thereof, which are repetitive and not clear.
Claims 10-12 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim should refer to other claims in the alternative only--, and/or, --cannot depend from any other multiple dependent claim. See MPEP § 608.01(n). Claim 10 refers to the method of any one of claims 1 or 6-9. Claim 11 and 12 refer to the method of any one of claims 1 or 6-10. Claim 7 depends on claim 6 while claim 9 depends on claim 8.
Claim Rejections - 35 USC § 112
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.
Claims 1-12 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.
Instant claims are to directed to “[a] method for treating spinocerebellar ataxia type 3 (SCA3) in a subject in need thereof, comprising administering to said subject an effective amount of a compound of Formula (I) … ”. The instant disclosure does not contain sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use the claimed invention without undue experimentation in full scope upon consideration of the factors set forth in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1998), as follows. See also MPEP § 2164.01(a) and § 2164.04.
To be enabling, 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 (Fed. Cir. 1993). The determination that "undue experimentation" would have been needed to practice the claimed invention in full scope is not a single, simple factual determination.
As stated in the MPEP 2164.01(a), “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." In In re Wands, 8 USPQ2d 1400 (1988), factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have need described. They are:
(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.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. Keeping that in mind, the Wands factors are relevant to the instant application for the following reasons:
The Breadth of The Claims/ Nature of The Invention
Independent claim 1 is directed to a method of treating SCA3 by administering a large scope of compounds of Formula (I) comprising vast variety of R groups. Claims 6-9 recite compound species that are not tested or inactive in in-vitro assay. Instant specification defines the term “treating” as including “preventing”, “inhibiting”, and “ameliorating” (See PGPub US 20240041886 A1 [0160]).
The nature of the claimed invention is to affect treating/preventing SCA3 by inducing exon 4 skipping in the ATXN3 pre-mRNA during splicing in a patient. To date there are no known disease-modifying therapies for SCA3 (Spec [0008]).
The State of the Prior Art and the Predictability or Lack Thereof in the Art
Spinocerebellar ataxia type 3 (SCA3), also known as Machado–Joseph disease (MJD), is an inherited neurodegenerative disorder and the most common form of autosomal dominant hereditary ataxia worldwide. The treatment of SCA3/MJD is highly unpredictable due to the complex nature of the disease, various etiology/mechanism, and the mode of action of treatment. There are many other factors contributing to the effectiveness/efficacy of compounds in treating SCA3/MJD disease, such as pharmacokinetic profile, bioavailability, administration route, dosage regimen, etc.
Wang (2018) reviews pathogenic mechanisms of SCA3/MJD and therapeutic strategies (See whole paper). Wang 2018 states: “Despite enormous progress toward elucidating the molecular pathogenesis of SCA3/MJD in the last 20 years, there is no cure available for SCA3/MJD patients” (See page 139, left column). “Pharmacological approaches for improving various symptoms have been developed and tested in clinical studies. However, most drug clinical trials for SCA3/MJD had negative or inconclusive results due to the multiple methodological issues of these studies” (See page 147, left column).
More generally, the invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity (e.g., cancer prevention) is generally considered an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
The Amount of Direction Present and Presence or Absence of Working Examples
The specification does not provide sufficient guidance/protocols for a skilled artisan to practice the claimed method of treating SCA3/MJD with compound of Formula I in its full scope.
Instant specification does not disclose the preparation of compound of Formula I (which was disclosed by incorporated WO2020167624, See [0201]). Instant specification disclosed 62 compound species (See [0086]-[0088]), but only 12 compounds were tested in in-vitro assay with varied activity. Instant specification discloses endogenous total ATXN3 (tATXN3) protein assay, wherein 12 compounds were tested, three compounds are inactive and three compounds show IC50 >1.0uM (See Example 1, Table1). In instant RT-qPCR assay to quantify Exon 4 Skipping in ATXN3 Pre-mRNA in cells, 12 compounds were tested, three compounds are inactive and three compounds show IC50 >1.5uM (See Example 2, Table 2).
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It’s noted there is no apparent correlation between the structure of those compounds that are indicated as “inactive” vs. mM level of activity. It’s also noted the assays do not indicate what “Cells” were used in the assays and whether they would be relevant to treating any disease in a subject. There is no in-vivo assay or working example of compounds treating a subject associated with SCA3.
The guidance provided by the assay do not clearly describe how the results are correlated with an expectation of any therapeutic effect with spinocerebellar ataxia type 3 (SCA3). One of ordinary skilled in the art would not know if the assay examples without a clear meaning of “Cells” and lack of analysis and explanation would support instantly claimed method of treatment of (SCA3) in a subject. Regarding dosing and effective amounts, all of the guidance provided regarding dosing and effective amounts is completely generic without any specificity related to response curves or any experimental data associated with spinocerebellar ataxia type 3 (SCA3).
The level of one of ordinary skill in the art
The level of skill required to make and/or use the instant invention would likely require many years of professional experience conducting research in the art (e.g., medicine, pharmaceutical science, biology, biochemistry, medicinal chemistry, and/or organic chemistry, etc.) as well as an advanced educational degree (e.g., M.D. and/or Ph.D.) commensurate in level with the advanced techniques involved in the preparation and/or use of the instant invention.
The quantity of experimentation needed
An unduly extensive amount of experimentation would be required for one of ordinary skill in the art to use the instantly claimed method The efficacy/ effectiveness of compound of Formula I needs to be evaluated/validated through in-vivo test/animal study to provide accurate evidence for effective treatment of SCA3 . Working examples would be needed to determine the therapeutically effective dose and administration route for different compound species due to the different activity. The therapeutically effective amount may vary depending on many factors, such the subjects being treated, the disease condition, intended outcome, patient response, etc. Thus, the skilled artisan would have to undergo exhaustive studies to evaluate each condition that falls under the umbrella compound of Formula I in order to be able to fully carry out the invention commensurate in scope with the claims.
Therefore, it would be a great burden for one of ordinary skill in the art to carry out undue experimentation to in full scope.
Conclusion
MPEP 2164.01(a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562,27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here with respect to instantly claimed method of treating SCA3 in a subject with compound of Formula I , in view of the analysis above pursuant to In re Wands. In other words, one skilled in the art could not practice the claimed invention in full scope without undue experimentation.
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.
Claims 1-12 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.
Claim 1 recites a compound of Formula I or a form thereof.
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The definition of R1 is unclear. It’s not clear if “5-8 membered” applies to both mono- and bi-cyclic alternatives, It’s not clear whether “carbon atom ring structure radical” is limited to “5-8 membered” or whether the “1-3 heteroatoms” are included in the counting of the members.
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The definition of R3 is ambiguous. It’s not clear where the C2-6 alkyl group is substituted with the amino or alkylamino group, at the chiral carbon, or other positions. The deutero-C1-6 alkylamino is also ambiguous regarding the deuterated atom.
The limitation regarding the “form” , wherein the form of the compound is selected from the group consisting of a salt, hydrate, solvate, and tautomer form thereof, is also ambiguous. There are variety of solvent and the scope of solvate is unclear. One of skilled in the art would not know how to evaluate the unambiguous language to determine the scope of formula I that are within the scope of the claims. Thus, claim 1 and its dependent claims are indefinite.
Claims 6-9 recite a method for treating spinocerebellar ataxia type 3 (SCA3) with compound species and a form thereof , wherein the form of the compound is selected from the group consisting of a salt ,hydrate, solvate, and tautomer form thereof. There are vast variety of solvent and the scope of solvate is ambiguous due to lack of direction regarding making or using the hydrate and/or solvates of instantly claimed compounds by instant disclosure.
Claim 10 refers to the method of any one of claims 1 or 6-9. Claim 11 and 12 refer to the method of any one of claims 1 or 6-10. The scope of compounds encompassed by claims 1 or 6-9 are different. One of skilled in the art would not know the scope of claims 10-12 since the resulting claims do not clearly set forth the metes and bounds of the patent protection desired.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 10 and 11 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 10 refers to the method of any one of claims 1 or 6-9. Claim 11 refer to the method of any one of claims 1 or 6-10. Claims 10 and 11 are each directed to an intended function of inducing exon skipping by administering compound of Formula I which do not impart any further physical or otherwise material characteristic to the method step of administering compound of Formula I.
In order to overcome this ground of rejection, Applicant may wish to (a) cancel the claims, rewrite claims to incorporate the subject matter of claims or present a sufficient showing that the dependent claims comply with the statutory requirements.
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.
Claims 1-12 are rejected under 35 U.S.C. 103 as being unpatentable over Slaugenhaupt et al. (WO 2016/115434, hereafter “Slaugenhaupt’ 434”, Applicant’s IDS dated 11/26/2024 ), in view of Wang (Neuroscience 2018, Vol. 371, pp 138-154, https://doi.org/10.1016/j.neuroscience.2017.11.051, Experimental and Clinical Strategies for Treating Spinocerebellar Ataxia Type 3).
Slaugenhaupt’ 434 teaches compound of Formula I, II, Ia, Ib, Ic, etc. or salt thereof, and composition comprising aforementioned compounds for treating diseases of central nervous system (e.g. familial dysautonomia, Fragile X tremor/ataxia, etc. ) by improving mRNA splicing in genes (See abstract, page 2, lines 10-25; page 3-7; page 20-26; page 27-32, lines 1-25; Table A; Examples claims 1-70).
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Slaugenhaupt’ 434 teaches compound species that are encompassed by or very similar to instant claimed compound of Formula I , e.g. compound 177-181, 206, 225, etc. (See Table A; Examples )
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Slaugenhaupt’ 434 compounds read on instant compound of Formula, wherein R1 is phenyl or heteroaryl (e.g. furanyl), R2 is H or C1-6 alkyl, R3 is C1-6 alkyl substituted with C1-6 alkyl-amino; R4 is H, C1-6 alkyl, R5 is H or halogen (e.g. chloro).
Slaugenhaupt’ 434 teaches primary splicing assay in different gene and efficacy thereof (See Example 44, page 261; Table 3-5). Slaugenhaupt’ 434 also teaches in vivo familial dysautonomia mouse model (See Example 46, page 271). Slaugenhaupt’ 434 teaches variety of disease associated with one or more mRNA splicing defects (e.g. familial dysautonomia, Fragile X tremor/ataxia, etc. ) (See page 196, lines 15-25; Table 1; page 197-200). Slaugenhaupt’ 434 teaches method of treating diseases of central nervous system by improving mRNA splicing in genes comprising improving exon inclusion ending in the nucleotide sequence(See abstract, page 199, lines 28-30; Table 1; page 206-207).
Slaugenhaupt’ 434 collectively teaches a method of treating neurological/neurodegenerative disease with pyrrolopyrimidine compounds that could improve mRNA splicing/ improving exon inclusion in the nucleotide sequence. According to MPEP § 2144.09, A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). Please note prior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious. In re Payne, 606 F.2d 303, 203 USPQ 245 (CCPA 1979). Further, a claimed compound may be obvious because it was suggested by, or structurally similar to, a prior art compound even though a particular benefit of the claimed compound asserted by patentee is not expressly disclosed in the prior art. It is the differences in fact in their respective properties which are determinative of non-obviousness.
Slaugenhaupt’ 434 is silent about treating SCA3/MJD associated with mutant ATXN3 (mATXN3) mRNA. Please note biological activity is the property of compound. Instantly recited limitation wherein compound of claim 1 induces exon skipping are considered to simply express the intended result of the process step of administering compound of Formula I, which does not necessarily contribute to patentable weight. See MPEP 2111.04: In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), the court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)).
Wang reviews pathogenic mechanisms of SCA3/MJD and therapeutic strategies for treating SCA3/MJD (See whole paper). Wang 2018 and its incorporated reference teach therapeutic interventions focus on directly targeting the mutant protein or attenuating the mutant atx-3-induced cellular toxicity, e.g. gene silencing or mutant protein clearance, mutant polyQ protein modification, etc.( See page 139, Table 1).
It is a common practice in the pharmaceutical industry to repurpose and/or explore different disease treatment with known active agent/ drug. It would have been prima facie obvious to one of the ordinary skilled in the art before the effective filling date of instant invention to further explore/ expand Slaugenhaupt’ 434 compounds for treating other neurological/neurodegenerative disease (e.g. SCA3/MJD) based on the combined teachings of Slaugenhaupt’ 434, Wang and general knowledge of structure similarity/ bioisosteric modification/ SAR study for treating neurological/neurodegenerative disease. At the time of instant invention was made, it was already known that Slaugenhaupt’ 434 compound could be used for treating neurological/neurodegenerative disease by improving mRNA splicing/ improving exon inclusion ending in nucleotide sequence. It was also known SCA3/MJD is neurological/neurodegenerative disease associated with mutant ATXN3 (mATXN3) RNA with expanded polyQ as taught by Wang. In searching for alternative treatment of SCA3/MJD, a skilled artisan would be motivated to further explore Slaugenhaupt’ 434 compound for treating SCA3/MJD and reasonably expect improving mRNA splicing might benefit treatment of SCA3/MJD in a subject.
One of ordinary skill in the art would have had reasonable expectation of success in producing the claimed invention based on the combined teachings of prior art and general knowledge of structure similarity/ bioisosteric modification/ SAR study for treating neurological/neurodegenerative disease/gene therapy. Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 1-12 are rejected under 35 U.S.C. 103 as being obvious over Wang’624 (WO2020167624 A1, family member of US 12398140 B2, Applicant’s IDS dated 11/26/2024) in view of Wang (Neuroscience 2018, Vol. 371, pp 138-154, https://doi.org/10.1016/j.neuroscience.2017.11.051, Experimental and Clinical Strategies for Treating Spinocerebellar Ataxia Type 3).
The applied reference has a common inventor and applicant with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Wang’624 disclosed pyrrolo[2,3-d]pyrimidine compound of Formula I or a form thereof, and a method for treating familial dysautonomia (See abstract, page 2, lines 1-25; claims 1 -11).
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Wang’624 disclosed compound species that are encompassed by instant compound of Formula I, and compound species as recited in instant claims 6-9, including instant elected species (See page 8-18, claims 6-7).
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Wang’624 disclosed IKBKAP-HTRF Assay (See Example 1) and a method of treating familial dysautonomia (FD) by targeting pre-mRNA splicing mechanisms (See abstract, page 1, lines 14-28; claim 8).
Wang’624 is silent about treating SCA3/MJD with pyrrolo[2,3-d]pyrimidine compound of Formula I.
The collective teachings of Wang (2018) is elaborated in preceding 103 rejection and applied as before. Wang 2018 reviews pathogenic mechanisms of SCA3/MJD and therapeutic strategies for treating SCA3/MJD (See whole paper).
It is a common practice in the pharmaceutical industry to repurpose and/or explore different disease treatment with known active agent/ drug. It would have been prima facie obvious to one of the ordinary skilled in the art before the effective filling date of instant invention to further explore/ expand Wang’624 compounds for treating other neurological/neurodegenerative disease (e.g. SCA3/MJD) based on the combined teachings of Wang’624 and Wang 2018. In searching for alternative treatment of SCA3/MJD, a skilled artisan would be motivated to further explore Wang’624 compound for treating SCA3/MJD and reasonably expect improving mRNA splicing might benefit treatment of SCA3/MJD in a subject.
One of ordinary skill in the art would have had reasonable expectation of success in producing the claimed invention based on the combined teachings of prior art and general knowledge of structure similarity/ bioisosteric modification of SAR study for treating neurological/neurodegenerative disease/gene therapy. Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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Claim 1-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1- 13 of U.S. Patent No. 12398140 B2, in view of Wang (Neuroscience 2018, Vol. 371, pp 138-154, https://doi.org/10.1016/j.neuroscience.2017.11.051, Experimental and Clinical Strategies for Treating Spinocerebellar Ataxia Type 3).
Reference claims are directed to compound formula I with the same core structure. Reference claims 8-11 recite compound species that read on instant claims 6-9. Reference claims 7 and 13 recite treating familial dysautonomia in a subject, wherein the method comprises administering to the subject in need thereof a therapeutically effective amount of reference compounds.
Reference claims are silent about treating spinocerebellar ataxia type 3 (SCA3).
The collective teachings of Wang (2018) is elaborated in preceding 103 rejection and applied as before. Wang 2018 reviews pathogenic mechanisms of SCA3/MJD and therapeutic strategies for treating SCA3/MJD (See whole paper).
It is a common practice in the pharmaceutical industry to repurpose and/or explore different disease treatment with known active agent/ drug. It would have been prima facie obvious to one of the ordinary skilled in the art to further explore/ expand reference compounds for treating other neurological/neurodegenerative disease (e.g. SCA3/MJD) based on the combined teachings of reference claims and Wang 2018.
The instant application shares at least one common inventor /applicant with the reference patent. Furthermore, the instant application is not related to the reference patent based on the record, thus no 35 USC 121 shield exists.
Claims 1-5 and 10-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of copending Application No. 18/264,189 (reference application), in view of Patani et al. (Chemical Reviews, 1996. Vol. 96, 8: 3147-3176).
Reference claims are directed to method for inhibiting or ameliorating spinocerebellar ataxia type 3 (SCA3) in a subject in need thereof, comprising administering to said subject an effective amount of a compound of Formula (I). Reference claims 14-15 recite inducing exon skipping that read on instant claims 10 and 11.
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The difference of reference compounds and instant claimed compound of Formula I is thiophene ring vs pyrrole ring. Patani teaches S, O, N and CH are classical bioisosteres that could be used within ring system as ring equivalents (See page 3158). A skilled artisan would have known S, O, N and CH are classical bioisosteres which is also illustrated by R1 reciting phenyl and heteroaryl comprising heteroatoms N, O and S.
According to MPEP § 2144.09, A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. The instant application shares at least one common inventor /applicant with the reference patent. Furthermore, the instant application is not related to the reference patent based on the record, thus no 35 USC 121 shield exists.
Claims 1-5 and 10-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of copending Application No. 18/264,187 (reference application), in view of Patani et al. (Chemical Reviews, 1996. Vol. 96, 8: 3147-3176).
Reference claims are directed to method for inhibiting or ameliorating spinocerebellar ataxia type 3 (SCA3) in a subject in need thereof, comprising administering to said subject an effective amount of a compound of Formula (I). Reference claims 11-12 recite inducing exon skipping that read on instant claims 10 and 11.
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The difference of reference compounds and instant claimed compound of Formula I are the heteroatoms on the ring. A skilled artisan would have known S, O, N and CH are classical bioisosteres as taught by Patani, which is also illustrated by R1 reciting phenyl and heteroaryl comprising heteroatoms N, O and S.
According to MPEP § 2144.09, A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. The instant application shares at least one common inventor /applicant with the reference patent. Furthermore, the instant application is not related to the reference patent based on the record, thus no 35 USC 121 shield exists.
Conclusion
NO claims are allowed.
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/LIYUAN MOU/Examiner, Art Unit 1628
/JARED BARSKY/Primary Examiner, Art Unit 1628