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 .
Election/Restrictions
Claim 2 is directed to an allowable product. Pursuant to the procedures set forth in MPEP § 821.04(B), claims 79-80, 86-87, 91 and 93, directed to the process of making or using an allowable product, previously withdrawn from consideration as a result of a restriction requirement, are hereby rejoined and fully examined for patentability under 37 CFR 1.104.
Because all claims previously withdrawn from consideration under 37 CFR 1.142 have been rejoined, the restriction requirement as set forth in the Office action mailed on 8/7/25 is hereby withdrawn. In view of the withdrawal of the restriction requirement as to the rejoined inventions, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Specification
The use of the term GENBANK, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. Please review entire specification for any other names or marks.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
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.
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 80, 86-87, 91 and 93 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claimed invention embraces treating or preventing an ATXN2-associated disease in a subject in need thereof using a therapeutically effective amount of the dsRNA of claim 2.
In addition, the claimed method embraces a step of using an additional agent or therapy suitable for preventing of an ATXN2-associated disease or disorder (claim 87). Paragraph 90 of the specification provides a list of agents, but a search of the prior art shows that none of these agents are known to be suitable for preventing an ATXN2-associated disease or disorder.
The specification discloses that reducing ATXN2 expression in the brain of the subject could lead to treatment of spinocerebellar ataxia (SCAs). Pages 1 and 46-49 of the specification disclose diseases or disorders. Page 4 of the specification discloses that there are no known cures for and treatment options are limited. Page 48 contemplates “therapeutically effective amount’ but does not disclose any actual amounts that are considered therapeutic for treating or preventing an ATXN2-associated neurodegeneration disease.
Costa et al. (Cell Death and Disease, 15:415, pages 1-14, 2024) disclose a CAG repeat sequence in the ATNX2 gene encodes a polyglutamine (polyQ) tract within the ATXN2 protein.
Claims 80, 91, and 93 embrace preventing the development of an ATXN2-associated neurodegenerative disease in a subject and/or a subject meeting at least one diagnostic criterion for the disease. The claimed method embraces spinocerebellar ataxia 2 (SCA2), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS). Page 46 of the specification discloses clinical features of the ATXN2-associated neurodegenerative disorders. Other than an expanded polyglutamine tract for SCA2, the specification does not appear to describe any criterion for this limitation required in the claimed method. If the subject had any of these clinical features associated with the disorders, then preventing the development of the disease would not be possible because the subject would already have the disease.
Item (e) of claim 80 and claim 93 disclose the subject being diagnosed with an ATXN2-associated disease. Claim 93 is dependent on claim 91, which is directed to preventing development of an ATXN2 associated neurodegenerative disease. Item (b) of claim 93 limits the disease to a neurodegenerative disease, but item (a) is broader and embraces any ATXN-2 disease, including neurodegenerative as described on page 46 of the specification. The specification does not appear to contemplate or describe any disease associated with ATXN2 that is not a neurodegenerative disease.
With respect to the limitation ‘the subject has been diagnosed with an ATNX2 associated disease’ as recited in the instant claims (item (d) in claim 80 and claim 93), the specification does not provide sufficient description of a subject diagnosed with at least one criterion for an ATXN2-associated disease other than an expanded polyglutamine tract in a subject having SCA2. While the specification contemplates the method and discloses species of ATXN2-neurodegenerative diseases (see page 46), the specification does not describe what criterion other than an expanded polyglutamine tract in SCA2 are considered criterion for a genus of ATXN2 associated diseases. Costa (supra) teaches that while a subject could meet at least one criterion for the disease (e.g., ALS, PD), it does not indicate that the subject will develop the disease. The art teaches whether these expansions are cytotoxic or neuroprotective is still a matter of debate (Costa, page 1-2). In view of the limited description in the specification of the instant disclosure and the current state of the art (Costa), the written description requirement for a claimed genus of diagnostic criterion for an ATXN2-associated disease is not satisfied through sufficient description of a representative number of species. As shown by Costa, there is a substantial variation within the species of expansion of polyQ in ATXN2-associated neurodegenerative diseases and a subject having the neurodegenerative disease and the specification does not describe a sufficient variety of species to reflect the variation within the genus of diagnostic criterion for an ATXN2-associated disease. See Enzo Biochem., 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004)(“[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.”). See also MPEP §2163.
In view of the foregoing, it is clear that the specification of the instant disclosure fails to convey to the skilled artisan that the applicant had possession of the claimed invention as of the effective filing date.
Claims 79-80, 86-87, 91 and 93 are 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 amelioration of an ATXN2-associated neurodegeneration disease in a subject in need thereof using direct administration of the dsRNA of claim 2 to the brain of the subject, wherein the disease is spinocerebellar ataxia (SCA), does not reasonably provide enablement for preventing an ATXN2-associated neurodegenerative disease in a subject in need thereof using the dsRNA of claim 2. 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.
The claimed invention embraces treating or preventing an ATXN2-associated disease in a subject in need thereof using a therapeutically effective amount of the dsRNA of claim 2. In addition, the claimed method embraces a step of using an additional agent or therapy suitable for preventing of an ATXN2-associated disease or disorder.
The specification (pages 1-4) and prior art of record (Scoles, Nature 2017 544, 362-366) cited on an IDS) and currently (Costa, Cell Death and Disease,15; 2024, pages 1-14) teach that ATXN2 contains a polyglutamine tract usually contains 22-glutamine tract. Long expansions (greater than 33 repeats) result in SCA2. Intermediate-length expansion (27-33 glutamines) contribute to susceptibility to amyotrophic lateral sclerosis (ALS) and Parkinson Disease (PD). ATXN2 has also been associated with SCA3, obesity and diabetes. Down-regulation of ATXN2 appears to result in cell metabolism disorders, including obesity and diabetes.
The specification provides working examples in cells lines and mice expressing hATXN2-IRES-gLuc constructs or in human mutant ATXN2-expressing mice.
The specification teaches using i.v. administration in wild-type mice to study expression of ATNX2 in the mice; intracerebroventricularly in a murine model of an ATXN2-associated neurodegeneration disease; and also contemplates using any route of administration for use in the methods. The specification does not provide a working of preventing an ATXN2 disease or disorder in a subject in need thereof or using a genus of routes of administration to deliver the dsRNA to the brain of a subject.
In view of the prior art (and currently) and the teaching in the as-filed specification, the claimed methods are only enabled for treating SCA2 in a subject using the claimed ATXN2-siRNA.
The claimed method embraces a large number of ATXN2-associated neurodegenerative diseases (see for example figure 4 of Costa). SCA2 is an incurable disease. In addition, a search of the prior art does not result in any known therapy or treatment that can prevent ATXN2-associated disease or disorder.
Also, the specification does not teach any therapy or agent that can be used to prevent the disease or disorder as set forth in item (h) in claim 87.
With respect to item (c) in claim 87, the specification and prior art of record do not teach ameliorating at least one sign or symptom or preventing progression of blindness.
The specification does not enable treating a genus of ATXN2 associated(neurodegenerative)-disease, including steps (a), (b), (c), and (h) in instant claim 87.
With respect to claims 79 and 80 directed to maintaining the cell produced in step (a) for a time sufficient to obtain degradation of the mRNA transcript of the ATXN2 gene, thereby inhibiting expression of the ATNX2 gene in the cell. The claimed method broadly reads on a cell in vitro or in vivo. Neither the specification or the art of record teach how to carry out step (b) when the cell is within a subject. It is not apparent how to maintain a cell in a subject since maintain would embrace using cell culture conditions or cell-culturing steps to maintain the cells.
With respect to instant claims 91 and 93, while the prior art teaches at least one criterion for ATXN2-associated neurodegenerative disease (expanded repeat of polyglutamine tract), the specification does not appear to teach any other criterion for a genus ATXN-2 associated disease. Costa (supra) teaches that while a subject could meet at least one criterion for a neurodegenerative disease (e.g., ALS, PD), it does not indicate that the subject will develop the disease. Whether these expansions are cytotoxic or neuroprotective is still a matter of debate (Costa, page 1-2). Thus, a skilled artisan could not reasonably determine or predict if administering the dsRNA of instant claim 2 resulted in preventing development of the disease or the subject never developed for another reason.
Instant claim 93 discloses that the subject being diagnosed with an ATXN2-associated disease, but is dependent on claim 91 directed to preventing development of an ATXN2 associated neurodegenerative disease. Item (b) of claim 93 limits the disease to a neurodegenerative disease, but item (a) is broader and embraces any ATXN-2 disease, including neurodegenerative. The specification does not appear to teach a genus of diseases associated with ATXN2 that is not a neurodegenerative disease and how diagnosing a subject with an ATNX2-associated disease who does not have an ATXN2 neurodegenerative disease can be used in the claimed method.
Furthermore, other than contemplating the methods and providing limited examples of reducing ATXN2 expression in cell lines or mice, the specification of the application does not disclose how to use the full scope of the claimed invention without an undue amount of experimentation. See Genentech Inc. v. Novo Nordisk A/S (CAFC) 42 USPQ2d 1001 clearly states: "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. See Brenner v. Manson, 383 U.S. 519, 536, 148 USPQ 689, 696 (1966) (stating, in context of the utility requirement, that "a patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.") Tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention." Thus, in view of the reasons set forth above, it would take an undue amount of experimentation for one of skill in the art to practice the full scope of the claimed invention.
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 80, 87 and 93 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.
Regarding claim 80(87,93), the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Allowable Subject Matter
Claims 2, 3, 5-9, 12, 14, 76, and 98-100 are in condition for allowance because the prior art does not teach or suggest the dsRNA of claim 2. In addition, the specification shows that one of skill in the art can use the dsRNA to reduce ATXN2 in a cell expressing ATXN2. See pages 185-281 of the as-filed specification.
Conclusion
See attached PTO-326 for disposition of claims.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brian Whiteman whose telephone number is (571)272-0764. The examiner can normally be reached on Monday thru Friday; 6:00 AM to 3:00PM.
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/BRIAN WHITEMAN/ Primary Examiner, Art Unit 1636
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