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, 5-6, 10, 16, 20, 22, 25, 27, 31-32, 38, 40, 46, 52, 66, and 70-73 are currently pending and under examination on the merits in the instant application.
Claim Objections
Claim 6 is objected to because of the following informalities: “authophagy” should be “autophagy”. 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 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, 32, 40, and 71-73 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.
Claims 1 and 71-72 recite “(miRNA inhibitor).” It is unclear whether the parenthetical recitation is part of the claimed limitation. If “miRNA inhibitor” is a required limitation, it is noted that claims 1 and 71-72 are indefinite as each of the claims simultaneously recite the broad limitation “miRNA inhibitor” and the narrower limitation “a compound that inhibits miR-485” within the broad limitation. The claims are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language “a compound that inhibits miR-485” is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. 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).
Solely for examination purpose, “(miRNA inhibitor)” will not be taken into consideration. As such, “the miRNA inhibitor” recited in dependent claims, for instance, claim 6, will be interpreted as referring to “the compound”.
Claim 32 recites “an extracellular vesicle” and also simultaneously recites the narrower limitation “an exosome”. The claim also recites “a lipid nanoparticle” as well as multiple narrower limitations such as “liposome” and “lipoplex”. The claim also recites “a nanoparticle mimic” and also recites “a nanotube” that is the narrower limitation. The simultaneous recitations of multiple broader limitations and multiple narrower limitations render the metes and bounds of the claim indefinite.
Claim 40 recites “polyethylene glycol (PEG)” in “(a)”, see line 5, and also simultaneously recites a specific formula, “(formula I)” in “(b)” specifying n=1-1000 the ethylene glycol, which is the narrower, specific range of the “polyethylene glycol (PEG)” in “(a)”. Hence, it is unclear whether “formula I” in (b) is merely exemplary of “PEG” in (a) recited in the claim or is a required limitation.
Claim 40 recites “(formula I)” to refer to two different structures. Note that claim 40 depends from claim 38 thus inherently recites “(formula I)” in claim 38. It is unclear why the two different structures are identified by the same name.
Claim 73 recites “(bradykinesia)”, “(chorea)”, “(micrographia)”, and “(akinesia)”. It is unclear whether the parenthetical recitations are required limitations. If so, claim 73 simultaneously recites broad limitations as well as the aforementioned narrower limitations in parentheses thus is deemed indefinite. That is, “bradykinesia”, “chorea”, and “akinesia” are specific types of movement impairment within the genus of “reduction of spontaneous movement”, “involuntary movements”, and “delayed start of movement”, respectively, and “micrographia” is a specific type of handwriting disorder within the genus of “impaired handwriting”.
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 1, 5-6, 10, 16, 20, 22, 25, 27, 31-32, 38, 40, 46, 52, 66, and 70-73 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 factors to be considered when analyzing claims for compliance with the written description requirement include: (A) actual reduction to practice; (B) sufficient relevant identifying characteristics (e.g., complete structure, partial structure, physical and/or chemical properties, structure/function correlation); (C) level of skill and knowledge in the art; and (D) predictability in the art.
Each factor is analyzed below.
(A) actual reduction to practice
The instant specification does not provide a disclosure that shows that the instantly clamed Huntington’s disease (HD) treatment method in a subject in need thereof is achieved by the administration of a compound that inhibits miR-485, which improves HD symptoms including impairments in movement and speech. The instant specification at best discloses in vitro methods comprising using Q74 Htt-transfected cells.
(B) sufficient relevant identifying characteristics
The instantly claimed HD treatment method requires “a compound that inhibits miR-485”, which as broadly claimed reads on a compound that inhibits miR-485-5p as well as a compound that inhibits miR-485-3p. In fact, the “compound” is not limited to a nucleic acid-based compound as broadly written thus reads on a non-nucleic acid compound. Now, it appears that the instant specification at best supports a nucleic acid compound that inhibits miR-485-3p, not miR-485-5p. In addition, the “compound that inhibits miR-485” as broadly claimed reads on an oligonucleotide of any length including up to “about 30 nucleotides in length.” See claim 16. It is noted that the minimally required nucleotide sequence of SEQ ID NO:2 is 7 nucleotides in length, and the maximally required nucleotide sequence of SEQ ID NO:28 or SEQ ID NO:88 is 20 nucleotides in length. The instant specification is completely silent regarding the extra nucleotides for the oligonucleotide that is “about 30 nucleotides in length” when the about 30-mer oligonucleotide comprises the mere 7-mer sequence or the 20-mer sequence. That is, the specification does not identify a representative number of nucleotide sequence species for the remaining about 23 nucleotides when the about 30-mer oligonucleotide comprises SEQ ID NO:2, nor does it identify a representative number of nucleotide sequence species for the remaining about 10 nucleotides when the about 30-mer oligonucleotide comprises SEQ ID NO:28, in order for the about 30-mer oligonucleotide should function as a therapeutic compound in a patient suffering from HD. The instant specification does not reasonably convey that the instant co-inventors possessed the entire genus of “about 7 to about 30 nucleotides in length” functioning as an inhibitor of miR-485 (both miR-485-3p and miR-485-5p) in providing treatment for an HD patient since the specification at best describes an in vitro function of SEQ ID NO:28, which is 20 nucleotides in length targeting only miR-485-3p for upregulating autophagy and decreasing aggregated Htt in the Q74-Htt-trasfected cells such as HEK293T, PC12, NSC-34, and primary cortical neurons. See Examples 2-4. The in vitro-tested 20-mer sequence of SEQ ID NO:28 is not a representative number of “compound” species even if there were a perfect in vitro-in vivo correlation recognized in the art, because the 20-mer sequence that is fully complementary to the first 20-mer sequence (nucleotide positions 1-20) of the 22-mer human miR-485-3p known to have the nucleotide sequence of 5’-GUCAUACACGGCUCUCCUCUCU cannot represent the myriad of distinct oligonucleotide sequences within the claimed genus of “about 7 to about 30 nucleotides in length” having only “about 50%” sequence identity to SEQ ID NO:28, thereby encompassing various sequences having mismatches, nor does the single oligonucleotide sequence of SEQ ID NO:28 represent any type of “compound” that is not limited to an oligonucleotide compound but rather includes any compound including a small molecule, non-nucleic acid compound. As for the various SEQ ID NO species claimed in the instant case, it is noted that there is no adequate written description support for the required function of treating HD by SEQ ID NO:2, for instance, as such sequence was not explored even in vitro thus it remains unknown whether SEQ ID NO:2, a 7-mer sequence, is capable of inducing autophagy, neurogenesis, and neural stem cell survival in the HD patient, who is required to have improved motor symptom as a result of the compound administration.
Regarding claim 5 that expressly requires that HD should be associated with (a), (b), and/or (c), it is noted that the instant specification is deficient in providing the required correlation between HD and decrease levels of SIRT1, CD36, and PGC-1a as there is no adequate written description support for the required correlation. In fact, there is no experimental demonstration showing that HD brains have decrease levels of SIRT1, CD36, and PGC-1a as evidenced by the fact that HD brains are not even explored by the instant co-inventors.
Regarding claims 6 and 10 requiring various effects including increased synapse development by the miR-485 inhibitor, the instant specification, the instant specification does not provide adequate written description support that the only actually exemplified inhibitor, SEQ ID NO:28 that inhibits miR-485-3p has the required function recited in claims 6 and 10.
Regarding claims 38, 40, 46, 52, 66, and 70, it is noted that the claims as broadly written encompass a myriad of structurally diverse delivery agents, while the instant specification at best discloses a single structure comprising PEG, polylyine (PLL), and vitamin B3 (nicotinamide), further comprising phenylalanine as the targeting moiety. This single structure cannot whatsoever represent the entire genus of all structural variants of micelles having the function of delivering the claimed compound to the brain of a subject having HD with the required effects of inducing neurogenesis in the subject, especially in light of the fact that the instant specification does not even disclose in vivo data. That is, the use of the single micelle structure loaded with the anti-miR-485 antisense oligonucleotide tested in a cell line in vitro cannot represent the ability of other structures encompassed by “(formula I)” and “(formula II)” for providing in vivo delivery of the claimed compound to a subject having HD with a HD treatment effect (e.g., improvement in HD symptoms) in the subject. Hence, the instant specification fails to adequately describe the structure-function correlation for the entire genus of “(formula I)” and “(formula II)” as of the filing date sought in the instant application. For instance, the PEG that is claimed as “a water-soluble biopolymer moiety” (WP) in claim 40 is claimed to have 1,000 repeat units of ethylene glycol as recited in “(b)”, and there is no adequate written description support that the “PEG” included in the single exemplified delivery agent comprises 1,000 repeat units of ethylene glycol or the entire range of “1-1000” as claimed.
(C) level of skill and knowledge in the art
It is noted that the actual use of short (e.g., 7-9-mer), miRNA seed sequence-targeting antisense oligonucleotides for inhibiting target miRNA was strictly limited to “fully LNA-modified and phosphorothiolated oligonucleotides” as evidenced by Obad et al. (US 2018/0201928 A1, applicant’s citation), wherein the 7-mer oligonucleotide showed “lower potency compared to the 8-mer” in cells in vitro, and wherein the “8-mer LNA-antimiR” was tested and shown to upregulate target protein in the kidney of mice in vivo. See paragraphs 0356, 0369, and 0524. In the instant case, the specification fails to adequately describe that the generically claimed sequences including chemically unmodified “about 7”-mer sequences have the function of treating a patient having HD, especially when a 7-mer that is fully LNA- and phosphorothioate-modified oligonucleotide was known to provide “lower potency” in vitro than an 8-mer. That is, the length-dependent unpredictability in in vitro functionality for shorter, fully LNA/phosphorothioate-modified anti-miRNA oligonucleotides was known in the prior art, and the instant specification does not provide any adequate written description support for the required structure-function correlation for the entire genus of oligonucleotide sequences/lengths including the 7-mer sequence in treating HD in a subject in vivo.
Now, as expressly acknowledged on the record in the instant specification, the state of the relevant prior art pertaining the HD treatment, especially by administration of a short oligonucleotide targeting a miRNA, was not known and the HD treatment in general was known to be “unpredictable” and “difficult”. See paragraph 0005 of the specification for the following: “There is no cure for Huntington’s disease and no way to slow or stop the degeneration of brain cells associated with the disease…However, individual responses to different treatment methods are unpredictable and finding an effective treatment regimen is difficult and time consuming. As such, there is a need for effective treatment for Huntington’s disease.” (emphasis added).
Consistent with the aforementioned disclosure in the specification, the relevant knowledge prior to the effective filing date sought in the instant application, July 1, 2020, was such that there is only one therapeutic agent, tetrabenazine, that is available for treating HD patients in several countries as of 2019, despite years of attempts to provide HD therapeutic agents using various animal models of HD such as “3’-NP, QA, R6/2 and N171-82Q”, which thus highlights the high level of unpredictability in developing HD therapeutic agents having the real world use. See page 18 of Kumar et al. (Pathology, Prevention and Therapeutics of Neurodegenerative Disease, 2019, pages 197-206): “So far, a number of compounds have been thoroughly evaluated in HD subjects at different stages of the disease. Only one is now available in several countries, i.e., tetrabenazine. There is no possible explanation for discrepancies existing between preclinical and clinical trials. These discrepancies emphasize the complexity in predicting the usefulness of new drugs in humans based on animal models of HD. Therefore, a cooperation has been made in the field that a particular drug or agent with impending therapeutic effects needs a systematic assessment in more than one animal model,…Only afterwards, the selected compounds can be anticipated for use in clinical trials.” (emphasis added). In the instant case, the instant specification does not even contain any art-recognized HD animal model treated with a miR-485-3p inhibitor in spite of the fact that use of one HD animal model was deemed insufficient thus “more than one animal model” for assessing new HD therapeutic agents was deemed necessary for translating into human HD subjects as taught by Kumar, who reported numerous failures of various HD therapeutic agents in clinical applications, wherein such teaching is completely in line with the disclosure of paragraph 0005 of the instant specification. Taken together, it is clear that the examples restricted to the in vitro cells transfected with exogenous 74 glutamine (Q) repeats cannot adequately support the instantly claimed in vivo HD treatment method in a subject in need thereof.
Even more interestingly, both miR-485-3p targeted by the claimed oligonucleotides and miR-485-5p as encompassed by the broadly recited “miR-485” were known to be downregulated, not upregulated, in the brain samples (e.g., the frontal cortex and the striatum) of HD patients with a statistical significance as evidenced by Table 2 of Marti et al. (Nucleic Acids Research, 2010, 20:7219-7235, applicant’s citation). That is, further downregulating the already significantly downregulated miR-485-3p in the HD patient’s brain by the anti-miR-485-3p inhibitor would have been deemed counterintuitive from a scientific point of view because downregulation of miR-485-3p was known to be correlated with HD pathology in human subjects, which would thus reasonably suggest that upregulation of miR-485-3p, not inhibition of miR-485-3p, would be a scientifically reasonable approach for addressing the HD pathology in the brain of a human subject having HD. Indeed, there is no prior art that teaches that inhibition of miR-485-3p in the brain of HD patients having the significantly downregulated expression levels of miR-485-3p in the HD-affected brain areas is therapeutically useful for treating HD, nor does the instant specification adequately and sufficiently supports that the administration of a miR-485-3p inhibitor into the brain of an HD patient having the already reduced miR-485-3p levels results in the treatment of the HD patient.
Regarding claims 6 and 10 requiring various effects including increased synapse development by the miR-485 inhibitor, wherein SEQ ID NO:28 that inhibits miR-485-3p is the only actually synthesized inhibitor sequence disclosed in the instant specification, the relevant prior art was such that an inhibitor of miR-485-5p, not miR-485-3p inhibited by SEQ ID NO:28 or all other SEQ ID NOs recited in claims 16, 20, 22, and 25, has the function of increasing synaptogenesis as evidenced by Cohen et al. (PNAS, 2011, 108:11650-11655, applicant’s citation). Note that Cohen teaches using “a miR-485 inhibitor” referred to as “miR-I” in order “to promote regeneration and synaptogenesis.” See pages 11651 and 11654. Note that Cohen discloses the nucleotide sequence of miR-485 as 5’-AGAGGCUGGCCGUGAUGAAUUC. See Figure S1C of Supporting Information attached herewith. It is prima facie apparent that the complementary sequence to the disclosed miR-485 nucleotide sequence is 5’-GAAUUCAUCACGGCCAGCCUCU, which has no similarity to any of the SEQ ID NOs claimed in the instant case, which is consistent with the scientific fact that miR-485-5p targeted by Cohen for increasing synaptogenesis is distinct and different from miR-485-3p targeted by the instant application’s SEQ ID NO:28, which is not shown to provide the required effects including increased synapse development.
(D) predictability in the art
As noted above, the instant specification expressly acknowledges on the record that HD treatment was considered “unpredictable” and “difficult” (see paragraph 0005) further corroborated by relevant artisans as evidenced by Kumar et al. (Pathology, Prevention and Therapeutics of Neurodegenerative Disease, 2019, pages 197-206) as explained above. Hence, one of ordinary skill in the relevant art would reasonably consider that the level of predictability of success in practicing the claimed HD treatment method comprising administering an inhibitor of miR-485 would be substantially low, especially in view of the lack of appropriate HD animal model studies, wherein Kumar expressly taught that a new therapeutic compound needs to be assessed in at least two HD animal studies given the “complexity” and “discrepancies” in experimental results and the actual translation to clinical use of a compound designed for HD treatment. See page 18 teaching that “discrepancies emphasize the complexity in predicting the usefulness of new drugs in humans based on animal models of HD” (emphasis added).
In view of the totality of the factors analyzed above, it is concluded that the instant specification fails to reasonably convey that the instant co-inventors completed and had possession of the HD treatment method of claims 1, 5-6, 10, 16, 20, 22, 25, 27, 31-32, 38, 40, 46, 52, 66, and 70-73 as of the filing date sought in the instant application.
Claims 1, 5-6, 10, 16, 20, 22, 25, 27, 31-32, 38, 40, 46, 52, 66, and 70-73 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.
The factors to be considered in determining whether undue experimentation is required are summarized In re Wands, 858 F.2d 731,737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). The Court in Wands states: “Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is ‘undue’, not ‘experimentation’.” (Wands, 8 USPQ2d 1404). 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.” These factors include: (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.
Each factor is analyzed below.
(A) The breadth of the claims
The instant claims are broadly drawn to treating an HD subject comprising administering an inhibitor of miR-485, wherein the treatment method encompasses reducing HD pathology and improving HD symptoms in the HD subject and the inhibitor of miR-485 encompasses a variety of chemical compounds that inhibit either or both of miR-485-5p and miR-485-3p.
(B) The nature of the invention
The claimed subject matter is strictly directed to an in vivo therapeutic method that must result in a treatment of a subject suffering from HD comprising administering a compound that was not known to have the instantly claimed HD treatment function before the effective filing date sought in the instant application.
(C) The state of the prior art
There is no relevant prior art that actually demonstrates that a compound that inhibits miR-485 results in the treatment of an HD subject. In fact, it is expressly acknowledged on the record in the instant specification that the state of the relevant prior art pertaining to HD treatment was in its infancy and the instantly claimed anti-miR-485 compound-based method was not known/practiced. See paragraph 0005 of the specification for the following: “There is no cure for Huntington’s disease and no way to slow or stop the degeneration of brain cells associated with the disease…However, individual responses to different treatment methods are unpredictable and finding an effective treatment regimen is difficult and time consuming. As such, there is a need for effective treatment for Huntington’s disease.” (emphasis added).
(D) The level of one of ordinary skill
The instantly claimed method that requires treatment of an HD subject by inhibiting miR-485 in the subject was not known in the art. Furthermore, HD therapy itself was deemed unsuccessful, unpredictable, and difficult and the use of a miRNA inhibitor for HD treatment was not known as evidenced by the instant specification’s disclosure (see paragraph 0005) and the teachings of Kumar et al. (Pathology, Prevention and Therapeutics of Neurodegenerative Disease, 2019, pages 197-206), which are explained in detail in the written description rejection above, which is fully incorporated by reference herein. Hence, the requisite level of one of ordinary skill in the relevant art pertaining to the instantly claimed miR-485 inhibitor-based HD treatment method would have been deemed nonexistent and insufficient.
(E) The level of predictability in the art
The teachings of the instant specification and the relevant prior art do clearly establish that the claimed HD treatment method in a subject in need thereof was deemed highly “unpredictable” as explained in the written description rejection above, which is fully incorporated by reference herein.
(F) The amount of direction provided by the inventor
The instantly claimed subject matter is entirely described in a merely prophetic, generic manner in the instant specification. Hence, the instant specification contains insufficient guidance/direction pertaining to the instantly claimed in vivo method performed in an HD subject comprising administering a compound that inhibits miR-485.
(G) The existence of working examples
The instant specification discloses in vitro working examples in which cells are transfected with Q74 Htt and SEQ ID NO:28. The specification does not disclose any in vivo working example commensurate in scope with the instant claims.
(H) The quantity of experimentation
Since neither the instant specification nor the relevant prior art provides adequate, sufficient teachings pertaining to the required therapeutic function of a compound that inhibits miR-485 including SEQ ID NO:28 in an HD subject, the quantity of experimentation necessary to practice the instantly claimed in vivo method in an HD subject would be undue.
In view of the totality of the factors (A)-(H) analyzed above, it is concluded that the instant specification fails to provide an enabling disclosure commensurate in scope with the instant claims.
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.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 5-6, 10, 16, 20, 22, 25, 27, 31-32, 66, and 71-73 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11,542,503 B2 in view of Roth (Pathology, Prevention and Therapeutics of Neurodegenerative Disease, 2019, pages 117-131).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are encompassed by and/or rendered obvious over the ‘503 patent claims drawn to a method of treating a brain disease including “mental retardation” in a subject in need thereof comprising administering a chemically modified miR-485-3p inhibitor complementary to SEQ ID NO:1. It would have been obvious to envisage the subject treated for mental retardation in the ‘503 patent claims reads on a subject having HD as evidenced by the fact that HD patients were known to have “mental retardation” as taught by Roth. See page 124. Since all of the instantly recited active method steps are fully satisfied by the ‘503 patent claims for a subject having mental retardation that is a symptom of HD, it necessarily follows that the method of the ‘503 patent claims performed in an HD subject would inherently result in all of the results recited in the instant claims, absent objective evidence to the contrary.
Claims 1, 5-6, 10, 16, 20, 22, 25, 27, 31-32, 38, 40, 46, 52, 66, and 70-73 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 78 and 84-86 of copending Application No. 17/622,518 in view of Roth (Pathology, Prevention and Therapeutics of Neurodegenerative Disease, 2019, pages 117-131).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are encompassed by and/or rendered obvious over the ‘518 claims drawn to a method of treating a neurodegenerative condition comprising administering a micelle comprising “a nucleic acid” and the cationic carrier unit, wherein the cationic carrier unit of the ‘518 claims is patentably indistinguishable from the instantly claimed carrier, wherein the “nucleic acid” as broadly claimed in the ‘518 claims is defined to read on “an antisense oligonucleotide payload targeting miR-485-3p” comprising SEQ ID NO:18 (5’-AGAGAGGAGAGCCGUGUAUGAC). See paragraph 0158. It would have been obvious to envisage the subject treated for mental retardation in the ‘518 claims reads on a subject having HD as evidenced by the fact that HD “is a dominantly inherited autosomal neuropsychiatric degenerative disease” as taught by Roth. See page 117. Since all of the instantly recited active method steps are fully satisfied by the ‘518 claims for a subject having a neurodegenerative disease that is HD, it necessarily follows that the method of the ‘518 claims performed in an HD subject would inherently result in all of the results recited in the instant claims, absent objective evidence to the contrary.
Claims 1, 5-6, 10, 16, 20, 22, 25, 27, 31-32, 38, 40, 46, 52, 66, and 70-73 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 29, 33, 48, 52, 54, 59, 63-64, 70, 72, 48, 84, 93, 106, and 108-110 of copending Application No. 17/760,343 in view of Roth (Pathology, Prevention and Therapeutics of Neurodegenerative Disease, 2019, pages 117-131).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are encompassed by and/or rendered obvious over the ‘343 claims drawn to a method comprising administering to a subject in need thereof a compound that inhibits miR-485 in a cationic carrier unit, wherein the cationic carrier unit of the ‘343 claims is patentably indistinguishable from the instantly claimed carrier. It would have been obvious to envisage the “subject in need thereof” recited in the ‘343 claims reads on the HD subject claimed in the instant case because the subject treated in the ‘343 claims has a disease associated with abnormal expression levels of SIRT1, CD36, and PGC-1a as claimed in the instant application, thereby clearly establishing that the “subject” being treated in the ‘343 claims is patentably indistinguishable from the subject being treated in the instant claims, absent objective evidence to the contrary. In addition, the subject having “mental retardation” as claimed in claim 102 reads on an HD subject as evidenced by Roth’s teaching. See page 124. Since all of the instantly recited active method steps are fully satisfied by the ‘343 claims for a subject having a disease associated with mental retardation and abnormal expression levels of SIRT1, CD36, and PGC-1a, it necessarily follows that the method of the ‘343 claims would inherently result in all of the results recited in the instant claims, absent objective evidence to the contrary.
Claims 1, 5-6, 10, 16, 20, 22, 25, 27, 31-32, 38, 40, 46, 52, 66, and 70-73 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 6-8, 12-13, 15, 18, 22, 24, 33-35, 40, 67, 73-74, and 77 of copending Application No. 17/906,174 in view of Roth (Pathology, Prevention and Therapeutics of Neurodegenerative Disease, 2019, pages 117-131).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are encompassed by and/or rendered obvious over the ‘174 claims drawn to a method of treating a subject having “mental retardation” comprising administering a compound that inhibits miR-485 in a cationic carrier unit, wherein the cationic carrier unit of the ‘174 claims is patentably indistinguishable from the instantly claimed carrier. It would have been obvious to envisage the subject treated for mental retardation in the ‘174 claims reads on a subject having HD as evidenced by the fact that HD patients were known to have “mental retardation” as taught by Roth. See page 124. Since all of the instantly recited active method steps are fully satisfied by the ‘174 claims for a subject having mental retardation that is a symptom of HD, it necessarily follows that the method of the ‘174 claims performed in an HD subject would inherently result in all of the results recited in the instant claims, absent objective evidence to the contrary.
Claims 1, 5-6, 10, 16, 20, 22, 25, 27, 31-32, 38, 40, 46, 52, 66, and 70-73 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 6-8, 12-13, 15, 18, 22, 24, 33-35, 40, 67, 73-74, and 77 of copending Application No. 17/906,175 in view of Roth (Pathology, Prevention and Therapeutics of Neurodegenerative Disease, 2019, pages 117-131).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are encompassed by and/or rendered obvious over the ‘175 claims drawn to a method of treating a subject comprising administering a compound that inhibits miR-485 in a cationic carrier unit, wherein the cationic carrier unit of the ‘175 claims is patentably indistinguishable from the instantly claimed carrier. It would have been obvious to envisage the subject treated for mental retardation in the ‘175 claims reads on a subject having HD as evidenced by the fact that HD patients were known to have “mental retardation” as taught by Roth. See page 124. Since all of the instantly recited active method steps are fully satisfied by the ‘175 claims for a subject having mental retardation that is a symptom of HD, it necessarily follows that the method of the ‘175 claims performed in an HD subject would inherently result in all of the results recited in the instant claims, absent objective evidence to the contrary.
Claims 1, 5-6, 10, 16, 20, 22, 25, 27, 31-32, 38, 40, 46, 52, 66, and 70-73 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 12-13, 47-48, 50, 64, 66, and 71 of copending Application No. 17/997,000 in view of Roth (Pathology, Prevention and Therapeutics of Neurodegenerative Disease, 2019, pages 117-131).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are encompassed by and/or rendered obvious over the ‘000 claims drawn to a method of treating a cognitive disorder in a subject in need thereof comprising administering a compound that inhibits miR-485 in a cationic carrier unit, wherein the cationic carrier unit of the ‘000 claims is patentably indistinguishable from the instantly claimed carrier. It would have been obvious to envisage the “subject” in need of treatment for cognitive disorder in the ‘000 claims reads on a subject having HD as evidenced by the fact that HD patients were known to have cognitive deficits as taught by Roth. See page 123. Since all of the instantly recited active method steps are fully satisfied by the ‘000 claims for a subject having cognitive disorder that is a symptom of HD, it necessarily follows that the method of the ‘000 claims performed in an HD subject would inherently result in all of the results recited in the instant claims, absent objective evidence to the contrary.
Claims 1, 5-6, 10, 16, 20, 22, 25, 27, 31-32, 66, and 71-73 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 45-46 of copending Application No. 18/145,352 in view of Roth (Pathology, Prevention and Therapeutics of Neurodegenerative Disease, 2019, pages 117-131).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are encompassed by and/or rendered obvious over the ‘352 claims drawn to a method of treating a neurodegenerative disorder in a subject in need thereof comprising administering the EV of claim 1. Although the EV of claim 1 of the ‘352 application does not expressly recite comprising SEQ ID NO:23 recited in claim 16 of the ‘352 application (identical to SEQ ID NO:28 claimed in the instant case), it would have been obvious to any person of ordinary skill in the art that the treatment method claims of the ‘352 application must comprise the active therapeutic agent within the EV in order to practice the method. It would have been obvious to envisage the subject treated for mental retardation in the ‘518 claims reads on a subject having HD as evidenced by the fact that HD “is a dominantly inherited autosomal neuropsychiatric degenerative disease” as taught by Roth. See page 117. Since all of the instantly recited active method steps are fully satisfied by the ‘352 claims for a subject having a neurodegenerative disease that is HD, it necessarily follows that the method of the ‘352 claims performed in an HD subject would inherently result in all of the results recited in the instant claims, absent objective evidence to the contrary.
Claims 1, 5-6, 10, 16, 20, 22, 25, 27, 31-32, 38, 40, 46, 52, 66, and 70-73 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 103-108 of copending Application No. 18/881,645 in view of Roth (Pathology, Prevention and Therapeutics of Neurodegenerative Disease, 2019, pages 117-131).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are encompassed by and/or rendered obvious over the ‘645 claim drawn to a method of treating a neurodegenerative disease comprising administering a micelle comprising a cationic carrier moiety and an anionic payload, wherein the cationic carrier moiety of the ‘645 application appears patentably indistinguishable from the instantly claimed cationic carrier. Regarding the “anionic payload” as broadly claimed, it is noted that the ‘645 specification expressly discloses that the payload is an “antimir” “targeting hsa-miR-485”. See paragraph 0278. It would have been obvious to envisage the subject treated for a neurodegenerative disease in the ‘645 claims reads on a subject having HD as evidenced by the fact that HD “is a dominantly inherited autosomal neuropsychiatric degenerative disease” as taught by Roth. See page 117. Since all of the instantly recited active method steps are fully satisfied by the ‘645 claims for a subject having a neurodegenerative disease that is HD, it necessarily follows that the method of the ‘645 claims performed in an HD subject would inherently result in all of the results recited in the instant claims, absent objective evidence to the contrary.
Conclusion
No claim is allowed.
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/DANA H SHIN/Primary Examiner, Art Unit 1635