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
Applicant’s election, without traverse, of Group IV, claims 42-43 and 52-67, drawn to a method of treating or preventing optic neuropathy, or preserving RGC function by administering an rAAV comprising a human SIRT1, in the reply filed on 12/21/2024 is acknowledged.
Furthermore, claims 1-5, 8, 13, 17-18, 26-30, 33, 38 and 51 have been canceled, claims 42-43 and 52 have been amended and claims 53-67 have been newly added.
Claim Status
Claims 42-43 and 52-67 are pending and are considered on the merits.
Priority
The instant application was filed 11/08/2023 and is a DIV of application 16/607,834 (filed on 10/24/2019), which is a 371 of PCT/US2018/029167 (filed 04/24/2018) and claims priority to provisional application 62/488,989 (filed 04/24/2017).
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows: The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, provisional Application No. 62/488,989, fails to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for one or more claims of this application. Review of the application No. 62/488,989 did not reveal support for the promoter sequence comprising a human gamma-synuclein gene promoter sequence cited in new claims 56-58 and 64-66. Searching of application No. 62/488,989 did not reveal the recitation of a human gamma-synuclein gene promoter sequence or nucleotides 1433-2362 of SEQ ID NO: 28. Thus the instant claims 42-43, 52-55, 59-63 and 67 are being given the filing date of 04/24/2017 from application 62/488,989, and claims 56-58 and 64-66 are being given the filing date of 04/24/2018 from PCT/US2018/029167.
Claim Objections
Claims 58-60 and 66-67 are objected to because of the following informalities:
Applicant is advised that should claims 57 and 65 be found allowable, claims 58 and 66 will be objected to under 37 CFR 1.75 as being a duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 706.03(k).
Claims 59 and 67 comprise typographical errors. Specifically, “glaucoma” is recited twice in line 2, and “tramautic” is recited in line 4, which should be “traumatic”.
Claim 60 recites “the eye of the subject” in lines 2-3. Since the base claim 52 only recites “administering to the subject” but is silent on administering to an eye, it is recommended to change this phrase to “an eye of the subject”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
(Scope of Enablement)
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 42-43 and 53-59 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 a method of treating optic neuropathy in a subject in need thereof by administering to an eye of the subject a recombinant AAV comprising human SIRT1 (Specification, p. 43, para 2 and Example 5), does not reasonably provide enablement for a method of preventing optic neuropathy in a subject in need thereof by administering to an eye of the subject a recombinant AAV comprising human SIRT1. 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 factors to be considered in determining whether undue experimentation is required are summarized In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). The Court in Wands states: “Enablement is not precluded by the necessity for some 'experimentation.'” Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single simple factual determination, but rather is a conclusion reached by weighing many factual considerations.” (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount or direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. While all of these factors are considered, a sufficient amount for a prima facie case is discussed below.
The office has analyzed the specification in direct accordance to the factors outlined in In re Wands. MPEP 2164.04 states: "[W]hile the analysis and conclusion of a lack of enablement are based on factors discussed in MPEP 2164.01(a) and the evidence as whole, it is not necessary to discuss each factor in written enablement rejection." These factors will be analyzed, in turn, to demonstrate that one of ordinary skill in the art would have had to perform "undue experimentation" to make and/or use the invention and therefore, Applicant's claims are not enabled commensurate with the scope of the invention.
SCOPE OF THE INVENTION
The breadth of the claims encompasses a genus of method of preventing any optic neuropathy caused by any condition or disorder in a subject by administering to an eye of the subject a recombinant AAV comprising human SIRT1.
As discussed supra, the specification fails to describe the genus of methods of preventing optic neuropathy. The specification only discloses and provides guidance for a method of treating optic neuropathy in a subject in need thereof by administering to an eye of the subject a recombinant AAV comprising human SIRT1 (Specification, p. 43, para 2 and Example 5).
Independent claim 42 encompasses a genus of method of preventing any optic neuropathy caused by any condition or disorder in a subject by administering to an eye of the subject a recombinant AAV comprising human SIRT1, while the specification only discloses a method of treating optic neuropathy in a subject in need thereof by administering to an eye of the subject a recombinant AAV comprising human SIRT1 (Specification, p. 43, para 2 and Example 5).
Dependent claims 43 and 53-59 encompass the dose, the capsid, the promoter, the ITRs of the AAV, and a list of conditions/disorders causing the optic neuropathy.
ACTUAL REDUCTION TO PRACTICE
The specification does not provide guidance for or a working example for a method for preventing any optic neuropathy caused by any condition or disorder in a subject by administering to an eye of the subject a recombinant AAV comprising human SIRT1. The absence of working examples directed to a method of preventing optic neuropathy by AAV-hSIRT1 necessitates further experimentation. Therefore, the specification does not provide sufficient guidance on how to make and use the claimed genus of methods for preventing optic neuropathy.
In regard to claim 42 encompassing a genus of method of preventing any optic neuropathy caused by any condition or disorder in a subject by administering to an eye of the subject a recombinant AAV comprising human SIRT1, the specification only discloses a method of treating optic neuropathy in a subject in need thereof by administering to an eye of the subject a recombinant AAV comprising human SIRT1 (Specification, p. 43, para 2 and Example 5).
In regard to claims 43 and 53-59 encompassing the dose, the capsid, the promoter, the ITRs of the AAV, and a list of conditions/disorders causing the optic neuropathy, the specification only discloses a method of treating optic neuropathy.
STATE OF THE ART & QUANTITY OF EXPERIMENTATION
In fact, the state of the art teaches that a method for preventing any optic neuropathy caused by any condition or disorder in a subject by administering to an eye of the subject a recombinant AAV comprising human SIRT1, is not a highly successful technique or has highly variable results. For example, Behbehani (Clinical Ophthalmology. 2007;1(3): 233-246) teaches there are multiple causes for optic neuropathy (see abstract, supported by the instant claim 59 reciting a list of conditions/disorders causing the optic neuropathy). One of ordinary skill in the art would have appreciated that some of the causes, such as traumatic, tumoral, toxic/nutritional or hereditary causes, could not have been prevented by AAV-hSIRT1 administration to an eye of the subject. Furthermore, Behbehani teaches non-arteritic ischemic optic neuropathy (NAION) has been linked to the sleep apnea syndrome, but it is unknown whether treatment of sleep apnea can prevent NAION (p. 237, right col, para 2), suggesting preventing optic neuropathy is highly unpredictable even if there is a causative factor.
Consequently, there is ample reason to conclude that there would be a high degree of unpredictability in preventing any optic neuropathy caused by any condition or disorder in a subject by administering to an eye of the subject a recombinant AAV comprising human SIRT1 as claimed in the instant invention.
Since the prior art did not provide guidance for preventing any optic neuropathy caused by any condition or disorder in a subject by administering to an eye of the subject a recombinant AAV comprising human SIRT1, it is incumbent upon the instant specification to do so. The physiological art is recognized as unpredictable (MPEP 2164.03). As set forth in In re Fisher, 166 USPQ 18 (CCPA 1970), compliance with 35 USC 112, first paragraph requires: “That scope of claims must bear a reasonable correlation to scope of enablement provided by specification to persons of ordinary skill in the art; in cases involving predictable factors, such as mechanical or electrical elements, a single embodiment provides broad enablement in the sense that, once imagined, other embodiments can be made without difficulty and their performance characteristics predicted by resort to known scientific laws; in cases involving unpredictable factors, such as most chemical reactions and physiological activity, scope of enablement varies inversely with degree of unpredictability of factors involved.” Moreover, the courts have also stated that reasonable correlation must exist between scope of exclusive right to patent application and scope of enablement set forth in the patent application (27 USPQ2d 1662 Ex parte Maize!.). In view of the foregoing, due to the lack of sufficient guidance provided by the specification regarding the issues set forth above, the state of the relevant art, and the breadth of the claims, it would have required undue experimentation for one skilled in the art to use the instant broadly claimed invention.
CONCLUSION
In conclusion, since the art teaches that the method for preventing optic neuropathy is prone to influence by multiple factors, and is highly unpredictable, and the specification does not provide ample guidance with respect to achieving prevention of optic neuropathy by administering an AAV-hSIRT1, one would be burdened with undue experimentation to use the claimed invention for preventing any optic neuropathy caused by any condition or disorder in a subject by administering to an eye of the subject a recombinant AAV comprising human SIRT1.
In conclusion, given the breadth of the claims and the limited scope of the specification, an undue quantity of experimentation is required to use the invention beyond the scope of treating optic neuropathy in a subject in need thereof by administering to an eye of the subject a recombinant AAV comprising human SIRT1.
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.
Claim 67 is 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 67 recites “the optic neuropathy” in line 1. There is insufficient antecedent basis for this limitation because the base claim 52 does not recite an optic neuropathy.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 42-43, 52-55, 59-63 and 67 are rejected under 35 U.S.C. 103 as being unpatentable over Zuo et al (Invest Ophthalmol Vis Sci. 2013; 54: 5097–5102, cited in IDS 11/08/2023) in view of Hauswirth et al. (Human Gene Therapy. 2008, 19: 979-990), Jacobson et al. (Molecular Therapy. 2006; 13(6): 1074-1084) and Bosch Tubert et al (US20160354489A1, cited in IDS 11/08/2023).
With respect to independent claims 42 and 52, Zuo teaches a method of treating optic neuropathy in a mouse model by overexpressing SIRT1 to promote RGC survival and to delay its loss of function (abstract), thus teaches preambles of claims 42 and 52.
In regard to SIRT1 gene therapy in the eyes of the mouse model, Zuo teaches overexpressing SIRT1 gene in the mouse eyes by recombining a SIRT1 gene into mouse beta-actin locus (page 5097, last para, line 3, also see Fig 2A&2B for SIRT1 overexpression in retina) prevents RGC loss (see Fig 3) and attenuates loss of RGC function (see Fig 4A). Zuo teaches this neuroprotection is dependent on SIRT1 expression in neurons as SIRT activator resveratrol fails to prevent RGC loss in homozygous neuron-specific SIRT1-KO mouse eyes that underwent optic nerve crush (Fig 3A, page 5099, col 2, para 1, last 5 lines). Thus, Zuo teaches a SIRT1 gene sequence can be engineered to be overexpressed in the eyes for treating optic neuropathy and to preserve RGC function in a mouse model.
However, Zuo is silent on administering to the eye a recombinant AAV virus comprising human SIRT1 in claims 42 and 52, nor teach the dose of the AAV (clams 43 and 60), the AAV capsid being an AAV2 capsid (claims 53 and 61), a hybrid promoter comprising a CMV enhancer and a chicken-beta actin promoter (claims 54 and 62), or the ITR sequencies being from AAV2 (claims 55 and 63).
In regard to administering to the eye a recombinant AAV virus comprising a human therapeutic gene to treat human patients, Hauswirth teaches a clinical trial in which a recombinant AAV virus comprising a human RPE65 gene is administered to the eyes of human patients to treat retinal diseases (see e.g., abstract, related to claims 42 and 52). Hauswirth teaches the recombinant AAV virus comprises an AAV2 capsid packaged with a recombinant AAV vector described in Jacobson et al., (p. 980, left col, last para, see p. 983 for AAV2 capsid immunogenic assay). Jacobson teaches the AAV-2/2.RPE65 vector comprises (a) an AAV2 5’ ITR sequence, (b) a hybrid promoter sequence, (c) a human RPE65 gene sequence and (d) an AAV2 3’ ITR sequence (see p. 1075, Results para 1 and Figure 1A and 1B, related to claims 42 and 52). Hauswirth uses a vector dose of 5.96 x 1010 vector genomes in 0.15 ml volume (see Table 1), thus teaches about 1 x 109 to about 1 x 1013 vector genomes of the recombinant AAV in an aqueous suspension are administered to the eye of the subject in clams 43 and 60. Hauswirth teaches the recombinant AAV virus comprises an AAV2 capsid (see p. 983 for AAV2 capsid immunogenic assay), thus teaches the AAV capsid being an AAV2 capsid in claims 53 and 61. Jacobson teaches the promoter is a hybrid promoter comprising the cytomegalovirus (CMV) immediate early enhancer and a chicken beta-actin promoter with first intron/exon junction (p. 1075, Results para 1 and Figure 1A and 1B), thus teaches a hybrid promoter comprising a CMV enhancer and a chicken-beta actin promoter in claims 54 and 62. Jacobson teaches the 5’ ITR and the 3’ ITR are AAV2 ITRs (p. 1075, Results para 1 and Figure 1 legend, thus teaches the ITRs are from AAV2 in claims 55 and 63. Hauswirth teaches neither vector-related serious adverse events nor systemic toxicities are detected (abstract).
In regard to making and using an AAV comprising SIRT1 in gene therapy, Bosch Tubert teaches an AAV8-SIRT1 virus for overexpressing SIRT1 in liver to treat non-alcoholic fatty liver disease (see example 1 and Figure 2).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of treating optic neuropathy or preserving RGC function by overexpressing SIRT1 gene in the eyes of the subject disclosed by Zuo, by substituting the step of knocking-in SIRT1 gene with the step of administering a recombinant AAV comprising SIRT1 gene to the eyes of the subjects as suggested by Hauswirth, Jacobson and Bosch Tubert with a reasonable expectation of success. Since Zuo teaches overexpressing SIRT1 gene in the eyes prevents RGC loss (see Fig 3) and attenuates loss of RGC function (see Fig 4A), and since Hauswirth and Jacobson teach AAV2-mediated gene delivery to eyes is safe and efficient in human clinical trial without vector-related serious adverse events or systemic toxicities (Hauswirth, abstract and Jacobson, abstract) and Bosch Tubert reduces to practice a method of treating diseases by administering an AAV comprising SIRT1 (example 1), one of ordinary skill in the art would have been motivated to substitute with the AAV2 gene delivery system of Hauswirth and Jacobson in the method of Zuo in order to efficiently deliver SIRT1 gene into eyes without systemic toxicities to treat optic neuropathy or to preserve RGC function in human patients. Furthermore, since Zuo aims to study the mechanisms of SIRT1 function to treat human patients (see 5097, para 1), and since Hauswirth uses a human therapeutic gene in human clinical trial, one of ordinary skill in the art would have been motivated to use a sequence encoding human SIRT1 in the AAV in order to treat human patients. Additionally, one of the ordinary skill in the art would have been motivated to have used the AAV comprising an AAV2 capsid and a genome comprising flanking AAV2 ITRs and a hybrid promoter in the taught dose and form of Hauswirth and Jacobson since Hauswirth and Jacobson have reduced to practice the AAV in human patients for eye delivery in a clinical trial without vector-related serious adverse events or systemic toxicities.
Finally, in regard to the reasonable expectation of success in using an AAV-SIRT1 in gene therapy, it would be predictably obvious to use AAV gene therapy when practicing a method of Zuo. In re O’Farrell, 853 F.2d 894, 903, 7 USPQ2d 1673, 1681 (Fed. Cir. 1988) (citations omitted) (The court held the claimed method would have been obvious over the prior art relied upon because one reference contained a detailed enabling methodology, a suggestion to modify the prior art to produce the claimed invention, and evidence suggesting the modification would be successful.). Therefore, one of ordinary skill in the art could have pursued the known potential option of using AAV-SIRT1 gene therapy to treat optical neuropathies or to preserve RGC function with a reasonable expectation of success. This reasonable expectation of success is supported by: (1) Zuo provides a suggestion to treat optical neuropathies and to preserve RGC function by SIRT1 gene overexpression in the eyes, (2) the reference of Hauswirth contains a detailed enabling methodology for AAV gene therapy that could easily be applied to other genes (i.e., SIRT1) to treat eye diseases, and (3) the success of making and using AAV-SIRT1 for gene therapy as taught by Bosch Tubert suggests modification of the method of Zuo to include AAV-SIRT1 gene therapy would be successful.
With respect to claims 59 and 67, note that claim 67 is examined as the subject having a condition of optic neuritis or traumatic optic neuropathy, Zuo teaches the SIRT1 overexpression, as well as a SIRT1 activator treatment, is used to treat, and to preserve RGC function in a mouse model having experimental optic neuritis induced by traumatic optic nerve crush injury (see e.g., abstract), thus teaches the subject has optic neuropathy being caused by a condition of optic neuritis or traumatic optic neuropathy in claims 59 and 67.
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Claims 56-58 and 64-66 are rejected under 35 U.S.C. 103 as being unpatentable over Zuo et al (Invest Ophthalmol Vis Sci. 2013; 54: 5097–5102, cited in IDS 11/08/2023) in view of Hauswirth et al. (Human Gene Therapy. 2008, 19: 979-990), Jacobson et al. (Molecular Therapy. 2006; 13(6): 1074-1084) and Bosch Tubert et al (US20160354489A1, cited in IDS 11/08/2023), as applied to claims 42 and 52 above, and further in view of Chaffiol et al (Molecular Therapy. 2017; 25(11): 2546-2560. Available online 20 July 2017. Cited in IDS 11/08/2023).
Claims 56 and 64 are directed to the promoter sequence comprising nucleotides 1433-2362 of SEQ ID NO: 28, which is drawn to a human gamma-synuclein gene promoter. Claims 57-58 and 65-66 are drawn to a human gamma-synuclein gene promoter.
In regard to promoters used in overexpress SIRT1 and in the AAVs, Zuo teaches a beta-actin promoter in driving SIRT1 transgene overexpression (p. 5097, last para), Hauswirth and Jacobson use a hybrid promoter comprising the cytomegalovirus (CMV) immediate early enhancer and a chicken beta-actin promoter with first intron/exon junction (Jacobson, p. 1075, Results para 1 and Figure 1A and 1B), and Bosch Tubert teaches a liver-specific promoter (hAAT promoter) in the recombinant AAV8-hAAT-Sirt1 vector ([0118]). Bosch Tubert suggests to use AAV in combination with a tissue-specific promoter to drive restricted SIRT1 expression to treat the diseased tissue (e.g. using a liver-specific promoter in treating liver disease, see e.g., [0010]).
However, Zuo, Hauswirth, Jacobson and Bosch Tubert do not teach a human gamma-synuclein gene promoter with a sequence of nucleotides 1433-2362 of SEQ ID NO: 28.
Chaffiol teaches a promoter to drive a therapeutic gene expression that allows optogenetic vision restoration with enhanced sensitivity in macaque retina (title, abstract). Chaffiol teaches a new promoter based on the regulatory region of the human gamma-synuclein gene (SNCG) allowing strong expression in ganglion cells across species, in combination with clinically proven adeno-associated virus 2 (AAV2), provides CatCh expression in peri-foveolar ganglion cells responding robustly to light under the illumination safety thresholds for the human eye up to 6 months post-injection (abstract, see Figs 1-5). Chaffiol teaches the promoter sequence in supplemental Figure S1B, which comprises a sequence 100% identical to nucleotides 1433-2362 of SEQ ID NO: 28 (see comparison below), related to claims 56-58 and 64-66.
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Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of treating optic neuropathy or preserving RGC function comprising administering to the eyes a recombinant AAV2 comprising a human SIRT1 driven by a CMV-chicken beta-actin hybrid promoter suggested by Zuo, Hauswirth, Jacobson and Bosch Tubert, by substituting the CMV-chicken beta-actin hybrid promoter with a human gamma-synuclein gene promoter with a sequence of nucleotides 1433-2362 of SEQ ID NO: 28 taught by Chaffiol with a reasonable expectation of success. One of ordinary skill in the art would have had a reason to do so for multiple reasons. First, substituting a non-mammalian promoter with a human promoter for a human transgene in potentially a human subject would have been obvious. Furthermore, Zuo teaches that overexpression of SIRT1 in retina can preserve the RGC function (see Fig 1 for overexpression in retina and Fig 3 for results), and since Chaffiol teaches the human gamma-synuclein gene (SNCG) promoter in combination with AAV2 provides strong therapeutic gene expression in the retinal ganglion cells (RGCs) across species up to 6 months post-injection (abstract, see Figs 1-5). Since the combined cited art teaches each and every step and/or composition necessary to use a human gamma-synuclein gene promoter to drive SIRT1 in an AAV2 vector, one of ordinary skill in the art would have had a reasonable expectation of success as well.
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Double Patenting Rejections
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 42-43 and 52-67 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 and 7-14 of US Patent No. 11,879,133 (‘133) in view of Zuo et al (Invest Ophthalmol Vis Sci. 2013; 54: 5097–5102, cited in IDS 11/08/2023). Although the claims at issue are not identical, they are not patentably distinct from each other.
Patented claims in ‘133 recite a method of treating optic neuropathy in a subject in need thereof, the method comprising delivery of the recombinant AAV according to claim 1 to an eye of the subject, the recombinant AAV comprising an AAV capsid, and a vector genome packaged therein, the vector genome comprising: (a) an AAV5′ ITR sequence; (b) a promoter sequence; (c) a sequence encoding human SIRT1; and (d) an AAV3′ ITR sequence, wherein the sequence encoding human SIRT1 comprises SEQ ID NO: 12 and is operably linked to the promoter sequence, wherein delivery of the recombinant AAV results in transduction and preservation of retinal ganglions cells in the eye to treat optic neuropathy (cited claims 7, 9 and 12, related to instant claims 42 and 52), about 1×109 to about 1×1013 vector genomes in an aqueous suspension are delivered to the eye of the subject (cited claims 8 and 13, related to instant claims 43 and 60), the AAV capsid being selected from a list of capsids such as an AAV2 capsid (cited claim 2, related to instant claims 53 and 61), CMV promoter or a hybrid promoter comprising a CMV enhancer and a chicken-beta actin promoter (cited claims 3 and 14, related to instant claims 54 and 62), the ITR sequencies being from AAV2 (cited claim 4, related to claims 55 and 63), the promoter sequence comprising nucleotides 1433-2362 of SEQ ID NO: 28 (cited claim 10, related to instant claims 56 and 64), the promoter sequence comprising a human gamma-synuclein gene promoter (cited claim 11, related to instant claims 57-58 and 65-66).
Accordingly, patent claims recite the subject matters in the instant claims, except that they are silent on the optic neuropathy being caused by one of conditions selected from a list in instant claims 59 and 67.
Zuo teaches the SIRT1 overexpression, as well as a SIRT1 activator treatment, is used to treat, and to preserve RGC function in a mouse model having experimental optic neuritis induced by traumatic optic nerve crush injury (see e.g., abstract, related to instant claims 59 and 67).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of treating optic neuropathy and preserving RGC function by administering an AAV virus comprising a human SIRT1 cited by the patent, by choosing a condition of an optic neuritis or a traumatic optic neuropathy taught by Zuo with a reasonable expectation of success. Since Zuo has taught overexpressing SIRT1 gene can be used to treat an experimental optic neuritis induced by traumatic optic nerve injury (abstract), one of ordinary skill in the art would have been motivated to use the cited method to treat and preserve RGC function in an optic neuritis or a traumatic optic neuropathy as suggested by Zuo.
Since the instant application claims are obvious over cited application claims, in view of Zuo, said claims are not patentably distinct.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jianjian Zhu whose telephone number is (571)272-0956. The examiner can normally be reached M - F 8:30AM - 4PM (EST).
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/JIANJIAN ZHU/Examiner, Art Unit 1631
/TAEYOON KIM/Primary Examiner, Art Unit 1631