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 .
Priority
The instant application is a national stage entry under 35 U.S.C. § 371 of PCT/US2022/025594 (filed 04/20/2022). Acknowledgement is made of Applicants’ claim for benefit of U.S. Provisional Application No. 63/178,810 (filed 04/26/2021).
Election/Restrictions
Applicant’s election without traverse of (a) siRNA or shRNA as the elected species of inhibitor in the reply filed on 05/18/2026 in response to an Election of Species requirement is acknowledged.
Applicants identified claims 1-9 and 13-19 as reading on the elected species. It is noted that claim 9 defines the inhibitor as a ribozyme, not siRNA or shRNA, so claim 9 does not read on the elected species. Claims 9-12 are withdrawn from consideration as being directed to non-elected species.
Claims 1-8 and 13-19 read on Applicants’ election and are examined on the merits herein.
Claim Interpretation
The following comments are made to establish broadest reasonable interpretation for the record.
Regarding claims 4, 7: These claims recited the limitation transcribed to form; e.g., “…administering to the subject a viral vector transcribed to form the inhibitory nucleic acid…” (claim 4). The term transcribed to form is interpreted as referring to the inherent transcription of the inhibitory nucleic acid molecule (e.g., siRNA) upon delivery into a cell. This interpretation is supported by the Specification of the instant application: “ ‘Transcribed to form’ indicates that the DNA is transcribed into an RNA, such as, but not limited to, an inhibitory nucleic acid molecule.” (pg. 16; lines 26-27); “…exemplary DNA that are transcribed to form shRNAs of use include…” (pg. 26; lines 2-3).
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 13 and 14 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 13: There is insufficient antecedent basis for the limtiation “[the] vector” in line 1 of claim 13. Parent claim 1 describes administering an inhibitor, but no reference to a vector is made in claim 1. Correction is required.
Claim 14 depends from claim 13, inherits the deficiency, and is rejected on the same basis.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3, 15, and 17-19 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Huang (WO 2020/206055).
Huang teaches H19, TET, TGF, HNF, or isoforms thereof, as novel pharmacological targets for the treatment of diseases or disorders, such as cancer, fibrosis, and diabetes (Abstract).
Regarding claims 1-3, 19: Huang teaches a method of treating a subject with type 2 diabetes (pg. 9; par. 4) comprising targeting transforming growth factor (TGF) protein Smad2 (pg. 7; par. 5) via administering an siRNA for inhibition thereof (pg. 8; par. 5); disclosed is an embodiment wherein the treatment further comprises a reduction in Smad2 (pg. 45; par. 1). Huang teaches an embodiment wherein the subject is a human (pg. 27; par. 6). This anticipates:
the method of treating a subject with type 2 diabetes, comprising administering to the subject a therapeutically effective amount of an inhibitor that decreases expression of Mothers Against Decapentaplegic Homolog (smad) 2, thereby treating the type 2 diabetes in the subject limitation recited in claim 1;
the wherein the inhibitor is an inhibitory nucleic acid molecule limitation recited in claim 2;
the wherein the inhibitory nucleic acid molecule is a small interfering RNA (siRNA) limitation recited in claim 3; and
the wherein the subject is human limitation recited in claim 19.
Regarding claim 15: Following the above discussion, Huang teaches an embodiment wherein an additional drug is administered to the subject (pg. 59; par. 5); this anticipates the administering an additional agent to the subject limitation recited in claim 15.
Regarding claims 17-18: Huang teaches the same method of treating a subject with type 2 diabetes via administration of an inhibitor which decreases Smad2 expression; thus, the method of Huang is the same as the claimed method of the instant application. Under the principles of inherency, when a reference discloses all claimed steps, the effect will necessarily be achieved, even if not explicitly recognized by the reference. See MPEP 2112.02.
Therefore, the method of Huang anticipates:
the wherein administering the therapeutically effective amount of the inhibitor reduces glucose intolerance in the subject limitation recited in claim 17; and
the wherein administering the therapeutically effective amount of the inhibitor reduces plasma glucose levels in the subject limitation recited in claim 18.
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.
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 1-6, 13, 15, and 17-19 are rejected under 35 U.S.C. 103 as being unpatentable over Huang (WO 2020/206055) in view of Quirin, et al. (Mol Ther Methods Clin Dev. 2018).
The teachings of Huang are set forth above; claims 1-3, 15, and 17-19 are anticipated by the same.
Quirin, et al. teaches recombinant adeno-associated virus (rAAV)-mediated gene delivery in pancreas (Abstract).
Regarding claims 4-6, 13: Following the above discussion, Huang does not explicitly teach all the limitations of the instant claims.
However, Quirin, et al. teaches retrograde intraductal infusion of an scAAV6 expressing GFP under the control of an EF1α promoter transduces the pancreas uniformly and efficiently (pg. 9; col. 2, pars. 1-3), including long-term gene expression (5 months post-delivery) in islet cells, among other pancreatic cells (Figs. 3-4).
It would have been prima facie obvious to a person having ordinary skill in the art to have modified the method of Huang by using the scAAV6 vector to deliver the Smad2 siRNA via retrograde intraductal infusion, as taught by Quirin, et al. This conclusion of obviousness is based on the ‘teaching, suggestion, or motivation rationale’. One would have been motivated to do so for the long-term, uniform, efficient transduction of the pancreas, as taught by Quirin, et al. Further, as Huang teaches use of an AAV vector to deliver an siRNA molecule which inhibits a TET protein in the same disclosure (pg. 9; par. 2), the skilled artisan would have more than a reasonable expectation of success.
Therefore, the modified method of Huang set forth above render obvious:
the administering to the subject a viral vector transcribed to form the inhibitory nucleic acid molecule limitation recited in claim 4;
the wherein the viral vector is a an adeno-associated virus (AAV) vector limitation recited in claim 5;
the wherein the viral vector is the AAV vector limitation recited in claim 6; and
the wherein the inhibitor or vector is administered intraductally into a pancreatic duct limitation recited in claim 13.
Claims 1-3, 7-8, 15, and 17-19 are rejected under 35 U.S.C. 103 as being unpatentable over Huang (WO 2020/206055) in view of Quirin, et al. (Mol Ther Methods Clin Dev. 2018), further in view of Xiao, et al. (PNAS. 2014).
The teachings of Huang and Quirin, et al. are set forth above; claims 1-3, 15, and 17-19 are anticipated by Huang.
Xiao, et al. teaches upregulation of TGFβ superfamily signaling inhibitor Smad7 in beta cells after pancreatic duct ligation (Abstract).
Regarding claims 7-8: It is set forth above the modified method of Huang renders obvious the viral vector of the instant claims. The modified method does not teach the beta cell-specific promoter limitations of claims 7 and 8.
However, Xiao, et al. teaches an AAV comprising rat insulin promoter (RIP) to express SMAD7 or GFP in beta cells (pg. 1214; col. 2, par. 1); RIP is effective to achieve extremely high specificity of expression in beta cells (pg. 1214; col. 2, par. 2; Fig 5B-C).
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art to have further modified the method of Huang by substituting the EF1α promoter with the rat insulin promoter of Xiao, et al. This conclusion of obviousness is based on the ‘teaching, suggestion, or motivation rationale’. One would have been motivated to do so for the extremely high specificity of expression in beta cells conferred by the rat insulin promoter, as disclosed by Xiao, et al. Additionally, as Xiao, et al. teaches use of the rat insulin promoter for expression of Smad7 (pg. 1214), and as both Smad2 and Smad7 are members of the Smad family of proteins, the skilled artisan would have more than a reasonable expectation of success.
Thus, the modified method of Huang set forth above renders obvious:
the wherein the viral vector transcribed to form the inhibitory nucleic acid molecule further comprises a beta cell-specific promoter operably linked to a nucleic acid molecule encoding the inhibitory nucleic acid molecule, and wherein the viral vector is administered to a pancreatic duct of the subject limitation recited in claim 7; and
the wherein the promoter is an insulin promoter limitation recited in claim 8.
Claims 1-3, 13-15, and 17-19 are rejected under 35 U.S.C. 103 as being unpatentable over Huang (WO 2020/206055) in view of Kumbhari, et al. (Gastrointest Endosc. 2018) and Hardt, et al. (Pancreatology. 2002).
The teachings of Huang are set forth above; claims 1-3, 15, and 17-19 are anticipated by the same.
Kumbhari, et al. teaches ERCP-guided hydrodynamic delivery of plasmid DNA in pigs (Abstract).
Hardt, et al. teaches detection of ductal morphology changes characteristic of chronic pancreatitis in patients with known diabetes mellitus (Abstract).
Regarding claim 14: Following the above discussion, Huang does not teach intraductal administration of the Smad2 siRNA.
However, Kumbhari, et al. teaches ERCP-mediated hydrodynamically delivery of plasmid DNA for liver-targeted gene therapy is minimally invasive, technically simple, and safe (pg. 8; par. 2); it is further disclosed other nucleic acid therapeutics, such as siRNA and shRNA, could be similarly delivered (“Conclusions”; Abstract).
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art to have modified the method of Huang by delivering the Smad2 siRNA via ERCP, as taught by Kumbhari, et al. This conclusion of obviousness is based on the ‘teaching, suggestion, or motivation’ rationale’. One would be motivated to do so for the benefits of ERCP disclosed by Kumbhari, et al.; namely, that ERCP is a simple, safe, and minimally invasive procedure effective to deliver nucleic acid molecules (pg. 8; par. 2). Further, Hardt, et al. teaches ERCP is the gold standard of pancreatic imaging (pg. 31; col. 1, par. 1), disclosing a retrospective analysis of 156 patients with diabetes, insulin-dependent and non-insulin-dependent, having undergone ERCP (pg. 31; col. 1, par. 2). Thus, as Hardt, et al. evidences ERCP is a standard procedure in patients with type 2 diabetes, the skilled artisan would have more than a reasonable expectation of success. This modified method renders obvious:
the wherein the inhibitor or vector is administered intraductally into a pancreatic duct limitation recited in claim 13; and
the wherein administering intraductally comprises the use of endoscopic retrograde cholangiopancreatography (ERCP) limitation recited in claim 14.
Claims 1-3, and 15-19 are rejected under 35 U.S.C. 103 as being unpatentable over Huang (WO 2020/206055) in view of UK Prospective Diabetes Study Group (Lancet. 1998).
The teachings of Huang are set forth above; claims 1-3, 15, and 17-19 are anticipated by the same.
UK Prospective Diabetes Study Group (hereinafter UKPDS) teaches the effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (Title).
Regarding claim 16: Following the above discussion, Huang does not teach the additional drug administered to the subject with type 2 diabetes as metformin, as required by the limitation recited in claim 16.
However, the UKPDS disclosure teaches intensive glucose control with metformin decreases risk of diabetes-related endpoints in overweight patients with type 2 diabetes, and is associated with less weight gain and fewer hypoglycemic attacks than insulin or sulfonylureas (pg. 854; col. 2, par. 1).
Therefore, it would have been prima facie obvious to have modified the method of Huang by using metformin as the additional drug administered to the subject with type 2 diabetes, as taught by UKPDS. This conclusion of obviousness is based on the ‘teaching, suggestion, or motivation’ rationale’. One would be motivated to do so for the decreased risk of diabetes-related endpoints, weight gain, and hypoglycemic attacks, as taught by UKPDS. Further, as metformin is commonly prescribed to type 2 diabetics, as evidenced by the UKPDS disclosure, the skilled artisan would have more than a reasonable expectation of success. This renders obvious the wherein the agent is metformin limitation recited in claim 16.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GINA PRONZATI whose telephone number is (571)270-5725. The examiner can normally be reached Monday - Friday 9:00a - 5:00p ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, CHRISTOPHER BABIC can be reached at (571)272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/GINA PRONZATI/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633
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