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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114 was filed in this application after appeal to the Patent Trial and Appeal Board, but prior to a decision on the appeal. Since this application is eligible for continued examination under 37 CFR 1.114 and the fee set forth in 37 CFR 1.17(e) has been timely paid, the appeal has been withdrawn pursuant to 37 CFR 1.114 and prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant’s submission filed on November 13, 2025 has been entered.
Status of Claims/Rejections
Claims 1, 10-12, 22, 24-29, 34-39, and 43-46 are currently pending in the instant application. Claims 10 and 26-28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Accordingly, claims 1, 11-12, 22, 24-25, 29, 34-39, and 43-46 are under examination on the merits in the instant application.
Any rejections not repeated in this Office action are withdrawn, and the following rejections are the only rejections applied in this application.
Response to Arguments
Applicant’s arguments with respect to the previous §103 rejection filed on December 5, 2025 have been considered but are moot because they do not pertain to the new ground of rejection as set forth hereinbelow.
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 12, 24-25, and 29 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.
Claims 12, 24-25, and 29 are drawn to a method of “increasing the expression of endogenous A20” comprising “delivering an agent that upregulates [endogenous] A20 expression in the liver of the subject” who is being treated for type 1 diabetes.
It is noted that the instant specification at best discloses an agent comprising an exogenous A20 gene, which is overexpressed in the liver of a subject, wherein the agent that increases exogenous A20 does not represent the agent that increases endogenous A20 claimed in claims 12, 24-25, and 29.
The instant specification does not appear to provide any species of the “agent” that actually upregulates endogenous A20 expression in the liver of a type 1 diabetes subject. In fact, the claims do not even expressly recite which “agent” is administered in order to increase the liver expression of “endogenous A20” for “treating type I diabetes”. As such, the “agent” of claims 12, 24-25, and 29 is extremely broad, whereas there is not even a single disclosed “agent” species having the required function of increasing endogenous A20 expression in the liver of a type 1 diabetes subject. That is, the instant specification fails to describe a representative number of species within the broadly claimed genus of “agent” that increases endogenous A20 in the liver of a type 1 diabetes subject, wherein the specification also fails to describe the distinguishing structural features of such agent that increases endogenous A20 in the liver of a type 1 diabetes subject. In fact, it appears that the instant co-inventors did not even identify a single “agent” that actually increases endogenous A20 in the liver of a type 1 diabetes subject, wherein the “agent restores euglycemia or improves glycemic control in the subject.” Moreover, none of the prior art references searched by the examiner and submitted by applicant in IDS of record teach the instantly claimed “agent” that increases endogenous A20 in the liver of the claimed subject. As such, there was a complete lack of relevant prior art knowledge pertaining to the instantly claimed method encompassing “increasing the expression of endogenous A20” in the liver of a type 1 diabetes subject, wherein such lack of prior art knowledge and predictability requires the instant specification to describe the claimed “agent” in sufficient detail as there is an inverse correlation between the level of prior art knowledge/predictability and the specificity of the specification’s disclosure. See MPEP §2163.
Accordingly, it is concluded that the instant specification fails to adequately describe the genus of claims 12 and 29 and the subject matter of claims 24-25 and that the specification also fails to reasonably convey that the instant co-inventors had possession of the claimed method requiring an agent that increases the expression of endogenous A20 in the liver of a type 1 diabetes subject as of the filing date sought in the instant application.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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, 11-12, 22, 29, 34-39, and 43-46 are rejected under 35 U.S.C. 103 as being unpatentable over Damrauer et al. (PLoS ONE, 2011, 6(3):e17715) in view of Yu et al. (Acta Pharmacologica Sinica, 2004, 25:721-726, applicant’s citation), Kolodka et al. (PNAS, 1995, 92:3293-3297), Klover et al. (The International Journal of Biochemistry & Cell Biology, 2004, 36:753-758, applicant’s citation), and Gao et al. (US 2003/0228282 A1).
Damrauer teaches a method of injecting a recombinant adenovirus A20 (“rAd.A20”) to a mouse, wherein A20 is expressed 30%-40% of hepatocytes of the mouse 5 days after the injection. See page 2.
Damrauer teaches that A20 overexpression in the liver “enhances the liver’s synthetic and metabolic function”. See page 4.
Damrauer does not teach the method of injecting “rAd.A20” is performed in a mouse having type I diabetes phenotype.
Yu teaches that overexpression of A20 via a plasmid (“pcDNA-A20”) in pancreas by direct delivery is useful for protecting a mouse from developing STZ-induced type I diabetes phenotype such that the blood glucose level increased more slowly and stayed lower in the pcDNA-A20 injected mice, wherein A20 is delivered into the pancreatic parenchyma before STZ injection. See pages 721 and 724; Figures 5 and 7.
Kolodka teaches that type 1 diabetes mellitus (IDDM) “results from the autoimmune destruction of the insulin-producing b cells of the pancreas”. See page 3293.
Kolodka teaches, “Since b cells are destroyed in IDDM, any attempt to reconstitute insulin gene expression must be directed at an ectopic organ. The liver is an obvious choice since it is the main target organ for insulin action and the principal effector organ in maintaining blood glucose homeostasis and ketogenesis.” See page 3293.
Klover teaches that the “hepatocytes play a critical role in glucose metabolism”. See page 754.
Gao teaches that an AAV2/8 pseudotyped vector comprising a TBG promoter operably linked to a transgene (e.g., “AAV2/8-TBG-hLDLr”, “AAV2/8TBGcFIX”, “AAV2/8 TBG LacZ3”) is delivered to the liver tissue of mice and the gene is expressed in the liver with high liver-specificity, wherein the TBG (human thyroid hormone binding globulin gene) promoter is “used to drive liver specific expression” and “AAV2/8 provides a substantial advantage over the other serotypes in terms of efficiency of gene transfer to liver” in view of the experimental finding that “AAV2/8 consistently achieved a 10 to 100-fold improvement in gene transfer efficiency as compared to the other vectors” thus the AAV2/8 is “the most efficient vector for liver-directed gene transfer due to increased numbers of transduced hepatocytes”, wherein about “70-80% of hepatocytes are stained positive” when “AAV2TBGcFIX” is delivered to mice. See paragraphs 0145-0146, 0151-0153, 0157, 0161-0165, 0181, 0183-0185, 0188, and 0193; Tables 3-5.
It would have been obvious to one of ordinary skill in the art before the effective filing date to apply Damrauer’s method to a subject having IDDM whose insulin-producing b cells of the pancreas are destroyed thus no longer functional in producing insulin and controlling blood glucose levels. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success in order to improve blood glucose level control in the IDDM subject, thereby treating the IDDM subject, because it was known in the art that A20 overexpression in hepatocytes via injection of a recombinant adenovirus A20 “enhances the liver’s synthetic and metabolic function” as taught by Damrauer, wherein liver’s metabolic function, especially hepatocyte’s metabolic function, was known to include “glucose metabolism” as evidenced by Klover and also as echoed by Kolodka such that the liver is “the principal effector organ in maintaining blood glucose homeostasis”, and because A20 overexpression in an IDDM mouse model, albeit in the pancreas, not in the liver, was also experimentally demonstrated to provide blood glucose level control as reported by Yu, thereby supporting a therapeutic function of A20 overexpression in relation to IDDM. Since the liver was suggested as an alternative organ for blood glucose level control in IDDM in which the “b cells are destroyed”, wherein it was art-recognized knowledge that “the autoimmune destruction of the insulin-producing b cells of the pancreas” results in IDDM as evidenced by Kolodka, and since the role of A20’s liver expression in glucose metabolism control and the therapeutic potential of A20 overexpression in IDDM were taught and suggested in the prior art as evidenced by the cited teachings as explained above, one of ordinary skill in the relevant art would have reasonably deemed Damrauer’s method of A20 overexpression in hepatocytes via a recombinant adenovirus expression vector is suitable in restoring and/or controlling blood glucose levels in an IDDM subject whose insulin-producing b cells in the pancreas are destroyed.
It would also have been obvious to one of ordinary skill in the art before the effective filing date to utilize Gao’s AAV2/8 serotype vector with a TGB promoter as the vehicle for overexpressing A20 in hepatocytes of an IDDM subject. One of ordinary skill in the art would have been motivated to use Gao’s liver-specific AAV vector and the liver-specific promoter in place of Damrauer’s recombinant adenovirus vector (“rAd.A20”) so as to significantly enhance hepatocyte expression of A20 in an IDDM subject, thereby further enhancing blood glucose level control in the IDDM subject, consequently providing an improved treatment to the IDDM subject, because not only was the AAV2/8 vector of Gao demonstrated to “the most efficient vector for liver-directed gene transfer due to increased numbers of transduced hepatocytes” among all AAV serotype vectors tested, but the TGB promoter included in the AAV2/8 vector was also known to be “used to drive liver specific expression”. Since the AAV2/8 was expressly deemed to provide “a substantial advantage” such as “a 10 to 100-fold improvement in [the liver-directed] gene transfer efficiency” as evidenced by Gao, and since AAV2/8 vectors comprising a TGB promoter operably linked to a transgene were experimentally demonstrated to be expressed in the majority of the hepatocytes such as “70-80% of hepatocytes” as evidenced by Gao, one of ordinary skill in the art would have reasonably predicted that use of Gao’s AAV2/8 vector comprising a TGB promoter would significantly enhance hepatocyte delivery as well as hepatocyte-specific expression of the therapeutically useful A20 in an IDDM subject compared to Damrauer’s “rAd.A20” that achieved A20 expression in 30%-40% of hepatocytes.
In view of the foregoing, claims 1, 11-12, 22, 29, 34-39, and 43-46 taken as a whole would have been prima facie obvious before the effective filing date.
Conclusion
No claim is allowed.
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/DANA H SHIN/Primary Examiner, Art Unit 1635