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 Application/Amendment/Claims
This Office action is in response to the communications filed on June 5, 2026.
Currently, claims 1, 10-12, 26-28, 34-39, and 43-46 are pending in the instant application. Claims 10 and 26-28 are withdrawn from further consideration as being drawn to nonelected inventions. Accordingly, claims 1, 11-12, 34-39, and 43-46 are under examination on the merits in the instant application.
The following rejections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application.
Response to Arguments and Amendments
Withdrawn Rejections
Any rejections/objections not repeated in this Office action are hereby withdrawn.
Maintained Rejections
Claim Rejections - 35 USC § 103
Claims 1, 11-12, 34-39, and 43-46 remain rejected under 35 U.S.C. 103 as being unpatentable over Damrauer et al. in view of Yu et al., Kolodka et al., Klover et al., and Gao et al. for the reasons as set forth in the Office action mailed on March 12, 2026 and for the reasons stated below.
Applicant's arguments filed on June 5, 2026 have been fully considered but they are not persuasive. Applicant argues that the claims are not obvious because the examiner failed to provide “any evidence that A20 expression in the liver impacts blood glucose level control in any setting”, wherein one skilled in the art would not have been motivated to practice the claimed method without such evidence, whereas Figures 1-2 of the instant application provide evidence that A20 expression in the liver controls blood glucose levels. In response, applicant’s attention is directed to the fact that there is no legal basis that a cited prior art should provide a working example demonstrating the effects of the claimed subject matter for obviousness under §103. Furthermore, for obviousness under §103, “all that is required is a reasonable expectation of success”, and it does not require “absolute predictability of success”. See In re O ’Farrell, 853 F.2d 894, 7 USPQ2d 1673 (Fed. Cir. 1988) at 1681. In the instant case, a recombinant adenovirus encoding A20 was known to be delivered and expressed in hepatocytes after injection as reported by Damrauer, who also taught that A20 overexpression in the liver “enhances the liver’s synthetic and metabolic function”, which was known in the relevant art to include glucose metabolism and insulin action as taught by Klover, wherein A20 overexpression in pancreas was already demonstrated to control blood glucose levels in type I diabetes animal model (the same STZ animal model used to generate Figures 1-2 of this application) as evidenced by Yu, wherein the liver was deemed an “obvious choice” of target organ for therapeutic gene expression that is alternative to the pancreas for type 1 diabetes treatment as taught by Kolodka. Hence, one of ordinary skill in the art, who “is also a person of ordinary creativity”, would have reasonably understood and expected that A20 overexpression in the liver would help control blood glucose level increase in view of the combined teachings and knowledge disclosed in the cited references, which provide a reasonable nexus between the functional role of A20 that “enhances the liver’s synthetic and metabolic function and the liver’s function in controlling glucose metabolism and insulin action. Note that a “person of ordinary skill is also a person of ordinary creativity, not an automaton.” KSR. International Co. v. Teleflex Inc., 550 US 398, 421, 82 USPQ2d 1385, at 1397 (U.S. Supreme Court, 2007).
Applicant argues that Damrauer teaches liver regeneration and mitochondrial genes in relation to glucose metabolism thus “Damrauer is silent regarding the role of A20 expression in the liver as it relates to controlling blood glucose levels.” Applicant argues that Yu teaches A20 in pancreas thus “Yu is silent regarding the role of A20 expression in the liver as it relates to controlling blood glucose levels.” Applicant argues that Kolodoka teaches attempts to express insulin in the liver for type 1 diabetes treatment thus “Kolodoka is silent regarding the role of A20 expression in the liver as it relates to controlling blood glucose levels.” Applicant argues that Gao teaches delivering genes to the liver thus “Gao is silent regarding the role of A20 expression in the liver as it relates to controlling blood glucose levels.” In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant argues that “Klover makes it clear that hormones secreted by the pancreas control the critical role played by hepatocytes in glucose metabolism” by pointing out page 753 thus “Klover is silent regarding the role of A20 expression in the liver as it relates to controlling blood glucose levels.” In response, it appears applicant attempts to argue that page 753 including the abstract of Klover teaches away from the claimed subject matter. It is noted that there is no teaching on Klover’s page 753 that the liver overexpressing A20 has no function in blood glucose levels/homeostasis when insulin-producing cells of the pancreas are deficient thus insulin action is impaired in type 1 diabetes. As noted in the last Office action and reiterated hereinabove, it was experimentally demonstrated in the prior art that A20 overexpression in type 1 diabetes animal model is therapeutically useful in controlling hyperglycemia as evidenced by Yu, wherein the animal model is the STZ animal model, which is also used in the instant application. Hence, A20 was known to provide its glucose metabolic regulation function in a subject having insulin deficiency. Again, applicant’s attention is directed to the fact that applicant cannot attack an individual reference to show nonobviousness when the obviousness rejection is established on combined teachings of cited references.
Applicant argues that one of ordinary skill in the art would not have been motivated to administer A20 to the liver for treating type 1 diabetes because Damrauer is the only reference that connects A20 administration to the liver but fails to teach the nexus between A20 expression in the liver and type 1 diabetes treatment, wherein no other cited reference cures the deficiency of Damrauer. Contrary to applicant’s argument, Damrauers’ teaching regarding A20 overexpression in the liver “enhances the liver’s synthetic and metabolic function” is sufficient to motivate a person of ordinary skill in the art to administer A20 to the liver for enhancing liver’s metabolic function pertaining to glucose in a subject having type 1 diabetes in view of the teachings provided in the cited references for the reasons stated in the last Office action and those reiterated hereinabove.
Applicant argues that the cited references in combination do not provide a reasonable expectation of success by pointing out Roder et al. and Tagliente et al., wherein the two references in combination teach the importance of insulin for glucose level regulation, wherein type 1 diabetes subjects lack insulin thus need to be treated with insulin. In response, applicant’s attention is directed to the fact that both Roder and Tagliente do not take into consideration the teachings of Yu pertaining to A20’s blood glucose level control function in the STZ mouse model that is deficient in insulin as STZ is toxic to pancreatic beta cells that produce insulin thus is an art-recognized type 1 diabetes animal model as disclosed and suggested at page 23 of the instant specification. That is, A20 was known to be therapeutically useful for treating or ameliorating hyperglycemia caused by insulin production deficiency thus A20 was suggested to regulate glucose metabolism in an insulin-independent manner when insulin-producing pancreatic beta cells are damaged and/or deficient. Neither Roder nor Tagliente rebuts the teachings and suggestions of Yu pertaining to the insulin-independent function of A20 in ameliorating hyperglycemia thus fails to support applicant’s asserted lack of a reasonable expectation of success.
Accordingly, this rejection is maintained.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANA H SHIN whose telephone number is (571)272-8008. The examiner can normally be reached Monday-Thursday: 8am - 6:30pm.
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/DANA H SHIN/Primary Examiner, Art Unit 1635
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