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
Status of Application/Amendment/Claims
Applicant's response filed 04/22/2026 has been considered. Rejections and/or objections not reiterated from the previous office action mailed 01/22/2026 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
With entry of the amendment filed on 04/22/2026, claims 1, 7, 9, 10, 12-18 and 22 are pending and currently under examination in the application.
The 103 rejection is maintained for the reasons of record.
The Double Patenting rejection is maintained for the reasons of record.
Maintained Rejections
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 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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
The rejection of claims 1, 7, 9, 10, 12-18 and 22 under 35 U.S.C. 103 as being unpatentable over Parker et al. (An integrative systems genetic analysis of mammalian lipid metabolism. Nature 567, 187–193 (2019) of record 892 filed 06/16/2025)), Gragnoli, Claudia ("Overweight condition and waist circumference and a candidate gene within the 12q24 locus." Cardiovascular Diabetology 12.1 (2013)), Song et al. ("Regulation and metabolic significance of de novo lipogenesis in adipose tissues." Nutrients 10.10 (2018)), Drew et al. (WO 2019/140488 cited on IDS filed 10/21/2024) and Parker, Richard (hereinafter Parker 2018)("The role of adipose tissue in fatty liver diseases." Liver Research 2.1 (2018): 35-42) is maintained for the reasons of record.
Applicant’s arguments have been acknowledged but are not found to be persuasive. Applicant asserts that the mechanisms governing liver fat and adiposity are overlapping only in part and are not the same. The relevant pathways are complex and distinct, as would have been understood by the skilled person. The in vivo models used in Drew reference and in the current application are entirely different. Drew reference discloses hepatic de novo lipogenesis in lean mice, whereas the present application concerns adiposity outcomes in obese subjects. A skilled person will not reasonably assume that a result in lean mice targeting the liver would translate to reductions in adiposity in obese animals. In response, the claims do not recite reducing adiposity in obese animals as argued. Drew et al. clearly teach antisense oligonucleotides suppressed PSMD9 expression in vivo and prevented pathological lipid accumulation (see Examples 6 page 86) and it would have been obvious for the skilled artisan to try the methods of Drew et al. in combination with the recited references to reduce adiposity in a subject.
Applicant further argues the complexity of the pathways involved in adiposity and fatty liver further demonstrates that PSMD9 inhibition would not have been expected to reduce adiposity. Applicants show that administration of a native PSMD9 antisense oligonucleotide significantly reduces weight gain and fat mass. See, current application, Figure 10A-1OC. In contrast, administration of a liver-targeted PSMD9 antisense (GalNac D9) results in no prevention of weight gain relative to controls. Thus, only the native PSMD9 antisense produces the adiposity-related outcome, while the liver-targeted version does not. These data show that the effect on adiposity depends on the delivery context and is not predictable from Drew reference, which focuses solely on liver targeting. In response, the claims are broadly drawn to administration of the PSMD9 inhibitor and does not claim reducing adiposity, adipose with gain or promoting adipose weight loss in any specific organ. Further, Applicant’s argument is not presented as unexpected results to negate the 103 rejection. Drew et al. was relied upon to teach it was obvious to use an inhibitor antisense oligonucleotide to inhibit PSMD9 expression and further teach dysregulated or elevated levels of PSMD9 in mice models produced elevated lipid and pathologic lipid species (see page 3 lines 5-10) and demonstrate pathological lipid accumulation (see Examples 6 page 86). It would have been obvious for the skilled artisan to try the methods of Drew et al. in combination with the recited references to reduce adiposity in a subject.
Applicant cites references describing different types of agents for the argument that hepatic targeting can reduce fatty liver without affecting obesity in humans and that a skilled person would understand that an effect on one condition such as fatty liver does not necessarily produce an effect on the other such as adiposity. In response, these references would not dissuade one skilled in the art to try using an inhibitory molecule targeted to PSMD9 in efforts to reduce adiposity as claimed. The combination of references teach PSMD9 is associated with risk of adiposity, demonstrates PSMD9 expression correlates with numerous indices of adiposity (Parker) and teach PSMD9 expression was found to be associated with overweight conditions as well as the size of waist circumference representing visceral obesity in subjects (Gragnoli). The prior art teach studies on adipose tissue will provide opportunities to combat obesity-associated diseases (Song) and thus motivation to use methods to target PSMD9 (Drew).
Applicant next argues Parker (2019) provides a general discussion that fatty liver disease is associated with changes in adipose tissue function. However, Parker does not teach that PSMD9 is involved in adiposity, does not teach that inhibition of PSMD9 reduces adipose tissue weight gain or causes adipose weight loss, and does not disclose administration of any PSMD9 targeting oligonucleotide. The reasoning provided by the Office is speculative and unsupported. It disregards the evidence showing that reduction of liver fat does not reliably correlate with reduction of adipose fat or body weight, and therefore does not provide the required reasonable expectation of success. To bolster the point, Applicant presents Loomba et al. 2020 ( purported to be in Exhibit B however there is no Exhibit filed with the response).
Applicant’s argument that because antisense targeted to DGAT2 had no effect at all on body weight, there would not be an expectation of success to use an antisense targeted to PSMD9 to decrease adiposity because reduction of liver fat did not translate into weight loss. This is not convincing. DGAT2 and PSMD9 are two entirely different genes. Loomas et al. describes DGAT2 as involved in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. The study was not designed to demonstrate methods of reducing adiposity. Applicant’s statement that This is particularly significant because DGAT2 is well understood to be heavily involved in adiposity and body fat regulation through catalysis of the final step in triglyceride synthesis, triglycerides being the principal components of fat stored in adipose tissue is not supported by any evidence. MPEP 2145 states an argument does not replace evidence wherein evidence is necessary, such as in this case. Moreover the arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965). (see MPEP 716.01(c)).
Further, Parker 2019 directly teach PSMD9 is associated with risk of adiposity and demonstrates that hepatic PSMD9 expression correlates with numerous indices of adiposity, across approximately 500,000 individuals (Extended Data Table 1). This not speculative and unsupported evidence as argued by Applicant. This provides one of skill the motivation to look at the role of PSMD9 plays in adiposity and use methods known in the art to try and decrease expression of PSMD9 in efforts to reduce adiposity.
Applicant argues Parker 2019 demonstrates PSMD9-ASO is not associated with significant changes in body weight as shown in Extended Data Figure 7E-7G. A review of the data shows that each PSMD9-ASO shows a decrease in body weight as compared to their respective controls. Further, the claims are drawn to methods to reduce adiposity, reduce adipose weight gain or promote adipose weight loss and these results would not dissuade and not methods of “significant changes in body weight” and one skilled in the art would use the references in combination as set out in the 103 rejection.
Applicant next argues that [a]lthough Parker (2019) reports that PSMD9 correlates with several indices of adiposity, those correlations are limited and do not represent the majority of indices. At most, Parker states that fatty liver can result from changes in adipose tissue; it does not teach that targeting PSMD9 in adipose tissue, or using the specific PSMD9 inhibitor of Drew, would reduce adiposity. In response, it is not clear what the majority of indices of adiposity includes and Applicant has not provided any evidence that the indices indicated by Parker 2019 would not be motivation to look for methods to targeted PSMD9 to reduce adiposity.
Applicant states a mere correlation carries limited evidentiary value and cannot substitute for a showing of reasonable expectation of success. This argument is not persuasive. One of skill in the art would have expected to be capable of using the PSMD9 inhibitor to increase lipid metabolism or decrease lipogenesis given Song et al. teach dysregulation of DNL contributes to human diseases such as obesity. Parker et al. further teach PSMD9 silencing was associated with decreased expression of genes and proteins involved in de novo lipogenesis. There is an expectation of an advantage for using an inhibitory oligonucleotide targeted to PSMD9 and evidence that PSMD9 correlates with several indices of adiposity Parker (2019), as pointed out by Applicant, and thus a motivation to combine the prior art references for methods of treatment of adiposity (see MPEP 2144). Conclusive proof of efficacy is not required to show a reasonable expectation of success and obviousness does not require absolute predictability, but at least some degree of predictability is required (MPEP 2143.02). The combination of references would provide some expectation that inhibition of PSMD9 using an inhibitory oligonucleotide would affect adiposity.
Applicant next argues Drew et al. silenced PSMD9 in lean mice and explicitly reported that administration of PSMD9 ASO for 4 weeks was not associated with significant changes in body weight. Applicant does not point to where this statement or data is represented in Drew et al. and it is unclear what is meant by significant changes in body weight. The claims are drawn to methods of reducing adiposity, adipose weight gain or promoting adipose weight loss. As stated previously, the combination of references would lead one of skill in the art to try reducing adiposity using an inhibitory oligonucleotide targeted to PSMD9.
Applicant argues the Office's triangulated obviousness rationale fails for an additional reason. Not only did the published PSMD9 studies fail to show reduced adipose weight, but inhibition of other proteins exhibiting a similar theoretical overlap between liver fat synthesis and de novo lipid synthesis, such as DGAT2, also failed to reduce body weight. In response, the claims are not drawn to reducing additional proteins and therefore the argument is not persuasive to overcome the obviousness rejection as explained above and in the 103 rejection of record.
The rejection is therefore maintained.
Double Patenting
The claims 1, 7, 9, 10, 12-18 and 22 rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-16 of Patent No. 12,221,491 is maintained for the reasons of record. Applicant’s request the rejection be reconsidered in light of the amendments. The rejection is still maintained and Applicant has not argued why the claims are unpatentable in view of the cited art below.
Conclusion
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 extension fee 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 KIMBERLY CHONG at (571)272-3111. The examiner can normally be reached Monday thru Friday 9-5 pm.
If attempts to reach the examiner by telephone are unsuccessful please contact the SPE for 1636 Neil Hammell at 571-270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KIMBERLY CHONG/Primary Examiner, Art Unit 1636
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