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 10/16/2025 has been considered. Rejections and/or objections not reiterated from the previous office action mailed 06/16/2025 are hereby withdrawn.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 10/16/2025, claims 1, 7, 9, 10, 12-18 and 22 are pending and currently under examination in the application.
The 102 rejection is withdrawn in response to claim amendments.
The 103 rejection is withdrawn in view of the new 103 rejection herein.
The 112(a) written description rejection is withdrawn.
The Double Patenting rejection is maintained for the reasons of record.
New Claim 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.
Claims 1, 7, 9, 10, 12-18 and 22 is/are rejected 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).
Regarding claims 1, 7, 9, 10, 12-16 and 18, Parker et al. teach that studies have demonstrated that PSMD9 is associated with risk of adiposity and demonstrates, one ski that hepatic PSMD9 expression correlates with numerous indices of adiposity, across approximately 500,000 individuals (Extended Data Table 1) and these findings collectively provide strong evidence that PSMD9 may have an important role in lipid metabolism in rodents and humans (page 191 col. 1). Parker et al. further teach PSMD9 silencing was associated with decreased expression of genes and proteins involved in de novo lipogenesis (Fig. 5d–f) and (page 191 col. 2).
Gragnoli teach PSMD9 expression was found to be associated with overweight conditions as well as the size of waist circumference representing visceral obesity in subjects (page 2 discussion).
Song et al. teach de novo lipogenesis (DNL) is a complex and highly regulated process in which carbohydrates from circulation are converted into fatty acids that are then used for synthesizing either triglycerides or other lipid molecules and dysregulation of DNL contributes to human diseases such as obesity, type 2 diabetes, and cardiovascular diseases (abstract). Song et al. teach adipose tissue dysfunction plays a pivotal role in the development of obesity and its associated diseases, including type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), non-alcoholic fatty liver disease (NAFLD), and several types of cancer. Therefore, studies on adipose tissue will provide opportunities to combat obesity-associated diseases (see introduction).
Drew et al. teach modified oligonucleotide sequences targeted to a PSMD9 gene wherein the modifications are as in claim 9 or are gapmers having a gap segment, a 5’ and 3’ wing segment (see Table 3 and pages 40-41). Drew et al. teach the modified oligonucleotide is a vector for expression of the oligonucleotide wherein the vector is a viral or adenoviral vector (see page 55). Drew et al. teach dysregulated or elevated levels of PSMD9 in mice models produced elevated lipid and pathologic lipid species (see page 3 lines 5-10). Drew et al. teach pathological lipids include diacylglycerol (DG) and triacylglycerol (TGs) (see page 3 lines 22-25). Drew et al. teach antisense oligonucleotides suppressed PSMD9 expression in vivo and prevented pathological lipid accumulation (see Examples 6 page 86).
Regarding claims 17 and 22, Parker 2018 teach adipose tissue is classified as subcutaneous or visceral dependent on its anatomical position.2 Visceral AT (VAT) is more inclined to become inflamed in obesity, and has a correspondingly greater impact on systemic inflammation and an adverse metabolic profile (see page 35 2.1). Parker teach weight loss can improve the effects of excessive adipose tissue (page 39). Parker 2018 teach there has been a significant increase in the prevalence of obesity in most parts of the world and although the total volume of adipose tissue increases in obesity and, visceral adipose tissue is more biologically active, with greater macrophage content. Disproportional increase in VAT is associated with greater cardiovascular risk and also associated with more severe non-alcoholic fatty liver disease (NAFLD) (page 36 3.1). This provides motivation to target adipose tissue and visceral adipose tissue in treatments of obesity.
The instant specification defines adiposity as obesity and overweight which is a storage of fat in adipose tissue and describes reducing adiposity as decreasing fatty acids, levels of lipids of diacylglycerol (DG) and triacylglycerol (TGs) or markers of lipolysis (page 3 lines 31-38, page 9 lines 17-25).
Because Parker et al. teach studies have demonstrated that PSMD9 is associated with a risk of adiposity and demonstrates that PSMD9 expression correlates with numerous indices of adiposity and Gragnoli teach PSMD9 expression was found to be associated with overweight conditions, a skilled artisan looking to find treatments for adiposity (obesity and overweight) would look for ways to inhibit PSMD9 expression to reduce adiposity, reduce adipose weight gain or promote adipose weight loss in a subject.
Given the specification defines reducing adiposity as decreased lipid levels of diacylglycerol (DG) and triacylglycerol (TGs) and Drew et al. teach dysregulated or elevated levels of PSMD9 in mice models produced elevated lipid and pathologic lipid species such as diacylglycerol (DG) and triacylglycerol (TGs) and teach antisense oligonucleotides suppressed PSMD9 expression in vivo and prevented pathological lipid accumulation, it would have been obvious for the skilled artisan to try the methods of Drew et al. to reduce adiposity in a subject. The Supreme Court held that "obvious to try" was a valid rationale for an obviousness finding, for example, when there is a "design need" or "market demand" and there are a "finite number" of solutions In KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007). There is a finite number of solutions because the prior art of Parker et al. and Gragnoli both teach PSMD9 is associated with adiposity and overweight conditions and Drew et al. teach dysregulated or elevated levels of PSMD9 expression in mice models produced elevated lipid and pathologic lipid species such as diacylglycerol (DG) and triacylglycerol (TGs) and teach antisense oligonucleotides suppressed PSMD9 expression in vivo and prevented pathological lipid accumulation and a person of skill in the art would have good reason to use the method of Drew et al. to reduce adiposity.
It would have further been obvious that the skilled artisan would use the methods of Drew we al. to reduce weight gain and promote adipose weight loss given Parker 2018 teach there has been a significant increase in the prevalence of obesity in most parts of the world and use the methods to reduce visceral adipose tissue given a disproportional increase in visceral adipose tissue is associated with a greater cardiovascular risk and also associated with more severe non-alcoholic fatty liver disease (NAFLD). Because Parker 2018 teach PSMD9 silencing was associated with decreased expression of genes, it would have been obvious to use the methods of Drew et al to decrease lipogenesis in the adipose tissue in the subject.
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. Further, one of skill in the art would have wanted to administer the PSMD9 oligonucleotide inhibitor over time and measure weight loss or reduced weight gain over a period of time to find the optimal dose and measure the effectiveness of the treatment. See MPEP §2144.05: "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." “[C]onducting clinical trials to test for an optimal dose for a drug ‘is generally a routine process[‘].” Eli Lilly and Co. v. Teva Pharmaceuticals USA, Inc., 619 F.3d 1329, 1342 (Fed. Cir. 2010). “In Mayo, the application of the natural law was merely routine optimization of drug dosage to maximize therapeutic effect.” Ariosa Dignostics, Inc. v. Sequenom, Inc., 809 F.3d 1282, 1293 (Fed. Cir. 2015) (Dyk, J., concurring).
Thus in the absence of evidence to the contrary, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed.
Maintained Rejections
Double Patenting
The claims 1, 2, 5-7, 9-18 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 arguments state the claims have been amended and requests the rejection be reconsidered in light of the amendments. The rejection is still maintained and Applicant has not argued why the claims ae unpatentable in view of the cited art below.
Patent ‘491 is drawn to treating a subject suffering from hepatic lipid dysregulation comprising administering a PSMD9 inhibitor polynucleotide. The instant claims are drawn to methods of reducing adipose tissue in a subject comprising administering a polynucleotide inhibitor. The instant claims do not teach treating hepatic lipid dysregulation however Parker, Richard (hereinafter Parker 2018)("The role of adipose tissue in fatty liver diseases." Liver Research 2.1 (2018): 35-42 of record cited on 892 mailed 06/16/2025) teach fatty liver is predominantly a consequence of obesity or excessive alcohol consumption and both are associated with profound changes in the function of adipose tissue (see introduction and abstract). Parker teach weight loss can improve the effects of excessive adipose tissue which in turn improves the result of a fatty liver which leads to liver disease (see page 39). The art of Yu et al. ("Visceral obesity predicts significant fibrosis in patients with nonalcoholic fatty liver disease." Medicine 94.48 (2015) of record cited on 892 mailed 06/16/2025) and also teach fatty liver disease such as NAFLD is associated with obesity, particular visceral obesity (see abstract). Yu et al. teach that studies of visceral adipose tissue participates in the pathogenesis of fatty liver disease (see page 1 introduction) and states visceral adipose tissue is probably the most important target for treatment of fatty liver (see page 6 last para.)
It would therefore have been obvious to use the methods of Drew et al. to use the inhibitor of PSMD9 to reduce adipose tissue weight gain for further treatments of fatty liver disease and obvious to measure the weight loss over a period of time to test the effectiveness of the inhibitor. One would have been motivated to do so given Parker and Yu et al. provide a strong correlation between obesity or the increase of adipose tissue, particularly visceral adipose tissue, with fatty liver disease.
MPEP 804 “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 determining whether a nonstatutory basis exists for a double patenting rejection, the first question to be asked is: Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent? If the answer is yes, then a nonstatutory double patenting rejection may be appropriate.”
Thus the claims are not patentably distinct.
Response to Arguments
Applicant argues Example 8 of Drew et al. demonstrates that inhibition of PSMD9 is not associated with weight loss because there is no significant change in the weight of mice given an ASO inhibitor targeted to PSMD9 and therefore is a teaching away and one of skill in the art would not use the ASO inhibitor for decreasing weight loss. In response, the example argued by Applicant describes using the ASO in mice to assess potential liver toxicity and states there is no significant change in body weight with no data shown. This experiment did not measure any pathological lipid to determine any reduction or test adipose tissue to determine any affect on obesity or adipose weight loss. Because there is no way to access or determine what the significance of the experiment demonstrated on body weight or how the body weight was measure (e.g. actual pounds, waist circumference or adipose tissue measurement), this cannot be used to represent an actual teaching away that would dissuade a skilled artisan from trying to use the ASO targeted against PSMD9 for reducing adiposity in a subject.
Applicant argues Parker et al. do not teach PSMD9 is involved in adiposity and do not teach inhibition of PSMD9 reduced adipose weight gain. In response and discussed above, Parker et al. teach that studies have demonstrated that PSMD9 is associated with risk of adiposity and demonstrates and that PSMD9 expression correlates with numerous indices of adiposity, across approximately 500,000 individuals (Extended Data Table 1) and these findings collectively provide strong evidence that PSMD9 may have an important role in lipid metabolism in rodents and humans. Thus Parker et al. in combination of the cited references provides a motivation to use a PSMD9 inhibitor to reduce expression and therefore reduce adiposity.
Applicant then argues that Drew et al. teaches targeting hepatic de novo lipogenesis in lean mice and not adipose tissue in obese models. Given the specification defines reducing adiposity as decreased lipid levels of diacylglycerol (DG) and triacylglycerol (TGs) and Drew et al. teach dysregulated or elevated levels of PSMD9 in mice models produced elevated lipid and pathologic lipid species such as diacylglycerol (DG) and triacylglycerol (TGs) and teach antisense oligonucleotides suppressed PSMD9 expression in vivo and prevented pathological lipid accumulation, it would have been obvious for the skilled artisan to try the methods of Drew et al. in combination with the evidence in the prior art to reduce adiposity in a subject.
Applicant next argues a skilled person would not reasonably assume that a result in lean mice targeting the liver would translate to reductions in adiposity in obese models and the complexity of the pathways involved in adiposity and fatty liver further demonstrates that PSMD9 inhibition would not have been expected to reduce adiposity. In response, a skilled artisan looking at the prior art as a whole would see there is a need to treat adiposity and see there is a correlation between expression of PSMD9 and adiposity and see that Drew et al. teach dysregulated or elevated levels of PSMD9 in mice models produced elevated lipid and pathologic lipid species such as diacylglycerol (DG) and triacylglycerol (TGs) and teach antisense oligonucleotides suppressed PSMD9 expression in vivo and prevented pathological lipid accumulation, it would have been obvious for the skilled artisan to try the methods of Drew et al. to reduce adiposity in a subject with a reasonable expectation that inhibition of PSMD9 expression would lead to a reduction of adiposity. Regarding the argument that the complexity of the pathways demonstrates that PSMD9 inhibition would not have been expected to reduce adiposity, there is no factual evidence provided to support this assumption. 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)).
Conclusion
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/KIMBERLY CHONG/
Primary Examiner Art Unit 1636