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, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on November 5, 2025 has been entered.
Status of Claims/Rejections
Claims 1-2 and 8-22 are currently pending in the instant application. Claims 11 and 15-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim.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 1-2, 8-10, 12-14, and 19-22 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Any rejections not repeated in this Office action are withdrawn, and the following rejections are the only rejections applied in this application.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 rejection under 35 U.S.C. 103 have been considered but are moot because they do not apply to the new grounds of rejection set forth hereinbelow.
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.
Claim 21 is 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.
Claim 21 recites the limitation "wherein the altered CLEC16A expression" in line 1. There is insufficient antecedent basis for this limitation in the claim.
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 1-2, 8-10, 12-14, and 19-22 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. This includes a new matter rejection.
For this rejection, the “patient” in claims 12 and dependent claims thereof is interpreted as an obese patient.
Claims 1-2, 8-10, 12-14, and 19-22 are drawn to a method of managing or reducing obesity in an obese patient comprising administering an siRNA that partially reduces CLEC16A expression, wherein the siRNA is one of SEQ ID NOs:1-582, wherein the method further comprises detection of body weight reduction in the patient.
Regarding the claimed subject matter, the instant specification at best describes that Clec16a knockout (KO) mice had the same body weight as the controls and lost body weight compared to controls one week after tamoxifen treatment. As such, the KO mice do not represent an “obese or overweight subject” or a patient in need of “management for obesity” required and claimed by the instant claims. Further, the genetic knockout of the Clec16a gene is far from adequately and sufficiently describing which of the 582 different SEQ ID NOs has the required functionality of providing the “management for obesity” or reducing obesity or body weight in the “obese or overweight subject”. It is further noted that the 582 different SEQ ID NOs are described to be targeted to NM_015226 (see page 29), which is a human CLEC16A mRNA sequence. Hence, it is prima facie apparent that the claimed “subject” reads on a human subject who is obese or overweight, wherein obesity is understood in the art as “a condition of abnormal or excessive fat accumulation in adipose tissue, to the extent that health may be impaired.” See page 1 or page 6 of Le Goff et al. (WO 2012/080503 A1). Note that the instant specification contains no definition or description of the term “obesity” or “obese”. As of the filing date sought in the instant case, use of an siRNA-mediated target inhibition for obesity treatment was applied to an obese subject, who was known to have an increased expression level of the gene/mRNA targeted by the siRNA as evidenced by Le Goff, who experimentally validated that adipose tissue samples obtained from obese patients show “an elevated expression” of the target ABCG1 gene/mRNA and that the increased “ABCG1 expression in adipose tissue from obese patients was positively correlated to the adipose diameter”, which is “a hallmark of adipocyte hypertrophy in obesity.” See page 31. Following the validation of the required nexus between the overexpression of the mRNA to be targeted by an siRNA in adipose tissues and the increased adipocyte diameter in obese patient, Le Goff demonstrates that local administration of an siRNA targeting ABCG1 into adipose tissue of high fat diet (HFD)-fed mice resulted in “significantly smaller” diameter of adipocytes and weight loss in the mice that gained weight due to the HFD. See pages 31-32. That is, the state of the prior art pertaining to a target-specific siRNA for obesity treatment purpose was such that the target mRNA should be increased in the obesity subject compared to controls. In the instant case, the instant specification does not even describe that an obese human subject has an increased expression level of CLEC16A, which is claimed to be partially inhibited for “managing or reducing obesity”. That is, the instant specification is completely silent regarding the required nexus between the obesity phenotype in a human subject and CLEC16A overexpression that is claimed be inhibited. In fact, there is no prior art that teaches that “an obese or overweight subject” has an increased CLEC16A expression that needs to be reduced for treating/managing obesity. In stark contrast to the underlying scientific principle inherently required by the claimed method such that CLEC16A should be increased in an obese human subject whose overexpressed CLEC16A should be reduced by the administered siRNA, a post-filing reference by Pan et al. (Journal of Cellular Physiology, 2021, 236:4944-4953) demonstrates a reduced expression level of Clec16a mRNA in obese (ob/ob) mice compared to control, wild-type mice with a statistical significance as shown in Figure 5(f) reproduced below.
PNG
media_image1.png
302
392
media_image1.png
Greyscale
In view of the complete lack of relevant prior art knowledge for the nexus between CLEC16A expression levels and obesity, and further in light of the disclosure of the post-filing reference by Pan et al., one of ordinary skill in the art would reasonably conclude that the instantly claimed “obese or overweight subject” would have a decreased mRNA expression level of Clec16a (or CLEC16A). That is, it was not known in the prior art that an obese mouse or an obese human has an increased expression of Clec16a (or CLEC16A) that needs to be partially reduced in order to provide the required effects of “managing or reducing obesity” as claimed in the instant case. Again, the instant specification is completely silent regarding the endogenous expression levels of CLEC16A “in obese or overweight subject” in need of obesity management.
As of the filing date sought in the instant case, reduction of CLEC16A was at best taught to be useful for treating symptoms of type 1 diabetes (T1D) as evidenced by Hakonarson et al. (US 2011/0286997 A1, of record), wherein “patients with T1D lose weight without treatment,” and “weight gain is not a symptom of T1D,” thus a “skilled artisan would have no expectation” or predictability that inhibition of CLEC16A would reduce body weight or obesity in an obese/overweight patient but would rather expect treatment of T1D “to cause weight gain” as stated by applicant on the record in the remarks filed on November 5, 2025. See pages 7-9 (emphasis added). Hence, it is clear on the record that the required nexus between CLEC16A and obesity was non-existent before the effective filing date. In view of the complete lack of relevant prior art knowledge pertaining to the claimed subject matter that requires CLEC16A expression should be positively correlated with obesity, the instant specification must provide detailed written description support for the claimed obesity treatment method comprising administering SEQ ID NOs:1-582 that reduce CLEC16A in an obese patient as the content/specificity of the specification’s disclosure inversely correlates with the state of the prior art knowledge and predictability. See MPEP §2163 teaching that “there is an inverse correlation between the level of skill and knowledge in the art and the specificity of disclosure necessary to satisfy the written description requirement. Information which is well known in the art need not be described in detail in the specification. See, e.g., Hybritech, Inc. v. Monoclonal Antibodies, Inc., 802 F.2d 1367, 1379-80, 231 USPQ 81, 90 (Fed. Cir. 1986). However, sufficient information must be provided to show that the inventor had possession of the invention as claimed.” (emphasis added).
In the instant case, not only does the specification fail to describe that an obese/overweight patient has overexpressed/increased CLEC16A, but the specification is also deficient in adequately describing the required structure-function correlation for any of SEQ ID NOs:1-582 having the required function of managing obesity or reducing body weight in an obese human subject. Interestingly, it is found that SEQ ID NO:582, for example, is 100% homologous to, not complementary to, the 21-mer sequence at positions 6743-6763 of NM_015226.1 (citation attached). As such, it would be scientifically impossible for a sequence set forth in SEQ ID NO:582 to have the activity in inhibiting CLEC16A because the target-homologous sequence would not be able to bind to the target sequence, absent objective evidence to the contrary.
In view of the foregoing, it is concluded that the instant specification fails to reasonably convey that the instant co-inventors completed and had possession of the instantly claimed obesity treatment/management method comprising administering agent comprising one of SEQ ID NOs:1-582 to an obese or overweight subject as of the filing date sought in the instant application.
Regarding the newly added claims, claims 22-23, applicant points out pages 22 and 27 of the specification and Figure 1 for support. In response, the pages and Figure 1 pointed out by applicant pertain to KO mice experiments, wherein the KO mice do not represent the instantly claimed “obese or overweight subject”. There is no disclosure/showing that the KO mice qualify as the instantly claimed “obese or overweight subject in need” of the “management for obesity” as required by the claims. As such, detecting reduction in body weight in the KO mice does not whatsoever describe the method step recited in claim 23 pertaining to the siRNA-treated “obese or overweight subject in need” of the “management for obesity”. In fact, the method step of “detecting body weight reduction” or the phrase is not even disclosed in the specification. Further, the limitation in claim 22 regarding the altered CLEC16A that is partially reduced by the siRNA “does not induce an autoimmune phenotype in the subject” who is “obese or overweight” is not described in the passages of the specification and Figure 1 pointed out by applicant. Page 27 at best describes a KO mouse that does not represent “the subject” who is “obese or overweight” and is treated with an siRNA comprising one of SEQ ID NOs:1-582. Interestingly, page 27 pointed out by applicant does not whatsoever describe/teach that reduced CLEC16A expression does not induce autoimmune responses. Pages 27-28 in fact teach “CLEC16A KO might trigger the autoimmune response” and “CLEC16A KO led to production of antinuclear antibodies indicative of systemic autoimmune disease”, wherein “upregulated specific antibodies in the sera from CLEC16A KO mice is interesting as these antibodies are also found in SLE and other systemic autoimmune diseases.” Hence, pages 27-28 contradict the recited “wherein” clause limitation of claim 21 thus fail to support the limitation of claim 21.
The instant specification including the passages and Figure 1 pointed out by applicant does not whatsoever contemplate or adequately describe the method claim 1 with the limitations of claims 22-23. Accordingly, claims 22-23 are not only inadequately described by the specification but they also introduce new matter that is not supported by the specification as originally filed.
Claims 1-2, 8-10, 12-14, and 19-22 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The factors to be considered in determining whether undue experimentation is required are summarized In re Wands, 858 F.2d 731,737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). The Court in Wands states: “Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is ‘undue’, not ‘experimentation’.” (Wands, 8 USPQ2d 1404). There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.” These factors include: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
For this rejection, the “patient” in claims 12 and dependent claims thereof is interpreted as a patient having obesity.
Claims 1-2, 8-10, 12-14, and 19-22 are drawn to an in vivo human patient treatment method of managing obesity and reducing body weight of an obese or overweight human patient in need of the treatment, wherein the treatment is provided by an siRNA molecule comprising one of SEQ ID NOs:1-582, which partially reduces the expression level of CLEC16A in the patient.
As of the filing date sought in the instant case, obesity therapy via partially reducing CLEC16A including reducing CLEC16A via an siRNA molecule was not known in the prior art as expressly acknowledged by the instant co-inventors at page 15 of the specification as following: “Specific siRNA preparations directed at inhibiting the expression of CLEC16A, as well as delivery methods are provided as a novel therapy to treat obesity.” (emphasis added). In fact, neither the instant specification nor the relevant prior art teaches the pathophysiological role of CLEC16A overexpression in obesity such that inhibition of CLEC16A expression is considered therapeutically useful for treating obesity. Before the effective filing date, inhibition of CLEC16A was at best taught to be useful in treating symptoms directly caused by type 1 diabetes (T1D) as evidenced by Hakonarson et al. (US 2011/0286997 A1, of record), wherein “patients with T1D lose weight without treatment,” and “weight gain is not a symptom of T1D,” thus a “skilled artisan would have no expectation” or predictability that inhibition of CLEC16A would reduce body weight or obesity in an obese/overweight patient but would rather expect treatment of T1D “to cause weight gain” as stated by applicant on the record in the remarks filed on November 5, 2025. See pages 7-9 (emphasis added). As such, there was no predictability in the relevant prior art that reduction of CLEC16A in an obese patient would result in the treatment/management of obesity.
The instant specification at best discloses working examples pertaining to Clec16a KO mice that do not represent the instantly claimed “obese or overweight subject in need” of obesity management, nor do the Clec16a KO mice represent the effects of administration of siRNA molecules comprising SEQ ID NOs:1-582. In fact, the specification contains no working example pertaining to any of SEQ ID NOs:1-582. That is, there is no enabling disclosure as to which SEQ ID NO or all of 582 SEQ ID NOs would indeed result in “managing or reducing obesity” “in an obese or overweight subject” as claimed. As such, it would impose an undue experimentation on a person of ordinary skill in the art to practice the instantly claimed, “novel” obesity therapy method as the person would have to test all 582 different siRNA molecules of SEQ ID NOs:1-582 in an obese/overweight animal model as the instant specification is completely silent regarding an actual enabling working example comprising administering any one of siRNA molecules claimed in the instant case to an obese/overweight subject for managing obesity and reducing body weight in the subject.
In view of the totality of factors (A)-(H) considered hereinabove, it is concluded that the instant specification fails to provide an enabling disclosure commensurate in scope with claims 1-2, 8-10, 12-14, and 19-22.
Claim Rejections - 35 USC § 102
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 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.
Claims 12-13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hakonarson et al. (US 2011/0286997 A1, of record).
Hakoarson teaches a method of inhibiting CLEC16A expression in a patient comprising “locally” or “directly” administering an siRNA molecule targeting CLEC16A to the patient. See paragraphs 0091-0092; claims 27-28.
Accordingly, claims 12-13 are described by Hakoarson et al.
Conclusion
No claim is allowed.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, RAM SHUKLA can be reached at 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/DANA H SHIN/Primary Examiner, Art Unit 1635