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 .
Election/Restrictions
Applicant elected the following species without traverse in the reply filed on August 6, 2025, is acknowledged:
a. intravenous infusion
b. sirt6 gene is from human origin
In light of the Applicant’s elected species, claims 5-9 and 13-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
DETAILED ACTION
The claims filed on December 9, 2025, have been acknowledged. Claims 2-3, and 12 were cancelled. Claims 1, 4-11, 18, and 20 were amended. In light of the Applicant’s elected species, claims 5-9 and 13-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 1, 4, 10-11, and 16-20 are pending and examined on the merits.
Priority
The applicant claims domestic priority from U.S. provisional application No. 63/222,557, filed on July 16, 2021. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Claims 1, 4, 10-11, and 16-20 receive domestic benefit from U.S. provisional application No. 63/222,557, filed on July 16, 2021.
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, 4, 10-11, and 16-20 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 is a new rejection substantially similar to a previous rejection in response to Applicant’s amendments to claims 1, 18, and 20. Any aspect of Applicant’s traversal that is relevant to the rejection as newly written is addressed below.
Claims 1 recites the following claim language, “A method for extending the lifespan of a subject comprising the administration of … the sirt6 gene or a variant thereof”, Claim 18 recites the following claim language, ““A method for increasing health span of a subject comprising the administration of … the sirt6 gene or a variant thereof”. Claim 20 recites the following claim language, ““A method for delaying the onset of age-related diseases of a subject comprising the administration of … the sirt6 gene or a variant thereof”. Claims 1, 18, and 20 also recite that the sirt6 gene or variant is of human origin.
The specification discloses that variants correspond to changes in the wild type coding sequence of the gene (paragraph 0008). As such, any change to the coding sequence of Sirt6 is considered a variant, including mutations that cause premature stop codons, missense mutations that alter protein folding, and missense mutations that alter Sirt6 expression levels compared to wild type.
The broadest reasonable interpretation is that any human sirt6 gene or human sirt6 gene variant can extend the lifespan or health span of any subject or delay the onset of any age-related disease of any subject.
Under the written description guidelines (see MPEP 2163) the Examiner is directed to determine whether one skilled in the art would recognize that the Applicant was in possession of the claimed invention as a whole at the time of filing. The following considerations are critical to this determination.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. An original claim may lack written description support when (1) the claim defines the invention in functional language specifying a desired result but the disclosure fails to sufficiently identify how the function is performed or the result is achieved or (2) a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc). The written description requirement is not necessarily met when the claim language appears in ipsis verbis in the specification. "Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement." Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002).
Accordingly, to satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.
Actual Reduction to Practice
Regarding claims 1, 18, and 20 encompassing a genus of human sirt6 genes and variants, and wherein sirt6 gene and variants extend the lifespan or health span of any subject or delay the onset of any age-related disease of any subject, the specification provides no examples of human sirt6 genes or variants capable of extending the lifespan or health span of any subject or delaying the onset of any age-related disease of any subject.
Accordingly, Applicant did not demonstrate a reduction to practice of administering a human sirt6 gene or variant resulting in extending the lifespan or health span of any subject or delaying the onset of any age-related disease of any subject, nor did Applicant adequately set forth in terms of distinguishing identifying characteristics as evidenced by other descriptions of the invention that are sufficiently detailed to show that Applicant was in possession of the claimed genus of human sirt6 genes and variants capable of accomplishing the recited results for each method.
Disclosure of structure
The Applicant has provided no examples of human sirt6 genes or variants capable of accomplishing the recited results for each method.
Sufficient relevant identifying characteristics
The specification discloses that variants correspond to changes in the wild type coding sequence of the gene (paragraph 0008). As such, any change to the coding sequence of Sirt6 is considered a variant, including mutations that cause premature stop codons, missense mutations that alter protein folding, and missense mutations that alter Sirt6 expression levels compared to wild type.
The breadth of the claims encompass a genus of human sirt6 genes and variants, and wherein the human sirt6 gene and variants extend the lifespan or health span of any subject or delay the onset of any age-related disease of any subject, yet the present specification provides no guidance nor description about which human sirt6 genes or variants are able to accomplish the required results of extending lifespan or health span or delaying age-related disease onset in which subjects, therefore the skilled artisan would not know what rational approach to take to identify human sirt6 genes or variants capable of extending lifespan or health span or delaying age-related disease onset when administered to a subject. Therefore, it is incumbent on the applicant to provide this nexus between structure and function, in order to be given credit for possession of the claimed genus of sirt6 genes and variants.
An applicant may show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. Enzo Biochem, 323 F.3d at 964, 63 USPQ2d at 1613.
STATE OF THE ART & QUANTITY OF EXPERIMENTATION
The method of extending lifespan or health span or delaying age-related disease onset with any human sirt6 gene or variants of the claimed invention is not well established. Although administering sirt6 genes to subjects to extend lifespan or health span or delaying age-related disease onset was known in the art, only a small subset of the breadth of human sirt6 genes and variants have been shown to work. Therefore, one of skill in the art would neither expect nor predict the appropriate combination of sirt6 gene or variant and subject to accomplish the claimed results of extending lifespan or health span or delaying age-related disease onset.
The following describes the state of the art with respect to administering sirt6 to a subject to extend lifespan or health span of the subject or delay age-related disease onset in the subject. The prior art teaches administering AAV vectors encoding either mouse or human coding regions of the sirt6 gene to mice or rats to extend lifespan or health span of the mice or rats or delay age-related disease onset in the mice, as identified by United States Patent Application No. 2019/0345224 (Davidsohn) and Zhang et al. (Oncotarget 8: 72302-72314. 2017).
Davidsohn teaches a method of increasing health span and lifespan through gene therapy. Davidsohn teaches that they used a combination of viral vectors encoding mouse Sirt6 and other genes to increase health span and lifespan (specifically, RJV-1, RJV-9, RJV-10, and RJV-12). Davidsohn teaches that the gene therapy vectors for encoding the Sirt6 can be AAV vectors (paragraphs 0006-0007, 0071, and 0161, Table 1, Appendix B, and Example 9) which are known to be non-integrating viral vectors.
Zhang teaches that they administered pAAV-SIRT6 (human SIRT6) to male Sprague-Dawley rats to Ang II-induced hypertensive rats and found that pAAV-SIRT6 treatment strikingly potentiated cardiac levels of pAMPKα and ACE2 as well as decreased levels of CTGF, FKN, TGFβ1, collagen I and collagen III, resulting in alleviation of Ang II-induced pathological hypertrophy, myocardial fibrosis, cardiac dysfunction and ultrastructural injury in hypertensive rats (abstract and Figures 1-10). Although Zhang did not specifically examine whether lifespan/health span was extended in these rats, this would be a downstream feature of the method of Zhang as the rats had improved cardiac function and the extended lifespan and health span would naturally flow from these cardiac improvements. AAV vectors are known to be non-integrating viral vectors. Furthermore, these changes would delay the onset of heart failure, an age-related disease.
Therefore, the art has identified that the full coding regions of the human or mouse sirt6 gene are capable of extending lifespan and health span and delaying age-related disease onset.
However, variants, such as sirt6 truncations, point mutations, non-coding sequences, and the breadth of subjects have not been taught by the prior art
Applicant has claimed a genus of human sirt6 genes and variants, and wherein human sirt6 gene and variants extend the lifespan or health span of any subject or delay the onset of any age-related disease of any subject, yet the specification has not disclosed such sirt6 genes capable of accomplishing the claimed results, has not set forth in terms of distinguishing identifying characteristics as evidenced by other descriptions of the invention that are sufficiently detailed to show that Applicant was in possession of the claimed genus of human sirt6 genes and variants, and wherein human sirt6 gene and variants extend the lifespan or health span of any subject or delay the onset of any age-related disease of any subject. Furthermore, the state of the art indicated a limited number of potential human sirt6 genes capable of accomplishing the stated results when administered to specific subjects. However, the claims are much broader to what is known in the art, and one of skill in the art would neither expect nor predict the claimed extension of the lifespan or health span of any subject or delay of the onset of any age-related disease of any subject according to the claimed genus of human sirt6 genes and variants beyond those described in the prior art.
CONCLUSION
Therefore, the Examiner concludes that there is insufficient written description of the instantly claimed genus of human sirt6 genes and variants, and wherein human sirt6 gene and variants extend the lifespan or health span of any subject or delay the onset of any age-related disease of any subject. Specifically, there is limited description of the structure-function relationship between the claimed genus of human sirt6 genes and variants, and their ability to extend the lifespan or health span of any subject or delay the onset of any age-related disease of any subject when administered. The Examiner further concludes a skilled artisan would find the specification inadequately describes the claimed genus of human sirt6 genes and variants.
Response to Arguments
Applicant's arguments filed December 9, 2025, are acknowledged.
Applicant argues that by defining the claimed genus of sirt6 genes and variants as of human origin overcomes the rejection. Applicant argues that one of ordinary skill in the art would recognize that the claimed human SIRT6 or a variant thereof would code for a histone deacetylase with the same functionality based on paragraph 0006 of the specification reciting that the SIRT6 gene codes for a histone deacetylase. Applicant argues that the subject and age-related disease are fully described in the specification. Therefore, there is sufficient written description in the claims.
Applicant's arguments have been fully considered but they are not persuasive.
Although Applicant has narrowed the genus of Sirt6 genes and variants to those of human origin, there is still an expansive breadth of human Sirt6 genes and variants that fall within this genus, including the wild type gene, truncations, point mutations, and non-coding sequences. Although Applicant identifies that the Sirt6 gene encodes a histone deacetylase, this does not limit the breadth of the claims to only those variants that would encode for a functional protein. Furthermore, the art only identifies that the full length coding sequence has been shown to have the intended result of extending life span, health span, or delaying onset of age related diseases while the Applicant has not reduced to practice any human Sirt6 gene capable of being used in the claimed methods. Therefore, there remains an insufficient written description of the instantly claimed genus of human sirt6 genes and variants, and wherein human sirt6 gene and variants extend the lifespan or health span of any subject or delay the onset of any age-related disease of any subject
Withdrawn Claim Rejections - 35 USC § 102
The prior rejection of claim(s) 1-4, 10-11, and 16-20 under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by United States Patent Application No. 2019/0345224 (Davidsohn) is withdrawn in light of Applicant’s amendments to claims 1, 18, and 20 to recite that the Sirt6 gene is of human origin.
The prior rejection of claim(s) 1-2, 4, 12, and 17-20 under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Zhang et al. (Oncotarget 8: 72302-72314. 2017) is withdrawn in light of Applicant’s amendments to claims 1, 18, and 20 to recite that the AAV vector has a specific serotype.
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.
The factual inquiries 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, 4, 10-11, and 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over United States Patent Application No. 2019/0345224 (Davidsohn) and further in view of Zhang et al. (Oncotarget 8: 72302-72314. 2017). This is a new rejection made in response to Applicant’s amendemnts to claims 1, 18, and 20. Applicant’s traversal has been fully considered but is moot in response to the new rejection.
Regarding claims 1 and 18, Davidsohn teaches a method of increasing health span and lifespan through gene therapy. Davidsohn teaches that they used a combination of viral vectors encoding Sirt6 and other genes to increase health span and lifespan (specifically, RJV-1, RJV-9, RJV-10, and RJV-12). Davidsohn teaches that the gene therapy vectors for encoding the Sirt6 can be AAV vectors (paragraphs 0006-0007, 0071, and 0161, Table 1, and Example 9) which are known to be non-integrating viral vectors. Davidsohn teaches that the subject for treatment can be a rat or a human (paragraph 0061). Davidsohn teaches that serotype any of serotypes 1-5 can be used (paragraph 0046).
Davidsohn does not teach wherein the sirt6 gene is from human origin.
However, Zhang teaches that they administered pAAV-SIRT6 to male Sprague-Dawley rats to Ang II-induced hypertensive rats and found that pAAV-SIRT6 treatment strikingly potentiated cardiac levels of pAMPKα and ACE2 as well as decreased levels of CTGF, FKN, TGFβ1, collagen I and collagen III, resulting in alleviation of Ang II-induced pathological hypertrophy, myocardial fibrosis, cardiac dysfunction and ultrastructural injury in hypertensive rats (abstract and Figures 1-10). Although Zhang did not specifically examine whether lifespan/health span was extended in these rats, this would be a downstream feature of the method of Zhang as the rats had improved cardiac function and the extended lifespan and health span would naturally flow from these cardiac improvements. AAV vectors are known to be non-integrating viral vectors. Zhang teaches that the SIRT6 gene was a human SIRT6 (page 72312, column 1, paragraph 3).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used human sirt6 as part of the method of increasing health span and lifespan through sirt6 gene therapy of Davidsohn, as identified by Zhang, to arrive at the instantly claimed invention. One of ordinary skill in the art would have a reason to use the human sirt6 gene with a reasonable expectation of success because Davidsohn and Zhang both deliver AAVs encoding Sirt6 to improve health span and lifespan and Zhang successfully reduces to practice AAVs encoding human Sirt6 can improve health span and lifespan in rats, one of the intended targets of the method of Davidsohn. Furthermore, Davidsohn specifically identifies humans as a potential target and it would have been obvious that a human Sirt6 gene would be encoded when delivering a Sirt6 gene to treat a disease in a human. As Zhang has already shown that human Sirt6 can be delivered to a subject to improve health span and lifespan, it would have been obvious to one of ordinary skill in the art that human Sirt6 could be used in the method of Davidsohn. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Regarding claim 4, Davidsohn teaches that the AAV vectors can be administered intravenously (paragraph 0156). Zhang teaches that they administered the pAAV-SIRT6 vector intravenously (page 72312, column 1, paragraph 3).
Regarding claims 10-11, Davidsohn teaches that the coding sequences of the gene therapy vectors can include promoters and enhancers (paragraph 0168).
Regarding claims 16-17, Davidsohn teaches that the subject for gene therapy can be humans or non-human mammals (i.e. animals) (paragraph 0061 and Example 9).
Regarding claims 19-20, Davidsohn teaches that their method provides for the slowing, inhibiting, forestalling or reversing of age-related diseases or conditions. Exemplary age-related or other diseases or conditions include one or more of cardiovascular diseases, diabetes, and neurological disorders (paragraph 0007 and Example 9).
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 KEENAN A BATES whose telephone number is (571)270-0727. The examiner can normally be reached M-F 7:30-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Doug Schultz can be reached at (571) 272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KEENAN A BATES/Examiner, Art Unit 1631
/JAMES D SCHULTZ/Supervisory Patent Examiner, Art Unit 1631