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 .
Information Disclosure Statement
The Information Disclosure Statement (IDS) filed on 08/15/2025 has been considered.
Claim Status
The claim set and Applicant’s remarks filed August 15, 2025 have been entered. Claims 1-11, 13-16 and 21-22 are canceled. Claims 23-25 are new. Thus, claims 12, 17-20 and 23-25 as amended are examined on the merits herein.
Withdrawn Objections and Rejections
With respect to the objections and/or rejections mailed in the non-final office action on May 19, 2025:
(I) The objection to the specification is withdrawn in view of the newly filed specification on August 15, 2025.
(II) The objection to claims 12, 18 and 21 are withdrawn in view of Applicants claim amendments to claims 12, 18 and 21 as discussed above in the claim set filed August 15, 2025.
(III) The rejection of claims 12-23 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph is withdrawn in view of Applicants deleting the limitation “an internal or external counter-ion” from R11 recited in claim 12.
(IV) The rejection of claims 13-16 and 21-22 under 35 U.S.C. 102(a)(1) or 102 (a)(2) and 35 U.S.C. 103 is withdrawn in view of Applicant canceling these claims as discussed in the Claim Status section above.
Response to Arguments
(I) The rejection of claims 12, 17, 19-20 and 23 under 35 U.S.C. 102(a)(1) or 102 (a)(2); and
(II) The rejection of claim 18 under 35 U.S.C. 103 are maintained.
Applicant argues:
(A) The method of claim 12 has been amended to include the limitation “for decreasing a bacterial load in affected organ(s) and/or in body fluids of a subject suffering from a bacterial infection, see Applicant’s remarks, pg. 14, second paragraph and the second to last paragraph from the bottom of the page.
(B) Sinclair fails to teach a therapeutic effect of NMN on bacterial infections, see Applicant’s arguments, pg. 14, second to last paragraph from the bottom of the page.
(C) Sinclair is silent with respect to any method directed to decreasing bacterial load during the treatment of disorders associated with infection, and that a person of ordinary skill in the art would recognize a method for reducing inflammation as Sinclair discloses by lowering the expression of inflammation-related markers is distinct from a method directed to decreasing bacterial load during the treatment of such disorders, see Applicant’s remarks, pg. 14, last paragraph of the page.
(D) Bacterial infections are not disclosed anywhere in Szczepankiewicz, see Applicant’s remarks, pg. 16, second to last paragraph from the bottom of the page.
(E) There is no substantial evidence, nor clear and particular evidence within the record of motivation for combining Sinclair and Szczepankiewicz, see Applicant’s remarks, pg. 17, second paragraph.
With respect to Applicant’s arguments (A)-(C), the Examiner respectfully notes Sinclair teaches administering an effective amount of an agent, specifically NMN, to increase NAD+ in a subject to treat disorders associated with inflammation including sepsis, tuberculosis, and pulmonary inflammation caused by Mycobacterium tuberculosis; and wherein Sinclair demonstrates that old mice treated with NMN showed decreased levels of the inflammatory marker TNFα.
The Examiner also reasonably interprets the method of treatment of disorders associated with inflammation as described by Sinclair above, by administering an effective amount of an agent that increase levels of NAD+, specifically NMN, will as evidenced by Singhal in the 102 rejection below, increase NAD+ levels and activate the enzymatic activity of SIRTs in infected cells, thereby resulting in reduced inflammation and induction of host anti-bacterial programs such as autophagy to reduce bacterial burden of the infection taught by Sinclair as discussed above.
With respect to Applicant’s arguments (D)-(E), the Examiner respectfully notes Sinclair and Szczepankiewicz are drawn to treating inflammation with compounds that modulation NAD+, for example NMN as disclosed by Sinclair and the compound represented by formula (I) of Szczepankiewicz.
The Examiner also respectfully notes Sinclair also teaches as discussed above inflammation associated with sepsis, bacterial meningitis and pulmonary infections caused by bacteria. Thus, there is a clear motivation to combine Sinclair and Szczepankiewicz by using the compound represented by formula (I) of Szczepankiewicz to treat the inflammation as taught by Sinclair by modulating NAD+.
Thus, Applicant’s arguments (A)-(E) have been fully considered but are not found persuasive.
New Claim Rejections
The following are new ground(s) or modified rejections necessitated by Applicant's amendment, filed on August 15, 2025, where the limitations in pending claims 12 and 17-20 as amended now have been changed and claims 23-25 have been newly added. Therefore, rejections from the previous Office Action, dated May 19, 2025, have been modified and are listed below.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 12, 17, 19-20 and 23-25 are rejected under 35 U.S.C. 102(a)(1) or 102 (a)(2) as being anticipated by Sinclair et al. (Published 24 September 2015, US-20150265642-A1, IDS filed 01/22/2025) as evidenced by Singhal et al. (Published 17 October 2018, International Immunology, Vol. 31, Issue 2, pp. 59-67, PTO-892)).
Regarding claims 12, 17, 19-20 and 23-25, Sinclair teaches treatment and prevention of disorders associated with inflammation by administering agents that increase levels of NAD+, such as NAD+ precursors, see abstract, paragraph 3. Sinclair teaches treating or preventing a disorder associated with inflammation in a subject in need thereof comprising administering to the subject an effective amount of an agent that increases the level of NAD+ in the subject, see paragraph [0033].
Sinclair teaches treatment of disorders associated with inflammation include septic shock or sepsis (i.e. sepsis, required in claims 24 and 25), tuberculosis or bacterial meningitis or pulmonary inflammation, wherein pulmonary inflammation is caused by infection, such as from Staphylococcus aureus, Streptococcus pneumoniae Mycobacterium tuberculosis and Bacillus anthracis (e.g. a bacterial infection, required in claims 12, 20 and 23-25), see paragraph [0217].
In some embodiments the agent is an NAD+ precursor, wherein the NAD+ precursor is NMN or a salt thereof, see paragraph [0033].
Sinclair teaches NMN stands for nicotinamide mononucleotide (NMN), see paragraph [0159]. The Examiner notes that nicotinamide mononucleotide shares all structural limitations as required by formula I-A in claim 19; and would meet the structural limitations of formula (I) of claim 12 when R8=NH2; Y=CH, R1=R3=R4=R6=H; R2=R5=OH (i.e. hydroxyl); X=O (i.e. oxygen) and R7=P(O)(OH)2.
Additionally, with respect to the limitation of “decreasing a bacterial load in affected organ(s) and/or bodily fluids”, required in claim 12, lines 1-2. The Examiner reasonably interprets this limitation as a functional consequence of administering a therapeutically effective quantity of at least one compound of formula (I) as recited in claim 12. Moreover, Sinclair exemplifies within Figure 26B that old mice who were treated with NMN had decreased expression of the inflammation-related marker TNFα, see paragraph [0467] and Figure 26B.
Furthermore, the Examiner reasonably interprets this limitation as a functional consequence of administering the NMN to the subject suffering from a bacterial infection as taught by Sinclair as discussed above which is supported as evidenced by Singhal which discloses targeting dysregulated NAD+ consumers and the cellular NAD+ milieu during a mycobacterial infection to induce the host cell antibacterial program, where the mycobacterial infection results in induction of TNFα and has been shown to increase CD38 expression in macrophages and T cells. Singhal teaches CD38 as a NAD+ consumer and where the activation of CD38 leads to a decreased NAD+ cellular pool and reduced enzymatic activity of sirtuins, resulting in abrupted cellular metabolism and immune responses which are associated with increased mycobacterial growth, see pg. 63, Fig. 2.
Singhal further discloses increasing NAD+ levels activate the enzymatic activity of SIRTs in infected cells, resulting in reduced inflammation and induction of host anti-bacterial programs such as autophagy, leading to the restriction of bacterial growth and decreased bacterial burden, see pg. 63, Fig. 2.
As a result, since Sinclair teaches administering an effective amount of an agent, specifically NMN, to increase NAD+ in a subject to treat disorders associated with inflammation including sepsis, tuberculosis, and pulmonary inflammation caused by Mycobacterium tuberculosis; and wherein Sinclair demonstrates that old mice treated with NMN showed decreased levels of the inflammatory marker TNFα; the Examiner reasonably interprets the method of treatment of disorders associated with inflammation as described by Sinclair above by administering an effective amount of the agent that increases levels of NAD+, specifically administering NMN, will as evidenced by Singhal, increase NAD+ levels and activate the enzymatic activity of SIRTs in infected cells, resulting in reduced inflammation and induction of host anti-bacterial programs such as autophagy to reduce bacterial burden of the infection taught by Sinclair which the Examiner respectfully notes includes mycobacterial infections as discussed above.
Thus, based on the teachings of Sinclair as evidenced by Singhal, the teachings of Sinclair anticipate claims 12, 17, 19-20 and 23-25.
Claim Rejections - 35 USC § 103
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Sinclair et al. (Published 24 September 2015, US-20150265642-A1, IDS filed 01/22/2025) as evidenced by Singhal et al. (Published 17 October 2018, International Immunology, Vol. 31, Issue 2, pp. 59-67, PTO-892)) as applied to claims 12, 17, 19-20 and 23-25 above, and further in view of Szczepankiewicz et al. (Filed 22 March 2019, US-10618927-B1, PTO-892 mailed 05/19/2025).
Sinclair as evidenced by Singhal address claims 12, 17, 19-20 and 23-25 as written above. Although, Sinclair does not teach a compound of formula (I) wherein R7 is represented as claimed in claim 18.
However, in the same field of endeavor of treating inflammation, Szczepankiewicz teaches the compound of formula (I) represented by
PNG
media_image1.png
321
566
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Greyscale
, see Col. 5, lines 1-15, wherein n in some embodiments is 2, see Col. 5, lines 15-20, which meets all the structural limitations of formula (I) of claim 12 when R8=NH2; Y=CH, R1=R1’=R3=R3’=R4=R4’=R6=R6’=H; R2=R2’=R5=R5’=OH (i.e. hydroxyl); X=X’=O (i.e. oxygen) and R7=as depicted in claim 18, wherein R9=OH; and n=2 as defined in claim 12.
Szczepankiewicz teaches compounds and compositions for the modulation of nicotinamide adenine dinucleotide (NAD+) and using such compounds or compositions to promote the increase of intracellular levels of nicotinamide adenine dinucleotide (NAD+) in cells and tissues for treating diseases, see abstract.
Szczepankiewicz teaches using the disclosed compounds and pharmaceutical compositions thereof for a variety of therapeutic applications including for example treating inflammation, see Col. 10, lines 15-25.
It would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have included formula (I) taught by Szczepankiewicz into the method taught by Sinclair above as within the scope of the artisan as combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to use formula (I) of Szczepankiewicz to treat the inflammation of the subject of Sinclair as discussed above. One of ordinary skill in the art would have had a reasonable expectation of success to have included formula (I) of Szczepankiewicz into the method of Sinclair, as Szczepankiewicz teaches formula (I) as useful in treating inflammation; in addition both the compound of Sinclair and Szczepankiewicz increase NAD+ levels as discussed above.
Thus, the claimed invention as a whole would have been prima facie obvious over the combined teachings of the prior art.
Conclusion
No claims are allowed in this action.
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 JARET J CREWS whose telephone number is (571)270-0962. The examiner can normally be reached Monday-Friday: 9:00am-5:30pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Renee Claytor can be reached at (571) 272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JARET J CREWS/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691