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 .
Election/Restrictions
Applicant's election with traverse of Group I claims 1 – 10 in the reply filed on January 23, 2026 is acknowledged. The traversal is on the ground(s) that the groups share a special technical feature, which is the use of an inhibitor of nicotinamide dinucleotide (NAD)degradation to protect NAD in a sample. This is not found persuasive initially because the several groups do not fall within any category defined by unity of invention, e.g., a composition, method of making and method of using the composition. Further, the concept of “using” an inhibitor of NAD degradation to protect NAD does not make a contribution over the prior art. In support, Balan teaches methods wherein inhibitors of NAD degradation are used to protect NAD in a sample (p.113-114).
The requirement is still deemed proper and is therefore made FINAL.
Claims 1 – 21 are pending; claims 11 – 21 are withdrawn as being drawn to non-elected inventions; claims 1 – 10 have been considered on the merits.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on May 12, 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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 – 10 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.
Claims 1 – 10 are drawn to a method of detecting and quantifying nicotinamide dinucleotide (NAD) in a biological sample wherein the NAD is protected by “using an inhibitor of NAD degradation.” These claims are considered genus claims that encompass a wide array of “inhibitors of NAD degradation.” The specification fails to set forth a representative number of examples in order to reasonably verify possession of such a potentially enormous number of inhibitors.
The MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic. It is unquestionable that the claims are broad generics, with respect to all inhibitors of all enzymes or actives that act to degrade NAD. The instant disclosure fails to identify a single inhibitor of a single active that degrades NAD. The possible variations of inhibitors are limitless with potentially millions of types of inhibitors.
In paragraph 0150 of the published application, the specification defines NAD as a labile metabolite that is the substrate for multiple enzymes such as NAD hydrolases, ADP ribosylation enzymes and deacetylases. Example 1 refers to figure 1A – 1J for describing the method steps of the claimed method, however these figures fail to describe any method steps. Rather they show the “signal linearity during the NAD detection window.” The description of figure 1 describes adding nicotinamide (NAM) or apigenin to homogenized brain tissue, blood, CSF. While addition of NAM (a precursor of NAD), shows higher levels of NAD than control samples, the addition of apigenin fails to afford protection to NAD (figure 1F). Additionally, no examples are provided to show the NAM serves to inhibit NAD degradation rather than as a substrate for the salvage pathway of NAD production (it’s primary role as discussed by Park et al., IDS 05.12.2023 NPL #2, page 102; Balan, page 113-114). Moreover, the example fails to show adding NAM inhibits NAD degradation as opposed to serving as a precursor to NAD and increasing NAD levels (see Park et al., p.102-103); or a method where apigenin acts as an inhibitor of NAD degradation or protect NAD in the samples.
The remaining examples demonstrate a correlation of NAD to presence of ALS where decrease in brain NAD relates to disease progression (example 2); SR1457 activates NAMPT thereby increasing NAD which delays progression of motor impairment (example 3); measures NAD in CSF, however no use of a NAD protecting agent (inhibitor of NAD degradation) is described (example 4); and measures NAD after a subject is treated with SR005 (SR1457 analog) or nicotinamide (NAM) indicating NAD as a pharmacodynamic biomarker (example 5). Moreover, the examples do not describe any method whereby NAD is protected by the addition of an inhibitor of NAD degradation as claimed. Notwithstanding, even if the examples were to show NAM “protects” NAD in a biological sample, the specification fails to correlate any particular structure with the relevant function of protecting NAD, or inhibiting NAD degradation, as claimed.
The purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by them. A patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that the inventor invented the claimed invention. Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations" and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." The specification lacks sufficient variety of species of inhibitors of NAD degradation to reflect this variance in the genus since the specification does not provide any examples of such a genus of inhibitors. Accordingly, the specification fails to provide adequate written description for the genus of “inhibitor or NAD degradation” and does not reasonably convey to one skilled in the relevant art that the inventors, at the time the application was filed had possession of the entire scope of the claimed invention Moreover, the specification neither describes the complete structure of a representative number of species, nor describes a representative number of species in terms of partial structure and relevant identifying characteristics. Absent of such teachings and guidance as to the structure and function of these inhibitors, the specification does not describe the claimed inhibitors of NAD degradation in such full, clear, concise and exact terms so as to indicate that Applicant had possession of these inhibitors at the time of filing of the present application.
Thus, the written description requirement has not been satisfied.
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.
Claims 1 – 10 are 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 1 and its dependents are drawn to a method for detecting and quantifying NAD in a biological sample, however are rendered indefinite because the claim fails to recite required active steps to carry out measuring or detecting NAD in the sample. The claim only requires “using an inhibitor of NAD degradation,” collecting a same and measuring NAD without any active step to carry out the detection or quantification. Moreover, the claim essentially recites a method for detecting and quantifying NAD by collecting a sample and measuring, with nothing more.
Claim 1 and its dependents are further indefinite for reciting “using an inhibitor” as the phrase fails to set forth positive and active steps for carrying out any method.
In claim 4, the recitations of “the addition of the inhibitor” and “diluting” lack proper antecedent basis.
Claim 8 is indefinite because the claim required fractionating the sample into components having specific molecular weights however fails to set forth what the components are that have the recited weights. Clarification is required.
In claim 9, the recitation of “one or more factors” renders the claim indefinite because the phrase is not adequately defined by the claim language or specification.
Claim 10 is indefinite for reciting “using an enzymatic cycling assay” as the phrase fails to set forth positive and active steps for carrying out any method.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1 – 10 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more.
Step 1: Yes, the claims are drawn to a method for detecting and quantifying nicotinamide dinucleotide (NAD) in a biological sample, which is a process.
Step 2A, Prong 1: Yes, the claim recites detecting and quantifying NAD in a biological sample, which is a natural phenomenon.
Step 2A, Prong 2: No, the claims do not recite additional elements that integrate the judicial exception into a practical application. Initially, the claims fail to recite any particular active step(s) that must be carried out to detect or quantify/measure NAD. Claim 1 recites protecting NAD in the sample by using an inhibitor of NAD degradation, however no active steps are recited to “use” the inhibitor. Further, while claim 1 recites steps for processing the sample, these steps are recited as optional, indicating they are not required to be performed. Likewise, claims 5 – 9 are not required steps as they merely define optional steps. Regarding claims 2 and 3, the limitations defining the inhibitor include nicotinamide (NAM) which is a component of the NAD metabolic cycle. In this regard, NAM is both a byproduct and recycled precursor of NAD metabolism/catabolism which means NAM is present in samples as part of the natural cycle, or the natural phenomenon.
Step 2B: No, the claims do not recite additional elements that amount to significantly more than the judicial exception. Claim 1 recites protecting NAD in the sample by using an inhibitor of NAD degradation, however no active steps are recited to “use” the inhibitor. Further, while claim 1 recites steps for processing the sample, these steps are recited as optional, indicating they are not required to be performed. Likewise, claims 5 – 9 are not required steps as they merely define optional steps. Regarding claims 2 and 3, the limitations defining the inhibitor include nicotinamide (NAM) which is a component of the NAD metabolic cycle. In this regard, NAM is both a byproduct and recycled precursor of NAD metabolism/catabolism which means NAM is present in samples as part of the natural cycle, or the natural phenomenon. Moreover, the claims do not recite any meaningful limitations beyond generally linking the use of the judicial exception to a particular technological environment.
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 1 – 2 and 4 – 10 are rejected under 35 U.S.C. 102a2 as being anticipated by Balan et al. (2010).
Regarding claims 1 - 2, Balan teaches a method for quantifying nicotinamide dinucleotide (NAD) in brain tissue (a biological sample), the method comprising adding nicotinamide mononucleotide (NMT, an inhibitor of NAD degradation) to the sample then quantifying (measuring) the amount of NAD in the tissue (abstract, p.113). Regarding the steps of disrupting, clarifying and fractionating the sample, it is noted that these steps are optional, and not required by the claimed method.
Regarding claim 4, the NMT is added to the tissue during the staining process, or dilution (p.113, 114).
Regarding claims 5 – 9, the steps are indicated as optional and are therefore not required by the rejected claims.
Regarding claim 10, Balan teaches measuring and quantifying the NAD using an enzymatic cycling assay, whereby NADH levels are quantified and visualized by converting a tissue stain to formazan (p.113 – 114).
The reference anticipates the claimed subject matter.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RUTH A DAVIS whose telephone number is (571)272-0915. The examiner can normally be reached Monday - Friday (8am - 4pm).
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/RUTH A DAVIS/Primary Examiner, Art Unit 1699
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