DETAILED ACTION
The present application is a national stage entry of PCT/EP2022/077247, filed 30 September 2022, which claims priority to US Provisional Application No. 63/250,362, filed 30 September 2021.
The preliminary amendment filed 28 March 2024 is acknowledged. Claims 2, 3, 7, 8 and 11-15 are pending in the current application and are examined on the merits herein.
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 .
Claim Rejections - 35 USC § 112(b)
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 8 and 14 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.
Regarding claims 8 and 14, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 112(a)
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 8 and 11-15 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating at least one condition selected from (a)-(l), does not reasonably provide enablement for preventing at least one condition selected from (a)-(l). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The Applicant’s attention is drawn to In re Wands, 8 USPQ2d 1400 (CAFC1988) at 1404 where the court set forth eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors: (1) The nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
The nature of the invention: The nature of the invention is administering a composition comprising nicotinamide riboside (NR) trioleates chloride (NRTOCl), a stable form of NR, for increasing intracellular levels of NAD+ in cells and tissues.
The state of the prior art: Prevent is defined as “keep from happening or existing”. See provided definition of prevent (definition of prevent, Merriam-Webster, cited in PTO-892). There is no prior art disclosing how to keep heart failure and kidney disease from happening.
The relative skill of those in the art: The relative skill of those in the art in treating the claimed conditions is high.
The predictability or unpredictability of the art: Each of the claimed conditions have multiple possible causes.
Risk factors for diabetes includes family history, race/ethnicity and environmental factors (MayoClinic, “Diabetes”, cited in PTO-892).
Alzheimer' s disease (AD) has traditionally been very difficult or impossible to prevent or treat effectively. See e.g. Damasio (Cecil Textbook of Medicine, 20th edition (1996), Vol. 2, cited in PTO-892) wherein it is stated that “[t]here is no cure for Alzheimer' s disease, and no drug tried so far can alter the progress of the disease” (p. 1994). Maczurek et al. (Advanced Drug Delivery Reviews, 2008, vol. 60, pp.1463-1470, cited in PTO-892) teaches that glucose metabolism is decreased in patients having AD, and that lipoic acid (LA) can ameliorate impaired glucose metabolism in type II diabetics (p.1466, 4.6. LA—a stimulator of glucose uptake and utilization). Maczurek et al. suggests that because the R form of lipoic acid (RLA) can increase glucose metabolism in vivo, it may be a contributing factor in the treatment of neurodegenerative disorders (p.1466, 4.6. LA—a stimulator of glucose uptake and utilization). Maczurek et al. teaches increased glucose metabolism may increase metabolites like acetyl-CoA wherein increasing production of acetyl-CoA by increasing glucose uptake is believed to be useful as a therapeutic strategy in treating AD (p. 1466, 4.6. LA—a stimulator of glucose uptake and utilization and p.1464, sections 3 and 4; see 4B).
Risk factors for cancer include age, lifestyle habits, family history and genetics, other health conditions, and the environment.
Thus, the risk factors for some of the claimed disorders/conditions vary. They include factors that cannot necessarily be changed or controlled, e.g. medications, diabetes, congenital heart disease, aging, other existing conditions. Thus, it is not deemed possible to prevent the claimed conditions, let alone with a single composition.
The breadth of the claims: The breadth of the claims includes preventing a neurodegenerative condition, cardiovascular disease, diabetes, a disease or disorder associated with aging, stress, inflammation, cancer, and an eye disorder.
The amount of direction or guidance presented: The presence or absence of working examples: There is no teaching or guidance on how one would administer the claimed composition to prevent a neurodegenerative condition, cardiovascular disease, diabetes, a disease or disorder associated with aging, stress, inflammation, cancer, and an eye disorder.
(8) The quantity of experimentation necessary: In order to practice the invention with the full range of all possible treatment methods beyond those known in the art, one skilled in the art would undertake a novel and extensive research program to show any and all forms of a neurodegenerative condition, cardiovascular disease, diabetes, a disease or disorder associated with aging, stress, inflammation, cancer, and an eye disorder could be prevented.
In order to determine the efficacy of the claimed therapies in the absence of any existing in vivo data, one skilled in the art would undertake animal testing in order to practice the invention. Animal experiments include, induction of the disease state, administration of the potential pharmaceutical compound and collection and analysis of data, additional burdens associated with compliance with animal welfare regulations, care, feeding and other maintenance of the animals, dissection of dead animals to collect data, and dispose of the dead animals after the research is finished. These trials would need to be run separately and repeatedly for each disorder to be treated, and success in treating each and every disorder would still not be definitive. The experimentation involved would therefore be significant, undue and unpredictable.
Genentech, 108 F.3d at 1366, sates that, “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion.” And “patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable.”
Therefore, in view of the Wands factors, as discussed above, particularly the breadth of the claims, Applicants fail to provide information sufficient to practice the claimed invention for preventing a neurodegenerative condition, cardiovascular disease, diabetes, a disease or disorder associated with aging, stress, inflammation, cancer, and an eye disorder.
Allowable Subject Matter
Claims 2 and 3 are allowed.
The closest prior art reference is disclosed by Szczepankiewicz et al. (US Patent Application Publication No. 20170189433, hereinafter the ‘433 Publication, cited in IDS submitted 28 March 2024).
The ‘433 Publication teaches nicotinamide riboside (NR) analogs, including esters of formula (I):
PNG
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202
234
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Greyscale
(claim 1). The NR analog is defined where R1 and R2 are -C(=O)-X-(C4-C18 straight chain or branched) alkyl or -C(=O)-X-(C2-C18 straight chain or branched) alkenyl; X is a covalent bond or O. The ‘433 Publication teaches preparing NR tri-butyrate, tri-pentanoate, tri-hexanoate, tri-ethyl carbonate and tri-benzoate (figure 3). The ‘433 Publication also teaches NR mono-oleate (figure 3, compound 13), as well as NR mono-tetra-decanoate, NR mono-nonanoate, mono-dodecanoate, mono-pentanoate, and mono-undecanoate. The goal of preparing the NR ester analogs is to provide bioavailable and stable prodrug forms of NR that are effective at elevating levels of NAD+ in desired tissues (para [0063]). Furthermore, the ‘433 Publication teaches the NR ester can be in the chloride form, from a list of counter anions (claim 18).
Figure 3 of the ‘433 Publication lists the amount of NR released from each NR analog at 0 min, 30 min, and 60 minutes. The NR+ tri-hexanoate hydrolyzed to NR to give 0 (peak area) at 0 minutes, 9310 (peak area) at 30 minutes, and 8370 (peak area) at 60 minutes, and formed a clear solution (figure 3, entry 6). The NR+ mono-oleate hydrolyzed faster at 0 min compared to NR+ tri-hexanoate, producing 6390 (peak area) NR at 0 minutes, 18000 (peak area) at 30 minutes, and 8420 (peak area) at 60 minutes (figure 3, entry 13). The NRH tri-benzoate was the most stable, and did not hydrolyze at 0 min, 30 min or 60 min (entry 8). Furthermore, turning to the different NR analogs, it is apparent the stability varies greatly between the different esters, including for example between NRH tri-butyrate versus NRH tri-isobutyrate.
To arrive at the claimed invention, one of ordinary skill in the art would have had to modify the exemplified NR mono-octanoate to the NR-tri-octanoate, and prepare the chloride salt form. Alternatively, one of ordinary skill in the art would have had to modify the exemplified NR tri-hexanoate to the longer fatty alkyl NR tri-octanoate, and prepare the chloride salt form.
While the ‘433 Publication teaches preparing NR triesters, and exemplifies preparing a mono-oleate ester, one of ordinary skill in the art would not have been motivated to prepare the tri-oleate ester of NR because the tri-benzoate ester was the most stable, with the long-chain esters being the least stable. Furthermore, the ordinary artisan would not have had a reasonable expectation of success, because the hydrolysis rates of the NR triesters varied significantly compared to one another. Furthermore, there is no stability data for a chloride salt form. And the salt forms do not necessarily improve the stability of the prodrugs. Thus, the present claims are allowable over the prior art of record.
Conclusion
Claims 2 and 3 are allowed.
Claims 8 and 11-15 are rejected.
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/BAHAR CRAIGO/
Primary Examiner
Art Unit 1699
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