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 without traverse of Group II, claims 15-21 and the species “elemental magnesium” and “GABA” (gamma-aminobutyric acid) as the individual amine moiety-containing compound in the reply filed on 12/06/23 has been acknowledged.
Claim Status
Claims 2, 9-11, 13, 16 and 24 are cancelled.
Claims 1, 3-8, 12, 14, 15, 17-23 and 25-34 are pending.
Claims 1, 3-8, 12, 14, 22, 23, 25-30 and 32-34 are withdrawn.
Claims 15, 17-21 and 31 are under examination as they read upon the elected subject matter.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 1/26/26 is in compliance with the provisions of 37 CFR 1.97. The information disclosure statements are being considered by the examiner.
Withdrawn rejections
Applicant's arguments filed 2/10/26 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Any rejection and/or objection not specifically addressed below is herein withdrawn.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
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 15, 17-21 and 31 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 a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Among these factors are: 1) scope or breadth of the claims; 2) nature of the invention; 3) relative level of skill possessed by one of ordinary skill in the art; 4) state of, or the amount of knowledge in, the prior art; 5) level or degree of predictability, or a lack thereof, in the art; 6) amount of guidance or direction provided by the inventor; 7) presence or absence of working examples; and 8) quantity of experimentation required to make and use the claimed invention based upon the content of the supporting disclosure. When the above factors are weighed, it is the Examiner’s position that one skilled in the art could not practice the invention without undue experimentation. While all of the factors have been considered, only those required for a prima facie case are set forth below. Applicant is not enabled for the claimed method as explained in the following analysis.
Scope and nature of the invention
Independent claim 15 is directed to:
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The preamble recites: “reducing nitrosamine formation from ingesting an amine compound”. Consideration of the preamble gives meaning and purpose to the manipulative steps in this case. “The preamble is therefore not merely a statement of effect that may or may not be desired or appreciated. Rather, it is a statement of the intentional purpose for which the method must be performed.” Jansen v. Rexall Sundown, Inc., 342 F.3d 1329, 1333 (Fed. Cir. 2003). Thus, “the claim was interpreted to require that the method be practiced with the intent to achieve the objective stated in the preamble. ” Jansen v. Rexall Sundown, Inc., 342 F.3d 1329, 1333 (Fed. Cir. 2003). The term “co-administration” is reasonably interpreted to mean to provide the ingredients at the same time to the subject. Examples 5-8 provide all the components simultaneously in a capsule for administration to a subject [0068-0071]. Thus, the amine compound, elemental metal and nitrate and/or nitrite are administered co-administered simultaneously together and that reduces nitrosamine formation from ingestion of the amine compound.
Relative skill level
MPEP 2141.03 (I) states: “The “hypothetical ‘person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988).
Formulation and administration of active agents falls within the purview of medical/pharmaceutical artisans with knowledge of the biochemistry/chemistry of the components in the formulation being administered. In addition, the prior art itself reflects an appropriate level (MPEP 2141.03(II)).
Knowledge in the art and level or degree of predictability, or a lack thereof, in the art
The instant application is directed to chemical processes under physiological conditions. MPEP 2164.03 states: “In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).”
Fine et al. (EP1429829; of record) teach that nitrite in acidic conditions produces the nitrosating agent nitric oxide [0013]:
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Fine et al. also teach that nitric oxide can be generated by chemical reduction reactions such as reaction of metallic copper (elemental copper) and dilute nitric acid to generate nitric oxide [0042].
Sulcius, A. (J. Chem. Educ. 2015;92:1971-1972; of record) discloses a method of generating nitric oxide gas by combining magnesium metal (elemental magnesium, a powerful reducing agent) with 10-20% HNO3, which is a source of nitrate anion in an acidic solution (page 1971, bottom left column; Figure 1A). Sulcius also states that the nitrate anion is reduced to nitric oxide (Associated content):
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Lakhmir Singh ([online] retrieved on 12/18 from: https://www.google.com/books/edition/Lakhmir_Singh_s_Science_for_Class_8/z2wtDAAAQBAJ?hl=en&gbpv=0; 2016; page 70) teaches that it is well-known that magnesium metal reacts with dilute HCl to form MgCl2 and hydrogen gas as shown on page 70:
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Amount of guidance or direction provided by the inventor and the presence or absence of working examples
Examples 1-3 are purported to demonstrate the effectiveness of the compositions and methods in reducing nitrosamine formation. However, the components were not co-administered. In fact, the elemental magnesium was administered 1 hour after administration of the amine compound and nitrite, which is sequential administration. In Examples 5-8 that actually administer a composition of components to a subject, the components are simultaneously administered in a capsule. Thus, co-administration is reasonably interpreted to mean simultaneous administration of the components. On the contrary, the claimed method of co-administration of the amine compound, elemental magnesium and nitrate/nitrite is most likely to result in promotion of nitrosamine formation in view of the knowledge in the art. The Examiner finds that ingested nitrite will spontaneously form nitrosating nitric oxide once it hits the acidic environment of the stomach, as taught by Fine et al., which will then nitrosate the amine. Through the teachings of Sulcius, it is expected that nitrate will be reduced to nitrosating nitric oxide by elemental magnesium to also nitrosate the amine. Furthermore, Lakhmir Singh teaches that elemental magnesium will spontaneously react with the hydrochloric acid in the stomach to produce hydrogen gas and magnesium chloride and thus serve as an elemental magnesium sink in competition with any potential reduction of nitrosamines. Therefore, it is predictable that co-administration of the claimed components produces nitrosamines rather than reduces nitrosamine formation as claimed.
Quantity of experimentation required to make and use the claimed invention based upon the content of the supporting disclosure
In order to actually achieve the claimed invention, it is clear from the discussion above that the skilled artisan could not rely upon Applicant's disclosure as required by 35 U.S.C. 112, first paragraph, and would have no alternative recourse but the impermissible burden of undue experimentation in order to practice the full scope of the embodiments presently claimed. The Examiner has established on the record a reasonable basis for questioning the adequacy of the disclosure to enable a person of ordinary skill in the art to make and use the claimed invention without resorting to undue experimentation. It is incumbent on the applicant to factually demonstrate that his or her application disclosure is in fact sufficient. See MPEP 2161.01 III.
The enablement requirement is not satisfied.
Response to Declaration and Arguments:
Applicant’s Declaration and arguments filed 2/10/26 have been carefully considered but are not persuasive.
On page 7 of remarks, Applicant states: “Where an examiner challenges operability or factual assertions in the specification, the Office must provide some evidence or sound technical reasoning that creates a legitimate doubt; mere skepticism is insufficient. In re Marzocchi, 439 F.2d 220, 224 (C.C.P.A. 1971).” The Examiner has provided sound technical reasoning in the rejection.
On page 7 of remarks, Applicant asserts that: “The enablement rejection hinges on construing "co-administering...to a subject" as requiring instantaneous, simultaneous delivery of all components in a single moment. That construction is not the broadest reasonable interpretation in view of the intrinsic record and is inconsistent with how co-administration is used in coordinated treatment regimens.” Applicant states: “the specification does not define "co-administering" as strictly simultaneous delivery. To the contrary, it teaches that the invention can be implemented through coordinated regimens that may include (i) sequential dosing and (ii) separate dosage units taken together as part of a combined regimen.” However, the term “sequential dosing” does not appear in the specification and, as acknowledged by Applicant, the “separate dosage units” are meant to be taken together ([0032] “a composition encompasses separate capsules that are packaged together and are meant to be taken together.”) The only reasonable conclusion is that the term “co-administered” means taken together and not sequentially over time.
On page 8 of remarks, Applicant asserts that the working examples demonstrate sequential co-administration where in Example 1, elemental magnesium is added 1 hour after forming nitrosation products. However, it remains the Examiner’s position that addition an hour later is not “taken together” in any reasonable sense of the phrase and does not reasonably encompass any coordinated time-delayed regimen.
On page 8, Applicant asserts that Example 10 provides administration at the same time. The Examiner is well aware of Example 10 but maintains the position that the oral administration of the capsule will produce nitrosamines and be contrary to the claimed method. As stated above, it is incumbent on the applicant to factually demonstrate that his or her application disclosure is in fact sufficient. Applicant has failed to present any evidence.
On pages 8-9, Applicant cites several Federal Circuit cases. However, what is controlling here is Applicant’s own specification which teaches that the components are “taken together”. Thus, the components co-administered are taken together and not sequentially over any time period.
On page 9 of remarks, Applicant asserts: “The Office Action's enablement theory further assumes that administration of an amine, nitrite/nitrate, and elemental metal would "predictably" promote nitrosamine formation. That assumption is inconsistent with Applicant's reported experimental observations. Moreover, it is scientifically workable that electropositive metals (including Mg and Zn) in acidic media can reduce nitroso and nitrosamine functional groups ("denitrosation"/"denitrosylation"), thereby destroying or reversing nitrosation products.” Respectfully, the Examiner does not agree. Simply because something is “scientifically workable” does not infer that it is enabled. While it is a fact that ingestion of nitrates with an amine rich diet will produce N-nitrosamines (See for example, Vermeer et al. Environmental Health Perspectives * Volume 106, Number 8, August 1998, Pages 459-463) and it is a fact that N-nitroso compound formation can be prevented by administration of vitamin C and vitamin E to the gastric fluid (See for example, Mergens et al. US4681756; Abstract; column 1, lines 17-20; column 3, lines 35-64; claims 1-3), it is entirely speculation by Applicant that highly reactive elemental magnesium will do so. It is incumbent on the applicant to factually demonstrate that his or her application disclosure is in fact sufficient. Examples 1-3 are not commensurate in scope with the claimed subject matter and cannot be relied upon for support.
On pages 10-11 of remarks, Applicants discussion of the chemistry of RSNOs and N-nitrosamines and metal/acid reductions has been carefully considered but not persuasive. Applicant’s analysis fails to consider all the components in an in vivo system whereas in contrast the Examiner has considered the interactions of the components in such a system. While an elemental metal can destroy nitrosation products after they have formed, as demonstrated by Applicant, that is not what is being claimed. Applicant is attempting to extrapolate from sequential administration in an in vitro environment to an in vivo method and the Examiner has reasonable doubt that coadministration produces the same result an in in vivo environment. Accordingly undue experimentation is required. Respectfully, Applicant’s arguments are not persuasive.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 ERNST V ARNOLD whose telephone number is (571)272-8509. The examiner can normally be reached M-F 7-3:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian Y Kwon can be reached at 571-272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ERNST V ARNOLD/Primary Examiner, Art Unit 1613
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