DETAILED ACTION
Claims 11-18 are currently pending and under examination.
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 of sodium nitrite, citric acid and mannitol, mixing nitric oxide generating composition is prepared at the desired concentration and surface which is part of human or animal body in the reply filed on 08/14/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
No claims are withdrawn as a result of the species election.
Priority
The instant application claims priority to notational stage entry PCT/GB2021/050934, 04/19/2021, which claims priority to foreign application GB2005986.1, filed 04/23/2020 and GB2008285.5, filed 06/02/2020.
Information Disclosure Statement
Applicant’s Informational Disclosure Statement, filed on 10/20/2022, 12/21/2023, 02/26/2024 and 07/11/2025 has been considered. Please refer to Applicant's copy of the 1449 submitted herein.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
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 11-14 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 a method of treating or alleviating tuberculosis or an infection arising from the bacterium M. tuberculosis in a human or animal subject comprising administering to the human or animal subject an antibacterially effective amount of one or more agent selected from nitric oxide, nitric oxide generating composition or mixtures thereof. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to prevent tuberculosis or an infection arising from the bacterium M. tuberculosis in a human or animal subject, the invention commensurate in scope with these claims.
The factors to be considered in determining whether a disclosure meets the enablement requirements of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 858 F.2d 731, 8 USPQ2d 1400 (Fed. Cir., 1988). The court in Wands states, “Enablement is not precluded by the necessity for some experimentation, such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is ‘undue’, not ‘experimentation’” (Wands, 8 USPQ2sd 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations” (Wands, 8 USPQ2d 1404). Among these factors are: (1) the nature of the invention; (2) the breadth of the claims; (3) the state of the prior art; (4) the predictability or unpredictability of the art; (5) the relative skill of those in the art; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
While all of these factors are considered, a sufficient amount for a prima facie case is discussed below.
(1) The nature of the invention and (2) the breadth of the claims:
The claims are drawn to a method of treating or alleviating or preventing tuberculosis or an infection arising from the bacterium M. tuberculosis in a human or animal subject comprising administering to the human or animal subject an antibacterially effective amount of one or more agent selected from nitric oxide, nitric oxide generating composition or mixtures thereof
(3) The state of the prior art and (4) the predictability or unpredictability of the art:
The instant specification demonstrates the effectiveness of an acidified solution of sodium nitrite, citric acid buffered to pH 5.8 using sodium hydroxide and mannitol to kill M abscessus, wherein the M abscessus is reduced however is not prevented (Figure 29, [0519]). Figures 24-27 additionally demonstrate tests regarding the antimicrobial activity against M tuberculosis wherein reduction is demonstrated however total prevention is not taught.
(5) The relative skill of those in the art:
The skill in the art is high, most likely at the Ph.D./MD level.
(6) The amount of direction or guidance presented and (7) the presence or absence of working examples:
The instant specification demonstrates the effectiveness of an acidified solution of sodium nitrite, citric acid buffered to pH 5.8 using sodium hydroxide and mannitol to kill M abscessus, wherein the M abscessus is reduced however is not prevented (Figure 29, [0519]). Figures 24-27 additionally demonstrate tests regarding the antimicrobial activity against M tuberculosis wherein reduction is demonstrated however total prevention or alleviation is not taught.
(8) The quantity of experimentation necessary:
Neither the instant specification or the prior art demonstrates prevention of antimicrobial resistance of microorganism in a human or animal individual. Thus the level of experimentation to obtain such a result is high.
Considering the disclosure of the instant specification and the instant claims, enablement of treating or alleviating tuberculosis or an infection arising from the bacterium M. tuberculosis in a human or animal subject comprising administering a composition comprising NO, nitric oxide generating compristion, a combination or combinable associate of ingredients for a nitric oxide generating compristion and mixtures there to a human or animal individual is found, however prevention is not enabled.
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 11-18 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.
Claims 11 and 15 contains the limitation of “one or more agent selected from nitric oxide (NO), nitric oxide generating composition, a combination or combinable association of ingredients for nitric oxide generating composition and mixtures there” and additionally “wherein the agent is or comprises nitric oxide generating composition or components thereof”. It appears applicant has defined “agent” twice in two different scopes in the same claim, thus leading to unclear metes and bounds. The first recitation allows for nitric oxide and the second recitation limits to nitric oxide generating composition or components.
Claims 11 and 15 contains the limitation of “one or more agent selected from nitric oxide (NO), nitric oxide generating composition, a combination or combinable association of ingredients for nitric oxide generating composition and mixtures there” and additionally “wherein the nitric oxide generating compristion or the combination or combinable association of ingredients for nitric oxide generating compristion comprises….”. It appears that the “nitric oxide generating composition” “or the combination or combinable association of ingredients for nitric oxide generating composition” is defined as the same ingredients by claim 11. Thus the use of multiple recitations make the claim unclear as to whether the scope is different for the composition or the combination or combinable association of ingredients, thus making the instant claim have unclear metes and bounds.
Claims 13-14 recites the limitation "the nitrite salt”, and “the organic polyol” components". There is insufficient antecedent basis for this limitation in the claim. Instant claim 11, from which claims 13-14 depend, contain one or more nitrite salt and one or more organic polyol, and thus the nitrite salt and the organic polyol do not properly refer back to one or more of nitrite salt and organic polyol.
Claims 13 and 17 recite the limitation “suitably with water”. It is unclear if water is required for the dilution or a preferable compound as the term “suitably” does not clearly convey water is required to be used in the dilution, thus the instant claim has unclear metes and bounds.
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(s) 11-12 and 15-16 is/are rejected under 35 U.S.C. 103 as being unpatentable over EP 1 435 924 (Applicant provided IDS 07/11/2025).
Regarding claims 11-12 and15-16, the limitation of a method of treating tuberculosis or an infection arising from the bacterium M. tuberculosis in a human or animal subject comprising administering to the human or animal subject an antibacterially effective amount of one or more agent selected form nitric oxide, nitric oxide generating compristion or mixture thereof is met by the ‘924 publication teaching nitric oxide for use in therapy using nitric oxide and nitric oxide precursors ([0001]-[0002]). NO is dispersed and/or dissolved in solution [0015]. Liquid formulations of nitric oxide may be administered by nebulizer for treatment of tuberculosis [0019], which reads on treating a surface which is part of a human or animal body. The liquid mixture may be made by the combination of nitrite with an organic acid such as ascorbic acid [0023] to treat tuberculosis [0037] and treatment of Mycobacterium tuberculosis [0035].
It must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious”. KSR v. Teleflex, 127 S,Ct. 1727, 1740 (2007)(quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious”, the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007). The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742.
Consistent with this reasoning, it would have been obvious to have selected various combinations of disclosed ingredients (nitric oxide or nitric oxide source composition for treatment of tuberculosis) from within the prior art disclosure of the ‘924 publication, to arrive at the instantly claimed treating a surface in the body to reduce M. tuberculosis bacteria or treat tuberculosis “yielding no more than one would have expected from such an arrangement”.
Claim(s) 11-18 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2009/0196930 in view of EP 1 435 924 (Applicant provided).
Regarding claims 11-18, the limitation of a method of treating tuberculosis or an infection arising from the bacterium M. tuberculosis in a human or animal subject comprising administering to the human or animal subject an antibacterially effective amount of one or more agent selected form nitric oxide, nitric oxide generating compristion or mixture thereof is met by the ‘930 publication teaching nitrite, nitrite salt or nitric oxide producing compounds suitable for aerosolization and use of such formulations for aerosol administration for treatment of pulmonary bacterial infections (abstract). The nitrite compound formulation for pulmonary delivery comprises an aqueous solution comprising sodium nitrite, citric acid [0045] wherein the liquid formulation includes the carrier such as water and glycerol to form a solution or suspension to be aerosolized can be prepared in conventional forms [0226] or excipient like mannitol [0224]. The bacteria may be gram-negative bacteria includes mycobacterium tuberculosis [0138]. The ’930 publication teaches upon admixture of nitrite compound and an acidic excipient to form the compristion [0038] wherein the composition may be subsequently diluted [0226], thus teaching the composition may be formed at the desired concentration or may need to be further diluted. Treatment of a human is taught [0110]. The ‘930 publication teaches methods of treating bacterial infection comprise administer nebulized nitrite to a subject infected, predisposed to or suspected of having an infection by a pathogenic bacterial in the lungs [0131] wherein an antimicrobial effect is taught [00134] and reduction of bacterial population is taught [0136].
The ’930 publication does not teach the specific combination of nitric oxide precursors for reduction in the amount of viable M. tuberculosis bacteria on the surface or in the space.
The ‘924 publication teaching nitric oxide for use in therapy using nitric oxide and nitric oxide precursors ([0001]-[0002]). NO is dispersed and/or dissolved in solution [0015]. Liquid formulations of nitric oxide may be administered by nebulizer for treatment of tuberculosis [0019], which reads on treating a surface which is part of a human or animal body. The liquid mixture may be made by the combination of nitrite with an organic acid such as ascorbic acid [0023] to treat tuberculosis [0037] and treatment of Mycobacterium tuberculosis [0035].
It would have been prima facie to one of ordinary skill in the art before the filing date of the claimed invention to use sodium nitrite, citric acid and mannitol to treat tuberculosis or reduce the amount of viable M. tuberculosis bacteria on the surface as the ‘930 publication teaches the composition which comprises sodium nitrite, citric acid and mannitol and may be administered to a human to treat bacteria such as Mycobacterium tuberculosis and the ‘924 publication specifically teaches nitric oxide sources to be administered by nebulizer to treat respiratory diseases such as Mycobacterium tuberculosis [0019]. One of ordinary skill in the art before the filing date of the claimed invention would be motivated to use sodium nitrite to reduce M. tuberculosis as the ‘924 publication and the ’930 publication both teach the use of nitric oxide generators in the treatment of M. tuberculosis and the ‘930 publication teaches methods of treating bacterial infection comprise administer nebulized nitrite to a subject infected, predisposed to or suspected of having an infection by a pathogenic bacterial in the lungs [0131] wherein an antimicrobial effect is taught [00134] and reduction of bacterial population is taught [0136], thus rendering it obvious to use inhaled sodium nitrite to reduce M. tuberculosis in the body surface such as the lung and the ‘924 publication provides the specific connection between nitric oxide generators and treatment of M. tuberculosis and tuberculosis.
Consistent with this reasoning, it would have been obvious to have selected various combinations of disclosed ingredients (sodium nitrite, citric acid and mannitol composition for treatment of tuberculosis and reduction in viable M. tuberculosis bacteria) from within the prior art disclosure of the ‘924 publication and the ‘924 publication, to arrive at the instantly claimed treating a surface in the body to reduce M. tuberculosis bacteria or treat tuberculosis “yielding no more than one would have expected from such an arrangement”.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNDSEY MARIE BECKHARDT whose telephone number is (571)270-7676. The examiner can normally be reached Monday-Thursday 9am to 4pm and Friday 9am to 2pm.
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/LYNDSEY M BECKHARDT/ Examiner, Art Unit 1613
/FREDERICK F KRASS/ Supervisory Patent Examiner, Art Unit 1612