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 .
DETAILED ACTION
This office action is in response to applicant’s reply filed on April 2, 2026.
Status of Claims
Amendment of claims 2 and 17; and addition of claims 20-22 is acknowledged.
Claims 2 and 4-22 are currently pending and are the subject of this office action.
The following claims are withdrawn because they do not encompass the elected species: bacterial infection wherein the bacteria are bacillus spizizenii and/or Staphylococcus aureus: claims 7-16.
Claims 2, 4-6 and 17-22 are presently under examination.
The following species are under examination:
1-
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as the compound of formula (I)(a), and
2- Bacterial infection, wherein the bacteria are bacillus spizizenii and/or Staphylococcus aureus,
Priority
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Rejections and/or Objections and Response to Arguments
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated (Maintained Rejections and/or Objections) or newly applied (New Rejections and/or Objections, Necessitated by Amendment or New Rejections and/or Objections not Necessitated by Amendment). They constitute the complete set presently being applied to the instant application.
Responses to Applicant’s arguments have been addressed immediately after the corresponding rejections, or in the section: Withdrawn Rejections and/or Objections, if the rejection was withdrawn.
Claim Rejections - 35 USC § 112 (New Rejection Necessitated by Amendment)
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.
Claim 20 is 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 20 recites:
“The method of claim 2, wherein the composition comprises from about 0.01% to about 9% weight of the one or more compounds of formula (I)”.
It is not clear if one or more compounds of formula (I) refers to compounds of formula (I) (a) or compounds of formula (I) (b), or both.
Claim Rejections - 35 USC § 103 (Modified Rejection Necessitated by Amendment).
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 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.
1) Claim(s) 2, 4-6, 17 and 19-22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Klink et. al. (Journal of Medical Microbiology (2003) 52: 303-308, cited by Applicant), Av-Gay et. al. (US 2015/0132345), Handa et. al. (US 2019/0358368), Schoenfisch et. al. (US 2021/0346424) in view of Nilsson et. al. (Drug Design Development and Therapy (2018) 12:685-694) and in view of Gustafsson et. al. (WO 2007/106034, cite by Applicant).
For claims 2, 4-6 and 17, Klink teaches that Nitric Oxide (NO) donors like nitroprusside or 3-morpholinosydnonimine are effective in treating bacterial infection in humans (see title, abstract and page 305 under: Effect of NO donors on the survival of bacteria).
Av-Gay teaches NO-releasing (i.e. NO-donors) agents are effective in killing a wide range of bacteria, viruses, fungi and yeasts associated with skin infections (see [0008]). Gel formulations containing NO-donors have been demonstrated to possess antibacterial activity against E. coli, C-P. aeruginosa, B. subitilis and S. aureus as well as significant anti-inflammatory activity (see [0008]).
Handa teaches NO-releasing agents, like S-nitrosothiols and N-diazeniumdiolates, are effective in treating bacterial infections (see [0037] and [0070]). Among the bacteria they mention Staphylococcus aureus (see [0030]).
Schoenfisch teaches that several chronic infections are caused by biofilm-forming pathogens like Pseudomonas aeruginosa and Staphylococcus aureus. They disclose NO-releasing cyclodextrins that are effective in treating biofilm-forming bacteria like Staphylococcus aureus (see [0006], [0107], [0173], [0469], [0472]-[0473], [0476] and [0481]).
In summary, the prior art teaches that NO-releasing agents, regardless of their structure, are effective in treating bacterial infections.
The prior art does not teach the treatment of bacterial infection with the instantly claimed compound of formula (I)(a) like:
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(PDNO)
However, Nilsson teaches (see title and abstract) that mononitrites of 1,2-propanediol (PDNO) like compound (1) (see Figure 1 on page 686):
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are NO-releasing agents that are effective in treating NO-related diseases like pulmonary hypertension.
Gustafsson teaches “a method for the manufacture of a medicament for the treatment of a condition where NO has a beneficial effect, wherein a compound obtainable through a method to any of claims 1-29, is administered to a patient with said condition” (see claim 40), wherein the compound can be the NO-donor compound I (see page 5 and page 15):
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(PDNO)
Gustafsson further teaches that the instant compounds have less side effects than previously known NO-donors (see background from pages 1 through 5).
Finally, Gustafsson teaches:
“The compounds (nitrites) were produced by first de-aerating a solution comprising the organic starting material” (see page 11, lines 4-5). “The de-aerated solution consisting of, or comprising the starting material is then saturated with NO by passing gaseous NO through the starting material” (see page 11, lines 16-17). Said starting material can be 1,2-ptopanediol (propylene glycol) (see page 13, last line). 1,2-propanediol is equivalent to the instant compound of formula (I) (b):
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wherein:
n = 0 and
R1 = R2 = R3 = H
“Preliminary results indicate that an organic nitrite is more stable against decomposition and the formation of unwanted reaction product if the organic nitrite, the corresponding organic starting material (i.e. 1,2-ptopanediol), and gaseous NO are simultaneously present: (see page 15, line 19 through page 16, line 2).
In other words, Gustafsson teaches compositions comprising:
1- the mononitrite PDNO:
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(i.e. the compound of formula (I)(a) wherein n = 0, R1 =R2 = H, and R3 = -NO), and
2- the organic starting material 1,2-propanediol. (i.e. the compound of formula (I)(b) wherein R1 = R2 = R3 = H).
In a preferred embodiment the formulation is for topical administration, such as a gel, ointment or solution, comprising an organic nitrite (PDNO), the corresponding starting material (1,2-propanediol) and gaseous NO (see page 16, lines 7-9). Gel and ointments can be considered “substantially non-aqueous compositions”.
To summarize, Gustafsson teaches compositions comprising:
1- the mononitrite PDNO:
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(i.e. the compound of formula (I)(a) wherein n = 0, R1 =R2 = H, and R3 = -NO),
2- the organic starting material 1,2-propanediol. (i.e. the compound of formula (I) wherein R1 = R2 = R3 = H), and
3- that the compositions are substantially non-aqueous compositions.
Since the prior art teaches a method of treating bacterial infections in general and Staphylococcus aureus in particular comprising the administration of compositions comprising a structurally diverse set of NO-donors, and since the prior art teaches that compounds like 2-hydroxy-propyl nitrite (PDNO):
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are NO-donors that can effectively be used in any a condition where NO has a beneficial effect, before the effective filing date of the claimed invention it would have been prima facie obvious for a person of ordinary skill in the art to substitute one functional equivalence (any NO-donor) for another (2-hydroxy-propyl nitrite, PDNO) with an expectation of success, since the prior art establishes that both function in similar manner. The skilled in the art will be further motivated to replace previously known NO-donors with 2-hydroxy-propyl nitrite, since this NO-donor is less toxic. Further, the skilled in the art will be motivated to have the nitrite (PDNO) in a substantially non-aqueous composition comprising the organic starting material (1,2-propanediol) as taught by Gustafsson.
All this will result in the practice of claims 2, 4-6 and 17, with a reasonable expectation of success.
For claim 19, the prior art does not explicitly teach that the treatment reduces or inhibits replication of the bacteria. However, it is inherent that reduction of the bacteria will occur in such treatment since according to the prior art NO gas is toxic to bacteria.
Further, the statement in claim 19: “wherein the treatment reduces or inhibits replication of the bacteria” does not require additional steps to be performed and simply expresses the intended result of carrying the process made obvious by the prior art: “a method for treating bacterial infections comprising the administration of a patient in need thereof a composition comprising a compound of formula (I) like 2-hydroxy-propyl nitrite".
MPEP 2111.04 states: “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure. However, examples of claim language, although not exhaustive, that may raise a question as to the limiting effect of the language in a claim are:
(A) “ adapted to ” or “adapted for ” clauses;
(B) “ wherein ” clauses; and
(C) “ whereby ” clauses.
The determination of whether each of these clauses is a limitation in a claim depends on the specific facts of the case. In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), the court held that when a “whereby’ clause states a condition that is material to patentability; it cannot be ignored in order to change the substance of the invention.” Id. However, the court noted (quoting Minton v. Nat ’l Ass ’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” (Emphasis added).
In the instant case “wherein the treatment reduces or inhibits replication of the bacteria” appears to be the result of the process made obvious by the prior art: “a method for treating bacterial infections comprising the administration of a patient in need thereof a composition comprising a compound of formula (I) like 2-hydroxy-propyl nitrite ", e. g. the intended result of a process step positively recited. As such, this limitation in the instantly claimed method has not been given any weight.
All this will result in the practice of claim 19 with a reasonable expectation of success.
For claims 20-22, the prior art does not teach the proportion of PDNO, 1,2-propanediol and water as instantly claimed. However, since the prior art already teaches substantially non-aqueous compositions comprising the nitrite (PDNO) and the organic starting material (1,2-propanediol), the skilled in the art will be motivated to optimize the amount and proportion of each ingredient to obtain the most effective and stable composition, thus resulting in the practice of claims 20-22 with a reasonable expectation of success.
2) Claim(s) 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Klink et. al. (Journal of Medical Microbiology (2003) 52: 303-308, cited by Applicant), Av-Gay et. al. (US 2015/0132345), Handa et. al. (US 2019/0358368), Schoenfisch et. al. (US 2021/0346424) in view of Nilsson et. al. (Drug Design Development and Therapy (2018) 12:685-694, cited by Applicant) and in view of Gustafsson et. al. (WO 2007/106034, cite by Applicant), as applied for claims 2, 4-6, 17 and 19-22, further in view of David (US 2005/0108047).
The prior art teaches all the limitations of claim 18, except for the symptoms of the infected patient being fever or pain. However, David teaches that symptoms bacterial infections are pain and fever (see [0086]), thus resulting in the practice of claim 18 with a reasonable expectation of success.
Response to Applicant’s arguments related to the above rejection
Applicant's arguments have been fully considered but are not persuasive.
Since a new rejection was issued (see above), only those arguments presented by Applicant that are relevant to the new rejection are being considered.
First, as disclosed by Gustafsson, and discussed in the above 103 rejection, it will be obvious to make a substantially non-aqueous composition comprising a compound of formula (I) (a) and a compound of formula (I) (b).
Second, Applicant argues about the unexpected results obtained when the compositions do not contain nitric oxide (NO) gas. However, this is not commensurate in scope with the claims, since the claims do not require the exclusion of NO gas.
Conclusion
No claims are allowed.
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 extension fee 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 date of this final action.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARCOS L SZNAIDMAN whose telephone number is (571)270-3498. The examiner can normally be reached Flexing M-F 7 AM-7 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L. Clark can be reached on 571 272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARCOS L SZNAIDMAN/
Primary Examiner, Art Unit 1628
April 9, 2026.
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