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 responsive to the Response to Election/Restriction filed 09/17/2025.
Claims 1 and 15-26 are pending.
Priority
This application claims the following priority:
PNG
media_image1.png
100
657
media_image1.png
Greyscale
Drawings
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they include the following reference character(s) not mentioned in the description: Fig. 9A and Fig. 9B. Corrected drawing sheets in compliance with 37 CFR 1.121(d), or amendment to the specification to add the reference character(s) in the description in compliance with 37 CFR 1.121(b) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Election/Restrictions
Applicant's election with traverse of Group I, and
PNG
media_image2.png
176
642
media_image2.png
Greyscale
in the reply filed on 09/17/2025, is acknowledged.
In the course of the search, the election of species requirement was withdrawn, as was the restriction between Groups I and III.
In view of the withdrawal of the restriction requirement as to the rejoined inventions, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application.
Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
The traversal is on the ground(s) that Claim 26, reads on claim 1 from Group I and should therefore be part of Group I. However, as discussed above, the restriction requirement between groups I and III has been withdrawn. Applicant provides no arguments traversing the restriction of Group II.
As such, the requirement is still deemed proper and is therefore made FINAL.
Claims 23 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1, 15-22, and 24-26 are examined on the merits herein.
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 1, 15-22, and 24-26 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.
-In claims 1 and 24, the term “oxido” in line 7, renders the claim indefinite, as this term is neither a term of art nor defined in the specification. It is not known if an oxido group is any group that contains an oxygen, such as hydroxyl or phenol, if it is a single oxygen atom, or if oxido means something else entirely. As such, the metes and bound of this phrase are unclear.
-In claims 1 and 24, the following renders the claim indefinite:
PNG
media_image3.png
160
592
media_image3.png
Greyscale
.
First, this phrase encompasses two Markush groups and two “including” groups. It is not clear what the final member of the first Markush group encompassing “counterion” is, or what the final member of the second Markush group encompassing “organic cations” is. Second, it is not clear where the examples (i.e., including) of “ammonium salts” ends and where the Markush group of “organic cations,” continues. Similarly, it is not clear where the examples of “inorganic cations” ends, and if the “or a pharmaceutically acceptable salt or tautomer thereof,” is referencing the inorganic cations, or the counterions, or the compound of formula (I) as a whole. Moreover, the “including” language, in lines 2 and 5, is open ended language that does not exclude additional elements/groups. Since the Markush group is a closed groups, the metes and bounds of the Markush groups cannot be determined. Further, it is not clear if the including language is exemplary of “ammonium salts” and “inorganic cations,” respectively, or if the specific ammonium salts and inorganic cations are members of their respective Markush groups.
Lastly, since the term “oxido” is indefinite, it is not clear how the counterion is “with” the recited counterions.
As such, the scope of “oxido with counterion” and the last six lines of claims 1 and 26, is unclear.
In view of compact prosecution, for the purpose of applying prior art, the last six lines of claims 1 and 26 are interpreted as, “wherein the counterion is selected from the group consisting of organic cations, inorganic cations and combinations thereof, and pharmaceutically acceptable salts or tautomers od formula (I).”
-In claims 15 and 16, it is not clear if “the pharmaceutically acceptable salt” recited in lines 1-2, of the claim, is one of the anions recited in lines 4-12 of the claim, or if the “pharmaceutically acceptable salt” of lines 1-2 is in addition to the anions of the amino groups. If the anions are not “the pharmaceutically acceptable salt,” then the recited anions are outside of the compound of formula (I), as recited in claim 1, since the compound of formula (I) of claim 1 only recites “pharmaceutically acceptable salts. . .thereof,” and does not further depict the amino groups as protonated.
In view of compact prosecution, for the purpose of applying prior art, the pharmaceutically acceptable salt is interpreted as the anions
All other claims not specifically recited are rejected for depending from an indefinite claim and failing to cure the deficiency.
Claim Rejections - 35 USC § 112(a)-Scope of Enablement
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, 15-22, and 24-26 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) a method of inhibiting or treating a Pseudomonas bacterial biofilm infection by administering a compound of formula (I) wherein R1, R2, and R3 are H, OH, or F, and salts thereof of the primary amine group, and b) a method of dispersing a biofilm formed by Pseudomonas bacteria by contacting water in an industrial water system with a compound of formula (I) wherein R1, R2, and R3 are H, OH, or F, and salts thereof of the primary amine group, does not reasonably provide enablement for a) a method of inhibiting or treating bacterial biofilm infection by administering a compound of formula (I) as defined in instant claim 1, or b) a method of dispersing a biofilm formed by Pseudomonas bacteria by contacting water in an industrial water system with a compound of formula (I) as defined in claim 24. 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 criteria for enablement set out in the In re Wands, MPEP 2164.01(a), considers the following factors:
Breadth of the Claims
Independent claim 1 is directed toward a method of treating any bacterial biofilm infection in a subject comprising administering any compound of formula (I) or salt or tautomer thereof as defined below:
PNG
media_image4.png
379
586
media_image4.png
Greyscale
.
Independent claim 24 is directed toward a method of dispersing a biofilm formed by any Pseudomonas bacteria in any industrial water system comprising contacting water in an industrial water system with any compound of formula (I) or salt or tautomer thereof, as defined below:
PNG
media_image4.png
379
586
media_image4.png
Greyscale
.
As such, the breadth of the claims is great.
Level of Skill in Art
The level of skill in the art is a clinician or an artisan with a PhD.
State of the Prior Art
Cottarel (US 2011/0015137, PTO-892) teaches a method of administering a RecA inhibitor such as
PNG
media_image5.png
114
262
media_image5.png
Greyscale
, to a subject suffering from or susceptible to a microbial infection, such as Pseudomonas aeruginosa, and administering at least one antibiotic agent to the subject (pg. 30, claim 1; [0211]-[0212]).
PNG
media_image5.png
114
262
media_image5.png
Greyscale
, meets the limitations of instant formula (I) when R1 and R2 are H, and R3 is the oxide, -OCH3. However, Cottarel does not teach the limitations of instant R1, R2, and R3.
Thus, Cottarel teaches a single structurally similar compound as a RecA inhibitor that is administered to treat microbial infections.
WO 01/77080 (IDS of 08/24/2023) teaches compounds of instant Formula (I) (pgs. 18-20), wherein these compounds are taught for the treatment of hyperproliferative disorders, such as tumor growth, lymphoproliferative diseases, and angiogenesis (abstract, pg. 20).
Thus, the prior art does not teach the instantly claimed compounds for use in treating bacterial biofilm infections.
Predictability in the Art
Patel (Antibiotics, NIH, PTO-892) teaches that not all antibiotics are effective against all types of bacteria. If a bacterium does not contain the target for a particular antibiotic, it is known to have intrinsic resistance. For example, vancomycin, an antibiotic known to target gram-positive bacteria, cannot cross the cell wall of gram-negative bacteria. Also, beta lactam antibiotics require a cell wall to function and therefore, are ineffective against bacteria such as Mycoplasma species that lack this cellular component (pg. 4).
Sharma (Microbial Biofilm: A Review on Formation, Infection, Antibiotic Resistance, Control Measures, and Innovative Treatment, Microorganisms, PTO-892) teaches that a biofilm is complex and consists of bacterial colonies that reside on an exopolysaccharide matrix. Sharma teaches that since the bacteria in the biofilm have developed antibiotic resistance, using antibiotics alone to treat infections brought on by biofilm, is ineffective (abstract).
Sharma concludes by stating that biofilm infections continue to be a major concern in the healthcare industry due to their high level of resistance to available antimicrobial medicines. Given the resistance to currently utilized antimicrobial drugs it is vital to find effective treatment options for biofilm-associated infections. There are a few novel and successful antibiofilm techniques that have been tested, including isolation of quorum-quenching compounds, dispersal of produced biofilms, and combining antibiotics with quorum-quenching compounds. Although the aforementioned strategies are significant areas of research, they are still in their infancy and have not yet completed clinical trials or made their way into the commercial market. Sharma teaches that the ubiquity of the biofilm phenotype has been acknowledged by the discipline of microbiology, and that understanding what distinguishes the biofilm phenotype from the planktonic phenotype in greater detail will hold the key to success for future measures to control biofilms (pg. 21, “8.”).
In view of the teachings of the prior art and the teachings of Patel and Sharma, the treatment of bacterial biofilm infection with pharmacological agents, is unpredictable.
Working Examples
Example 2, beginning on pg. 51 of the specification, determines the structure-activity-relationship of compounds that reduce the total cellular c-di-CMP levels in P. aeruginosa samples. As can be seen by Table 2, while all fifteen tested compounds share the same core structure, these fifteen compounds vary in efficacy, ranging from causing a 5% reduction of c-di-GMP levels to an 80% reduction of cellular c-di-GMP levels.
In Table 2, compounds of instant formula I, wherein R1 and R2 are H, and R3 is F, vary in the reduction of c-di-GMP level from a 40% to an 80% reduction.
In Table 2, compounds of instant formula I, wherein R1 is H, and R2 and R3 are F, vary in the reduction of c-di-GMP level from a 35% to a 77% reduction.
None of the compounds in Table 2 comprise salts or counterions of oxido.
In reference to instant formula (I), fourteen of the compounds depict R1 as H, and R2 and R3 as either H and F; F and F; F and OH; H and H; H and OH; or OH and OH; and one of the compounds depict R1, R2 and R3 as F, F, and F.
Example 10, beginning on pg. 64 of the specification teaches the improved aqueous solubility of compounds of formula (I), and their reduction of c-di-GMP content. The following compounds are exemplified:
PNG
media_image6.png
722
598
media_image6.png
Greyscale
PNG
media_image7.png
577
602
media_image7.png
Greyscale
In reference to instant formula (I), all of the compounds depict R1 and R2 as H, and R3 as F, but vary in their salt form at the -NH2, wherein the salts are tetrafluoroboric acid, sodium trifluoroacetate, hexafluorophosphoric acid, acetic acid, citric acid, succinic acid salt, HCl salt, phosphoric acid salt, and sulfuric acid salt, and these compounds vary in reduction in c-di-GMP content in water or DMSO stock from ~23% to ~75%.
Examples 11 and 11a, beginning on pg. 66 demonstrate the treatment of catheter associated urinary tract infection in mice when they are intraperitoneally injected or orally administering a single species of compound, H6-335-PI HCl.
Direction and Guidance
In view of the teachings of the prior art, the unpredictability of the art, and the working examples, wherein the bacterial biofilms are limited to those formed by the bacteria Pseudomonas, and wherein compounds of formula (I) are limited to those wherein R1, R2, and R2 are H, OH, or F, and the salts are tetrafluoroboric acid, sodium trifluoroacetate, hexafluorophosphoric acid, acetic acid, citric acid, succinic acid salt, HCl salt, phosphoric acid salt, and sulfuric acid salt, the specification lacks sufficient guidance and direction to use the invention as instantly claimed.
Quantity of Experimentation
In view of the great number of distinct bacterial biofilm infections, the great number of compounds of formula (I), and the great number of combinations of treating bacterial biofilm infection with compounds of formula (I), the amount of experimentation required to determine which compounds of formula(I) treat which bacterial biofilm infections/biofilms in industrial water complexes, is astronomical, amounting to invention and not development; it is an undue amount of experimentation.
Thus, while being enabling for a) a method of inhibiting or treating a Pseudomonas bacterial biofilm infection by administering a compound of formula (I) wherein R1, R2, and R3 are H, OH, or F, and salts thereof, and b) a method of dispersing a biofilm formed by Pseudomonas bacteria by contacting water in an industrial water system with a compound of formula (I) wherein R1, R2, and R3 are H, OH, or F, and salts thereof, the specification does not reasonably provide enablement for a) a method of inhibiting or treating bacterial biofilm infection by administering a compound of formula (I) as defined in instant claim 1, or b) a method of dispersing a biofilm formed by Pseudomonas bacteria by contacting water in an industrial water system with a compound of formula (I) as defined in claim 24.
Free of the Prior Art
Claims 1, 15-22, and 24-26 are free of the prior art.
The closest prior art is US 2011/0015137 to Cottarel which teaches a method of administering a RecA inhibitor of
PNG
media_image5.png
114
262
media_image5.png
Greyscale
, to a subject suffering from or susceptible to a microbial infection, and administering at least one antibiotic agent to the subject (pg. 30, claim 1).
This compound meets the limitations of instant formula (I) when R1 and R2 are H.
However, Cottarel does not teach R3 as instantly claimed, which is a distinct feature of the instantly claimed invention. Moreover, the prior art provides no motivation to modify the compound of Cottarel to substitute the -OCH3 group with instant R3.
Conclusion
No claim are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAUREN WELLS whose telephone number is (571)272-7316. The examiner can normally be reached M-F 7:00-4:30.
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, James (Jim) Alstrum-Acevedo can be reached on 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/LAUREN WELLS/Examiner, Art Unit 1622