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 .
A Request for Continued Examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous office action has been withdrawn pursuant to 37 CFR 1.114. Applicant’s submission filed 27 April 2026 has been entered.
The Request for Continued Examination filed has been considered. The following information has been made of record in the RCE filed for the instant application:
1. Claims 1-4, 6-12, 15-16, and 18-26 have been canceled.
2. New Claims 31-39 have been added.
3. Claim 5 has been amended.
4. Remarks drawn to rejections under 35 USC 112, 103 and double patenting.
The following objection(s)/rejection(s) have been overcome:
5. The rejection of Claims 5, 13-15, 17 and 26 under 35 U.S.C. 112, first paragraph, for lack of enablement for prevention has been overcome by amendment. In claim 5 the term preventing has been deleted.
Claims 5, 13-14, 17, and 27-39 are pending in the case.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 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 5, 13-14, 17, and 27-39 are rejected under 35 U.S.C. 112, first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 5, 13-14, 17, and 27-39 are directed to a method inhibiting or treating a microbial infection in a subject via inhalation of a formulation comprising cationic pillararene, or a salt thereof wherein the infection is caused by Gram negative bacteria.
The MPEP states that for a generic claim, the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. See MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitutes a sufficient number of representative species, the courts have indicated what does not constitute a representative number of species to adequately describe a broad genus. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618. Furthermore, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or sub-combinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Additionally, in Carnegie Mellon University v. Hoffman-La Roche Inc., Nos. 07-1266, -1267 (Fed. Cir. Sept. 8, 2008), the Federal Circuit affirmed that a claim to a genus described in functional terms was not supported by the specification’s disclosure of species that were not representative of the entire genus.
The Guidelines for Examination of Patent Applications under the 35 USC § 112, first paragraph, “Written Description” Requirement”, published at Federal Register, Vol. 66, No. 4, pp. 1099-1111 outline the method of analysis of claims to determine whether adequate written description is present. The first step is to determine what the claim as a whole covers, i.e., discussion of the full scope of the claim. Second, the application should be fully reviewed to understand how applicant provides support for the claimed invention including each element and/or step, i.e., compare the scope of the claim with the scope of the description. Third, determine whether the applicant was in possession of the claimed invention as a whole at the time of filing. This should include the following considerations: (1) actual reduction to practice, (2) disclosure of drawings or structural chemical formulas, (3) sufficient relevant identifying characteristics such as complete structure, partial structure, physical and/or chemical properties and functional characteristics when coupled with a known or disclosed correlation between function and structure, (4) method of making the claimed invention, (5) level of skill and knowledge in the art and (6) predictability of the art. For claims 5, 13-14, 17, and 27-39, each of these factors has been considered, with the most relevant factors discussed below. For each claim drawn to a genus, each of these factors is to be considered to determine whether there is disclosure of a representative number of species that would lead one skilled in the art to conclude that applicant was in possession of the claimed invention. Where skill and knowledge in the art is high, adequate written description would require fewer species to be disclosed than in an art where little is known; further, more species would need to be disclosed to provide adequate written description for a highly variable genus.
First, what do the claims as a whole cover? Claims 5, 13-14, 17, and 27-39 are directed to a method inhibiting or treating a microbial infection in a subject via inhalation of a formulation comprising cationic pillararene, or a salt thereof wherein the infection is caused by Gram negative bacteria.
Second, how does the scope of the claims compare to the scope of the disclosure? The specification as originally filed mentions cationic cavity-containing compound (specification, page 6, line 15 through page 7, line 15).
Third, the factors need to be considered, with the most relevant factors discussed below.
Reduction to Practice: The method reduced to practice in the instant specification in Example 1 at page 16 is a powder formulation which is obtained by mixing pillar[5]arene together with trehalose, raffinose, mannitol, sodium citrate and l-leucine, and the interaction of this formulation with P. aeruginosa (Example 2). Claim 5 recites cationic pillararene as the active agent, whereas examples 1-2 show the use of a formulation which has pillar[5]arene by itself mixed with other components. Even though l-leucine is used, there is no clear showing that the pillar[5]arene is cationically modified.
Level of Skill in the Art and Knowledge in the Art: The level of skill in the art is one having experience in pharmaceutical formulations and administration. Applicant’s disclosure of the use of a formulation wherein pillar[5]arene in combination with the other components as in the examples is not representative of a cationic pillararene as claimed.
Having analyzed the claims with regard to the Written Description guidelines, it is clear that the specification does not disclose the claimed method for the use of a cationic pillararene as the active agent as in the instant claims. Thus, one of ordinary skill in the art would be led to conclude that Applicant was not in possession of the claimed invention.
Claim Rejections - 35 USC § 103
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.
Claim(s) 5, 13-14, 17, and 27-39 are rejected under 35 U.S.C. 103 as being unpatentable over Jonkergouw et al (WO 2020/074776 A1; newly cited necessitated by amendment) in view of Grare et al (US 2014/0066365 A1; of record and newly cited in this rejection necessitated by amendment).
Jonkergouw teaches that Gram negative bacteria which are pathogenic to humans use quorum sensing, which plays a central role in their virulence. One such bacteria is P. aeruginosa (page 2, lines 1-4; Gram negative bacterial infection as in claims 5 and 17). The invention of Jonkergouw uses the contact of a macrocyclic cavity-containing compound with a subject infected with Gram negative bacteria (page 2, lines 5-16; method of claim 5). The active agent used is a pillar[5]arene (page 4, lines 6-34; Figure 1; as in claim 5). The pillar[5]arene can be the one recited in claims 27-28 (page 5, lines 19-24). The bacterial infection treated can also be some of the others recited in claim 17 (page 5, line 31 through page 6, line 19). The composition comprising the active agent is administered by inhalation and can be in powder form (page 17, lines 16-18; as in claims 5 and 31). The infection can be chronic, acute, or local like lung infection (page 14, lines 28-32; as in claims 13-14). The pillararene can be present as microparticles and can have additives like trehalose, sodium citrate and leucine (page 18, Example 3; as in claims 32-33). The particles have a size of 1-5mm (page 18, lines 26-27; as in claim 34). According to Jonkergouw pyocyanin is a toxin produced by P. aeruginosa and is responsible for the death of cells in the lung during cystic fibrosis. The production of this toxin is related to quorum based signaling (page 17, lines 30-36; cystic fibrosis as in claims 37-38). Therefore, the active agent can be administered to a subject having cystic fibrosis as in claims 35-38. The artisan would have a reasonable expectation of success in treating a subject having non-cystic fibrosis bronchiectasis as in claim 39.
Jonkergouw does not teach the limitations of claims 29 and 30.
Grare et al teaches the use of antibacterials like beta-lactams, aminoglycosides, fluroquinolones etc., in combination with macrocyclic cavity containing compounds for treating bacterial infections in a subject (see above: as in claims 29-30). In view of this teaching, it would be obvious to one of ordinary skill in the art to administer an inhalable composition comprising cationic pillararenes and an inhalable composition of cationic pillararenes in combination with antibacterials in the claimed method. It would be obvious to use all of the other antibacterials recited in claim 26 in view of Grare et al. It would also be obvious to the artisan to use the compounds for treating the infections as in claims 13-14 and all the other infections as in claim 17. There is also a reasonable expectation of success in treating infections caused by all the other Gram-negative bacteria recited in claim 17.
MPEP 2141 states, "The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit. The Court quoting In re Kahn, 441 F.3d 977, 988, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006), stated that "[R]ejections on obviousness cannot be sustained by mere conclusatory statements; instead, there must be some articulated reasoning with some rational underpinning to support the legal conclusion of obviousness.'" KSR, 550 U.S. at, 82 USPQ2d at 1396. Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) " Obvious to try " choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
According to the rationale discussed in KSR above, the rationale in (G) above is seen to be applicable here since based on the prior art teachings, both cationic pillararenes and antibacterials are individually taught in the art to be used in a method of treating/inhibiting Gram-negative bacterial infection.
Thus, the claimed invention as a whole would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention over the combined teachings of the prior art. Method improvement is the motivation. Since the prior art teaches that cationic pillararenes are highly effective against Gram-negative infections and suggest the use of a combination of a cavity containing compound and other antibacterials for treating Gram-negative bacterial infections, the artisan would be motivated to also use pillararene and an antibacterial in combination in order to produce an enhanced effect in the claimed method.
Response to Applicant’s Remarks
In view of the amendment to claim 5 the above rejection under 35 USC 103 is made of record.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 5, 13-14, 17, and 27-39 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 10, 15, 18, 26, 31, 37, 41-43 of copending Application No. 17/917,338 (‘338, reference application) in view of Jonkergouw et al (WO 2020/074776 A1; newly cited necessitated by amendment) in view of in view of Grare et al (US 2014/0066365 A1; of record). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claim 5 is drawn to a method of inhibiting/treating/ an infection caused by Gram-negative bacteria in a subject via administration of an inhalable formulation comprising a cationic pillararene. Dependent claims 13-14, 17, and 27-39 recite limitations drawn to type of infections, specific bacteria, antimicrobial agents, dry powder formulation, additives present, microparticles, their size, and disease or disorder that increases risk of infection.
Claim 10 of ‘338 is drawn to a method of sensitizing a gram-negative bacterium or reducing build-up of resistance of a gram-negative bacterium towards an antimicrobial agent by exposing the microbe to a pillararene and the antimicrobial agent. Claim 15 is drawn to a method of inhibiting and/or treating and/or preventing a microbial infection in a subject having microbial infection or being at risk of a microbial infection or formation of a biofilm by a gram-negative bacterium in the subject by administering an antimicrobial agent and a pillararene to the subject. Dependent claims 18, 26, 31, 37 and 41-43 recite limitations drawn to the type of cavity containing compounds, type of microbial infection, and antimicrobial agent.
The teachings of Jonkerogouw and Grare are set forth above.
In view of Jonkerogouw and Grare the method of claim 10 in ‘338 is also seen as treating/inhibiting a gram-negative microbial infection in a subject using the claimed active agents.
The copending claims of ‘338 differ from the instant claims in that the instant claims are drawn to administration of a cationic pillararene via inhalation, and an additional antimicrobial agent, whereas the claims of ‘338 require the administration of the pillararene and the antimicrobial agent.
One of ordinary skill in the art would readily recognize that the method taught by '338 could be employed in the instant invention with a reasonable expectation of success since the instant pillararene and antimicrobial agents belong to same class and are useful for the treatment of microbial infections including Gram-negative bacterial infections, especially in view of Jonkerogouw and Grare.
Therefore, one of ordinary skill in the art would have reasonably expected that the instant method of treating Gram-negative bacterial infections using a cationic pillararene and an antimicrobial agent, would have same or substantially similar beneficial therapeutic effects and usefulness in method for treating Gram-negative bacterial infection via inhalation, based on the reasonable expectation that structurally similar species usually have similar properties. See, e.g., Dillon, 919 F.2d at 693, 696, 16 USPQ2d at 1901, 1904. See also Deuel, 51 F.3d at 1558, 34 USPQ2d at 1214, and if the claimed invention and the structurally similar prior art species share any useful property, that will generally be sufficient to motivate an artisan of ordinary skill to make the claimed species. In fact, similar properties may normally be presumed when compounds are very close in structure. Dillon, 919 F.2d at 693, 696, 16 USPQ2d at 1901, 1904, as noted in MPEP 2144.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Applicant’s Remarks
Applicant has stated that the rejection is acknowledged and will take appropriate corrective action of filing a terminal disclaimer or distinguishing the claims once allowable subject matter is obtained in one of the applications.
The filing of a terminal disclaimer, or filing a showing that the claims subject to the rejection are patentably distinct from the reference application’s/patents claims is necessary. Since neither has been made of record the rejection(s) are being maintained.
Conclusion
1. Elected claims 5, 13-14, 17, and 27-39 (Group II) are rejected.
2. Claims 1-4, 6-12, 15-16, and 18-26 have been canceled.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GANAPATHY KRISHNAN whose telephone number is (571)272-0654. The examiner can normally be reached M-F 8.30am-5pm.
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, Scarlett Goon can be reached at 571-270-5241. 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.
/GANAPATHY KRISHNAN/Primary Examiner, Art Unit 1693
Prosecution Insights