DETAILED ACTION
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 .
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.
Response to Amendment
The amendment filed July 15, 2026 has been entered. Claims 1, 3, and 31 have been amended, claims 5-7, 10-13, 15-30, 32, 34-35, 37-45, and 51 are cancelled, and claims 53-56 have been added. Applicants amendments have overcome the drawing and claim rejections previously set forth in the Non-Final Office action mailed April 28, 2026.
Applicant’s arguments filed July 15, 2026 were fully considered but they were not persuasive. Maintained/New Rejections and response to amendments as they currently apply are addressed below.
Claims 1-4, 8-9, 14 ,31, 33, 36, 46-50, and 52-56 are pending in this application.
Priority
This application is 371 National Stage Application of PCT/US20/45566, filed August 10, 2020, which claims the benefit of priority to U.S. Provisional Patent Application No. 62/884,464, filed August 8, 2019, and U.S. Provisional Patent Application No. 62/951,753, filed December 20, 2019.
Election/Restrictions
Applicant’s election of Group I claims and the following elected species:
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in the reply filed on August 4, 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)).
In the amendment filed April 9, 2026, Applicant amended the claims such that the elected species is no longer encompassed by the claims. In the response filed April 9, 2026, Applicant requested the search be extended to the following species:
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wherein R1 and R2 are hydrogen and 2-hydroxyethyl (C2alkyl substituted with one hydroxy). Thus, the Examiner has expanded the search to this species.
Claims 1-4, 8-9, 14 ,31, 33, 36, 46-50, and 52-56 are encompassed by the election and are examined herein.
Based on the cited art, the search was further expanded to include
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as well, which is encompassed by claims 1-4, 8-9, 14, 31, 33, and 36.
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.
Claims 1-4, 8-9, 14 ,31, 33, 36, 46-50, and 52-56 are rejected under 35 U.S.C. 103 as being unpatentable over Tevyashova (Antimicrobial Agents and Chemotherapy, 2013, IDS filed August 14, 2024) in view of Burke (US 9,738,677, IDS filed September 25, 2024).
Regarding claims 1-4, 8-9, 14 ,31, 33, 36, 46-50, and 52-56: Tevyashova teaches structure-antifungal activity relationships for amphotericin B (AMB) and its semisynthetic derivatives (abstract, pg. 3816, figure 1). Tevyashova teaches the following compounds 1b and 1c of formula 1
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and antifungal activity thereof (pg. 3818, figure 1, compounds 1b and 1c). The antifungal activity of these compounds was determined in liquid medium comprising water (i.e. a carrier, pg. 3816, col. 2, para. 3).
The compounds of Tevyashova differs from the elected compounds in the stereochemistry at the C2’ position of the mucosamine is opposite:
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( Tevyashova)
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(claimed) (i.e. epimer). Tevyashova does not explicitly teach administering to a subject for the treatment of a fungal infection.
However, Burke teaches an amphotericin B derivative with opposite stereochemistry at C2’ position of the mucosamine (abstract col. 2, lines 1-65). Burke teaches that opposite stereochemistry at this position has the added benefit of maintaining antifungal potency while having lower toxicity to human cells (abstract). Burke teaches the compounds can be utilized in pharmaceutical compositions with a carrier (col. 2, lines 45-67). Burke further teaches that the C2’epiAmB was more effective in reducing fungal burden compared to AmB (col. 64, lines 35-47).
Taken together, it would have been prima facie obvious to a person of ordinary skill in the art to modify the compounds of Tevyashova by switching the stereochemistry of the C2’ position of the mucosamine group as taught by Burke. A person of ordinary skill in the art would have the motivation to do so with a reasonable expectation of success in order to improve the AmB analogues by improving ability to reduce fungal burden and lowering toxicity to subjects. It would also have been prima facie obvious to administer the compounds for the treatment of fungal infections in a subject as the compounds are established generally to have anti-fungal activity.
Maintained/New 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 1-4, 8-9, 14, 31, 36, 46-50, and 52-56 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending Application No. 18/877,792 (US 20250387422, cited in previous action). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding claims 1-4, 8-9, 14, 31, 36, 46-50, and 52-56: The copending claims teach a composition comprising a lipid polymer excipient and a compound of the following formula:
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(copending claim 1). The copending claims specifically teach the compound may be the elected compounds
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(copending claim 19). The copending claims teach wherein the compositions can be used to treat a fungal infection (copending claim 51).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 33 is provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over the claims of copending Application No. 18/877,792 (US 20250387422, cited in previous action) as applied to claims 1-4, 8-9, 14, 31, 36, 46-50, and 52-56 above in view of Burke (US 9,738,677, IDS filed September 25, 2024). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding claim 33: As discussed above the elected compound is encompassed by the copending claims.
They do not teach formulation with a pharmaceutical carrier.
However, Burke teaches an amphotericin B derivative with opposite stereochemistry at C2’ position of the mucosamine (abstract col. 2, lines 1-65). Burke teaches that opposite stereochemistry at this position has the added benefit of maintaining antifungal potency while having lower toxicity to human cells (abstract). Burke teaches the compounds can be utilized in pharmaceutical compositions with a carrier (col. 2, lines 45-67). Burke further teaches that the C2’epiAmB was more effective in reducing fungal burden compared to AmB (col. 64, lines 35-47).
Taken together, it would have been prima facie obvious to a person of ordinary skill in the art to modify the composition of the copending application by including a pharmaceutical carrier as taught by Burke. A person of ordinary skill would have had the motivation to do so with a reasonable expectation of success given that Burke establishes inclusion of a carrier is a routine practice in the art of anti-fungal therapeutics.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant’s arguments filed July 15, 2026 have been fully considered but they are not persuasive.
On pages 13-14 of Applicant’s response, Applicant argues that the compound of Tevyashova has lower antifungal activity against fungal species compared to AmB and thus a person of ordinary skill would not have been motivated to select the hydroxy-substituted derivative over Amb.
However, Tevyashova demonstrates that the compound has appreciable activity, and disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use (See MPEP 2123 (II)). Additionally, on page 16 of applicant’s response, Applicant demonstrates that the claimed compound has lower antifungal activity against fungal species compared to AmB (table 1).
On page 14 of Applicant’s response, Applicant argues Burke teaches the C2-epi stereochemistry has the added benefit of maintaining antifungal potency while having lower toxicity to human cells (last para.). On page 15 of Applicant’s response, Applicant argues the C2-epi AmB has reduced antifungal activity compared with AmB, according to Burke figure 5 (para. 1).
However, as discussed above, Tevyashova teaches an amide AmB amide derivative which only differs from the claimed invention in that it lacks the claimed stereochemistry (i.e. C2’-epimer). Burke teaches an amphotericin B derivative with opposite stereochemistry at C2’ position of the mucosamine (abstract col. 2, lines 1-65). Burke teaches that opposite stereochemistry at this position has the added benefit of maintaining antifungal potency while having lower toxicity to human cells (abstract). Additionally, while Burke teaches the C2’epiAmB has a higher MIC, Burke further teaches that the C2’epiAmB was more effective in reducing fungal burden compared to AmB (i.e. more biological activity, col. 64, lines 35-47, see drawings, figure 7). Thus, a person of ordinary skill in the art would recognize the added benefit of reversing the stereochemistry at the C2’ position of the mucosamine (i.e. the epimer), thus having the requisite motivation to do so with a reasonable expectation of success in improving both antifungal ability and reducing toxicity. The art recognizes the added benefit of C2’ epimer to reduce overall toxicity and to improve potency, thus, such a result cannot be considered unexpected.
On pages 15-16 of Applicant’s response, Applicant argues that the instantly claimed compound exhibits an unexpectedly improved effect for antifungal activity over C2’-epi AmB, while maintaining reduced toxicity (para. 4). Applicant argues that figure 5 of Burke recognizes that C2’-epi Amb has reduced toxicity compared to modified native AmB, but the C2’-epi AmB also has reduced antifungal activity as compared with AmB (pg. 15, para. 5). On page 16 of Applicants response, Applicant argues that modification of AmB with a C2’-epi reduces toxicity at a loss of antifungal activity, and further installation of the amide group recovers improves (paras. 1-2, table 1). In short, Applicant is arguing the unexpected benefit of both improving antifungal activity with amide incorporation and reducing toxicity with C2’ epimer compared to AmB.
However, Applicants evidence of unexpected results is found to not be persuasive. As discussed above, Tevyashova teaches an AmB amide derivative which only differs from the claimed invention in that it lacks the claimed stereochemistry (i.e. C2’-epimer). The claimed subject matter must be compared with the closest prior art to be effective to rebut a prima facie case of obviousness (See MPEP 716.02e). Tevyashova teaches the amphotericin B N-(2-hydroxyethyl)amide derivatives has lower antifungal properties amphotericin B, however, this is also reflected in the data presented by Applicant (remarks, pg. 16, table 1). Burke teaches an amphotericin B derivative with opposite stereochemistry at C2’ position of the mucosamine (abstract col. 2, lines 1-65). Burke teaches that opposite stereochemistry at this position has the added benefit of maintaining antifungal potency while having lower toxicity to human cells (abstract). While figure 5 of Burke shows a lower MIC for the C2’-epi, biological results actually demonstrate the C2’-epi Amb actually has higher potency compared to AmB in reducing fungal potency (col. 64, lines 35-47, drawings figure 7). Thus, a person of ordinary skill in the art would recognize the added benefit of reversing the stereochemistry at the C2’ position of the mucosamine (i.e. the epimer), thus having the requisite motivation to do so. The art recognizes the added benefit C2’ epimer to reduce overall toxicity and improved ability to reduce fungal burden, thus, such a result cannot be considered unexpected. Furthermore the Examiner notes that even if found to be a persuasive showing of unexpected results, whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." (See MPEP 716.02(d). In other words the claims are not limited to this particular species which is claimed to have the unexpected properties and Applicant has not demonstrated this effect occurs for all of the claimed compounds, should the election be withdrawn.
To summarize, Applicant argues that the claimed compound which possesses an amide modification and C2’ epimer exhibits improved fungal potency and reduced toxicity as a result of these two modifications of AmB wherein both are unexpected properties.
The Examiner argues that the prior art demonstrates that C2 epimerization reduces toxicity and also improves potency in AmB derivatives. Tevyashova teaches the hydroxyethylamide derivative while Burke acknowledges that C2’ epimerization has a net reduction in toxicity for AmB derivatives and improved biological activity for reducing fungal burden. Thus, it would be obvious to incorporate this feature with a reasonable expectation of success in reducing toxicity and improving potency that is not considered unexpected. There is no evidence that the epimerization of the hydroxyethylamide derivative also exhibits improved activity that would be unexpected.
Applicant’s reply is considered to be a bona fide attempt at a response and is being accepted as a complete response. The 35 USC § 103 rejection and double patenting rejections are maintained for reason of record and foregoing discussion.
Conclusion
No claims are allowed in this action.
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 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 SAMUEL L GALSTER whose telephone number is (571)270-0933. The examiner can normally be reached Monday - Friday 8:00 AM - 5:00 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Scarlett Y 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.
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/S.L.G./Examiner, Art Unit 1693
/ANDREA OLSON/Primary Examiner, Art Unit 1693
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