DETAILED ACTION
Previous Rejections
Applicants' arguments, filed 28 August 2026, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The anticipation rejection is overcome in view of the amendment to the claim. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 112 – 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.
Claims 19-34 are rejected under 35 U.S.C. 112(a) because the specification, while being enabling for treatment of some fugal conditions with some antifungal polyenes (such as amphotericin B), does not reasonably provide enablement for treatment of all fungal orders (such as the Mucorales order) using polyenes generally. 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.
To be enabling, the specification of the patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993). Explaining what is meant by “undue experimentation,” the Federal Circuit has stated:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which the experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996).1
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation:
1) the quantity of experimentation necessary,
2) the amount of direction or guidance provided,
3) the presence or absence of working examples,
4) the nature of the invention,
5) the state of the prior art,
6) the relative skill of those in the art,
7) the predictability of the art, and
8) the breadth of the claims.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
The nature of the invention, state and predictability of the art, and relative skill level: The invention relates to methods of treating or preventing infections caused by a fungus. The relative skill of those in the art is high, that of an M.D. or Ph.D. That factor is outweighed, however, by the unpredictable nature of the art. As illustrative of the state of the art, the examiner cites the instant specification. It is noted in the specification there are only three antifungal agents active against the Mucorales order of fungi (page 1, lines 8-15). These include Amphotericin B and two other non-polyene antifungal agents (page 1, lines 11-14). The Examiner cannot ascertain the predictability of the art, as there appears to be no guidance in the art as to how to make and use the full scope of the invention.
The breadth of the claims: The claims are broadly drawn to treating and preventing infections caused by fungus, including but not limited to fungus of the Mucorales order (claim 20), and doing so using antifungal polyenes, which includes amphotericin B as well as other polyenes such as nystatin (specification, page 6, lines 20-22).
The amount of direction or guidance provided and the presence or absence of working examples: The specification provides no direction or guidance for practicing the claimed invention in its “full scope”. No reasonably specific guidance is provided concerning useful therapeutic protocols for treating fungus infections generally, other than using amphotericin B. The latter is corroborated by the working examples.
The quantity of experimentation necessary: Because of the known unpredictability of the art, and in the absence of experimental evidence, no one skilled in the art would accept the assertion that the instantly claimed agents could be predictably used polyene antifungal agents other than amphotericin B to treat fungus infections (including those of the Mucorales order) as inferred by the claim and contemplated by the specification. Accordingly, the instant claims do not comply with the enablement requirement of §112, since to practice the claimed invention in its “full scope” a person of ordinary skill in the art would have to engage in undue experimentation, with no reasonable expectation of success.
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 19-28 and 30-34 are rejected under 35 U.S.C. 103 as being unpatentable over Majumdar et al. (US Patent Application Publication 2021/0330598) in view of Millenbaugh et al. (US Patent Application Publication 2018/0250362).
Majumdar et al. discloses compositions of amphotericin loaded nanolipid carriers comprising PEG-molecules and their use as treating fungal infections (title & abstract). The polyethylene-molecules are in the surface of the nanolipid carrier (paragraph [39]) and the amphotericin (which can be amphotericin B) is in the carrier (paragraph [38])
Majumdar et al. further suggests the inclusion of surfactants in the composition (paragraph [40]), and the suggested surfactants include polyethylene glycol hydroxystearate (HS-15) (paragraph [37]), which is the elected species of polyglycol ester of a hydroxy fatty acid. While Majumdar et al. does not state the surfactant would form an envelope on the lipid nanoparticle, to do so according to the instant specification this surfactant needs to be mixed with the lipids (example 1), and this is the manner in which the ingredients are combined according to Majumdar et al. (example 2).
Majumdar et al. thus teaches all of the limitation of instant claim 19 except for the specific fungus being treated. While Majumdar et al. suggests using the compositions to treat subjects with a fungal infection (paragraph [41]), the specific type of the Mucorales order of fungi is not suggested.
Millenbaugh et al. discloses methods of treating fungal infections (abstract). Useful agents include amphotericin B (paragraph [48]), which can be used to treat the Mucorales order of fungi (paragraph [40]).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to have used the amphotericin B formulation taught by Mujumdar et al. to treat fungal infections of the Mucorales order. Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07.
Instant claim 20 further limits the fungus treated, and the Mucorales order of fungi cited above reads upon the instantly recited limitation.
Instant claims 21-24 further limit the hydroxy fatty acid, and the polyethylene glycol hydroxystearate (HS-15) cited above reads upon these limitations.
Instant claim 25 further limits the polyene antifungal, and this antifungal is taught by the above references.
Instant claims 26-27 and 31 further limit the amounts of the ingredients. Amphotericin B is loaded in from 0.01 to about 0.5 wt% of the dispersion (claim 10), and also such as 0.3 wt% of the composition (table 2). And the PEG-based molecules are present in from, for example, 0.3 wt% (table 2). These amounts overlap the instantly recited amounts. And in cases involving overlapping ranges, where the instantly claimed ranges “overlap or lie inside ranges disclosed by the prior art”, a prima facie case of obviousness exists. See MPEP 2144.05.
Additionally, and alternatively, generally differences in concentration and tempera-ture will not support the patentability of subject mat-ter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to dis-cover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05(II)(A).
Instant claim 28 recites limitations to the size of the particles, and the ranges disclosed by Mujumdar et al. overlap this range (paragraph [36]).
Instant claim 30 recites that the aqueous phase is free of the polyene antifungal. And Mujumdar et al. teaches that the amphotericin B is loaded into the nanolipid carrier.
Instant claims 32-34 recite the further inclusion of triazole antifungal agents. Such agents are discussed by Mujumdar et al. as being used to treat the same conditions (paragraph [4]). Generally, it is prima facie obvious to combine two compositions, each of which is taught by the prior art to be useful for same purpose, in order to form a third composition to be used for the very same purpose. The idea for combining them flows logically from their having been individually taught in the prior art. See MPEP 2144.06.
Response to Arguments
The Applicant argues that the scope of enablement rejection is not proper for several reasons. The Applicant states that the examples in the instant specification use four different genera from the order Mucorales. And the inventive composition was shown to be effective against these genera (and thus can be expected to work on other genus of the same order). As for other polyene antifungal agents, these are part of the same chemical family, and thus it is expected that these are relevant for the invention.
The Examiner acknowledges the arguments presented, but does not consider them persuasive. With respect to the use of amphotericin B, this is reasonably expected to be effective against the Mucorales order (as stated by the rejection rationale). But the rejection is not overcome, as the other polyene antifungals are not reasonably expected to be enabled. The instant specification clearly states that there are only three antifungal agents active against the Mucorales order of fungi (page 1, lines 8-15).
The Applicant argues that the obviousness rejection is not proper for several reasons. The Applicant argues that for patients infected by Mucorales order, there are only three antifungal agents available. However, the inventive formulations provide for unexpectedly better (lower) MICs. These show that lipid nanoparticles according to the invention foster cell penetration. And this unexpected outcome overcomes the obviousness rejection.
The Examiner acknowledges the arguments presented, but does not consider them persuasive. The effect is acknowledged, and considered unexpected. However, once unexpectedness has been established, the probative value of the evidence as compared to the invention as claimed must be determined, i.e., claims must be “commensurate in scope” with the showing. See MPEP 716.02(d). In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range or whether or not there is adequate basis for reasonably concluding that the number and variety of species included by the claims would behave in the same manner as those tested.
And the showing is not considered to support a conclusion that the scope of the claim would possess the unexpected effect. Only one active agent was evaluated, and it is unclear whether other actives would also possess the same improvement against the Mucorales order. Also, the lipid nanoparticles evaluated do not appear commensurate in scope with the claims.
Conclusion
THIS ACTION IS MADE FINAL. 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 Brian Gulledge whose telephone number is (571) 270-5756. The examiner can normally be reached Monday - Friday 7am - 4pm.
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, Fereydoun Sajjadi can be reached at (571) 272-3311. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Brian Gulledge/Primary Examiner, Art Unit 1699
1 As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is “undue”, not “experimentation”.
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