00Notice 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
Claim 1-41 are pending and are under consideration in the instant office action.
Receipt and consideration of Applicants' amended claim set and remarks/arguments filed on 4/20/2026 are acknowledged. Claims 1, 12, 26 and 38 are amended and new claim 36 is added. Claims under consideration in the instant office action are claims 1-4, 7, 12-14, 16-29 and new claim 36.
Applicants' arguments, filed 4/20/2026, have been fully considered but they are not deemed to be persuasive. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. 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
The following is a quotation of the second paragraph of 35 U.S.C. 112:
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 and 41 are rejected under 35 U.S.C. 112, second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claims 1-15 and 41 are vague and indefinite because the claim as written is not clear and it is impossible to ascertain the metes and bounds of the limitations in the claim for the following reasons (1) in step (i), the claim requires rapidly freezing a solution comprising voriconazole or a salt thereof using a thin film freezing process to produce a voriconazole powder with a nanostructured morphology,, but it is not clear if this treatment is initiated in the patient of the preamble. Is this step done in the treatment process just before step (ii) which is administration of the voriconazole powder as inhalation to the patient suffering from fungal infection. Is it even practical to be actually trying to manufacture the voriconazole powder just before the administration to the patient? The claim therefore is unclear as to the inclusion of the step of preparing the voriconazole powder during the treatment period. The treatment a fungal infection with Voriconazole powder at the concentration claimed will occur irrespective of the method in which the voriconazole powder was manufactured. The claim as interpreted by the one of ordinary skill in the art as written, implies that the voriconazole was prepared just before the administration of the powder to the patient by thin film freezing process, which is impractical and not enabled by the instant specification.
For the purposes of this action, the claim is interpreted as follows:
A method of treating a fungal infection in a subject in need thereof, the method comprising administering by inhalation to said subject the voriconazolepowder or a salt thereof in an amount of about 20 mg to about 120 [[80]] mg, wherein the administration by inhalation achieves a maximum circulating plasma concentration of voriconazole of less than 1,000 ng/m, wherein the voriconazole is prepared by rapidly freezing a solution comprising voriconazole or a salt thereof using a thin film freezing process to produce a voriconazole powder with a nanostructured morphology.
The essential inquiry pertaining to this requirement is whether the claims set out and circumscribe a particular subject matter with a reasonable degree of clarity and particularity. Definiteness of claim language must be analyzed, not in a vacuum, but in light of:
(A) The content of the particular application disclosure;
(B) The teachings of the prior art; and
(C) The claim interpretation that would be given by one possessing the ordinary level of skill in the pertinent art at the time the invention was made. In reviewing a claim for compliance with 35 U.S.C. 112, second paragraph, the examiner must consider the claim as a whole to determine whether the claim apprises one of ordinary skill in the art of its scope and, therefore, serves the notice function required by 35 U.S.C. 112, second paragraph, by providing clear warning to others as to what constitutes infringement of the patent. See, e.g., Solomon v. Kimberly-Clark Corp., 216 F.3d 1372, 1379, 55 USPQ2d 1279, 1283 (Fed.Cir.2000) (MPEP 2173.02).
In the instant case the claim as written is indefinite in that considered in light of what is there in the art and the instant disclosure does not make it clear.
Accordingly, applicants are recommended to amend the claims to clarify their invention.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 16-27 and 29-40 are rejected under 35 U.S.C. 102 (a) (1) and under 35 U.S.C 102(a)(2) as being anticipated by Hilberg et al. (European Respiratory Journal 2012:271-273, reference already of record)
Instant claims are drawn to a method of increasing delivery of voriconazole to the lung of a subject in need thereof, the method comprising administering to said subject by inhalation voriconazole or a salt thereof in an amount of about 20 mg to about 80 mg, wherein the delivery of voriconazole to the lung by inhalation results in about 50-fold higher relative concentration in the lung compared to the oral administration of voriconazole after about 12 hours following administration (claim 16) and method for reducing systemic circulation of voriconazole compared with the oral administration of voriconazole comprising administering to said subject by inhalation voriconazole or a salt thereof in an amount of about 20 mg to about 80 mg, wherein the administration by inhalation achieves a maximum circulating plasma concentration of voriconazole of less than 1,000 ng/mL (claim 29)
Hilberg et al. discloses administration of voriconazole by inhalation as useful for the treatment of invasive pulmonary aspergillosis (IPA) caused by e.g. Aspergillus fumigatus, whereby a solution of voriconazole was nebulized, whereby 1, 2 or 3 daily doses of 40 mg were administered corresponding to 40 mg, 80 mg or 120 mg per day, whereby the patients were immunodeficient in that they underwent lung transplantation or received corticosteroids and whereby it is expected, as seen in animal studies, that the delivery directly to the lungs will result in high local concentrations and effective inhibition of fungal growth, while systemic concentrations and side-effects were reduced (whole document).
Hilberg et al. does not disclose that a maximum circulating plasma concentration of voriconazole of less than 1,000/500/300 ng/ml was achieved (claims 1-3, 29-31), that the systemic circulation of voriconazole is reduced compared with the oral administration (claim 29) or that the delivery of voriconazole to the lung by inhalation resulted in about 50/100/200-fold higher relative concentration in the lung compared to the oral administration of voriconazole after about 12 hours following administration (claims 16-18). However these are functional limitations of the treatment of a patient with pulmonary aspergillosis with 20-80 mg voriconazole and would occur upon such a treatment. Since Hilberg et al. disclose the treatment of the same subject population, with the same agent voriconazole at the same concentrations, these functional limitations wilt inherently occur. It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph). It is also noted that, "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art's functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430,433 (CCPA 1977). See also MPEP § 2112.01 with regard to inherency and product-by-process claims. In addition, it is also noted that “Products of identical chemical composition cannot have mutually exclusive properties.” A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). As such the instantly claimed functional limitations of the voriconazole upon treatment for fungal infections at the same concentrations instantly claimed would be present in these agents taught by Hilberg et al. when administered to the same subject population.
Therefore the method and inhalable composition of voriconazole disclosed by Hilberg et al. fully anticipates instant claims 16-27 and 29-40.
Claims 16-27, 29-35 and 36-40 are rejected under 35 U.S.C. 102 (a) (1) and under 35 U.S.C 102(a)(2) as being anticipated by Anderson et al. Basic and Clinical Pharmacology and Toxicology, vol. 121, no.5, 2017; 430-434, reference already of record)
Instant claims are as stated above.
Anderson et al. discloses administration of voriconazole by inhalation as useful for the treatment of infection with aspergillosis (IPA) , whereby a solution of voriconazole was nebulized, whereby 1, 2 or 3 daily doses of 40 mg were administered corresponding to 40 mg, per day, whereby the patients were immunodeficient in that they were patients who had to undergo bronchoscopy due to hemoptysis and whereby it is expected, as seen in animal studies, that the delivery directly to the lungs will result in high local concentrations and effective inhibition of fungal growth, while systemic concentrations and side-effects were reduced (whole document). They further disclose that a twelve hours after the last dose, median (95% CI) plasma voriconazole concentration was 8 (4–26) ng/mL in the inhalation group and 1224 (535– 2341) ng/mL in the oral group and a( 153 fold lower plasma concentration compared to oral administration (8 ng/ml vs 1224 ng/ml), while achieving delivery of voriconazole to the lung (whole document, particularly abstract; p. 430, left col., 1st and 2nd par.) and disclose that voriconazole concentrations after the initial dose were 98 (44–136) ng/mL, 67 (26–116) ng/mL, and 43 (22–76) ng/mL at 15, 30 and 60 min., respectively (page 432, col.1, 3rd para).
Therefore the method and inhalable composition of voriconazole disclosed by Hilberg et al. fully anticipates instant claims, 16-27, 29-35 and 36-40.
Response to arguments filed on 4/20/2026
Applicants argue that they have amended claim 1 to overcome the rejections. While their amendment interpreted as stated above overcomes the anticipation rejection on claims 1-5 and 8-14, they do not overcome the rejections on claims 16-27, 29-35 and 36-40.
Claim Rejections - 35 USC § 103
New Grounds of rejection necessitated by the amendment dated 4/20/2026
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1-41 are rejected under 35 U.S.C. 103(a) as being unpatentable over by Hilberg et al. (European Respiratory Journal 2012:271-273, reference already of record) and Anderson et al. Basic and Clinical Pharmacology and Toxicology, vol. 121, no.5, 2017; 430-434, reference already of record) further in view Moon et al. (Journal of drug delivery science and technology 54, 2019, pages 1-11)
Instant claims are drawn to a method of treating a fungal infection in a subject in need thereof, the method comprising administering by inhalation to said subject voriconazole or a salt thereof in an amount of about 20 mg to about 80 mg, wherein the administration by inhalation achieves a maximum circulating plasma concentration of voriconazole of less than 1,000 ng/m (independent claim 1), method of increasing delivery of voriconazole to the lung of a subject in need thereof, the method comprising administering to said subject by inhalation voriconazole or a salt thereof in an amount of about 20 mg to about 80 mg, wherein the delivery of voriconazole to the lung by inhalation results in about 50-fold higher relative concentration in the lung compared to the oral administration of voriconazole after about 12 hours following administration (claim 16) and method for reducing systemic circulation of voriconazole compared with the oral administration of voriconazole comprising administering to said subject by inhalation voriconazole or a salt thereof in an amount of about 20 mg to about 80 mg, wherein the administration by inhalation achieves a maximum circulating plasma concentration of voriconazole of less than 1,000 ng/mL (claim 29)
Hilberg et al. discloses administration of voriconazole by inhalation as useful for the treatment of invasive pulmonary aspergillosis (IPA) caused by e.g. Aspergillus fumigatus, whereby a solution of voriconazole was nebulized, whereby 1, 2 or 3 daily doses of 40 mg were administered corresponding to 40 mg, 80 mg or 120 mg per day, whereby the patients were immunodeficient in that they underwent lung transplantation or received corticosteroids and whereby it is expected, as seen in animal studies, that the delivery directly to the lungs will result in high local concentrations and effective inhibition of fungal growth, while systemic concentrations and side-effects were reduced (whole document).
Anderson et al. discloses administration of voriconazole by inhalation as useful for the treatment of infection with aspergillosis (IPA) , whereby a solution of voriconazole was nebulized, whereby 1, 2 or 3 daily doses of 40 mg were administered corresponding to 40 mg, per day, whereby the patients were immunodeficient in that they were patients who had to undergo bronchoscopy due to hemoptysis and whereby it is expected, as seen in animal studies, that the delivery directly to the lungs will result in high local concentrations and effective inhibition of fungal growth, while systemic concentrations and side-effects were reduced (whole document). They further disclose that a twelve hours after the last dose, median (95% CI) plasma voriconazole concentration was 8 (4–26) ng/mL in the inhalation group and 1224 (535– 2341) ng/mL in the oral group and a( 153 fold lower plasma concentration compared to oral administration (8 ng/ml vs 1224 ng/ml), while achieving delivery of voriconazole to the lung (whole document, particularly abstract; p. 430, left col., 1st and 2nd par.) and disclose that voriconazole concentrations after the initial dose were 98 (44–136) ng/mL, 67 (26–116) ng/mL, and 43 (22–76) ng/mL at 15, 30 and 60 min., respectively (page 432, col.1, 3rd para).
The references above do not teach the voriconazole as voriconazole inhalation powder or the method in which the voriconazole inhalation powder was made by using a thin film freezing process.
However, Moon et al. discloses preparation of voriconazole nano aggregates as dry powder for inhalation and disclose that new technologies for developing dry powder inhalation formulations ,thin film freezing (TFF) is also an advanced particle engineering technology that uses high supercooling, which can produce powder formulations for DPIs that consist of nanostructured brittle matrices (25–27) or nanoaggregates (abstract, page 2, col.1,2nd para). They disclose a scaled up process to manufacture voriconazole nanoaggregates in which the surface texture is modified and maintained by mannitol and describe the preparation using the thin film freezing process in detail (entire document). Moon et al. discloses Voriconazole as a triazole antifungal agent used as the first line treatment against invasive pulmonary aspergillosis (introduction).
As such it would have been prima facia obvious to a person of ordinary skill in the art to arrive at the instant claims motivated and guided by the combined teachings of Hilberg et al. Anderson et al. and Moon et al. to arrive at the instant claims.. An ordinarily skilled artisan would be motivated from all three references to treat fungal infections caused by Aspergillus in patients who are immunocompromised with Voriconazole which is already an established antifungal agent , all three references also provides motivation to an ordinarily skilled artisan to develop either an aqueous or dry inhalation formulation of Voriconazole to avoid systemic side effects experienced with oral formulation. Moon et al., provides motivation and methods to prepare dry powder inhalation formulation of voriconazole using thin film freezing process As such a person of ordinary skill in the art would be imbued with a reasonable expectation of success in treating fungal infections with inhalation formulation of voriconazole more successfully than the oral formulation and therefore arrive at the instant claims, absence of evidence to the contrary.
Conclusion
Claims 1-41 are rejected. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAVITHA RAO whose telephone number is (571)270-5315. The examiner can normally be reached on Mon-Fri 7.00 am to 4.00 pm. If attempts to reach the examiner by telephone are unsuccessful, the examiner' s supervisor, Renee Claytor can be reached on (571) 272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SAVITHA M RAO/Primary Examiner, Art Unit 1691
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