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
Claim 1-41 are pending and are under consideration in the instant office action.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/16/2023, 08/10/2023 and 08/27/2024 complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, it has been placed in the application file and the information therein has been considered as to the merits. See attached copy of the PTO-1449.
Priority
This application claims the benefit of and priority to U.S. provisional patent application number 63/291,055, which was filed on December 17, 2021.
Claim Rejections - 35 USC § 112 (d)
The following is a quotation of the fourth paragraph of 35 U.S.C. 112:
Subject to the following paragraph, a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 12, 26 and 38 are rejected under 35 USC § 112 4th Paragraph as being of improper dependent form for failing to further limit the subject matter of a previous claim. Claim 12 which depends on claim 1 and claim 26 which depends on claim 16 and claim 38 which depends on claim 29 recites the amount of voriconazole at 40 mg-120 mg which is broader than the independent claims upon which they depend which is 20-80 mg. Applicant is required to cancel the claim(s), or amend the claim(s) to place the claim(s) in proper dependent form, or rewrite the claim(s) in independent form..
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 1-5, 8-14, 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 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/ml (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).
Hilberg et al. does not disclose that a maximum circulating plasma concentration of voriconazole of less that 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 1-5, 8-14, 16-27 and 29-40.
Claims 1-5, 8-14, 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 1-5, 8-14, 16-27, 29-35 and 36-40.
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.
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 Rundfeldt et al. (US 2011/0190245)
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.
However, Rundfeldt et al. discloses nanocrystalline dry powder of azole derivative useful as antifungal agent. [0049], the azole derivative includes voriconazole [0056] and the composition may be administered using standard dry powder technologies [0061-0062] which is suitable for prevention and treatment of fungal infections in immune compromised or immune suppressed patients [0084] wher in the infection is an infection by Aspergillus species (claims 5, 17,18 and 20).
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 Rundfeldt 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 Aspergilus 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. 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
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 am to 4 pm..
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Dierdre (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