DETAILED ACTION
Claims 1-3, 9, 16, 29, 32, 47-48, 72, 75, 105, 110, 115, 141, 170-171, 178, 193, 196, 205-206, 236, 246, 271, 300, and 308-310 are pending. Of these, claims 170-171, 178, 193, 196, 205-206, 236, 246, 271, 300, and 308-310 are withdrawn as directed to a nonelected invention. Therefore, claims 1-3, 9,16, 29, 32, 47-48, 72, 75, 105, 110, 115, and 141 are under consideration on the merits.
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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 on 6/29/26 has been entered.
Status of the Rejections
The 103 rejections are revised.
A new 112(b) rejection is applied.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
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 1-3, 9,16, 29, 32, 47-48, 72, 75, 105, 110, 115, and 141 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites “the surface of the carrier” in the last line of the claim. There is no antecedent basis for this limitation, since the claim earlier refers only to a reduced temperature surface and not to a surface of the carrier. Clarification is required. Since dependent claims 2-3, 9,16, 29, 32, 47-48, 72, 75, 105, 110, 115, and 141 fail to clarify the point of confusion, they are also rejected.
Additionally, the last clause of claim 1 is unclear because it recites “one or more particles wherein the active pharmaceutical ingredient has been deposited on the surface of the carrier,” and it is unclear if the one or more particles comprise the carrier on which the active has been deposited or rather if “wherein the active pharmaceutical ingredient has been deposited on the surface of the carrier” is a separate limitation unrelated to “one or more particles.” If the former, it is suggested that the claim should recite “one or more particles comprising the active pharmaceutical ingredient deposited on a surface of the carrier” or the like. Clarification is required. Since dependent claims 2-3, 9,16, 29, 32, 47-48, 72, 75, 105, 110, 115, and 141 fail to clarify the point of confusion, they are also rejected.
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 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 1-3, 9, 16, 29, 32, 47-48, 72, 75, 105, 110, 115, and 141 are rejected under 35 U.S.C. 103 as unpatentable over Lerner et al. (US Pat. Pub. 2008/0057129; of record in IDS) in view of Sahakijpijarn et al. (Pharmaceutics 2020,12, 1002).
As to claims 1-3, 9, 16, 29, 32, 47-48, 72, 75, 105, 110, 115, and 141, Lerner discloses a method of preparing a pharmaceutical composition comprising powders for inhalation (paragraph 20), the method comprising dissolving an active pharmaceutical ingredient and a polymer that forms a dispersion with the drug such as Poloxamer 407 and PEG 6000 (“excipients” of claim 2 that are “pharmaceutically acceptable polymers” of claim 32) in an organic solvent and sublimable carrier to form a solution, adding a plurality of pharmaceutical carrier particles such as sugar particles such as lactose particles (a "carrier" that is a “sugar” of claim 9 and which is “sparingly soluble” in the solvent as recited by claim 1) to the solution to obtain a dispersion that is a suspension (claim 16) which is placed in a freezer (a device comprising a "reduced temperature surface" of claim 71) to obtain a frozen suspension, which is then subjected to lyophilization or a vacuum oven to dry the frozen suspension, thereby forming a composition comprising an agglomeration of particles of the API deposited on the surface of the carrier particles (claim 105)(Abstract, paragraphs 19, 24, 49, 60-63, 92, and Example 7 at paragraph 110). The placement of the composition into the freezer is viewed as an “applying” onto a reduced temperature surface as recited by claim 1, because the reduced temperature of the freezer will render its internal surface to have a reduced temperature as well. Lerner further disclose that the active may be cyclosporin (which is an immunosuppressant that is a species of the elected genus of actives, i.e., an immunomodulating drug (claims 47-48)(see, e.g., Example 5). Lerner further teaches that the solvent may be an organic solvent such as ethanol, which is a polar solvent (paragraph 60), and that the formulation further may comprise pharmaceutically acceptable excipients such as additives to stabilize the composition during manufacturing or storage (paragraph 75).
Regarding claim 29, the lactose carrier is present in the amount of 1 gm lactose /1.2gm total weight of ingredients after removal of the menthol, or about 83 wt%, which is within the claimed range (paragraph 110).
As to claims 1-3, 9, 16, 29, 32, 47-48, 72, 75, 105, 110, 115, and 141, Example 7 of Lerner does not further expressly disclose that the dispersion is dropped from a height of between 5-20 cm onto the reduced temperature surface as recited by claim 1. Nor does Lerner expressly disclose that the excipient is an amino acid (claim 3) or the temperature range of the surface during the freezing process as recited by claim 72. Nor does Lerner expressly disclose that the polar solvent is aprotic as recited by claim 1 nor the specific surface area of the composition (claim 110) or that the relative standard deviation of the homogeneity of the composition is within the range of claim 141 or the specific surface area of the composition relative to the specific surface area of the carrier (claim 115).
Sahakijpijarn discloses a method of preparing a pharmaceutical composition in the form of a dry powder for inhalation, the method comprising dissolving remdesivir (an “active pharmaceutical ingredient”) in a solvent comprising acetonitrile (an “aprotic organic solvent”) along with mannitol and lactose as sugar carriers and leucine (an amino acid excipient), followed by application to a rotating stainless steel drum (a “reduced temperature surface” that rotates at a speed) cryogenically cooled to -100 degrees Celsius (which is within the range of claim 72) by dropping from a height of 10 cm, followed by drying in a lyophilizer (Title, Abstract, and section 2.2).
As to claims 1-3, 9,16, 29, 32, 47-48, 72, 75, 105, 110, 115, and 141, it would have been prima facie obvious to one of ordinary skill in the art at the effective filing date of the present invention to modify the method formulating pharmaceutical particles for inhalation via freeze drying as taught by Lerner by adding leucine as an excipient and by using an aprotic organic solvent such as acetonitrile as the organic solvent and by applying the dispersion to a reduced temperature surface such as a rotating cryogenically cooled stainless steel drum having a surface temperature within the range of claim 72 and by dropping onto the rotating drum from a height within the recited 5-20 cm of claim 1, because Lerner does not place any limitations on the identity of the organic solvent and expressly teaches that the composition may comprise pharmaceutically acceptable excipients and Sahakijpijarn expressly teaches a method comprising the above steps as an alternative means of forming a composition of particles comprising a pharmaceutical active for inhalation via freeze drying, and further expressly teaches that leucine is a suitable excipient for use in such a process and that acetonitrile is a suitable solvent for use in such a process. The foregoing modifications are merely the simple substitution of one prior art element for another according to known methods to achieve predictable results, which is prima facie obvious. MPEP 2143.
Regarding claims 110, 115, and 141, the resulting composition will possess a specific surface area of the composition within the range of claim 110 and a relative standard deviation of the homogeneity of the composition within the range of claim 141 as well as a specific surface area of the composition relative to the specific surface area of the carrier within the range of claim 115 because it is formed by a method comprising the same steps recited by the claims. The U.S. Patent Office is not equipped with analytical instruments to test prior art compositions for the countless ways that an Applicant may present previously unmeasured characteristics. When the prior art appears to contain the same ingredients that are disclosed by Applicants' own specification as suitable for use in the invention, a prima facie case of obviousness has been established, and the burden is properly shifted to Applicants to demonstrate otherwise. See MPEP 2112.01. Additionally, discovering optimum or working ranges involves only routine skill in the art in cases where the general conditions of a claim are disclosed in the prior art. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Response to Applicant’s Arguments
Applicant argues that the Lerner methods all comprise a step of subliming a sublimable carrier from a solid solution, thereby depositing micronized microparticles of the drug on the surface of the pharmaceutical carrier. Applicant concludes that the presence of a sublimable carrier is a fundamental feature of Lerner, and argues that replacing a sublimable carrier with a polar aprotic solvent as required by the claims is not merely a substitution of one known element for another to achieve predictable results, because the Lerner method would not work without a sublimable carrier such that the proposed modification would change the principle of operation of Lerner’s invention. Applicant further argues that nothing in Sahakijpijarn provides a suggestion that the artisan could have successfully modified the principle of operation of Lerner because Sahakijpijarn does not relate to sublimable carriers nor teach other key limitations including the use of a sparingly soluble carrier and adding that carrier to a solution of the active to obtain a dispersion.
In response, the Office agrees that the Lerner method involves the use of a sublimable carrier, but Lerner also expressly teaches that the method may involve the presence of an organic solvent in addition to the sublimable carrier as discussed in the rejection. The rejection does not propose to replace the sublimable carrier of Lerner with a polar aprotic solvent, but rather proposed to use both the sublimable carrier and the organic solvent as expressly suggested by Lerner, and further by selecting a polar aprotic solvent such as acetonitrile as the polar aprotic solvent based upon the teachings of Sahakijpijarn. Therefore, the proposed modification to Lerner does not change the principle of operation of Lerner and therefore would not render unworkable the Lerner method.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GAREN GOTFREDSON whose telephone number is (571)270-3468. The examiner can normally be reached M-F 9AM-6PM.
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/GAREN GOTFREDSON/Examiner, Art Unit 1619
/ANNA R FALKOWITZ/Primary Examiner, Art Unit 1600
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