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 Of these, claims 170-171, 178, 193, 196, 205-206, 236, 246, 271, 300, and 308-310 are withdrawn as directed to a nonelected invention.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 .
Status of the Rejections
The 112(b) rejections are withdrawn in view of the amendment.
The 103 rejections are maintained.
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 docetaxel (an “active pharmaceutical ingredient”) and Poloxamer 407 and PEG 6000 (“excipients” of claim 2 that are “pharmaceutically acceptable polymers” of claim 32) in melted menthol (a "solvent") to form a solution, adding lactose (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 vacuum oven to dry the frozen suspension by removing the solvent (Example 7 at paragraph 110), thereby forming a composition comprising an agglomeration of particles of the API deposited on the surface of particles of the carrier (claim 105)(Abstract and paragraph 24). 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. The broader teachings of 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). The broader teachings of Lerner disclose that the solvent may be an organic solvent such as ethanol (paragraph 60).
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 active is the elected species, i.e., cyclosporin or 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 solvent is aprotic (claim 42) or the specific surface area of the composition (claim 110) or the relative standard deviation of the homogeneity of the composition 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 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 Lerner method of Example 7 by selecting cyclosporin as the active, because the broader disclosure of Lerner expressly teaches that the active may be cyclosporin. Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. MPEP 2123. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). It further would have been prima facie obvious to modify the method of 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 as the 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 Sahakijpijarn expressly teaches such a method as an alternative means of forming a composition of particles comprising a pharmaceutical active for inhalation via freeze drying and that leucine is a suitable excipient for use in such a process and acetonitrile is a suitable solvent for use in such a process. Such a modification is 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 rejection combines multiple elements from each reference without clear guidance, i.e., selecting from Sahakijpijarn a polar aprotic solvent and the dropping of the dispersion to a reduced temperature surface from a height of 5 cm to 20 cm, and therefore treats the elements of the claimed method as LEGO blocks that can be thrown into a bag, shaken, and randomly pulled out to assemble a new method. Lerner and Sahakijpijarn are argued to be distinct in that Sahakijpijarn relates to a film freezing process, such that there must be a more explicit suggestion to modify the references in the manner alleged by the rejection, which allegedly requires making selections from each reference at will.
In response, both Lerner and Sahakijpijarn are directed to method of generating pharmaceutical powders for inhalation by forming a solution of the active, adding a lactose carrier, freezing, and lyophilizing to form the powders. The two references use different methods for the freezing step; Lerner places the composition into a freezer, while Sahakijpijarn utilizes the known and commonly used drop freezing technique by dropping the dispersion onto a reduced temperature surface from a distance. The rejection merely proposes switching out the freezing method of Lerner for the freezing method of Sahakijpijarn, both of which are disclosed as producing a composition that can be lyophilized to form a powdered pharmaceutical formulation suitable for inhalation. Therefore, the rejection simply proposes to substitute one known prior art element for another according to known methods to achieve predictable results, which is prima facie obvious. MPEP 2143. Regarding the solvent choice, there is no evidence of record of any unexpected result from using an aprotic organic solvent rather than the protic organic solvent disclosed by Lerner, and Sahakijpijarn makes it clear that aprotic solvent, i.e. acetonitrile, is suitable for use for dissolving an active to form a dispersion that is then frozen and lyophilized into a powder as discussed in the rejection. This again is merely the substitution of one known element for another according to known methods to achieve predictable results.
Applicant argues that the amended claims recite the use of a polar aprotic solvent and also specify that the carrier should be sparingly soluble in the solvent, and that Lerner does not expressly teach or suggest these limitations.
In response, this argument is not persuasive because both Lerner and Sahakijpijarn teach the use of carriers that are not soluble in the solvent taught therein, and therefore discloses the claimed limitation, regardless of the fact that they do not expressly discuss the fact that the disclosed carrier is not soluble in the disclosed solvent. Regarding the use of a polar aprotic solvent, the references must be considered not individually but rather for what they teach as a whole. Although Lerner does not disclose a polar aprotic solvent, the rejection relies on the teachings of Sahakijpijarn to supply this element as discussed in the rejection.
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.
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/GAREN GOTFREDSON/Examiner, Art Unit 1619
/ANNA R FALKOWITZ/ Primary Examiner, Art Unit 1600