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 .
Notice of Pre-AIA or AIA Status
DETAILED ACTION
Status of the Claims
Claims 2, 5-9, and 18-66 are cancelled. Claims 68-74 are new. Claims 1, 3, 4, 10-17, and 67-74 are pending and under examination.
Priority
This application claims priority from US provisional applications 63/597,934 filed on 11/10/2023, 63/501,086 filed on 5/9/2023, and 63/385,847 filed on 12/2/2022.
Information Disclosure Statement
The information disclosure statements filed on 3/5/2024 and 8/16/2024 have been considered by the examiner.
Election/Restrictions
In the response to the restriction requirement mailed on 10/28/2025, Applicant has cancelled claims 18, 20, 23-35, 37-39, 40-50 and 52 that were toward Groups II and III, and new claims 68-74 were added that are dependent on composition claims 1 and 67 (response filed on 1/28/2026). Claims 1, 3, 4, 10-17, and 67-74 are all under group I and will be examined. This will be treated as an election without traverse as applicant has not argued the restriction requirement, but chose to move forward with the claims belonging to Group I while cancelling claims to other groups.
Claim Rejections - 35 USC § 112(b)
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 67-68 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being 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 67 recites the limitation "The pharmaceutical formulation.." at the beginning of this claim, which is now an independent claim. There is no introduction of “A pharmaceutical formulation”. There is insufficient antecedent basis for this limitation in the claim.
Claim 68 is rejected as being dependent on an indefinite claim.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), 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.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], 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 3, 4, 70, 73 and 74 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claims 3 and 73 allow for “about 97.9 weight percent of lactose” and claims 4, 70 and 74 allow for “about 10.3 weight percent of Compound I” and “about 88.5 weight percent of lactose”. These claims are dependent on claim 1, which has the ranges of 0.5-11 weight percent for the compound and 87.0-99.0 for lactose Since the applicant’s specification allows for +/- 10% for “about”, this presents situations in claims 3, 4, 70, 73 and 74 where about will allow extension outside of the ranges presented in claim 1. “About 10.3” can extend to “11.03”, “about 97.9” can extend up to near 100, and “about 88.5” extends down to 79.65. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. Applicant may remove recitations of “about” for these instances as one possible option.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
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, 4, 11-17 and 69-74 are rejected under 35 U.S.C. 103 as being unpatentable over Munro US 20190031687A1, Rosales US 20130289015A1, and Keller US 20040202616A1.
Munro teaches polymorphic forms of (S)-3-(3-(1-methyl-2-oxo-5-(pyrazolo[1,5-a]pyridine-3-yl)-1H-imidazo[4,5-b]pyridine-3(2H)-yl)piperidin-1-yl)-3-oxopropanenitrile and use as a therapeutic agent for the treatment of respiratory diseases (abstract). Munro teaches “the following diffraction angles (2Theta) based on cupric Kα1: at approximately 8.25°; at approximately 13.25°; at approximately 15.40°; at approximately 17.65°; and at approximately 25.39° (claim 5 of Munro). The compound structure is found in paragraph 5. Munro teaches lactose as excipient in claim 15 of Munro. Munro teaches using the form II polymorph with lactose and optionally magnesium stearate and average particle size of 1 to 5 microns (paragraph 63). Munro teaches dry powder compositions for inhalation for respiratory indications (paragraph 45). Munro teaches capsules as a dosage form (paragraph 57).
Munro does not teach amounts of magnesium stearate or lactose of the claims, although it provides these as excipients to use. Munro does not teach the amounts of active compound. Munro does not teach information on MMAD, FPF, or percent drug delivered of the dose.
Rosales teaches JAK inhibitor compounds (abstract). Rosales teaches example 7i that is (S)-3-(3-(1-methyl-2-oxo-5-(pyrazolo[1,5-a]pyridin-3-yl)-1H-imidazo[4,5-b]pyridin-3(2H)-yl)piperidin-1-yl)-3-oxopropanenitrile among the other compounds made (paragraph 891). Rosales teaches suitable doses of 0.01 to 100 mg/kg per day (paragraph 825) and that doses depend on the nature and severity of the disease to be treated, age, general condition and body weight of the patient (paragraph 825). Rosales teaches powders and inhalation forms that can be aerosols (paragraphs 823-824). Rosales also teaches lactose and magnesium stearate for excipients (paragraph 818). Rosales teaches capsules (paragraph 818).
Keller teaches “to improve the moisture resistance of dry powder formulations for inhalation which contain a pharmaceutically ineffective carrier of not-inhalable particle size and a finely divided pharmaceutically active compound of inhalable particle size and to also improve the storage stability of said formulations.” (abstract). Keller provides for maintaining a high fine particle fraction (abstract). Keller teaches “a pharmaceutically active component comprising at least one finely divided pharmaceutically active compound having particles of inhalable size, said method comprising the step of mixing said carrier, said pharmaceutically active component and pulverulent magnesium stearate” (claim 22 of Keller). Keller teaches mean particle size of 1 to 6 microns (claim 34 of Keller). Keller teaches 0.1 to 2% by weight of magnesium stearate in the formulation (claim 35 of Keller). Keller teaches lactose as a carrier (claim 39 of Keller). Keller teaches carrier (lactose is option of a carrier of Keller) from 80 to 99.9 wt% of the formulation (paragraph 36). Keller teaches “The carrier is preferably present in the formulation obtainable according to the invention in a particle size which is not inhalable. The carrier particles, however, should on the other hand not be too large, as this can have a disadvantageous effect on the FPF” (paragraph 33). Keller teaches FPF of 59.2 and 57.2 for a formulation 4-F of table 4. This is “about 60%”. 4-E in table 4 has an FPF of 58.1%. Keller provides for at most 10 um for MMAD (paragraph 26). Keller notes the importance of dosing accuracy (paragraph 32). Keller teaches capsules as a suitable form (paragraph 25). Keller teaches “Typically, the active compound concentration can be approximately 0.1 to 10% by weight” (paragraph 31). Keller teaches “or the exact volumetric dosage of most active compounds or formulations, dilution of the active compound with a pharmaceutically inactive excipient is necessary in order to obtain a dosable unit amount meeting the demands on dosage accuracy. For this purpose, the microfine, inhalable active compound particles are mixed with pharmacologically inactive substances (carriers)” (paragraph 32).
One of ordinary skill in the art before the time of filing would have formulated the doses of compounds taught by Munro and Rosales into mixtures with percentages of lactose and magnesium stearate of Keller in order to make suitable inhalable dry powder aerosolized formulations that will have improved moisture resistance and storage stability. Keller also provides the importance of fine particle fraction including values of “about 60%” and teaches at most 10 microns (less than 10 microns) for MMAD. Thus, making such formulations and adjusting amounts of drug, magnesium stearate and lactose in dry powder inhalation forms were provided by the prior art as well as the importance of high fine particle fraction and low MMAD as considerations. Although the references do not directly mention fine particle mass, the references allow for amounts and the polymorph of the active compound, the form of capsules and formulation ingredients and considerations that would reasonably allow for such fine particle masses to be achieved when aerosolized. Note that fine particle mass is an occurrence that happens after aerosolization, and so the limitations of claims 14-15 that have patentable weight are the capsule form and the amount of compound contained. Capsules, doses and dose adjustment reasons are taught in the combination of the references. Thus, there was a reasonable expectation of success in combining the teachings of the references and achieving formulations of applicant’s claims in order to achieve more stable dry powder inhalation formulations of the drug taught by Munro which can be delivered by inhalation.
Claim 10 in addition to Claims 1, 3, 4, 11-17 and 69-74 are rejected under 35 U.S.C. 103 as being unpatentable over Munro US 20190031687A1, Rosales US 20130289015A1, Keller US 20040202616A1 and Senderak (Drug Dev Ind Pharm, 2009, volume 35, pages 735-737).
Munro, Rosales, and Keller teach the claims as indicated above
Munro, Rosales and Keller do not teach the content uniformity of claim 10 in regards to the compound.
Senderak teaches the USP content uniformity RSD should not exceed 7.8% (abstract). Senderak teaches it for validating batches of suppositories, transdermal systems and inhalations (abstract). Senderak teaches that the test is required for every drug product sold in the US (abstract).
One of ordinary skill in the art before the time of filing would have adjusted the formulation to have an RSD of less than 7.8% by the combined teachings with Senderak as this is necessary for the drug development process in order to sell the drug product. Thus, there was a reasonable expectation of success in obtaining such a product with RSD of less than 7.8% as it is needed to sell/distribute the product.
Claims 67-68 are rejected under 35 U.S.C. 103 as being unpatentable over Munro US 20190031687A1 and Keller US 20040202616A1.
Claim 67 is written as an independent claim.
Claims 67-68 are product-by-process claims with combining steps and co-milling steps (MPEP 2113). If the prior art teaches the formulation with ingredients and allowing for amounts of magnesium stearate of the claims, then it will read on the formulation of the claim. Note that as the preblends in applicant’s claims are made with other ingredients and then combined with no particular mention of a weight ratio of first to second preblend, the amounts of magnesium stearate will become diluted (e.g. 10% of first preblend with 4 wt% magnesium stearate and 90% of second preblend with 0.4 wt% magnesium stearate would provide 0.76 wt% magnesium stearate in the total formulation). Thus, prior art teaching amounts below a value found in the range of 4.4 to 15.1 weight percent magnesium stearate will teach the limitation.
Munro teaches polymorphic forms of (S)-3-(3-(1-methyl-2-oxo-5-(pyrazolo[1,5-a]pyridine-3-yl)-1H-imidazo[4,5-b]pyridine-3(2H)-yl)piperidin-1-yl)-3-oxopropanenitrile and use as a therapeutic agent for the treatment of respiratory diseases (abstract). Munro teaches “the following diffraction angles (2Theta) based on cupric Kα1: at approximately 8.25°; at approximately 13.25°; at approximately 15.40°; at approximately 17.65°; and at approximately 25.39° (claim 5 of Munro). The compound structure is found in paragraph 5. Munro teaches lactose as excipient in claim 15 of Munro. Munro teaches using the form II polymorph with lactose and optionally magnesium stearate and average particle size of 1 to 5 microns (paragraph 63). Munro teaches dry powder compositions for inhalation for respiratory indications (paragraph 45). Munro teaches capsules as a dosage form (paragraph 57).
Munro does not teach amounts of magnesium stearate in its formulations.
Keller teaches “to improve the moisture resistance of dry powder formulations for inhalation which contain a pharmaceutically ineffective carrier of not-inhalable particle size and a finely divided pharmaceutically active compound of inhalable particle size and to also improve the storage stability of said formulations.” (abstract). Keller provides for maintaining a high fine particle fraction (abstract). Keller teaches “a pharmaceutically active component comprising at least one finely divided pharmaceutically active compound having particles of inhalable size, said method comprising the step of mixing said carrier, said pharmaceutically active component and pulverulent magnesium stearate” (claim 22 of Keller). Keller teaches mean particle size of 1 to 6 microns (claim 34 of Keller). Keller teaches 0.1 to 2% by weight of magnesium stearate in the formulation (claim 35 of Keller). Keller teaches lactose as a carrier (claim 39 of Keller). Keller teaches carrier (lactose is option of a carrier of Keller) from 80 to 99.9 wt% of the formulation (paragraph 36). Keller teaches “The carrier is preferably present in the formulation obtainable according to the invention in a particle size which is not inhalable. The carrier particles, however, should on the other hand not be too large, as this can have a disadvantageous effect on the FPF” (paragraph 33). Keller teaches FPF of 59.2 and 57.2 for a formulation 4-F of table 4. This is “about 60%”. 4-E in table 4 has an FPF of 58.1%. Keller provides for at most 10 um for MMAD (paragraph 26). Keller notes the importance of dosing accuracy (paragraph 32). Keller teaches capsules as a suitable form (paragraph 25). Keller teaches “Typically, the active compound concentration can be approximately 0.1 to 10% by weight” (paragraph 31). Keller teaches “or the exact volumetric dosage of most active compounds or formulations, dilution of the active compound with a pharmaceutically inactive excipient is necessary in order to obtain a dosable unit amount meeting the demands on dosage accuracy. For this purpose, the microfine, inhalable active compound particles are mixed with pharmacologically inactive substances (carriers)” (paragraph 32).
One of ordinary skill in the art before the time of filing would have formulated the doses of compounds taught by Munro into mixtures with percentages of lactose and magnesium stearate of Keller in order to make suitable inhalable dry powder aerosolized formulations that will have improved moisture resistance and storage stability. Keller also provides the importance of fine particle fraction including values of “about 60%” and teaches at most 10 microns (less than 10 microns) for MMAD. Thus, making such formulations and adjusting amounts of drug, magnesium stearate and lactose in dry powder inhalation forms were provided by the prior art as well as the importance of high fine particle fraction and low MMAD as considerations. Thus, there was a reasonable expectation of success in combining the teachings of the references and achieving formulations of applicant’s claims in order to achieve more stable dry powder inhalation formulations of the drug taught by Munro which can be delivered by inhalation.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARK V STEVENS whose telephone number is (571)270-7080. The examiner can normally be reached M-F 9:00 am to 6:00 pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian-Yong Kwon can be reached at (571)272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARK V STEVENS/Primary Examiner, Art Unit 1613