DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 08/17/26 has been entered.
Receipt is acknowledged of Amendments and Remarks filed on 08/17/26. Claims 1, 3, 6, 10, 14-15, 17-19 have been amended, new claims 22-26 have been added and no claims have been canceled. Accordingly, claims 1-26 are pending. Claim 20 has been withdrawn by Applicant. Thus claims 1-19 and 21-26 are under examination on the merits.
Rejections and/or objections not reiterated from the previous Office Action are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
Claim Objection
Claim 24 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 10. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). New claim 24 depends on claim 1 and is directed to a single capsule comprising between 400 ug and 1.2 mg of vismodegib. Claim 1 lacks support for a capsule, however if the capsule is the unit dose, claim 10 recites the same dosage range and thus claim 24 is a duplicate of claim 10.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 26 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Claim 26 is directed to the unit dose of claim 1, having a dry powder particle distribution less than 5.4 µm MMAD. However, the Specification does not provide support for a particle size distribution less than 5.4 µm MMAD. The Specification only supports the three MMAD particle sizes disclosed in paragraphs 0112 and 0113 (as reproduced below).
A cascade impactor study was performed to measure aerosol performance for Hedgehog inhibitor dry powder formulations. Three different particle size distributions were tested:
2.7 μm MMAD
3.6 μm MMAD
5.4 μm MMAD
Results:
[0113]
The 2.7 and 3.6 μm formulations delivered approximately double the lung dose compared to the 5.4 μm formulation. The 5.4 μm formulation showed a sharp drop in deep lung delivery, aligning with established particle deposition models. These results confirm that an optimal range of 3-4 μm balances deep lung penetration and adequate mass deposition
The Speciation does not provide support for the range, including values such as 0.5 µm, 0.01 µm, etc, as encompassed by the recitation.
This is a new matter rejection.
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 10, 14 and 22 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 10 is indefinite for reciting “the unit dose is between approximately 400 µg and 1.2 mg of vismodegib”. This is indefinite because it is not clear what “unit dose is” means. The unit dose of claim 1 comprises vismodegib, L-leucine and other excipients, as in claim 5.
Claim 14 is indefinite for reciting “wherein a single unit dose is between approximately 400 µg and 1.2 mg of vismodegib”. This is indefinite because it is not clear what “unit dose is” means. The unit dose of claim 1 comprises vismodegib, L-leucine and other excipients, as in claim 5.
Claim 22 is indefinite for reciting that the L-leucine comprises a surface enrichment of the collapsed sphere particles. This is indefinite because “surface enrichment” is a property, as evidenced by the Specification, and not a component. The L-leucine does not comprise a surface enrichment but rather provides for or achieves a surface enrichment. See [0094] of the Specification:
The formulations with 10% leucine did not have significant leucine crystallization, indicating insufficient leucine surface enrichment. Formulation with trehalose with 26% leucine had the largest leucine crystallites, and therefore more extensive leucine surface enrichment creates a hydrophobic shell which protects against water uptake on stability, and it is a dispersibility enhancer, leading to better aerosol performance.
Claim interpretations:
In Claim 1, the limitations of “having a therapeutic effect in a pulmonary progressive fibrotic disorder” and “to achieve the therapeutic effect upon inhalation of the unit dose by cellular….. disorder” are intended use limitations.
The term “majority” is a relative term and is interpreted as 51% or more.
Limitations of “less than 1.2 mg” in claim 2, “less than 3.6 mg” in claim 3, “less than 5 mg per day” in claim 6 and “smaller than 5 µm” in claim 7, encompass 0.
In claims 7-8, the geometric particle size distribution is interpreted as “average geometric particle size distribution”, i. e, 50%. (See Amighi et al at [0888] and [0895]).
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.
Claims 1, 4-5, 7-8, 12, 17-19, 21-23 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al (WO 2023024804 or US 20240115496 (recitation are from the US document)) in view of Xie (US 20220354832) as evidenced by Amighi et al (US 20160263232).
Liu et al teach a compound dry powder inhalant, comprising baicalin, ambroxol hydrochloride, L-leucine and phosphate, wherein based on a mass of the compound dry powder inhalant, L-leucine, wherein compound dry powder inhalant has a Dv90≤5 μm for alleviating pulmonary edema and reducing pulmonary dysfunction and pulmonary fibrosis (See abstract).
Regarding claims 1, 4, 7-8, 21, 23, in part, Liu et al teach a compound dry powder inhalant for treating idiopathic pulmonary fibrosis, consisting of baicalin, ambroxol hydrochloride, L-leucine and phosphate, wherein based on a mass of the compound dry powder inhalant, L-leucine accounts for 10-40%, or 15-25% and the compound dry powder inhalant has a Dv90≤5 μm. The said dry powder is formulated into a dry powder inhalant (DPI) and administered via pulmonary inhalation which can improve and treat pulmonary fibrosis by reducing the expression of inflammatory factors, improving lung injury and enhancing lung function (See [0006]-[0007], [0044]-[0047] and claim 1).
Further regarding claims 1, 4, 7-8, 21, 23, in part, Liu et al teach that in FIG. 4 , BA/AH-DPI dry powders with different ratios showed monodisperse particle size range, irregular folded flocculation, rough surface and pleated morphology of spherical morphological particles, which was consistent with that in the references. It could also be seen in FIG. 4 that the surface folded morphology of BA/AH-DPI derived from L-leu content from 10% to 40% was better and in uniform spherical size.(See [0077]).
Regarding claims 1 and 12, in part, Liu et al teach that “It could be seen from FIG. 7 that BA, AH, L-leu and the physical mixture of the three were all in crystalline form, in which BA had strong diffraction peaks at 8.52°, and L-leu also had strong diffraction peaks at 6.13°, …. . The physical mixture of the three also exhibited the same diffraction peaks, … suggesting that the drugs were all crystalline, and the crystalline form did not change after mixing” (See [0084]).
Regarding claims 17-19, in part, Liu et al teach that the particle size distribution of DPI dry powder was measured by dry dispersion method using laser particle size analyzer, and Dv10, Dv50, Dv90, VMD (Volume median diameter) were determined. The results were shown in Table 5.
PNG
media_image1.png
220
419
media_image1.png
Greyscale
As can be seen, D10 for the said dry powder is slightly below the claimed 1 micron, but D50 and D90 are well within the claimed range.
Regarding claim 26, Liu et al disclose the MMAD range for the said dry powder particles as from 2.1 to 5.01 µm (See at least Table 7).
Liu et al lack a disclosure on the active agent being vismodegib. This is known in the art as taught by Xie.
Xie teaches methods of reducing fibrosis by administering to a subject a therapeutically effective amount of at least one hedgehog pathway inhibitor (See abstract). The said fibrosis may be pulmonary fibrosis, cystic fibrosis, idiopathic pulmonary fibrosis, cirrhosis, atrial fibrosis, etc, (See [0050]).
Regarding claims 1, 4-5, 7-8, 12, 17-19, 21-23 and 26, in part, Xie teaches that the at least one hedgehog pathway inhibitor comprises at least one of: vismodegib, taladegib, itraconazole, etc, (See [0007], [0014], [0048] and [0062]).
It is disclosed that a single dose (i.e., each dose of the at least one hedgehog pathway inhibitor) or single dosage form contains from about 15 mg to about 1000mg and preferably from 50-250 mg of at least one hedgehog pathway inhibitor. For example, vismodegib is available as 150 mg capsules. Vismodegib is administered to a subject in a single daily dose of 150 mg (See [0064]-[0065] and claims 7-8).
The said fibrosis may be pulmonary fibrosis, cystic fibrosis, idiopathic pulmonary fibrosis, cirrhosis, atrial fibrosis, etc, (See [0050]).
Xie further discloses that the said pharmaceutical formulations, suitable for oral administration may be presented as discrete units, such as a capsule, each containing a predetermined amount of the active ingredient. The active ingredient may be present as a powder (See [0044] and [0047]).
As evidenced by Amighi et al:
Amighi et al teach a pharmaceutical formulation comprising a folate receptor (FR)-targeting antineoplastic substance or composition, wherein the pharmaceutical formulation is configured for administration by inhalation, wherein the composition is used in the treatment of a proliferative disease affecting at least part of the respiratory tract. The said pharmaceutical formulation further comprises an excipient (See abstract).
It is disclosed that the said antineoplastic agent may be vismodegib (See [0777]). The said microparticles may be essentially spherical. and have a mass median geometric diameter (MMGD) ranging from about 1.0 μm to about 5.0 μm, or from about 1.0 μm to about 3.0 μm. The terms “mass median geometric diameter (MMGD)”, “particle size diameter (PSD)”, “median diameter”, or “mass median diameter (MMD)” may be used interchangeably (See [0839], [0886] and [0896]).
It would have been prima facie obvious to a person of ordinary skilled art at the time the invention was made to have combined the teachings of Xie as evidenced by Amighi et al with that of Liu et al to arrive at the instant invention. It would have been obvious to do so because Liu et al teach effective dry powder formulations for inhalation to the lung for treating pulmonary fibrosis, wherein the dry powder formulation comprises two active agents and L-leucine, with particle size and particle size distribution range that is suitable for deep lung delivery and deposition. Liu et al also teach that the particles are sphere and have folded surface (i.e. collapsed). Xie teaches that hedgehog pathway inhibitors such as vismodegib and taladegib are effective and suitable agents for treating pulmonary fibrosis.
As is evidence by Amighi et al, a dry powder composition comprising vismodegib and leucine and other excipients for administration to the subject’s lung is known and envisioned.
Thus, one of ordinary skill in the art given the teachings of the prior art of record is motivated to combine or substitute the active agents of Xie with those of Liu et al to prepare a dry powder composition comprising visomdegib and L-leucine and optionally other excipients to deliver the active agent to the subject’s deep lung for treating pulmonary fibrosis.
Regarding claim 22, it is noted that the prior art teach a collapsed shepherd particle comprising an active agent and L-leucine. According to the Specification, the said L-leucine provided surface enrichment to the particle. Thus, the prior art meets this limitation.
That is, the Specification states:
The formulations with 10% leucine did not have significant leucine crystallization, indicating insufficient leucine surface enrichment. Formulation with trehalose with 26% leucine had the largest leucine crystallites, and therefore more extensive leucine surface enrichment creates a hydrophobic shell which protects against water uptake on stability, and it is a dispersibility enhancer, leading to better aerosol performance. (See [0094]).
In other words, all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention.
Additionally, the claims would have been obvious because a person of ordinary skill has good reasons to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
Claims 1-14, 16-19 and 21-26 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al (WO 2023024804 or US 20240115496 (recitation are from the US document)) in view of Xie (US 20220354832), Kuo et al (US 20090117193) and Newman (Aerosol deposition considerations in inhalation therapy) as evidenced by Amighi et al (US 20160263232).
The teachings of Liu et al, Xie and Amighi et al are delineated above and incorporated herein.
Liu et al teach delivering the said dry powder with a dry powder inhaler but lacks specifics of the device or delivery such as emitted fraction efficiency, MMAD value of the particles or the unit dose being a capsule. These are known in the art as taught by Kuo et al. The combined references also lack a disclosure of the claimed amounts of vismodegib. These would have been obvious over the teachings of Xie and Newman et al.
Kuo et al teach discovery of a particular class of excipients, which, when incorporated into dry powder formulations for aerosolization and delivery to the lung, notably improves the dispersivity and aerosolization properties of the dry powders, irrespective of the type of active agent contained in the formulation. The said excipient is a di or tri-peptide comprising at least two leucines (See Abstract and [0006]).
The said dry powder typically contains from about 2% by weight to about 99% by weight di- or tri-peptide, and may optionally contain additional excipients or carriers, such as carbohydrates, amino acids, polymers, etc (See [0007]).
Kuo et al disclose that the presence of the di- or tri-peptide is effective to notably increase the emitted dose of the dry powder (See [0008]). Exemplary amino acids (outside of the dileucyl-peptides of the invention), include lysine, leucine, isoleucine, etc, (See [0055]).
Regarding claim 5, Kuo et al teach that the said dry powder formulations may comprise other excipients including carbohydrates such as mannitol and trehalose (See [0056]).
Regarding claims 11 and 16, Kuo et al teach that “Emitted Dose” or “ED” provides an indication of the delivery of a drug formulation from a suitable inhaler device after a firing or dispersion event. More specifically, for dry powder formulations, the ED is a measure of the percentage of powder which is drawn out of a unit dose package and which exits the mouthpiece of an inhaler device (See [0027]). Kuo et al show emitted dose percentage of some of the disclosed formulations which include 84%, 86% (in Table 9) and from 83% to 93% (in Table 13).
Regarding claims 1 and 24, Kuo et al disclose that when administered using a device of this type, the powder is contained in a receptacle having a puncturable lid or other access surface, preferably a blister package or cartridge, where the receptable may contain a single dosage unit or multiple dosage units. Suitable for delivering the said powders are dry powder inhalers wherein a premeasured dose of dry powder for delivery to a subject is contained within a hard gelatin capsule. Suitable inhalers include Discus® (Glaxo), SpirosTM inhaler (Dura Pharmaceuticals), and the Spinhaler® (Fisons) (See [0084]-[0086]).
Regarding claim 26, Kuo et al teach that the mass median aerodynamic diameters of the powders will characteristically range from about 0.1-10 μm, preferably from about 0.2-5.0 μm MMAD, more preferably from about 1.0-4.0 μm MMAD, and even more preferably from about 1.5 to 3.5 μm (See [0074]).
Regarding claims 2-3, 6, 9-10, 14 and 24-25, Xie teach that a single dose (i.e., each dose of the at least one hedgehog pathway inhibitor) or single dosage form contains from about 15 mg to about 1000mg and preferably from 50-250 mg of at least one hedgehog pathway inhibitor. For example, vismodegib is available as 150 mg capsules. Vismodegib is administered to a subject in a single daily dose of 150 mg orally (See [0064]-[0065] and claims 7-8).
Newman teach that the advantages and features of aerosol therapy to effectively treat disease. It is disclosed that inhalation has several well-established advantages over the oral and intravenous routes, including 1-a small dose of drug can be used, a few hundred micrograms of inhaled beta-agonist may be as effective as 10 mg oral dose, 2- there is a rapid onset of action, and 3- there is a low incidence of systemic side effects (See page 152S, 1st col).
Thus, one of ordinary skill in the art is more than capable of determining the inhalable dosage of vismodegib from its disclosed safe and effective oral dosage amount.
It would have been prima facie obvious to a person of ordinary skilled in the art at the time the invention was made to have combined the teachings of Kuo et al, Xie, and Newman et al as evidenced by Amighi et al with that of Liu et al to arrive at the instant invention.
The reasons for combining Liu et al and Xie is delineated above and incorporated herein.
The person of ordinary skill in the art having possession of Liu et al and Xie, as evidenced by Amighi et al would have also been motivated to have taken advantage of the teachings of Kuo et al because one would be interested in effective delivery of the dry powder formulations to the subject’s pulmonary system for optimum treatment. Kuo et al teach the advantage of features of a dry powder composition and inhaler including emitted dose and state that adding excipients including amino acids improves the said emitted dose efficiency.
In other words, the claims would have been obvious because a person of ordinary skill has good reasons to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
Regarding the dosage amounts of the active agent, vismodegib, it would have been prima facie obvious to a person of ordinary skilled in the art at the time the invention was made to have modified the teaching of Liu et al with the teachings of Xie and Newman et al to arrive at the instant invention. The person of ordinary skill in the art having possession of Liu et al and Xie’s teachings would have also been motivated to have modified the oral dosage amounts with guidance from Newman to inhalable dosage amounts with a reasonable expectation of success. Xie teaches that the formulations may be in a powder form and comprise one or more of the said hedgehog pathway inhibitors for treating diseases such as fibrosis and disclose their typical doses for oral administration. Thus, the person of ordinary skill in the art would have been motivated to have looked in the art for dosing amounts of vismodegib or other hedgehog pathway inhibitors as taught by Xie suitable for delivery via a dry powder inhaler. That is, for delivery of these agents via inhalation, as disclosed by Liu et al, one of ordinary skill in the art would need to adjust the dose and can do that based on the teachings in the art such as Newman which teach that the dose for inhalation is typically one 10th or more of the oral dose. Newman teach that a small dose is one of the advantages of delivery via inhalation.
In other words, the claims would have been obvious because a person of ordinary skill has good reasons to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
Claims 1 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al (WO 2023024804 or US 20240115496 (recitation are from the US document)) in view of Xie (US 20220354832), Kuo et al (US 20090117193), Newman (Aerosol deposition considerations in inhalation therapy) and Burns et al (5,284,133) as evidenced by Amighi et al (US 20160263232).
The teachings of Liu et al, Xie, Kuo et al, Newman et al and Amighi et al are delineated above and incorporated herein.
Liu et al and Kuo et al teach delivering the said dry powder with a dry powder inhaler but lack an express disclosure on the inhaler device having an indicator displaying the number of doses for delivery. This is known in the art as taught by Burns et al.
Specifically, Kuo et al disclose a device, comprising a powder contained in a receptacle having a puncturable lid, preferably a blister package, a cartridge or a capsule, comprising a single dosage unit or multiple dosage units. Suitable inhalers include Discus® (Glaxo), SpirosTM inhaler (Dura Pharmaceuticals), and the Spinhaler® (Fisons) (See [0084]-[0086]).
Burns et al teach an inhalation device with a mechanism to assure patient compliance with a drug dosage regimen. The control mechanism includes a controller (24), a timer (26), an actuator (28) and a signaling device (30) (See abstract).
Regarding claim 15, Burns et al teach a patient compliance system, comprising: a drug delivery means; a controller connected to said drug delivery means programmed or preset with dose and time of dose information for a drug being delivered by said drug delivery means, said dose and time of dose information setting forth a number of actuations of said drug delivery means to be provided at prescribed intervals; a timer connected to said controller for tracking the time between actuations of said drug delivery means; an actuator connected to said drug delivery means and said controller for actuating said drug delivery means. The said drug delivery means is a powdered drug inhaler (See Columns 3-4 and claims 1 and 5).
It would have been prima facie obvious to a person of ordinary skilled in the art at the time the invention was made to have combined the teachings of Burns et al, Kuo et al, Xie and Newman et al as evidenced by Amighi et al with that of Liu et al to arrive at the instant invention.
The reasons for combining Liu et al, Xie, Kuo et al and Newman et al is delineated above and incorporated herein.
The person of ordinary skill in the art having possession of Kuo et al, Liu et al and Xie, as evidenced by Amighi et al would have also been motivated to have taken advantage of the teachings of Burns et al to add to the disclosures of Liu et al and Kuo et al because one would be interested in effective delivery of the dry powder formulations to the subject’s pulmonary system for optimum treatment. Kuo et al teach the advantage of features of a dry powder composition and inhaler including single dose units such as cartridges and capsule (sealed compartments) and emitted dose efficiency. Burns et al also teach the specifics of an effective delivery device including a dry powder inhaler that comprises a control feature for indicating the delivered doses.
In other words, the claims would have been obvious because a person of ordinary skill has good reasons to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. de los Rios et al (US 20230201196).
de los Rios et al teach methods and dry compositions for treating fibrosis, particularly pulmonary fibrosis, which may be idiopathic or arise following an infection of the lung (See abstract and claim 1). IPF is a dysregulated wound healing process causing progressive fibrotic lung scarring. Targeting the Hedgehog pathway is a logical therapeutic approach to slow, halt or reverse progression of the disease (See [0044]).
It is disclosed that the said dry pharmaceutical composition comprises 14.5-17.7% taladegib (See claim 13). Taladegib is orally bioavailable, wherein the mean oral bioavailability is from about 72% to about 91% (See [0031]).
de los Rios et al teach that taladegib is well-suited to target the lung compared to vismodegib. In animal models, taladegib is greater than 20-fold more potent than vismodegib at inhibiting GIi1 in the lungs, a downstream effector molecule that is expressed when the Hh pathway is activated. The clinically established MTD for taladegib is 400 mg. Taladegib has been evaluated at a dose as low as 50 mg. Vismodegib inhibits GIi1 mRNA at its MTD of 150 mg. Taladegib has a better clinical safety profile than vismodegib, with substantially lower occurrence of muscle spasms. Thus, while vismodegib proved unsuitable for IPF, clinical studies with vismodegib indicated inhibition of the Hh pathway can improve lung function in IPF patients (See [0033]).
Further disclosed is that the dosage of taladegib, is begun at 200 mg/day. In some embodiments, the dosage is provided in a single daily dose. The dosage may be stepped down in decrements of 50 mg/day (See [0056]).
The said compositions comprise a suitable carrier and/or excipient selected from lactose, sorbitol, mannitol, etc (See [0023] and claim 17).
de los Rios et al teach that the formulations can comprise a ratio of 80/20 amorphous to crystalline forms, 85/15 amorphous to crystalline forms, or the like (See [0075] and [0079]).
Schuler et al (WO 2022170081)
Schuler et al teach pharmaceutical compositions comprising an antiarrhythmic agent for treatment of a heart condition via inhalation, in a dry powder drug product (See abstract and [0006]).
Regarding claims 1, 4-5, 7-8, 12, 17-19, 21-23 and 26, in part, Schuler et al disclose that the compositions comprise particles that are approximately spherical and may be collapsed, deformed or fractured (See [0114] and [0228]). It is disclosed that the said dry inhalable powder is formulated for administration via oral inhalation and has a mass median aerodynamic diameter of about 0.3 µm to about 5.0 µm (See [0013], [0106] and claims).
Regarding claims 1 and 5, Schuler et al disclose that the said pharmaceutical composition further comprises a pharmaceutically acceptable excipient or carrier including mannitol, trehalose and amino acids or combinations thereof. Examples of such amino acids include L-leucine and that the “use of amino acids as pharmaceutically acceptable excipients is known in the art as disclosed in WO 95/31479, WO 96/32096, and WO 96/32149, which are incorporated herein by reference in their entireties” (See [0010], [0081], [0090] and [0114]).
The said pharmaceutical composition contain a combination of antiarrhythmic pharmaceutical agents including antineoplastics (See [0091]-[0092]).
Regarding claims 17-19, Schuler et al exemplify formulations wherein the amount of active agent is 48%, leucine is 48% having the particle size distribution of X10 being 1 µm, X50 being 2.3 µm and X90 is 6.6 µm. In another formulation, X10 is 1.3 µm, X50 is 2.4 µm and X90 is 4.2 µm (See Table 8, formulations F and E).
Response to Arguments
Applicants’ arguments with respect to claim(s) 08/17/26 have been considered but are moot because the new ground of rejection does not rely on the prior rejection of record as challenged in the argument.
Claims 1-19 and 21-26 are rejected. Claim 20 is withdrawn.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mina Haghighatian whose telephone number is (571)272-0615. The examiner can normally be reached M-F, 7-5 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sue X. Liu can be reached at 571-272-5539. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Mina Haghighatian/
Mina Haghighatian
Primary Examiner
Art Unit 1616
Prosecution Insights