DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 09/05/2025 has been entered.
Applicants' arguments, filed 09/05/2025, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Specification
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives.
Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps.
Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
The abstract of the disclosure is objected to because the abstract refers to purported merits or speculative applications of the invention and compares the invention with the prior art. For example, the abstract recites that the formulations are improved, have improved chemical and physical stability as compared to formulations in the art, and recites that the improvement over the prior art comprises the presence of HSH in the pharmaceutical formulation. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Objections
Claim 7 is objected to because of the following informalities: “tap density about” should read “tap density of about.” Appropriate correction is required.
Claim 13 is objected to because of the following informalities: “therapeutic-agent” should read “therapeutic agent.” Appropriate correction is required.
Claim Rejections - 35 USC § 112(b) or pre-AIA 4th ¶
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.
Claim 16 is 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 16 recites the limitation "comprising at least one receptacle, wherein said receptacle comprises…,” in lines 1 and 2. There is insufficient antecedent basis for this limitation in the claim. The claim is indefinite as it is unclear as to which of the at least one receptacle “said receptacle” is referring to. See MPEP 2173.05(e). The examiner suggests replacing “said receptacle” with “the at least one receptacle.”
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-4, 6, 7, 9-11, and 13-16, stand rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Trofast et al (US 20050152847), in view of Leonard et al (US 20040067920), as evidenced by WHO (“Asthma”, retrieved 2024).
Trofast et al teaches a pharmaceutical composition for oral and nasal inhalation comprising a drug (i.e., therapeutic agent) and maltitol, the drug is preferably budesonide, etc. (abs, ¶ 14, claim 1, 6). Maltitol has properties which make it suitable as an inhalation excipient, e.g. has good thermal and chemical stability (¶ 16). The compositions are formulated for respiratory administration via a dry powder inhaler (¶ 30).
Trofast et al does not explicitly teach the fine particle fraction, the amount of HSH of claim 2, the inclusion of a buffering agent of claims 3-6, the tap density, the method of specifically treating a disease or inflammatory disorder of claims 9 and 14, nor a kit of claim 16.
Leonard et al teaches respirable dry powder formulations comprising a carrier and dehydroepiandrosterone (therapeutic agent) for the treatment of asthma, etc. (¶ 3). As evidenced by WHO, asthma is a chronic lung disease. The dry powder formulation further comprises an excipient including polyols or higher sugar alcohols, such as sorbitol, etc., in a mounts ranging from about 0.1 to about 99% w/w composition (¶ 108, claim 4). The formulation may comprise buffering agents, as will be appreciated by those in the art, there are a large number of suitable buffers that may be used, such as sodium acetate, sodium citrate, etc. (¶¶ 57, 111). In preferred embodiments, the tap density is less than about 0.4 g/cm3 (¶ 103). The dry powder formulation preferably has a fine particle fraction of at least about 20% being preferred (¶ 102). Other useful therapeutic agents include anti-inflammatory agents such as budesonide (¶¶ 14, 134). A kit is also provided comprising a delivery device, such as a nebulizer, aerosolizer, dry powder inhaler, etc., either comprising the powder formulation, where the kit also comprises capsules, cartages or blisters with the formulation for insertion into the device (¶ 37).
Regarding the hydrogenated starch hydrolysate of claim 1, it appears maltitol reads on Applicants’ definition of a hydrogenated starch hydrolysate (HSH), where HSH is defined as a generic term for sugar alcohols, polyhydric alcohols, or polyols, and where HSHs have the chemical structure (G)nS, where G is glucose, S is sorbitol, and n is greater than or equal to zero (see pg. 5 of the instant specification). Therefore, maltitol (having the formula (G)1S) appears to be an HSH.
Regarding the fine particle fraction of claim 1, it would have been obvious to formulate the composition of Trofast et al, to have a fine particle fraction known to be suitable for dry powder inhalation formulations, such as at least about 20%, as taught by Leonard et al.
With regards to claim 2, it would have been obvious to formulate the composition of Trofast et al and Leonard et al with maltitol, in the amounts from about 0.1 to about 99 wt% for sugar alcohols in dry powder formulations for inhalation, as taught by Leonard et al. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
With regards to claims 3, 4, and 6, it would have been obvious to include buffering agents to the composition of Trofast et al and Leonard et al, such as sodium acetate, sodium citrate, etc., which are known to be used in dry powder formulations for inhalation, as taught by Leonard et al.
With regards to claim 7, it would have been obvious to formulate the composition of Trofast et al and Leonard et al, with a known tap density suitable for dry powder inhalation formulations, such as about 0.4 g/cm3, as taught by Leonard et al.
With regards to claims 9, 10, 14, and 15, it would have been obvious to administer the composition of Trofast et al and Leonard et al for the method of treating a disease condition, where Trofast et al teaches administration to the respiratory tract via a dry powder inhaler, and Leonard et al teaches budesonide can be used in dry powder formulations for the treatment of asthma. Further, it appears any dry powdered inhaler would have a receptacle containing the composition.
With regards to claim 11, it would have been obvious to formulate the composition of Trofast et al and Leonard et al, with a tap density of about 0.4 g/cm3, for the same reasons discussed above by Leonard et al, and used for the method of claim 9, as discussed above.
Regarding claim 13, it would have been obvious to select budesonide as the therapeutic agent, a preferred drug as taught by Trofast et al.
With regards to claim 16, it would have been obvious to include the composition of Trofast et al and Leonard et al, in the form of a kit comprising a delivery device comprising a powder formulation, where the kit also comprises capsules, cartages or blisters (i.e. receptacles) with the formulation for insertion into the device, as taught by Leonard et al, for convenience to the user.
Response to Arguments
First, Applicants assert Trofast et al do not teach the claimed composition comprising HSH. Applicants assert HSH is defined by the instant specification as not containing a specific polyol as the majority component. Applicants make reference to Wikipedia and USP-NF to support their argument that the ordinary and customary meaning of hydrogenated starch hydrolysates comprise excipients that do not include a specific polyol as the majority component. Second, Applicants assert the preferred embodiment of the present application discloses an HSH with approximately 1% sorbitol, 3.5% mannitol, and 95.5% higher-order polyols.
First, respectfully, this argument is not persuasive. Consistent with the well-established axiom in patent law that a patentee or applicant is free to be his or her own lexicographer, a patentee or applicant may use terms in a manner contrary to or inconsistent with one or more of their ordinary meanings if the written description clearly redefines the terms. See MPEP 2173.05(a)(III). Here, one of the clearly defined definitions of hydrogenated starch hydrolysates in the written description is as a generic term for sugar alcohols, polyhydric alcohols, or polyols, and where HSHs have the chemical structure (G)nS, where G is glucose, S is sorbitol, and n is greater than or equal to zero (see pg 5 of the instant specification). Therefore, maltitol (having the formula (G)1S) appears to be an HSH as defined by the instant specification. While Examiner acknowledges that the instant specification additionally discloses that HSHs are also recited as not containing a specific polyol as the main component, the instant specification appears to allow for sugar alcohols and polyols generally to read on HSHs.
Second, respectfully, this argument is not persuasive. While Applicants point to a preferred embodiment for HSH in the instant specification, the examiner notes that the claims are not limited to Applicants preferred embodiments, and the specification appears to allow for alcohols, polyhydric alcohols, or polyols generally to read on HSHs, for the same reasons discussed above and of record.
Claim 5 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Trofast et al (US 20050152847) and Leonard et al (US 20040067920), as applied to claims 1-4, 6, 7, 9-11, and 13-16 above, and further in view of Pipkin et al (US 20070175472 A1).
Trofast et al and Leonard et al are discussed above but do not specifically teach citric acid as a buffer.
Pipkin et al teach it was known to use citric acid as a buffer in inhalable dry powder formulations (abs, ¶ 224).
Where Leonard et al makes obvious the inclusion of a buffering agent, as discussed above, and teach there are a large number of suitable buffers that can be used, it would have been obvious to select from any known buffer suitable for inhalable dry powder formulations, such as citric acid, as taught by Pipkin et al.
Claims 1-4, 6, 7, 9-11, and 13-16, stand rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Trofast et al (US 20050152847), in view Cavanak (GB 2012168), Conrad (US 3329507), and Leonard et al (US 20040067920).
Trofast et al is discussed above, but for the sake of argument, if maltitol does not read on hydrogenated starch hydrolysate (HSH), then the following applies.
Cavanak discloses a stabilized composition comprising a prostaglandin and a hydrogenated starch hydrolysate (abs, claims 1 and 2). The composition is in the form of a spray-dried powder (claim 11). The weight ratio of prostaglandin (active agent) to hydrogenated starch hydrolysate is from 1:20 to 1:500 (pg 1 lines 36-38, claim 7).
Conrad teaches substitutes for sugar alcohols from the saccharification of starch, that is then hydrogenated, producing products that are weakly hygroscopic, and retains its structure for an unlimited period of time even in damp atmospheres; further, the product does not ferment (col 1 line 71 – col 2 line 14, col 2 lines 39-67). Sorbitol syrup, a sugar alcohol, rapidly takes up moisture from air and reverts to liquid form (col 1 lines 56-61).
Leonard et al are discussed above.
Regarding the hydrogenated starch hydrolysate of claim 1, it would have been obvious to substitute maltitol of Trofast et al with known excipient used in powdered pharmaceutical compositions, such as HSH, as taught by Cavanak, where both are directed to dry powder pharmaceutical formulations.
Further, the examiner notes that the excipient concentrations and osmolarity of Trofast is simply a preferred embodiment, and while reducing the risk of bronchoconstriction, etc., may be preferable, the reference can be relied upon for all it teaches, even non preferred embodiments. See MPEP 2123(I). Even so, when selecting an HSH, which can be defined as a mixture of molecules that do not contain a specific polyol as the majority component (see instant specification at ¶¶ 11-12), it would have also been obvious for the skilled artisan to reasonably select from suitable mixtures having the preferred osmolarity of Trofast et al. Additionally, it would have been well within the relative skills of the skilled artisan to routinely optimize the HSH in order to achieve a preferred osmolarity, etc., to limit the risk of bronchoconstriction, for example. See MPEP 2144.05(II)(A).
Additional motivation is provided by Conrad, where it would have been obvious to substitute maltitol alone for an HSH, in order to provide the benefits of improved dryness, reduced hygroscopicity, and improved long term stability, as taught by Conrad.
Regarding the fine particle fraction of claim 1, it would have been obvious to formulate the composition of Trofast et al, Cavanak, and Conrad, to have a fine particle fraction known to be suitable for dry powder inhalation formulations, such as at least about 20%, as taught by Leonard et al.
With regards to claim 2, it would have been obvious to include HSH in an amount from about 50 wt% to about 95 wt%, such as 95 wt%, where Cavanak teaches a range which equates to 95 wt% to 99.8 wt%. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Claims 3, 4, 6, 7, 9-11, and 13-16 are rejected for the same reasons discussed above.
Response to Arguments
First, Applicants assert Trofast et al do not teach or suggest replacing sugars with an HSH, rather, Applicants assert Trofast et al teach selecting weakly osmotic or non-osmotic excipients to avoid high local osmolarity and bronchoconstriction. Applicants assert maltitol is specifically selected in Trofast et al for its osmotic characteristics, and the skilled artisan simply could not substitute any HSH for maltitol, as HSH is a mixture of polyols and higher-order saccharides without a majority component, as doing so would likely incorporate components with varying osmotic properties. Applicants assert that doing so could elevate local osmolarity, thereby rendering the formulation of Trofast et al unsuitable for its stated purpose. Second, Applicants assert Cavanak and Conrad disclose excipients in general, but Trofast et al expressly limits acceptable excipients to those that are weakly osmotic to avoid bronchoconstriction. Applicants assert substituting maltitol with an HSH would introduce components with potentially higher osmolarity, defeating the intended purpose of Trofast et al, rendering the modification improper under MPEP 2143.01. Third, Applicants assert Leonard discloses xylitol and mannitol as preferred excipients, both of which are smaller polyols with higher osmolarity per gram than maltitol and are identified in Table 1 in Trofast et al as unsuitable for minimizing osmotic effects. Fourth, Applicants assert WHO adds nothing relevant to HSH or osmotic suitability.
First, respectfully, this argument is not persuasive. As discussed in the previous Office Action, while Trofast et al teach the formulations can minimize the risk of high local osmolarity causing bronchoconstriction or other adverse effects by selecting non-hydroscopic excipients, where it is preferable to select an excipient with a concentration of at least greater than 5.5%, the prior art can be relied upon for all it teaches, even non preferred embodiments. While reducing the risk of bronchoconstriction, etc., may be preferable, a risk of bronchoconstriction does not render the composition of Trofast et al unsuitable for use as a dry powder inhalation formulation. Even so, Table 1 of Trofast et al disclose maltitol, lactose, sucrose, and dextrose (glucose), all have osmolarity values greater than 5.5%. Therefore, it was known from Trofast et al that multiple different polyols are suitable, and knowing this, when choosing an HSH as taught by Cavanak, a skilled artisan could reasonably select a combination of polyols to formulate an HSH with desired inhalation properties.
Second, respectfully, this argument is not persuasive. As noted above, while the examiner recognizes that Trofast et al teach the formulations can minimize the risk of high local osmolarity causing bronchoconstriction or other adverse effects by selecting non-hydroscopic excipients, where it is preferable to select an excipient with a concentration of at least greater than 5.5%, a reference can be relied upon for all it teaches, even non-preferred embodiments. While it may be preferable to reduce the risk of bronchoconstriction, modifying maltitol to an HSH would not be expected to render the composition unsuitable for use as a dry powder inhalation formulation. Nevertheless, where HSHs were known and made obvious above, it would have been further obvious for the skilled artisan to select from mixtures of polyols in concentrations that were known to be weakly osmotic or non-osmotic, such as to limit the risk of bronchoconstriction.
Third, respectfully, this argument is not persuasive. Regarding the excipients of Leonard et al, as discussed in the previous Office Action, the examiner notes that Leonard et al were not relied upon for teaching specific hydrogenated starch hydrolysates.
Fourth, respectfully, this argument is not persuasive. WHO was cited for simply evidencing that asthma is a chronic lung disease.
Claim 5 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Trofast et al (US 20050152847), Cavanak (GB 2012168), Conrad (US 3329507), and Leonard et al (US 20040067920), as applied to claims 1-4, 6, 7, 9-11, and 13-16 above, and further in view of Pipkin et al (US 20070175472 A1).
The references are discussed above but do not specifically teach citric acid as a buffer.
Pipkin et al are discussed above.
It would have been obvious to select from any known buffer suitable for inhalable dry powder formulations, such as citric acid, as taught by Pipkin et al, for the same reasons discussed above.
Nonstatutory Double Patenting
Claims 1-7 and 9-16 stand provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending Application No. 17/892,436 (reference application), hereinafter referred to as ‘436, in view of Trofast et al (US 20050152847), Leonard et al (US 20040067920), and Pipkin et al (US 20070175472 A1). Although the claims at issue are not identical, they are not patentably distinct from each other because ‘436 discloses a respirable, dry powder particle surfactant formulation for pulmonary delivery comprising 10 to 30 wt% of an excipient selected from hydrogenated starch hydrolysate, etc., and a surfactant protein (therapeutic agent). Further disclosed is a method of treating a patient in need of lung surfactant therapy resulting from asthma, etc.
It would have been obvious to select hydrogenated starch hydrolysate as the excipient, as taught by ‘436.
It would have been obvious to adjust the amount of hydrogenated starch hydrolysate from about 50 wt% to 95 wt%, where Leonard et al teaches excipients can be from about 0.1 to about 99 wt%, for the same reasons discussed above.
It would have been obvious to include a buffering agent, such as sodium acetate, sodium citrate, etc., as taught by Leonard et al and for the same reasons discussed above.
It would have been obvious to include citric acid as a buffer, as taught by Pipkin et al, for the same reasons discussed above.
It would have been obvious to prepare the formulation with a tap density and fine particle fraction of instant claims 7 and 11, for the same reasons discussed above by Leaonard et al.
It would have been obvious to substitute the surfactant protein for another therapeutic agent, such as budesonide, a known active used in pharmaceutical inhalation formulations, as taught by Trofast et al.
It appears the method of treating a patient in need of lung surfactant therapy resulting from asthma, etc., reads on the method of instant claims 9 and 14, where a patient is being treated with a disease or inflammatory disorder, such as asthma.
It would have been obvious make a kit for administration, such as the kit of instant claim 16, as taught by Leonard et al and for the same reasons discussed above.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
First, Applicants asserts copending Application No. 17/892,436 has a later effective filing date than the instant application. Second, Applicants assert it is believed the rejections are overcome for the reasons above.
First, the examiner acknowledges Applicants assertion that the ‘436 application has a later effective filing date than the instant application. Currently, the claims stand rejected, as the double patenting rejection is not the only remaining rejection in the instant application and Applicants have not provided arguments with respect to the obviousness rejections.
Second, this argument is not persuasive. The claims stand rejected for the same reasons above and of record.
Claims 1-7 and 9-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending Application No. 18/989,671 (reference application), hereinafter referred to as ‘671, in view of Trofast et al (US 20050152847), Leonard et al (US 20040067920), and Pipkin et al (US 20070175472 A1), as evidenced by Drug Bank (Sinapultide: Uses, Interactions, Mechanisms of Action, 2015, pp. 1-9). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘671 disclose a container comprising: a capsule containing a respirable, dry powder particle surfactant formulation for pulmonary delivery comprising: about 10 to about 30 wt% of a particle excipient selected from hydrogenated starch hydrolysate (HSH), about 1 to about 10 wt% of a surfactant protein, such as sinapultide, etc. (i.e., therapeutic agent), etc. (claims 1, 6, 7, 8). As evidenced by Drug Bank, sinapultide possesses anti-inflammatory mechanisms (mechanisms of action).
The claims of ‘671 do not disclose an amount of HSH of claim 2, the inclusion of a buffering agent of claims 3-6, the tap density of claims 7 and 11, a method of treating a disease of claims 9 and 10, wherein the therapeutic agent is budesonide of claim 13, a method of treating a patient suffering from an inflammatory disorder of claims 14 and 15, nor a kit with a receptacle specially for use with a dry powder inhaler.
It would have been obvious to adjust the amount of hydrogenated starch hydrolysate from about 50 wt% to 95 wt%, where Leonard et al teaches excipients can be from about 0.1 to about 99 wt%, for the same reasons discussed above.
It would have been obvious to further include a buffering agent, such as sodium acetate, sodium citrate, etc., as taught by Leonard et al and for the same reasons discussed above.
It would have been obvious to include citric acid as a buffer, as taught by Pipkin et al, for the same reasons discussed above.
It would have been obvious to prepare the formulation with a tap density and fine particle fraction of instant claims 7 and 11, for the same reasons discussed above by Leaonard et al.
It would have been obvious to treat a disease condition in a patient comprising administering to the respiratory tract of the patient, and effective amount of the composition made obvious above, where the dry powder formulations of ‘671 comprise a therapeutic agent for respiratory delivery.
It would have been obvious to substitute the surfactant protein for another therapeutic agent, such as budesonide, a known active used in pharmaceutical inhalation formulations, as taught by Trofast et al.
It would have been obvious to substitute the surfactant protein for another therapeutic agent, such as budesonide, a known active used in pharmaceutical inhalation formulations, as taught by Trofast et al.
It would have been obvious to use the composition made obvious above for treating a patient suffering from an inflammatory disorder, where sinapultide has anti-inflammatory action, as evidenced by Drug Bank.
It would have been obvious make a kit for administration, such as the kit of instant claim 16, as taught by Leonard et al and for the same reasons discussed above.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Nonstatutory Double Patenting - Withdrawn
The nonstatutory double patenting rejection over the claims of U.S. Patent No. 8,614,255 B2, has been obviated by the filing and approval of the terminal disclaimer dated 09/05/2025.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSHUA A ATKINSON whose telephone number is (571)270-0877. The examiner can normally be reached M-F: 9:00 AM - 5:00 PM + Flex.
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/JOSHUA A ATKINSON/Examiner, Art Unit 1612