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 .
DETAILED ACTION
Response to Amendment
Status of the Claims
Receipt of Applicant’s response, filed 29 Sep 2025 has been entered.
Claims 1, 3-15, 22 and 23 remain pending in the application.
Claims 1, 3-6, 9-13, 15, 22 and 23 are amended.
Claims 2 and 16-21 are cancelled.
Claims 1, 3-15, 22 and 23 are under consideration
Rejections Withdrawn
Rejections Pursuant to 35 USC § 112
The rejections of claims 2-5, 12 and 13 pursuant to 35 U.S.C. 112(b) set forth in the Non-Final Office Action mailed 14 Aug 2025 are hereby withdrawn in light of applicant’s amendment of the claims.
Rejections 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, 3-15, 22 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (US 2018/0056022, published 01 Mar 2018) in view of Ingvarsson et al. (WO 2020/127950, published 25 June 2020, filed 20 Dec 2019) and Yadidi (US 2017/0348333, published 07 Dec 2017).
Liu teaches inhaler devices and methods that deliver fine powder by positive pressure combined with inhalation by the user ([0003]). Liu teaches that many diseases such as obesity require a long-term treatment ([0025]) and that the invention may be used in methods of treating diabetes and obesity ([0003], [0032]). Liu teaches proteins and peptides may be delivered as aerosols and that the optimal particle properties of aerosols, such as size, size distribution, surface characteristics and drug load are essential for successful protein-based therapies ([0030]). Liu teaches that most biologics currently administered by injection or inhalation can be delivered with positive pressure dry powder inhalation and that dry powder inhalation may replace most injections forms of the drugs which eliminates drawbacks such as difficulty in manufacturing the stable dose, difficulty in keeping a long shelf-life, and in storage and transportation, the pain and risk of infection during injection and the high cost and inconvenience of having to perform the injection by a medical professional ([0086]). Liu teaches a variety of compounds that may be used in the inhalation method such as liraglutide ([0078]), albiglutide and dulaglutide but does not limit the method to these drugs ([0086]). Liu teaches that the particle size of any dry powder has a significant impact on the therapeutic result due to its distribution in the respiratory tract and that the aerodynamic diameter of powdered medicament is less than 10 micrometers and preferably within 2-5 microns ([0095]), rendering obvious the diameters of claims 1, 7, 8, and 14.
Liu teaches that the medicaments are preferably delivered together with excipients (carriers) suitable for inhalation such as lactose, mannitol and amino acids ([0096]). Liu teaches that the carrier for the formulation may be from about 50.00 to about 99.99% w/w of the dry powder formulation ([0079]). Liu teaches example formulations where the active ingredient is combined only with the carrier such as lactose ([0101]). The formulation comprising 50-99.99% carrier with the remainder being the active component indicates a ratio of the active to carrier components of 1:1 to 1:9,999, which overlaps with and renders obvious the ratio limitations of claims 9, 10, 22 and 23. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). Liu teaches that the particles of powdered medicament may be produced by conventional techniques such as spray drying micronization ([0095]).
Liu does not teach semaglutide or the excipient leucine. These deficiencies are made up for in the teachings of Ingvarsson and Yadidi.
Ingvarsson teaches a process for spray drying the GLP-1 peptide semaglutide (abstract, page 1 lines 2-3). Ingvarsson teaches that the product may be used in a pharmaceutical composition together with one or more pharmaceutically acceptable excipients and be used in the treatment of type 2 diabetes and/or obesity (page 6 lines 14-22, page 10 line 28).
Yadidi teaches the pulmonary delivery of dry powder formulations ([0002]) and that the pulmonary delivery of therapeutic agents offers several advantages over other modes of delivery such as rapid onset, convenience of patient self-administration, potential for reduced drug side-effects, ease of delivery by inhalation and the elimination of needles ([0003]). Yadidi teaches that the particles of the compositions may have a mass median aerodynamic diameters from about 1-5 micrometers ([0004]), further supporting the obviousness of the claimed diameters. Yadidi teaches that the compositions comprise an amino acid excipient such as leucine ([0019]) which may be present from about 0.1 to about 40% w/w ([0006-0007], [0024]). Yadidi teaches that the particles may be produced by spray drying ([0153]).
Therefore, it would have been prima facie obvious to one of ordinary skill in the
art, before the effective filing date of the claimed invention to have used semaglutide and leucine as part of a dry powder inhalation formulation with a diameter between 2-5 microns. Dry powder inhalation formulations are known to be suitable for use in treating conditions such as obesity and diabetes and may be used with biologic components such as peptides such as liraglutide, albiglutide, and dulaglutide, as taught by Liu. Semaglutide is a GLP-1 peptide that may be used in pharmaceutical compositions for treating diabetes and obesity, as taught by Ingvarsson, rendering it obvious to use semaglutide as part of a powdered inhalation formulation as taught by Liu as Liu and Ingvarsson teach the same intended use for the compositions. One of ordinary skill would have been further motivated to use semaglutide as part of the dry powder inhalation formulation of Liu as powdered inhalation formulations are known to offer many benefits such as difficulty in manufacturing the stable dose, difficulty in keeping a long shelf-life, and in storage and transportation, the pain and risk of infection during injection and the high cost and inconvenience of having to perform the injection by a medical professional, as taught by both Liu and Yadidi. Further, one would have a reasonable expectation of success as similar peptide compounds to semaglutide are taught by Liu as suitable for the composition and semaglutide may be formed into particles with spray drying which is a method for forming particles for the powdered compositions taught by Liu. It further would have been obvious to use leucine as the excipient component in the dry powder formulation as the dry powders of Liu preferably have excipients such as amino acids, as taught by Liu, and leucine is an amino acid excipient known as suitable for pulmonary dry powder formulations, as taught by Yadidi. Thus, the use of leucine merely represents using a prior art amino acid element known as suitable for powder formulations with an inhalable powder formulation that is taught as comprising amino acids. As leucine is known as suitable with powder formulations, one of ordinary skill would have a reasonable expectation of successfully forming an inhalable powder formulation with leucine.
Regarding claim 11, the language “is obtained by a spray freeze drying process” is a product-by-process limitation. “Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted). In the instant case, the dry powder inhalable formulation rendered obvious over Liu, Ingvarsson and Yadidi appears to be the same product claimed.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references.
Response to Arguments
Applicant's arguments filed 29 Sep 2025 have been fully considered but they are not persuasive. Applicant argues that there is no motivation to combine the references (page 7 of remarks), and that there is no reasonable expectation of success (page 8 of remarks). The applicant argues that Liu only mentions amino acids once and that lactose is the preferred and exemplified excipient of Liu (page 7 of remarks). The examiner does not find this argument persuasive as the rejection with was made under 35 U.S.C. 103 which requires that “a patent for a claimed invention may not be obtained… if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been prima facie 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.” “A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton.” KSR, 550 U.S. at ___, 82 USPQ2d at 1397. “[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle.” Id. Office personnel may also take into account “the inferences and creative steps that a person of ordinary skill in the art would employ.” Id. At, 82 USPQ2d at 1396. While Liu may not provide a specific embodiment using the amino acid leucine, the examiner maintains that the invention as claimed is nonetheless obvious. It is not necessary for the art to embody the instant invention or to repeat a specific teaching multiple times for it to be obvious. Liu clearly teaches amino acids (and mannitol) and there is nothing to indicate that one would not recognize these components as suitable for the invention. The applicant argues that Yadidi is related to delivery of NSAIDs instead of polypeptides (page 8 of remarks) but this is not persuasive to overcome the rejection as Yadidi teaches pulmonary delivery of dry powder formulations, providing a clear link to the teachings of Liu. Further, it is again noted that amino acids are already taught by Liu to be suitable for the invention, providing a strong reason their inclusion and Yadidi provides clear teaching as to the use of the specific amino acid leucine with powder formulations, rendering it obvious to one of ordinary skill that the specific amino acid leucine is a suitable excipient for powder formulations and providing a reasonable expectation of success in including leucine.
The applicant further argues for surprising results with the instant invention (page 9 of remarks). The applicant argues that direct sieving of semaglutide did not result in the desired powder formulation, that lactose and trehalose were not suitable for semaglutide while leucine and other amino acids and mannitol were able to provide the desired claimed diameters. These results are not persuasive as unexpected results. As a first note, the data are not commensurate in scope with the instant claims. For example, examples 8-10 test semaglutide and leucine at ratios of 1:2, 2:1 and 4:1 but claim 1 does not require any ratio limitation and claims 15, 22 and 22 have the ratio extended up to 14:1, which the applicant has not shown results for. Additionally, the results pointed to are not persuasive as establishing unexpected results. It is a normal procedure for one of ordinary skill to determine the optimal range of components and conditions for formulating a pharmaceutical. Determining a preferred set of optimal conditions is not in itself sufficient to establish unexpected results that overcome the case of obviousness. The art teaches each of the limitations of the instant claims, such as the use of amino acids including leucine, with a clear reason for combination as noted in the rejection. The applicant determining a preferred excipient or production method is unexpected and does not overcome the case of obviousness, especially when the conditions and components are taught in the art. The limited evidence is insufficient to overcome the strong showing of obviousness in this case to select the amino acid leucine and the polypeptide semaglutide for use in the podwer formulation of Liu. See Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1372 (Fed. Cir. 2007) (“[W]e hold that even if Pfizer showed that amlodipine besylate exhibits unexpectedly superior results, this secondary consideration does not overcome the strong showing of obviousness in this case. Although secondary considerations must be taken into account, they do not necessarily control the obviousness conclusion.”).
Claim 11 is rejected above as the process of forming the powder by spray freeze drying is a process limitation that does not distinguish the final product from what is obvious over the prior art. Claim 11 is alternatively rejected below where the process limitation is rendered obvious from the art.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (US 2018/0056022, published 01 Mar 2018) in view of Ingvarsson et al. (WO 2020/127950, published 25 June 2020, filed 20 Dec 2019) and Yadidi (US 2017/0348333, published 07 Dec 2017) as applied to claims 1, 3-15, 22 and 23 above and further in view of Truong-Le et al. (WO 03/086443, published 23 Oct 2003).
The teachings of Liu, Ingvarsson and Yadidi are described supra.
Liu additionally teaches that the biologics undergo a freeze-drying or dry spray process before being packed into a dry powder dosage ([0086]). Liu, Ingvarsson, Yadidi do not, however, specify a spray freeze drying process.
Truong-Le teaches methods to preserve bioactive materials such as peptides in freeze dried particles suitable for intranasal administration where the method involves spray freeze drying of formulations to form stable freeze dried particles for intranasal administration (abstract, [0002]). Truong-Le teaches that bulk lyophilization and spray drying are commonly used to remove water from biological materials to provide stability in storage ([0003]). Truong-Le teaches that freeze dried cakes must be laboriously ground and sized to a small and narrow size for administering by inhalation and the size reduction step leads to additional loss from incomplete product recovery and potency loss from the shear stress associated with the grinding and the process can force a biomolecule to undergo significant chemical and physical degradation ([0004-0005]). Truong-Le teaches that spray drying is also well known but can often be unsuitable for sensitive biologic materials due to the shear stress, heat stress, oxidative stress and conformational changes that can occur with loss of hydration water at high temperatures ([0007]). Truong-Le teaches that the heat and stress of bulk freeze drying and common spray drying can be reduced by spray freeze drying methods ([0008]).
Therefore, it would have been prima facie obvious to one of ordinary skill in the
art, before the effective filing date of the claimed invention to have used a spray freeze drying method to form the powder formulation rendered obvious by Liu, Ingvarsson and Yadidi. It is known that freeze drying and spray drying may be used to form the particles, as taught by Liu, but a technique of spray freeze drying offers benefits of reducing heat and stress which is beneficial for biological components, as taught by Truong-Le. Thus, one of ordinary skill would utilize a spray freeze drying technique to reduce the stress on the semaglutide biologic component in the powder and one would have a reasonable expectation of success as the spray freeze drying technique is known for forming powders suitable for pulmonary administration.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references.
Response to Arguments
Applicant's arguments filed 29 Sep 2025 have been fully considered but they are not persuasive. Applicant argues that Truong-Le does not supply a motivation to combine the cited references and that one of skill would not have had a reasonable expectation of success in the combination of references. The examiner disagrees with this assessment. As noted in the rejection, it is known from Liu that freeze drying and spray drying may be used to form the particles and it is known from Truong-Le that a technique of spray freeze drying offers benefits of reducing heat and stress which is beneficial for biological components. Thus, it is obvious to utilize a spray freeze drying technique to reduce the stress on the semaglutide biologic component in the powder and there is a reasonable expectation of success as the spray freeze drying technique is known for forming powders suitable for pulmonary administration.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EDWIN C MITCHELL whose telephone number is (571)272-7007. The examiner can normally be reached Mon-Fri 8:00-5:00.
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/E.C.M./Examiner, Art Unit 1619
/BENNETT M CELSA/Quality Assurance Specialist , Art Unit 1600
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