FINAL 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 .
Status of Claims
Receipt is acknowledged of the claim amendments filed on 13 July 2026.
Claim 1 has been amended.
Claims 5-7, 9-11, 13-14, 16-21, 24-31, 33-94, 96-106, 108-113, 115-174, 176-184 and 186-189 are cancelled.
Claims 22-23, 95, 114, 185 and 191-194 remains withdrawn from consideration.
Claims 1-4, 8, 12, 15, 32, 107, 175, and 190 are presented for examination herein to the extent that the biologically active polynucleotide is a virus and the first excipient is a sugar alcohol and the second excipient is an amino acid residue, e.g., shifted species due to the claim amendments filed 29 May 2025.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 1-4, 8, 12, 15, 32, 107, 175 and 190 are rejected under 35 U.S.C. 103 as being unpatentable over JOHNSTON (US 2010/0221343 A1, publication date of 2 September 2010) in view of MCINTOSH (US 20140294969 A1, publication date of 02 October 2014) and FINLAY (US 2011/0293671 A1, publication date of 1 December 2011).
Johnston is primarily directed towards composition and methods for treating and delivering medicinal formulations using an inhaler (abstract).
Regarding claims 1, 4, 12, 107 and 175, Johnston discloses that the general method of delivery of drugs to the lungs for the treatment of numerous pulmonary disorders is through inhalation of the drug particles (paragraph [0007]). Johnston discloses a medicinal formulation for use in a dry powder inhaler having non-tightly packed porous flocculated web composition comprising one or more brittle-matrix particles of one or more active agents (e.g. dry powder)(paragraph [0014]). Johnston discloses that carrier particles are not needed for pulmonary delivery (paragraph [0189]). Johnston discloses that the brittle-matrix particles are made using ultra-rapid freezing (URF) (paragraph [0190]). Johnston discloses that the brittle matrices are produced by thin film freezing (TFF) which exhibit exceptional respirable properties and is useful for highly efficient delivery of thermally labile, highly potent and poorly soluble drugs (paragraph [0201]). Johnston discloses that the particles which have low-density and is porous allows highly efficient deep lung delivery via a dry powder inhaler (paragraph [0201]). Johnston discloses producing including dry powders using TFF, where the dry powder comprises an active and sugar excipient including mannitol (paragraph [0202]). Johnston discloses leucine is added to enhance dispersability of dry powders for inhalation (paragraph [0187]).
Regarding claim 8, Johnston discloses TFF powders with a diameter predominantly between 2.0-3.5µm, on a volume basis, that is ideal for pulmonary delivery (paragraph [0180]).
Regarding claim 15, Johnston discloses that the sugar excipient which includes mannitol is at a ratio to the active of 1 to 1 (e.g. 50%) (paragraph [0202]).
Johnston does not specifically teach a ratio of from about 50:50 to about 95:50 of a sugar alcohol to amino acid residue. Johnston does not specifically teach that the active is a virus. The deficiency is made up for by the teachings of Mcintosh and Finlay.
Mcintosh is primarily directed towards drug delivery in the form of dry powder for inhalation (abstract).
Regarding claim 1, Mcintosh teaches a dry powder formulation comprising an active and an amorphous glass matrix comprising one or more mono, di- or polysaccharides and L-leucine (paragraphs [0033-0036]). Mcintosh teaches that L-leucine stabilizes particles such that agglomerations is inhibited. Mcintosh teaches that the particles formed are protected from degradation (paragraph [0014]). Mcintosh teaches that the higher the fine particle fraction (FPF), the higher the chance of the drug reaching the alveoli and getting absorbed into the bloodstream (paragraph [0101]). Mcintosh teaches that formulations containing leucine had highest FPF of greater than 68% (paragraph [0118]). Mcintosh teaches ratio of leucine to mannitol of including 5:95 and 10:90 (paragraph [0134]). The ratio of leucine to mannitol of 5:95 and 10:90 overlaps the range of about 50:50 to about 95:5 recited in claim 1. Thus, the range is rendered prima facie obvious. See In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). See also MPEP 2144.05. Mcintosh teaches that increase in leucine content decreased cohesion and improves flowability (paragraph [0136]).
Finlay is primarily directed towards a respirable composition for treatment of a bacterial infection includes one or more active bacteriophages (abstract).
Regarding claims 1, 32 and 190, Finlay teaches that bacteriophages are viruses that specifically attack and kill different types of bacteria (paragraph [0007]). Finlay teaches respirable compositions for delivery of bacteriophages to the lungs of individuals, for use in treating persons infected with a bacterial infection capable of treatment with bacteriophages (paragraph [0012]). Finlay teaches drug delivery system including dry powder inhaler (paragraph [0019]). Finlay teaches bacterial infection is caused by one or more Burkholderia cepacia complex (BCC) strains and include individuals with cystic fibrosis (paragraph [0020]).
It would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to produce a dry powder inhaler comprising a dry powder comprising bacteriophages (e.g., virus), a sugar excipient including mannitol (e.g., sugar alcohol) and leucine (e.g., amino acid residue); wherein the dry powder is made by an ultra-rapid freezing that comprises thin film freezing; wherein the powder have a diameter predominantly between 2.0-3.5µm, on a volume basis; and wherein the ratio of the mannitol to leucine includes 95:5 and 90:10. The person of ordinary skill in the art would have been motivated to make those modifications to: 1) obtain a composition comprising bacteriophages as active for treatment of Burkholderia cepacia complex infection including cystic fibrosis, as taught by Finlay, that has the benefits of dry powder that has been produced by an ultra-rapid freezing that comprises thin film freezing disclosed by Johnston, wherein the benefits include exceptional respirable properties and highly efficient deep lung delivery that is highly potent without the need of carrier particles; and 2) optimized the amount of leucine to mannitol using ratios of including 5:95 and 10:90 of leucine to mannitol in order to obtain dry powder with including desired flowability and chance of reaching the alveoli. The person of ordinary skill in the art would have reasonably expected success because Johnston discloses a medicinal formulation for use in a dry powder inhaler having non-tightly packed porous flocculated web composition comprising one or more brittle-matrix particles of one or more active agents (e.g. dry powder)(paragraph [0014]). Johnston discloses that carrier particles are not needed for pulmonary delivery (paragraph [0189]). Johnston discloses that the brittle-matrix particles are made using ultra-rapid freezing (URF) (paragraph [0190]). Johnston discloses that the brittle matrices are produced by thin film freezing (TFF) which exhibit exceptional respirable properties and is useful for highly efficient delivery of thermally labile, highly potent and poorly soluble drugs (paragraph [0201]). Johnston discloses that the particles which have low-density and is porous allows highly efficient deep lung delivery via a dry powder inhaler (paragraph [0201]). Johnston discloses producing including dry powders using TFF and lyophilization (e.g. removing solvent), where the dry powder comprises an active and sugar excipient including mannitol (paragraph [0202]). Johnston discloses that active agents include nucleic acids (paragraph [0220]). Mcintosh teaches a dry powder formulation comprising an active and an amorphous glass matrix comprising one or more mono, di- or polysaccharides and L-leucine (paragraphs [0033-0036]). Mcintosh teaches that L-leucine stabilizes particles such that agglomerations is inhibited. Mcintosh teaches that the particles formed are protected from degradation (paragraph [0014]). Mcintosh teaches that the higher the fine particle fraction (FPF), the higher the chance of the drug reaching the alveoli and getting absorbed into the bloodstream (paragraph [0101]). Mcintosh teaches that formulations containing leucine had highest FPF of greater than 68% (paragraph [0118]). Mcintosh teaches ratio of leucine to mannitol of including 5:95 and 10:90 (paragraph [0134]). Finlay teaches that bacteriophages are viruses that specifically attack and kill different types of bacteria (paragraph [0007]). Finlay teaches respirable compositions for delivery of bacteriophages to the lungs of individuals, for use in treating persons infected with a bacterial infection capable of treatment with bacteriophages (paragraph [0012]). Finlay teaches drug delivery system including dry powder inhaler (paragraph [0019]). Finlay teaches bacterial infection is caused by one or more Burkholderia cepacia complex (BCC) strains and include individuals with cystic fibrosis (paragraph [0020]).
Regarding the recitation “wherein the biologically active polynucleotides retain substantial biological activity and/or have been stabilized by the URF process” and claims 2-3, the dry powder inhaler comprising a dry powder comprising bacteriophages (e.g., virus), a sugar excipient including mannitol (e.g., sugar alcohol) and leucine; wherein the dry powder is made by an ultra-rapid freezing that comprises thin film freezing; wherein the powder have a diameter predominantly between 2.0-3.5µm, on a volume basis; and wherein the ratio of the mannitol to leucine includes 95:5 and 90:10; is prima facie obvious in light of the disclosure of Johnston and the teachings of Mcintosh and Finlay (described above). The dry powder that is prima facie obvious in light of the disclosure of Johnston and the teachings of Finlay is the same and is produced by the same process as the instantly claimed dry powder, thus, the dry powder that is prima facie obvious in light of the disclosure of Johnston and the teachings of Finlay necessarily possesses the same characteristics as the instantly claimed dry powder, e.g., bacteriophages retain substantial biological activity and/or have been stabilized by the URF process, the bacteriophages retain at least about 0.5% of biological activity compared to an equal amount of the bacteriophages in solution prior to the URF process, and the bacteriophages is stabilized such that at least 50% more of the bacteriophages in the dry powder are undegraded relative the same bacteriophages in a solution.
Response to Arguments
Applicant argues that the favorable characteristics of the instantly claimed compositions could not have been predicted based upon the teachings of any of Johnston, Mcintosh, Finley, or the combination thereof. Applicant argues that Johnston discloses that “brittle matrices produced by thin film freezing (TFF) exhibit exceptional respirable properties and may prove to be a useful platform for highly efficient delivery of thermally labile, highly potent, and poorly soluble drugs” (page 17 of Johnston). Applicant argues that a person of skill in the art would not reasonably form an expectation based on the data of Johnston that the provided formulations methods would necessarily successfully provide compositions comprising biologically active polynucleotide such as viruses. Applicant argues that a person of skill in the art would recognize the significant structural and functional differences between a small molecule or protein (e.g., drugs in Johnston’s exemplary compositions) and a biologically active polynucleotide such as a virus. Applicant argues that the data of Johnston is limited to aerosol performance and particle characterization and Johnston is silent on the effect of the TFF process on the biological activity of the active agent. Applicant argues that Johnston does not provide compositions comprising a biologically active polynucleotide or a virus and Johnston is silent on the effect of the TFF process on the bioactivity of compositions comprising viruses. Applicant argues that Mcintosh is limited to compositions comprising the peptide hormone oxytocin or influenza antigen hemagglutinin and that the exemplified compositions of Mcintosh are prepared by spray-drying. Applicant argues that Mcintosh provide no reason for a person of skill in the art to expect that compositions comprising a biologically active polynucleotide such as a virus are formulated by TFF would retain biological activity because the active agents of the composition of Mcintosh do not comprise a nucleic acid active and are not formulated by TFF. Applicant argues that Finlay teaches compositions comprising bacteriophage that are prepared by lyophilization but Finlay is silent on formulating the compositions therein by TFF. Applicant argues that a person of skill in the art would have no reason based upon Finlay to expect that the compositions comprising a nucleic acid, even the bacteriophage of Finlay, would retain biological activity when exposed to the conditions associated with the TFF process, because Finlay does not provide evidence that any active agent retains biological activity when exposed to the conditions of TFF.
Applicant's arguments filed on 13 July 2026 have been fully considered but they are not persuasive. In response, Johnston discloses that the brittle matrices are produced by thin film freezing (TFF) which exhibit exceptional respirable properties and is useful for highly efficient delivery of thermally labile, highly potent and poorly soluble drugs (paragraph [0201]). Johnston discloses producing including dry powders using TFF, where the dry powder comprises an active and sugar excipient including mannitol (paragraph [0202]). Johnston discloses leucine is added to enhance dispersability of dry powders for inhalation (paragraph [0187]). Mcintosh teaches a dry powder formulation comprising an active and an amorphous glass matrix comprising one or more mono, di- or polysaccharides and L-leucine (paragraphs [0033-0036]). Mcintosh teaches that L-leucine stabilizes particles such that agglomerations is inhibited. Mcintosh teaches that the particles formed are protected from degradation (paragraph [0014]). Mcintosh teaches that the higher the fine particle fraction (FPF), the higher the chance of the drug reaching the alveoli and getting absorbed into the bloodstream (paragraph [0101]). Mcintosh teaches that formulations containing leucine had highest FPF of greater than 68% (paragraph [0118]). Mcintosh teaches ratio of leucine to mannitol of including 5:95 and 10:90 (paragraph [0134]). Finlay teaches that bacteriophages are viruses that specifically attack and kill different types of bacteria (paragraph [0007]). Finlay teaches respirable compositions for delivery of bacteriophages to the lungs of individuals, for use in treating persons infected with a bacterial infection capable of treatment with bacteriophages (paragraph [0012]). Finlay teaches drug delivery system including dry powder inhaler (paragraph [0019]). Finlay teaches bacterial infection is caused by one or more Burkholderia cepacia complex (BCC) strains and include individuals with cystic fibrosis (paragraph [0020]). Finlay teaches that carbohydrates including mannitol provides good cryoprotection for bacteriophage (paragraphs [0075-0077]). Therefore, in light of the disclosure of Johnston and the teachings of Mcintosh and Finlay, it would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to produce a dry powder comprising bacteriophages (e.g., virus), a sugar excipient including mannitol (e.g., sugar alcohol) and leucine (e.g., amino acid residue); wherein the dry powder is made by an ultra-rapid freezing that comprises thin film freezing; wherein the powder have a diameter predominantly between 2.0-3.5µm, on a volume basis; and wherein the ratio of the mannitol to leucine includes 95:5 and 90:10. The person of ordinary skill in the art would expect that the dry powder made by the thin film freezing disclosed by Johnston which include sugar including mannitol would be suitable for the bacteriophages of Finlay that can be cryoprotected by carbohydrate matrix including mannitol, in order to produce dry powder comprising bacteriophage of Finlay that are cryoprotected (e.g., still viable/retain bioactivity) and that have advantages of the dry powder of Johnston including exhibiting exceptional respirable properties and highly efficient delivery. Additionally, one of ordinary in the art would optimize the excipients including leucin and mannitol using ratio of leucine to mannitol of including 5:95 and 10:90 in order to obtain desired properties including protection from degradation which is provided by the leucine, as taught by Mcintosh.
Thus, for the reasons of record and for the reasons presented above claims -4, 8, 12, 15, 32, 107, 175, and 190 are rejected under 35 U.S.C. 103(a).
Conclusion and Correspondence
No claims are allowed.
THIS ACTION IS MADE FINAL.
Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any 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 JOHN P NGUYEN whose telephone number is (571)270-5877. The examiner can normally be reached Monday-Friday 10am-6pm EST.
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/JOHN P NGUYEN/
Examiner, Art Unit 1619
/ANNA R FALKOWITZ/Primary Examiner, Art Unit 1600
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