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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 16 December 2025 has been entered.
Status of Claims
Receipt is acknowledged of the claim amendment filed on 16 December 2025.
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Claims 22-23, 95, 114, 185 and 191-194 remains withdrawn from consideration.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Rejections Withdrawn
The rejection of claims 1-4, 8, 12, 15, 32, 107, 175 and 190 under 35 U.S.C. 103(a) as being unpatentable over JOHNSTON (US 2010/0221343 A1, publication date of 2 September 2010) in view of FINLAY (US 2011/0293671 A1, publication date of 1 December 2011), is withdrawn in view of Applicant’s claim amendments.
New Grounds of Rejections
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’s arguments will be addressed as they pertain to the new grounds of rejection above.
Applicant argues that as noted in the instant specification, other freezing processes caused reduced infectivity of the virus or bacterium. Applicant argues that Tables 19 and 20 of the instant specification show that the nucleic acids prepared using other freezing methods such as flash freezing and shelf freezing result in significantly reduced infectivity. Applicant argues that selection of URF processing was shown to be viable processing method, which is not suggested in Finley. Applicant argues none of the references suggest using a combination of the first and second excipients in particular ratios in the compositions with viruses and bacteria and that those compositions would result in high infectivity. Applicant also points to Figures 10 and 11 for similar data increased viability.
Applicant's arguments filed on 16 December 2025 have been fully considered but they are not persuasive. In response, Table 19 shows viability of E. coli using different excipients (e.g., 10% sucrose, no excipients, 1.7% trehalose, 5% sucrose and 3.75% mannitol, 1.7% trehalose in 1mM CaCl2, and 1.7% trehalose and 3.75% mannitol) and lyophilization methods including thin-film freezing and flash freezing. Table 20 of the instant specification appears to show that compared to shelf-freeze without excipients, thin-film freeze without excipients provided more recovery of cells, e.g., 88.89% versus 14.72, respectively. 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]). 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 would be suitable for thermal labile actives and Johnston discloses the same thin film freezing method, therefore, the thin film freezing method of Johnston would necessarily also provide the same results of reduced infectivity of viruses and bacteria. 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.
Regarding Figures 10 and 11 of the instant specification, Figure 10 shows that Dv50 of the PBS containing powders was generally smaller than its no-buffer and SM buffer counterparts. Figure 11 shows that incorporating buffer system reduced titer loss in both freezing and drying steps regardless of excipient compositions. It is noted that the features upon which applicant relies (i.e., PBS) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Thus, for the reasons of record and for the reasons presented above claims 1-4, 8, 12, 15, 32, 107, 175, and 190 are rejected under 35 U.S.C. 103(a).
Conclusion and Correspondence
No claims are allowed.
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