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 .
Priority
This application is a divisional of application 17/127,416 filed on December 18, 2020. Applicant’s claim for the benefit of a prior-filed application 17/127,416, and the provisional application 62/951,523 filed on December 20, 2019, under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Status of the Claims
In response filed on September 17, 2025, Applicant have amended claim 1, 9, 13 , 17 and 22 and canceled claims 4, 10, 16, and 23.
Applicant’s election without traverse of species, disease affecting the airways and/or lungs, alpha-1-antitrypsin deficiency, and SEQ ID: 3 (Claims 1-26) in the reply filed on Feb. 14, 2025, is acknowledged.
Election was made without traverse in the reply filed on Feb. 14, 2025.
Currently, claims 1-3, 5-9, 11-15, 17-22 and 24-26 have been examined on their merits.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on Sept. 17, 2025, is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Withdrawn Objections & Rejections
Rejections and/or objections not reiterated from the previous office action are hereby withdrawn due to amendment. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
The rejection of claims 1-13 and 16, 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn due to applicant amendments to the claims no longer citing “a disease affecting the airways or lungs.”
The rejection of claims 1-12 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, scope of enablement rejection is withdrawn due to the amendment to the claims no longer citing a method “for providing prophylactic relief of one or more signs or symptoms of a disease affecting the airways and/or lungs in a subject in need thereof”.
The rejection of claims 1-26 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 is withdrawn due to the amendment to the claims, which are now only reciting alpha-1-antitrypsin.
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, 5-8, 12-15, 17-21, and 25-26 are rejected under 35 U.S.C. 103 as being unpatentable over Gonda et al., (U.S. Patent 7,244,714, published 2007, cited IDS 9/13/24, prior art of record) in view of Glorioso et al., (WO2015009952A1, published 2015, prior art of record), and Bowling, et al. (Applied and environmental microbiology 85.17: e00747-19, published Sept. 2019, prior art of record).
This rejection is a new rejection necessitated by amendments to the claims. However, since it is substantially similar to a rejection set forth in the non-final Official action mailed on Sept. 17, 2025, therefore any aspect of applicant's response considered relevant to the rejection as newly set forth is responded to following the statement of rejection.
Regarding claim 1, and 13, Gonda discloses a method of providing therapeutic relief of one or more signs or symptoms of a disease affecting the airways and/or lungs in a subject in need thereof (i.e. mucosal clearance)(e.g. Abstract, and col. 1-2, 6, 8 and 10). Further, Gonda discloses delivering a polypeptide (i.e. alpha-1-antityprsin) to one or more cells of the respiratory tract of a subject (see e.g. abstract, Examples 3-4, and col. 20, and col. 28).
Regarding claim 1 and 13, step a, Gonda discloses wherein the nucleic acids are delivered encapsulated in viral delivery particles, e.g. herpes simplex virus (see e.g. col. 22, lines 56-67, Example 1).
Regarding claim 1 and 13, step b, Gonda discloses a pharmaceutical acceptable carrier (e.g. col. 27, lines 49-58), and wherein the inhaled therapeutic polypeptide is alpha-1-antityprsin (see e.g. col. 20, and col. 28). Further, Gonda discloses wherein the pharmaceutical compositions are formulated for administration to the mammalian respiratory tract via inhalation of an aerosol (e.g. col. 27, lines 12-27; col. 28, lines 20-27), including the use of devices which allows one to control aerodynamic particle size, e.g. metered-dose inhalers and nebulizers (col. 15, lines 12-17).
Gonda et al is silent regarding the herpes simplex virus is a herpes simplex virus type 1 (HSV-1).
However, Glorioso et al., teaches a herpes virus comprising a recombinant herpes virus genome wherein the herpes virus is herpes simplex virus type 1 (HSV-1) (Abstract, Example 1).
Regarding claim 1 and 13, Glorioso teaches a modified HSV-1 to be non-toxic by inactivating mutations in essential immediate early genes (e.g. para. 8, 16, 104, 60, 98, 106; Figures 1 and 9), and a pharmaceutically acceptable excipient or buffer (see e.g. para. 71).
Accordingly, it would have been obvious to an artisan of ordinary skill at the time of the effective filing date to have modified the method of Gonda and prepare the pharmaceutical composition comprising HSV (as taught by Gonda) and choose HSV-1 (as taught by Glorioso) with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to do so because Glorioso teaches an HSV-1 vector that has been modified to reduce its toxicity for gene therapy (see e.g. para. 42, 60, 98, 106, 119). In regard to the reasonable expectation of success of doing so, Glorioso teaches that the HSV-1 vector can be used to infect lung and epithelial cells (see e.g. para. 55, see also claim 50 of Glorioso) and, Gonda provides preferred embodiments of composition comprising an artificial viral envelope (AVE) formatted for a nebulizer (AERxTM) (see Example 1). Further, Gonda teaches that the “methods may be used for optimization of transfection efficiency and expression in vivo, and for in vivo expression, for example for generating an immune response, or inducing immunological tolerance” (see e.g. abstract). Glorioso teaches that “the inventive HSV vector does not express any toxic viral genes in non-complementing cells, yet is capable of vigorous, persistent transgene expression” (see e.g. para. 5). Thus, providing motivation to do.
Regarding claims 2 and 14, Gonda discloses wherein the subject is a human (see e.g. col. 10-12, fig. 2-3).
Regarding claims 3 and 15, Gonda discloses wherein the pharmaceutical composition is administered intratracheally, or via inhalation to the subject (see e.g. col. 3, 8, and 16-19).
Regarding claims 17, Gonda discloses, wherein the disease is selected from the group consisting of alpha-1-antitrypsin deficiency, (see e.g. col. 3).
Regarding claims 5 and 18, as discussed above, Gonda discloses the delivery device of a nebulizer (see e.g. col. 15).
Gonda et al., is silent wherein the nebulizer is a vibrating mesh nebulizer.
However, Bowling et al., teaches that a vibrating mesh nebulizer (see e.g. abstract).
Accordingly, it would have been obvious to an artisan of ordinary skill at the time of the effective filing date to have modified the method of Gonda and prepare the pharmaceutical composition comprising a vibrating mesh nebulizer (as taught by Bowling) with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to do so because Bowling teaches improved aerosol performance (see e.g. abstract). Further, both Gonda and Bowling teach using nebulizer for respiratory diseases. Additionally, Bowling teaches that exploration of aerosol generators is recommended when developing new animal models for human respiratory infections (see e.g. conclusions). Thus, providing motivation to do.
Regarding claims 6-8 and 19-21, as discussed above, Gonda is silent regarding HSV-1.
However, Glorioso teaches wherein the recombinant HSV -1 genome comprises an inactivating mutation in the ICP22 HSV-1 gene (see e.g. abstract, claims 3-5, 9 and 12-14).
Regarding claims 6-8, 12, 19-21, and 25, Glorioso wherein the inactivating mutation in the ICP22 HSV-1 gene is a deletion of at least a portion of the coding sequence of the ICP22 HSV-1 gene (see e.g. para. 43, 106). Further, Glorioso discloses a recombinant HSV-1 genome comprises an inactivating mutation in one or more essential immediate early genes (i.e. ICP22)(see e.g. para. 43, 60, 98, and 106, Example 2). Additionally, Glorioso teaches that the HSV-1 is replication defective (see e.g. Example 2, para. 86).
Accordingly, it would have been obvious to an artisan of ordinary skill at the time of the effective filing date to have modified the method of Gonda and prepare the pharmaceutical composition comprising HSV (as taught by Gonda) and choose HSV-1 with the inactivating mutation in the ICP22 gene (as taught by Glorioso) with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to do so because Glorioso teaches an HSV-1 vector that has been modified to reduce its toxicity for gene therapy (see e.g. para. 42, 60, 98, 106, 119). Further, Glorioso teaches that the recombinant herpes virus comprising an inactivating deletion in the regulatory region in the essential immediate early gene of ICP22 HSV-1 in order to reduce its toxicity (see e.g. 0060, 0098, 0106). In regard to the reasonable expectation of success of doing so, both Gonda and Glorioso teaches that the HSV-1 vector can be used to infect lung and epithelial cells, as discussed above. Further, Glorioso teaches that “the inventive HSV vector does not express any toxic viral genes in non-complementing cells, yet is capable of vigorous, persistent transgene expression” (see e.g. para. 5). Thus, providing motivation to do.
Regarding claim 26, Gonda discloses wherein one or more cells of the respiratory tract is an airway epithelial cell (see e.g. abstract and col. 6 and 26).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Response to Traversal:
1.132 Affidavits or declarations traversing rejections or objections.
When any claim of an application or a patent under reexamination is rejected or objected to, any evidence submitted to traverse the rejection or objection on a basis not otherwise provided for must be by way of an oath or declaration under this section. [48 FR 2696, Jan. 20, 1983, effective Feb. 27, 1983; revised, 61 FR 42790, Aug. 19, 1996, effective Sept. 23, 1996; revised, 65 FR 54604, Sept. 8, 2000, effective Sept. 8, 2000; revised 65 FR 57024, Sept. 20, 2000, effective Nov. 29, 2000]
Applicant argues a lack of prima facie case asserting that the combination of cited references fails to teach or suggest an HSV-1 that delivers and expresses the one or more polynucleotides encoding an alpha-1-antitrypsin polypeptide to the airways ( claim 1) or one or more cells of the respiratory tract (claim 13) of the subject (See Remarks, page 10).
Applicant arguments are acknowledged, have been fully considered, and have been deemed unpersuasive.
In response to applicant's argument that there is a lack of prima facie case regarding the amendments to the claims, contrary to Applicants response, a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure of Gona, Glorioso, and Bowling et al., is capable of performing the intended use (i.e. “an HSV-1 that delivers and expresses the one or more polynucleotides encoding an alpha-1-antitrypsin polypeptide to the airways ( claim 1) or one or more cells of the respiratory tract (claim 13) of the subject”), then it meets the claim.
On Sept. 17th, 2025, Applicant filed “Secondary Considerations” (See Remarks, pages 10-16, Exhibit A, pages 20-23, and Exhibit B, pages 24-29).
“Rebuttal evidence and arguments can be presented in the specification, In re Soni, 54 F.3d 746, 750, 34 USPQ2d 1684, 1687 (Fed. Cir. 1995), by way of an affidavit or declaration under 37 CFR 1.132, e.g., Soni, 54 F.3d at 750, 34 USPQ2d at 1687; In re Piasecki, 745 F.2d 1468, 1474, 223 USPQ 785, 789-90 (Fed. Cir. 1984), or otherwise presented during prosecution. See, e.g., MPEP §§ 714 to 716 et seq. However, arguments presented by applicant cannot take the place of factually supported objective evidence. See, e.g., In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984).” (See MPEP 2145)
It is noted that Applicant’s response of secondary considerations has not been submitted in declaration form (see above, 37 CFR 1.132).
Although evidence of unexpected results must compare the claimed invention with the closest prior art, applicant is not required to compare the claimed invention with subject matter that does not exist in the prior art. In re Geiger, 815 F.2d 686, 689, 2 USPQ2d 1276, 1279 (Fed. Cir. 1987) (Newman, J., concurring) (Evidence rebutted prima facie case by comparing claimed invention with the most relevant prior art. Note that the majority held the Office failed to establish a prima facie case of obviousness.); In re Chapman, 357 F.2d 418, 148 USPQ 711 (CCPA 1966) (Requiring applicant to compare claimed invention with polymer suggested by the combination of references relied upon in the rejection of the claimed invention under 35 U.S.C. 103 "would be requiring comparison of the results of the invention with the results of the invention." 357 F.2d at 422, 148 USPQ at 714.)
The secondary considerations submitted on Sept. 17th, 2025, are acknowledged, considered, and are deemed insufficient to overcome the rejection of instant claims based upon 35 U.S.C 103 as set forth in the last Office action for the following reasons: the secondary considerations assert that the invention works as intended, which includes statements which amount to an affirmation that the claimed subject matter of an HSV-A1AT pharmaceutical composition functions (i.e. HSV-A1AT is well tolerated) as it was intended to function (i.e. no serious adverse events)(fig. 1-4 of Exhibit A)(see Remarks, page 8-9). Furthermore, the issues raised are not relevant to the issue of nonobviousness of the claimed subject matter and provides no objective evidence thereof. See MPEP § 716.
Applicant asserts that “Applicant has successfully demonstrated the in vivo delivery of a replication-defective herpes simplex virus type 1 comprising a recombinant genome encoding an inhaled therapeutic polypeptide (specifically, an alpha-1 antitrypsin (A1AT) polypeptide, termed "HSV-A1AT") to lung tissue by inhalation using a vibrating mesh nebulizer that provides a consistent dose of HSV-A1AT with limited biodistribution and in the absence of any adverse events (see Figures 1-4 of Exhibit A, attached herewith)(Remarks, page 11-13).
Applicant arguments are acknowledged, have been fully considered, and have been deemed unpersuasive.
In response to Applicants argument, it is acknowledged that the Applicant has successfully delivery with limited biodistribution. However, it is unclear how these results are unexpected in view of the prior art. As discussed above, the biodistribution results do not speak to the composition compared with the prior art which is required (see MPEP716). Furthermore, these results are not unexpected as Gonda discloses successful delivery of a formulated composition through a nozzle (i.e. nebulizer) causes increase expression and does not affect cell viability (col. 29-30 of Gonda). Thus, it is unclear how the secondary considerations are compared to the prior art of Gonda, especially if the composition is working as expected.
Applicant argues that the total aerosol concentration and repeatability, determined by both gravimetric (GPA) and chemical (BioSampler) methods (Fig. 2) teaches that the vibrating mesh nebulizer is capable of delivering consistent repeatable doses of HSV-A1AT at the appropriate mass median aerodynamic diameter (MMAD) of 1-5μm to reach human lung tissue upon inhalation (Figure 2C)(Remarks, page 12).
Applicant arguments are acknowledged, have been fully considered, and have been deemed unpersuasive.
In response to Applicants argument, it is acknowledged that there is a total aerosol concentration and repeatability by both gravimetric (GPA) and chemical (BioSampler) methods (Fig. 2). It is noted that the results of delivery and repeatability are important to the method claims. However, it is unclear how this asserts unpredictability and is in commensurate in scope with claimed composition. It is acknowledged that HSV-A1AT was measured to have a mass median aerodynamic diameter (MMAD) of 1-5μm to reach human lung tissue upon inhalation (Figure 2C). However, there is not a claim limitation directed to MMAD and it is unclear how this is significant over the prior art of record. As states supra, these results do not appear to be unexpected as Gonda discloses that delivery with DNA formulated with artificial viral envelope (AVE) through a nozzle (i.e. nebulizer) causes increase expression and does not affect cell viability (col. 29-30 of Gonda). The MMAD range results are not being compared with the composition with the closest prior art (see MPEP716).
Applicant argues that HSV-A1AT exposure was highest in the lungs, with little-to-no detection in other tissues, 24 hours (day 23, Figure 5) after the last dose of HSV-A1AT was administered, demonstrating successful delivery to, and retention within, the targeted tissue (lungs) after inhaled delivery to mice (Figure 3)(Remarks, Page 12).
Applicant arguments are acknowledged, have been fully considered, and have been deemed unpersuasive.
In response to Applicants argument, it is acknowledged that there is a high level of detection in the lungs regarding the high dosage of HSV-A1AT (Fig. 3). However, it is noted that at low dosage of HSV-A1AT there is detection in the lymph nodes of the males (Fig. 3). It is noted that there is not a claim limitation directed to the dosage of HSV-A1AT and/or time period of the pharmaceutical composition. Thus, the argument is not commensurate in scope with the claims. As discussed above, Applicant has not indicated how this is unexpected over the prior art of Gonda, which discloses aerosolized pharmaceutical formulations can be delivered successfully to the lungs.
Applicant argues that one of ordinary skill in the art would have no reason to expect the superior results presented in Exhibit A in view of the combined teachings of Gonda, Glorioso, and Bowling, which yields unexpectedly improved properties sufficient to rebut any prima facie case of obviousness.
Applicant arguments are acknowledged, have been fully considered, and have been deemed unpersuasive.
In response to Applicants arguments, the unexpected evidence is directed to A1AT and are not commensurate in scope with the claims (see list of inhaled therapeutic polypeptides)(see claim 45). As discussed above, Applicants have not shown unexpected results (i.e. delivery of composition) compared to Gonda to rebut any prima facie case of obviousness (see MPEP 716.02). It is acknowledged that Applicants have shown “minor, non-adverse HSV-A1AT-related effects” (Fig. 4, Remarks, page 12)). However, these results do not speak to the composition with the closest prior art (see MPEP716). Thus, it is unclear how the secondary considerations are compared to the prior art of Gonda, especially if the composition is working as expected. In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Applicant argues a successful open-label, single dose escalation study in adult patients with apha-1 antitrypsin deficiency (AATD), where the study was designed to include up to three dose escalation cohorts evaluating single administrations of 109, 1010, and 1011 PFU of a replication-defective HSV-1 comprising a recombinant HSV-1 genome encoding an inhaled therapeutic polypeptide (specifically, an alpha-1 antitrypsin (A1AT) polypeptide, termed "HSV-A1AT"). Applicant asserts that they have evidence of successful gene delivery in two patients showing a high rate of transduction and A1AT expression (page 14), to where they efficiently produced the encoded human A1AT transgene in a dosage range that is functional and clinically relevant as evidenced by neutrophil elastase inhibition (see Figures 5-8 of Exhibit B, attached herewith)(Remarks, page 13-14).
Applicant arguments are acknowledged, have been fully considered, and have been deemed unpersuasive.
Applicants’ response is reminded that in submitting evidence asserted to establish unobvious results, there is a burden on an applicant to indicate how the examples asserted to represent the claimed invention are considered to relate to the examples intended to represent the prior art and, particularly, to indicate how those latter examples do represent the closest prior art. See In re Borkowski, 595 F.2d 713, 184 USPQ 29 (CCPA 1974); In re Goodman, 339 F.2d 228, 144 USPQ 30 (CCPA 1964). It should also be established that the differences in the results are in fact unexpected and unobvious and of both statistical and practical significance. In re Merck, 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986); In re Longi, 759 F. 2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Klosak, 455 F2d 1077, 173 UAPQ 14 (CCPA 1972); In re D’Ancicco, 429 F.2d 1244, 169 USPQ 303 (CCPA 1971 ). Ex parte Gelles, 22 USPQ2d 1318 (BPAI 1992).
In the instant case, it is understood that the open label study showed that the method was well tolerated and shows an additive effect (i.e. dose escalation study of SERPENTINE and HSV-A1AT)(Exhibit B, fig. 5-8). It is acknowledged that Applicant claims that the method efficiently produced the encoded human A1AT transgene in a range that is functional and clinically relevant as evidenced by neutrophil elastase inhibition (i.e. increase in fee A1AT levels in the lung post dose) and that the percentage of free neutrophil elastase in ELF is reduced after a single dose of HSV-AIA dose (Fig. 7B). However, the additive effect of the results does not speak to the method compared to the prior art which is required (see MPEP716). Furthermore, these results are not unexpected as Gonda discloses that delivery with DNA formulated with artificial viral envelope (AVE) through a nozzle (i.e. nebulizer) causes increase expression and does not affect cell viability (col. 29-30 of Gonda). Thus, it is also not unexpected that a person of ordinary skill in the art would expect the percentage of free neutrophil elastase in the epithelial lining fluid (ELF) to be reduced upon application of the composition because expression would be increased as taught by Gonda. Furthermore, it is unclear how the secondary considerations are compared to the prior art of Gonda, especially if the composition is working as expected.
Applicant argues that patients not on background IV A1AT augmentation had free A1AT levels in the lung epithelial lining fluid increase over 8-fold after HSV-A1AT dosing (Fig. 7B). Further, Applicant asserts that the unbound neutrophil elastase in epithelial lining fluid dropping from 97.2% at baseline to 40.2%, representing a greater than 50% absolute reduction achieved within 48 hours after dosing (Fig. 7B) (Remarks, page 15).
Applicant arguments are acknowledged, have been fully considered, and have been deemed unpersuasive.
In response to Applicants arguments, it appears that the free A1AT levels in the lung epithelial lining fluid (ELF) post dose (Fig. 7B) are significant. It is noted that there is not claim limitation directed to the unbound neutrophil elastase in epithelial lining fluid. As discussed above, it is unclear how the results of free A1AT levels in the lung are compared with the closest prior art (i.e. Gonda) (MPEP 716.02). Therefore, there is not enough data to conclude that the results are unexpected.
Applicant argues that patients on background IV A1AT augmentation are clinically meaningful and support successful gene delivery and expression in the HSV-A1AT treated lung (Fig. 8). Further, Applicant asserts that the levels of A1AT in the serum increased from 4.4 μM to 9.7 μM after HSV-A1AT dosing (Exhibit B)(Remarks, page 15-16).
Applicant arguments are acknowledged, have been fully considered, and have been deemed partially persuasive.
In response to Applicants arguments, it appears that the level of A1AT in the serum increases after dosage showing successful delivery (Fig. 4) is significant. As discussed above, it is unclear how the results of free A1AT levels in the lung are compared with the closest prior art (i.e. Gonda)(MPEP 716.02). Therefore, there is not enough data to conclude that the results are unexpected.
Applicant argues that one of ordinary skill in the art would have no reason to expect the superior results (i.e. well-tolerated with no serious adverse events, transduced relevant airway epithelia, and efficiently produced the encoded human A1AT transgene in a functionally and clinically relevant range) presented in Exhibit B in view of the combined teachings of Gonda, Glorioso, and Bowling, which yields unexpectedly improved properties sufficient to rebut any prima facie case of obviousness.
Applicant arguments are acknowledged, have been fully considered, and have been deemed unpersuasive.
In response to Applicants arguments, Applicants response has not shown unexpected results (i.e. delivery of composition) compared to Gonda to rebut any prima facie case of obviousness (see MPEP 716.02). It is acknowledged that Applicants have shown “minor, non-adverse HSV-A1AT-related effects” (Figs. 1-8). However, these results do not speak to the claimed method with the closest prior art (see MPEP716). Thus, it is unclear how the secondary considerations are compared to the prior art of Gonda, especially if the composition and method are working as expected. In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Claims 9 and 22 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Gonda et al., (U.S. Patent 7,244,714, published 2007, of record cited IDS 9/13/24, prior art of record) in view of Glorioso et al., (WO2015009952A1, published 2015, prior art of record) and Bowling, et al. (Applied and environmental microbiology 85.17: e00747-19, published Sept. 2019, prior art of record), as applied to claims 1-8, 10, 12-21, 23, and 25-26, and further in view of Strom et al., (WO2015191892A2, PCT/2015/035385, published 2015, prior art of record).
This rejection is repeated with regard to claims 11 and 24 for the same reasons of record as set forth in the Official action mailed on Sept. 17, 2025, therefore any aspect of applicant's response considered relevant to the rejection as newly set forth is responded to following the statement of rejection.
The teachings of Gonda et al., apply here as indicated above.
Gonda et al., are silent regarding the inhaled therapeutic polypeptide comprises a sequence having at least 95% sequence identity to an amino acid sequence SEQ ID NO: 3 (i.e. alpha 1 -antitrypsin polypeptide (AAT)).
However, Strom et al., teaches a recombinant polypeptide comprising an alpha 1 -antitrypsin polypeptide (AAT)(see e.g. abstract and claim 1).
Regarding claims 9 and 22, Strom teaches wherein the inhaled therapeutic polypeptide comprises a sequence having at least 95% sequence identity to the AAT amino acid sequence of SEQ ID NO: 3 (i.e. SEQ ID 10)(See search result 20241218_162835_us-18-884-441-3.rapm, Result 26, score alignment of 100% below).
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Accordingly, it would have been obvious to an artisan of ordinary skill at the time of the effective filing date to have modified the method of Gonda and prepare the pharmaceutical composition comprising the inhaled therapeutic polypeptide of alpha 1 -antitrypsin polypeptide (A1AT) SEQ ID NO: 3 (i.e. SEQ ID NO: 10) as taught by Strom with a reasonable expectation of success. One of ordinary skill in the art would have done so because both disclose the usage of A1AT as a desirable therapeutic for subjects with A1AT deficiency and respiratory complications (i.e. pulmonary diseases). Further, Strom discloses that A1AT can be purified with an increased half-life which can be used in therapeutic compositions (see e.g. page 2).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Response to Traversal:
Applicant argues that Strom does not remedy the deficiencies of Gonda, Glorioso and Blowing and asserts that the claims are not obvious in view of the prior art and respectfully traverses the rejection as described in the remarks above (Remarks, page 16).
Applicant arguments are acknowledged, have been fully considered, and have been deemed unpersuasive.
In response to Applicants argument, the prior art of Strom discloses SEQ ID NO: 10 (i.e. SEQ ID NO:3) which is 100% identical to the A1AT SEQ ID NO:3. As discussed above, it would have been obvious to a person of ordinary skill in the art to have modified the method of Gonda with the alpha 1 -antitrypsin polypeptide (A1AT) as taught by Strom because Strom discloses that A1AT can be purified with an increased half-life which can be used in therapeutic compositions (see e.g. page 2).
Since Applicant’s response has not provided any additional further arguments the previous arguments have been addressed above.
Claims 11 and 24 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Gonda et al., (U.S. Patent 7,244,714, published 2007, of record cited IDS 9/13/24, prior art of record) in view of Glorioso et al., (WO2015009952A1, published 2015, prior art of record) and Bowling, et al. (Applied and environmental microbiology 85.17: e00747-19, published Sept. 2019, prior art of record), as applied to claims 1-8, 10, 12-21, 23, and 25-26 above, and further in view of Hover, et al. (Journal of General Virology 98.3: 345-351; published 2017, prior art of record), and Zheng, et al. (Biochemical and biophysical research communications 446.4: 990-996; published 2014, prior art of record).
This rejection is repeated with regard to claims 11 and 24 for the same reasons of record as set forth in the Official action mailed on Sept. 17, 2025, therefore any aspect of applicant's response considered relevant to the rejection as newly set forth is responded to following the statement of rejection.
The teachings of Gonda et al., apply here as indicated above.
Gonda et al., are silent regarding the recombinant HSV-1 genome does not comprise a polynucleotide encoding cystic fibrosis transmembrane conductance regulator (CFTR).
However, the prior art of Hover et al discloses that the “modulation of host cell ion channel activity by viral proteins is being increasingly identified as an important virus–host interaction” (See e.g. abstract).
Regarding claims 11 and 24, Hover discloses that a respiratory viruses were shown to downregulate the cystic fibrosis transmembrane conductance regulator (CFTR) that conducts Cl− and thiocyanate ions across epithelial cell membranes (See virus-mediated respiratory disease section). Further, Hover discloses that “Cl− channel modulation was found to affect viral (i.e. HSV-1) fusion processes by inhibiting viral protein binding to lipid rafts and interrupting Ca2+ homeostasis” citing the prior art of Zheng et al. (See e.g. page 346-347, ref. 14).
Accordingly, it would have been obvious to an artisan of ordinary skill at the time of the effective filing date to have modified the method (as taught by Gonda, Glorioso, and Bowling) and prepare the recombinant HSV-1 genome which does not comprise a polynucleotide encoding cystic fibrosis transmembrane conductance regulator (CFTR) as suggested by Hover and Zheng because Zheng suggests that calcium channel modulation was found to affect viral entry of HSV-1 (see e.g. page 346-347, ref. 14). Therefore, a person of ordinary skill in the art would comprise a recombinant HSV-1 genome that does not comprise a polynucleotide encoding cystic fibrosis transmembrane conductance regulator (CFTR) because they would want to optimize the delivery of the respiratory tract of the subject as suggested by Hover (see e.g. abstract). Furthermore, an artisan of ordinary skill in the art of using a recombinant HSV-1 genome in a pharmaceutical composition has good reason to pursue the known options within his or her technical grasp (KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (US 2007).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Response to Traversal:
Applicant argues that Hover and Zheng do not remedy the deficiencies of Gonda, Glorioso and Blowing, and Applicant asserts that the claims are not obvious in view of the prior art and respectfully traverses the rejection as described in the remarks above (Remarks, page 17).
Applicant arguments are acknowledged, have been fully considered, and have been deemed unpersuasive. As stated supra, a person of ordinary skill in the art would have modified the method (as taught by Gonda, Glorioso, and Bowling) and prepare the recombinant HSV-1 genome which does not comprise a polynucleotide encoding cystic fibrosis transmembrane conductance regulator (CFTR) as suggested by Hover and Zheng because Zheng suggests that calcium channel modulation was found to affect viral entry of HSV-1 (see e.g. page 346-347, ref. 14). Therefore, a person of ordinary skill in the art would comprise a recombinant HSV-1 genome that does not comprise a polynucleotide encoding cystic fibrosis transmembrane conductance regulator (CFTR) because they would want to optimize the delivery of the respiratory tract of the subject as suggested by Hover (see e.g. abstract).
Since Applicant’s response has not provided any additional further arguments the previous arguments have been addressed above.
Conclusion
No claim is 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
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JOSEPHINE GONZALES
Examiner
Art Unit 1631
/JOSEPHINE GONZALES/Examiner, Art Unit 1631
/JAMES D SCHULTZ/Supervisory Patent Examiner, Art Unit 1631