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
Applicants claim priority to a provisional application 62/951,523 is acknowledged. The effective filing date for claims 45, 119-120, and 122-124 is Dec. 20, 2019.
Claim Status
In response filed on June 6, 2025, Applicant have amended claims 45, 119, 123, filed new claims 129-130 and canceled claims 1-44, 46-118, 120-122, and 124-128.
Applicant election without traverse of Group I (Claims 45, 119-120, and 122-124) and species (A) inhaled therapeutics polypeptides and alpha-1-antitrypsin polypeptide SEQ ID NO: 3 in the reply filed on January 20, 2023, is acknowledged.
Currently, claims 45, 119, 123 and 129-130 are under examination in this application.
Withdrawn Objections & Rejections
Rejections and/or objections not reiterated from the previous office action are hereby withdrawn due to amendment.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.
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 45, 119, 123, and 129-130 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Gonda et al (U.S. Patent 7,244,714; of record cited IDS 8/4/23, previously presented), in view of Strom and Koulmanda (US2017/0190762A1, Application US15/317,136, hereinafter as “Strom”; previously presented), Glorioso et al (U.S. 2016/0153000 of record cited IDS 8/4/23, previously presented), Suk et al. (US2013/0323313A1, published 2013, previously presented), and Coffin et al. (KR100802403, published Feb 13, 2008, previously presented).
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 Jan. 21, 2026, 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 45, 119, and 129-130, Gonda discloses a pharmaceutical composition useful for delivering and expressing one or more polynucleotides encoding an inhaled therapeutic polypeptide to the airways of a subject (see e.g. abstract, col. 19-23, col. 22, lines 56-67, col. 27, lines 12-27, 49-58, col. 28, lines 20-27). Gonda discloses a replication-defective herpes simplex virus (HSV), comprising a recombinant HSV genome (see e.g. col. 22), wherein the recombinant HSV genome comprises the one or more polynucleotide encoding the inhaled therapeutic polypeptide (see e.g. col. 19-22, and esp. col. 22. lns. 31-42). Gonda discloses the use of devices which allows one to control aerodynamic particle size, such as nebulizers (see e.g. col. 15, esp. lines 12-17), with a pharmaceutically acceptable excipient (i.e. buffer)(see e.g. col. 27-28). Further, Gonda discloses wherein the inhaled therapeutic peptide is alpha-1-antityprsin (i.e. AAT)(see e.g. col 20, line 18).
Gonda does not explicitly state wherein the inhaled therapeutic peptide is alpha-1-antityprsin (i.e. AAT) has at least 95% sequence identity to an amino acid sequence SEQ ID NO: 3.
However, the prior art of Strom teaches an Alpha-1 antitrypsin (AAT) amino acid sequence (SEQ ID NO: 10; see .rapbn file; results Dec. 17, 2025, database: Published_Applications_AA_Main), which is an inhaled therapeutic polypeptide having 100% sequence identity to an amino acid sequence SEQ ID NO: 3 (see score alignment below).
[AltContent: textbox ([img-media_image1.png]
[img-media_image2.png])]Accordingly, it would have been obvious for one of ordinary skill in the art to prepare the pharmaceutical composition comprising a recombinant HSV as taught by Gonda and incorporate the alpha-1-antityprsin (i.e. AAT) sequence of SEQ ID NO: 3 (i.e. SEQ ID NO: 10) as taught by Strom because both Gonda and Strom disclose utilizing AAT as an inhaled therapeutic polypeptide (Gonda col. 19-22. and Strom para .101). A person of ordinary skill in the art would have a reasonable expectation of success because both disclose using AAT with viral vectors such as a herpes virus (Gonda col. 22 and Strom para. 83). Moreover, a person of ordinary skill in the art would have combined similar gene therapy techniques, which would have led to predictable results with a reasonable expectation of success. Furthermore, an artisan of ordinary skill in the art of (i.e. gene therapy) 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).
Gonda does not explicitly state wherein the herpes simplex virus (HSV) is HSV-1, has reduced toxicity compared to wild-type, where the HSV-1 genome does not comprise a polynucleotide encoding cystic fibrosis transmembrane conductance regulator (CFTR), and a vibrating mesh nebulizer, wherein the recombinant HSV-1 genome comprises an inactivating mutation in one or both copies of the Infected Cell Protein (ICP) 4 herpes simplex virus gene and an inactivating mutation in the ICP22 herpes simplex virus gene, wherein the recombinant HSV-1 genome does not comprise an inactivating mutation in an ICP27 herpes simplex virus gene.
However, the prior art of Glorioso discloses non-toxic HSV vectors for pharmaceutical compositions comprising the herpes simplex virus type 1 (HSV-1) that is modified to be non-toxic by inactivating mutations of essential immediate early genes (e.g. infected cell protein (ICP22))(see e.g. abstract, paras. 3-8, 16, 60-64, 71, 98, 104-106, Figures 1 and 9, claim 5, Example 1). Glorioso discloses vectors having deletions in the genes ICP0, ICP4, ICP22, ICP27 or ICP47, or alternative inactivating mutations (see e.g. abstract, Example 2-3, page 10). Further, Glorioso discloses wherein the replication-defective HSV-1 (i.e. J∆NI) has reduced cytotoxicity as compared to a corresponding wild-type HSV-1 (i.e. KOS) (see e.g. para. 14-19, Fig. 11-12). Further, Glorioso discloses growth of replication-defective HSV (i.e. JΔNI8 relative to JΔNI5) in complementing cells (U2OS-ICP4/27) after infection (see fig. 18 description), an inactivating deletion of the gene encoding infected cell proteins ICP0, ICP4, and a deletion of the promoter and start codon of the gene encoding ICP47 (see e.g. claim 21), corresponding to the claim limitation wherein the inactivating mutation in one or both copies of the ICP4 herpes simplex virus gene is a deletion of at least a portion of the coding sequence of the ICP4 herpes simplex virus gene, and wherein the recombinant HSV-1 genome further comprises an inactivating mutation in a herpes simplex virus gene selected from the group consisting of ICPO, ICP47. Although Glorioso discloses the embodiment of inactivation ICP27, the prior art of Aubert discloses that herpes simplex virus ICP27 is important for prevention apoptosis (see e.g. abstract, and p. 2812).
Accordingly, it would have been obvious to a person of ordinary skill in the art to have modified the pharmaceutical composition as taught by Gonda and substituted the HSV of Gonda and Tang with the HSV-1 as taught by Glorioso because Glorioso teaches the modified HSV-1 to be non-toxic with the inactivating mutations in essential immediate early genes (e.g. ICP22) (see e.g. paras. 3-8, 16, 104, 60, 98, 106]; Figures 1 and 9, claim 5). Thus, one ordinary skill in the art would have done so because Glorioso teaches an HSV-1 vector that has been modified to reduce its toxicity for gene therapy (see e.g. 0042, 0119), and Aubert discloses that herpes simplex virus ICP27 is important for prevention apoptosis (see e.g. abstract and p. 2812). A person of ordinary skill in the art would have a reasonable expectation of success because both Gonda and Glorioso disclose using herpes simplex virus as a vector for efficient gene delivery for therapeutic applications (see e.g. abstracts, respectively). Moreover, a person of ordinary skill in the art would have combined similar gene therapy techniques, which would have led to predictable results with a reasonable expectation of success. Furthermore, an artisan of ordinary skill in the art of (i.e. gene therapy) 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).
Glorioso discloses that that non-toxic HSV-1 vector may encode one or more prophylactically or therapeutically active proteins in relation to a lung disease. Although Glorioso gives the example of a transmembrane conductance regulator CFTR (see e.g. para. 76).
Nevertheless, the prior art of Strom discloses that Alpha 1-antitrypsin (AAT) compositions and treatments were known for treating a variety of inflammatory diseases including those associated with autoimmunity (e.g. chronic obstructive pulmonary diseases (COPD), diabetes, or graves’ disease)(see e.g. abstract, para. 21, and 114-115) which do not need a transmembrane conductance regulator CFTR.
Accordingly, it would have been obvious for a person of ordinary skill in the art to not have encoded CFTR for any patient with a lung disease, for example a patient with an autoimmune disorder with chronic obstructive pulmonary diseases (COPD). A person of ordinary skill in the art would not have had the recombinant HSV-1 genome encode anything additional to the patient (i.e. anything that the patient did not need for gene therapy). Therefore, it would have been obvious to a person of ordinary skill in the art to have modified the pharmaceutical composition as taught by Gonda and incorporated the HSV-1 as taught by Glorioso with no CFTR as suggested by Strom because Glorioso teaches a modified non-toxic HSV-1 for gene therapy (see e.g. Figures 1 and 9, claim 5). Thus, a person of ordinary skill in the art would have had a reasonable expectation of success. Furthermore, an artisan of ordinary skill in the art of (i.e. gene therapy) 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).
Gonda, Glorioso, and Strom et al., are silent regarding a vibrating mesh nebulizer.
However, the prior art of Suk discloses aerosolized pharmaceutical formulations can be delivered to the lungs, preferably using be a vibrating mesh nebulizer (see e.g. paras. 28, 172, 175, 179).
Accordingly, it would have been obvious to one of ordinary skill in the art to modify the method of Gonda with the vibrating mesh nebulizer as taught by Suk because Suk teaches that the vibrating mesh nebulizer is more effective because it applies a force to which breaks up the liquid formulation into smaller droplets (see e.g. paras. 28, 172, 175, 179). A person of ordinary skill in the art would be motivated to use the electromechanical driving force and improve the nebulizer as taught by Suk in order to generate small droplets as a form a slow moving aerosol stream which can be entrained in an inspiratory flow (see para. 177). Thus, it could have been done with a reasonable expectation of success.
Regarding claims 123, as stated supra, Gonda does not explicitly state wherein the herpes simplex virus (HSV) is HSV-1.
However, Glorioso et al, discloses a pharmaceutical wherein the herpes virus is herpes simplex virus type 1 (HSV-1) (e.g. para. 8, 16, 104, Figures 1 and 9).
Regarding claims 123, as stated supra, Glorioso teaches 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. para. 60, 98, and 106). Further, Glorioso teaches 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. para. 60, 0098, 0106).
Although Gonda teaches HSV and Glorioso teaches that the ICP22 HSV-1 is not to be expressed and teaches deletion of the regulatory region, they do not explicitly state a deletion in the coding region of the ICP22 HSV-1 gene.
However, the prior art of Coffin teaches a recombinant HSV-1 comprising a deletion in the coding region of the ICP22 HSV-1 gene (p. 13, 7th para. of translation).
Accordingly, it would have been obvious to prepare the pharmaceutical composition comprising an inactivated ICP22 HSV-1 gene as taught by Gonda and Glorioso and delete a coding region of the ICP22 HSV-1 gene as taught by Coffin because Coffin teaches that deletion of the coding region of ICP22 HSV-1 gene was a well-known and efficient method for inactivating the gene and would avoid possible expression through cryptic promoters or enhancers. Thus, a person of ordinary skill in the art would have had a reasonable expectation of success. Further, Glorioso discloses that the ICP22 HSV-1 gene should not be expressed, therefore a deletion of the coding gene would have been immediately apparent to one of ordinary skill in virology.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Response to Traversal:
Applicant argues a lack of prima facie case asserting that the combination of cited references (i.e. Gonda, Strom, Glorioso, Suk, and/or Coffin) fails to teach or suggest a pharmaceutical composition comprising a recombinant HSY-1 genome comprising an inactivating mutation in ICP4 and ICP22 without an inactivating mutation in ICP27 (remarks, p. 5-9).
Applicants’ arguments with respect to the previous rejection has been fully considered and are persuasive due to the amendments to the claims.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). As discussed above, the obviousness rejection has been amended to include the prior art of Aubert, which is cited for disclosing that a person of ordinary skill in the art would want ICP27 for preventing apoptosis in the cells (see e.g. abstract, and p. 2812).
Applicant asserts that Glorioso teaches or suggest inactivation mutation in ICP27 and that the prior art of Krisy et al., discloses that one of ordinary skill in the art would not be motivated to engineer an HSV vector having an inactivating mutation in ICP4, ICP22, and ICP27 (remarks. P. 7)
Applicants’ arguments with respect to the previous rejection has been fully considered and are persuasive due to the amendments to the claims.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Applicant is reminded that preferred embodiments are not the only teaching of a reference. “The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain.” In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989). As discussed above, Glorioso is no longer cited for teaching ICP27 and the prior art of Aubert is cited for disclosing that a person of ordinary skill in the art would want ICP27 for preventing apoptosis in the cells (see e.g. abstract, and p. 2812).
Contrary to Applicants assertion the statement regarding Krisy et al., disclosing that “Notably, the DHZ.l HSY vector of Krisky, having an inactivating mutation in ICP4 and ICP22, was more toxic than viruses deleted for three IE genes (e.g. ICP4, ICP22, and ICP27) (see Krisky at page 1599 column 2), would be motivation for a person of ordinary skill in the art to want to keep the three IE genes because without them the virus is more toxic.
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.
Conclusion
No claim is allowed.
Applicants’ 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPHINE GONZALES whose telephone number is (571)272-1794. The examiner can normally be reached M-Th: 10AM - 5:00PM (EST).
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Josephine Gonzales PhD
Examiner
Art Unit 1638
/JOSEPHINE GONZALES/ Examiner, Art Unit 1638
/Tracy Vivlemore/ Supervisory Primary Examiner, Art Unit 1638
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