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 .
Response to Arguments
The Amendment filed 04/15/2026 in which claims 1 and 17 were amended has been entered. Claims 2 and 3 have been cancelled.
Claims 1, 4, 5, 7 – 15, and 17 – 22 are under examination on the merits.
This Action is made NON-FINAL
Nucleotide and/or Amino Acid Sequence Disclosures
(New objection)
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
I. Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
The file must be submitted in bytes not kilobytes.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
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.
(New rejection) Claims 1, 17, and 18 is rejected under 35 U.S.C. 103 as being unpatentable over Stasakova et al. (Journal of General Virology, 2005, DOI10.1099/vir.0.80422-0, hereinafter, “Stasakova”), as evidenced by Sachet et al (US20090123495A1, hereinafter, “Sachet”) and Saavedra-Montanez et al (BLAST direct submission, 2018, hereinafter, “Saavedra-Montanez”).
Stasakova teaches modified influenza a viruses (IAVs) with mutations to the NS1 protein (Abstract). Stasakova also teaches NS1 mutants that lack or possess nonfunctional RNA binding domains while retaining effector domain functionality (Abstract, Figure 1). Stasakova teaches that NS1 functionality greatly influences cytokine response patterns (Abstract).
Regarding claim 1, Stasakova teaches a replication deficient influenza virus that induces type 1 IFN (Figure 3, Section: NS1 protein is required for virus replication in primary human macrophages). Stasakova also teaches that the virus is comprised of a NS1 protein that is truncated from amino acids 40-80 that does not have a functional RNA binding domain but retains a functional effector domain (Figure 1, reproduced below, Abstract, Section: NS1 mutant viruses induce two different cytokine patterns in primary human macrophages).
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Stasakova does not teach the exact amino acid sequence of the modified NS1 protein.
However, Sachet evidences apathogenic virus compositions that can alter interferon pathways (Abstract). Sachet evidences viruses with mutated NS1 proteins (Claim 42). Sachet evidences a full-length amino acid sequence of NS1 that is 100% identical to the full-length amino sequence of NS1 recited by the instant application (Reproduced below, “Qy” is SEQ ID NO: 1 - NS1, “Db” is Sachet).
RESULT 1
US-12-063-388A-4
(NOTE: this sequence has 15 duplicates in the database searched)
Sequence 4, US/12063388A
Publication No. US20090123495A1
GENERAL INFORMATION
APPLICANT: SACHET, MONIKA
APPLICANT: BERGMANN, MICHAEL
APPLICANT: MUSTER, THOMAS
APPLICANT: EGOROV, ANDREJ
TITLE OF INVENTION: IMMUNE RESPONSE INDUCING PREPARATIONS
FILE REFERENCE: SONN:121US
CURRENT APPLICATION NUMBER: US/12/063,388A
CURRENT FILING DATE: 2009-01-12
PRIOR APPLICATION NUMBER: PCT/AT2006/000335
PRIOR FILING DATE: 2006-08-08
PRIOR APPLICATION NUMBER: A 1332/2005
PRIOR FILING DATE: 2005-08-08
NUMBER OF SEQ ID NOS: 4
SEQ ID NO 4
LENGTH: 230
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic peptide
Query Match 100.0%; Score 1171; Length 230;
Best Local Similarity 100.0%;
Matches 230; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MDPNTVSSFQVDCFLWHVRKRVADQELGDAPFLDRLRRDQKSLRGRGSTLGLDIETATRA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MDPNTVSSFQVDCFLWHVRKRVADQELGDAPFLDRLRRDQKSLRGRGSTLGLDIETATRA 60
Qy 61 GKQIVERILKEESDEALKMTMASVPASRYLTDMTLEEMSRDWSMLIPKQKVAGPLCIRMD 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GKQIVERILKEESDEALKMTMASVPASRYLTDMTLEEMSRDWSMLIPKQKVAGPLCIRMD 120
Qy 121 QAIMDKNIILKANFSVIFDRLETLILLRAFTEEGAIVGEISPLPSLPGHTAEDVKNAVGV 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 QAIMDKNIILKANFSVIFDRLETLILLRAFTEEGAIVGEISPLPSLPGHTAEDVKNAVGV 180
Qy 181 LIGGLEWNDNTVRVSETLQRFAWRSSNENGRPPLTPKQKREMAGTIRSEV 230
||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 LIGGLEWNDNTVRVSETLQRFAWRSSNENGRPPLTPKQKREMAGTIRSEV 230
Accordingly, a deletion of amino acids 40-80 (highlighted in red in Result 1) would lead to a sequence of MDPNTVSSFQVDCFLWHVRKRVADQELGDAPFLDRLRRDMASVPASRYLTDMTLEEMSRD
WSMLIPKQKVAGPLCIRMDQAIMDKNIILKANFSVIFDRLETLILLRAFTEEGAIVGEISPLPSLPGHTAEDVKNAVGVLIGGLEWNDNTVRVSETLQRFAWRSSNENGRPPLTPKQKREMAGTIRSEV, which has a 100% sequence identity to instant SEQ ID NO: 11 (shown below, Sequence1 is SEQ ID NO: 11, Sequence2 is truncated 40-80 NS1 from Stasakova based on the full length NS1 sequence evidenced by Sachet).
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347
775
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Stasakova teaches a truncated NS1 protein with a non-functional RBD and a functional effector domain (Figure 3, reproduced above). Stasakova also teaches the deletion of amino acids 40 – 80 of the NS1 protein (Figure 3 - see PR8/NS1del40-80, reproduced above). Stasakova fails to teach the exact sequence of the modified NS1 protein. However, one of ordinary skill in the art would readily come to the sequence of instant SEQ ID NO: 11 given that the NS1 protein sequence is known (as evidenced by Sachet). Together, one would be able to reasonably conclude that the deletion of amino acids 40 – 80 taught by Stasakova would result in instant SEQ ID NO: 11.
Regarding claim 17 and 18, Saavedra-Montanez evidences the nucleic acid sequence for influenza a virus segment 8 which encodes NEP, NS1, and NS2. This sequence has an 86.2% identity to SEQ ID NO: 12 (Reproduced below, “Qy” is SEQ ID NO: 12, “Db” is Saavedra-Montanez.
RESULT 2
NASEQ2_06172026_202833
Query Match 82.5%; Score 633; DB 1; Length 900;
Best Local Similarity 86.2%;
Matches 766; Conservative 0; Mismatches 0; Indels 123; Gaps 1;
Qy 1 AGCAAAAGCAGGGTGACAAAGACATAATGGATCCAAACACTGTGTCAAGCTTTCAGGTAG 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 AGCAAAAGCAGGGTGACAAAGACATAATGGATCCAAACACTGTGTCAAGCTTTCAGGTAG 60
Qy 61 ATTGCTTTCTTTGGCATGTCCGCAAACGAGTTGCAGACCAAGAACTAGGTGATGCCCCAT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ATTGCTTTCTTTGGCATGTCCGCAAACGAGTTGCAGACCAAGAACTAGGTGATGCCCCAT 120
Qy 121 TCCTTGATCGGCTTCGCCGAGAT------------------------------------- 143
|||||||||||||||||||||||
Db 121 TCCTTGATCGGCTTCGCCGAGATCAGAAATCCCTAAGAGGAAGGGGCAGCACCCTCGGTC 180
Qy 144 ------------------------------------------------------------ 143
Db 181 TGGACATCGAGACAGCCACACGTGCTGGAAAGCAGATAGTGGAGCGGATTCTGAAAGAAG 240
Qy 144 --------------------------ATGGCCTCTGTACCTGCGTCGCGTTACCTAACTG 177
||||||||||||||||||||||||||||||||||
Db 241 AATCCGATGAGGCACTTAAAATGACCATGGCCTCTGTACCTGCGTCGCGTTACCTAACTG 300
Qy 178 ACATGACTCTTGAGGAAATGTCAAGGGACTGGTCCATGCTCATACCCAAGCAGAAAGTGG 237
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 ACATGACTCTTGAGGAAATGTCAAGGGACTGGTCCATGCTCATACCCAAGCAGAAAGTGG 360
Qy 238 CAGGCCCTCTTTGTATCAGAATGGACCAGGCGATCATGGATAAGAACATCATACTGAAAG 297
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 CAGGCCCTCTTTGTATCAGAATGGACCAGGCGATCATGGATAAGAACATCATACTGAAAG 420
Qy 298 CGAACTTCAGTGTGATTTTTGACCGGCTGGAGACTCTAATATTGCTAAGGGCTTTCACCG 357
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 CGAACTTCAGTGTGATTTTTGACCGGCTGGAGACTCTAATATTGCTAAGGGCTTTCACCG 480
Qy 358 AAGAGGGAGCAATTGTTGGCGAAATTTCACCATTGCCTTCTCTTCCAGGACATACTGCTG 417
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 AAGAGGGAGCAATTGTTGGCGAAATTTCACCATTGCCTTCTCTTCCAGGACATACTGCTG 540
Qy 418 AGGATGTCAAAAATGCAGTTGGAGTCCTCATCGGGGGACTTGAATGGAATGATAACACAG 477
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 AGGATGTCAAAAATGCAGTTGGAGTCCTCATCGGGGGACTTGAATGGAATGATAACACAG 600
Qy 478 TTCGAGTCTCTGAAACTCTACAGAGATTCGCTTGGAGAAGCAGTAATGAGAATGGGAGAC 537
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 TTCGAGTCTCTGAAACTCTACAGAGATTCGCTTGGAGAAGCAGTAATGAGAATGGGAGAC 660
Qy 538 CTCCACTCACTCCAAAACAGAAACGAGAAATGGCGGGAACAATTAGGTCAGAAGTTTGAA 597
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 CTCCACTCACTCCAAAACAGAAACGAGAAATGGCGGGAACAATTAGGTCAGAAGTTTGAA 720
Qy 598 GAAATAAGATGGTTGATTGAAGAAGTGAGACACAAACTGAAGATAACAGAGAATAGTTTT 657
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 GAAATAAGATGGTTGATTGAAGAAGTGAGACACAAACTGAAGATAACAGAGAATAGTTTT 780
Qy 658 GAGCAAATAACATTTATGCAAGCCTTACATCTATTGCTTGAAGTGGAGCAAGAGATAAGA 717
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 GAGCAAATAACATTTATGCAAGCCTTACATCTATTGCTTGAAGTGGAGCAAGAGATAAGA 840
Qy 718 ACTTTCTCGTTTCAGCTTATTTAATAATAAAAAACACCCTTGTTTCTAC 766
|||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 ACTTTCTCGTTTCAGCTTATTTAATAATAAAAAACACCCTTGTTTCTAC 889
The missing portions of Saavedra-Montanez corresponds to the 41 amino acid deletion taught by Stasakova. Accordingly, a deletion of amino acids 40-80 (bolded text in Result 1) would lead to a nucleic acid sequence of SEQ ID NO: 12 (Amino acid to nucleic acid translation of deleted 40 amino acids below).
RESULT 3
NASEQ2_06172026_160605
Alignment Scores:
Length: 123
Score: 196.00 Matches: 41
Percent Similarity: 100.0% Conservative: 0
Best Local Similarity: 100.0% Mismatches: 0
Query Match: 100.0% Indels: 0
DB: 1 Gaps: 0
AASEQ1_06172026_160538 (1-41) x NASEQ2_06172026_160605 (1-123)
Qy 1 GlnLysSerLeuArgGlyArgGlySerThrLeuGlyLeuAspIleGluThrAlaThrArg 20
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 CAGAAATCCCTAAGAGGAAGGGGCAGCACCCTCGGTCTGGACATCGAGACAGCCACACGT 60
Qy 21 AlaGlyLysGlnIleValGluArgIleLeuLysGluGluSerAspGluAlaLeuLysMet 40
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GCTGGAAAGCAGATAGTGGAGCGGATTCTGAAAGAAGAATCCGATGAGGCACTTAAAATG 120
Qy 41 Thr 41
|||
Db 121 ACC 123
In view of the foregoing, all the claimed limitations are found in one reference and are taught to be optional variations to a ‘base’ method they exemplify. As such, the claimed invention is within the scope of Stasakova, and thus Stasakova renders the invention prima facie obvious. The rationale to support this conclusion of obviousness is that Stasakova provides a teaching, suggestion, and motivation to substitute different variables disclosed within the reference. Furthermore, there is no evidence on the record that indicates that the claimed virus exhibits any unexpected results compared to the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
(New rejection) Claims 4, 5, 12, 13, and 20 – 22 are rejected under 35 U.S.C. 103 as being unpatentable over Stasakova as applied to claims 1, 17, and 18 above, and in view of Wolschek et al. (US20100136052A1, hereinafter, “Wolschek”).
As discussed above, claims 1, 17, and 18 were rendered prima facie obvious by the teachings of Stasakova.
While the reference teaches a replicant deficient IAV with a truncated NS1 protein that retains effector domain function and lacks a functional RNA binding domain, the reference fails to further teach modified viral segments, a composition comprising an IAV with a pharmaceutically acceptable carrier formulated for local or systemic administration.
However, Wolschek teaches a replicant deficient influenza virus comprising a modified NS1 protein lacking a functional RNA binding domain (Abstract). Wolschek also teaches that this virus can have modifications of at least one amino acid within positions 1 – 73 (Claim 1). Wolschek also teaches modifications to influenza virus beyond the NS1 protein (¶0131). Wolschek teaches that this virus can be used as a vector to express proteins in subjects (Abstract).
Regarding claim 4, Wolschek teaches PA, PB1, PB2, HA, NA, M and NP segments derived from Vero-cell adapted influenza A H1N1 virus strain (GHB01) that are cloned into the truncated NS1 IAV (¶0131).
Regarding claim 5, Wolschek teaches a pharmaceutically acceptable carrier that can be used in a preparation (¶0111).
Regarding claims 12 and 13 Wolschek teaches using an inhaler to deliver the truncated NS1 influenza A virus with an aerosolizing agent (¶0109).
Regarding claims 20, 21, and 22 Wolschek teaches systemic administration of the truncated NS1 influenza A virus using an inhaler or nebulizer (¶0109).
Stasakova and Wolschek are considered to be analogous to the claim invention because they both teach modified IAVs with truncated NS1 regions. Stasakova teaches NS1 mutants that lack or possess nonfunctional RNA binding domains while retaining effector domain functionality (Abstract, Figure 1). Wolschek teaches preparations and compositions comprising IAV with modified viral segments and pharmaceutically acceptable carriers that can be delivered locally or systemically with nebulizers (¶0131, 0111, 0109).
Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to insert the modified NS1 protein that retains function of the effector domain and a nonfunctional RNA binding domain, as taught by Stasakova, in a composition comprising virus with modified viral segment and pharmaceutically acceptable aerosolizing agents, as taught by Wolschek, because doing so would advantageously deliver replicant deficient virus that induce an IFN in a subject. One of ordinary skill in the art would have had a reasonable expectation of success of using a truncated NS1 IAV with modified viral segment along with pharmaceutically acceptable aerosolizing agents to deliver the treatment given that this method was well known, has been successfully demonstrated, and commonly used as evidenced by the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
(New rejection) Claims 7, 14, 15, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Stasakova as applied to claims 1, 4, 5, 12, 13, 17, 18, and 20 – 22 above, and further in view of Martinez-Sobrido et al. (US20200206341A1, hereinafter, "Martinez-Sobrido").
As discussed above, claims 1, 4, 5, 12, 13, 17, 18, and 20 – 22 were rendered prima facie obvious by the teachings of Stasakova.
While the references teach a replicant deficient IAV with a truncated NS1 protein that retains effector domain function and lacks a functional RNA binding domain along with other modified viral segments in a composition further comprising a pharmaceutically acceptable carrier formulated for local or systemic administration, the reference fails to teach a prophylactic or therapeutic treatment of an infection caused by IFN-sensitive viruses by a truncated NS1 IAV combined with an active substance, or to a subject, which can be a human, dog, cat, horse, camelid, cow or pig, who is at risk of infection from an IFN-sensitive virus.
However, regarding claims 7 and 19, Martinez-Sobrido teaches the use of a canine influenza virus (CIV), a member of the influenza A virus family, comprising a truncated NS1 region as a treatment and preventive measure against the IFN-sensitive CIV in dogs (Figure 7).
Regarding claims 14 and 15, Martinez-Sobrido teaches the administration of truncated NS1 IAV and a biologically active agent delivered nasally to dogs (¶0119, 0126, 0131).
Stasakovaand Martinez-Sobrido are considered to be analogous to the claim invention because they teach modified IAVs with truncated NS1 regions. Stasakova teaches NS1 mutants that lack or possess nonfunctional RNA binding domains while retaining effector domain functionality (Abstract, Figure 1). Martinez-Sobrido teaches a prophylactic or therapeutic treatment of an infection caused by IFN-sensitive viruses by a truncated NS1 IAV combined with an active substance, or to a subject, which can be a human, dog, cat, horse, camelid, cow or pig, who is at risk of infection from an IFN-sensitive virus (Figure 7, ¶0119, 0126, 0131).
Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to insert the modified NS1 protein that retains function of the effector domain and a nonfunctional RNA binding domain in a composition comprising virus with modified viral segment, as taught by Stasakova, for a prophylactic or therapeutic treatment of an infection caused by IFN-sensitive viruses because doing so would advantageously permit prophylactic and therapeutic treatment for infections caused by IFN-sensitive viruses. One of ordinary skill in the art would have had a reasonable expectation of success of using a truncated NS1 IAV to treat IFN- sensitive viruses and related physiological symptoms and conditions associated with infection via intranasal delivery with other biologically active agents given that this method was well known, has been successfully demonstrated, and commonly used as evidenced by the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
(New rejection) Claims 8 - 9 are rejected under 35 U.S.C. 103 as being unpatentable over StasakovaMartinez-Sobrido, as applied to claims 1, 7, 14, 15, 17 and 19 above, and further in view of Chen et al. (US20190125858A1, hereinafter, “Chen”).
As discussed above, claims 1, 7, 14, 15, 17 and 19 were rendered prima facie obvious by the teachings of Stasakovaand Martinez-Sobrido.
While the using a truncated NS1 IAV to treat IFN- sensitive viruses and related physiological symptoms and conditions associated with infection, the references fail to teach the IFN-sensitive virus of interest can be a coronavirus, including MERS-CoV.
However, regarding claims 8 and 9, Chen teaches the use of truncated NS1 IAV as a prophylactic or therapeutic treatment, for the treatment of MERS-CoV, a coronavirus (¶0025).
Stasakova, Wolschek, Martinez-Sobrido, and Chen are considered to be analogous to the claim invention because they teach modified IAVs with truncated NS1 regions. Stasakova teaches NS1 mutants that lack or possess nonfunctional RNA binding domains while retaining effector domain functionality (Abstract, Figure 1). Martinez-Sobrido teaches a prophylactic or therapeutic treatment of an infection caused by IFN-sensitive viruses by a truncated NS1 IAV combined with an active substance, or to a subject, which can be a human, dog, cat, horse, camelid, cow or pig, who is at risk of infection from an IFN-sensitive virus (Figure 7, ¶0119, 0126, 0131). Chen teaches the use of truncated NS1 IAV as a prophylactic or therapeutic treatment, for the treatment of MERS-CoV, a coronavirus (¶0025).
Therefore, it would have been prima facie obvious before the effective filing date of the claimed invention to insert the modified NS1 protein that retains function of the effector domain and a nonfunctional RNA binding domain in a composition comprising virus with modified viral segment and pharmaceutically acceptable aerosolizing agents, as taught by Stasakova and Martinez-Sobrido, for a prophylactic or therapeutic treatment of an infection caused by IFN-sensitive viruses, as taught by Chen, with a reasonable expectation of success because doing so would advantageously permit prophylactic and therapeutic treatment for infections caused by IFN-sensitive viruses such as MERS-CoV and other SARS viruses. One of ordinary skill in the art would have had a reasonable expectation of success of using a truncated NS1 IAV to treat IFN- sensitive viruses such as MERS-CoV and other SARS viruses and related physiological symptoms and conditions associated with infection via intranasal delivery with other biologically active agents given that this method was well known, has been successfully demonstrated, and commonly used as evidenced by the prior art.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
(New rejection) Claims 10 - 11 are rejected under 35 U.S.C. 103 as being unpatentable over Stasakova, Martinez-Sobrido, and Chen as applied to claims 1, 7 - 9, 14, 15, 17 and 19 above, and further in view of Wu et al. (Nature, 2020, hereinafter “Wu”).
As discussed above, claims 1, 7 - 9, 14, 15, 17 and 19 were rendered prima facie obvious by the teachings of Stasakova,Martinez-Sobrido, and Chen. As further discussed above, Chen teaches the use of truncated NS1 IAV as a prophylactic or therapeutic treatment for the treatment of MERS-CoV, a coronavirus. Chen also teaches the use of truncated NS1 IAV to treat pneumonia caused or associated with MERS-CoV (Figure 12).
The references do not teach treatment of a condition caused by SARS-Cov-2. However, Wu teaches that SARS-CoV-2 is a SARS virus that shares many similarities with other virulent coronaviridae. It would have been prima facie obvious before the effective filing date of the claimed invention to modify Stasakova,Martinez-Sobrido, and Chen because doing so would advantageously permit prophylactic and therapeutic treatment for infections SARS-CoV2. It would have been obvious for one of ordinary skill in the art to apply truncated NS1 IAV treatment to SARS-CoV-2, an IFN- sensitive virus closely related to MERS-CoV and other SARS virus, and related physiological symptoms and conditions associated with infection given that this method is well known, has been successfully demonstrated, and commonly used in the prior art for SARS viruses.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 04/15/2026 have been fully considered while persuasive to overcome the 35 U.S.C. § 103 rejection of claims 1, 4, 5, 7 – 15, and 17 – 22 in the office action dated 12/18/2025, do not overcome the new grounds of rejection set forth above.
Applicant contends on page 5 of the Remarks: That Wolschek (US20100136052A1) teaches an influenza A virus with an engineered NS1 that lacks both the effector domain functionality and function of the RNA-binding domain. Instant claim 1 recites an influenza A virus with an engineered NS1 that retains the effector domain functionality and function of the RNA-binding domain. Additionally, Martinez-Sobrido, Chen, and Wu fail to provide the deficiencies of Wolschek.
In response: Examiner agrees that Wolschek, Martinez-Sobrido, Chen, and Wu fail to teach an influenza A virus with an engineered NS1 that retains the effector domain functionality and function of the RNA-binding domain. However, as discussed in detail above, the prior art teaches that an influenza A virus with an engineered NS1 that retains the effector domain functionality and function of the RNA-binding domain was well known has been successfully demonstrated, and commonly used in the prior art. As discussed above, Stasakova teaches deletion of amino acids 40 – 80 of the NS1 protein and teaches the resulting effects on cytokine responses within subjects. Stasakova teaches that by modulating cytokine response, the modified NS1 protein might stimulate a robust immune response leading to a protective effect from further viral infection (Section: PKR inhibitor prevents IL1β release and development of fast apoptosis in influenza A virus-infected macrophages ¶10). Stasakova also teaches that the modification of the NS1 protein can be used as a basis of a vaccine (Section: PKR inhibitor prevents IL1β release and development of fast apoptosis in influenza A virus-infected macrophages ¶10). Therefore, the invention described in claim 1 is obvious to one of ordinary skill of the art for the reasons discussed above.
Conclusion
NO CLAIMS ARE ALLOWED
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Danyal H Alam whose telephone number is (571)272-1102. The examiner can normally be reached M - F 9am - 5pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas J. Visone can be reached at 571-270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/DANYAL HASSAN ALAM/Examiner, Art Unit 1672
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672
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