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 .
Applicant’s amendment filed on December 23, 2023 is acknowledged. Claims 8-23 are pending and under examination in this Office action.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on December 23, 2025 has been considered by the examiner.
Claim Rejections - 35 USC § 112
Rejection of Claims 8-19 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in view of Applicant’s amendment.
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 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.
Rejection of Claims 8, 11, 12, 14, 17, and 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Palese et al. (US Patent 10,736,956) is maintained. New claims 20-23 are rejected under 35 U.S.C. 103 as being unpatentable over Palese et al. (US Patent 10,736,956).
Regarding new claims 20-23. Palese et al. teach a method of treating an influenza infection in a patient, including swine, poultry and birds comprising administering a vaccine comprising a recombinant vector capable of expressing a recombinant Influenza virus haemagglutinin (HA) stem polypeptide in the target and a pharmaceutically acceptable carrier; wherein said recombinant Influenza virus HA stem polypeptide comprises a headless Influenza virus HA stem domain, a trimerization domain, and a transmembrane domain (see claims 1-24, Examples 1-4, column 191, lines 28-67, column 182, lines 27-67, columns 180-181 and Figures 1-13 and figure description). It is noted that the limitations of present claims 22 and 23 are obvious and expected outcomes of the vaccination with the influenza vaccine. Claims 22 and 23 do not add any additional method steps.
Palese teaches n an exemplary embodiment, the non-influenza virus vector is a Newcastle disease virus (NDV). In another embodiment, the non-influenza virus vector is a vaccinia virus. In other exemplary, non-limiting, embodiments, the non-influenza virus vector is adenovirus, adeno-associated virus (AAV) (see paragraph 398).
Palese does not expressly teach that their target patient already has antibodies against an influenza virus.
It would have been prima facie obvious to the person of ordinary skill in the art to administer the influenza vaccine to a patient who has previously been vaccinated and/or infected with an influenza virus, and has influenza specific antibodies, because Palese teaches that influenza viruses are constantly undergoing change: every 3-5 years the predominant strain of influenza A virus is replaced by a variant that has undergone sufficient antigenic drift to evade existing antibody responses, thus isolates to be included in vaccine preparations must therefore be selected each year based on the intensive surveillance efforts of the World Health Organization (WHO) collaborating centers (see column 2, lines 26-54).
Thus, since Palese teach that influenza virus is constantly undergoing a change, and that the vaccine is recommended to be administered annually, it is apparent that a patient receiving an influenza vaccine already has antibodies to influenza virus from either previous vaccination and/or infection. It would therefore have been obvious to provide the method of Palese wherein the vaccine is administered to a patient who already has antibodies against an influenza virus.
Thus, the present invention would have been prima facie obvious at the time the invention was made.
Response to Applicant’s arguments.
Applicant argues that the pending claims are directed to a method of using a vaccine in target subjects, comprising a recombinant vector encoding a recombinant influenza virus HA stem polypeptide, where the influenza virus HA stem polypeptide comprises the three parts: (i) a headless Influenza virus HA stem domain, (ii) a trimerization domain, and (iii) a transmembrane domain, and where the subjects have antibodies to Influenza virus HA head domain at the time of vaccination.
Applicant argues that a key aspect of the invention is a method to vaccinate a target subject that has pre-existing' antibodies to Influenza virus HA head domain - i.e., antibody-positive target subjects, where the pre-existing antibodies may interfere with the efficiency of the influenza vaccine. This is highlighted in the present application at [0009] of the published application, which states:
"The vaccinated target human or animal may contain (maternally derived) antibodies against influenza resulting from a prior contact with the virus from a vaccination or a field-infection, either of the target itself, or of their mother. Applicant states that the pre-existing antibodies in the target are known to interfere with the efficacy of Influenza vaccination. This severely reduces the efficacy of Influenza vaccination of such antibody-positive targets, leaving them exposed tofield infections. Applicant states that no effective solution has been provided for this problem so far. "
Applicant argues that Prior to the present invention, this issue of overcoming pre-existing antibody interference and/or maternal derived antibodies (MDA) had not been achieved.
Applicant states that Palese discloses different forms of the HA antigen, such as, e.g., a headless HA antigen; a HA chimera (containing the head of one serotype, and the stem of another serotype); a stalk (stem); or a stalk fragment, Palese fails to disclose the claimed haemagglutinin (HA) stem polypeptide that comprises the headless influenza virus HA stem domain, (ii) a trimerization domain, and (iii) a transmembrane domain.
Applicant argues that even when Palese discloses a headless HA antigen, it lacks the transmembrane domain and the trimerization domain. See, e.g., FIG 8C. For these reasons alone, Palese fails to teach or suggest the claimed invention. As such, even at its broadest interpretation, Palese fails to teach or suggest the claimed method of administering a vaccine comprising a recombinant vector encoding the specific recombinant haemagglutinin (HA) stem polypeptide as currently claimed, irrespective of the target subject the vaccine is administered to.
Applicant argues that Palese is focused on using the different forms of HA antigens for use in combination with a neuraminidase (NA) antigen for broad immune protection, see, e.g., Col. 3 (lines 3-30), Col. 4 (line 45) and FIG. 8C, and Col. 30 (lines 51-70), and is focused on methods for humans. Specifically, Example 1 (Section 6.1) of Palese assesses the efficacy of NA antigens in mice, Example 2 (Section 6.2) describes the use of NA antigen in combination with a HA stalk antigen, but does not disclose any data. Example 3 (Section 6.3) discusses immunizing ferrets with a VSV vector expressing the chimeric HA (see Col. 229), and Experiment 4 (Section 6.4) relates to assessing chimeric HA in combination with NA antigens in ferrets.
Applicant argues that Palese does not teach or suggest that use of any of their disclosed forms of the HA antigen in a vaccine for use in a method of administering to a subject that has pre- existing antibodies to the influenza HA head domain, as required by the claims, and/or avoids interference in subjects that have pre-existing antibodies to Influenza virus HA head domain.
Thus, since Palese teach that influenza virus is constantly undergoing a change, and that the vaccine is recommended to be administered annually, it is apparent that a patient receiving an influenza vaccine already has antibodies to influenza virus from either previous vaccination and/or infection. It would therefore have been obvious to provide the method of Palese wherein the vaccine is administered to a patient who already has antibodies against an influenza virus.
In response, Examiner notes that Palese expressly teaches headless influenza virus HA stem domain a trimerization domain and the transmembrane domain.
Palese throughout the specification: “In certain embodiments, a chimeric influenza virus hemagglutinin polypeptide provided herein comprises a transmembrane domain. In embodiments where a chimeric influenza virus hemagglutinin polypeptide provided herein comprises a transmembrane domain, the transmembrane domain might be based on any influenza transmembrane domain known to those of skill in the art. In certain embodiments, the transmembrane domains are based on influenza A transmembrane domains. In certain embodiments, the transmembrane domains are based on a transmembrane domain of an influenza A hemagglutinin selected from the group consisting of H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16, H17, and H18. In certain embodiments, the transmembrane domain might be any transmembrane domain deemed useful to one of skill in the art. In certain embodiments, the transmembrane domain is selected from SEQ ID NOS:67-82. In certain embodiments, the transmembrane domains are from the same hemagglutinin as the stem domain. In certain embodiments, the transmembrane domains are from influenza virus strain or subtype as the stem domain HA2 subunit.
In certain embodiments, provided herein are influenza hemagglutinin short stem domain polypeptides consisting of an HA1 N-terminal stem segment covalently linked to a linker, in turn covalently linked to an HA1 C-terminal short stem segment in binding association with an HA2 stem domain that is covalently linked to an HA2 luminal domain that is in turn covalently linked to an HA2 transmembrane domain. In certain embodiments, provided herein are influenza hemagglutinin short stem domain polypeptides consisting of an HA1 N-terminal stem segment covalently linked to a linker, in turn covalently linked to an HA1 C-terminal short stem segment, in turn covalently linked to an HA2 stem domain that is covalently linked to an HA2 luminal domain that is in turn covalently linked to an HA2 transmembrane domain. In certain embodiments, provided herein are influenza hemagglutinin short stem domain polypeptides consisting of a signal peptide covalently linked to an HA1 N-terminal stem segment covalently linked to a linker, in turn covalently linked to an HA1 C-terminal short stem segment, in turn covalently linked to an HA2 stem domain that is covalently linked to an HA2 luminal domain that is in turn covalently linked to an HA2 transmembrane domain.
Claim 12. The vaccine formulation of claim 1, wherein the first chimeric HA further comprises the H1 influenza virus HA transmembrane and cytoplasmic domains, the second chimeric HA further comprises the H3 influenza virus HA transmembrane and cytoplasmic domains, and the third chimeric HA further comprises the influenza B virus transmembrane and cytoplasmic domains.
Claim 17. The vaccine formulation of claim 11, wherein the first chimeric HA further comprises the H1 influenza virus HA transmembrane and cytoplasmic domains, the second chimeric HA further comprises the H3 influenza virus HA transmembrane and cytoplasmic domains, and the third chimeric HA further comprises the influenza B virus transmembrane and cytoplasmic domains.
In certain embodiments, provided herein are influenza hemagglutinin stem domain polypeptides consisting of an HA1 N-terminal stem segment covalently linked to a linker, in turn covalently linked to an HA1 C-terminal stem segment in binding association with an HA2 stem domain that is covalently linked to, in sequence, a protease cleavage site, a trimerization domain, and a purification tag. In certain embodiments, provided herein are influenza hemagglutinin stem domain polypeptides consisting of an HA1 N-terminal stem segment covalently linked to a linker, in turn covalently linked to an HA1 C-terminal stem segment, in turn covalently linked to an HA2 stem domain that is covalently linked to, in sequence, a cleavage site, a trimerization domain and a purification tag. In certain embodiments, provided herein are influenza hemagglutinin stem domain polypeptides consisting of a signal peptide covalently linked to an HA1 N-terminal stem segment covalently linked to a linker, in turn covalently linked to an HA1 C-terminal stem segment, in turn covalently linked to an HA2 stem domain that is covalently linked to, in sequence, a protease cleavage site, a trimerization domain and a purification tag.
Contrary to Applicant’s assertion, Palese discloses a method of treating an influenza infection in a patient, including swine, poultry and birds comprising administering a vaccine comprising a recombinant vector capable of expressing a recombinant Influenza virus haemagglutinin (HA) stem polypeptide in the target and a pharmaceutically acceptable carrier; wherein said recombinant Influenza virus HA stem polypeptide comprises a headless Influenza virus HA stem domain, a trimerization domain, and a transmembrane domain.
Palese teach that influenza virus is constantly undergoing a change, and that the vaccine is recommended to be administered annually, it is apparent that a patient receiving an influenza vaccine already has antibodies to influenza virus from either previous vaccination and/or infection. It would therefore have been obvious to provide the method of Palese wherein the vaccine is administered to a patient who already has antibodies against an influenza virus.
Thus, in view of the foregoing the rejection is maintained.
Conclusion
SEQ ID NO: 4, 6, 8, 10 and 12 are free of prior art.
Contact Information
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AGNIESZKA BOESEN whose telephone number is (571)272-8035. The examiner can normally be reached on 8:30 - 5:00 PM.
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/AGNIESZKA BOESEN/Primary Examiner, Art Unit 1648
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