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 Amendment
The amendment filed 01 May 2026 I which claims 1, 3, 17, 23, and 31 were amended, claim 16 was cancelled, and claim 34 was added has been entered.
Claims 1, 3-14, 17-18, 21, 23, 27, 29, 31-32, and 34 are under examination on the merits.
Specification
(Previous objection, withdrawn). Applicant’s amendments to the Specification submitted 01 May 2026 have overcome the objection previously set forth in the Non-Final Office Action.
Drawings
(Previous objection, withdrawn). Applicant’s amendments to the Drawings submitted 01 May 2026 have overcome the objection previously set forth in the Non-Final Office Action.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
(new rejection, necessitated by amendment to claim 1) Claims 6-7 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 6 recites that the HA stem polypeptide is presented on a protein nanoparticle, but claim 1 recites that the protein must be ferritin, so the limitation of a protein nanoparticle is broader than the limitation of a ferritin nanoparticle on which it depends.
Claim 7 recites that the HA stem polypeptide is presented on a ferritin nanoparticle, but claim 1 already includes the ferritin nanoparticle as a limitation, so the limitation does not appear to further limit the claimed invention.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112(a)
Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
(Previous rejection, maintained as to claims 1, 3-14, 17, 21, 23, 27, 29, and 31-32, withdrawn as to claim 16 due to cancellation of the claim, and extended to newly added claim 34 as set forth below). Claims 1, 3-14, 17, 21, 23, 27, 29, 31-32, and 34 are rejected 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. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus. See, e.g., Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010); University of California v. Eli Lilly & Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) at 1406; Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021) ("[T]he written description must lead a person of ordinary skill in the art to understand that the inventor possessed the entire scope of the claimed invention. Ariad, 598 F.3d at 1353–54 ('[T]he purpose of the written description requirement is to ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor's contribution to the field of art as described in the patent specification.' (internal quotation marks omitted).").
A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). The issue is whether the skilled artisan would understand inventor to have invented, and been in possession of, the invention as claimed.
The Federal Circuit has clarified the application of the written description requirement to inventions in the field of biotechnology. See University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568,43 USPQ2d l398, 1406 (Fed. Cir. 1997). The Court stated that a written description of an invention requires a precise definition, one that defines the structural features of the chemical genus that distinguishes it from other chemical structures. A definition by function does not suffice to define the genus because it is only an indication of what the genus does, rather than what it is. Further, the Court held that to adequately describe a claimed genus, an applicant must describe a representative number of species of the claimed genus, and that one of skill in the art should be able to “visualize or recognize the identity of the members of the genus.”
Instant claims 1, 3-14, 17, 21, 23, 27, 29, 31-32, and 34 broadly encompasses an immunogenic composition comprising at least one isolated influenza HA stem polypeptide. An immunogenic composition inherently requires the function of immune stimulation/modulation.
Instant claim 17 further recites that the isolated influenza HA stem polypeptide has at least 90% identity, 95% identity, 98% identity, or 99% identity with SEQ ID NOs 1-4.
The Specification defines an ‘isolated influenza HA stem polypeptide’ a polypeptide comprising a full-length influenza HA stem region or an immunogenic fragment or variant of an influenza HA stem region (pg. 6 lines 29-33).
The Specification has failed to sufficiently describe the structural features that must be retained by the members of the claimed genus as to establish a structure-function relationship with respect to the vaccine and immune stimulation.
“[A]t least one isolated influenza HA stem polypeptide” encompasses a large pool of variant polypeptides when accounting for immunogenic fragments and variants and the Specification does not adequately describe the necessary epitope that must remain for the fragments and variants to be immunogenic.
An amino acid sequence having at least 90% identity with SEQ ID NOs: 1-4 encompasses a large pool of variant polypeptides when allowing for changes of up to 10% of the amino acid residues.
While the instant claims are drawn to a genus that comprises innumerable permutations of sequences and HA stem polypeptides, the Specification has only adequately described and successfully reduced to practice specific sequences/HA stem polypeptides, SEQ ID NOs: 1-4, 6-9, and 13-16. As such, the Specification reasonably demonstrates that Applicant was in possession of vaccine compositions consisting of SEQ ID NOs: 1-4, 6-9, and 13-16. However, this is not representative of the extremely large genus of sequences/HA stem polypeptides claimed since these sequences only encompass 4 flu strains and not the innumerable sequences contained within a genus of sequences comprising up to 10% of amino acid substitutions and within a genus of HA stem polypeptides comprising the innumerable fragments and variants thereof.
The data generated for SEQ ID NOs: 1-4, 6-9, and 13-16 described in the Specification cannot reasonably be extrapolated and applied to support possession of the entire claimed genus of variants and fragments because no one species, combination, or variant accounts for the variability amongst the claimed genus. As in Ariad, merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials consisting the genus and showing that one has invented a genus and not just a species. “A patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.” Brenner v. Manson, 383 U.S. 519, 536 (1966).
Gomez Lorenzo provides a review of the state of the art in influenza HA stem vaccines. Influenza vaccine that use the HA stem region do not use portions of this region, rather the intact HA stem region is used (Steps Toward Development of a Universal Influenza Vaccine, pg. 505 column 2). While Applicant may have described fragments or variants of these proteins, as the fragments/variants have not been shown to be immunogenic, these fragments would not reasonably be considered an immunogenic composition.
Accordingly, the claims as currently written are not adequately described and one of skill in the art would readily appreciate that Applicant was not in possession of the claimed genus at the time of filing.
Claim Rejections - 35 USC § 102
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
(Previous rejection, maintained and modified as to claims 1, 3-4, 6-14, 17-18, 21, 23, 27, 29, and 31 necessitated by amendment of claims 1, 3, and 31, withdrawn as to claim 16 due to cancellation of the claim, and extended to newly added claim 34 as set forth below). Claims 1, 3-4, 6-14,17-18, 21, 23, 27, 29, 31, and 34 are rejected under 35 U.S.C. 102 (a)(1) and a(2) as being anticipated by Nabel.
(modified) Regarding claim 1, Nabel discloses an antigenic influenza-ferritin polypeptide, which is defined as a molecule comprising a ferritin an influenza polypeptide where the ferritin and polypeptide are fused and the molecule is antigenic (¶0079) at comprises at least one isolated influenza HA stem polypeptide and at least one ferritin nanoparticle subunit and the linker SGG which connects the two (SEQ ID NO: 43, Table 1, ¶0061, and Figure 25A-C). Nabel further discloses that the antigenic influenza-ferritin polypeptide can be formulated with squalene-based adjuvant (AF03) and used as a vaccine (¶0061).
(modified) Regarding claim 3, Nabel discloses administering (¶0061) the HA stem polypeptide which is linked to a ferritin nanoparticle subunit by the linker SGG (SEQ ID NO: 43) and squalene (AF03) adjuvant vaccine to Cynomolgus Macaques to elicit an immune response (¶0061 and Figure 25A-C)
(maintained) Regarding claim 4, Nabel discloses that the stem polypeptides are engineered stabilized stem antigens (¶0028).
(maintained) Regarding claims 6-10, Nabel discloses that the HA stem polypeptide is presented on a ferritin nanoparticle, where the ferritin is H. pylori ferritin or Trichoplusia ferritin (¶0068, ¶0071, ¶0053).
(maintained) Regarding claims 11-12, Nabel discloses that the composition is composed of two different Influenza A proteins, selected from H1, H3, H7, and H10 (¶0028).
(maintained) Regarding claims 13-14, Nabel discloses a single nanoparticle with the first HA stem fused with an insect ferritin heavy chain and a second HA stem fused with an insect ferritin light chain (¶00107 and ¶00111-00112)
(maintained) Regarding claims 17-18, Nabel discloses SEQ ID NO: 43 which comprises an amino acid sequence with 100% identity to instant SEQ ID NO: 1 (SEQ ID NO: 43).
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(maintained and new for 34) Regarding claims 21, 23, 27, 29, and 34 Nabel discloses using the AS03 adjuvant (¶0208). AS03 consists of squalene, DL-α-tocopherol, and 4.86 mg of polysorbate 801 as evidenced by Yam. (pg. 2 column 1).
(modified) Regarding claim 31, Nabel discloses administering (¶0061) the HA stem polypeptide which is linked to a ferritin nanoparticle subunit by the linker SGG (SEQ ID NO: 43) and squalene (AF03) adjuvant vaccine to Cynomolgus Macaques to elicit an immune response that is 2-fold higher than the immune response to the vaccine without the adjuvant (¶0061 and Figure 25A-C).
Accordingly, Nabel anticipates the claimed inventions.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
(Previous rejection, maintained as to claim 5). Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Nabel as applied to claims 1, 3-4, 6-14, 17-18, 21, 23, 27, 29, 31, and 34 above, and further in view of Impagliazzo.
(Previous rejection, maintained as to claim 32). Claim 32 is rejected under 35 U.S.C. 103 as being unpatentable over Nabel as applied to claims 1, 3-4, 6-14, 17-18, 21, 23, 27, 29, 31, and 34 above, and further in view of Ruecki and Godeaux.
Response to Arguments
Applicant contends on pages 9-13 of the Remarks submitted on 01 May 2026 that the claimed invention is directed towards a particular fusion protein and that one skill in the art would understand that the present claims are directed to a defined genus of a specific fusion protein.
In response: The instant Specification defines an ‘isolated influenza HA stem polypeptide’ as a polypeptide comprising a full-length influenza HA stem region or an immunogenic fragment or variant of an influenza HA stem region (pg. 6 lines 29-33). A fragment or variant of the HA stem region is a large genus with innumerable permutations and the Specification does not further define the amino acids that must remain to maintain the structure-function relationship between the HA stem polypeptide and the immunogenicity of the peptide. (see 112 rejection above for further clarification). The rejection is maintained.
Applicant contends on pages 13-14 of the Remarks submitted on 01 May 2026 that that Nabel does not disclose a fusion protein having at least one isolated influenza HA stem polypeptide with at least one ferritin nanoparticle subunit and connected with the recited linkers with a squalene adjuvant.
In response: Nabel does disclose a fusion protein having at least one isolated influenza HA stem polypeptide with at least one ferritin nanoparticle subunit and connected with the recited linkers with a squalene adjuvant. (See claim 1 rejection above)
Conclusion
NO CLAIMS ARE ALLOWED
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 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 Cassandra Senn Grizer whose telephone number is (571)272-2292. The examiner can normally be reached M-Th 0630 - 1700 ET.
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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.
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/CASSANDRA SENN GRIZER/Examiner, Art Unit 1672
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672
1 For claim 27, Examiner is interpreting consists essentially of following guidelines laid out in MPEP 2111.03. Adding D/L-α-tocopherol to the squalene emulsion adjuvant does not materially affect the basic and novel characteristics of the adjuvant as claimed.
Prosecution Insights