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
Acknowledgment is made of Applicants’ claim for benefit to prior filed US provisional application 63/162,063 (filed on 17 March 2021).
Election/Restriction
Applicant’s election with traverse of Group I, corresponding to claims 1-2, 4, 8, 12, 14-15, 17-20, 24-25, and 29 and SEQ ID No: 101 in claim 14, Dengue virus in claim 15, and SEQ ID NO: 116 in claim 17, in the reply filed 09 February 2026 is acknowledged. The traversal on the ground(s) that the special technical feature of the claimed invention is not a recombinant flavivirus prM glycoprotein but a recombinant flavivirus prM glycoprotein with specific mutations and Courageot does not disclose these mutations. However, this is not found persuasive at least because unity of invention will only be fulfilled if there is a technical relationship among those in invention involving one or more of the same or corresponding special technical features. The inventions are drawn to a recombinant flavivirus prM glycoprotein which is a special technical feature over Courageot, which is also drawn to a recombinant flavivirus prM glycoprotein. The requirement is still deemed proper and is therefore made final.
Claims 30-31, 33, 39, and 41-42 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions/species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 09 February 2026.
Claim Rejections - 35 USC § 112 – Improper Dependency
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.
Claim 8 is 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 8 recites, inter alia, an amino acid substitution of 87R, but SEQ ID NO: 104 in claim 1 already possesses 87R, so this substitution 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 – 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.
Claims 1, 2, 4, 8, 12, 15, 18-20, 24, 25, and 29 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, 2, 4, 8, 12, 15, 18-20, 24, 25, and 29 are drawn to a recombinant flavivirus prM glycoprotein comprising at least one amino acid substitution at position 85-89 in the furin cleavage site where at least one amino acid substitution is more basic than the original amino acid residue and the furin cleavage site has enhanced cleavability by a furin enzyme.
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 ability of the furin cleavage site to have enhanced cleavability by the furin enzyme.
A recombinant flavivirus prM glycoprotein with at least one amino acid substitution at positions 85-89 in the furin cleavage site where at least one of the substations is for an amino acid residue that is more basic than the original amino acid encompasses a large pool of glycoproteins, as allowing for changes in 5 amino acid residues allows for many permutations of proteins. A variant with substitutions for all 5 amino acid residues, even with the requirement for one of those substitutions to be a more basic amino acid, allows for an enormous genus of up to 2.88 x 106 sequences (18 amino acids are more basic than glutamic acid).
While the instant claims are drawn to a genus that comprises innumerable permutations of sequences, the Specification has only adequately described, and successfully reduced to practice specific recombinant flavivirus prM glycoprotein furin cleavage sites (SEQ ID NOs: 1-103). As such, the Specification reasonably demonstrates that the Applicant was in possession of SEQ ID NOs: 1-103. However, this is not representative of the extremely large genus of glycoproteins claimed since these sequences only encompass the claimed glycoproteins with these furin cleavage sites and not the innumerable glycoproteins contained within the genus of all recombinant flavivirus prM glycoproteins with at least one substitution at positions 85-89 in the furin cleavage site where at least one of the substations is for an amino acid residue that is more basic than the original amino acid and the Specification does not adequately describe what amino acids residues are required for enhanced cleavability. The claims defines the glycoprotein based on what it does – not what it is.
The data generated for SEQ ID NOs: 1-103 as described in the Specification cannot reasonably be extrapolated and applied to support possession of the entire claimed genus of variants because no one species, combination, or variant account 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).
While Applicants may have possession of all proteins with the substituted residues in the furin cleavage site, the amino acid residues (structural features) that must be retained to have enhanced cleavability by a furin enzyme (function) was not sufficiently described to establish a structure-function relationship and glycoproteins with these substitutions have not all been shown to have enhanced cleavability by a furin enzyme
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 following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 8, 12, 15, 17-20, 24-25, and 29 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Baumhof, et al. (US 2021 0069315 A1, US-IDS, filed, 09/15/2023, hereinafter “Baumhof”) and evidenced by Vanderbilt (http://www.vanderbilt.edu/AnS/Chemistry/Rizzo/stuff/AA/AminoAcids.html available on the WayBack Machine at https://web.archive.org/web/20000123054350/http://www.vanderbilt.edu/AnS/Chemistry/Rizzo/stuff/AA/AminoAcids.html, published Jan 23 2000 and accessed April 16 2026) Tian, et al. (Sci Rep. 2012;2:261., NPL-IDS, filed, 03/01/2024, hereinafter “Tian”).
Regarding claim 1, Baumhof discloses a recombinant flavivirus prM glycoprotein with an amino acid substitution at position 86 compared to instant SEQ ID NO: 104, the reference sequence has the amino acid arginine instead of histidine at position 86 (SEQ ID NO: 1022). As evidenced by Vanderbilt, arginine is more basic than histidine. Absent evidence to the contrary, the recombinant flavivirus prM glycoprotein with a more basic amino acid substitution in the furin cleavage site taught by Baumhof would have enhanced cleavability by the furin enzyme. The cleavability of the furin cleavage site is an inherent property based on the amino acids present.
PNG
media_image1.png
349
885
media_image1.png
Greyscale
Regarding claim 8, Baumhof discloses a recombinant flavivirus prM glycoprotein with an arginine at position 87 (SEQ ID NO: 1022).
PNG
media_image2.png
349
885
media_image2.png
Greyscale
Regarding claim 12, the recombinant flavivirus prM glycoprotein of claim 1 was anticipated by Baumhof as discussed above. The Pi-Tou score of the substituted furin cleavage site is, absent evidence to the contrary, an inherent property of the furin cleavage site. A chemical composition and its properties are inseparable. Therefore, as the prior art teaches the identical composition, the properties that are claimed by Applicant must also be present. "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). See also MPEP § 2112.01(II). Therefore, as the recombinant flavivirus prM glycoprotein was anticipated, the Pi-Tou score of the furin cleavage site is also anticipated. “[T]he claiming of a[n]… unknown property which is inherently present in the prior art does not necessarily make the claim patentable.” See MPEP 2112. The Pi-Tou score is inherent to the amino acids present in the furin cleavage site as evidenced by Tian (Abstract). Therefore, these properties are inherent to the furin cleavage site of the recombinant flavivirus prM glycoprotein and the recombinant flavivirus prM glycoprotein has been anticipated, so too is the Pi-Tou score of the furin cleavage site.
Regarding claim 15, Baumhof discloses a recombinant flavivirus prM glycoprotein with the backbone being from dengue 4 (SEQ ID NO: 1022).
Regarding claim 17, Baumhof discloses a recombinant flavivirus prM glycoprotein that is 99.3% identical to instant SEQ ID NO: 116 (SEQ ID NO: 1022).
PNG
media_image3.png
762
660
media_image3.png
Greyscale
Regarding claim 18, Baumhof discloses a nucleic acid molecule that encodes reference SEQ ID NO: 1022 (¶0078).
Regarding claim 19, Baumhof discloses that nucleic acid that encodes the recombinant flavivirus prM glycoprotein in mRNA (claim 11).
Regarding claim 20, Baumhof discloses a virus-like particle comprising the prM glycoprotein (¶0134).
Regarding claim 24, Baumhof discloses an artificial nucleic acid sequence or vector (¶0047 and 0134).
Regarding claim 25, Baumhof discloses making multiple VLPs from a recombinant prM glycoprotein (¶0134).
Regarding claim 29, Baumhof discloses a composition comprising a recombinant prM glycoprotein and a pharmaceutically acceptable carrier (¶0328).
Accordingly, Baumhof anticipates the claimed inventions.
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.
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.
4. Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Baumhof as applied to claims 1, 8, 12, 15, 17-20, and 24-25 above, and further in view of Jinjhon, et al. (J Virol. 2010 Aug;84(16):8353-8., NPL-IDS, filed, 09/15/2023, hereinafter “Jinjhon”).
As discussed above, claims 1, 8, 12, 15, 17-20, and 24-25 were anticipated by Baumhof.
Regarding claim 2, Baumhof does not teach a furin cleavage site that comprises a substitution at position 89. However, Jinjhon teaches the influence of amino acid substitutions in the prM furin cleavage site on the proportion of mature and immature viral particles (Abstract). Jinjhon further teaches that the substation of an Alanine instead of glutamic acid at position 89/P3 (Instant Specification pg. 2 line 15) has enhanced prM cleavage (pg. 8356, column 2).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Baumhof for a recombinant flavivirus prM glycoprotein with the teachings of Jinjhon for an amino acid substitution at position 89. Jinjhon provides motivation by teaching that an amino acid substitution from E to A at position 89 enhances prM cleavage (pg. 8356, column 2). One of ordinary skill would have had a reasonable expectation of success combining Baumhof and Jinjhon because they both teach recombinant flavivirus glycoproteins.
Accordingly, the claimed inventions were prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
Allowable Subject Matter
Claim 14 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
NO CLAIMS ARE ALLOWED
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.
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.
/CASSANDRA SENN GRIZER/ Examiner, Art Unit 1672
/THOMAS J. VISONE/ Supervisory Patent Examiner, Art Unit 1672
Prosecution Insights