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
Acknowledgement is made of Applicants claim for benefit to prior filed US Provisional application 63/191,013 (filed 05/20/2021).
Response to Amendment
The amendment filed 08 July 2026 in which claims 8, 9, 24, 58, and 123 were amended and claims 124-128 were added has been entered.
Election/Restrictions
Applicant’s election with traverse of the trimerization domain (claim 2), VSV-G (claims 4-6), SEQ ID NO: 7 (claims 8, 47), Type I transmembrane polypeptide (claim 23), ACE2 (claim 24), SEQ ID NO: 59 (claims 39, 47), VSV-G transmembrane domain (claim 41), VSV-G cytosolic domain (claims 43, 45), ACE2 (claim 45), D4 post-fusion trimerization domain of VSV-G protein (claim 45), SEQ ID NO: 4 (claims 47), SEQ ID NO: 73 (claim 123) in the reply filed 08 July 2026 is acknowledged.
The traversal is on the ground(s) that the special technical claimed invention is not a recombinant fusion protein comprising a transmembrane domain, a display polypeptide, and an oligomerization domain but a recombinant fusion protein comprising a transmembrane domain, a display polypeptide, and an oligomerization domain expressed on the surface of an enveloped particle and displayed in an oligomeric format and Beauchesne does not disclose an enveloped particle or oligomeric format.
However, this is not found persuasive at least because unity of invention will only be fulfilled is there is a technical relationship among those inventions involving one or more of the same or corresponding special technical features. The inventions are drawn to a recombinant fusion protein comprising a transmembrane domain, a display polypeptide, and an oligomerization domain which is a special technical feature or Beauchesne, which is also drawn to a recombinant fusion protein comprising a transmembrane domain, a display polypeptide, and an oligomerization domain. The requirement is still deemed proper and is therefore made final.
Claims 3, 6, and 7 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions/species, there being no allowable generic or linking claim.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 08 July 2026.
In view of Examiner’s search in regard to the oligomerization domain, transmembrane domain, display polypeptide, and recombinant fusion protein sequences, the species election is withdrawn as to claims 8, 23, 41, 43, 45, 47, 49, and 123-128.Claims 1-2, 4-5, 8-9, 14, 16-19, 23-24, 31-32, 39, 41, 43, 45, 47-50, 53-56, 58, and 123-128 were examined on the merits.
Claim Objections
Claim 1 is objected to because of the following informalities: ”wherein when the recombinant fusion protein is expressed on a surface of an enveloped particle, the recombinant fusion protein is displayed in an oligomeric format” should read “”wherein when the recombinant fusion protein is expressed on a surface of an enveloped particle, and the recombinant fusion protein is displayed in an oligomeric format”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 8, 39, 47-50, 53-56, 58, and 123 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The phrase “at least about” in claims 8, 39, 47-49, 53-56, 58, and 123 is a relative phrase which renders the claim indefinite. The phrase “at least about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The percent identity of the sequences and the valency are rendered indefinite by use of the phrase “at least about”.
The term “about” in claim 50 is a relative term which renders the claim indefinite, The term “about: is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The valency is rendered indefinite by use of the term “about”.
Claim Rejections - 35 USC § 112(a)
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 8, 39, 47-49, and 123 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 8, 39, 47-49, and 123 are drawn to a recombinant fusion protein comprising a transmembrane domain, a display polypeptide, and an oligomerization domain, which has written description support. However, the instant claims also broadly encompass recombinant fusion proteins with oligomerization domain comprising an amino acid sequence with 90% sequence identity to SEQ ID NO: 7, a display polypeptide comprising an amino acid sequence with 90% sequence identity with SEQ ID NO: 59, a transmembrane domain comprising an amino acid sequence with 90% identity with SEQ ID NO: 4, and/or a cytosolic domain comprising an amino acid sequence with 90% sequence identity with SEQ ID NO: 5 and a recombinant fusion protein comprising an amino acid sequence with 90% sequence identity with SEQ ID NO: 73.
The Specification has failed to sufficiently describe the amino acids that must be retained by the members of the claimed genus as to establish a structure-function relationship with respect of the ability of the proteins to be an oligomerization domain (claims 8 and 47), display polypeptide (claims 39 and 47), transmembrane domain (claims 47 and 49), cytosolic domain (claim 48), a recombinant fusion protein (claim 123).
Sequences with at least 90% sequence identity encompasses a vast genus of proteins and the Specification does not adequately describe the necessary amino acids that must remain for the amino acid sequences to be an oligomerization domain (claims 8 and 47), display polypeptide (claims 39 and 47), transmembrane domain (claims 47 and 49), cytosolic domain (claim 48), a recombinant fusion protein (claim 123).
While the instant claims are drawn to a genus that comprises innumerable permutations of sequences, the Specification has only adequately described and reduced to practice recombinant fusion proteins with full-length domains of the full-length fusion protein. As such, the Specification reasonably demonstrates that Applicant was in possession of the full-length of domains and recombinant fusion proteins. However, this is not representative of the extremely large genus of proteins since only the full-length domains and recombinant fusion proteins are supported and not the innumerable sequences contained with a genus of 90% identical to the amino acid sequences of the domain or recombinant fusion protein.
The data generated for the recombinant fusion proteins comprising the full-length domains cannot be reasonably extrapolated and applied to support possession of the entire claimed genus of domains and recombinant fusion proteins because no one species, combination, or variant accounts for the variability among 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).
Gormord, et al. (US 20190160167 A1, US-IDS, filed, 01/26/2024, hereinafter “Gormord”) provides a review of recombinant fusion proteins a display polypeptide, oligomerization domain, transmembrane domain, and or cytosolic domain, these recombinant fusion proteins require the full-length domains to perform the intended function (¶0019-0026) while applicant claims sequences and proteins that are not full length. While Applicant may have possession of the protein that have sequences that are 90% similar to the claimed sequences, this alone does not establish a structure-function relationship as it is still unknown which amino acids are required to perform the claimed function.
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 1-2, 9, 14, 16-17, 23, and 31-32 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Gormord.
Regarding claim 1, Gormord discloses a recombinant fusion protein that comprises a transmembrane domain, an oligomerization domain, and a display polypeptide (¶0019). Gormord further discloses that recombinant fusion protein is expressed in the surface of an enveloped particle in an oligomeric format (¶0028).
Regarding claim 2, Gormord discloses the oligomerization domain leads to the formation of trimers (¶0019).
Regarding claim 9, Gormord discloses that the oligomerization domain is outside of the enveloped particle (¶0028 and Fig. 1B, reproduced below).
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Regarding claim 14, Gormord discloses that the recombinant fusion peptide is arranged from the N-terminal to C-terminal end in the order of the signal peptide, the display polypeptide, the oligomerization domain, and the transmembrane domain (¶0044).
Regarding claim 16, Gormord discloses that the recombinant fusion peptide is arranged from the N-terminal to C-terminal end in the order of the signal peptide, the display polypeptide, the oligomerization domain, the transmembrane domain, and the cytosolic domain (¶0026).
Regarding claim 17, Gormord discloses that the enveloped particle is a VLP (¶0164).
Regarding claim 23, Gormord teaches that the display polypeptide (protein or peptide of interest) is a scFv (¶0060).
Regarding claim 31, Gormord teaches that that the display polypeptide (protein or peptide of interest) is a cytokine (¶0061).
Regarding claim 32, Gormord teaches that the display polypeptide (protein of interest) is an immunoglobulin, which is either a neutralizing or non-neutralizing antibody (¶0060).
Accordingly, the claimed invention is anticipated by Gormord.
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 4-5 are rejected under 35 U.S.C. 103 as being unpatentable over Gormord as applied to claims 1-2, 9, 14, 16-17, 23, and 31-32 above, and further in view of Sun, et al. (Future Virol. 2010;5(1):85-96., hereinafter “Sun”).
As discussed above, claims 1-2, 9, 14, 16-17, 23, and 31-32 were anticipated by Gormord.
Regarding claims 4-5, Gormord teaches that the oligomerization domain leads to the formation of trimers (¶0019). Gormord does not teach that the trimerization domain is a post-fusion oligomerization domain or the D4 post-fusion trimerization domain of VSV-G. However, Sun teaches the domains of the VSV-G protein trimer including domain IV, the fusion domain (pg. 6, ¶2).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to have substituted the trimerization domain taught by Gormord for the domain IV fusion domain of VSV-G taught by Sun. Gormord teaches that many different oligomerization domains can be used in making the recombinant fusion proteins (¶0019). One of skill in the art would have substituted the trimerization domain taught by Gormord with the domain IV VSV-G trimerization domain taught by Sun to create a recombinant fusion protein with a post-fusion trimerization domain (see MPEP 2143(I), KSR rationale B) Simple substitution of one known element for another to obtain predictable results). One of skill in the art would have had a reasonable expectation of success of substituting the trimerization domains because they are both oligomerization domains.
Accordingly, the invention was 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.
Claims 8 and 124 are rejected under 35 U.S.C. 103 as being unpatentable over Gormord as applied to claims 1-2, 9, 14, 16-17, 23, and 31-32 above, and further in view of Lahusen, et al. (WO 2018187231 A2 FOR-IDS, filed, 01/26/2024, hereinafter “Lahusen”).
As discussed above, claims 1-2, 9, 14, 16-17, 23, and 31-32 were anticipated by Gormord.
Regarding claim 8 and 124, Gormord teaches an oligomerization domain but does not teach that the oligomerization domain comprises a sequence selected from instant SEQ ID NOs: 6-19. However, Lahusen teaches SEQ ID NO: 23, which is 100% identical to instant SEQ ID NO: 6 (see alignment below).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to have substituted the trimerization domain taught by Gormord for the sequence taught by Lahusen. Gormord teaches that many different oligomerization domains can be used in making the recombinant fusion proteins (¶0019) as all oligomerization domains contain oligomerization sequences that allow the protein of interest to be expressed in an oligomerized form (¶0028). One of skill in the art would have substituted the trimerization domain taught by Gormord with the sequence taught by Lahusen to create a recombinant fusion protein with a VSV-G glycoprotein (see MPEP 2143(I), KSR rationale B) Simple substitution of one known element for another to obtain predictable results). One of skill in the art would have had a reasonable expectation of success of substituting the trimerization domains because they are both known oligomerization domains
Accordingly, the invention was 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.
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Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Gormord as applied to claims 1-2, 9, 14, 16-17, 23, and 31-32 above, and further in view of Momen-Heravi, et al. (Nanomedicine. 2014 Oct;10(7):1517-27., hereinafter “Momen”).
As discussed above, claims 1-2, 9, 14, 16-17, 23, and 31-32 were anticipated by Gormord.
Regarding claim 18, Gormord does not teach that an extracellular vesicle or one that comprises an exosome or ectosome. However, Momen teaches that the exosomes are extracellular vesicles (pg. 1, Background) that can be used for loading and carting bio-macromolecules for nanomedicine applicants (pg. 2, ¶2).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to have substituted the VLP by Gormord for the exosome taught by Momen. Momen provides motivation by teaching that exosomes have excellent biocompatibility making them an attractive platform for nanomedicine applications (pg. 2, ¶2). One of skill in the art would have substituted VLP taught by Gormord with the exosome taught by Momen to create a recombinant fusion protein expressed on an exosome (see MPEP 2143(I), KSR rationale B) Simple substitution of one known element for another to obtain predictable results). One of skill in the art would have had a reasonable expectation of success of substituting the trimerization domains because they are both enveloped particles.
Accordingly, the invention was 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.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Gormord as applied to claims 1-2, 9, 14, 16-17, 23, and 31-32 above, and further in view of Oda (US 20180044404 A1, US-IDS, filed, 01/26/2024).
As discussed above, claims 1-2, 9, 14, 16-17, 23, and 31-32 were anticipated by Gormord.
Regarding claim 19, Gormord further teaches that the display polypeptide targets a cell surface protein to trigger an immune response (¶0051). Gormord does not teach that the cell surface protein is multimerized. However, Oda teaches that interactions between multimerization domains promote signal transduction in a host cell in a statistically significant matter compared to monomers (¶0120).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to have combined the teachings of Gormord for a recombinant fusion protein with a display polypeptide that targets a cell surface protein of a target cell for agonistic or antagonistic functions with the teachings of Ord for the cell surface protein being multimerized. Ord provides motivation by teaching that interactions between multimerization domains promote signal transduction in a host cell in a statistically significant matter compared to monomers (¶0120). One of skill in the art would have had a reasonable expectation of success in combining the teachings of Gormord and Ord because they both teach fusion proteins.
Accordingly, the invention was 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.
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Gormord as applied to claims 1-2, 9, 14, 16-17, 23, and 31-32 above, and further in view of Lobb, et al. (US 10508143 B1, US-IDS, filed, 01/26/2024, hereinafter “Lobb”).
As discussed above, claims 1-2, 9, 14, 16-17, 23, and 31-32 were anticipated by Gormord.
Regarding claim 24, Gormord further teaches that the display polypeptide is an scFv (¶0060) but does not teach that the display polypeptide is an anti-CD19 scFv. However, Lobb teaches that a display polypeptide that is an anti-CD19 scFv (column 2 lines 23-25).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to have substituted the scFv display polypeptide taught by Gormord for the anti-CD19 scFv taught by Lobb. Gormord teaches that many different display polypeptides can be used in making the recombinant fusion proteins (¶0060). One of skill in the art would have substituted the scFv display polypeptide taught by Gormord with the anti-CD19 scFv taught by Lobb to create a recombinant fusion protein with an anti-CD19 scFv display polypeptide which allows for the recombinant fusion protein to recognize and bind CD19 positive B cells for immune system activation (column 23 lines 41-46) (see MPEP 2143(I), KSR rationale B) Simple substitution of one known element for another to obtain predictable results). One of skill in the art would have had a reasonable expectation of success of substituting the scFv polypeptides because they are both scFv polypeptides.
Accordingly, the invention was 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.
Claims 39 and 125 are rejected under 35 U.S.C. 103 as being unpatentable over Gormord as applied to claims 1-2, 9, 14, 16-17, 23, and 31-32 above, and further in view of Eba, et al. (EP 218431 A, hereinafter “Eba”).
As discussed above, claims 1-2, 9, 14, 16-17, 23, and 31-32 were anticipated by Gormord.
Regarding claims 39 and 125, Gormord teaches a display polypeptide but does not teach that the display polypeptide comprises a sequence selected from instant SEQ ID NOs: 20-51 and 56-70. However, Eba teaches a polypeptide having the amino acid sequence as claimed in claim 4 which is 100% identical to instant SEQ ID NO: 39 (see alignment below).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to have substituted the display polypeptide taught by Gormord for the sequence taught by Eba. Gormord teaches that many different display polypeptides can be used in making the recombinant fusion proteins (¶0054-62). One of skill in the art would have substituted the display polypeptide taught by Gormord with the sequence taught by Eba to create a recombinant fusion protein with a murine IL-4 (see MPEP 2143(I), KSR rationale B) Simple substitution of one known element for another to obtain predictable results). One of skill in the art would have had a reasonable expectation of success of substituting the display polypeptides because they are both peptides.
Accordingly, the invention was 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.
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Claims 41 and 43 are rejected under 35 U.S.C. 103 as being unpatentable over Gormord as applied to claims 1-2, 9, 14, 16-17, 23, and 31-32 above, and further in view of Palese, et al. (US 20190125859 A1, US-IDS, filed, 01/26/2024, hereinafter “Palese”).
As discussed above, claims 1-2, 9, 14, 16-17, 23, and 31-32 were anticipated by Gormord.
Regarding claims 41 and 43, Gormord teaches that the recombinant protein can further include a domain for anchoring the plasma membrane consisting of a transmembrane and cytosolic domains (¶0026). Gormord does not teach the specific transmembrane or cytosolic domains. However, Palese teaches a fusion protein (¶0560) comprising influenza hemagglutinin cytoplasmic and transmembrane domains (¶0365) used as an immunogen.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to have substituted the cytosolic and transmembrane domains taught by Gormord for the HA cytoplasmic and transmembrane domains taught by Palese. Gormord teaches that many different cytosolic and transmembrane domains can be used in making the recombinant fusion proteins (¶0026). One of skill in the art would have substituted the cytosolic and transmembrane domains taught by Gormord with the HA cytoplasmic and transmembrane domains taught by Palese to create a recombinant fusion protein with an HA cytosolic and transmembrane domain. (see MPEP 2143(I), KSR rationale B) Simple substitution of one known element for another to obtain predictable results). One of skill in the art would have had a reasonable expectation of success of substituting the cytosolic and transmembrane domains because they are both cytosolic and transmembrane domains.
Accordingly, the invention was 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.
Claim 45 is rejected under 35 U.S.C. 103 as being unpatentable over Gormord as applied to claims 1-2, 9, 14, 16-17, 23, and 31-32 above, and further in view of Lobb, Palese, and Sun.
As discussed above, claims 1-2, 9, 14, 16-17, 23, and 31-32 were anticipated by Gormord.
Regarding claim 45, Gormord teaches a recombinant fusion protein comprising a display polypeptide, a transmembrane domain, and an oligomerization domain (see claim 1). Gormord does not teach the specific peptides for the domains. However, Lobb teaches an anti-CD19 scFv display polypeptide (see claim 24), Palese teaches an HA transmembrane domain (see claim 41), and Sun teaches a D4 post-fusion trimerization domain of VSV-G (see claim 5).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to have substituted the display polypeptide, transmembrane domain, and oligomerization domain taught by Gormord with the anti-CD19 scFv taught by Lobb, the HA transmembrane domain taught by Palese, and the D4 post-fusion trimerization domain of VSV-G taught by Sun. Gormord teaches that many different display polypeptides (¶0054-0062), transmembrane domains (¶0026), and oligomerization domains (¶0019) can be used in making recombinant fusion proteins. One of skill in the art would have substituted the display polypeptide, transmembrane domain, and oligomerization domain taught by Gormord with the anti-CD10 scFv taught by Lobb, the HA transmembrane domains taught by Palese, and D4 post-fusion trimerization domain of VSV-G taught by Sun to create a recombinant fusion protein with an anti-CD19 scFv display polypeptide, HA transmembrane domain, and a D4 post-fusion trimerization domain of VSV-G (see MPEP 2143(I), KSR rationale B) Simple substitution of one known element for another to obtain predictable results). One of skill in the art would have had a reasonable expectation of success of substituting the display polypeptide, transmembrane domain, and oligomerization domain with the above because they are all examples of the peptides.
Accordingly, the invention was 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.
Claims 48 and 126 are rejected under 35 U.S.C. 103 as being unpatentable over Gormord and Palese as applied to claims 41 and 43 above, and further in view of Clarke, et al. (US 20070218078 A1, US-IDS, filed, 01/26/2024, hereinafter “Clarke”).
As discussed above, claims 41 and 43 were rendered prima facie obvious over Gormord and Palese.
Regarding claims 48 and 126, Gormord and Palese teach a recombinant fusion protein with a cytosolic domain (¶0026) but does not teach the specific sequence for the cytosolic domain. However, Clarke teaches SEQ ID NO: 1 which comprises a sequence with 100% identity to instant SEQ ID NO: 5 (see alignment below).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to have substituted the cytosolic domain taught by Gormord and Palese for the sequence taught by Clarke. Gormord teaches that many different cytosolic domains can be used in making the recombinant fusion proteins (¶0026). One of skill in the art would have substituted the cytosolic domain taught by Gormord and Palese with the sequence taught by Clarke to create a recombinant fusion protein with the specific cytosolic domain represented by the sequence. One of skill in the art would have had a reasonable expectation of success substituting the cytosolic domains because they are both peptides.
Accordingly, the invention was 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.
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Claims 49 and 127 are rejected under 35 U.S.C. 103 as being unpatentable over Gormord as applied to claims 1-2, 9, 14, 16-17, 23, and 31-32 above, and further in view of Bellier, et al. (FR 3072973 A1, FOR-IDS, filed, 01/26/2024, hereinafter “Bellier”).
As discussed above, claims 1-2, 9, 14, 16-17, 23, and 31-32 were anticipated by Gormord.
Regarding claims 49 and 127, Gormord teaches a transmembrane domain (¶0019) but does not teach that the display polypeptide comprises a sequence selected from instant SEQ ID NOs: 1-4 and 52-55. However, Bellier teaches SEQ ID NO: 4 which is 100% identical to instant SEQ ID NO: 1 (see alignment below).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to have substituted the transmembrane domain taught by Gormord for the sequence taught by Bellier. Gormord teaches that many different transmembrane domains can be used in making the recombinant fusion proteins (¶0019). One of skill in the art would have substituted the transmembrane domain taught by Gormord with the sequence taught by Bellier to create a recombinant fusion protein with the transmembrane domain of VSV-G. (see MPEP 2143(I), KSR rationale B) Simple substitution of one known element for another to obtain predictable results). One of skill in the art would have had a reasonable expectation of success of substituting the transmembrane domains because they are both peptides.
Accordingly, the invention was 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.
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Claims 47, 123, and 128 are rejected under 35 U.S.C. 103 as being unpatentable over Gormord as applied to claims 1-2, 9, 14, 16-17, 23, and 31-32 above, and further in view of Eba, Bellier, and Lahusen.
As discussed above, claims 1-2, 9, 14, 16-17, 23, and 31-32 were anticipated by Gormord.
Regarding claim 47, Gormord teaches a recombinant fusion protein with a display polypeptide, transmembrane domain, and oligomerization domain (see claim 1) but does not teach the instant sequences. However, in claim 4, Eba teaches a sequence with 100% identity to instant SEQ ID NO: 39 (see also claims 39 and 125), Bellier teaches SEQ ID NO: 4 which comprises a sequence 100% identical to instant SEQ ID NO: 1 (see claims 49 and 127), and Lahusen teaches SEQ ID NO: 23 which comprises a sequence 100% identical to instant SEQ ID NO: 6 (see claims 8 and 124).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to have substituted the display polypeptide, transmembrane domain, and oligomerization domain taught by Gormord with the sequences for the display polypeptide (taught by Eba), the transmembrane domain (taught by Bellier), and the oligomerization domain (taught by Lahusen). Gormord teaches that many different display polypeptides (¶0054-0062), transmembrane domains (¶0026), and oligomerization domains (¶0019) can be used in making recombinant fusion proteins. One of skill in the art would have substituted the display polypeptide, transmembrane domain, and oligomerization domain taught by Gormord with sequences for the display polypeptide (taught by Eba), the transmembrane domain (taught by Bellier), and the oligomerization domain (taught by Lahusen) to create a recombinant fusion protein with these specific peptides (see MPEP 2143(I), KSR rationale B) Simple substitution of one known element for another to obtain predictable results). One of skill in the art would have had a reasonable expectation of success of substituting the display polypeptide, transmembrane domain, and oligomerization domain with the above because they are all examples of the peptides.
Regarding claims 123 and 128, Gormord does not teach a recombinant fusion protein comprising an amino acid sequence with SEQ ID NOs: 71-100. However, as discussed above Gormord, Eba, Bellier, and Lahusen teach together a recombinant fusion protein expressed on the surface of an enveloped particle wherein the display polypeptide is murine IL-4 (claim 4, see claims 39 and 125), the transmembrane domain is VSV-G (SEQ ID NO: 4, see claims 49 and 127), and the oligomerization domain is D4 (SEQ ID NO: 23, see claims 8 and 124). Taken together they teach SEQ ID NO: 92 which comprises a murine IL-4 display polypeptide, a D4 oligomerization domain, and a VSV-G transmembrane domain. One of skill in the art would have had a reasonable expectation of success in combining these three domains to create a recombinant fusion protein with a murine IL-4 display polypeptide, a D4 oligomerization domain, and a VSV-G transmembrane domain to express on the surface on an enveloped particle.
Accordingly, the invention was 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.
Claims 50, 53-56, and 58 are rejected under 35 U.S.C. 103 as being unpatentable over Gormord as applied to claims 1-2, 9, 14, 16-17, 23, and 31-32 above, and further in view of O’Rourke, et al. (Curr Opin Virol. 2015 Apr;11:76-82., hereinafter “O’Rourke”) and Dagan, et al. (Vaccine. 2010 Aug 2;28(34):5513-23., hereinafter “Dagan”).
As discussed above, claims 1-2, 9, 14, 16-17, 23, and 31-32 were anticipated by Gormord.
Regarding claims 50, 53-56, and 58, Gormord teaches the recombinant fusion and expression of the recombinant protein on a surface of an enveloped particle (see claim 1 above). Gormord does not teach the number of copies of the recombinant fusion protein on the surface of the enveloped particle. However, routine optimization of the number of copies of the recombinant fusion protein taught by Gormord would have led to the claimed range of 10-1000 copies of the fusion protein expressed on the surface of the enveloped particle. O’Rourke teaches that antigens that contain repeated epitopes with a spacing of 50–100 Angstroms, which includes most virus particles, optimally induce B cell responses and that increased valency increase immunogenicity (Introduction ¶1 and references 7 and 8). Dagan further teaches that increasing valency can cause interference and reduced immune responses (abstract). One of skill in the art would have found it obvious to optimize the valency of the recombinant fusion protein expressed on the surface of the enveloped particles to optimize the immunogenicity, as taught by O’Rourke, without causing interference, as taught by Dagan.
Accordingly, the invention was 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.
Conclusion
NO CLAIMS ARE ALLOWED
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/CASSANDRA SENN GRIZER/ Examiner, Art Unit 1672
/THOMAS J. VISONE/ Supervisory Patent Examiner, Art Unit 1672
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