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 .
Status of the Application
1. Claims 33 and 35-48 are pending and subject to examination on the merits. Claims 39-48 are withdrawn from consideration as being drawn to non-elected subject matter.
Election/Restrictions
2. Applicant's election with traverse of Group I (Claims 33 and 35-38) in the reply filed on 05 September 2025 is acknowledged. The traversal is on the ground(s) that claim 33 was amended to include the technical feature of “a polypeptide forming a P2 domain of Tetanus toxin is linked to the N-terminus or C-terminus of the extended receptor binding domain.” This is not found persuasive because although Yuan et al. does not teach this newly added claim limitation, Wen et al (Wen et al., 2014, Vaccine—cited herein) teaches the improvement of vaccine potential of a rotavirus vaccine by introducing a tetanus toxoid universal CD4+ T-cell epitope P2 to the rotavirus P[8] or P[6]ΔVP8* construct (abstract) – See below.
Even assuming arguendo that unity relies on a polypeptide forming a P2 domain of Tetanus toxin is linked to the N-terminus or C-terminus of the extended receptor binding domain. Unity of invention is still lacking in view of the art cited below.
Priority
3. Acknowledgement is made of applicant’s claim for foreign priority based on an application filed in KR (KR10-2020-0052855 on 29 April 2020. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
4. The information disclosure statements (IDS) submitted on 31 October 2022, 02 August 2024, and 29 August 2025 have been considered by the examiner. See initialed and signed PTO/SB/08’s.
Specification
5. 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, requires the specification to be written in “full, clear, concise, and exact terms.” The specification is replete with terms which are not clear, concise and exact. The specification should be revised carefully in order to comply with 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112. Examples of some unclear, inexact or verbose terms used in the specification are: multiple instances where “polypeptide” is being used instead of “amino acids.” It appears the applicant is referring to short peptide linkers but utilizes the term “polypeptides” instead. There are multiple instances; one example is found below:
On page 8, the specification states:
“The P2 peptide and/or foldon peptide may be provided in a form linked to the Extended_S_RBD through a linker. The linkage may be linked by a linker consisting of at least three polypeptides. For example, the linker is 16 polypeptides or less in length and may preferably consist of 6 or less polypeptides. The polypeptides used in the linker may be at least one of G (Gly, glycine), S (Ser, serine), and A (Ala, alanine). Preferably, the linker may be at least one peptide linker selected from the group consisting of Gly-Ser-Gly-Ser-Gly (GSGSG), Gly-Ser-Ser-Gly (GSSG), Gly-Ser-Gly-Gly- Ser (GSGGS), Gly-Ser-Gly-Ser (GSGS), and Gly-Ser-Gly-Ser-Ser-Gly (GSGSSG), and preferably may be a GSGSG peptide linker for the purpose of the present invention.”
Compliance with Sequence Rules
6. The sequence listing, filed in computer readable form (CRF) and paper copy on , has been received and entered. This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 C.F.R. § 1.821(a)(1) and (a)(2). However, this application fails to fully comply with the requirements of 37 C.F.R. § 1.821 through 1.825; Applicants’ attention is directed to the final rulemaking notice published at 55 FR 18230 (May 1, 1990), and 1114 OG 29 (May 15, 1990).
The following parts of the Specification contain sequences that contain four or more specifically defined amino acids without any corresponding SEQ ID NO:
a) On page 8, lines 12-13, all of the listed peptide linkers (Gly-Ser-Gly-Ser-Gly (GSGSG), Gly-Ser-Ser-Gly (GSSG), Gly-Ser-Gly-Gly- Ser (GSGGS), Gly-Ser-Gly-Ser (GSGS), and Gly-Ser-Gly-Ser-Ser-Gly (GSGSSG)) should have corresponding SEQ ID NOs:.
b) On page 24, line 8, MFVFLVLLPLVSS should have a corresponding SEQ ID NO:.
Applicants must amend the specification to identify the sequences appropriately by SEQ ID NO:. — See also MPEP 2422.
Claim Objections
7. Claim 33 objected to because of the following informalities: the typographical error “inked” should be changed to “linked.” Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
8. 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.
9. Claims 33 and 35-37 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.
10. The term “P2 domain” in claims 33 and 35-37 renders the claim indefinite. The tetanus toxin does not have a “P2 domain.” It has 3 domains, termed A, B, and C (Wang et al., 2021, Cell Reports—cited herein; p. 1, column 2, 1st full paragraph). For examination purposes, “P2 domain” will be interpreted as “tetanus toxoid universal CD4+ T-cell epitope P2” (Wen et al., 2014, Vaccine—cited herein; abstract).
11. The term “the foldon domain of SEQ ID NO: 4” in claim 35 renders the claim indefinite. It is unclear if there is a foldon domain within SEQ ID NO: 4 or if SEQ ID NO: 4 is the foldon domain. It is recommended to amend the limitation to “the foldon domain consisting of or comprising SEQ ID NO: 4.”
12. Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). The term “polypeptide” in claims 36-37 is used by the claim to mean “peptide linker,” “linker,” or even “amino acid,” while the accepted meaning is “single peptide chain of 20-50 amino acids.” The term is indefinite because the specification does not clearly redefine the term, specifically, p. 8 states that, “The polypeptides used in the linker may be at least one of G (Gly, glycine), S (Ser, serine), and A (Ala, alanine).”, where G, S, and A are single amino acids. For examination purposes, the term “polypeptides” in claims 36 and 37 will be interpreted to include all of the above definitions/alternative terms, i.e. an amino acid, linker, and/or peptide linker.
13. The term “the wildtype RBD polypeptide sequence of SEQ ID NO: 33” in claim 37 renders the claim indefinite. The term “the wildtype RBD polypeptide sequence of SEQ ID NO: 33” is indefinite because SEQ ID NO: 33 is a DNA sequence not an amino acid sequence.
Claim Rejections - 35 USC § 103
14. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
15. 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.
16. Claims 33, 36-37 are rejected under 35 U.S.C. 103 as being unpatentable over Yuan et al (Yuan et al., 2020, Science—cited on the IDS dated 31 October 2022) and Wen et al (Wen et al., 2014, Vaccine—cited herein). Regarding claim 33, drawn to a recombinant protein for preventing or treating infection of SARS-Coronavirus-2 comprising a polypeptide that forms an extended receptor binding domain (RBD) of a SARS-Coronavirus-2 spike protein, wherein a polypeptide forming a P2 domain of Tetanus toxin is linked to the N-terminus or C-terminus of the extended receptor binding domain, Yuan et al. teaches the sequence and crystal structure of the RBD spike protein at 3.1 angstrom resolution, where specifically, the RBD is represented by amino acids 319-541 of the spike protein (abstract, Fig. 2). Regarding claim 37, drawn to an extended receptor binding domain of a spike protein of SARS-Coronavirus-2 contain the wild type RBD polypeptide sequence of SEQ ID NO: 33, Yuan et al. teaches the sequence of the RBD spike protein being amino acids 319-541, where SEQ ID NO: 33, when translated, shares 100% identity with amino acids 332-525 in Figure 2 (See Alignment: “SEQ ID NO: 33 translated vs Yuan RBD,” downloaded 15 October 2025 from < abss.uspto.gov/abss4examiners/>).
Yuan et al does not teach a polypeptide forming a P2 domain of Tetanus toxin is linked to the N-terminus or C-terminus of the extended receptor binding domain (claims 33 and 36). Regarding the P2 domain of the Tetanus toxin linked to the RBD of SARS-Coronavirus-2 spike protein, Wen et al. teaches the further improvement of vaccine potential by adding the tetanus toxoid universal CD4* T cell epitope P2 to the P[8] or P[6]ΔVP8* for the prevention of rotavirus (title, abstract). Regarding claim 36, drawn to the presence of a linker between the RBD domain and the P2 domain of Tetanus, Wen et al. teaches the utilization of the GSGSG linker sequence in the vector construction of the fusion protein (p. 4421, column 2, 1st full paragraph).
Therefore, it 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 combine the teachings of Yuan et al. with Wen et al. to construct a SARS-Coronavirus-2 RBD linked to a Tetanus P2 domain because tetanus toxoid has traditionally been considered to be a good carrier molecule to develop new vaccines, as taught by Wen et al (p. 4425, column 2, paragraph 2). One would be motivated to combine these teachings to arrive at the instant claims to produce a vaccine candidate consisting of SARS-Coronavirus-2 RBD linked to a P2 domain of Tetanus toxin to improve vaccine potential as taught by Wen et al. Further, one would be motivated to link the P2 domain of Tetanus toxin to RBD to activate specific T cells for the synthesis of certain cytokines that are necessary for T and B cell activation and interaction as well as proliferation (p. 4426, 1st column, 1st paragraph). There would be reasonable expectation of success, yielding no surprising results when combining the teachings of Yuan et al. and Wen et al. to produce a vaccine candidate consisting of a RBD domain from SARS-Coronavirus-2 and the P2 domain of Tetanus toxin, since the addition of Tetanus toxin is generally considered to be a good carrier molecule to develop new vaccines for poorly immunogenic protective epitopes because of widespread use in vaccination in humans without causing any serious harmful side effects, as taught by Wen et al (p. 4425, 2nd column, 2nd paragraph).
17. Claim 35 is rejected under 35 U.S.C. 103 as being unpatentable over Yuan et al (Yuan et al., 2020, Science—cited on the IDS dated 31 October 2022) and Wen et al (Wen et al., 2014, Vaccine—cited herein) as applied to claims 33 and 36-37 above, and further in view of Jiang et al (Jiang et al., 2015, US 9,115,186 B2—cited herein).
The teachings of Yuan et al. and Wen et al. are discussed above and incorporated into the instant rejection.
Yuan et al. and Wen et al. do not teach the utilization of a SEQ ID NO: 4, foldon domain, between the RBD and P2 Tetanus toxin domain. Jiang et al. teaches the construction of HIV-1 GP41 fusion polypeptides with an N-terminal heptad repeat and a Foldon trimerization motif (title). Specifically, Jiang et al. utilizes the Foldon domain consisting of SEQ ID NO: 30, which shares 100% identity to SEQ ID NO: 4 (See Supplemental file: 20251014_091523_us-17-922-407-4.rai, result 3).
Therefore, it 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 combine the teachings of Yuan et al. and Wen et al. with that of Jiang et al. to produce a vaccine candidate consisting of RBD of SARS-Coronavirus-2 and P2 Tetanus toxin domain to increase the stability of the polypeptides as taught by Jiang et al. (Column 5, lines 52-65). One would be motivated to combine these teachings to arrive at the instant claims to increase potency, solubility, and stability over the fused domains without the Foldon domain as taught by Jiang et al (Column 3, lines 10-16). There would be reasonable expectation of success, yielding no surprising results when combining the teachings of Yuan et al. and Wen et al. with Jiang et al. to produce a SARS-Coronavirus-2 RBD, P2 Tetanus toxin domain, and Foldon as a linker between the two domains, since Jiang et al. teaches the utilization of Foldon as a linker between two domains, NHR- or CHR-peptide, in a HIV targeting vaccine candidate.
Allowable Subject Matter
18. Claim 38 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
19. Claims 33 and 35-37 are rejected. Claim 38 is objected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CIARA A MCKNIGHT whose telephone number is (703)756-4791. The examiner can normally be reached M-F 8:00am-4:30pm.
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/CIARA A MCKNIGHT/Examiner, Art Unit 1656
/SUZANNE M NOAKES/Primary Examiner, Art Unit 1656