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 .
DETAILED ACTION
Acknowledgement is hereby made of receipt and entry of the communication filed on Nov. 29, 2023. Claims 1-5, 45 and 50-63 are pending and are currently examined.
Claim Objection
Claims 1-6 are objected to because of the following informalities:
These claims recite the phrases “…comprising the sequence as set forth in SEQ ID NOs…” or “…identity to the sequence as set forth in SEQ ID NOs…”, where the “set forth” should be deleted and the phrases should be “…comprising the sequence of SEQ ID NOs…” or “…identity to the sequence of SEQ ID NOs…”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1-5, 45 and 50-63 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.
Claims 1-5 are drawn to an EBV vaccine comprising the sequence as set forth in SEQ ID NOs: 304, 305, 306, 307, 308, 309, 310, 311, 312, or 313 or a sequence having at least 90% sequence identity to the sequence as set forth in SEQ ID NOs: 304, 305, 306, 307, 308, 309, 310, 311, 312, or 313.
Claims 50-63 are drawn to a method of stimulating an anti-EBV immune response in a subject comprising administering to the subject a therapeutically effective amount of the EBV vaccine of claim 1 to the subject, thereby stimulating an EBV immune response in the subject, where the EBV vaccine of claim 1 comprises the sequence as set forth in SEQ ID NOs: 304, 305, 306, 307, 308, 309, 310, 311, 312, or 313 or a sequence having at least 90% sequence identity to the sequence as set forth in SEQ ID NOs: 304, 305, 306, 307, 308, 309, 310, 311, 312, or 313, comprises the sequence as set forth in SEQ ID NOs: 294, 295, 296, 297, 298, 299, 300, 301, 302, or 303 or a sequence having at least 90% sequence identity to the sequence as set forth in SEQ ID NOs: 294, 295, 296, 297, 298, 299, 300, 301, 302, or 303, or comprises the sequence as set forth in SEQ ID NOs: 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 or a sequence having at least 90% sequence identity to the sequence as set forth in SEQ ID NOs: 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15.
The written description rejection is made because the claims are interpreted as being drawn to a EBV vaccine recited as being “at least 90% identity” to the instant claimed SEQ ID NOs: 304-313, SEQ ID NOs: 294-303 or SEQ ID NOs: 6-15. This means that up to 10% amino acids sequences of the EBV vaccine of claim 1 can vary. For example, the claimed SEQ ID NO: 310 is a synthetic protein with the length of 932 amino acids, which show 99% percent identity to the EBV glycoprotein B encoded by the EBV BALF4 gene (See Table A below). If there are 10% sequence variations, it would differ by over 90 amino acids along the entire length of the sequence.
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464
601
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The instant specification discloses that their invention provides anti-Epstein Barr virus (EBV) vaccines and uses of the same, and the EBV vaccine antigens can be formulated to treat an EBV-infected subject or a subject at risk of EBV infection. Treating EBV can reduce EBV infection and/or treat a condition associated with EBV infection (See [0008]- [0009]). The instant specification also discloses that the primary goal of most vaccine design strategies is to elicit production of neutralizing antibodies, which are a type of antibody that can inhibit the biological function of its target. Neutralizing antibodies against viruses such as EBV typically function by blocking a virus from entering a cell (See [0034]).
However, the specification does not indicate which portions of the claimed SEQ ID NOs are essential to retain the ability to be a functional vaccine to induce the subject’s immune responses, and which portions of SEQ ID NOs can be modified or altered up to 10% and still retain the ability of eliciting the claimed immune responses.
It is a common knowledge in the art that the sequence variations in EBV can significantly alter the stimulated immune response, for example, a minor sequence changes within critical T-cell epitopes can affect immune recognition. This can be evidenced by Cirac’s study (J Immunol Sci. (2018); 2(3): 51-55). Cirac et al. teaches that their study clearly demonstrated that sequence variations in EBV strains may reside within T-cell epitopes and potentially compromise the antiviral CD8+ T-cell response (See page 52, right column, paragraph 2). Another evidence is from Zhang’s study (Proc Natl Acad Sci U S A. 2022 Aug 9;119(32): e2202371119). Zhang et al. teaches a point mutation in the glycoprotein of EBV can change its binding to the neutralizing antibody. Zhang et al. disclsoes two anti-EBV gB neutralizing antibodies, 3A3 and 3A5, that effectively neutralized EBV infection of both B and epithelial cells. They also potently protected against EBV-induced lymphoproliferative disorders in humanized mice. Importantly, the 3A3 and 3A5 epitopes are major targets of protective gB-specific neutralizing antibodies elicited by natural EBV infection in humans, providing potential targets for antiviral therapies and vaccines (See Abstract and Significance). However, Zhang et al. also teaches that gB with the point mutations of E356A or D360A completely abolished binding with mAb 3A3, while H352A retained a weak interaction with 3A3 (Fig. 6A) (See page 8, right column).
The applicable standard for the written description requirement can be found in MPEP 2163; University of California v. Eli Lilly, 43 USPQ2d 1398 at 1407; PTO Written Description Guidelines; Enzo Biochem Inc. v. Gen-Probe Inc., 63 USPQ2d 1609; Vas- Cath Inc. v. Mahurkar, 19 USPQ2d 1111; and University of Rochester v. G.D. Searle & Co., 69 USPQ2d 1886 (CAFC 2004).
The court clearly states in Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.).
As discussed above, the skilled artisan cannot envision the detailed genomic sequence of the EBV vaccine that are "at least 90% identical” to SEQ ID NOs for still being able to stimulate an anti-EBV immune response in a subject or become a EBV vaccine, therefore, the full breadth of the claims does not meet the written description provision of 35 U.S.C. 112, first paragraph.
Allowable Subject Matter
The amino acids sequence SEQ ID NOs: 6-15 and 294-313 are free of prior art.
The amino acids sequence having at least 90% sequence identity to the sequence as set forth of SEQ ID NOs: 6-15 and 294-313 are free of prior art.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RUIXUE WANG whose telephone number is (571)272-7960. The examiner can normally be reached Monday-Friday 8:00 am-4:30 pm, EST.
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/RUIXUE WANG/Examiner, Art Unit 1672
/THOMAS J. VISONE/ Supervisory Patent Examiner, Art Unit 1672