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 .
Applicant’s amendments, filed 1/06/2026, is acknowledged.
Claims 23-42 are currently pending.
Claims 23-30, 35, 36, 38, 41, and 42 stand withdrawn from further consideration pursuant
to 37 CPR l.142(b), as being drawn to nonelected inventions.
Claims 31-34, 37, 39, and 40 are under examination.
Applicant’s amendments to claim 31, filed 1/06/2026, has obviated the previous 35 U.S.C. § 101 rejection in the Office Action mailed on 8/06/2025, and this rejection is withdrawn.
In view of the amendments and remarks filed on 1/06/2026, the following rejections remain.
Claim Objections
Claims 37 and 39 are objected to because they recite separate products with two distinct structural features (i.e., "a recombinant peptide" and "a nucleic acid"). Appropriate correction is required. Amending the claims to recite the elected invention (i.e., a nucleic acid or a recombinant host cell comprising a nucleic acid) will resolve this issue.
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 31-34, 37, 39, and 40 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 claims contain 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 inventors, at the time the application was filed, had possession of the claimed invention. This is a new grounds of rejection necessitated by Applicant’s amendments.
Claims 31-34, 37, 39, and 40 are rejected under 35 U.S.C.§ 112(a) written description for the same reasons discussed in the Office Action mailed on 8/06/2025. Briefly, the claims encompass nucleic acids encoding the recited peptide sequences and variants with one amino acid exchanged, all with the function of "bind to molecule(s) of the major histocompatibility complex (MHC) and/or induce T cells cross-reacting", and there is inadequate written description support in the specification for a broad class of nucleic acids encoding peptides and variants all with the recited function.
Applicant’s remarks, filed 1/06/2026, have been fully considered, but have been found to be not convincing.
Applicant has amended the claims to recite a more limited number of amino acid sequences, as well as variants with one residue difference to the recited sequences, with the function of “bind to molecule(s) of the major histocompatibility complex (MHC) and/or induce T cells cross-reacting". Applicant argues (remarks pg. 12): “[o]ne skilled in the art would recognize that peptides differing from the recited SEQ ID NOs by one terminal extension or a single amino-acid exchange would still possess the desired functional properties…”
This has been found to be not convincing. As discussed in the Office Action mailed on 8/06/2025, there is an unpredictability in the art in varying a peptide’s amino acid sequence and maintaining binding to both MHC complexes and TCRs.
Additionally, Ben-Nun et al. (Eur J Immunol. 2006 Feb;36(2):478-93. doi: 10.1002/eji.200535363) teaches that a single amino acid substitution in an epitope con disrupt cross-reactivity with T-cells (Table 4 and pg. 484): “reactivity of the T cell lines to MOG37–41A–52 (Arg to Ala substitution) and to MOG37–47A–52 (Val to Ala substitution) was considerably reduced (by ~70%). Most strikingly, the Ala substitution of MOG44F almost
totally abrogated (96% reduction) the capacity of MOG37–44A–52 to stimulate the encephalitogenic line T cells selected from MOG35–55- or MOG37–52-primed cells (Table 4).”
Furthermore, Bonomi et al. (Hum Immunol. 2000 Aug;61(8):753-63. doi: 10.1016/s0198-8859(00)00147-6) teaches that different single amino acid substitutions can alter a peptide epitope binding to peptide-specific T-cells (pg. 756 and Table 1): “[a]s summarized in Table 1, both clones reacted against wild-type pep23 and against a pep23 analogue in which aspartic acid in position 2 had been substituted with alanine. The proliferation of clone 2 and 30 was abolished when a D8A substitution was introduced in pep23. On the contrary, clone 2, but not clone 30, failed to react against pep23 carrying a W4A or I9A or K11A substitution. Interestingly, the two clones also exhibited a different pattern of reactivity when the K11 residue was substituted by residues other than alanine. In fact, as shown in Table 1, the K11G pep23 analogue was recognized by clone 30, but not by clone 2, whereas substitution of lysine in position 11 with either leucine or isoleucine led to failure to respond of both clones.”
Bonomi et al. further teaches fusion of an epitope to the C-terminus of a second peptide GST reduced the immunogenicity of the peptide and activation of T-cells (pg. 757 and Fig. 1): “[w]e then assessed the ability of APC to induce activation of clone 2 when pulsed with the amounts of GST-23 or 23-GST thus determined. Figure 1B shows that, in spite of the conditions of equivalence set, clone 2 is unresponsive to 23-GST over a 100-fold concentration range (0.05±5 mM)…”.
Both Ben-Nun et al. and Bonomi et al. demonstrate that single amino acid substitutions can significantly alter a peptide’s binding to TCRs and subsequent T-cell activation, and Bonomi et al. demonstrates that N or C-terminal fusions can also significantly alter TCR binding and T-cell activation.
Thus, the prior art teaches that even single amino acid substitutions, as well as N or C-terminal fusions, can disrupt a peptide’s immunogenicity and cross-reactivity with T-cells, and there is no predictable structure function relationship between which substitutions/fusions would retain immunogenicity. Therefore, there is significant unpredictability as to which peptide variants in the instant claims would retain the function of “bind to molecule(s) of the major histocompatibility complex (MHC) and/or induce T cells cross-reacting", or how to distinguish these peptides from ones without this function.
Claims 31-34, 37, 39, and 40 do not meet the requirements of 35 U.S.C. 112(a) for written description.
Amending the claims to recite the amino acid sequences without variants would overcome this rejection.
Claim Rejections - 35 USC § 102
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.
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 31-33 are rejected under 35 U.S.C. 102(a)(1)/(2) as being anticipated by Diamond et al. (WO9919349) as evidenced by Davison et al. (J Mol Biol. 1989 Dec 20;210(4):771-84. doi: 10.1016/0022-2836(89)90108-3). This is a new grounds of rejection necessitated by Applicant’s amendments.
Diamond et al. teaches MHC reactive peptides (claim 1), including SEQ ID NO: 7 (pg. 15 and claim 9), which is 100% identical to instant SEQ ID NO: 25:
Qy 1 TPRVTGGGAM 10
||||||||||
Db 1 TPRVTGGGAM 10
Diamond et al. further teaches DNA encoding the peptide and viral vectors (i.e., “expression vector”) comprising the DNA (claim 20): “[a] viral vector containing a DNA sequence encoding an immunologically active peptide…” (pg. 12): “…viral vector that contains DNA encoding the peptide fragment under the control of appropriate expression regulatory sequences…”.
Diamond et al. teaches that SEQ ID NO: 7 is a pp65 epitope (pg. 35 and Table 6): “[t]able 6 shows the pp65 epitopes…” Diamond et al. additionally teaches cells comprising DNA encoding the peptides (pg. 21): “[a] CRA utilizing autologous and HLA mismatched LCL as targets, infected with vaccinia viruses expressing truncation products of the pp65 protein, was conducted…”
Diamond et al. teaches vaccinia viral vectors comprising DNA encoding the claimed peptides (claim 22). Davison et al. is provided as an evidentiary reference demonstrating vaccinia virus has vaccinia virus promoters (i.e., “heterologous promoter”, Davison et al. Abstract): “…elements of vaccinia virus late promoters were characterized…”
Diamond et al., as evidenced by Davison et al., anticipates the invention of claims 31-33.
Claim Rejections - 35 USC § 103
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.
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 31-34 are rejected under 35 U.S.C. 103 as being unpatentable over Diamond et al (supra) in view of Darnell et al. (Molecular Cell Biology. 1986. W.H. Freeman and Co., in Office Action mailed on 8/06/2025), as evidenced by Davison et al. (supra).
The teachings of Diamond et al. as evidenced by Davison et al. have been discussed in the 35 U.S.C. 102 rejection supra. The claimed invention differs from the reference teachings only by the recitation of a method for producing a polypeptide (instant claim 34).
Darnell et al. teach that in order to prepare an unlimited amount of a pure gene or (i.e., “a nucleic acid”, the limitations instant claim 31), a vector containing the gene can be grown in a host cell and DNA extracted (i.e., “a nucleic acid encoding a polypeptide”; the limitations of instant claims 32 and 33). Darnell et al. also teach an expression vector in order to take advantage of “bacterial tricks” that increase mRNA synthesis to produce large quantities of desired proteins using a eukaryotic vector and host cell, or a prokaryotic and bacterial vector and host cell (page 255-258 in particular).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to express the polypeptide taught by Diamond et al. as evidenced by Davison et al. using the encoding nucleic acids, vectors, host cells and the method of producing the polypeptide as taught by Darnell et al.
One of ordinary skill in the art at the time the invention was made would have been motivated to do so because a vector containing the gene that is grown in a host cell offers to prepare an unlimited amount of an encoding nucleic acid as well as to produce large quantities of desired polypeptides/peptides as taught by Darnell et al.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 31-33, 37, 39, and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Diamond et al (supra) in view of Levner et al. (WO2013096851, in Office Action mailed on 8/06/2025), as evidenced by Davison et al. (supra).
The teachings of Diamond et al. as evidenced by Davison et al. have been discussed in the 35 U.S.C. 102 rejection supra. Diamond et al. as evidenced by Davison et al. does not teach pharmaceutical compositions comprising the nucleic acid and an acceptable carrier (claim 37), or kits comprising the nucleic acid and another element such as a buffer (claims 39 and 40).
Levner et al., in the same field of endeavor, teaches compositions and methods to detect analytes in vitro and in vivo (entire document). A sample is contacted with a composition comprising at least one detection probe, followed by detecting the probe (¶[0055] and claim 1). The detection probe can be a nucleic acid that can be used to detect target DNA via methods such as in situ hybridization (¶[00102] and ¶[00119]). Levner et al. additionally teaches probe reagents in pharmaceutical compositions with an acceptable carrier for in vivo administration (¶[0059]). Levner further teaches kits comprising the detection probes (¶[00276]-[00277]), and further comprising other reagents such as wash buffers used in the detection method (i.e., “buffer”; ¶[00280] and [00282]), as well as informational material such as instructions for use and a delivery device (¶[00286]-[00287]). Levner et al. teaches the kit has a container to place all the items into (¶[00289]).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the instant invention, to have modified the nucleic acid of Diamond et al. as evidenced by Davison et al. in view of Levner et al. to create pharmaceutical compositions and kits comprising the nucleic acid as a probe for detection in vitro and in vivo of pp65 DNA encoding SEQ ID NO: 25, as Levner et al. teaches methods of detection of target analytes in this format. One would have been motivated to make this change for the purposes of using the encoding nucleic acid molecule of Diamond et al. as evidenced by Davison et al. as a probe in compositions and kits for in vivo detection of pp65 DNA, and to package the DNA probe into kits with instruction for use to ease the use of the probe and detection method.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 ALEC JON PETERS whose telephone number is (703)756-5794. The examiner can normally be reached Monday-Friday 8:30am - 6:00pm EST.
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/ALEC JON PETERS/Examiner, Art Unit 1641
/MAHER M HADDAD/Primary Examiner, Art Unit 1641