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 .
Election/Restrictions
For the purpose of expedited prosecution, claim 4 has been rejoined for prosecution.
Because a claimed invention previously withdrawn from consideration under 37 CFR 1.142 has been rejoined, the species election restriction requirement in the Office action mailed on February 16, 2024 is hereby withdrawn. In view of the withdrawal of the restriction requirement as to the rejoined inventions, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application.
Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claims 1, 4, 6-13, 15-18, 21, 22, 24-26, 29-31, and 34-38 are pending and being examined on the merit.
Withdrawal of Rejections/Objections
Previous objection to claims 1, 3, 5-18, 21-22. 24-26, 29-34 and claims 35-37 for typographical error is withdrawn in view of claim amendments.
Previous rejection of claims 1, 3, 5-18, 21-22. 24-26, 29-30, 33-34 and 35-37 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in view of claim amendments.
Previous rejection of claims 1, 6-13, 15-18, 21, 22, 24-26, 29-31, and 34-38 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in view of claim amendments.
Previous rejection of claims 21-22, 24-26 and 36 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph is withdrawn in view of claim amendments.
New Rejections Necessitated by Rejoinder
Claim Rejections - 35 USC § 112
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 15-17, 34 and 35 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.
Claims 15 and 16 are dependent from claim 14, which is a cancelled claim. Further, claim 34 is dependent from claim 33, which is a cancelled claim. Thus, the metes and bounds of claims 15, 16, and 34 are unclear.
Claim 17 recites the limitation "said nucleic acid". There is insufficient antecedent basis for this limitation in the claim. Claim 17 is dependent from claim 1. Claim 1 recite DNA and not nucleic acid. Claim 35 is dependent from claim 17 and does not remedy the deficiency. Thus, the metes and bounds of the claim is unclear.
Regarding claim 34, the phrase "(residues 412 to 682 of SEQ ID No.3)" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP 2173.05(d).
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 4 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 1 is directed to a cancer vaccine comprising nucleic acids encoding for a truncated MAGED4B that is between 400-700 amino acids in length. Claim 4 is dependent from claim 1 and limits the nucleic acid to comprise the sequences of SEQ ID NO:7, 16, or 17. SEQ ID NO:7, 16, or 17 are comprised of 7446, 2226, or 2226 nucleotides, which encodes for a cancer vaccine that is more than 700 amino acids long. Thus, claim 4 does not further limit the limitations of claim 1.
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.
New Rejections Necessitated by newly filed IDS
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.
Claim(s) 1,6, 12, 13, 15, 16, 18, 22, 26, 34, 31, and 37 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kipps (US6287569), Lim (Cancer Research, 2012, AACR 103 annual Meeting, Abstract 1573, IDS entered on December 3, 2025), and Chomez (Cancer Research, 2001, 61:5544-5551).
Page 5 of the instant specification defined a helper motif as a nucleic acid sequence that stimulates an immune response directly or indirectly.
Regarding claims 1, 6, 12, and 15 Kipp teaches a method of treating cancer comprised of administering a pharmaceutical composition comprising a plasmid DNA encoding a chimeric immunogen comprising (1) a ubiquitin molecule (same as a helper motif), connecting to (2) intervening amino acid sequences (same as linker), and (3) a MAGE-4B (same as MAGED4B) protein (column 2, see “Summary of the Invention”; claims 1 and 3) (ubiquitin-linker-MAGED4B), wherein the MAGE-4B includes a full length MAGE-4B protein as encoded by nucleic acid sequence of SEQ ID NO:10 (table 1) or a portion of a protein (abstract; column 3, paragraph 6).
Alignment of instant SEQ ID NO:3 (MAGED4B) and translated nucleic acid sequence of SEQ ID NO:10 (MAGE-4B) of Kipps:
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995
655
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Kipp teaches that the nucleic acid encodes a chimeric protein comprising an antigen protein and the ubiquitin molecule, wherein the ubiquitin enhances the degradation of the protein leading to enhance cellular immunity and MHC-I presentation to stimulate T cell-mediated immunity against the protein (column 1, paragraph 2; column 2, see “Summary of the invention”). Kipp further teaches that cellular processing of the chimeric immunogen induces a greater immune response and generation of specific antibodies (column 3, 3rd paragraph).
Regarding claim 13, Kipp teaches that the chimeric protein comprises a removable leader sequence (same as signal peptide), intervening amino acid and ubiquitin acceptor linked together (column 5, paragraphs 2-3). Regarding claim16, Kipp teaches that the DNA plasmid constructure further comprises a promoter operably linked to the coding sequence, and a polyadenylation signal downstream of the antigen protein (column 12, paragraphs 2-3). Regarding claim 22, the Kipp teaches administering the DNA plasmid to a human to treat cancer (column 3, paragraphs 3 and 5; column 10, last paragraph)
Kipp does not teach that the MAGED4B protein of ubiquitin-linker-MAGED4B is comprised of 400-700 amino acid that is 95% sequence identity to SEQ ID NO:3, and comprises removal of a part of a MAGE homology domain comprising 412-682 of SEQ ID NO:3. However, this deficiency is made up in Lim and Chomez.
Lim teaches that MAGED4B (same as MAGE-4B) is a member of the MAGE family that is overexpressed in 50% of oral squamous cell carcinoma (OSCC) (lines 2-3). Lim teaches generation of the of MAGED4B specific peptides for vaccination to treat OSCC (page 1). Lim teaches that MAGED4B specific peptides leads peptide specific cytotoxicity against MAGED4B-expressing OSCC cells (page 2). Lim further teaches that the MAGED4B specific peptides are capable of inducing anti-tumor specific immune response.
Chomez teaches that the MAGE4D family members have low homology with other MAGE family of proteins, but does have a high homology to other MAGED proteins (figures 3, 4, and 7). Chomez teaches that residues 479-682 of MAGE4D has the highest homology with other MAGED proteins (figures 6 and 7).
One of ordinary skill in the art before the effective filing date would have been motivated to modify MAGED4B of the cancer vaccine comprising nucleic acids to encode for ubiquitin-linker-MAGE4B of Kipp, to comprise residues 1-478 of MAGED4B (same as instant SEQ ID NO:35), which are unique residues of MAGED4B as taught in Chomez, in order to generate a specific MAGED4B vaccine that can induce a cellular immunity against OSCC. Kipp teaches a cancer vaccine that induces cellular immunity comprising nucleic acids to encode for ubiquitin-linker-MAGED4B, wherein the MAGED4B protein is a full-length or a portion of said protein, Lim teaches that MAGED4B is overexpressed in 50% of OSCC, and Chomez teaches that residues 1-478 is unique to MAGED4B (same as instant SEQ ID NO:35). Thus, it would be obvious to a skill artisan to generate a vaccine for MAGED4B comprising residues 1-478 of MAGED4B, which are the unique residues for MAGED4B. Furthermore, regarding claim 13, it would obvious that the DNA plasmid encoding ubiquitin-linker-residues 1-489 of MAGED4B would also comprise a signal peptide because Kipp teaches adding a nucleic acid encoding a signal peptide.
The modified plasmid DNA encoding a chimeric protein comprising ubiquitin-linker-residues 1-478 of MAGED4B of Kipp, Lim and Chomez, is comprised of a truncated MAGED4B with 489 amino acids which has a 100% sequence identity to a sequence set forth in instant SEQ ID NO:3 and SEQ ID NO:35. Regarding claim 6, further ubiquitin of a chimeric protein comprising ubiquitin-linker-residues 1-489 of MAGED4B is an immunological fragment of a protein. Regarding claim 21, the modified plasmid DNA encoding a chimeric protein comprising ubiquitin-linker-residues 1-489 of MAGED4B of Kipp, Lim and Chomez can be used in combination with anti-cancer agents.
One of ordinary skill in the art before the effective filing date would have had a reasonable expectation of success for generating a MAGED4B specific vaccine comprising DNA encoding for a chimeric protein comprising ubiquitin-linker-residues 1-478 of MAGED4B for the treatment of OSCC, because Kipp teaches a cancer vaccine comprising a DNA encoding for a chimeric protein comprising ubiquitin and a portion of MAGED4B, Chomez teaches that residues 1-478 of MAGED4B is unique to MAGED4B, and Lim teaches that OSCC has overexpression of MAGED4B.
Claim(s) 9-11, 21, and 24-25 is/are rejected under 35 U.S.C. 103 as being unpatentable over 1,6, 13, 15, 16, 18, 22, 26, and 34 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kipps (US6287569), Lim (Cancer Research, 2012, AACR 103 annual Meeting, Abstract 1573, IDS entered on December 3, 2025), and Chomez (Cancer Research, 2001, 61:5544-5551) as applied to claim 1 above, and further in view of Chai (WO2018169385A1).
The teachings of Kipps, Lim, and Chomez are described above.
The combined teachings of Kipps, Lim, and Chomez do not teach that the DNA plasmid comprising nucleic acid sequences of a chimeric protein comprising ubiquitin-linker-residues 1-478 of MAGED4B also comprises a truncated FJX1 protein comprising the amino acid sequence of SEQ ID NO:4. However, these deficiencies are made up in Chai et al.
Regarding claims 9-11, Chai teaches a method of treating MAGED4B expressing cancer (page 3, paragraph 4), comprised of administering a peptide comprising Four-jointed box 1 (FJX1) and MAGED4B (Page 7, paragraph 1). Chai teaches that 100% of the OSCC cells has a high expression of both FJX1 and MAGED4B (page 7, last paragraph; table 1). Chai teaches a peptide composition comprising a FJX1 peptide and MAGED4B peptide which binds to MHC-I to induce an anti-cancer response (claim 1), wherein FJX1 peptide is comprised of SEQ ID NO:1 (same as a truncated peptide of instant SEQ ID NO:4) (claim 3). Regarding claims 21, and 24-25, Chai teaches a therapeutic comprising the immunogenic peptide comprising FJX1 and MAGED4B, and an anti-PD-1 antibody (claims 12-15). Chai teaches that the immunogenic peptide comprised of both FJX1 and MAGED4B peptides enhanced the activation of CD8 cells more than either peptide alone (figure 2).
One of ordinary skill in the art before the effective filing date would have been motivated to modify the DNA plasmid encoding for ubiquitin-linker-residues 1-478 MAGED4B of combined teachings of Kipp, Lim and Chomez to also comprise the FJX1 peptide of Chai to generate a chimeric protein comprising ubiquitin-linker-residues 1-478 MAGED4B-FJX1 to more effectively mount an MHC-I T cell-mediated response against OSCC. Kipp teaches that cellular processing of immunogenic peptides and MHC-I presentation of antigen peptide is more effective at stimulating T cell immunity, and Chai teaches that both FJX1 and MAGED4B are overexpressed in OSCC, and immunogenic peptides comprising both FJX1 an MAGED4B are more effective at inducing an MHC-I response. Thus, one of ordinary skill in the art before the effective filing date would have had a reasonable expectation of success for generating a MAGED4B specific vaccine comprising DNA encoding for a chimeric protein comprising ubiquitin-linker-residues 1-478 of MAGED4B-FJX1 to specifically target MAGED4B and FJX1 expressing OSCC, because the combined teachings of Kipp, Lim, and Chomez teaches a cancer vaccine comprising a DNA encoding for a chimeric protein comprising ubiquitin-linker-residues 1-478 of MAGED4B to target only MAGED4B expressing cancer cells, and Chai teaches that OSCC overexpresses MAGED4B and FJX1, a vaccine comprising peptides for both MAGED4B and FJX1 are more effective at inducing an MHC-I immune response against OSCC.
Regarding claims 21, and 24-25, it would be obvious to modify the combined methods of treating OSCC comprised of administering a cancer vaccine comprising a DNA plasmid comprising nucleic acids encoding for ubiquitin-linker-residues 1-478 of MAGED4B-FJX1 of Kipp, Lim, Chomez, and Chai, with an anti-PD-1 antibody as taught in Chai in order to enhance the immune response against OSCC. One of ordinary skill in the art before the effective filing date would have had a reasonable expectation of success for treating OSCC comprised of administering a cancer vaccine comprising a DNA plasmid comprising nucleic acids encoding for a chimeric protein comprising ubiquitin-linker-residues 1-478 of MAGED4B-FJX1 and anti-PD-1 antibody because both the chimeric protein ubiquitin-linker-residues 1-478 of MAGED4B-FJX1 and anti-PD-1 antibody functions to enhance the immune response against cancer cells.
Claim(s) 7 and 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kipps (US6287569), Lim (Cancer Research, 2012, AACR 103 annual Meeting, Abstract 1573, IDS entered on December 3, 2025), and Chomez (Cancer Research, 2001, 61:5544-5551), as applied to claims 1 above, and further in view of Bedi et a. (WO2009018500A1).
The teachings of Kipps, Lim, and Chomez are described above.
The combined teachings of Kipps, Lim, and Chomez do not teach a DOM helper motif. However this deficienciegs are made up in Bedi et al.
Bedi teaches an immunogenic peptide comprising an antigenic peptide and a helper motif, wherein the helper motif, including DOM-1 of tetanus toxin, enhances the T cell immunity against the antigenic peptide (paragraphs 0008 and 0013). Bedi further teaches that addition of DOM-1 will enhance the activation of CD4 T helper cells and overall immunity (paragraphs 0323 and 0364).
One of ordinary skill in the art before the effective filing date would have been motivated to modify the DNA plasmid encoding for ubiquitin-linker-residues 1-478 MAGED4B of combined teachings of Kipp, Lim and Chomez to also comprise a helper motif comprising the DOM-1 of Bedi in order to generate a chimeric protein that can mount a strong T cell immunity against cells expressing the antigenic peptide. Bedi teaches that addition of a DOM-1 motif will enhance the immune response against the antigen. Thus, one of ordinary skill in the art before the effective filing date would have had a reasonable expectation of success for generating a MAGED4B specific vaccine comprising DNA encoding for a chimeric protein comprising ubiquitin-linker-residues 1-478 of MAGED4B with DOM-1 to specifically target MAGED4B expressing OSCC, because the combined teachings of Kipp, Lim, and Chomez teaches a cancer vaccine comprising a DNA encoding for a chimeric protein comprising ubiquitin-linker-residues 1-478 of MAGED4B to target only MAGED4B expressing cancer cells, and Bedi teaches that attachment of DOM-1 to a vaccine peptide will enhance the T cell immunity against the antigen peptide. .
Claim(s) 38 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kipps (US6287569), Lim (Cancer Research, 2012, AACR 103 annual Meeting, Abstract 1573, IDS entered on December 3, 2025), Chomez (Cancer Research, 2001, 61:5544-5551), Chai (WO2018169385A1), and Bedi (WO2009018500A1).
The combined teachings of Kipps, Lim, Chomez, and Chai are described above. The combined teachings of Kipps, Lim, Chomez, and Chai teaches a DNA encoding for a chimeric protein comprising ubiquitin-linker-residues 1-478 of MAGED4B-FJX1 to specifically target MAGED4B and FJX1 expressing OSCC cells.
The combined teachings of Kipps, Lim, Chomez, and Chai does not teach that the chimeric protein comprising ubiquitin-linker-residues 1-478 of MAGED4B-FJX1 also comprise a DOM-1 domain.
The teachings of Bedi are described above.
One of ordinary skill in the art before the effective filing date would have been motivated to modify the DNA plasmid encoding for ubiquitin-linker-residues 1-478 MAGED4B-FJX1 of combined teachings of Kipp, Lim, Chomez and Chai to also comprise a helper motif comprising the DOM-1 of Bedi in order to generate a chimeric protein that can mount a strong T cell immunity against cells expressing the antigenic peptide. Bedi teaches that addition of a DOM-1 motif will enhance the immune response against the antigen. Thus, one of ordinary skill in the art before the effective filing date would have had a reasonable expectation of success for generating a MAGED4B specific vaccine comprising DNA encoding for a chimeric protein comprising ubiquitin-linker-residues 1-478 of MAGED4B-FJX1 attached to DOM-1 to specifically target MAGED4B and FJX1 expressing OSCC, because the combined teachings of Kipp, Lim, Chomez, and Chai teaches a cancer vaccine comprising a DNA encoding for a chimeric protein comprising ubiquitin-linker-residues 1-478 of MAGED4B-FJX1 to target only MAGED4B expressing cancer cells, and Bedi teaches that attachment of DOM-1 to a vaccine peptide will enhance the T cell immunity against the antigen peptide.
Conclusion
No claims allowed.
Applicant's submission of an information disclosure statement under 37 CFR 1.97(c) with the timing fee set forth in 37 CFR 1.17(p) on 3 December 2025 prompted the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 609.04(b). 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.
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/JULIE WU/ Supervisory Patent Examiner, Art Unit 1643