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
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12/05/2025 has been entered.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Claims 39-54 have an effective filing date of 28 AUG 2018.
Election/Restriction
In the response file on 5/6/2024, Applicant elected, without traverse:
Group I, claims 1-17 (Current claims 39-54)
Species
- Oligonucleotide specific to CEMIP as depicted in claim 12a (Current claim 50a)
- MHC Class I or II
- LNA nucleosides
Status of Claims
Claims 39-54 are currently pending and presented for examination on the merits.
Claims 1-38 are canceled.
Claims 39 and 41 are amended.
Rejections Withdrawn
The rejections filed under 35 U.S.C. 102(a)(1) are withdrawn in view of Applicant’s amendments to claims.
The rejections filed under 35 U.S.C. 103 are withdrawn in view of Applicant’s amendments to claims.
New Rejections
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.
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 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.
Claims 39-41, and 43-44 are rejected under 35 U.S.C. 103 as being unpatentable over Gilboa et al (Expression of new antigens on tumor cells by inhibiting nonsense-mediated mRNA decay, Immunol Res (2013) 57:44–51), and further in view of Wilton et al (WO 2018141027 A1).
Gilboa et al teaches a targeting siRNA to cells [Abstract, pg. 44]. Gilboa further teaches expressing new antigens in cells in situ [Left column, pg. 45]. Gilboa further teaches increasing the level of antigens expressed in the tumor cells potentiate their immunogenicity [Left column, pg. 45]. Gilboa further teaches using oligonucleotide aptamer ligands to increase new antigen expression [Abstract, pg. 44]. Gilboa further teaches the oligonucleotide targets Smg-1 using siRNA [Right column, pg. 47]. Gilboa further teaches inhibiting Smg-1 will inhibit the expression of nonsense-mediated mRNA decay (NMD) [Left column, pg. 47]. Gilboa further teaches siRNA-mediated inhibition of NMD stimulates a tumor specific response that can inhibit tumor growth [Right column, pg. 47]. Gilboa further teaches the oligonucleotide inhibition of NMD will cause aberrantly spliced transcripts [Right column, pg. 45]. Gilboa further teaches targeting PSMA-expressing tumor cells [Left column, pg. 48]. Gilboa further modulates the splicing by allowing aberrant spliced exons leading to aberrantly expressed antigens [Right column, pg. 45].
With respect to claims 39 and 41, the invention of Gilboa meets the limitations of a method for engineering a peptide epitope in a cell, said method comprising administration of an effective amount of an RNA modifying oligonucleotide to the cell, wherein the RNA modifying oligonucleotide targets a target RNA to modulate the coding sequence of the target RNA to produce an aberrant RNA transcript encoding an aberrant polypeptide containing the peptide epitope.
Gilboa et al does not specifically teach targeting an RNA, modulating the sequence coding, and coding sequence produces an aberrant product. However, this deficiency is made up in the teachings of Wilton et al.
Wilton et al teaches using an antisense oligomer to target an RNA sequence to modulate cleavage factor binding of the target RNA to trigger the masking of a binding site for a native protein that would otherwise cause cleavage to the shorter NEAT1 isoform and/or alters the three- dimensional structure of the targeted RNA [0053]. Wilton et al further teaches the antisense oligomer is RNA 10 to 50 nucleotides [0047-0048].
One of ordinary skill, before the effective filing date, would have been motivated to combine Gilboa’s method of engineering cells to express new epitopes/antigens in cells, with Wilton’s method of using RNA 10-50 nucleotides long to target RNA thereby modulating the coding sequence of the target RNA to produce an aberrant polypeptide. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to combine Gilboa and Wilton’s methods for a method of using an RNA oligonucleotide to target RNA, modify the coding sequence, and the target RNA produces an aberrant polypeptide, because Wilton teaches using an RNA oligonucleotide to target RNA, thereby modulating the coding sequence of the target RNA, and the target RNA producing an aberrant polypeptide.
In regard to claim 40, Wilton et al teaches the RNA is a splice modulating oligonucleotide [0053].
In regards to claim 43 and 44, at the Abstract, Gilboa teaches that the invention inhibits tumor cells, and at p. 47, Gilboa et al. discuss in vivo studies in mice.
Claims 48 is rejected under 35 U.S.C. 103 as being unpatentable over Gilboa et al (Expression of new antigens on tumor cells by inhibiting nonsense-mediated mRNA decay, Immunol Res (2013) 57:44–51), Wilton et al (WO 2018141027 A1) as applied to claims 39-41, and 43-44, and further in view of Bauer et al (WO 2014068063 A1).
Gilboa does not specifically teach the polypeptide comprising a membrane binding domain. However, this deficiency is made up in the teachings of Bauer et al.
In regards to claim 48, Bauer et al teaches a method of treating cancer comprising a pre-mRNA trans-splicing molecule (RTM) [Abstract]. Bauer et al further teaches the RTM comprises a binding domain [4th Paragraph, pg. 7]. Bauer et al further teaches the RTM targets cancer cells that selectively express the pre-mRNA [4th Paragraph, pg. 7]. Bauer et al further teaches the pre-mRNA encode SLC01B3, a transmembrane protein [4th Paragraph, pg. 8-9].
One of ordinary skill, before the effective filing date, would have been motivated to combine Gilboa and Wilton’s method of using an RNA oligonucleotide to target RNA, modify the coding sequence, and the target RNA produces an aberrant polypeptide, with Bauer’s method of treating cancer using pre-mRNA to create a membrane binding domain. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to combine the methods of Gilboa, Wilton, and Bauer et al., because the prior art teaches administering siRNA to a cell to express a new antigen. Furthermore there would have been a reasonable expectation that the resultant invention is capable of treating cancer.
Therefore the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention, as evidenced by the references.
Claims 45-47 and 49 are rejected under 35 U.S.C. 103 as being unpatentable over Gilboa et al (Expression of new antigens on tumor cells by inhibiting nonsense-mediated mRNA decay, Immunol Res (2013) 57:44–51), Wilton et al (WO 2018141027 A1), as applied to claims 39-41, 43, and 44, and further in view of Li et al (Central Role of CEMIP in Tumorigenesis and Its Potential as Therapeutic Target, Journal of Cancer 2017, Vol. 8).
Gilboa does not specifically teach a target RNA that is an RNA which is over-expressed in a cancer cell. However, this deficiency is made up in the teachings of Li et al.
Li et al teaches CEMIP as a target for therapy [Abstract, pg. 2238]. Li et al further teaches CEMIP is a mediator of cellular mortality [Right Column, pg. 2239]. Li et al further teaches over-expressed CEMIP is highly associated with tumor malignancy [Left Column, pg. 2245].
One of ordinary skill, before the effective filing date, would have been motivated to combine Gilboa and Wilton’s method of using an RNA oligonucleotide to target RNA, modify the coding sequence, and the target RNA produces an aberrant polypeptide, with Li’s identifying CEMIP (KIAA1199) as a target for cancer patients. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. CEMIP is a known target that is over-expressed in malignant tumors providing a cancer immunotherapy target. Furthermore there would have been a reasonable expectation that the resultant invention is capable of treating cancer.
With respect to claim 46, one of ordinary skill in the art would appreciate that the invention of the cited references could elicit immune responses against both secreted and membrane-bound epitopes.
With respect to claim 47, one of ordinary skill in the art would appreciate that peptide epitopes are generally presented by MHC Class I or II molecules.
Therefore the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention, as evidenced by the references.
Claim 50 is rejected under 35 U.S.C. 103 as being unpatentable over Gilboa et al (Expression of new antigens on tumor cells by inhibiting nonsense-mediated mRNA decay, Immunol Res (2013) 57:44–51), Wilton et al (WO 2018141027 A1), as applied to claims 39-41, 43, and 44, and further in view of Sadanandam et al (WO2014080381 A1).
Gilboa does not specifically teach SEQ ID NO: 1. However, this deficiency in made up in the teachings of Sadanandam et al.
Sadanandam et al teaches the genes that are useful in diagnosing cancer [Abstract]. Sadanandam et al further teaches the expression of KIAA1199 (CEMIP) [Table 2, pg. 25]. Sadanandam et al further teaches SEQ ID NO: 378. A comparison of instant SEQ ID NO: 1 and SEQ ID NO: 378 is shown below.
Instant SEQ ID NO: 1 and SEQ ID NO: 378 of Sadanandam et al.
Query Match 100.0%; Score 14; Length 172434;
Best Local Similarity 100.0%;
Matches 14; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GAAAAACATAACAA 14
||||||||||||||
Db 108341 GAAAAACATAACAA 108328
One of ordinary skill, before the effective filing date, would have been motivated to combine Gilboa and Wilton’s method of using an RNA oligonucleotide to target RNA, modify the coding sequence, and the target RNA produces an aberrant polypeptide, with Sadanandam’s CEMIP comprising SEQ ID NO:378. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. Furthermore there would have been a reasonable expectation that the resultant invention is capable of treating cancer.
Therefore the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention, as evidenced by the references.
Claims 42, and 51-53 are rejected under 35 U.S.C. 103 as being unpatentable over Gilboa et al (Expression of new antigens on tumor cells by inhibiting nonsense-mediated mRNA decay, Immunol Res (2013) 57:44–51), Wilton et al (WO 2018141027 A1), as applied to claims 39-41, 43, and 44, and further in view of Kotula et al (Aptamer-Mediated Delivery of Splice-Switching Oligonucleotides to the Nuclei of Cancer Cells, Vol 22, Num 3, 2012).
Gilboa does not specifically teach LNA nucleosides. However, this deficiency is made up in the teachings of Kotula et al.
Kotula et al teaches the antisense agent LNAs [Right Column, pg. 193].
One of ordinary skill, before the effective filing date, would have been motivated to combine Gilboa and Wilton’s method of using an RNA oligonucleotide to target RNA, modify the coding sequence, and the target RNA produces an aberrant polypeptide, with Kotula’s use of LNAs. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. Furthermore there would have been a reasonable expectation that the resultant invention is capable of treating cancer.
With respect to claim 42, LNAs may be engineered such that nitrogenous bases are deleted or added.
With respect to claim 52, it is known in the art that LNA oligonucleotides comprise modified internucleoside linkages.
Therefore the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention, as evidenced by the references.
Claim 54 is rejected under 35 U.S.C. 103 as being unpatentable over Gilboa (Expression of new antigens on tumor cells by inhibiting nonsense-mediated mRNA decay, Immunol Res (2013) 57:44–51), Wilton et al (WO 2018141027 A1), as applied to claims 39-41, 43, and 44, and further in view of Hunziker et al (WO2018052374 A1).
Gilboa does not specifically teach morpholino oligonucleotides. However, this deficiency is made up in the teachings of Hunziker et al.
Hunziker et al teaches pre-mRNA anti-sense therapy that includes morpholino oligonucleotide [0033].
One of ordinary skill, before the effective filing date, would have been motivated to combine Gilboa and Wilton’s method of using an RNA oligonucleotide to target RNA, modify the coding sequence, and the target RNA produces an aberrant polypeptide, with Hunziker’s pre-mRNA therapy comprising morpholino oligonucleotides. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. Furthermore there would have been a reasonable expectation that the resultant invention is capable of treating cancer.
Therefore the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention, as evidenced by the references.
Applicant’s Arguments:
Gilboa does not teach or suggest that the oligonucleotide that targets Smg-1 modulating the coding sequence of the target RNA [Smg-1], wherein said coding sequence of said target RNA [again, Smg-1] produces an aberrant RNA transcript, as is required by claim 39. Instead, an siRNA- inactivated Smg gene (or Upf-1, Upf-2 or Upf-3 gene) will disrupt or inactivate NMD complexes on other genes, causing those other genes to produce aberrant transcripts. The Office Action confuses which transcripts are targeted, and which ones are aberrantly spliced. This is a distinction with a substantial difference, and as a result, Gilboa cannot anticipate claim 39.
The alignment for KIAA 1199 depicted at page 10 of the Office Action shows the sequence to be 172434 nucleotides long. As noted above, claim 39, from which claim 50 depends, is amended herein to specify an oligonucleotide length of 10-30 nucleotides
Examiner’s Response:
Applicant states, “Gilboa does not teach or suggest that the oligonucleotide that targets Smg-1 modulating the coding sequence of the target RNA [Smg-1], wherein said coding sequence of said target RNA [again, Smg-1] produces an aberrant RNA transcript, as is required by claim 39.”
Wilton et al teaches using an antisense oligomer to target an RNA sequence to modulate cleavage factor binding of the target RNA to trigger the masking of a binding site for a native protein that would otherwise cause cleavage to the shorter NEAT1 isoform and/or alters the three- dimensional structure of the targeted RNA [0053].
Applicant states, “claim 50 depends, is amended herein to specify an oligonucleotide length of 10-30 nucleotides”.
Wilton et al teaches the antisense oligomer is RNA 10 to 50 nucleotides [0047-0048].
One of ordinary skill, before the effective filing date, would have been motivated to combine Gilboa’s method of engineering cells to express new epitopes/antigens in cells, with Wilton’s method of using RNA 10-50 nucleotides long to target RNA thereby modulating the coding sequence of the target RNA to produce an aberrant polypeptide. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to combine Gilboa and Wilton’s methods for a method of using an RNA oligonucleotide to target RNA, modify the coding sequence, and the target RNA produces an aberrant polypeptide, because Wilton teaches using an RNA oligonucleotide to target RNA, thereby modulating the coding sequence of the target RNA, and the target RNA producing an aberrant polypeptide.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DENNIS JOHN SULLIVAN whose telephone number is (571)272-0509. The examiner can normally be reached Mon - Fri: 7:30AM - 4:30PM.
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/DENNIS J SULLIVAN/ Examiner, Art Unit 1642
/NELSON B MOSELEY II/ Primary Examiner, Art Unit 1642