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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 10/13/2025 has been entered.
Response to Amendment/Status of Claims
Receipt of Arguments/Remarks filed on 10/13/2025 is acknowledged. Claim 16 was cancelled. Claims 15,28 and 47 were amended. Claims 1-3,5-10,12,15,16,20, 23,28,38,39,41 and 47-55 are pending. Claims 1-3,5-10,12,23,38,39 and 41 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/05/2024. Claims 15,20,28 and 47-55 are directed to the elected invention and are under examination.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Response to Arguments
Applicant’s arguments and amendments, see page 7, filed 10/13/2025, with respect to the 35 U.S.C. 112(b) rejection of claim 47 have been fully considered and are persuasive due to the amendment to claim 47 to correctly depend from claim 15. The 35 U.S.C. 112(b) rejection of claim 47 has been withdrawn.
Information Disclosure Statement
The information disclosure statement filed 01/16/2026 includes an NPL reference missing a date. See NPL citation No. 1, “Homo sapiens ribosomal protein L35a (RPL35A), transcript variant 2, mRNA”, NCBI Reference Sequence: NM_000996.3”. No publication date or date of retrieval has been provided in accordance with 37 CFR 1.98(b). Where the actual publication date of a non-patent document is not known, the applicant must, at a minimum, provide a date of retrieval (e.g., the date a webpage was retrieved) or a time frame (e.g., a year, a month and year, a certain period of time ) when the document was available as a publication. The examiner has added the date of the Reference Sequence number of NM_000996.3 of April 11, 2018 to the IDS for that reference.
Claim Rejections-Written Description
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 15,20,28 and 47-55 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 15,20 and 47 encompass a method of inhibiting the expression of a large genus of cancer associated genes or large genus of cancer associated long non-coding RNA in a genus of mammalian cells, which may be in vitro or in vivo, by introducing a large genera of tRNA-derived polynucleotides comprising a sequence that is at least 90 or at least 95% complementary to an intronic region of a genus of cancer associated target genes or intronic region of a genus of cancer associated long non-coding RNA, wherein the tRNA-derived polynucleotide fragment has 14-35 nucleotides (tsRNA) and the tRNA comprises a stem-loop/hairpin structure.
Claims 28 and 48-55 encompass a method of treating a large genus of cancers, including blood and tissue cancers, comprising administering by a genus of administration routes, an effective amount of a pharmaceutical composition comprising a large genus of tRNA-derived polynucleotides comprising a sequence that is at least 90 or at least 95% complementary to an intronic region of a genus of cancer associated target genes or intronic region of a genus of cancer associated long non-coding RNA, wherein the tRNA-derived polynucleotide fragment has 14-35 nucleotides (tsRNA) and wherein the tRNA comprises a stem-loop/hairpin structure to a mammalian subject in need thereof.
Regarding the state of the art of tRNA-derived polynucleotides, Li et al. (Genes, Review, 9, 246, Published 10 May 2018) teach that high-throughput sequencing has unveiled various tsRNAs in bacteria, fungi, plants and mammals, and that various types of tsRNA can be generated from diverse tRNA sources (Section 2, page 2). Li et al. teach tRFs are evolutionarily ancient and present in both prokaryotes and eukaryotes, and that some tsRNAs preferentially associate with Ago1, Ago3, and Ago4 proteins but not Ago2 in a cell type specific manner, which indicates that tRFs have other functions than direct binding with the target genes as miRNAs (Section 3.1, page 4).
Maute et al. (PNAS Vol. 110, No. 4, Published 22 January 2013, pages 1404-1409) teach a class of abundantly expressed small RNAs whose sequences matched either to mature or precursor tRNA transcripts and that other groups have reported similar small RNA species expressed in a variety of human cell types and other organisms, yet the role of how these small RNAs act has not been determined (page 1404). Maute et al. teach three categories of tRNA fragments, tRF-5, tRF-3 and tRF-1, and that tRF-3s are the most abundant expressed in mature B cells (page 1404). Maute et al. teach a tRF-3 designated CU1276 which is a 22-nt small RNA differentially expressed in three stages of mature B-cell differentiation and one GC-derived lymphoma cell line (page 1404). Maute et al. teach that the tRNA-derived CU1276 can repress mRNA targets in an Argonaute-dependent, miRNA-like fashion (page 1405), and therefore the data presented demonstrates that a tRNA fragment can post-transcriptionally regulate endogenous genes in a sequence-specific, miRNA-like fashion (page 1408).
There is a lack of teaching in the state of the art in regards to tRNA-derived polynucleotides from tRNA comprising a stem-loop/hairpin structure and their used for inhibiting gene expression of cancer associated genes or cancer associated long non-coding RNA and treating cancer.
Regarding the state of the art of the genus of cancer associated genes or cancer associated long non-coding RNA and treating a genus of cancers, Kryzyszczyk et al. (Technology, 2018; 6(3-4): 79-100, pages 1-27) teach cancer is a complex and heterogeneous condition, and there are over 100 types of cancers, located in different organs and sub-tissues and originating from different cell types, and some cancer types such as colon, breast and non-Hodgkin’s lymphoma contain even more specific classifications based on their molecular subtypes (Intro, page 2). Kryzyszczyk et al. teach expression of markers within the same tumor can change depending on the location or stage of cancer (Intro, page 2).
Therefore, the state of the art shows the large genus of tsRNAs and large genus of possible gene targets in different organisms, and that the tRNA fragments can repress mRNA targets and can post-transcriptionally regulate endogenous genes in a sequence-specific fashion, as well as the complexity and heterogeneity of different cancers.
The specification discloses tsRNAs having the sequence comprising SEQ ID NOs: 4,5 or 6 (pages 10,38 and 39). Example 2, pages 37-38 discloses transfecting tsRNAs in cells, and Figures 13A,B shows levels of EGFR mRNA were reduced upon transfection of tsRNA EGFR. Example 3, page 38 discloses transfecting tsRNAs into cells, and that MET mRNA levels were reduced upon transfection with tsRNA MET (Figures 13A, B). However, these examples do not disclose the structure of the tsRNA necessary for performing this function. Example 4, page 38, discloses transfecting BT549 cells with tsRNA EGFR/MET, and that the tsRNA is single stranded and has SEQ ID NO: 4, and Figure 15 shows the number of dead cells increased with increasing amount of tsRNA EGFR/MET, and Figure 16 shows the number of live cells decreased with increasing amount of tsRNA EGFR/MET. Example 5, page 39 discloses transfecting MCF7 (breast cancer cell line) cells with tsRNAs of SEQ ID NO: 5 to target BCL2 which led to downregulation of steady state BCL2 mRNA levels (Figure 18), and that BCL-2 levels decreased with increasing amount of tsRNA (Figure 19). Example 6, pages 39-40 discloses transfecting BT549 cells with tsRNA LINC00665 of SEQ ID NO: 6, and that LINC0665 levels were reduced (Figure 22, 23A,B), and fewer live cells (Figure 25).
Claims 15,20,28 and 47-55 are directed to encompass tsRNAs, cancer associated genes or cancer associated long non-coding RNA and cancer which only correspond in some undefined way to specifically instantly disclosed tsRNAs of SEQ ID NOs: 4,5 and 6, specific cancer associated genes EGFR/MET, BCL2 and LINC00665, and specific breast cancer cells and lung cancer cells. The specification lacks chemical structural information for what they are and chemical structures are highly variant and encompass millions of possible tsRNAs and many possible specific cancer associated genes. The specification provides insufficient written description to support the genus encompassed by the claim. Note: MPEP 2163.
Additionally, regarding claims 50-52, the specification does not provide written description for the genus of tsRNAs that are double stranded and which have the recited function of treating a genus of cancers. All of the structurally defined tsRNAs of the examples are single stranded as shown above, and have the function of decreasing target mRNA levels of the specific cancer associated genes. The specification does not provide any structure-function correlation for double-stranded tsRNAs with the function of treating cancer.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, (Fed. Cir. 1991), makes clear 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.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
With the exception of the tsRNAs having the sequence comprising SEQ ID NOs:
4,5 or 6 wherein SEQ ID NO: 4 corresponds to the target gene EGFR/MET in a breast cancer cell line, SEQ ID NO: 5 corresponds to the target gene BCL2 in a breast cancer cell line and lung cancer cell line, and SEQ ID NO: 6 which corresponds to the target LINC0665 in breast cancer cell lines and lung cancer cell lines, and which reduce gene expression thereof, the skilled artisan cannot envision the detailed chemical structure of the encompassed tsRNAs with the recited functions, as there is no structure-function correlation.
University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404, 1405 (Fed.
Cir. 1997) held that:
...To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.
Furthermore, to the extent that a functional description can meet the requirement for an adequate written description, it can do so only in accordance with PTO guidelines stating that the requirement can be met by disclosing “sufficiently detailed, relevant identifying characteristics,” including “functional characteristics when coupled with a known or disclosed correlation between function and structure.” Univ. of Rochester v. G.D. Searle, 68 USPQ2d 1424, 1432 (DC WNY 2003).
Therefore, only the above chemically structurally defined tsRNAs of SEQ ID NOs: 4,5 and 6 and their respective target genes in the cancer cell lines as stated above, but not the full breadth of the claim(s) meet the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph. The species specifically disclosed are not representative of the genus because the genus is highly variant. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 USC § 112 is severable from its enablement provision. (See page 1115.)
Response to Arguments
Applicant's arguments filed 10/13/2025 have been fully considered but they are not persuasive.
Applicant states on page 8 that the skilled person would readily understand that the examples to which the Action refers are non-limiting, and the invention is described in the specification with representative examples and is generally applicable to the genus of cancer, and there is no reason why a person skilled in the art would not understand Applicant to be in possession of the full genus of the claimed invention. Applicant argues that while the Action acknowledges SEQ ID NOs: 4,5, and 6, Applicant submits that SEQ ID NO: 4 in particular applies to a range of target cancers, as disclosed on lines 32-34 of page 36 of the application as filed, and a skilled person would understand from the description that the invention is not limited to a specific subset of cancers.
This is not found persuasive. While examples may be non-limiting, the specification must still provide written description support. MPEP 2163 II A.3.ii., states for claims drawn to a genus as in the present claims, the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus (see i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. See Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021). As stated in the written description rejection above, applicant has provided three species of tsRNAs (SEQ ID NOs: 4,5,6) which correspond only to a few cancer associated target genes or cancer associated long non-coding RNA in breast cancer or lung cancer cell lines. The examiner maintains that this is not a representative number of species by actual reduction to practice. In addition, the specification has not provided written description support for treating a genus of cancers.
Regarding the genus of tRNA, Applicant argues claims 15 and 28 state the tRNA-derived polynucleotide fragment comprises a stem-loop/hairpin structure, while the state of the art referred to in the office action shows a large genus of tRNA fragments can repress mRNA targets and regulate gene expression but does not disclose any tRNA molecule that is alternatively folded as claimed and that can be recognized by Dicer and processed into tsRNA in the nucleus. Applicant argues the application demonstrates that tsRNAs are generated in a Dicer-dependent manner, and that tsRNAs are effective at targeting genes associated with cancer and provides multiple examples demonstrating cancer cell killing mediated by the tsRNA molecules (page 3, paragraph 3 and page 37, paragraph 2).
This is not found persuasive, as there are no limitations recited in the present claims that the tRNA is generated in a Dicer-dependent manner. In addition, if the state of the art does not teach the presently recited tRNA derived polynucleotide fragments from tRNA comprising a stem-loop/hairpin structure, and the required structure for performing the recited functions, then the state of the knowledge in the art is low and the specification must provide sufficient support for the claimed genus. The ordinary artisan would not know what the core structure is of the tRNA-derived polynucleotide that is required achieve the claimed effect of inhibiting expression of a genus of cancer associated genes or cancer associated long non-coding RNA, as each cancer associated gene or long non-coding RNA has a different nucleotide sequence, and therefore each tRNA-derived polynucleotide would have to correspond to a specific sequence in order to inhibit expression of that cancer associated gene. No structure-function correlation has been shown in the instant specification.
Applicant argues on page 9 that Figure 2b shows the secondary structure of the tRNA molecules can fold into short hairpin structures and resemble miRNA precursors, and therefore it would be clear to those skilled in the art from the written description which of the structural features are required of the tRNA to achieve the technical features of the claimed methods. Regarding the genus of biological systems, applicant argues that as amended, claim 15 encompasses a mammalian cell rather than any biological system, and claim 28 has been amended to recite treatment of cancer in a mammalian subject. As demonstrated by Examples 1-6, studies of the present invention have been undertaken in mammalian cell lines and therefore support is provided for the genera of mammalian cells and subjects now claimed.
This is not found persuasive. Figure 2b shows secondary structures formed by tRNA, and does not show the structure of the tRNA derived polynucleotide fragments (tsRNA) that carry out the recited functions. No structure-function correlation is provided in the instant specification. The claims still encompass inhibiting the expression of a large genera of cancer associated genes or cancer associated long non-coding RNA in a genus of mammalian cells and treating a large genera of cancers including tissue and blood cancers, with a large genera of tRNA-derived polynucleotides in a mammalian subject. While the amendments further limited the biological system to a mammalian cell and mammalian subject, there are many types of mammalian cells, and there is only support for specific cancer cells (breast cancer and lung cancer cells). For example, there is no written support for the cells occurring in non-cancerous mammalian cells. There are still many possible cancer-associated genes and many types of cancers being treated that are encompassed by the claims, as well as many possible introns and intronic regions within the cancer associated target gene. The specification only provides written description for 3 different tsRNA sequences (SEQ ID NOs: 4,5,6) that each pertain to a specific cancer associated target gene or long non-coding RNA (EGFR/MET, BCL2, and LINC00665), and which show reduced expression of the target gene, and reduce cell proliferation in vitro in either breast cancer cells lines or lung cancer cell lines. 3 disclosed sequences for 3 cancer associated target genes or lncRNA in two types of mammalian cancer cells is not a sufficient number to provide sufficient written support for the claimed genus, and therefore the written description rejection is maintained.
Claim Rejections- Scope of Enablement
Claims 15,20 and 47 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of inhibiting gene expression of target genes EGFR and MET comprising introducing a tRNA-derived polynucleotide of SEQ ID NO: 4, inhibiting gene expression of target gene BCL2 comprising introducing a tRNA-derived polynucleotide of SEQ ID NO: 5, and inhibiting gene expression of target gene LINC00665 comprising introducing a tRNA-derived polynucleotide of SEQ ID NO: 6 into a cancer cell, does not reasonably provide enablement for inhibiting the expression of a genus of cancer associated genes or genus of cancer associated long non-coding RNA in a genus of mammalian cells, the method comprising introducing a tRNA-derived polynucleotide comprising a sequence that is at least 90 or 95% complementary to a genus of intronic regions of cancer associated target genes or genus of cancer associated long non-coding RNA, wherein the tRNA-derived polynucleotide fragment has 14-35 nucleotides (tsRNA). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
As stated in MPEP §2164.01(a), “there are many factors to consider when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any experimentation is ‘undue’.” These factors include, but are not limited to:
1. The breadth of the claims;
2. The nature of the invention;
3. The state of the prior art;
4. The level of skill in the art;
5. The level of predictability in the art;
6. The amount of direction provided by the inventor;
7. The presence or absence of working examples;
8. The quantity of experimentation necessary needed to make or use the invention based on the disclosure.
The Breadth of the Claims and Nature of the Invention
Claims 15,20 and 47 encompass an in vitro or in vivo method of inhibiting the expression of a large genera of cancer associated target genes or large genera of cancer associated long non-coding RNA in a genus of mammalian cells which may be cancer or non-cancer cells, by introducing a large genera of tRNA-derived polynucleotides comprising a sequence that is at least 90 or 95% complementary to a genus of intronic regions of cancer associated target genes or genus of cancer associated long non-coding RNA, wherein the tRNA-derived polynucleotide fragment has 14-35 nucleotides (tsRNA).
The State of the Prior Art
Before the effective filing date, the state of the art is limited regarding a method of inhibiting the expression of a cancer-associated target gene or of a cancer-associated long non-coding RNA in a mammalian cell using a tRNA-derived polynucleotide fragment from tRNA comprising a stem-loop/hairpin structure.
Li et al. (Genes, Review, 9, 246, Published 10 May 2018) teach that high-throughput sequencing has unveiled various tsRNAs in bacteria, fungi, plants and mammals, and that various types of tsRNA can be generated from diverse tRNA sources (Section 2, page 2). Li et al. teach tRFs are evolutionarily ancient and present in both prokaryotes and eukaryotes, and that some tsRNAs preferentially associate with Ago1, Ago3, and Ago4 proteins but not Ago2 in a cell type specific manner, which indicates that tRFs have other functions than direct binding with the target genes as miRNAs (Section 3.1, page 4).
Maute et al. (PNAS Vol. 110, No. 4, Published 22 January 2013, pages 1404-1409) teach a class of abundantly expressed small RNAs whose sequences matched either to mature or precursor tRNA transcripts and that other groups have reported similar small RNA species expressed in a variety of human cell types and other organisms, yet the role of how these small RNAs act has not been determined (page 1404). Maute et al. teach three categories of tRNA fragments, tRF-5, tRF-3 and tRF-1, and that tRF-3s are the most abundant expressed in mature B cells (page 1404). Maute et al. teach a tRF-3 designated CU1276 which is a 22-nt small RNA differentially expressed in three stages of mature B-cell differentiation and one GC-derived lymphoma cell line (page 1404). Maute et al. teach that the tRNA-derived CU1276 can repress mRNA targets in an Argonaute-dependent, miRNA-like fashion (page 1405), and therefore the data presented demonstrates that a tRNA fragment can posttranscriptionally regulate endogenous genes in a sequence-specific, miRNA-like fashion (page 1408).
Therefore, the state of the art shows the large genus of tsRNAs and large genus of possible gene targets in different organisms, and that the tRNA fragments can repress mRNA targets in an Argonaute-dependent, miRNA-like fashion and can posttranscriptionally regulate endogenous genes in a sequence-specific fashion.
The Amount of Direction Provided by the Inventor and The presence or Absence of Working Examples
The specification discloses tsRNAs having the sequence comprising SEQ ID NOs: 4,5 or 6 (pages 10,38 and 39). Example 2, pages 37-38 discloses transfecting tsRNAs in cells, and Figures 13A,B shows levels of EGFR mRNA were reduced upon transfection of tsRNA EGFR. Example 3, page 38 discloses transfecting tsRNAs into cells, and that MET mRNA levels were reduced upon transfection with tsRNA MET (Figures 13A, B). However, these examples do not disclose the structure of the tsRNA necessary for performing this function. Example 4, page 38, discloses transfecting BT549 cells with tsRNA EGFR/MET, and that the tsRNA is single stranded and has SEQ ID NO: 4, and Figure 15 shows the number of dead cells increased with increasing amount of tsRNA EGFR/MET, and Figure 16 shows the number of lives cells decreased with increasing amount of tsRNA EGFR/MET. Example 5, page 39 discloses transfecting MCF7 (breast cancer cell line) cells with tsRNAs of SEQ ID NO: 5 to target BCL2 which led to downregulation of steady state BCL2 mRNA levels (Figure 18), and that BCL-2 levels decreased with increasing amount of tsRNA (Figure 19). Example 6, pages 39-40 discloses transfecting BT549 cells with tsRNA LINC00665 of SEQ ID NO: 6, and that LINC0665 levels were reduced (Figure 22, 23A,B), and fewer live cells (Figure 25).
The Level of Predictability in the Art
Regarding claims 15,20 and 47, the instant claimed invention is highly unpredictable due to the claims encompassing a method of inhibiting the expression of a large genera of cancer-associated target genes or large genera of cancer-associated long non-coding RNA in a genus of mammalian cells by introducing a large genera of tRNA-derived polynucleotides comprising a sequence that is at least 90 or 95% complementary to a genus of intronic regions of cancer associated target genes or genus of cancer associated long non-coding RNA, wherein the tRNA-derived polynucleotide fragment has 14-35 nucleotides (tsRNA) and the tRNA comprises a stem-loop/hairpin structure.
The large number of species encompassed by the genus of tsRNAs, genus of intronic regions of a cancer associated gene or cancer associated long non-coding RNA, and genus of mammalian cells adds to the unpredictability of the claimed invention, and therefore one skilled in the art cannot use the information provided by the specification regarding the tsRNAs of SEQ ID NOs: 4,5 and 6 which are used to inhibit expression of EGFR and MET, BCL2 and LINC00665, respectively, and apply to the other species of the genus. It is unpredictable for example, that the method would result in a method of inhibiting expression of a cancer associated gene or cancer associated long non-coding RNA in a non-cancer mammalian cell or a cell that does not express a cancer associated gene. If one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains (e.g., A method of inhibiting expression of a target cancer associated gene or of a cancer associated long non-coding RNA in a mammalian cell, the method comprising: introducing into the biological system a tRNA-derived polynucleotide comprising a sequence that is at least 90 or 95% complementary to an intronic region of a cancer associated target gene or an intronic region of a cancer associated long non-coding RNA wherein said tRNA-derived polynucleotide is a tRNA-derived polynucleotide fragment that has 14 to 35 nucleotides (tsRNA), wherein the tRNA comprises a stem-loop/hairpin structure), then there is a lack of predictability in the art. The court has indicated that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. (See In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970)). This is because it is not obvious from the disclosure of one species, what other species will work.
The Quantity of Experimentation Necessary
Regarding claims 15,20 and 47, in light of the unpredictability surrounding the breadth of the claimed method of inhibiting expression of a cancer associated gene or cancer associated long non-coding RNA in a mammalian cell, the method comprising: introducing into the mammalian cell a tRNA-derived polynucleotide comprising a sequence that is at least 90 or 95% complementary to an intronic region of a cancer associated target gene or an intronic region of a cancer associated long non-coding RNA wherein said tRNA-derived polynucleotide is a tRNA-derived polynucleotide fragment that has 14 to 35 nucleotides (tsRNA), wherein the tRNA comprises a stem-loop/hairpin structure), one wishing to practice the presently claimed invention would be unable to do so without engaging in undue experimentation. One of ordinary skill in the art would not be able to use the information provided by the instant specification to carry out the full scope of the invention as claimed, as there is no instruction as to how to use other tsRNAs to carry out the claimed invention, or how to carry out the invention in cells that are non-cancerous or other cancer cells other than breast cancer and lung cancer cells. The specification only shows that three tsRNA sequences are capable of decreasing expression of 4 different target genes, all of which are associated with cancer, and limited to the method occurring in specific cancer cell lines (breast and lung cancer cell lines). In absence of such information in the specification as well as the state of the art, a person of ordinary skill in the art would reasonably require an undue quantity of experimentation to practice the full scope of the claimed method.
Conclusion of 35 U.S.C. 112(a) (Enablement) Analysis
After applying the Wands factors and analysis to claims 15,20 and 47, in view of the applicant’s entire disclosure, it is concluded that the specification is not enabled for the full scope as discussed above. Therefore, claims 15,20 and 47 are rejected under 35 U.S.C. §112(a) for failing to disclose sufficient information to enable a person of skill in the art to use the invention commensurate in scope with these claims.
Response to Arguments
Applicant's arguments filed 10/13/2025 have been fully considered but they are not persuasive.
Applicant states on page 10 that based on the extensive experimental details and data provided in the application as filed, the description provides sufficient teaching to enable the skilled person to identify tsRNAs that are complementary to a cancer-associated target gene or long non-coding RNA and can be subsequently used in the treatment of cancer, and therefore the skilled person would be able to implement the present invention across the full scope of the claimed methods as currently presented. Applicant argues the pending claims define a tsRNA that targets a specific subset of genes or long non-coding RNA which is cancer-associated and a skilled person would be able to follow the teachings in the application to identify and/or design tRNA derived molecules that are complementary to the intronic regions of these cancer associated genes and long non-coding RNAs as outlined below. Applicant argues that Example 1 provides extensive detail on methods to predict tsRNA targets and determine tsRNA disease-association, and Figure 4a shows a bioinformatic workflow was utilized by the inventor to predict genes targeted by Dicer and Ago-associating tsRNAs. The inventor extracted sequences from photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation experiments, and this data was mapped to tRNA genes. The inventor sequence mRNA from wildtype and Dicer knockdown cells and determined genes upregulated in Dicer knockdown via DESeq2, and then employed miRanda to generate a list of genes that are predicted to be targeted by Dicer and Ago-associated tsRNAs. Applicant argues these techniques are available to the skilled person to predict Dicer-dependent tsRNA that can target introns of genes which can then be experimentally validated using standard techniques in the art. Applicant argues on page 11 that Example 1 also provides details on methods employed by the inventor to identify genes that are regulated globally by the distinct gene silencing mechanism described in the application. Chromatin-associated RNA sequence was performed to detect levels of nascent tsRNA transcripts in 4 different cell lines. Figure 7b shows a workflow for predicting target genes using chrRNA-seq data followed by disease-gene association analysis, and can be validated as shown in Figure 9. This method determines tsRNAs that can target the intronic region of a specific gene to downregulated its expression.
Regarding Applicants arguments above regarding the specification disclosing how to identify tsRNAs and predicting target genes, this is not found persuasive. While applicant has pointed out that Example 1 shows how to predict tsRNA targets and determine disease association with genes, it does not show how to use them commensurate in scope with the claims regarding using the instantly claimed genus of tRNA-derived polynucleotides in mammalian cells to inhibit expression of a genus of cancer associated genes or cancer associated long non-coding RNA. The instant specification only provides 3 tsRNA sequences specific for 4 cancer associated genes/long non-coding RNA (MET/EGFR, BCL2, AND LINC00665 respectively) shown in in vitro cell experiments in cancer cells lines (breast cancer and lung cancer cells).
Applicant argues on page 11 regarding how to use the claimed invention for treating a genus of cancers that the description teaches the skilled person that once that have identified tsRNAs that can target the intronic region of a target gene, they can determine which of these tsRNAs are associated with various diseases such as cancer as shown in Figures 10,11 and 12. This would then allow the skilled person to determine if the identified tsRNA is suitable for use in a method of treating cancer. The inventor utilized DisGeNET, a platform for documenting human disease-related genes which demonstrated that the genes they identified as being targeted by Dicer-dependent tsRNA for silencing are significantly disease-associated when compared to non-target genes, and the skilled person can utilize known techniques to generate a heat-map of gene-disease associations and would be able to determine which tsRNAs can target a cancer-associated target gene or long non-coding RNA. Applicant also points to pages 27-33 of the specification as having extensive details to enable the skilled person to arrive at a tsRNA-derived polynucleotide which is suitable for use in a method of inhibiting the expression of a cancer associated gene or of a cancer associated long non-coding RNA in a biological system.
This is not found persuasive. As stated above, showing how to identify tsRNAs and their target cancer associated genes does not provide enablement for how to use the identified tsRNAs commensurate in scope with the claims. MPEP 2164.03 states “in applications directed to inventions in arts where the results are unpredictable, the disclosure of a single species usually does not provide an adequate basis to support generic claims. In re Soll, 97 F.2d 623, 624, 38 USPQ 189, 191 (CCPA 1938). In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) (contrasting mechanical and electrical elements with chemical reactions and physiological activity). See also In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); In re Vaeck, 947 F.2d 488, 496, 20 USPQ2d 1438, 1445 (Fed. Cir. 1991). This is because in art areas having a high degree of uncertainty (i.e. the unpredictable arts) it is not reasonably predictable from the disclosure of one species, what other species will work”. In the instant case, Applicant’s have provided 3 species of tsRNAs that correspond to specific cancer-associated genes and long non-coding RNA in specific cancer cell-lines. While this is more than a single species referred to in MPEP above, there is unpredictability in the field regarding physiological activity.
Claim Rejections- Scope of Enablement
Claims 28 and 48-55 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating breast cancer or lung cancer in vitro comprising administering an effective amount of a pharmaceutical composition comprising a tsRNA having SEQ ID NO: 4 or 5 to a cancer cell in vitro, does not reasonably provide enablement for a method of treating a genus of cancers comprising administering an effective amount of a pharmaceutical composition comprising a genus of tRNA-derived polynucleotides comprising a sequence that is at least 90 or 95% complementary to a genus of intronic regions of a cancer associated target gene or genus of intronic region of a cancer associated long non-coding RNA, wherein said tRNA-derived polynucleotide fragment has 14-35 nucleotides in vivo to a human subject in need thereof. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
As stated in MPEP §2164.01(a), “there are many factors to consider when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any experimentation is ‘undue’.” These factors include, but are not limited to:
1. The breadth of the claims;
2. The nature of the invention;
3. The state of the prior art;
4. The level of skill in the art;
5. The level of predictability in the art;
6. The amount of direction provided by the inventor;
7. The presence or absence of working examples;
8. The quantity of experimentation necessary needed to make or use the invention based on the disclosure.
The Breadth of the Claims and Nature of the Invention
Claims 28 and 48-55 encompass a method of treating a large genus of cancers comprising administering by any route of administration, a large genus of isolated tRNA-derived polynucleotides comprising a sequence that is at least 90 or 95% complementary to an intronic region of a large genus of cancer associated target gene or an intronic region of a cancer associated long non-coding RNA, wherein said tRNA-derived polynucleotide fragment has 14-35 nucleotides to a mammalian subject in need thereof. The claims encompass treating both solid tissue cancers as well as blood cancers.
The State of the Prior Art
Li et al. (Genes, Review, 9, 246, Published 10 May 2018) teach that high-throughput sequencing has unveiled various tsRNAs in bacteria, fungi, plants and mammals, and that various types of tsRNA can be generated from diverse tRNA sources (Section 2, page 2). Li et al. teach tRFs are evolutionarily ancient and present in both prokaryotes and eukaryotes, and that some tsRNAs preferentially associate with Ago1, Ago3, and Ago4 proteins but not Ago2 in a cell type specific manner, which indicates that tRFs have other functions than direct binding with the target genes as miRNAs (Section 3.1, page 4).
Maute et al. (PNAS Vol. 110, No. 4, Published 22 January 2013, pages 1404-1409) teach a class of abundantly expressed small RNAs whose sequences matched either to mature or precursor tRNA transcripts and that other groups have reported similar small RNA species expressed in a variety of human cell types and other organisms, yet the role of how these small RNAs act has not been determined (page 1404). Maute et al. teach three categories of tRNA fragments, tRF-5, tRF-3 and tRF-1, and that tRF-3s are the most abundant expressed in mature B cells (page 1404). Maute et al. teach a tRF-3 designated CU1276 which is a 22-nt small RNA differentially expressed in three stages of mature B-cell differentiation and one GC-derived lymphoma cell line (page 1404). Maute et al. teach that the tRNA-derived CU1276 can repress mRNA targets in an Aurgonaute-dependent, miRNA-like fashion (page 1405), and therefore the data presented demonstrates that a tRNA fragment can posttranscriptionally regulate endogenous genes in a sequence-specific, miRNA-like fashion (page 1408).
Holle et al. (Advanced Drug Delivery Reviews 97 (2016), 270-279) teach that there are many examples of drugs that have cytotoxic behavior in cancer cells in vitro but losing efficacy in vivo which is the result of poorly understood chemoresistant effects conferred by the cancer environment (Abstract).
Regarding the state of the art of the genus of cancer associated genes or cancer associated long non-coding RNA and treating a genus of cancers, Kryzyszczyk et al. (Technology, 2018; 6(3-4): 79-100, pages 1-27) teach cancer is a complex and heterogenous condition, and there are over 100 types of cancers, located in different organs and sub-tissues and originating from different cell types, and some cancer types such as colon, breast and non-Hodgkin’s lymphoma contain even more specific classifications based on their molecular subtypes (Intro, page 2). Kryzyszczyk et al. teach expression of markers within the same tumor can change depending on the location or stage of cancer (Intro, page 2).
Therefore, the state of the art shows the large genus of tsRNAs and large genus of possible gene targets, as well as the unpredictability of in vitro to in vivo correlation of results regarding cancer treatment.
The Level of Predictability in the Art
Regarding claims 28 and 48-55, the instant claimed invention is highly unpredictable due to the claims encompassing treating any cancer (including tissue and blood cancers) by administering by any route of administration, an effective amount of a pharmaceutical composition comprising a large genera of tRNA-derived polynucleotides as instantly recited in claim 28. The large number of species encompassed by the genus of tRNA-derived fragments, and the number of species encompassed by all of the possible intronic regions of any cancer associated target genes or cancer associated long non-coding RNA, as well as administration to the mammalian subject by any route and which results in treating a large genus of cancer adds to the unpredictability of the claimed invention. The genus of isolated tRNA-derived polynucleotides comprising a sequence that is at least 90% or at least 95% complementary to an intronic region of a cancer associated target gene or of a cancer associated long non-coding RNA encompasses thousands of different structures, and therefore one skilled in the art cannot use the information provided by the specification regarding SEQ ID NOs: 4-6 as the tsRNAs and the target genes EGFR/MET, BCL2 and LINC00665 and apply to the other species of the genus and use them commensurate in scope with the claims. The specification does not show how to carry out the claimed invention of claims 50-52 with a genus of double stranded tsRNAs.
The specification does not show in vivo treatment of cancer with any specific tsRNAs in a subject. As shown by Holle et al. above, there are many examples of drugs that have cytotoxic behavior in cancer cells in vitro but losing efficacy in vivo which is the result of poorly understood chemoresistant effects conferred by the cancer environment. If one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains then there is a lack of predictability in the art. The court has indicated that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. (See In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970)). This is because it is not obvious from the disclosure of one species, what other species will work.
For example, it would be unpredictable that administering a pharmaceutical composition comprising a tsRNA as recited in the instant claims that is at least 90% or 95% complementary to a gene associated with leukemia can be administered to any subject by any route of administration to treat breast cancer. In addition, different types of cancers start in different cells and parts of the body. A drug that would be able to treat tissue cancers that start in epithelial cells may be able to treat other tissue cancers that start in epithelial cells, but it would not be predictable that a drug that can treat a tissue cancer would be capable of treating cancers that begin in different cells, such as leukemia, lymphoma and myeloma. See Kryzyszczyk et al. above regarding the unpredictability in different cancers.
Also as shown by Holle et al. above, there is a high level of unpredictably in the art of cancer treatment with limitations in the in vitro and in vivo studies.
The Amount of Direction Provided by the Inventor and The presence or Absence of Working Examples
The specification discloses tsRNAs having the sequence comprising SEQ ID NO:s 4,5 or 6 (pages 10,38 and 39). Example 2, pages 37-38 discloses transfecting tsRNAs in cells, and Figures 13A,B shows levels of EGFR mRNA were reduced upon transfection of tsRNA EGFR. Example 3, page 38 discloses transfecting tsRNAs into cells, and that MET mRNA levels were reduced upon transfection with tsRNA MET (Figures 13A, B). However, these examples do not disclose the structure of the tsRNA necessary for performing this function. Example 4, page 38, discloses transfecting BT549 cells with tsRNA EGFR/MET, and that the tsRNA is single stranded and has SEQ ID NO: 4, and Figure 15 shows the number of dead cells increased with increasing amount of tsRNA EGFR/MET, and Figure 16 shows the number of lives cells decreased with increasing amount of tsRNA EGFR/MET. Example 5, page 39 discloses transfecting MCF7 (breast cancer cell line) cells with tsRNAs of SEQ ID NO: 5 to target BCL2 which led to downregulation of steady state BCL2 mRNA levels (Figure 18), and that BCL-2 levels decreased with increasing amount of tsRNA (Figure 19). Example 6, pages 39-40 discloses transfecting BT549 cells with tsRNA LINC00665 of SEQ ID NO: 6, and that LINC0665 levels were reduced (Figure 22, 23A,B), and fewer live cells (Figure 25).
The specification provides no guidance on how to practice the claimed invention for treating cancer as recited in claims 28 and 48-55. The specification only shows a method of decreasing expression of a few cancer associated target genes in a few cancer cell lines. There are no in vivo working examples. In vitro experimental results with cancer cell lines cannot be extrapolated to cancer treatment in a human subject. See Holle et al. above.
The Quantity of Experimentation Necessary
Regarding claims 28 and 48-55, in light of the unpredictability surrounding the breadth of the claimed method of treating any cancer comprising administering an effective amount of a pharmaceutical composition comprising a tRNA-derived polynucleotide as recited in instant claim 28, one wishing to practice the presently claimed invention would be unable to do so without engaging in undue experimentation. One of ordinary skill in the art would not be able to use the information provided by the instant specification to carry out the full scope of the invention as claimed, as there is no instruction as to how to use other tsRNAs to carry out the claimed invention and no instruction on how to administer the recited tsRNA to a mammalian subject to treat a genus of cancers. In absence of such information in the specification as well as the state of the art, a person of ordinary skill in the art would reasonably require an undue quantity of experimentation to practice the full scope of the claimed method.
Conclusion of 35 U.S.C. 112(a) (Enablement) Analysis
After applying the Wands factors and analysis to claims 28 and 48-55, in view of the applicant’s entire disclosure, it is concluded that the specification is not enabled for the full scope as discussed above. Therefore, claims 28 and 48-55 are rejected under 35 U.S.C. §112(a) for failing to disclose sufficient information to enable a person of skill in the art to use the invention commensurate in scope with these claims.
Response to Arguments
Applicant's arguments filed 10/13/2025 have been fully considered but they are not persuasive.
Applicant states on page 12 of response that the skilled person would understand that the examples are non-limiting, and that the present invention has shown surprising inhibition of gene expression achieved by the claimed method that has been demonstrated to be highly effective in a range of unrelated, distinct genes, and is therefore generally applicable to the genus of cancer. Applicant argues that Examples 2,3 and 4 disclose the successful reduction in nascent levels of mRNA of EGFR, MET and EGFR/MET in combination, and Example 5 demonstrates the successful reduction in BCL2 expression; Example 6 describes the use of a tRNA comprising a stem-loop/hairpin structure complementary to long noncoding RNA LINC00665 which is a diagnostic marker and therapeutic target in many cancers, and therefore demonstrates that the tRNA targets the intronic region of LINC00665 to downregulated its expression through cleaving nascent RNA in an Ago2-dependent manner. Applicant argues based on all of this data, the skilled person would appreciate that the application can be applied to a range of cancer-associated target genes or long non-coding RNA and can employ the techniques in the Examples to implement a method of treating cancer.
Applicant argues on page 12 that regarding claims 50-52, that Figures 36d shows levels of target SPINT1 RNA in cells transiently transfected with varying amount of double-stranded synthetic tsRNA targeting SPINT1, and as shown in Figure 36 and Example 6, both single and double-stranded forms of intron-targeting tRNA can lead to gene silencing of the relevant targets.
This is not found persuasive. As stated in the above enablement rejection, the instant specification does not show how to use the claimed invention for treating a genus of cancers in vivo in a subject. Applicants arguments above refer to the examples showing the ability to downregulate expression of the specific cancer associated target genes, not treating cancer as in instant claims 28 and 48-55. No specific route of administration is claimed or exemplified that would result in treatment of such a large genus of cancers as instantly claimed. Holle et al. and Kryzyszczyk et al. cited in the enablement rejection provide support regarding the unpredictability in different cancers and high level of unpredictably in the art of cancer treatment with limitations in the in vitro and in vivo studies. Therefore, the claimed invention remains unpredictable.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 15,20,28 and 47-55 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 15,28,29 and 37 of copending Application No. 18/254,324 (‘324) (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because claim 15 of ‘324 is directed to an in vitro or ex vivo method of inhibiting expression of a target gene or of long non-coding RNA in a biological system comprising introducing the tRNA-derived polynucleotide comprising a sequence that is complementary to an exonic region of a target gene or of a long non-coding RNA wherein said tRNA-derived polynucleotide is a tRNA-derived polynucleotide fragment that has 14-35 nucleotides (tsRNA), into the biological system, claim 28 is directed to a method for treating cancer in a subject in need thereof comprising administering to the subject an effective amount of the tRNA-derived polynucleotide; claim 29 is a method of inhibiting expression of a gene or of long non-coding RNA in a biological system; and claim 37 is a method of mediating target specific RNA interference by introducing a tRNA-derived polynucleotide of claim 1 into a biological system.
Instant claims 15 and 47 are directed to a method of inhibiting expression of a cancer associated gene or a cancer associated long non-coding RNA in a mammalian cell comprising introducing a tRNA-derived polynucleotide comprising a sequence that is at least 90 or 95% complementary to an intronic region of a cancer associated target gene or an intronic region of a cancer associated long non-coding RNA wherein said tRNA-derived polynucleotide is a tRNA-derived polynucleotide fragment that has 14-35 nucleotides (tsRNA) and comprises a stem-loop/hairpin structure. Instant claims 28 and 48-55 are directed to a method for treatment of cancer comprising administering to a mammalian subject an effective amount of the tRNA-derived polynucleotide comprising a sequence that is at least 90 or 95% complementary to an intronic region of a cancer associated target gene or an intronic region of a cancer associated long non-coding RNA wherein said tRNA-derived polynucleotide is a tRNA-derived polynucleotide fragment that has 14-35 nucleotides (tsRNA) and comprises a stem-loop/hairpin structure. The specification of ‘324 recognizes that the sequences of the tsRNA are SEQ ID NOs: 4-6 as shown in examples 4-6, which are the same sequences exemplified in examples 4-6 of the instant specification. Therefore, it doesn’t appear that the sequences of the tsRNA that are claimed in the copending application are of a different structure than those in the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant requests on page 13 of the response that the rejection be held in abeyance until allowable subject matter is indicated in the present application, and applicant will consider filing a terminal disclaimer at that time.
Therefore, the double patenting rejection is maintained.
Conclusion
Claims 15,20,28 and 47-55 are rejected.
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/STEPHANIE L SULLIVAN/Examiner, Art Unit 1635
/ABIGAIL VANHORN/Primary Examiner, Art Unit 1636