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 .
1. Claims 1-16 are pending and under examination.
Claim Objections
2. Claim 1 is objected to because of the recitation “an mRNA of the TUBB2B gene”. Correction to “the TUBB2B mRNA” is required.
3. Claim 3 is objected to because of the recitation “previous RNAi molecule”. Correction to “said RNAi molecule” is required.
4. Claim 4 is objected to because of the recitation “the RNAi molecule comprises a sequence”. Correction to “the RNAi molecule has a sequence” is required.
5. Claims 5 and 10 are objected to because of the recitation “a shRNA”. Correction to “the shRNA” is required.
6. Claim 6 should be rewritten as follows:
The method of claim 5, wherein the shRNA is encoded by a lentiviral vector.
7. Claim 7 should be rewritten as follows:
The method according to claim 6, wherein the lentiviral vector comprises a promoter operably linked to the shRNA.
8. Claim 9 should be rewritten as follows:
The method according to claim 5, further comprising administering a RNAi molecule delivered by gold nanoparticles, wherein the RNAi molecule has a sequence selected from the group consisting of SEQ ID NO.12, SEQ ID NO.13, SEQ ID NO.14, SEQ ID NO.15 and a combination thereof.
9. Claim 11 should be rewritten as follows:
The method of claim 10, wherein the shRNA is encoded by a lentiviral vector.
10. Claim 12 should be rewritten as follows:
The method according to claim 10, further comprising administering a RNAi molecule delivered by gold nanoparticles, wherein the RNAi molecule has a sequence selected from the group consisting of SEQ ID NO.12, SEQ ID NO.13, SEQ ID NO.14, SEQ ID NO.15 and a combination thereof.
11. Claim 14 should recite “wherein the breast cancer is triple negative breast cancer”.
Double Patenting
12. A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
13. Claims 1-16 are provisionally rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 1-16 of copending Application No. 18/148,466 (reference application). This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented.
Claim Rejections - 35 USC § 112(d)
14. 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.
15. Claim 2 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.
The limitations recited in claim 2 does not further limit the parent claim 1 because the shRNA recited in claim 1 necessarily comprises the sequence complementary to the RNAi.
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.
Claim Rejections - 35 USC § 102
16. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
17. Claims 1, 2, 5, 8, and 15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jaglin et al. (Nature Genetics, 2009, 41: 746-752).
Jaglin et al. teach an anti-TUBB2B shRNA (i.e., comprising an RNAi molecule and its complementary sequence) and delivering the anti-TUBB2B shRNA to mouse cells in utero via a plasmid to inhibit TUBB2B expression in the mouse cells (claims 1, 2, 5, and 8) (see Abstract; paragraph bridging p. 747 and 749; p. 751, column 2, second and third full paragraphs). Since the shRNA is delivered to mouse cells in utero, the shRNA is necessarily formulated as a pharmaceutical composition (claim 15). Thus, Jaglin et al. teach all claim limitations and anticipate the claimed invention.
Claim Rejections - 35 USC § 103
18. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
19. Claims 1, 2, 5-8, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Jaglin et al., in view of An et al. (Human Gene Therapy, 2003, 14: 1207-1212).
The teachings of Jaglin et al. are applied as above for claims 1, 2, 5, 8, and 15. Jaglin et al. teach a plasmid and not a lentiviral vector (claims 6 and 7). An et al. teach that lentiviral vectors expressing the shRNA from a Pol III promoter mediate more efficient and stable silencing compared to plasmids (see Abstract; paragraph bridging p. 1207 and 1208). One of skill would have found obvious to modify Jaglin et al. by replacing the plasmid with a lentiviral vector comprising a Pol III promoter and operably linking the anti-TUBB2B shRNA to the Pol III promoter, to achieve the predictable result of obtaining a composition capable of mediating enhanced silencing.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
20. Claims 1, 2, 4, 5, 8, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Jaglin et al., in view of Ito et al. (FEBS Lett., 2005, 579: 5988-5995).
The teachings of Jaglin et al. are applied as above for claims 1, 2, 5, 8, and 15. Jaglin et al. do not specifically teach SEQ ID NOs: 1-11 (claim 4). Ito et al. teach that siRNA effectiveness depends on the targeted site on the target mRNA; Ito et al. teach walking along the entire mRNA and shifting one base at a time in order to identify the siRNAs with optimal activity (see p. 5990, column 2, second paragraph; p. 5991, Fig. 2). Based on these teachings, one of skill in the art would have found obvious to walk along the TUBB2B mRNA as taught by Ito et al. to achieve the predictable result of identifying the siRNAs capable of efficiently silencing TUBB2B. By doing so, one of skill in the art would have identified the siRNAs set forth by SEQ ID NOs: 1-11 as efficient for inhibiting TUBB2B in the mouse cells. Routine optimization is not considered inventive and no evidence has been presented that the selection the claimed sequences was other than routine or that the results should be considered unexpected in any way as compared to the closest prior art (see MPEP 2144.05 II).
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
21. Claims 1-3, 5, 8, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Jaglin et al., in view of Bertero et al. (Current Protocols in Stem Cell Biology, 2018, 44: 5C.4.1-5C.4.48).
The teachings of Jaglin et al. are applied as above for claims 1, 2, 5, 8, and 15. Jaglin et al. do not specifically teach the limitations of claim 3. However, the claimed 5’ to 3’ sequence was routinely used in the prior art (see Bertero et al., p. 5C.4.5, Fig. 5C.4.3 A). One of skill in the art would have found obvious to use an shRNA comprising in 5’ to 3’ order CTCGAG-anti-TUBB2B sense strand-CTCGAG- anti-TUBB2B antisense strand-TTTTTG, to achieve the predictable result of obtaining a composition capable of inhibiting TUBB2B expression.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
22. Claims 1, 2, 5, 10, 13, 15, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Benvenisty et al. (PGPUB 2012/0171213), in view of Liu et al. (Mol. Med. Reports, 2019, 20: 3475-3848; cited on the IDS filed on 04/26/2023).
Benvenisty et al. teach using anti-TUBB2B siRNA or shRNA to treat cancer such as neuroblastoma and breast cancer (claim 1) (see Abstract; [0060]; [0075]-[0076]; [0105]). Neuroblastoma and the anti-TUBB2B siRNA are both disclosed within broad Markush groups and Benvenisty et al. do not specifically provide the motivation to specifically select the anti-TUBB2B siRNA to treat neuroblastoma. Liu et al. teach that TUBB2B is upregulated in neuroblastoma, that there is a significant association between increased TUBB2B and neuroblastoma, and that TUBB2B may contribute to neuroblastoma development (see Abstract; p. 3483, Fig. 7; p. 3484, column 2, first full paragraph). Based on these teachings, one of skill in the art would have found obvious to deliver the anti-TUBB2B siRNA or shRNA taught by Benvenisty et al. to subjects affected by neuroblastoma with the reasonable expectation that doing so would treat the cancer in these subjects. By doing so, one of skill in the art would have practiced the method recited in claims 5, 10, and 13 and would have used a pharmaceutical composition comprising the anti-TUBB2B shRNA (claim 15).
With respect to claim 16, one of skill in the art would have found obvious to add a chemotherapeutic drug to achieve the predictable result of treating neuroblastoma in the subject, as chemotherapeutic agents were routinely used in the prior art to treat cancers.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
23. Claims 1, 2, 5-7, 10, 11, 13, 15, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Benvenisty et al. taken with Liu et al., in further view of An et al. (Human Gene Therapy, 2003, 14: 1207-1212).
The teachings of Benvenisty et al. and Liu et al. are applied as above for claims 1, 2, 5, 10, 13, 15, and 16. Benvenisty et al. and Liu et al. do not specifically teach a lentiviral vector (claims 6, 7, and 11). An et al. teach that lentiviral vectors expressing the shRNA from a Pol III promoter mediate efficient and stable silencing (see Abstract; paragraph bridging p. 1207 and 1208). One of skill would have found obvious to use a lentiviral vector in the method of Benvenisty et al. and Liu et al. where the lentiviral vector expresses the anti-TUBB2B shRNA from a Pol III promoter, to achieve the predictable result of obtaining a composition capable of mediating efficient therapy.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
24. Claims 1, 2, 5, 10, and 13-16 are rejected under 35 U.S.C. 103 as being unpatentable over Benvenisty et al. taken with Liu et al., in further view of Melo et al. (Nature, 2015, 523: 1-25).
The teachings of Benvenisty et al. and Liu et al. are applied as above for claims 1, 2, 5, 10, 13, 15, and 16. Benvenisty et al. and Liu et al. do not specifically teach that the breast cancer is triple negative breast cancer (TNBC; claim 14). Melo et al. teach that TUBB2B is expressed by the MDA-MB-231 TNBC cells but not by the normal breast epithelial cells (see paragraph bridging p. 2 and 3; Table 1 on p. 24-25). Based on these teachings, one of skill in the art would have found obvious to deliver the anti-TUBB2B siRNA or shRNA taught by Benvenisty et al. to subjects affected by TNBC with the reasonable expectation that doing so would treat the cancer in these subjects.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
25. Claims 1, 2, 4, 5, 9, 10, 12, 13, 15, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Benvenisty et al. taken with Liu et al., in further view of both Oshi et al. (Chemistry Letters, 2006, 35: 1046-1047) and Ito et al. (FEBS Lett., 2005, 579: 5988-5995).
The teachings of Benvenisty et al. and Liu et al. are applied as above for claims 1, 2, 5, 10, 13, 15, and 16. Benvenisty et al. and Liu et al. do not teach administering the siRNA via gold nanoparticles (claims 9 and 12). Oshi et al. teach that thiolated siRNA could be delivered via gold nanoparticles, where the gold nanoparticles facilitate efficient delivery to the cytoplasm via the exchange reaction with the cytoplasmic glutathione (see p. 1046-1047). Based on these teachings, one of skill in the art would have found obvious to modify the teachings of Benvenisty et al. and Liu et al. by administering both shRNA and thiolated siRNA-gold nanoparticles to achieve the predictable result of treating cancer by inhibiting TUBB2B. MPEP 2144.06 [R-6] I states:
“It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980)
Benvenisty et al. Liu et al., and Oshi et al. do not specifically teach that the siRNA comprises one of SEQ ID NOs: 12-15 (claim 9 and 12). Ito et al. teach that siRNA effectiveness depends on the targeted site on the target mRNA; Ito et al. teach walking along the entire mRNA and shifting one base at a time in order to identify the siRNAs with optimal activity (see p. 5990, column 2, second paragraph; p. 5991, Fig. 2). Based on these teachings, one of skill in the art would have found obvious to walk along the TUBB2B mRNA as taught by Ito et al. to achieve the predictable result of identifying the siRNAs capable of efficiently silencing TUBB2B. By doing so, one of skill in the art would have identified the siRNAs set forth by SEQ ID NOs: 1-11 recited in claim 4 as efficient for inhibiting TUBB2B and would have used them as taught by Oshi et al. Routine optimization is not considered inventive and no evidence has been presented that the selection the claimed sequences was other than routine or that the results should be considered unexpected in any way as compared to the closest prior art (see MPEP 2144.05 II).
SEQ ID NO: 12 corresponds to SEQ ID NO: 1 (with SEQ ID NO: 13 being its complementary strand), while SEQ ID NO: 14 corresponds to SEQ ID NO: 2 (with SEQ ID NO: 15 being its complementary strand) (see the specification, [0077]; [0079]). The difference is that they contain two additional Ts at their 3’ end compared to SEQ ID NOs: 1 and 2; however, there is no evidence that adding TT to the 3’ end of SEQ ID NOs: 1 and 2 imparts unexpected properties with respect to silencing activity. As per MPEP § 716.02, [a]ny differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
26. No claim is allowed. No claim is free of prior art.
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/ILEANA POPA/Primary Examiner, Art Unit 1633