Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Application Status
The action is written in response to applicant’s correspondence received on 5/10/2024. Claims 1-10 are currently pending.
Priority
The instant application claims priority to US provisional application 61/521,715, with an effective filing date of 8/9/2011.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, “the list may not be incorporated into the specification but must be submitted in a separate paper.” Therefore, unless the references have been cited by the examiner on the form PTO-892, they have not been considered.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Written Description
Claims 1-10 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP § 2163.II.A3.(a).(i) states, “whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. The factors to be considered when analyzing claims for compliance with the written description requirement include: (A) actual reduction to practice; (B) disclosure of drawings or structural chemical formulas; (C) sufficient relevant identifying characteristics (e.g., complete structure, partial structure, physical and/or chemical properties, structure/function correlation); (D) level of skill and knowledge in the art; and (E) predictability in the art.
For claims drawn to a genus, MPEP § 2163.II.A3.(a).(i) states, “written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species” where “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is a substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus”.
Each of the relevant factors (A)-(E) listed above is analyzed below along with interpretations of the recited claims:
Regarding claims 1-10, Applicant broadly recites a method for inhibiting the growth and/or proliferation of a MYC-driven tumor comprising the step of contacting the tumor with at least one inhibitor, wherein the inhibitor can be any inhibitor, that inhibits the gene function of one of the listed genes, in claim 1. Therefore, the genus of the claimed invention is immensely broad as it can be any inhibitor known in the art such as small molecules, peptides, antibodies, nucleic acid inhibitors, or aptamers. Applicant recites the target gene selected from Table 2 which represents 102 different genes.
Claims 2-4, 7, and 10 do not limit the genus of inhibitors, the genus of gene targets, or the claimed function and are rejected for the reasons stated above for claim 1.
Claims 5-6 recite additional functional requirements for the inhibitors, but do not limit the genus of inhibitors. Therefore, claims 5 and 6 require an even more specific function without limiting the structure of the inhibitors. Applicant does not disclose descriptive or functional examples of antibodies or DNA aptamers that function to generically inhibit gene function, which includes inhibiting mRNA transcription of genes. Looking towards the specification, applicant explicitly discloses “the MYC family of oncoproteins, which are broadly implicated in many human cancers, are difficult to inhibit with small molecules or antibody-based therapies (see pg. 9, line 13). Furthermore, applicant only discloses a single example of small molecule inhibitor targeting CSNK1e, which is IC261 (see pg. 13, line 8).
Claims 8-9 limit the gene products to genes disclosed in Table 1 of the instant specification. However, it is still not predictable on how to inhibit such genes with small molecules, antibodies, or aptamers, absent objective evidence to the contrary.
Actual Reduction to Practice
Regarding reduction to practice, applicant discloses siRNA screening to identify a network of genes required for the survival of c-MYC overexpressing cells (see pg. 10, line 17). Applicant discloses out of the genes screened, CSNK1e was chosen for preclinical validation because siRNAs and stable knock-down had showed minimal toxicity to normal HFFs (see Fig. 1). Furthermore, applicant discloses Table 2 which includes target genes as well as the corresponding SEQ ID NOs but does not provide SEQ ID NOs for the target siRNAs.
In the Brief description of the drawings, applicant shows CSNK1e mRNA levels following lentiviral-mediated shRNA knock-down (see Fig. 1C and 2) and the use of a small molecule inhibitor IC261 (Fig. 3). Applicant does not show the use of all inhibitors encompassed by the broad terminology of the claim, such as oligonucleotides, antibodies, DNA aptamers, and microRNAs.
Disclosure of Drawings
Applicant discloses Table 2 of the instant specification which discloses target genes and their respective SEQ ID NOs, which include 102 genes hits that could be targets for inhibition. However, applicant does not disclose SEQ ID NOs of specific siRNAs used for the inhibition of the listed genes.
Predictability in the Art
The art is unpredictable about the use of small molecule inhibitors, DNA aptamers, and antibodies for gene inhibition. This includes whether the millions of known small molecules could target multiple genes presented in Table 1 or 2 of the instant specification or if the disclosure of a single DNA aptamer would be applicable to all target genes. The art acknowledges that antisense and CRISPR nucleic acids that directly bind to (or are 100% identical to) the claimed target are known and predictable in the art. However, the art is silent on the predictable nature of DNA aptamers, antibodies, and small molecules.
Polanowska et al. (The periodic down regulation of Cyclin E gene expression from exit of mitosis to end of G1 is controlled by a deacetylase- and E2F-associated bipartite repressor element, Oncogene, Volume 20, pgs. 4115-4127, published 2001) discloses CERC2 inhibition with trichostatin A (TSA) (see Fig. 8). TSA is a HDAC Class I/II inhibitor and does not share structural similarity to IC261, absent evidence to the contrary.
Stoltenburg et al. (SELEX-A (r)evolutionary method to generate high-affinity nucleic acid ligands, Biomolecular Engineering, Volume 24, Issue 4, pgs. 381-403, published 10/2007) teaches SELEX as a method to screen for nucleic acid ligands. Stoltenburg discloses limitations of such technology as “in reality, not any target molecule is suitable for an aptamer select” and “there is no standardized SELEX protocol applicable for any kind of target. The selection conditions have to be adapted to the current circumstances (target, desired features of the aptamers, applications)” (see section 5). Therefore, it is unpredictable on whether a DNA aptamer that can inhibit one gene presented in table 1 or 2 would be applicable to all genes listed, without experimentation.
Although Applicants may argue that it is possible to screen for antibodies, aptamers, and small molecules that function to “inhibit gene function” of one of the claimed genes, the court found in that screening assays are not sufficient to provide adequate written description for an invention because they are merely a wish or plan for obtaining the claimed chemical invention. Rochester v. Searle, 358 F.3d 916, Fed Cir., 2004. “As we held in Lilly, “[a]n adequate written description of a DNA … ‘requires a precise definition, such as by structure, formula, chemical name, or physical properties,' not a mere wish or plan for obtaining the claimed chemical invention.” 119 F.3d at 1566 (quoting Fiers, 984 F.2d at 1171). For reasons stated above, that requirement applies just as well to non-DNA (or RNA) chemical inventions.” Knowledge of screening methods provides no information about the structure of any future antibody, aptamers, or small molecule yet to be discovered that may function as claimed.”
To conclude, applicant broadly recites any means of gene inhibition for inhibiting the growth and/or proliferation of a MYC-driven tumor cell. As applicant presents only examples with siRNA and a single small molecule inhibitor, it is clear that applicant does not possess or describe all inhibitors, which can broadly range from oligonucleotides, miRNA, ASOs, and small molecule inhibitors. Furthermore, applicant only discloses IC261, which inhibits CSNK1e, but does not disclose on whether this inhibitor can be applied to all the genes listed in Table 2.
The written description requirement for genus claims can be satisfied by disclosure of a representative number of species by actual reduction to practice, reduction to drawings, 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 structure and function, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. The failure to disclose any example, at any level of description, would not convey to one of skill in the art that Applicant was in possession of the recited genus. Accordingly there is a failure to satisfy the written description requirement for the genus of representative number of species of the genus of inhibitors that interfere with the transcription of a gene from Table 2.
In view of the foregoing, claims 1-10 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement.
Indefiniteness
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1, 8 and 10 recite elements directed towards a table. See MPEP 2173.05(s): “Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant's convenience.”
Claims 1 and 2 are indefinite because it is unclear what are the metes and bounds of the limitation “MYC-driven tumor cell”. More specifically, it is unclear when a tumor cell is “MYC-driven” and when it is not. The specification at pages 7 and 8 gives examples of what “MYC-driven” may mean, but does not provide any limiting definition that would make clear what are the metes and bounds of the claims. The specification indicates that MYC-driven “includes” cells that have increased expression of a MYC transcription factor, but sets no standard for comparison, and in any case, does not exclude tumor cells that do not overexpress MYC relative to normal cells.
Claims 3-10 are rejected for depending on claim 1 and not remedying the indefiniteness.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of pre-AIA 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) the invention was known or used by others in this country, or patented or described in a printed publication in this or a foreign country, before the invention thereof by the applicant for a patent.
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claims 1-3, 5, and 8 are rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by Weber et al (Int. J. Cancer: 80, 935–943, 1999).
Regarding claims 1-3, 5, and 8, Weber teaches a method of inhibiting the growth of small cell lung cancer cells in vitro by administration of retinoic acid. This treatment functioned to inhibit the activity of cdk2 (a protein encoded by a gene listed in instant Table 2), and reduced the expression of myc. In view of the fact that decreased expression of myc was associated with decreased cell growth, the cells are considered to be myc-driven tumor cells. See abstract. While the authors speculate that cdk2 inhibition appears likely to be due to an increase in p27Kip1 expression, it is noted that the instant claims do not require that the recited inhibitor must act directly on the gene listed in Table 2. Thus, because administration of retinoic acid to the small cell lung cancer cells caused inhibition of cdk2 activity (directly or indirectly), and because the cells were “MYC-driven”, Weber anticipates the claims.
Claims 1-3 and 6-9 are rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by Wen et al (UROLOGY 73: 1407–1411, 2009), taken with the evidence of Luoto et al (Cancer Res; 70(21); 8748–59, 2010).
Wen taught that treatment of PC-3, DU145, and LAPC4 prostate cancer cells in vitro with siRNA directed to PAK6 resulted in inhibition of cell growth. See abstract. Luoto taught that inhibition of MYC expression in DU145 cells resulted in killing of tumor cells. This is considered to be evidence that DU145 cells are “MYC-driven”. Therefore Wen taught a method of inhibiting growth of MYC-driven tumor cells (DU145 by administration of siRNA against PAK6 and anticipated claims 1-3 and 6-9. Please note that claim 6 is included in this rejection in the event that Applicant intended to use the term “translation” instead of the term "transcription". The siRNA of Wen clearly interferes with translation of transcribed PAK6 mRNAs.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-4 and 6-10 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Wen et al (UROLOGY 73: 1407–1411, 2009) and Chang et al (US 20050002998), taken with the evidence of Luoto et al (Cancer Res; 70(21); 8748–59, 2010).
The teachings of Wen and Luoto are discussed above. Wen taught that treatment of PC-3, DU145, and LAPC4 prostate cancer cells in vitro with siRNA directed to PAK6 resulted in inhibition of cell growth. Since Du145 cells are considered to be “MYC-driven” in view of the evidence of Luoto, Wen anticipated and rendered obvious claims 1-3 and 6-9.
Wen did not teach the use of an inhibitor in vivo as required by instant claims 4 and 10.
Chang taught an animal model of prostate cancer in which Du145 cells were xenografted into mice, and methods of delivering nucleic acids to the tumor. Chang exemplified targeted delivery of complexes comprising plasmid DNA, and also exemplified the synthesis of similar complexes comprising siRNA instead of DNA. See Figs. 4-7 for examples of targeted delivery of plasmid DNA to DU145 xenograft. See Example 11 for synthesis of similar complexes with siRNA instead of DNA.
It would have been obvious to one of ordinary skill in the art at the time of the invention to have extended the work of Wen by delivering PAK6 siRNA to DU145 cells in vivo, e.g. in the model system of Chang. One would have been motivated to do so because Wen stated that PAK6 could be a valuable molecular target for the treatment of prostate cancer (abstract), and the use of an animal model represents a logical step in the process of evaluating PAK6 as such a target. One would have been motivated to use siRNA because Wen demonstrated that siRNA functioned in the in vitro model, and one would have had a reasonable expectation of success because Chang demonstrated that DU145 cells could be targeted for nucleic acid delivery in vivo.
Thus the invention as a whole was prima facie obvious.
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 1-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. US 9273317 B2, published on 3/1/2016. Although the claims at issue are not identical, they are not patentably distinct from each other because all the claims at issue are directed towards a method for inhibiting the growth and/or proliferation of a MYC-driven tumor (where issued patent recites increased expression of a MYC transcription factor compared to a control) wherein the tumor is a neuroblastoma tumor cell or an ovarian tumor (claim 2 of the instant application recites wherein the MYC-driven tumor cell is a neuroblastoma cancer or an ovarian cancer). Furthermore, both the issued patent (claim 3 and 4) and instant application (claims 3 and 4) recite where the tumor cell is contacted in vitro and in vivo and the target genes of both instant and copending application overlap (CERC2, TIE1, PES1).
In view of the foregoing, it is obvious to one with ordinary skill in the art that the scope of the claimed invention is patentably indistinct between the instant application and the copending application.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID YU whose telephone number is (571)272-1118. The examiner can normally be reached Monday-Friday 7:30 am -5 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ram Shukla can be reached at 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/D.T.Y./Examiner, Art Unit 1635
/CATHERINE KONOPKA/Primary Examiner, Art Unit 1635
Prosecution Insights