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 .
Applicant’s election without traverse of group I, SEQ ID NO: 3, and promoter region in the reply filed on 2/23/24 is acknowledged. SEQ ID NOs: 4, 7, and 8 have been searched and examined because SEQ ID NO: 3 is free of the prior art.
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.
Claims 1, 24-27, 31-33, 35, 36, and 39 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 HER2-amplified breast cancer or HER2-amplified ovarian cancer via delivery of a specific TFO targeting the coding region of HER2, does not reasonably provide enablement for a method of inducing a DNA double strand break in any breast or ovarian cancer cell comprising any amplified gene that has any polypurine site with a TFO targeted to any polypurine site and activating apoptosis.
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.
Factors to be considered in a determination of lack of enablement include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)
The claims are directed to a method of inducing a DNA double strand break in any breast or ovarian cancer cell comprising any amplified gene that has any polypurine site with a TFO targeted to any polypurine site and activating apoptosis; or wherein the cell is p53-depleted.
The specification demonstrates transfection of human breast cancer cell lines with SEQ ID NO: 4, an oligomer that binds to a specific polypurine sequence in the coding region of the HER2 gene; and subcutaneous injection in mice.
Treatment of HER2-positive breast cancer with a TFO targeted to a specific polypurine site in an amplified HER2 gene is not representative of: a method of inducing a DNA double strand break in any breast or ovarian cancer cell comprising any amplified gene that has any polypurine site with a TFO targeted to any polypurine site and activating apoptosis.
The specification does not draw an adequate nexus between delivery of any TFO targeted to any polypurine site in any amplified gene in any breast or ovarian cancer cell with the resultant outcome of inducing a double stranded break and activating apoptosis.
For example, the claims encompass a method of inducing a double stranded break in any type of cancer cell (i.e. pancreatic) that comprises a amplified VEGF or STAT3 gene via delivery of a triplex forming molecule targeted to any polypurine site that has not been shown to cause induction of a DNA double stranded break and activation of apoptosis. The single species of the specification is not commensurate in scope with delivery of a TFO targeted to any length of any polypurine site in any amplified gene in any breast or ovarian cancer.
The scope of the claims in view of the specification as filed together do not reconcile the unpredictability in the art to enable one of skill in the art to make and/or use the claimed invention, namely a broad method of activating apoptosis in any cancer encompassing in vivo effects.
MPEP 2164.01
Any analysis of whether a particular claim is supported by the disclosure in an application requires a determination of whether that disclosure, when filed, contained sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use the claimed invention.
Also, MPEP 2164.01(a)
A conclusion of lack of enablement means that, based on the evidence regarding each of
the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed
invention without undue experimentation. In re Wright, 999 F.2d 1557,1562, 27
USPQ2d 1510, 1513 (Fed. Cir. 1993).
Given the teachings of the specification as discussed above, one skilled in the art could not predict a priori whether introduction of any TFO of any sequence or structure in vivo by the broadly disclosed methodologies of the instantly claimed invention, would result in each of the recited outcomes. Without further guidance, one of skill in the art would have to practice a substantial amount of trial and error experimentation, an amount considered undue and not routine, to practice the instantly claimed invention.
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation (see MPEP 2164.01(a)).
Response to Arguments
Applicant argues that the specification provides more than sufficient guidance to enable the full scope of the amended claims. Applicant argues that the specification provides comprehensive enablement for the claimed invention through detailed mechanistic explanations, broad experimental validation, and explicit guidance for implementation. Applicant argues that the disclosure clearly explains how triplex-forming oligonucleotides (TFOs) binding to polypurine sites within amplified genes impede replication fork progression, resulting in fork collapse and double-strand break formation that selectively targets cancer cells with gene amplifications. Working examples demonstrate the method's broad applicability across different cancer types, including HER2-positive breast and ovarian cancers, while detailed guidance on target site selection provides identification of over 519,971 unique targeting sequences throughout the human genome. Moreover, the specification shows that the method produces predictable results regardless of gene function or p53 status, with TFO treatment activating p53-independent apoptosis without altering target gene expression levels, demonstrating the robustness and wide applicability of the approach.
Contrary to applicant’s arguments, the specification does not enable targeting any possible polypurine site in any amplified gene with a predictable result of inducing a double strand break and activating apoptosis in any breast or ovarian cancer cell, even those that are not HER2-positive and wherein the TFO does not target any specific region or length of a HER2 gene.
The specification discloses that the approach employs TFOs that recognize unique polypurine sites within the amplified chromosomal region; and that binding of TFOs within the major groove of the double helix causes DNA perturbation and DSB formation (page 63). The specification discloses that HER2-205 is a TFO that binds within the coding region at position 205 of HER2 and that this is a favorable polypurine site for high affinity triplex formation (page 63). However, the specification is not commensurate in scope with the instant claims. The claims do not require for the TFO to be targeted to any specific polypurine site and encompass targeting any polypurine site at any location within any amplified gene.
The specification teaches successful targeting of HER2-positive ovarian cancers that have high HER2 copy number gains (page 64). The specification hypothesizes that HER-2 targeted TFO could potentially be sued to treat HER2-positive cancers (page 65).
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 25-27, 31, 32, 35, 36, and 39 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5 and 9-13 of copending Application No. 17/850,793 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of application ‘793 are directed to a method of inducing DNA damage, wherein instantly recited DNA double strand breaks are a species of DNA damage, comprising administering to cancer cells that comprise an amplified gene that comprises a polypurine site a TFO targeted to the polypurine site. The instant claims utilize open language that can encompass the first and second TFOs of application ‘793. The addition of a second TFO is an obvious variation. Instant recitation of activation of apoptosis is an intended outcome, whereas both claim sets recite the same method step of delivering the TFO targeted to a polypurine site of an amplified gene.
Claim 13 of application ‘793 recites breast and ovarian cancers, which are recited in instant claim 1. Claims 11 and 12 of application ‘793 recites chemical modifications, which are recited in instant claims 31 and 39.
The claims are obvious variations of each other. The claims recite different variations of the intended use, but recite methods of delivering the same agents with the same steps and recite the same types of cancer cells.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 25-27, 31, 32, 35, 36, and 39 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 9,587,238 B1. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of US ‘238 B1 are directed to methods of delivering TFOs specific for a polypurine site in an amplified HER2 gene, which is a species that anticipates the instant genus of any gene. The TFOs of US ‘238 B1 have the same structural requirements as instantly claimed and would therefore necessarily induce a DNA double strand break and recites induction of apoptosis. The claims are obvious variations of each other. The claims of US ‘238 B1 recite inducing apoptosis in breast cancer cells, which is recited in instant claim 1. The instant claims utilize open language that can encompass additional elements.
Claims 1, 25-27, 31, 32, 35, 36, and 39 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 11,401,340 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of US ‘340 B2 are directed to methods of delivering TFOs specific for a polypurine site in an amplified HER2 gene, which is a species that anticipates the instant genus of any gene. The TFOs of US ‘340 B1 have the same structural requirements as instantly claimed and would therefore necessarily induce a DNA double strand break and each of the recited outcomes as instantly claimed. The claims are obvious variations of each other. The claims of US ‘340 B2 recited that the cancer cells are p53 depleted, which is instantly claimed (instant claim 25). US ‘340 B2 recites breast and ovarian cancer cells (claim 14) as recited in instant claim 1.
Response to Arguments
Applicant argues that the rejection should be withdrawn in view of the amendments. The rejection has been amended in response to the claim amendments.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Amy R Hudson whose telephone number is (571)272-0755. The examiner can normally be reached on M-F 8:00am-6:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached on 571-270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/AMY ROSE HUDSON/Primary Examiner, Art Unit 1636