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 with traverse of group I and the species TROLL-2, breast cancer, TAP63 regulated, and siRNA in the reply filed on 10/1/25 is acknowledged. The traversal is on the ground(s) that the office action has not shown that there is a serious burden. This is not found persuasive because search burden is not a consideration in 371 applications. Additionally, the present of six different TROLL gene/transcripts, each having a different sequence and activities does in fact present a serious search burden. siRNAs targeting each of the TROLL transcripts have different sequences and activities.
The requirement is still deemed proper and is therefore made FINAL.
Claims 9, 10, 13-20, 23, and 24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 10/1/25.
Drawings
The drawings filed on 7/13/22 are objected to because they are not legible. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Sequence Compliance
This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 through 1.825 because the claims (9, 11, 13, 15, 17, and 19) recite GenBank accession numbers rather than referring to the sequences by an appropriate SEQ ID NO. These sequences cannot be fully searched and examined without recitation of a SEQ ID NO.
A complete response to this office action must correct the defects cited above regarding compliance with the sequence rules and a response to the action on the merits which follows.
The aforementioned instance of failure to comply is not intended as an exhaustive list of all such potential failures to comply in the instant application. Applicants are encouraged to thoroughly review the application to ensure that the entire application is in full compliance with all sequence rules. This requirement will not be held in abeyance.
2422.01 Nucleotide and/or Amino Acids Disclosures Requiring a “Sequence Listing” [R-07.2022]
I. LENGTH THRESHOLDS
37 CFR 1.821(a) presents a definition for “nucleotide and/or amino acid sequences.” This definition sets forth limits, in terms of numbers of amino acids and/or numbers of nucleotides, at or above which compliance with the sequence rules is required. Nucleotide and/or amino acid sequences as used in 37 CFR 1.821 through 37 CFR 1.825 are interpreted to mean an unbranched sequence of four or more amino acids or an unbranched sequence of ten or more nucleotides. Branched sequences are specifically excluded from this definition. Sequences with fewer than ten specifically defined nucleotides or four specifically defined amino acids are specifically excluded from 37 CFR 1.821. “Specifically defined” means those amino acids other than “Xaa” and those nucleotide bases other than “n” defined in Appendices A-F to 37 CFR part 1, Subpart G (see MPEP § 2422(I)).
The limit of four or more amino acids was established for consistency with limits in place for industry database collections whereas the limit of ten or more nucleotides, while lower than certain industry database limits, was established to encompass those nucleotide sequences to which the smallest probe will bind in a stable manner.
Improper Markush Rejection
Claims 1, 2, 5, 7, 8, 21, and 22 are rejected on the judicially-created basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). The improper Markush grouping includes species of the claimed invention that do not share both a substantial structural feature and a common use that flows from the substantial structural feature. The members of the improper Markush grouping do not share a substantial feature and/or a common use that flows from the substantial structural feature for the following reasons: The claims are directed to a method of knocking down six different lncRNAs, each being over a thousand nucleotides in length and having different isoforms. The sequence and activity of each is different, wherein the activity is dependent upon the specific sequence of nucleotides.
Additionally, the claims are directed to delivery of antisense oligonucleotides, siRNA, shRNA, ribozymes, TALEN, AFNs, or CRISPR/Cas nucleases, each of which has a different structure and acts via a different mechanism.
In response to this rejection, Applicant should either amend the claim(s) to recite only individual species or grouping of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claims(s) in fact share a substantial structural feature as well as a common use that flows from the substantial structural feature. This is a rejection on the merits and may be appealed to the Board of Patent Appeals and Interferences in accordance with 35 U.S.C. 134 and 37 CFR 41.31(a)(1).
When the Markush grouping is for alternatives of chemical compounds, they shall be regarded as being of a similar nature where the following criteria are fulfilled:
(A) All alternatives have a common property or activity; and
(B) (1) A common structure is present, i.e., a significant structural element is shared by all of the alternatives; or
(B) (2) In cases where the common structure cannot be the unifying criteria, all alternatives belong to a recognized class of chemical compounds in the art to which the invention pertains.
In paragraph (B)(1), above, the words “significant structural element is shared by all of the alternatives” refer to cases where the compounds share a common chemical structure which occupies a large portion of their structures, or in case the compounds have in common only a small portion of their structures, the commonly shared structure constitutes a structurally distinctive portion in view of existing prior art, and the common structure is essential to the common property or activity. The structural element may be a single component or a combination of individual components linked together.
In paragraph (B)(2), above, the words “recognized class of chemical compounds” mean that there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention. In other words, each member could be substituted one for the other, with the expectation that the same intended result would be achieved.
In order for the members of the Markush group to belong to “recognized class of chemical compounds” there must be an expectation that the members of the class will behave in the same way in the context of the claimed invention. In other words, each member of the class could be substituted one for the other with the expectation that the same intended result would be achieved. In the instant case, activity of any specific type of RNA-targeted therapeutic is dependent upon the specific structure. There is no expectation that any one of the therapeutics as claimed can be substituted for any of the other with a different structure that acts via a different mechanism with the expectation of the same activity; and there is no expectation that knocking down the expression of any one target would result in the same outcome as knocking down a different target with a different sequence. Additionally, agents targeting each of the targets each have different structures and/or sequences, resulting in different activities.
As set forth in MPEP2117, “Note that where a Markush group includes only materials from a recognized scientific class of equivalent materials or from an art-recognized class, "the mere existence of such a group in an application tend[s] to prove the equivalence of its members and when one of them [is] anticipated the group [is] therefore rendered unpatentable, in the absence of some convincing evidence of some degree of non-equivalency of one or more of the remaining members." In re Ruff, 256 F.2d 590, 598-99, 118 USPQ 340, 348 (CCPA 1958)("[A]ctual equivalence is not enough to justify refusal of a patent on one member of a group when another member is in the prior art. The equivalence must be disclosed in the prior art or be obvious within the terms of Section 103." Id. at 599, 118 USPQ at 348).”
In the instant case, art against any one therapeutic or target sequence would not be evidence against any of the remaining members that have completely different structures and/or sequences and do not have identical activity.
Claim Rejections - 35 USC § 112
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.
Claim 12 is 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.
Claim 12 recites administration to the subject the siRNA as set forth in SEQ ID NO: 13, SEQ ID NO: 14, and/or SEQ ID NO: 15. The metes and bounds of the language “as set forth in” is not definite. It is unclear whether the siRNA comprises one of the recited sequences, consists of one of the recited sequences, or if the sequences comprise smaller sequences that are siRNA sequences. Additionally, each of the sequences are a single stranded sequence and therefore do not represent a full siRNA duplex on its own.
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, 2, 5, 7, 8, 11, 21, and 22 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.
The claims recite a genus of lncRNAs, wherein TROLL-2 is the elected lncRNA. However, the specification does not adequately describe the structure required for the genus of “TROLL-2” sequences. Instant claim 11 recites a TROLL-2 isoform by Genbank Accession number, which is evidence that the term “TROLL-2” is not limited to any specific sequence. The specification does not disclose any other isoforms of TROLL-2 and does not specifically disclose the sequence of the isoform recited in claim 11. Without further description of the structure required, one would not be able to recognize which sequences are necessarily included or excluded from the terminology “TROLL-2”.
With regards to claim 11, the specification discloses a single species of TROLL-2 sequences by Genbank accession number “NR_026825.2” and the name “RPSAP52”, which is not adequate to describe even this single isoform. Applicant is required to refer to the sequence in the claims by a SEQ ID NO. The term “RPSAP52” does not appear to be a term of the art. Without further description of the specific sequence in the specification, one would not be able to recognize that applicant was in possession of the entire claimed genus at the time of filing.
The claims do not recite a specific TROLL-2 nucleotide sequence by SEQ ID NO, but rather refer to the undefined genus of TROLL-2 sequences.
The claims encompass knocking down the expression of TROLL-2 via any possible means and therefore a method of introducing any type of TROLL-2 inhibitor to inhibit the expression of any TROLL-2 sequence, as well as encompass any TROLL-2 homolog or allele from any species known or yet to be discovered of TROLL-2, as well as DNA genomic fragments, spliced variants or fragment that retains TROLL-2 -like activity. The specification does not adequately describe this genus and does not disclose even a single species of TROLL-2 sequences by SEQ ID NO.
Although the specification discloses some inhibitory molecules such as antisense oligonucleotides, siRNA, shRNA, ribozymes, transcription activator-like effector nucleases (TALEN), zinc finger nucleases (ZFNs) and/or clustered regularly interspaced short palindromic repeats/associated (CRISPR/Cas) nucleases, disclosure of this broad genus is not an adequate description of the actual genus of compounds that would result in the function of knocking down the expression of TROLL-2. Claim 1 is not limited to these agents and even with regards to claim 8, which recites these agents, the agents are not required to have any specific structural relationship with any specific TROLL-2 sequence. Additionally, the agents can act on any target that has a secondary effect of knocking down TROLL-2, which is a genus of agents that has not been adequately described in the specification.
Instant claim does not recite what step is actually required for the knockdown of TROLL-2. The specification does not adequately describe the step required for the outcome or the structure required to be delivered to result in the recited function. The minimal species of the specification, delivery of the siRNAs of instant claim 12, which are specifically targeted to a specific isoform of TROLL-2 (instant claim 11) is not representative of the entire claimed genus of any mode of knocking down the expression of any possible TROLL-2 sequence.
The specification does not describe agents directed to any other species of TROLL-2 to describe the instantly claimed genus of any TROLL-2. Each of the instantly disclosed agents are siRNAs specifically targeted to a single sequence, although the claims are drawn to any TROLL-2. One of ordinary skill in the art could not make such agents to any TROLL-2 without knowledge of the sequence and knowledge of the structure of the agent. Given the breadth of sequences embraced in the instantly claimed genus, one could not envision the member agents that target such a broad genus.
With regards to instant claim 5, the specification does not adequately describe the genus of breast cancers that are “Tap63 regulated”. Without further knowledge of the genus, one would not be able to readily envision which breast cancers are regulated in any manner by Tap63.
The MPEP states that for a generic claim, the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. See MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitute a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad genus. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618. Additionally, in Carnegie Mellon University v. Hoffman-La Roche Inc., Nos. 07-1266, -1267 (Fed. Cir. Sept. 8, 2008), the Federal Circuit affirmed that a claim to a genus described in functional terms was not supported by the specification’s disclosure of species that were not representative of the entire genus. Furthermore, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The Guidelines for Examination of Patent Applications under the 35 USC § 112, first paragraph, “Written Description” Requirement”, published at Federal Register, Vol. 66, No. 4, pp. 1099-1111 outline the method of analysis of claims to determine whether adequate written description is present. The first step is to determine what the claim as a whole covers, i.e., discussion of the full scope of the claim. Second, the application should be fully reviewed to understand how applicant provides support for the claimed invention including each element and/or step, i.e., compare the scope of the claim with the scope of the description. Third, determine whether the applicant was in possession of the claimed invention as a whole at the time of filing.
With regards to the elected species, siRNA, it appears that the structure is required to have an antisense strand that is fully complementary to a target sequence in order to achieve the desired function. For example, Elbashir et al. (The EMBO Journal, Vol. 20, No. 23, pages 6877-6888, 2001) teaches that duplexes of 21-23 nt RNAs are the sequence specific mediators of RNAi and that even single mismatches between the siRNA duplex and the target mRNA abolish interference (abstract and page 6888).
Thus, having analyzed the claims with regard to the Written Description guidelines, it is clear that the specification does not disclose a representative number of species for instant genuses that have the required functions. Thus, one skilled in the art would be led to conclude that Applicant was not in possession of the claimed invention at the time the application was filed.
Claims 1, 2, 5, 7, 8, 11, 12, 21, and 22 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 a TROLL-2 sequence via delivery of a TROLL-2 specific shRNA, does not reasonably provide enablement for a method of treating any possible cancer via knocking down the expression of any TROLL-2 sequence. 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 treating any possible cancer via knocking down the expression of any TROLL-2 sequence.
The specification does not draw an adequate nexus between knockdown of any TROLL-2 sequence and the predictable outcome of the treatment of any possible cancer, which encompasses an enormous genus of cancers that have not been shown to be reliant upon TROLL-2 expression alone.
The specification demonstrates “shRNA for TROLL-2” delivery, but is silent as to the sequence of the shRNA or the specific TROLL-2 target in breast cancer, lung cancer, and melanoma in tumor xenografts in mice. Mice were fed doxycycline containing food to induce the expression of the shRNA to target the lncRNA TROLL-2 (page 54). The resultant inhibition of this TROLL-2 isoform via shRNA specifically targeted to it in these cancers is not enabling for a method of treating any cancer via knocking down the expression of any TROLL-2 sequence in any manner with any agent.
Importantly, the specification is silent as to the effect of the shRNA targeting the TROLL-2 sequence in any specific cancer. The are not legible so it is not evident if this information is present in the drawings. The TROLL-2 inhibition is not representative of treatment of any possible cancer or any possible metastatic cancer or any possible breast cancer, lung cancer, ovarian cancer, colon cancer, or melanoma via inhibition of TROLL-2 alone via any means of knocking down the expression.
The specification discloses that certain lncRNAs are “Tap63 regulated”, but does not demonstrate a predictable method of treating any Tap63 regulated cancer via knockdown of expression of any TROLL-2 sequence alone.
Instant claim 11 requires for the expression of TROLL-2 to be knocked down by “targeting the RPSAP52/NR_026825.2 isoform”. The specification is not enabling for “targeting” in any manner the “RPSAP52/NR_026825.2 isoform” (undisclosed sequence) with a predictable outcome of treating any possible cancer. The specification has not drawn an adequate nexus between the expression of the “RPSAP52/NR_026825.2 isoform” alone and any possible cancer.
With regards to instant claim 12, the specification does not draw an adequate nexus between administration of the recited siRNAs and the treatment of any possible cancer. The siRNAs target the “RPSAP52/NR_026825.2 isoform”, which has not been adequately correlated to the presence of any cancer and its inhibition has not been adequately correlated to the treatment of any cancer.
There is no guidance in the specification as filed that teaches how to knock down the expression in any manner of any TROLL-2 sequence in vivo with the predictable outcome of treating any possible cancer.
With regards to siRNAs, the elected species, the siRNA is not required to have any specific structural relationship to any specific TROLL-2 sequence. Elbashir et al. (The EMBO Journal, Vol. 20, No. 23, pages 6877-6888, 2001) teaches that duplexes of 21-23 nt RNAs are the sequence specific mediators of RNAi and that even single mismatches between the siRNA duplex and the target mRNA abolish interference (abstract and page 6888).
Fujita et al. (Int. J. Mol. Sci. 2015, 16, 5254-5270) teach that two types of small RNA molecules, small interfering RNAs (siRNAs) and microRNAs (miRNAs), have a central function in RNAi technology. The success of RNAi-based therapeutic delivery may be dependent upon uncovering a delivery route, sophisticated delivery carriers, and nucleic acid modifications (page 5254). Fujita et al. teach that the success of an RNAi-based therapy in clinical trials rests on careful selection of target genes and miRNAs. Moreover, we suggest that a delivery route, sophisticated delivery carriers, chemical modification, and modified RNAi platforms are needed to enhance RNAi effects in cancer cells (pages 5262-5263).
As outlined above, it is well known that there is a high level of unpredictability in the RNAi art for therapeutic in vivo applications. 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 mediating RNA interference 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 knocking down the expression via any manner of any TROLL-2 sequence in vivo by the broadly disclosed methodologies of the instantly claimed invention, would result in successful treatment of any possible cancer. To practice the claimed invention, one of skill in the art would have to de novo determine; the stability of the molecule in vivo, delivery of the molecule to the whole organism, specificity to the target and the target tissue in vivo, dosage and toxicity in vivo, and entry of the molecule into the cell in vivo and the effective action therein. 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)).
Claim Rejections - 35 USC § 103
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 2, 7, 8, 11, 21, and 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Helgason et al. (US 2018/0051340 A1), in view of Oliveira-Mateos et al. (Nature Communications, 2019, 10, 3979, 1-18).
The references are considered as enabled as the instant claims.
Helgason et al. teach that RSAP52 (the TROLL-2 isoform recited in instant claim 11) is upregulated in metastatic prostate cancer (Table 4, page 19) (instant claim 22).
Helgason et al. teach that this lncRNA may be used in combination with PCAT18 to treat prostate cancer (page 18). Helgason et al. teach a method of administering an inhibitor of PCAT18 to treat prostate cancer and that PCAT18 is a lncRNA upregulated in prostate cancer (abstract and Figures).
Helgason et al. teach silencing of PCAT18 using PCAT18 siRNAs (Example 5, pages 30-31).
It would have been obvious to treat metastatic prostate cancer in a subject having metastatic prostate cancer via knocking down the expression of TROLL-2 (isoform RPSAP52) with a TROLL-2 targeted siRNA because Helgason et al. teach siRNA inhibition of an upregulated lncRNA (PCAT18) to treat prostate cancer and teach that RSAP52 is another lncRNA upregulated in metastatic prostate cancer and teach that both lncRNAs can be used in combination for the treatment method (instant claims 1, 7, 8, 11, and 21). Additionally, the sequence of RSAP52 was known, as evidenced by Oliveira-Mateos et al. (RPSAP52 transcript NR_026825.2, pages 2 and 15).
Helgason et al. do not offer motivation to knock down the expression of RPSAP52 to treat breast cancer. However, Helgason et al. does offer motivation to inhibit the expression of an upregulated lncRNA for the treatment of the cancer.
Oliveira-Mateos et al. teach that RPSAP52 is overexpressed in breast cancer (page 2, column 1) (instant claim 2). It would have been obvious to utilize a siRNA targeting RPSAP52 to knock down the expression of RPSAP52 to treat breast cancer because Helgason et al. offers motivation to inhibit the expression of an upregulated lncRNA for the treatment of the cancer; and teaches utilizing siRNAs targeting lncRNAs; and teaches that RPSAP52 is upregulated in prostate cancer and can be used in the method to treat prostate cancer.
Oliveira-Mateos et al. teach that upon RPSAP52 knockdown, all three breast cell lines tested (the non-transformed MCF10A and the tumorigenic Hs578T and HCC1143 cells) proved to be significantly less proliferative (page 4, column 1).
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, 2, 5, 7, 8, 21, and 22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7, 8, 14, and 15 of copending Application No. 18/277,760 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of application ‘760 are directed to a method of treating cancer via administering an anti-cancer agent, wherein the instant agent for knocking down TROLL-2 is an anti-cancer agent, and wherein the claims of application ‘760 require assaying for TROLL-2 expression before administration of the agent. Assaying for expression of the target that is the same target as instantly recited would be an obvious step to incorporate into the instant method given that the purpose of the instant method is to inhibit TROLL-2. One would want for TROLL-2 to be expressed in order to inhibit it. The claims of application ‘760 recite that the agent is a siRNA that targets TROLL-2 and wherein the cancer is TAP63 regulated and wherein the cancer is breast cancer. The claims are obvious variations of each other. The only difference is the addition of the step to confirm expression of the intended target.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 2, 5, 7, 21, and 22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7 and 21 of copending Application No. 17/791,706 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of application ‘706 are directed to a method of treating cancer via administering an anti-cancer agent, wherein the instant agent for knocking down TROLL-2 is an anti-cancer agent, and wherein the claims of application ‘706 require assaying for TROLL-2 expression before administration of the agent. Assaying for expression of the target that is the same target as instantly recited would be an obvious step to incorporate into the instant method given that the purpose of the instant method is to inhibit TROLL-2. One would want for TROLL-2 to be expressed in order to inhibit it. The claims of application ‘706 recite that the cancer is TAP63 regulated and wherein the cancer is breast cancer. The claims are obvious variations of each other. The instant agents are species of the genus of application ‘706. The only difference is the addition of the step to confirm expression of the intended target.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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/AMY ROSE HUDSON/Primary Examiner, Art Unit 1636