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 .
Election/Restrictions
REQUIREMENT FOR UNITY OF INVENTION
As provided in 37 CFR 1.475(a), a national stage application shall relate to one invention only or to a group of inventions so linked as to form a single general inventive concept (“requirement of unity of invention”). Where a group of inventions is claimed in a national stage application, the requirement of unity of invention shall be fulfilled only when there is a technical relationship among those inventions involving one or more of the same or corresponding special technical features. The expression “special technical features” shall mean those technical features that define a contribution which each of the claimed inventions, considered as a whole, makes over the prior art.
The determination whether a group of inventions is so linked as to form a single general inventive concept shall be made without regard to whether the inventions are claimed in separate claims or as alternatives within a single claim. See 37 CFR 1.475(e).
When Claims Are Directed to Multiple Categories of Inventions:
As provided in 37 CFR 1.475 (b), a national stage application containing claims to different categories of invention will be considered to have unity of invention if the claims are drawn only to one of the following combinations of categories:
(1) A product and a process specially adapted for the manufacture of said product; or
(2) A product and a process of use of said product; or
(3) A product, a process specially adapted for the manufacture of the said product, and a use of the said product; or
(4) A process and an apparatus or means specifically designed for carrying out the said process; or
(5) A product, a process specially adapted for the manufacture of the said product, and an apparatus or means specifically designed for carrying out the said process.
Otherwise, unity of invention might not be present. See 37 CFR 1.475 (c).
Restriction is required under 35 U.S.C. 121 and 372.
This application contains the following inventions or groups of inventions which are not so linked as to form a single general inventive concept under PCT Rule 13.1.
In accordance with 37 CFR 1.499, applicant is required, in reply to this action, to elect a single invention to which the claims must be restricted.
Group I, claim(s) 1-13,15-17,22, drawn to a nucleic acid construct.
Group II, claim(s) 24, drawn to a method of measuring homologous recombination activity.
Group III, claim(s) 25, drawn to a method of identifying a candidate of an agent.
Group IV, claim(s) 28, drawn to a diagnostic method for homologous recombination deficient cancer.
Group V, claim(s) 32,41, drawn to a detection method for homologous recombination restored cancer cells.
Group VI, claim(s) 35, drawn to a method of predicting an effect of an anticancer drug on homologous recombination deficient cancer.
Group VII, claim(s) 44, drawn to a method of predicting whether or not a gene mutation is pathogenic mutation.
The groups of inventions listed above do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons:
Groups I-VII lack unity of invention because even though the inventions of these groups require the technical feature of a nucleic acid construct, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Czochor et al. (Mol Cancer Res 2016, cited below) which teaches a nucleic acid construct (p. 365-369).
During a telephone conversation with Gerald Murphy on 7/23/2026 a provisional election was made with traverse to prosecute the invention of Group I. Affirmation of this election must be made by applicant in replying to this Office action. Claims 24,25,28,32,35, 41,44 withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
The examiner has required restriction between product or apparatus claims and process claims. Where applicant elects claims directed to the product/apparatus, and all product/apparatus claims are subsequently found allowable, withdrawn process claims that include all the limitations of the allowable product/apparatus claims should be considered for rejoinder. All claims directed to a nonelected process invention must include all the limitations of an allowable product/apparatus claim for that process invention to be rejoined.
In the event of rejoinder, the requirement for restriction between the product/apparatus claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the rejoined claims must meet all criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103 and 112. Until all claims to the elected product/apparatus are found allowable, an otherwise proper restriction requirement between product/apparatus claims and process claims may be maintained. Withdrawn process claims that are not commensurate in scope with an allowable product/apparatus claim will not be rejoined. See MPEP § 821.04. Additionally, in order for rejoinder to occur, applicant is advised that the process claims should be amended during prosecution to require the limitations of the product/apparatus claims. Failure to do so may result in no rejoinder. Further, note that the prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues. See MPEP § 804.01.
Claim Summary
Claims 1-13, 15-17,22, 24-25, 28, 32, 35, 41,44 are pending. Claims 14,18-21,23,26-27,29-31,33-34,36-40,42-43 have been cancelled.
Claims 24-25, 28, 32, 35, 41,44 are withdrawn as being drawn to nonelected inventions.
An action on the merits for claims 1-13, 15-17,22 is set forth below.
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.
Claims 1-13, 15-17,22 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 1-13, 15-17,22 are indefinite over the cleavage site of claim 1. In particle the first nucleic acid molecule comprises a promoter region and a mutant gene sequence placed downstream. The claim requires that mutant gene encodes a protein and a cleavage site arranged inside thereof. It is not clear if the “inside thereof” intends that the cleavage site is within the mutant gene sequence or if the cleavage site is inside the first nucleic acid molecule itself.
Claims 1-13, 15-17,22 are indefinite over “a protein whose sequence is 80% or more identical to that of the previously mentioned protein”. This phrase is unclear as it is not clear if the claim is referring to the first nucleic acid molecule or if the claims encompass another non-referred to protein sequence. It is not clear the metes and bounds of the term “previously mentioned”.
Claim 3 is not clear as iii does not require a base sequence and as such it is not clear which base sequence the claim is referring to in claim 3.
Claim 13 is unclear. The claim requires that the gene sequence is a gene sequence encoding a protein which intracellular expression is detectable”. This appears to be a recitation of a use of the reagent and as such it is not clear how the “intracellular expression is detectable” alters the structure of claim 13.
Claim 17 is unclear. The claim requires that the gene sequence is a gene sequence encoding a protein whose intracellular expression is detectable”. This appears to be a recitation of a use of the reagent and as such it is not clear how the “intracellular expression is detectable” alters the structure of claim 13.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-13, 15-17,22 are rejected under 35 U.S.C. 101 because the claimed invention is directed to nucleic acid construct without significantly more. The claim(s) recite(s) broad claim language that is interpreted as the same structure as a product of nature. This judicial exception is not integrated into a practical application because the claims do not require a particular structure other than structures that can be found in nature. . The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because, the claims read on the nucleotides found in nature. The native nucleotide sequence is a product of nature and is not patentable.
Question 1
The claimed invention is directed to a naturally occurring product.
Question 2A – Prong 1
The claims are directed towards a naturally occurring product of a structure of nucleic acids.
MPEP 2106.04(b)(II) discusses products of nature. The MPEP specifically discusses DNA, primers and probes. The isolated DNA of Myriad and the primers of Ambry Genetics were described as products of nature by the courts. Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 580, 106 USPQ2d 1972, 1975 (2013); University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 758-59, 113 USPQ2d 1241, 1243 (Fed. Cir. 2014). As explained in those decisions, products of nature are considered to be an exception because they tie up the use of naturally occurring things, but they have been labeled as both laws of nature and natural phenomena. See Myriad Genetics, Inc., 569 U.S. at 590-91, 106 USPQ2d at 1979 (claims to isolated DNA held ineligible because they "claim naturally occurring phenomena" and are "squarely within the law of nature exception"). The Federal Circuit in Ambry reviewed “[t]he Supreme Court held ineligible claims directed to segments as short as 15 nucleotides, suggesting that even short strands identical to those found in nature are not patent eligible.”
In the instant case, the claims include naturally occurring genes. The court in Myriad held that “[a] naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated”. The court found that while Myriad had located and sequenced an important gene, Myriad had not created anything, and that “separating that gene from its surrounding genetic material is not an act of invention” (page 2118).
Here, the specification discloses that constructs can include BRCA1 or BRCA2 (p. 2). It is not clear how these claimed constructs are different from naturally occurring BRAC1 or BRAC2.
Accordingly, the claims are directed to judicial exceptions.
Question 2A – Prong 2
The judicial exceptions are not integrated into practical application because the claims do not recite additional elements that integrate the judicial exceptions into practical application of the exceptions.
Accordingly, claims are directed towards judicial exceptions.
Question 2B
The claims are directed to judicial exceptions with no additional limitations.
Thus, the claims do not recite additional elements that amount to significantly more than the judicial exceptions.
For those reasons, the claims are rejected under section 101 as being directed to non-statutory subject matter.
Claim Rejections - 35 USC § 102
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.
Claim(s) 1 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Czochor et al. (Mol. Cancer Res., 2016, 14: 363-373 .
With regard to claim 1, Czochor et al. teach a plasmid comprising in 5’ to 3’ order: a promoter, operably linked to a luciferase cDNA mutated to comprise the I-SceI site within the luciferase coding region, and a promoterless copy of the luciferase cDNA in reverse orientation; the promoterless luciferase cDNA copy serves as a donor template for homologous recombination (HR). Czochor et al. teach linearizing the plasmid by cleaving it with I-SceI and introducing the linearized plasmid into test cells to determine HR activity in the test cells; determining HR activity takes place by measuring and comparing the luciferase levels in the test cells and HR-proficient control cells; a lower luciferase expression in the test cells compared to the control cells indicates that the test cells have lower HR activity (claims 46, 53, 54, 56, 57, 59, 61, 70, and 91) (see p. 365, column 2, second full paragraph; p. 368, column 2, last paragraph; p. 369).
Czochor et al. teach a full copy but this would encompass a continuous partial sequence of the luciferase cDNA (claims 46, 48, and 50).
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.
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) 1-6,8-13,15-17,22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Czochor et al. (Mol. Cancer Res., 2016, 14: 363-373 IDS ), in view of Pierce et al. (Genes & Development, 1999, 13: 2633-2638; IDS), as evidenced by the attached NEB Data Sheet (IDS)
With regard to claim 1, Czochor et al. teach a plasmid comprising in 5’ to 3’ order: a promoter, operably linked to a luciferase cDNA mutated to comprise the I-SceI site within the luciferase coding region, and a promoterless copy of the luciferase cDNA in reverse orientation; the promoterless luciferase cDNA copy serves as a donor template for homologous recombination (HR). Czochor et al. teach linearizing the plasmid by cleaving it with I-SceI and introducing the linearized plasmid into test cells to determine HR activity in the test cells; determining HR activity takes place by measuring and comparing the luciferase levels in the test cells and HR-proficient control cells; a lower luciferase expression in the test cells compared to the control cells indicates that the test cells have lower HR activity (claims 46, 53, 54, 56, 57, 59, 61, 70, and 91) (see p. 365, column 2, second full paragraph; p. 368, column 2, last paragraph; p. 369).
Czochor et al. teach a full copy and not a continuous partial sequence of the luciferase cDNA (claims 46, 48, and 50). Pierce et al. teach similar a construct which comprises a continuous partial sequence as the donor template, where the construct is used to measure HR activity in cells; the partial donor template sequence has upstream and downstream regions adjacent to the I-SceI site (see p. 2634, paragraph bridging columns 1 and 2 and Fig. 1). Modifying Czochor et al. by using a continuous partial luciferase cDNA sequence overlapping with the I-SceI site would have been obvious to one of skill in the art to achieve the predictable result of obtaining a linearized construct suitable for determining HR activity in the test cells.
With regard to claim 2 and 8, Pierce et al. disclose that the I-SceI site has the sequence: , where the underlined nucleotides represent termination codons (see Fig. 1). As evidenced by the NEB Data Sheet, I-SceI cleaves at the sites indicated by the arrowheads: (see p. 1). Thus, the mutated luciferase cDNA
comprises a stop codon upstream of the cleavage site.
With respect to claim 3-4, the cited prior art does not teach that the continuous partial luciferase sequence comprises a stop codon. However, since the continuous partial luciferase sequence taught by Czochor et al. and Pierce et al. is promoterless and cannot be expressed unless HR takes place; thus, there is no need for a stop codon. Importantly, there is no evidence of record indicating that the stop codon provides unexpected properties over the cited prior art. The specification discloses that adding a stop codon to the continuous partial sequence is not necessary because this sequence is not expressed before HR occurs (see [0034]). Adding a stop codon is not significant if it does not provide a novel feature.
With respect to claim 5-6, since it is a fragment of the luciferase cDNA, the continuous partial luciferase sequence necessarily has homologous sequences having a length of at least 20 nucleotides.
With regard to claims 9-10, Czochor et al. teach a full copy and not a continuous partial sequence of the luciferase cDNA (claims 46, 48, and 50). Pierce et al. teach similar a construct which comprises a continuous partial sequence as the donor template, where the construct is used to measure HR activity in cells; the partial donor template sequence has upstream and downstream regions adjacent to the I-SceI site (see p. 2634, paragraph bridging columns 1 and 2 and Fig. 1). Modifying Czochor et al. by using a continuous partial luciferase cDNA sequence overlapping with the I-SceI site would have been obvious to one of skill in the art to achieve the predictable result of obtaining a linearized construct suitable for determining HR activity in the test cells.
With regard to claims 11-13, these limitations appear to be the intended use of the claims and do not provide any structural changes that is not recited in claim 1.
With regard to claims 15-17 and 22, these claims encompass the identical structure of claim 1. The terms “screening system” and “diagnostic agent” and “therapeutic agent” does not limit or add any structure to the nucleic acid construct taught by claim 1.
20.Claims 7 are rejected under 35 U.S.C. 103 as being unpatentable over Czochor et al. taken with Pierce et al., as evidenced by the attached NEB Data Sheet, in further view of Klauer et al. (Wiley Interdiscip. Rev. RNA, 2012, 3: 1-16 IDS).
With regard to claim 7, The teachings of Czochor et al. and Pierce et al. are applied as above for claims 1-6,8-13,15-17,22. Czochor et al. and Pierce et al. do not specifically teach a polyA downstream of the mutated luciferase gene (claim 52). Klauer et al. teach that the absence of a polyA tail leads to mRNA degradation (see p. 2, first paragraph). Thus, including a polyA tail downstream of the mutated luciferase gene to achieve the predictable result of expressing the luciferase reconstituted upon HR.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
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 1-13, 15-17,22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 46-69 of copending Application No. 17799533 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because each require a nucleic acid constructure that comprise a promoter region, a mutant gene, cleavage site, continuous particular sequences that 80% or more identical to the other protein.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE D SALMON whose telephone number is (571)272-3316. The examiner can normally be reached 9-530.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu Cheng (Winston) Shen can be reached at 5712723157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KATHERINE D SALMON/ Primary Examiner, Art Unit 1682
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