Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Status of the Claims
Claims 74-92 are the subject of this NON-FINAL Office Action. This is the first action on the merits.
Objection to Claims
Claim 86 is objected to because a space is missing in this: “8nucleotides.”
Claim Rejection - 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 74-92 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Specifically, the claims are directed to the natural sequences of CRH and IGF2, UPK1B and ANXA10, which are not markedly different from products of nature.
First, under Step 1, the claims are directed to a primer product. Thus, the claims are directed to statutory products.
However, under markedly different analysis, the primers are natural sequences. See MPEP §§ 2106.04(b)(II) & (c). The primers directed to the claimed genes are not markedly different from a natural sequence because no other additional elements are recited (e.g. label). Natural sequences perform the same functions in nature as they do in primers. Moreover, lyophilization does not change the sequences themselves, or the functions thereof. Nor does the inclusion of other generic natural components (ABL sequence, probe sequences that read on natural sequences) or generic “instructions” into a kit of parts, separately packaged. See MPEP § 2112.01(III).
Double Patenting- Obvious Type
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 obviousness-type 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); and 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 a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Instant claims 74-92 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over conflicting claims 1-25 of U.S. 12000001.
The instant claims are obvious over the conflicting claims because the conflicting claims teach a method of using the same composition claimed. Specifically, the conflicting claims teach:
1. A method of monitoring anti-androgen therapy response in a human subject with bladder cancer comprising detecting the levels of each marker of a set of three to six bladder cancer markers in a sample from the subject at a first time point; detecting the levels of each marker of the set of bladder cancer markers at a second time point that is after the first time point; and comparing the levels of each marker at the first time point to the levels of each marker at the second time point, wherein the set of bladder cancer markers comprises uroplakin 1B (UPK1B) and insulin-like growth factor 2 (IGF2) and at least one marker selected from androgen receptor (AR), corticotrophin releasing hormone (CRH), keratin 20 (KRT20), and annexin 10 (ANXA10), wherein the subject is undergoing anti-androgen therapy at the second time point, wherein detecting comprises contacting RNA from the sample with a set of bladder cancer marker primer pairs comprising a primer pair for detecting UPK1B and a primer pair for detecting IGF2, forming a set of bladder cancer marker amplicons, and contacting the bladder cancer marker amplicons with a set of bladder cancer marker probes comprising a probe for detecting the UPK1B amplicon and a probe for detecting the IGF2 amplicon, wherein the probe for detecting the IGF2 amplicon comprises at least 8 contiguous nucleotides of SEQ ID NO: 34, wherein each probe is less than 30 nucleotides long, and wherein a decrease in the level of at least one marker in the set of bladder cancer markers at the second time point relative to the first time point indicates that the subject is responding to anti-androgen therapy.
2. The method of claim 1, wherein the subject is undergoing anti-androgen therapy at the first time point and second time point.
3. The method of claim 1, wherein the set of bladder cancer markers comprises:
(a) UPK1B, CRH, IGF2, and ANXA10;
(b) UPK1B, CRH, IGF2, and KRT20;
(c) AR, UPK1B, CRH, IGF2, KRT20, and ANXA10; or
(d) AR, UPK1B, CRH, IGF2, and KRT20.
4. The method of claim 1, wherein the method further comprises detecting an endogenous control and/or exogenous control.
5. The method of claim 4, wherein the endogenous control is ABL.
6. The method of claim 1, wherein the detecting comprises RT-PCR.
7. The method of claim 6, wherein the method comprises detecting an endogenous control and comparing a Ct value or a ΔCt value to a threshold Ct value or ΔCt value, wherein ΔCt is the Ct value for the endogenous control minus the Ct value for each marker of the set of bladder cancer markers.
8. The method of claim 6, wherein the RT-PCR reaction takes less than 2 hours from an initial denaturation step through a final extension step.
9. The method of claim 1, wherein each bladder cancer marker primer pair produces an amplicon that is 50 to 500 nucleotides long.
10. The method of claim 1, wherein at least one bladder cancer marker primer pair spans an intron in the genomic sequence of a marker detected by the primer pair.
11. The method of claim 1, wherein the primer pair for detecting UPK1B comprises a first primer comprising at least 8 contiguous nucleotides of SEQ ID NO: 51 and a second primer comprising at least 8 contiguous nucleotides of SEQ ID NO: 52.
12. The method of claim 1, wherein the probe for detecting UPK1B comprises at least 8 contiguous nucleotides of SEQ ID NO: 53, wherein the probe is less than 30 nucleotides long.
13. The method of claim 1, wherein each bladder cancer marker probe comprises a dye, and wherein the dye for each probe is detectably different from the other dyes.
14. The method of claim 1, wherein the set of bladder cancer markers are detected in a single multiplex reaction.
15. The method of claim 1, wherein the subject has a history of bladder cancer and/or is being monitored for recurrence of bladder cancer.
16. The method of claim 1, wherein the bladder cancer is low grade bladder cancer.
17. The method of claim 1, wherein the second time point is at least one month after the first time point.
18. The method of claim 17, wherein the method comprises detecting the levels of each marker of the set of bladder cancer markers in a sample from the subject at least once every month, at least once every two months, at least once every three months, at least once every four months, at least once every five months, at least once every six months, at least once every nine months, at least once per year, or at least once every two years, and comparing the levels of each marker at each subsequent time point to the levels of each prior time point, and wherein the subject is undergoing anti-androgen therapy at each subsequent time point or at each of the time points.
19. The method of claim 1, wherein the probe for detecting the IGF2 amplicon comprises SEQ ID NO: 34.
20. The method of claim 19, wherein the primer pair for detecting IGF2 comprises a first primer comprising at least 8 contiguous nucleotides of SEQ ID NO: 32.
21. The method of claim 1, wherein the primer pair for detecting IGF2 comprises a first primer comprising at least 8 contiguous nucleotides of SEQ ID NO: 32.
22. The method of claim 1, wherein the set of bladder cancer marker primer pairs comprises at least one additional primer pair for detecting CRH, AR, KRT20, and/or ANXA10.
23. The method of claim 22, wherein the set of bladder cancer marker amplicons comprises at least one additional amplicon selected from a CRH amplicon, an AR amplicon, a KRT20 amplicon, and an ANXA10 amplicon, and wherein the set of bladder cancer marker probes comprises at least one additional probe for detecting the at least one additional amplicon.
24. The method of claim 22, wherein the primer pair for detecting CRH comprises a first primer comprising at least 8 contiguous nucleotides of SEQ ID NO: 35 and a second primer comprising at least 8 contiguous nucleotides of SEQ ID NO: 36.
25. The method of claim 22, wherein the primer pair for detecting ANXA10 comprises a first primer comprising at least 8 contiguous nucleotides of SEQ ID NO: 38 or SEQ ID NO: 48 and a second primer comprising at least 8 contiguous nucleotides of SEQ ID NO: 39.
A skilled artisan would have recognized that the method requires a reaction solution (composition) that contains the claimed primers and probes. Thus, the conflicting claims anticipate the instant claims.
Subject Matter Allowable Over Prior Art
The claims are directed to a composition comprising two primer pairs, one of which has a primer that is at least 8 contiguous bases or SEQ ID NO: 35 or 36, another directed to IGF2, UPK1B or ANXA10. Primers to each target are ubiquitous in the art (US 20050221332, CRH; US 20070254296, CRH; US 20080160523, CRH; US 20080188447, CRH; US 20090247558, CRH; US 20010007749, IGF2; US 20060216719, ANAXA10; US 20130267435, UPK1B). However, the prior art does not teach or suggest the specific primers with 8 contiguous bases of SEQ ID NO: 35 or 36, along with primer pairs to one of IGF2, UPK1B or ANXA10. At best, WO 2007097741 teaches “[t]he present invention provides for a method of diagnosing IUGR in a subject by measuring the gene expression of an IUGR-associated gene selected from the group consisting of . . . IGF2 . . . CRH.” However, this reference fails to teach or suggest the specific primer sequences claimed.
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/YUNG-SHENG M TSUI/ Primary Examiner, Art Unit 1684
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