DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
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 1-8 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 12,054,792. Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘792 claims disclose a master mix comprising a primer pair for each of Atopobium vaginae, Megasphaera, L. jensenii and L. crispatus 16S ribosomal RNA gene, wherein at least one primer of each pair is detectably labeled, and wherein all primer pairs in the master mix are specific for organisms associated with bacterial vaginosis or Lactobacilli species. The ‘792 claims also disclose a kit comprising the master mix and a swab, that the label is fluorescent, and the specific SEQ ID NOs recited in the instant claims. The difference is scope is that the ‘792 claims additionally require a primer pair for Gardnerella vaginalis, which is not a feature recited in the instant claims.
Claims 9-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 12-26 of U.S. Patent No. 12,054,792. Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘792 claims disclose a master mix comprising a primer pair and probe for each of Atopobium vaginae, Megasphaera, L. jensenii and L. crispatus 16S ribosomal RNA gene, wherein the probe is detectably labeled, and wherein all primer pairs and probes in the master mix are specific for organisms associated with bacterial vaginosis or Lactobacilli species. The ‘792 claims also disclose a kit comprising the master mix and a swab, that the label is fluorescent, and the specific SEQ ID NOs recited in the instant claims, and that there are no more than six primer pairs in the master mix. The difference is scope is that the ‘792 claims additionally require a primer pair and probe for Gardnerella vaginalis, which is not a feature recited in the instant claims.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1, 8, 9 and 20 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over De Backer et al. (BMC Microbiology 7:115; 19 December 2007, IDS reference) in view of Zozaya-Hinchliffe et al. (App. Env. Micro. 74(5):1656-1659 (2008)), Marras et al. (Clinica Chimica Acta 363:48-60 (2006), IDS reference) and Reed (US 7,608,399, IDS reference).
De Backer disclosed primer pairs for quantitative determination of four vaginal lactobacillus species (L. crispatus, L. gasseri, L. iners, and L. jensenii), Atopobium vaginae, and Gardnerella vaginalis (see title, table 4 on page 4). The primers were specific for the 16S rRNA gene (see table 4).
Of bacterial vaginosis (BV), De Backer disclosed that both G. vaginalis and A. vaginae were associated with this disorder (page 2, second paragraph under “Background”). De Backer disclosed that the authors “developed real-time PCR primers for L. iners, L. jensenii and A. vaginae and used these, together with described real-time PCR formats of L. crispatus, L. gasseri and G. vaginalis, in an attempt to quantify some of the important bacterial species in the normal and disturbed vaginal microflora” (page 2, right column, last paragraph under “Background”).
De Backer did not disclose that the primers were detectably labeled with a fluorescent label as recited in instant claims 1 and 8. De Backer did not disclose probes with detectable fluorescent labels as recited in claims 9 and 20. Instead of using labeled primers or probes, De Backer’s real-time quantitative PCR was based on the use of SYBR Green I (a dye that binds to double-stranded DNA, upon which it becomes fluorescent, which fluorescent signal increases as PCR product accumulates; see page 11, “Real-time PCR”). De Backer did not disclose primers and probes for Megasphaera as recited in claims. De Backer did not disclose putting the primers and probes into a “master mix”.
Zozaya-Hinchliffe disclosed quantitative PCR targeting the 16S rRNA gene for two types of Megasphaera and found these to be present in higher concentrations in women with bacterial vaginosis (Abstract). Like De Backer, Zozaya-Hinchliffe’s assay used SYBR Green as the signaling mechanism (page 1656, right column, first paragraph).
Marras disclosed alternatives to SYBR Green-based real-time assays in which fluorescently labeled probes (Figure 1A-D) or primers (Figure 1E-F) were used. Marras disclosed (“Conclusions” section of Abstract) that the assays “can be combined with nucleic acid amplification, enabling the detection of rare target nucleic acids. These assays can be followed in real time, providing quantitative determination of target nucleic acids over a broad range of concentrations.” Marras disclosed (in discussing the “Molecular Beacon” type probes of Figure 1A): “Molecular beacons can possess differently colored fluorophores, enabling assays to be carried out that simultaneously detect different targets in the same reaction” (page 52, left column, 2nd full paragraph). Similarly, in discussing “Amplifluor primers” of the type shown in Figure 1F, Marras noted (page 57, right column, lines 3-5, citation omitted): “Recently, a multiplex real-time PCR assay, utilizing amplifluor primers, was reported.” Marras remarked (page 58, left column, last paragraph preceding “Acknowledgements”): “In order to develop high-throughput assays, it is desirable to perform multiplex assays, where more than one target nucleic acid can be identified in the same solution.”
Reed disclosed putting primers and probes for 16S ribosomal RNA gene targets into a master mix (column 18, lines 11-16).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to modify the method of De Backer for quantifying important bacterial species in normal and disturbed vaginal microflora by including primers for Megasphaera, since Zozaya-Hinchliffe demonstrated that Megasphaera species were also associated with bacterial vaginosis. Furthermore, it would have been obvious to modify the method by using fluorescently-labeled primers or probes, instead of SYBR Green, since Marras disclosed these formats as alternatives to the use of SYBR Green. As discussed in MPEP 2144.06, it is prima facie obvious to substitute equivalents known for the same purpose. Here, the cited art clearly demonstrates that SYBR Green, labeled primers, and labeled probes were alternative formats for carrying out real-time quantitative PCR. Moreover, labeled primers or probes would have provided an ability to detect multiple targets in the same reaction, which Marras noted was desirable for the purpose of developing high-throughput assays. It would not have escaped the ordinary skilled worker that the multiplexing capability described by Marras for Molecular Beacons (Marras Figure 1A) and Amplifluor Primers (Marras Figure 1F) would have been equally true for any of the other formats shown in Marras’ Figure 1, as it is simply based on using different fluorescent labels on different primers or probes. Finally, it would have been obvious to put the primers and probes into a master mix as disclosed by Reed, as Reed demonstrates this was known to do when setting up PCR assays.
Claims 2 and 10 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over De Backer et al. (BMC Microbiology 7:115; 19 December 2007, IDS reference) in view of Zozaya-Hinchliffe et al. (App. Env. Micro. 74(5):1656-1659 (2008)), Marras et al. (Clinica Chimica Acta 363:48-60 (2006), IDS reference) and Reed (US 7,608,399, IDS reference) as applied to claims 1, 8, 9 and 20 above, and further in view of Polansky (US 2004/0023207, IDS reference).
The teachings of De Backer, Zozaya-Hinchliffe, Marras and Reed have been discussed. It is noted that De Backer collected samples with swabs (page 10, “Samples”).
These references did not discuss putting the primers, probes and swabs into a “kit”.
Polansky disclosed (paragraph [0919]): “Well known advantages of commercial kits include convenience and reproducibility due to manufacturing standardization, quality control and validation procedures.”
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to put the primers, probes and swabs into a kit in order to obtain the benefits of kits disclosed by Polansky.
Claims 3, 11 and 12 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over De Backer et al. (BMC Microbiology 7:115; 19 December 2007, IDS reference) in view of Zozaya-Hinchliffe et al. (App. Env. Micro. 74(5):1656-1659 (2008)), Marras et al. (Clinica Chimica Acta 363:48-60 (2006), IDS reference) and Reed (US 7,608,399, IDS reference) as applied to claims 1, 8, 9 and 20 above, and further in view of AF325325.1 (submitted 2003, IDS reference).
The disclosures of De Backer, Zozaya-Hinchliffe, Marras and Reed have been discussed. De Backer also disclosed how primers were selected based on aligning the target sequence to closely related sequences and selecting primers based on specificity to the target sequence, using publicly available algorithms to create alignments and to check for primer specificity (page 11, “Primers”). These references did not disclose the sequences of the primers and probes recited in claims 3, 11 and 12.
AF325325.1 discloses the 16S rRNA gene from an Atopobium vaginae clone. SEQ ID. NO: 11 matches this sequence from bases 722 to 741. SEQ ID NO: 12 matches the complement of bases 877-858. SEQ ID NO: 13 matches bases 784-808.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to select alternate sequences for primers and probes based on the known sequence for the A. vaginae 16S rRNA gene by following the routine practice disclosed by De Backer for choosing specific sequences based on aligning a target sequence with related sequences using an algorithm such as CLUSTAL, selecting regions where differences occur, and checking those regions for specificity using an algorithm such as BLAST. Even Applicant’s specification admits: “A number of computer programs, such as Primer Express (Applied Biosystems, Foster City, Calif.), can be used to rapidly obtain optimal primer/probe sets.” One of ordinary skill in the art would have merely regarded the claimed primers and probes as equivalent to the primers/probes suggested by the prior art for the purpose of detecting and quantifying these bacteria. Thus, one of ordinary skill would have had a reasonable expectation of success in arriving at the claimed primers as alternatives to those used by De Backer or probes as suggested by Marras.
Claims 4, 13 and 14 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over De Backer et al. (BMC Microbiology 7:115; 19 December 2007, IDS reference) in view of Zozaya-Hinchliffe et al. (App. Env. Micro. 74(5):1656-1659 (2008)), Marras et al. (Clinica Chimica Acta 363:48-60 (2006), IDS reference) and Reed (US 7,608,399, IDS reference) as applied to claims 1, 8, 9 and 20 above, and further in view of AY271950.1 (submitted 2004, IDS reference).
The disclosures of De Backer, Zozaya-Hinchliffe, Marras and Reed have been discussed. De Backer also disclosed how primers were selected based on aligning the target sequence to closely related sequences and selecting primers based on specificity to the target sequence, using publicly available algorithms to create alignments and to check for primer specificity (page 11, “Primers”). These references did not disclose the sequences of the primers and probes recited in claims 4, 13 and 14.
AY271950.1 teaches the 16s rRNA gene from a Megashaera sp. clone. SEQ ID. NO: 14 matches this sequence from bases 307-326. SEQ ID NO: 15 matches the complement of bases 547-528. SEQ ID NO: 16 matches bases 478-502.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to select alternate sequences for primers and probes based on the known sequence for the Megasphaera 16S rRNA gene by following the routine practice disclosed by De Backer for choosing specific sequences based on aligning a target sequence with related sequences using an algorithm such as CLUSTAL, selecting regions where differences occur, and checking those regions for specificity using an algorithm such as BLAST. Even Applicant’s specification admits: “A number of computer programs, such as Primer Express (Applied Biosystems, Foster City, Calif.), can be used to rapidly obtain optimal primer/probe sets.” One of ordinary skill in the art would have merely regarded the claimed primers and probes as equivalent to the primers/probes suggested by the prior art for the purpose of detecting and quantifying these bacteria. Thus, one of ordinary skill would have had a reasonable expectation of success in arriving at the claimed primers as alternatives to those used by Zozaya-Hinchliffe or probes as suggested by Marras.
Claims 7 and 19 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over De Backer et al. (BMC Microbiology 7:115; 19 December 2007, IDS reference) in view of Zozaya-Hinchliffe et al. (App. Env. Micro. 74(5):1656-1659 (2008)), Marras et al. (Clinica Chimica Acta 363:48-60 (2006), IDS reference) and Reed (US 7,608,399, IDS reference) as applied to claims 1, 8, 9 and 20 above, and further in view of AF325325.1 (submitted 2003, IDS reference) and AY271950.1 (submitted 2004, IDS reference).
The disclosures of De Backer, Zozaya-Hinchliffe, Marras and Reed have been discussed. De Backer also disclosed how primers were selected based on aligning the target sequence to closely related sequences and selecting primers based on specificity to the target sequence, using publicly available algorithms to create alignments and to check for primer specificity (page 11, “Primers”). These references did not disclose the sequences of the primers and probes recited in claims 7 and 19.
AF325325.1 discloses the 16S rRNA gene from an Atopobium vaginae clone. SEQ ID. NO: 11 matches this sequence from bases 722 to 741. SEQ ID NO: 12 matches the complement of bases 877-858. SEQ ID NO: 13 matches bases 784-808.
AY271950.1 teaches the 16s rRNA gene from a Megashaera sp. clone. SEQ ID. NO: 14 matches this sequence from bases 307-326. SEQ ID NO: 15 matches the complement of bases 547-528. SEQ ID NO: 16 matches bases 478-502.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to select alternate sequences for primers and probes based on the known sequence for the Atopobium vaginae and Megasphaera 16S rRNA genes by following the routine practice disclosed by De Backer for choosing specific sequences based on aligning a target sequence with related sequences using an algorithm such as CLUSTAL, selecting regions where differences occur, and checking those regions for specificity using an algorithm such as BLAST. Even Applicant’s specification admits: “A number of computer programs, such as Primer Express (Applied Biosystems, Foster City, Calif.), can be used to rapidly obtain optimal primer/probe sets.” One of ordinary skill in the art would have merely regarded the claimed primers and probes as equivalent to the primers/probes suggested by the prior art for the purpose of detecting and quantifying these bacteria. Thus, one of ordinary skill would have had a reasonable expectation of success in arriving at the claimed primers as alternatives to those used by Zozaya-Hinchliffe or probes as suggested by Marras.
Claims 5, 15 and 16 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over De Backer et al. (BMC Microbiology 7:115; 19 December 2007, IDS reference) in view of Zozaya-Hinchliffe et al. (App. Env. Micro. 74(5):1656-1659 (2008)), Marras et al. (Clinica Chimica Acta 363:48-60 (2006), IDS reference) and Reed (US 7,608,399, IDS reference) as applied to claims 1, 8, 9 and 20 above, and further in view of AY262350.1 (submitted 2003, IDS reference).
The disclosures of De Backer, Zozaya-Hinchliffe, Marras and Reed have been discussed. De Backer also disclosed how primers were selected based on aligning the target sequence to closely related sequences and selecting primers based on specificity to the target sequence, using publicly available algorithms to create alignments and to check for primer specificity (page 11, “Primers”). These references did not disclose the sequences of the primers and probes recited in claims 5, 15 and 16.
AY262350.1 teaches the 16s rRNA gene from a Lactobacillus jensenii clone. SEQ ID. NO: 4 matches this sequence from bases 100-119. SEQ ID NO: 5 matches the complement of bases 227-208. SEQ ID NO: 6 matches bases 160-184.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to select alternate sequences for primers and probes based on the known sequence for the L. jensenii 16S rRNA gene by following the routine practice disclosed by De Backer for choosing specific sequences based on aligning a target sequence with related sequences using an algorithm such as CLUSTAL, selecting regions where differences occur, and checking those regions for specificity using an algorithm such as BLAST. Even Applicant’s specification admits: “A number of computer programs, such as Primer Express (Applied Biosystems, Foster City, Calif.), can be used to rapidly obtain optimal primer/probe sets.” One of ordinary skill in the art would have merely regarded the claimed primers and probes as equivalent to the primers/probes suggested by the prior art for the purpose of detecting and quantifying these bacteria. Thus, one of ordinary skill would have had a reasonable expectation of success in arriving at the claimed primers as alternatives to those used by De Backer or probes as suggested by Marras.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMUEL C WOOLWINE whose telephone number is (571)272-1144. The examiner can normally be reached 9am-5:30pm.
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/SAMUEL C WOOLWINE/Primary Examiner, Art Unit 1681