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 .
Claim Interpretation
Attention is directed to MPEP 904.01 [R-08.2012].
The breadth of the claims in the application should always be carefully noted; that is, the examiner should be fully aware of what the claims do not call for, as well as what they do require. During patent examination, the claims are given the broadest reasonable interpretation consistent with the specification. See In re Morris, 127 F.3d 1048, 44 USPQ2d 1023 (Fed. Cir. 1997). See MPEP § 2111 - § 2116.01 for case law pertinent to claim analysis.
It is noted with particularity that narrowing limitations found in the specification cannot be inferred in the claims where the elements not set forth in the claims are linchpin of patentability. In re Philips Industries v. State Stove & Mfg. Co, Inc., 186 USPQ 458 (CA6 1975). While the claims are to be interpreted in light of the specification, it does not follow that limitations from the specification may be read into the claims. On the contrary, claims must be interpreted as broadly as their terms reasonably allow. See Ex parte Oetiker, 23 USPQ2d 1641 (BPAI, 1992). In added support of this position, attention is directed to MPEP 2111 [R-11.2013], where, citing In re Prater, 415 F.2d 1393, 1404-05, 162 USPQ 541, 550-51 (CCPA 1969), is stated:
The court explained that “reading a claim in light of the specification, to thereby interpret limitations explicitly recited in the claim, is a quite different thing from ‘reading limitations of the specification into a claim,’ to thereby narrow the scope of the claim by implicitly adding disclosed limitations which have no express basis in the claim.” The court found that applicant was advocating the latter, i.e., the impermissible importation of subject matter from the specification into the claim.
Additionally, attention is directed to MPEP 2111.01 [R-01.2024], wherein is stated:
II. IT IS IMPROPER TO IMPORT CLAIM LIMITATIONS FROM THE SPECIFICATION
“Though understanding the claim language may be aided by explanations contained in the written description, it is important not to import into a claim limitations that are not part of the claim. For example, a particular embodiment appearing in the written description may not be read into a claim when the claim language is broader than the embodiment.” Superguide Corp. v. DirecTV Enterprises, Inc., 358 F.3d 870, 875, 69 USPQ2d 1865, 1868 (Fed. Cir. 2004).
Attention is also directed to MPEP 2111.02 II [R-07.2022]. As stated herein:
II. PREAMBLE STATEMENTS RECITING PURPOSE OR INTENDED USE
PNG
media_image1.png
18
19
media_image1.png
Greyscale
The claim preamble must be read in the context of the entire claim. The determination of whether preamble recitations are structural limitations or mere statements of purpose or use "can be resolved only on review of the entirety of the [record] to gain an understanding of what the inventors actually invented and intended to encompass by the claim" as drafted without importing "'extraneous' limitations from the specification." Corning Glass Works, 868 F.2d at 1257, 9 USPQ2d at 1966. If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020) (The court found that the preamble in one patent’s claim is limiting but is not in a related patent); Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See also Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997) ("where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation")… (Emphasis added)
Attention is directed to MPEP 2111 [R-10.2019]. As stated therein:
During patent examination, the pending claims must be "given their broadest reasonable interpretation consistent with the specification." The Federal Circuit’s en banc decision in Phillips v. AWH Corp., 415 F.3d 1303, 1316, 75 USPQ2d 1321, 1329 (Fed. Cir. 2005) expressly recognized that the USPTO employs the "broadest reasonable interpretation" standard:
The Patent and Trademark Office ("PTO") determines the scope of claims in patent applications not solely on the basis of the claim language, but upon giving claims their broadest reasonable construction "in light of the specification as it would be interpreted by one of ordinary skill in the art." In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1364[, 70 USPQ2d 1827, 1830] (Fed. Cir. 2004). Indeed, the rules of the PTO require that application claims must "conform to the invention as set forth in the remainder of the specification and the terms and phrases used in the claims must find clear support or antecedent basis in the description so that the meaning of the terms in the claims may be ascertainable by reference to the description." 37 CFR 1.75(d)(1). (Emphasis added).
Attention is directed to MPEP 2173.04 [R-10.2019]. As stated therein:
Breadth of a claim is not to be equated with indefiniteness. In re Miller, 441 F.2d 689, 169 USPQ 597 (CCPA 1971); In re Gardner, 427 F.2d 786, 788, 166 USPQ 138, 140 (CCPA 1970) ("Breadth is not indefiniteness."). A broad claim is not indefinite merely because it encompasses a wide scope of subject matter provided the scope is clearly defined. But a claim is indefinite when the boundaries of the protected subject matter are not clearly delineated and the scope is unclear. For example, a genus claim that covers multiple species is broad, but is not indefinite because of its breadth, which is otherwise clear. But a genus claim that could be interpreted in such a way that it is not clear which species are covered would be indefinite (e.g., because there is more than one reasonable interpretation of what species are included in the claim). (Emphasis added)
Claim Rejections - 35 USC § 112, Written Description
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.
Standard for Written Description.
Attention is directed to MPEP 2163.02 Standard for Determining Compliance With the Written Description Requirement [R-07-2022]:
An objective standard for determining compliance with the written description requirement is, "does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed." In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989). Under Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), to satisfy the written description requirement, an applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention, and that the invention, in that context, is whatever is now claimed. (Emphasis added)
Attention is also set directed to MPEP 2161.01 I [R-07-2022], wherein is stated:
For instance, generic claim language in the original disclosure does not satisfy the written description requirement if it fails to support the scope of the genus claimed. Ariad, 598 F.3d at 1349-50, 94 USPQ2d at 1171 ("[A]n adequate written description of a claimed genus requires more than a generic statement of an invention’s boundaries.") (citing Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1405-06); Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002) (holding that generic claim language appearing in ipsis verbis in the original specification did not satisfy the written description requirement because it failed to support the scope of the genus claimed); Fiers v. Revel, 984 F.2d 1164, 1170, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993) (rejecting the argument that "only similar language in the specification or original claims is necessary to satisfy the written description requirement").
As set forth in Fiers v. Revel 25 USPQ2d 1601, 1604-5 (CAFC, January 1993):
We thus determined that, irrespective of the complexity or simplicity of the method of isolation employed, conception of a DNA, like conception of any chemical substance, requires a definition of that substance other than by its functional utility.
Fiers' attempt to distinguish Amgen therefore is incorrect. We also reject Fiers' argument that the existence of a workable method for preparing a DNA establishes conception of that material. (Emphasis added)
Conception of a substance claimed per se without reference to a process requires conception of its structure, name, formula, or definitive chemical or physical properties...
The difficulty that would arise if we were to hold that a conception occurs when one has only an idea of a compound, defining it by its hoped-for function, is that would-be inventors would file patent applications before they had made their inventions and before they could describe them. That is not consistent with the statute or the policy behind the statute, which is to promote disclosure of inventions.
As set forth in the en banc decision in Ariad Pharmaceuticals Inc. v. Eli Lilly and Company, 94 USPQ2d 1161 (Fed. Cir. 2010) at 1171:
We held that a sufficient description of a genus instead requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can “visualize or recognize” the members of the genus. Id. at 1568-69. We explained that an adequate written description requires a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials. Id. at 1568 (quoting Fiers v. Revel, 984 F.2d 1164, 1171 [25 USPQ2d 1601] (Fed. Cir. 1993)). We have also held that functional claim language can meet the written description requirement when the art has established a correlation between structure and function. See Enzo, 323 F.3d at 964 (quoting 66 Fed. Reg. 1099 (Jan. 5, 2001)). But merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species.
***
In Fiers, we rejected the argument that “only similar language in the specification or original claim is necessary to satisfy the written description requirement.” 984 F.2d at 1170 (emphasis added). Rather, we held that original claim language to “a DNA coding for interferon activity” failed to provide an adequate written description as it amounted to no more than a “wish” or “plan” for obtaining the claimed DNA rather than a description of the DNA itself. Id. at 1170-71. That Fiers applied § 112, first paragraph, during an interference is irrelevant for, as we stated above, the statute contains no basis for ignoring the description requirement outside of this context. And again in Enzo we held that generic claim language appearing in ipsis verbis in the original specification does not satisfy the written description requirement if it fails to support the scope of the genus claimed. 323 F.3d at 968. We concluded that “[a] claim does not become more descriptive by its repetition, or its longevity.” Id. at 969.
***
The written description requirement also ensures that when a patent claims a genus by its function or result, the specification recites sufficient materials to accomplish that function—a problem that is particularly acute in the biological arts.
Attention is also directed to MPEP 2163 Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112(a) or Pre-AIA 35 U.S.C. 112, first paragraph, “Written Description” Requirement [R-01-2024], at part II ii):
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus (see i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. See Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021) ( "[T]he written description must lead a person of ordinary skill in the art to understand that the inventor possessed the entire scope of the claimed invention. Ariad, 598 F.3d at 1353–54 ('[T]he purpose of the written description requirement is to ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor's contribution to the field of art as described in the patent specification.' (internal quotation marks omitted).") (Emphasis added)
Attention is also directed to the decision of University of California v. Eli Lilly and Co. (CA FC, July 1997) 43 USPQ2d 1398 wherein is stated:
In claims involving chemical materials, generic formulas usually indicate with specificity what the generic claims encompass. One skilled in the art can distinguish such a formula from others and can identify many of the species that the claims encompass. Accordingly, such a formula is normally an adequate written description of the claimed genus. In claims to genetic material, however, a generic statement such as “vertebrate insulin cDNA” or “mammalian cDNA,” without more, is not an adequate written description of the genus because it does not distinguish the claimed genus from others, except by function. It does not specifically define any of the genes that fall within its definition. It does not define any structural features commonly possessed by members of the genus that distinguish them from others. One skilled in the art therefore cannot, as one can do with a fully described genus, visualize or recognize the identity of the members of the genus. A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is See Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen). It is only a definition of a useful result rather than a definition of what it achieves as a result. Many such genes may achieve that result. The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 222 USPQ 369, 372-373 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”). Accordingly, naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material.
Thus, as we have previously held, a cDNA is not defined or described by the mere name cDNA,” even if accompanied by the name of the protein that it encodes, but requires a kind of specificity usually achieved by means of the recitation of the sequence of nucleotides that make up the cDNA. See Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606.
Holding and Rationale
Claims 1, 2, 5, 7-11, 19-21, and 23-30 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.
Claims 1, 19, and 21 are the only independent claims pending. For convenience, each of claims 1, 19 and 21 are reproduced below.
PNG
media_image2.png
456
483
media_image2.png
Greyscale
PNG
media_image3.png
501
486
media_image3.png
Greyscale
PNG
media_image4.png
538
461
media_image4.png
Greyscale
PNG
media_image5.png
273
449
media_image5.png
Greyscale
As is evidenced above, claims 1 and 19 require “a drop-off probe having a sequence complementary to a wild type microsatellite repeat sequence in huma genomic DNA” and “a reference probe having a sequence that is complementary to a reference sequence in human genomic DNA that is not a microsatellite repeat sequence”. Claim 21 requires “a drop-off probe designed to hybridise to the MSS in the human genomic DNA”, and “a reference probe designed to hybridize to an invariant human genomic sequence”.
A review of the disclosure does identify a Sequence Listing. Said Sequence Listing comprises some 28 sequences, each of which is identified as being an “Artificial Sequence: Synthetic”.
A review of the disclosure fails to find where applicant has disclosed any “wild type microsatellite repeat sequence in human genomic DNA”, much less disclose the genus of “reference sequence[s] in the human genomic DNA that is not a microsatellite repeat sequences”.
In addition to applicant’s non-disclosure, it is noted that the last human chromosome to be sequenced, the Y chromosome, was not sequenced until 2022, which is some 3 years after applicant’s filing date, and six years after applicant’s priority date. (Rhie et al., “The complete sequence of a human Y chromosome”, Nature, vol. 621, 14 September 2023, pp. 344-353.)
In view of applicant’s non-disclosure of such essential material1, and the state of the art, it stands to reason that applicant was not in possession of either the target sequences (wild type microsatellite repeat sequences in the human genome) or the requisite “drop-off probes” and amplification primers.
In view of the above analysis and in the absence of convincing evidence to the contrary, claims 1, 2, 4, 5, 7-11, 19-21, and 23-29 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.
Response to argument
Applicant’s representative, at pages 8-14 of the response of 15 December 2025, hereinafter the response, traverses the rejection of claims for not satisfying the written description requirement.
At page 8 of the response said representative asserts:
Examples of "wild-type microsatellite repeat sequence[s] in human genomic DNA" are set forth within FIG. 1 (Table 1) of the pending application (reproduced below). Indeed, the specification of the pending application indicates that FIG. 1 provides a "list of commonly detected microsatellites and [their] genomic location." (Specification at p.7). SEQ ID NOS: 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, and 21 set forth the sequences of the human microsatellites BAT-25, BAT- 26, NR-21, NR-24, MONO-27, BAT-40, DS123, D5S346, D17S250, PentaC, PentaD, and MYCL1 described in FIG. 1. Given these disclosures, it is only in error that the Patent Office contends that the specification fails to disclose any wild-type microsatellite repeat sequences in human genomic DNA. As such, Applicant submits that the person of ordinary skill in the art at the time of the invention would have understood that Applicant was in possession of the claimed kits and reaction mixtures at the time of filing the instant invention. Accordingly, the written description rejection should be withdrawn. (Emphasis added)
The above argument has been considered and has not been found persuasive for a review of the Sequence Listing finds that applicant has labeled each of these sequences as an “Artificial Sequence: Synthetic oligonucleotide”. For convenience, the Sequence Listing for each of SEQ ID NO: 10-21 are reproduced below.
PNG
media_image6.png
503
554
media_image6.png
Greyscale
PNG
media_image7.png
273
562
media_image7.png
Greyscale
PNG
media_image8.png
181
556
media_image8.png
Greyscale
PNG
media_image9.png
180
557
media_image9.png
Greyscale
PNG
media_image10.png
182
561
media_image10.png
Greyscale
PNG
media_image11.png
533
555
media_image11.png
Greyscale
PNG
media_image12.png
317
569
media_image12.png
Greyscale
PNG
media_image13.png
195
578
media_image13.png
Greyscale
PNG
media_image14.png
315
581
media_image14.png
Greyscale
PNG
media_image15.png
303
570
media_image15.png
Greyscale
PNG
media_image16.png
307
573
media_image16.png
Greyscale
PNG
media_image17.png
244
565
media_image17.png
Greyscale
As is evidenced above, applicant has labeled each of SEQ ID NO. 1-21 as not just an “Artificial Sequence”, but a “synthetic polynucleotide”. Such labeling by applicant has not been found to support the position that these sequences are not artificial and are “a wild type microsatellite repeat sequence in human genomic DNA”. It is further noted that such “Artificial Sequences” are not “a reference sequence in human genomic DNA that is not a microsatellite repeat sequence”, much less a reference sequence that exists on the Y chromosome, which was not sequenced until 2022. Applicant’s non-disclosure of such essential materials has also not been found to satisfy the written description requirement.
At pages 10-11 of the response said representative directs attention to various publications. While applicant’s representative has sought to underpin their argument by reliance upon publications, such showings do not take the place of sworn (declarations/affidavits) evidence and from which assurances that any statements or representations made are correct, as provided by 35 U.S.C. 25 and 18 USC 1001. Ex parte Gray 10 USPQ2d 1922 at 1928 (BPAI 1989). Accordingly, applicant’s representative’s argument is non-persuasive.
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.
Holding and Rationale
Claims 1, 10 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Thomas et al. 2013 (Qiagen's Investigator™ Quantiplex Kit as a predictor of STR amplification success from low-yield DNA samples, J Forensic Sci, 2013 Sep;58(5):1306-1309. doi: 10.1111/1556-4029.12171. Epub 2013 Jun 20) in view of Mokarram et al., 2014 (Microsatellite instability typing in serum and tissue of patients with colorectal cancer: comparing real time PCR with hybridization probe and high-performance liquid chromatography, Mol Biol Rep, 2014 May;41(5):2835-44. doi: 10.1007/s11033-014-3138-1. Epub 2014 Jan 23), Marras (2006) (Selection of Fluorophore and Quencher Pairs for Fluorescent Nucleic Acid Hybridization Probes; Part I of Methods in Molecular Biology, Fluorescent Energy Transfer Nucleic Acid Probes, Design and Protocol, 2006), and US 2002/0142336 A1 (Smith et al.).
Thomas et al. 2013 teaches “Qiagen’s InvestigatorTM Quantiplex kit, a total human DNA quantitation kit, has a 200-base pair internal control, fast cycling time, and scorpion molecules containing a covalently linked primer, probe, fluorophore, and quencher. The InvestigatorTM Quantiplex kit was evaluated to investigate a value under which complete short tandem repeat (STR) failure was consistently obtained. Buccal swabs were extracted using the Qiagen QIAamp_ DNA Blood Mini Kit, quantified with the InvestigatorTM Quantiplex kit using a tested half-volume reaction, amplified with the ABI AmpFlSTR_ Identifiler kit, separated on the 3100Avant Genetic Analyzer, and data analyzed with GeneMapper® ID v.3.2.” (See abstract). Thomas et al. 2013 teaches that the primer is covalently linked to a hairpin loop structure that includes the probe, reporter dye, and quencher dye (Fig. 1).
Regarding length of a probe, Thomas et al. 2013 teaches that “The Investigator TM Quantiplex kit produces an amplicon length more comparable with an STR locus for both the target amplicon and Internal Positive Control (146 base pairs and 200 base pairs, respectively) versus the Quantifile Human kit (62 base pairs and 79 baserTM pairs) (15,20). (See right column, first page of Thomas et al. 2013).
Regarding various fluorophores and quenchers used in nucleic acid hybridization probes, Marras (2006) teaches Selection of Fluorophore and Quencher Pairs for Fluorescent Nucleic Acid Hybridization Probes. (See Tile, Table 3 and Table 4)
Thomas et al. 2013 and Marras (2006) do not teach detection of microsatellite repeat sequences.
Mokarram et al., 2014 teaches “Allelic variation of BAT-25 (a 25-repeat quasimonomorphic poly T) and BAT-26 (a 26-repeat quasimonomorphic polyA) loci as two mononucleotide microsatellite markers, were analyzed with high-performance liquid chromatography (HPLC) compared with Real-Time PCR using hybridization probes. BAT-26 and BAT-25 markers were used to determine an appropriate screening technique with high sensitivity and specificity to diagnose microsatellite instability (MSI) status in patients with colorectal cancer (CRC). (See abstract).
Neither Thomas et al., 2013, Mokarram et al., nor Marras have been found to specify the distance of separation of the fluorophore and quencher.
Smith et al., in paragraph [0087], teach:
Any fluorescent dye and quencher combination may be used for this application, as long as the quencher is capable of effectively absorbing the electromagnetic energy emitted by the fluorophore by FRET when attached at a minimum separation of one nucleotide from the fluorophore. (Emphasis added)
It would have been prima facie obvious for a skilled artisan to utilize the methodology of detection of short tandem repeat (STR) taught by Thomas et al. 2013 to detect microsatellite repeat sequence taught by Mokarram et al., 2014 based on guidance from Marras (2006) regarding selection of Fluorophore and Quencher Pairs for Fluorescent Nucleic Acid Hybridization Probes with reasonable expectation of success. It would have also been an obvious commercial expediency to include multiple probes to different target wild type microsatellite repeat sequences in the human genome in a kit and to have had the probes labeled differently so as to enhance the ability to detect multiple target sequences in a simultaneous manner (claims 10 and 11), and that the members of a FRET pair, fluorophore and quencher, would be separated by “as little as 1 or 3 nucleotide residues”. To do so would clearly satisfy the limitation that “the first quencher of the drop-off probe is positioned within ten nucleotides of the first detectable label”.
In view of the above presentation and in the absence of convincing evidence to the contrary, claims 1, 10 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Thomas et al. 2013 (Qiagen's Investigator™ Quantiplex Kit as a predictor of STR amplification success from low-yield DNA samples, J Forensic Sci, 2013 Sep;58(5):1306-1309. doi: 10.1111/1556-4029.12171. Epub 2013 Jun 20) in view of Mokarram et al., 2014 (Microsatellite instability typing in serum and tissue of patients with colorectal cancer: comparing real time PCR with hybridization probe and high-performance liquid chromatography, Mol Biol Rep, 2014 May;41(5):2835-44. doi: 10.1007/s11033-014-3138-1. Epub 2014 Jan 23), Marras (2006) (Selection of Fluorophore and Quencher Pairs for Fluorescent Nucleic Acid Hybridization Probes; Part I of Methods in Molecular Biology, Fluorescent Energy Transfer Nucleic Acid Probes, Design and Protocol, 2006), and US 2002/0142336 A1 (Smith et al.).
Conclusion
Objections and/or rejections which appeared in the prior Office action and which have not been repeated hereinabove have been withdrawn.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
US 2016/0326576 A1 (Cook et al.), at paragraph [0279], teach:
In the dual labeled (fluorophore-quencher) probes, the donor moiety is preferably separated from the quencher by at least about 6, preferably at least about 8, preferably at least about 10 nucleotides, and more preferably by at least about 15 nucleotides.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Bradley L. Sisson whose telephone number is (571)272-0751. The examiner can normally be reached Monday to Thursday, from 6:30 AM to 5 PM..
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Shen can be reached at 571-272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Bradley L. Sisson/Primary Examiner, Art Unit 1682
1 Attention is directed to 37 CFR 1.57(d), which sates in part:
(d) "Essential material" may be incorporated by reference, but only by way of an incorporation by reference to a U.S. patent or U.S. patent application publication, which patent or patent application publication does not itself incorporate such essential material by reference. "Essential material" is material that is necessary to:
(1) Provide a written description of the claimed 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 set forth the best mode contemplated by the inventor of carrying out the invention as required by 35 U.S.C. 112(a);
(2) Describe the claimed invention in terms that particularly point out and distinctly claim the invention as required by 35 U.S.C. 112(b); or
(3) Describe the structure, material, or acts that correspond to a claimed means or step for performing a specified function as required by 35 U.S.C. 112(f). (Emphasis added)
(e) Other material ("Nonessential material") may be incorporated by reference to U.S. patents, U.S. patent application publications, foreign patents, foreign published applications, prior and concurrently filed commonly owned U.S. applications, or non-patent publications. An incorporation by reference by hyperlink or other form of browser executable code is not permitted.
Prosecution Insights