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 .
Drawings
New corrected drawings in compliance with 37 CFR 1.121(d) are required in this application because:
The lettering is not of proper size, uniform density, and well-defined in Figure(s) 1 - 10C. See 37 CFR 1.84(p)(1) – (5). (“Numbers, letters, and reference characters must measure at least .32 cm (1/8 inch) in height.”)
The margins are not of proper size in Figure(s) 1 – 10C. See 37 CFR 1.84(g).
Each panel needs to be individually labeled, e.g., FIG. 7A, 7B, 8A, 8B, 8C, and 8D, not “7 (continued)”, “7”, “8A (continued)”, and”8B (continued)”, . See 37 CFR 1.84(u)(1) and (2),
In Figure(s) 1, 4, 6, 7(continued), 7, 8A, 8A (continued) and 8B the reference characters, sheet numbers, and view numbers are not all oriented in the same direction so as to avoid having to rotate the sheet. See 37 CFR 1.84(p)(1).
Applicant is advised to employ the services of a competent patent draftsperson outside the Office, as the U.S. Patent and Trademark Office no longer prepares new drawings. The corrected drawings are required in reply to the Office action to avoid abandonment of the application. The requirement for corrected drawings will not be held in abeyance.
INFORMATION ON HOW TO EFFECT DRAWING CHANGES
Replacement Drawing Sheets
Drawing changes must be made by presenting replacement sheets which incorporate the desired changes and which comply with 37 CFR 1.84. An explanation of the changes made must be presented either in the drawing amendments section, or remarks, section of the amendment paper. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). A replacement sheet must include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of the amended drawing(s) must not be labeled as “amended.” If the changes to the drawing figure(s) are not accepted by the examiner, applicant will be notified of any required corrective action in the next Office action. No further drawing submission will be required, unless applicant is notified.
Identifying indicia, if provided, should include the title of the invention, inventor’s name, and application number, or docket number (if any) if an application number has not been assigned to the application. If this information is provided, it must be placed on the front of each sheet and within the top margin.
Annotated Drawing Sheets
A marked-up copy of any amended drawing figure, including annotations indicating the changes made, are required by the examiner. The annotated drawing sheet(s) must be clearly labeled as “Annotated Sheet” and must be presented in the amendment or remarks section that explains the change(s) to the drawings.
Timing of Corrections
Applicant is required to submit acceptable corrected drawings within the time period set in the Office action. See 37 CFR 1.85(a). Failure to take corrective action within the set period will result in ABANDONMENT of the application.
If corrected drawings are required in a Notice of Allowability (PTOL-37), the new drawings MUST be filed within the THREE MONTH shortened statutory period set for reply in the “Notice of Allowability.” Extensions of time may NOT be obtained under the provisions of 37 CFR 1.136 for filing the corrected drawings after the mailing of a Notice of Allowability.
Specification
The disclosure is objected to because of the following informalities:
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. See, for example, page 31, lines 5-6.
Appropriate correction is required.
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
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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, Second Paragraph / (b)
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.
Standard for Definiteness.
Attention is directed to MPEP 2171 [R-11.2013]:
Two separate requirements are set forth in 35 U.S.C. 112(b) and pre-AIA 35 U.S.C. 112, second paragraph, namely that:
(A) the claims must set forth the subject matter that the inventor or a joint inventor regards as the invention; and
(B) the claims must particularly point out and distinctly define the metes and bounds of the subject matter to be protected by the patent grant.
The first requirement is a subjective one because it is dependent on what the inventor or a joint inventor for a patent regards as his or her invention. Note that although pre-AIA 35 U.S.C. 112, second paragraph, uses the phrase "which applicant regards as his invention," pre-AIA 37 CFR 1.41(a) provides that a patent is applied for in the name or names of the actual inventor or inventors.
The second requirement is an objective one because it is not dependent on the views of the inventor or any particular individual, but is evaluated in the context of whether the claim is definite — i.e., whether the scope of the claim is clear to a hypothetical person possessing the ordinary level of skill in the pertinent art.
Attention is directed to MPEP 2173.02 I [R-01.2024]:
During prosecution, applicant has an opportunity and a duty to amend ambiguous claims to clearly and precisely define the metes and bounds of the claimed invention. The claim places the public on notice of the scope of the patentee’s right to exclude. See, e.g., Johnson & Johnston Assoc. Inc. v. R.E. Serv. Co., 285 F.3d 1046, 1052, 62 USPQ2d 1225, 1228 (Fed. Cir. 2002) (en banc). As the Federal Circuit stated in Halliburton Energy Servs., Inc. v. M-I LLC, 514 F.3d 1244, 1255, 85 USPQ2d 1654, 1663 (Fed. Cir. 2008):
“We note that the patent drafter is in the best position to resolve the ambiguity in the patent claims, and it is highly desirable that patent examiners demand that applicants do so in appropriate circumstances so that the patent can be amended during prosecution rather than attempting to resolve the ambiguity in litigation.”
***
During examination, after applying the broadest reasonable interpretation to the claim, if the metes and bounds of the claimed invention are not clear, the claim is indefinite and should be rejected. Packard, 751 F.3d at 1310 (“[W]hen the USPTO has initially issued a well-grounded rejection that identifies ways in which language in a claim is ambiguous, vague, incoherent, opaque, or otherwise unclear in describing and defining the claimed invention, and thereafter the applicant fails to provide a satisfactory response, the USPTO can properly reject the claim as failing to meet the statutory requirements of § 112(b).”); Zletz, 893 F.2d at 322, 13 USPQ2d at 1322.
Attention is also directed to MPEP 2173.02 III B [R-01-2024], which states in part:
To comply with 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph, applicants are required to make the terms that are used to define the invention clear and precise, so that the metes and bounds of the subject matter that will be protected by the patent grant can be ascertained. See MPEP § 2173.05(a), subsection I. It is important that a person of ordinary skill in the art be able to interpret the metes and bounds of the claims so as to understand how to avoid infringement of the patent that ultimately issues from the application being examined. See MPEP § 2173.02, subsection II (citing Morton Int ’l, Inc. v. Cardinal Chem. Co., 5 F.3d 1464, 1470 (Fed. Cir. 1993)); see also Halliburton Energy Servs., 514 F.3d at 1249, 85 USPQ2d at 1658 (“Otherwise, competitors cannot avoid infringement, defeating the public notice function of patent claims.”). Examiners should bear in mind that “[a]n essential purpose of patent examination is to fashion claims that are precise, clear, correct, and unambiguous. Only in this way can uncertainties of claim scope be removed, as much as possible, during the administrative process.” Zletz, 893 F.2d at 322, 13 USPQ2d at 1322 [Fed. Cir. 1989]. (Emphasis added)
Attention is also directed to MPEP 2173.04 [R-10-2019], which states in part:
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).
Holding and Rationale
Claims 6, 11, and 15 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 6, 11, and 15 are indefinite as a result of the use of the term “optionally”. It is less than clear is the clause that follows “optionally” does, or does not, further limit the claim.
The term "about" in claim 6 is a relative term which renders the claim(s) indefinite. The term "about” is not defined by the claim(s), the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Attention is directed to MPEP 2173.05(b) III A, which states in part:
In determining the range encompassed by the term "about", one must consider the context of the term as it is used in the specification and claims of the application. Ortho-McNeil Pharm., Inc. v. Caraco Pharm. Labs., Ltd., 476 F.3d 1321, 1326, 81 USPQ2d 1427, 1432 (Fed. Cir. 2007). In< W. L. Gore & Associates, Inc. v. Garlock, Inc., 721 F.2d 1540, 220 USPQ 303 (Fed. Cir. 1983), the court held that a limitation defining the stretch rate of a plastic as “exceeding about 10% per second” is definite because infringement could clearly be assessed through the use of a stopwatch. However, the court held that claims reciting “at least about” were invalid for indefiniteness where there was close prior art and there was nothing in the specification, prosecution history, or the prior art to provide any indication as to what range of specific activity is covered by the term “about.” Amgen, Inc. v. Chugai Pharmaceutical Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991).
"The use of the word 'about,' avoids a strict numerical boundary to the specified parameter." Ortho-McNeil Pharmaceutical, Inc. v. Caraco Pharmaceutical Laboratories, Ltd., 476 F.3d 1321, 1326 (Fed. Cir. 2007) (quoting Pall Corp. v. Micron Separations, Inc., 66 F.3d 1211, 1217 (Fed. Cir. 1995)); see also In re Harris, 409 F.3d 1339, 1343 (Fed. Cir. 2005) ("[U]se of the term 'about' shows that the applicants did not intend to limit the claimed ranges to their exact end-points."). However, "the word 'about' does not have a universal meaning in patent claims[;]" rather, "the meaning depends on the technological facts of the particular case." Pall Corp., 66 F.3d at 1217; see also Eiselstein v. Frank, 52 F.3d 1035, 1040 (Fed. Cir. 1995) ("The meaning of the word 'about' is dependent on the facts of a case, the nature of the invention, and the knowledge imparted by the totality of the.., disclosure to those skilled in the art."). Thus, in evaluating the scope of the "about," it is appropriate to look how the Specification and other claims use the term, as well as considering the effects of varying the parameter described by the term. Pall Corp., 66 F.3d at 1217.
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
Claim(s) 1-12 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over US 2019/0112653 A1 (Cheng et al.) in view of US 2016/0145674 A1 (Uehara), US 2021/0054369 A1 (Meltzer et al.), US 2010/0045147A1 (Harnack et al.), US 2014/0296094 A1 (Domanus), US 2021/0198730 A1 (Glezer et al.), US 2018/0349548 A1 (Walsh et al.), US 2014/0187577 A1 (Funahashi et al.), US 2021/0230669 A1 (Lakdawalla et al.), US 2003/0198955 A1 (Li et a.), and US 6,066,449 (Ditkoff et al.).
Cheng et al., at paragraph [0049], teach:
[0049] The present disclosure provides methods for determining whether a patient having thyroid nodules with indeterminate cytology will benefit from diagnostic surgery, e.g., lobectomy. These methods are based on screening a patient's thyroid nodules and detecting alterations in target nucleic acid sequences corresponding to a specific set of thyroid cancer-related genes using a highly sensitive PCR-based NGS assay. Kits for use in practicing the methods are also provided. (Emphasis added)
Cheng et al., at paragraph [0136] and [0139], teach:
[0136] In some embodiments, the kits further comprise buffers, enzymes having polymerase activity, enzymes having polymerase activity and lacking 5′→3′ exonuclease activity or both 5′→3′ and 3′→5′ exonuclease activity, enzyme cofactors such as magnesium or manganese, salts, chain extension nucleotides such as deoxynucleoside triphosphates (dNTPs), modified dNTPs, nuclease-resistant dNTPs or labeled dNTPs, necessary to carry out an assay or reaction, such as amplification and/or detection of alterations in target nucleic acid sequences corresponding to the specific set of thyroid cancer-related genes disclosed herein.
[0137] In one embodiment, the kits of the present technology further comprise a positive control nucleic acid sequence and a negative control nucleic acid sequence to ensure the integrity of the assay during experimental runs, A kit may further contain a means for comparing the levels and/or activity of one or more of the preselected set of thyroid cancer-related genes described herein in a tumor sample with a reference nucleic acid sample (e.g., a non-tumor sample). The kit may also comprise instructions for use, software for automated analysis, containers, packages such as packaging intended for commercial sale and the like. (Emphasis added)
[0139] The kits of the present technology may include components that are used to prepare nucleic acids from a solid tumor test sample for the subsequent amplification and/or detection of alterations in target nucleic acid sequences corresponding to the specific set of thyroid cancer-related genes disclosed herein. Such sample preparation components can be used to produce nucleic acid extracts from tissue samples. The test samples used in the above-described methods will vary based on factors such as the assay format, nature of the detection method, and the specific tissues, cells or extracts used as the test sample to be assayed. Methods of extracting nucleic acids from samples are well known in the art and can be readily adapted to obtain a sample that is compatible with the system utilized. Automated sample preparation systems for extracting nucleic acids from a test sample are commercially available, e.g., Roche Molecular Systems' COBAS AmpliPrep System, Qiagen's BioRobot 9600, and Applied Biosystems' PRISM™ 6700 sample preparation system.
The above presentation is deemed to render obvious aspects of claims 1 and 20.
Cheng et al. have not been found to teach of varying concentrations of a surfactant.
Uehara, at paragraph [0025], teaches:
[0025] The nucleic acid amplification reaction mixture may further contain a surfactant. The surfactant is not particularly limited, however, examples thereof include NP-40, Triton X-100, and Tween 20. The concentration of the surfactant is not particularly limited, but is preferably a concentration which does not inhibit the nucleic acid amplification reaction, and may be from 0.001% to 0.1% or less, and is preferably from 0.002% to 0.02%, and most preferably from 0.005% to 0.01%. The surfactant may be a carry-over from a stock solution of the enzyme described above, however, a surfactant solution may be added to the nucleic acid amplification reaction mixture independently of the stock solution of the enzyme. (Emphasis added)
The above presentation is deemed to fairly suggest limitations of claim 2.
Meltzer et al., at paragraph [0104], teach:
[0104] A Gene-specific (also referred to herein as “target-specific”) amplification: At least two cycles of annealing/extension are performed with a temperature which is at, or above, the denaturing temperature of the hairpin stem structure of the hairpin primers and within the annealing range of the gene-specific primer sequence. (Emphasis added)
The above presentation is deemed to fairly suggest limitations of claim 3.
Harnack et al., at paragraph [0032], teach:
[0032] An alternative or complementary use of the storage system is the use as an independent storage system, even outside of a workstation, for example in cooling or freezing units, incubation units, for the intermediary storage of molecular-biological products, such as the temporary storage of amplification products or amplification reagents before, during or after a PCR process… (Emphasis added)
The aspect of storing, in a freezing unit, that which is undergoing a PCR process, is deemed to fairly suggest performing “a step of freeze and thawing the amplified mixture” (claim 4) and the limitation of “a step of freezing and thawing the amplified mixture between the one or more amplification steps” as is recited in claim 5.
Domanus, at paragraph [0059], teaches:
[0059] In some embodiments, regions of interest, along with control regions, are amplified prior to sequencing. In some embodiments, a control on the same chromosome as the region of interest is included. In some embodiments, a second control on a different chromosome is included. For example, a control located in the same chromosome is used for normalization for locus specific amplification. A second control located on a different nucleic acid (e.g., of known copy number) (e.g., a plasmid, mitochondrial DNA, synthetic DNA, or a different chromosome) is used to normalize copy number or gene expression. In some embodiments, the ratio of nucleic acid of control 1 to control 2 is compared to the ratio of nucleic acid from the region of interest to control 2. An increase in the amount of nucleic acid from the region of interest compared to control 2 relative to the amount of nucleic acid of control 1 compared to control 2 is indicative of genomic amplification of the region of interest (e.g., C1/C2 vs. ROI/C2), while a decrease is indicative of a copy number decrease or deletion. (Emphasis added)
The above presentation is deemed to fairly suggest limitations of claim 6. The amount (copy number) of control that one uses is deemed to be a matter of an obvious design choice.
Glezer et al., at paragraph [0099], teach:
[0099] In an aspect is provided a method of amplifying tagged complements of a plurality of sample polynucleotides, the method including: (a) hybridizing to each of the plurality of sample polynucleotides a plurality of interposing oligonucleotide barcodes, each of the interposing oligonucleotide barcodes including from 5′ to 3′: (i) a first hybridization pad complementary to a first sequence of a sample polynucleotide; (ii) a first stem region comprising a sequence common to the plurality of interposing oligonucleotide barcodes… (Emphasis added)
The above presentation is deemed to fairly suggest limitations of claim 7.
Walsh et al., at paragraph [0043], teach:
[0043] Another aspect of the present disclosure provides a method of diagnosing thyroid cancer. The method may comprise (a) obtaining a biological sample comprising gene expression products, wherein the biological sample may comprise a fine needle aspirate (FNA) of thyroid tissue from a subject; (b) assaying by sequencing, array hybridization, or nucleic acid amplification the gene expression products of the biological sample, which gene expression products may be associated with a benign or malignant thyroid condition. (Emphasis added)
The above presentation is deemed to fairly suggest limitations of claim 8 and 9.
Funahashi et al., at paragraph [0039], teach:
[0039] The biological samples that are used to obtain the nucleic acid or protein for analysis include, but are not limited to, a blood sample, a plasma sample, a serum sample, circulating tumor cells, circulating DNA, a urine sample, a thyroid tissue sample, a thyroid nodule sample, a renal tissue sample, or a tumor sample. (Emphasis added)
The above presentation is deemed to fairly suggest limitations of claim 10.
Lakdawalla et al., at paragraph [0150], teach:
For example, a sample may be obtained by a puncture method to obtain a bodily fluid comprising blood and/or plasma. Such a sample may comprise both cells and cell-free nucleic acid material. (Emphasis added)
The above presentation is deemed to fairly suggest limitations of claim 11.
Li et al., at paragraph [0667], teach:
[0667] Panel 2D Summary: Ag2200 This gene is most highly expressed in a thyroid cancer sample (CT=29). Interestingly, expression of this gene is not detectable in the matched adjacent normal thyroid tissue. This gene is also expressed at low but significant levels in an additional thyroid tumor. Therefore, expression of this gene may be used to distinguish thyroid cancer from normal thyroid tissue. (Emphasis added)
The above presentation is deemed to fairly suggest limitations of claim 12.
As noted above, Cheng et al., teach of using a kit and of what it may comprise. Attention is also directed to Ditkoff et al., who teach at column 2, lines 25-29:
This invention also provides a test kit for performing the above-described method. Specifically, this invention also provides the above-described test kit, wherein the kit comprises specific primers specific for amplification of nucleic acid encoding thyroglobulin or thyroid peroxidase.
In view of the above presentation, it would have been quite obvious to one of ordinary skill in the art to have combined the methods of Cheng et al., Uehara, Meltzer et al., Harnack et al., Domanus, Glezer et al., Walsh et al., Funahashi et al., Lakdawalla et al., and Li et al., and the kits of Cheng et al., and Ditkoff et al., for to do so would capitalize on the well-developed method for the detection of medically significant thyroid-specific nucleic acids, and to have on hand those “thyroid-specific nucleic acid detection mixture” (claim 20) that would enable said ordinary artisan to detect such medically significant sequences. In view of the clearly well developed state of the art, said ordinary artisan would have been well motivated and would have had a most reasonable expectation of success.
In view of the above presentation ad in the absence of convincing evidence to the contrary, claims 1-12 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over US 2019/0112653 A1 (Cheng et al.) in view of US 2016/0145674 A1 (Uehara), US 2021/0054369 A1 (Meltzer et al.), US 2010/0045147A1 (Harnack et al.), US 2014/0296094 A1 (Domanus), US 2021/0198730 A1 (Glezer et al.), US 2018/0349548 A1 (Walsh et al.), US 2014/0187577 A1 (Funahashi et al.), US 2021/0230669 A1 (Lakdawalla et al.), US 2003/0198955 A1 (Li et a.), and US 6,066,449 (Ditkoff et al.).
Claim(s) 13-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2019/0112653 A1 (Cheng et al.) in view of US 2016/0145674 A1 (Uehara), US 2021/0054369 A1 (Meltzer et al.), US 2010/0045147A1 (Harnack et al.), US 2014/0296094 A1 (Domanus), US 2021/0198730 A1 (Glezer et al.), US 2018/0349548 A1 (Walsh et al.), US 2014/0187577 A1 (Funahashi et al.), US 2021/0230669 A1 (Lakdawalla et al.), US 2003/0198955 A1 (Li et a.), and US 6,066,449 (Ditkoff et al.) as applied to claims 1-12 and 20 above, and further in view of US 2017/0101674 A1 (So et al.), US 2021/0189475 (Tentori et al.) and US 2003/0003468 A1 (Li et al.).
See above for the basis of the rejection as it pertains to the teachings of Cheng et al., Uehara, Meltzer et al., Harnack et al., Domanus, Glezer et al., Walsh et al., Funahashi et al., Lakdawalla et al., and Li et al.
So et al., at paragraph [0067], teach:
[0067] The disclosure also provides a method of tracking tumor-specific somatic mutations using tumor genomic DNA (gDNA) isolated from a subject's tumor and normal gDNA isolated from non-tumor tissue from the subject; comprising: (a) sequencing a DNA library prepared from the tumor gDNA without pre-amplification to produce a first dataset; (b) sequencing a DNA library prepared from the normal gDNA without pre-amplification to produce a second dataset; (c) analyzing the first and second dataset to identify one or more tumor-specific somatic mutations in the subject; and (d) detecting the presence or absence of the tumor-specific somatic mutations in cell-free DNA isolated from a liquid sample from the subject. In some embodiments, the liquid sample is selected from the group consisting of plasma, serum, sputum, saliva, urine, cerebral spinal fluid, mucosal secretions, amniotic fluid, bodily fluid and sweat. In some embodiments, the DNA library of step (a) or (b) is prepared using any of the methods described herein. In some embodiments, the sequencing comprises sequencing at least 200 cancer-related In some embodiments, the cancer-related genes are selected from the group consisting of ABCA1, BRAF, CHD5, EP300, FLT1, ITPA, MYC, PIK3R1, SKP2, TP53, ABCA7, BRCA1, CHEK1, EPHA3, FLT3, JAK1, MYCL1, PIK3R2, SLC19A1, TP73, ABCB1, BRCA2, CHEK2, EPHA5, FLT4, JAK2, MYCN, PKHD1, SLC1A6, TPM3, ABCC2, BRIP1, CLTC, EPHA6, FN1, JAK3, MYH2, PLCB1, SLC22A2, TPMT, ABCC3, BUB1B, COL1A1, EPHA7, FOS, JUN, MYH9, PLCG1, SLCO1B3, [and] TPO… (Emphasis added)
It is noted that the gene abbreviation for thyroid peroxidase, “TPO” is present in the Markush group of claims 13, 14, and 18. The aspect of the sample being s plasma sample is deemed to suggest limitations of claim 19.
So et al., have not been found to teach taking samples and performing the assay at different times.
Tentori et al., at paragraph [1135], teach:
In some examples, the methods described herein can be performed on multiple similar biological samples or cells obtained from the subject at a different time points (e.g., before or after treatment with an agent, different stages of differentiation, different stages of disease progression, different ages of the subject, before or after physical perturbation, before or after treatment with a perturbation agent as described herein, or before or after development of resistance to an agent). (Emphasis added)
The above presentation is deemed to fairly suggest limitations of claim 16.
Al-Murrani et al., at paragraph [0024], teach:
[0024] The invention provides, therefore, a method (Method 1) of diagnosing hyperthyroidism or measuring risk of, or predisposition to, hyperthyroidism in a feline, by measuring the expression level of one or more biomarkers in said feline, said one or more biomarkers selected from the group consisting of the genes listed on Table A (e.g., TGFB1 and/or CSTD) and B (e.g., DCN and/or SEPP1), or any of the following genes: IYD, TG, SLC5A5, NIS, TPO, TSHR, DUOX1 and DUOX2 (ThOX)… (Emphasis added)
It is noted that the gens identified by Al-Murrani et al., encompass multiple genes identified in claims 13, 14, and 18.
In view of the above presentation, it would have been obvious to one of ordinary skill in the art to have combined known methods of sample collection and analysis whereby one determines he presence of any of a variety of thyroid-specific nucleic acids, including specified genes, and that such samples can be collected at different time points, therein providing information as to the state(s) of a thyroid disease, if there was any.
In view of the well-developed state of the art and the medical significance of monitoring the state of one’s thyroid, said ordinary artisan would have been quite motivated to have combined such known technologies and would have also had a most reasonable expectation of success.
In view of the above analysis and in the absence of convincing evidence to the contrary, claims 13-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2019/0112653 A1 (Cheng et al.) in view of US 2016/0145674 A1 (Uehara), US 2021/0054369 A1 (Meltzer et al.), US 2010/0045147A1 (Harnack et al.), US 2014/0296094 A1 (Domanus), US 2021/0198730 A1 (Glezer et al.), US 2018/0349548 A1 (Walsh et al.), US 2014/0187577 A1 (Funahashi et al.), US 2021/0230669 A1 (Lakdawalla et al.), US 2003/0198955 A1 (Li et a.), and US 6,066,449 (Ditkoff et al.) as applied to claims 1-12 and 20 above, and further in view of US 2017/0101674 A1 (So et al.), US 2021/0189475 (Tentori et al.) and US 2003/0003468 A1 (Li et al.).
Conclusion
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/Bradley L. Sisson/Primary Examiner, Art Unit 1682
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