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 Status
Currently, claims 8-21 are pending in the instant application. Claim 1-7 have been canceled. Claims 18-19 are withdrawn and claims 20-21 are added. This action is written in response to applicant' s correspondence submitted 10/28/2025. All the amendments and arguments have been thoroughly reviewed but were found insufficient to place the instantly examined claims in condition for allowance. The following rejections are either newly presented, as necessitated by amendment, or are reiterated from the previous office action. Any rejections not reiterated in this action have been withdrawn as necessitated by applicant' s amendments to the claims. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action. This action is Final.
Claims 8-17 and 20-21 are under examination with regard to the combination of SEQ ID NO 1-13, 28-29, 20-24, and 27. As indicated in the remarks mailed 05/19/2025 the claims are intended to require the entire combination of primers recited within the claims.
Withdrawn Rejections
The rejection of claims 9-12, 15-17 under 35 USC 112(b) is withdrawn in view of the amendment to the claims.
The rejection of claims 8-17 under 35 U.S.C. 103 as being unpatentable over Xiang (US 2018/0201998 A1, cited on IDS) in view of Mirasena (Naruesuan University Journal, 2007, 15:43-53), Mishra (Analytical Biochemistry, 2017, 537, pp 93-98), and Marini (Indian J Med Res 2012, 135, pp 31-35) is withdrawn in view of the amendment to the claims.
Maintained Rejections
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 8-17 and 20-21 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception without significantly more. The claims recite a law of nature and this judicial exception is not integrated into a practical application. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
The following three inquiries are used to determine whether a claim is drawn to patent-eligible subject matter:
Step 1. Is the claim directed to a process, machine, manufacture, or composition of matter? Yes, all of the claims are directed to a composition of matter.
Step 2. Is the claim directed to a law of nature, a natural phenomenon or an abstract idea (judicially recognized exception) and does the claim recite additional elements that integrate the judicial exception into a practical application?
The claims are drawn to a composition of matter, which is a law of nature. Claim 8 recites a kit comprising a first group of primers having sequence set forth in SEQ ID NO 1-13, 28, and 29, a second group of primers having a sequence set forth in SEQ ID NO 20-24 and 27 and PCR reagents comprising a mutated Taq polymerase with the intended use of rapid detection of mutations causing genetic disorders from unprocessed human blood sample in a single tube reaction. SEQ ID NO 1-13, 28 and 29 encompasses naturally occurring sequences of HBB gene. SEQ ID NO 20-24 and 27 encompasses naturally occurring sequences of SMNT gene. The broadly recited naturally occurring primers do not have markedly different characteristics from their naturally occurring counterparts because the primers convey the same genetic information.
The kit also include PCR reagents comprising mutated Taq polymerase. While the mutated Taq polymerase is not naturally occurring, this is well understood routine and conventional in the art for PCR. The specification addressed that mutated Taq polymerase for various purposes has been developed and there are establish protocols and kits available (see pg. 2 lines 23-25). The specification further teaches using HemoKlen Taq, a mutated Taq polymerase which is commercially available, see example 1. There are also naturally occurring products that do not have any markedly different structural properties as compared to their naturally occurring counterparts.
Claims 9-12 and 15-17 limit the intended use method recited within the kit which does not structurally change the primers or reagents of the kit. Claim 13-14 comprise instructions for performing the intended use. Neither of these claims further limit the product and do not provide any additional limitations that structurally change the naturally occurring products recited within the claims.
The specification does not define primer or reagents. The specification teaches established kits are available for the detection of mutations resulting in genetic disorders such as hemoglobinopathies and maculopathies (see pg. 2, lines 23-27). There is no recitation within the claims that indicate that the nucleic acid claimed have any structural or functional characteristics that differ from the naturally occurring nucleic acids. Thus the claims encompasses naturally occurring nucleic acids contained within a kit. There is no indication in the specification that the nucleic acids claimed here have any structural or functional characteristics that differ from the naturally occurring nucleic acids. Additionally the claims reciting a kit and instructions comprise naturally occurring nucleic acids and the recitation of kit and instructions does not result in a structure that is markedly different than the naturally occurring nucleic acid sequence because the reagent, kit, and instructions convey the same nucleic acid sequence. Instructions for use or does not result in a significantly different nucleic acid structure. Instructions for use encompass printed matter which is non-patent eligible subject matter (see MPEP 2106). The claimed kit comprising reagents include nucleic acids and enzymes that do not display markedly different characteristic compared to the naturally occurring counterpart.
The claimed nucleic acids do not display markedly different characteristic compared to the naturally occurring counterpart and there is no indication that the kit comprising primers and reagents results in changing the structure, function or other properties of the naturally occurring nucleic acid. According the nucleic acids and enzymes are a product of nature exception and the claim is directed to at least one exception. This judicial exception is not integrated into a practical application because the claims recite primers that are naturally occurring and the reagents that are naturally occurring. The recitation of primer is nothing more than an attempt to generally link the product of nature to a technological environment and is a nominal extra solution component of the claim and does not structurally change the nucleic acid sequence. Many cited prior art references in this record demonstrate the primers are naturally occurring sequences.
Step 2B - Does the claim recite additional elements that amount to significantly more than the judicial exception? No.
Herein the claims as a whole are not considered to recite any additional elements that amount to significantly more than the naturally occurring nucleotide sequences. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. Besides the nucleic acids, the claims recite a kit in the preamble and a mutated Taq polymerase. At the time the invention was made, a kit or combination of reagents and mutated Taq polymerase was well-established, routine and conventional. Additionally where a composition such as a kit is recited at such a high level of generality it does not meaningfully limit the claim. The recitation of instructions is not significantly more and does not structurally change the nucleic acid sequence is not significantly more than the naturally occurring sequence. Thus the claims as a whole does not amount to significantly more than each “product of nature” by itself and the claims do not qualify as eligible subject matter.
Accordingly, it is determined that the instant claims are not directed to patent eligible subject matter.
Response to Arguments
The response traverses the rejection on pages 7-8 of the remarks mailed 10/28/2025. The response addresses the analysis of 101. The response the asserts that claim 8 recites the additional element of a mutated Taq polymerase. The response asserts the Taq polymerase comprises specific mutations that are not naturally occurring and are not a product of nature. The response asserts because the kit comprises a mutated Taq polymerase that is not naturally occurring the claim as a whole recite additional elements that integrate the recited primers into a practical application and therefore the claims are patent eligible. This response has been reviewed but not found persuasive. Mutated Taq polymerase for use in PCR amplification were well-known routine and conventional in the art. The addition of a mutated Taq polymerase in a kit for amplification does not integrate the judicial exception. The specification addressed that mutated Taq polymerase for various purposes has been developed and there are establish protocols and kits available (see pg. 2 lines 23-25). The specification further teaches using HemoKlen Taq, a mutated Taq polymerase which is commercially available, see example 1. Marx (US2016/0298174 A1) teaches mutated DNA polymerase with high selectively and activity, demonstrating mutated Taq polymerases were well-known, routine and conventional in art. For these reasons and reasons of record this rejection is maintained,
New Grounds of Rejection
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 8-17 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Xiang (US 2018/0201998 A1, cited on IDS) in view of Mirasena (Naruesuan University Journal, 2007, 15:43-53), Mishra (Analytical Biochemistry, 2017, 537, pp 93-98), Marini (Indian J Med Res 2012, 135, pp 31-35), and Marx (US2016/0298174 A1). This rejection is a new grounds of rejection.
Xiang teaches a kit comprising primers for detecting spinal muscular atrophy and beta thalassemia (see para 21). Xiang teaches kit comprising allele-specific primers, common primers, instructions, dNTPs, and polymerases (see para 171). Xiang teaches buffers (see para 140). Xiang teaches a HotStartTaq DNA polymerase (see para 182). Xiang does not teach the specific primers comprising SEQ ID NO 1-13, 27, 28 for HBB gene and SEQ ID NO 20-24 and 27 for SMNT gene. While Xiang teaches a modified Taq polymerase, Xiang does not teach a mutated Taq polymerase.
However primers for HBB gene and SMNT gene were well known in the art. Marim teaches allele specific primers for SMNT, including telSMNex7 forward primer and telSMNint7 rev primer which are identical to SEQ ID NO 22 and SEQ ID NO 24. Marim teaches primers for beta-globin, the forward primer comprises SEQ ID NO 1 (see allele specific PCR). Mishra teaches allele specific primers for common mutations in HBB. Mishra teaches codon15, IVS 1-5, codon 41 and 619 bp deletion. Mishra teaches primer for IVS 1-5 which is identical to SEQ ID NO 5, primer for Codon 41/42 which is identical to SEQ ID NO 7, primer for 619 bp deletion identical to SEQ ID NO 28 (see table 1). Mishra further teaches CM23 primer which is identical to SEQ ID NO 1. Mirasena teaches ARMS PCR detection of beta thalassemia mutations. Mirasena teaches primers comprising SEQ ID NO 1, 2, and 5. Mirasena teaches SEQ ID NO 1, primer G (table 1), SEQ ID No 2, primer B (table 2), SEQ ID NO 5, IVSI-5, SEQ ID NO 7, Codons 41/42 (table 1). Mirasena teaches primers were designed using a computer program (see primer design).
Marx teaches mutated DNA polymerases with improved activity. Marx teaches mutated Taq DNA polymerases. KlenTaq polymerase which has a higher thermostability and lower error rate than Taq (see para 78). Marx additionally teaches mutations at KlenTaq R550V mutation allows for improve genotyping amplification (see ex 6), increased selectivity and activity with mutations (see para 403). Marx teaches kits comprising instructions for use of DNA polymerase, labels, and mutated Taq polymerases (see para 370-373). Marx teaches the kit comprises 50 or more primers (see para 380)
The ordinary artisan would have been motivated to combine additional known elements with a reasonable expectation of success to combine primers for HBB and SMNT gene as taught by Marim, Mishra, and Mirasena and included mutated Taq polymerase with improved activity as taught by Marx in the kit of Xiang to include additional primers that function to detect known mutations of HBB and SMNT associated with spinal muscular atrophy and beta thalassemia and include polymerases with improved activity. Because Marim, Mishra, and Mirasena teach primers for detecting mutations associated with spinal muscular atrophy and beta thalassemia and primer design, including primers comprising SEQ ID NO 1-2, 5, 7, 22, and 25, the ordinary artisan would have been motivated to design and include additional primers, including SEQ ID NO 1-13, 20-24, 27-29 in the kit of Xiang. Because Marx teaches a kit comprising mutated Taq polymerase and primers, the ordinary artisan would have been motivated to replace the Taq polymerase taught by Xiang with a KlenTaq R660V with improved selectivity and activity.
Designing primers and probes which are equivalent to those taught in the art is routine experimentation. The prior art teaches the parameters and objectives involved in the selection of oligonucleotides that function as primers, see Marim, Mishra, and Mirasena et al. Moreover there are many internet web sites that provide free downloadable software to aid in the selection of primers drawn from genetic data recorded in a spreadsheet. The prior art is replete with guidance and information necessary to permit the ordinary artisan in the field of nucleic acid detection to design primers and probes. As discussed above, the ordinary artisan would be motivated to have designed and provide new primers to obtain additional primers that function to detect mutations in HBB and SMNT to detect spinal muscular atrophy and beta thalassemia. Thus, for the reasons provided above, the ordinary artisan would have designed additional primers to detect the known mutations in HBB and SMNT to include kits with primers for detecting spinal muscular atrophy and beta thalassemia using the teachings in the art at the time the invention was made.
With regard to claims 9-17, the limitations of the claims do not limit the structural requirements of the primers or reagents of the kit and are intended use. As stated in MPEP 2111.02, if a prior art structure is capable of performing the intended use as recited in the claims, then it meets the claim. See, e.g., In re Schreiber, 128 F.3d 1473, 1477, 44 USPQ2d 1429, 1431 (Fed. Cir. 1997) (anticipation rejection affirmed based on Board' s factual finding that the reference dispenser (a spout disclosed as useful for purposes such as dispensing oil from an oil can) would be capable of dispensing popcorn in the manner set forth in appellant' s claim 1 (a dispensing top for dispensing popcorn in a specified manner)) and cases cited therein. As such the teachings of Xiang in view of Marim Mishra and Mirasena render obvious a kit that is capable of performing the intended use of claims 9-17.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Xiang (US 2018/0201998 A1, cited on IDS) in view of Mirasena (Naruesuan University Journal, 2007, 15:43-53), Mishra (Analytical Biochemistry, 2017, 537, pp 93-98), Marini (Indian J Med Res 2012, 135, pp 31-35), and Marx (US2016/0298174 A1) as applied to claims 8-17 and 20 above, and further in view of Yaron (Genetic Testing, Vol 10, 2006, pp. 18-23). This rejection is a new ground of rejection.
Xiang in view of Mirasena, Mishra, Marini, and Marx teach a kit comprising primers comprising SEQ ID NO 1-13, 28-29, 20-24 and 27, a mutated Taq polymerase and a buffer. Xiang in view of Mirasena, Mishra, Marini, and Marx does not teach the buffer comprises Tricine.
However it was well known in the art to use Tricine for PCR amplification. Yaron teaches detection of SMNT carriers by nested PCR using a Tricine (see First round – outer PCR).
Therefore it would have been prima facie obvious to include well-known buffers used in PCR amplification, such as Tricine as taught by Yaron in the kit comprising primers comprising SEQ ID NO 1-13, 28-29, 20-24 and 27, a mutated Taq polymerase and a buffer for the expected benefit of amplification of SMNT carriers as known in the art.
Response to Arguments
The response traverses the rejection on pages 9 of the remarks. While this is a new grounds of rejection the traversal with respect to primers and unprocessed blood sample is relevant to the newly applied rejection. The response traverses the rejection of Xiang in view of Mirasena, Mishra, and Marini, does not teach a mutated Taq polymerase. As addressed in the newly applied rejection, Marx teaches mutated Taq polymerase and improved selectivity and activity for detecting mutations. The skilled artisan would have been motivated to include in the kit a mutated Taq polymerase with improved activity.
The response further asserts that the combination of Xiang in view of Mirasena, Mishra, and Marini, does not teach a single reaction capable of simultaneously detecting all three genotyping’s from unprocessed whole blood or dried blood spots. The response asserts that each of the references extract DNA prior to amplification and do not teach or suggest using in connection with unprocessed human blood samples. The response further asserts that none of the references teach or suggests combining the primers for identification of multiple genotypes in a single reaction. This response has been thoroughly reviewed but not found persuasive. The claims are not directed to a method, the claims are directed to a product which comprises a combination of reagents in a kit. Applicant is arguing a function of the primers and not the combination of reagents. In response to applicant's argument that the combination of references does not teach a single reaction capable of simultaneously detecting all three genotyping’s from unprocessed whole blood or dried blood spots a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. There are no structural requirements of the kit that results in a difference from the prior art.
Conclusion
No claims are allowable.
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 SARAE L BAUSCH whose telephone number is (571)272-2912. The examiner can normally be reached M-F 9a-4p.
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/SARAE L BAUSCH/Primary Examiner, Art Unit 1699
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