DETAILED ACTION
Status of the Claims
Claims 1-3, 5-15, and 18-23 are currently pending and are examined herein.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 06/03/2024 and 10/31/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.831-1.834 because it does not contain a “Sequence Listing XML” as a separate part of the disclosure. A “Sequence Listing XML” is required because the Application contains at least 3 nucleotide sequences of ten or more nucleotides which are not marked with "SEQ ID NOs", nor are there CRF depositions on file for them. For example, see Tables 18-21 on pp. 41-50 of the instant specification. The foregoing analysis should not to be deemed exhaustive, as there may be other polynucleotide or polypeptides disclosed which similarly require sequence identifiers.
Required response - Applicant must provide:
• A “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2.; together with
o A statement that indicates the basis for the amendment, with specific references to particular parts of the application as originally filed, as required by 37 CFR 1.835(a)(3);
o A statement that the “Sequence Listing XML” includes no new matter as required by 37 CFR 1.835(a)(4)
AND
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(a)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
o A statement that the substitute specification contains no new matter.
Claim Interpretation
As per MPEP § 2111 and § 2111.01, during patent examination, the pending claims must be interpreted as broadly as their terms reasonably allow while being consistent with the specification. The words of a claim must be given their ‘plain meaning’ unless such meaning is inconsistent with the specification, wherein ‘plain meaning’ of a term means the ordinary and customary meaning given to the term by those of ordinary skill in the art at the relevant time. The ordinary and customary meaning of a term may be evidenced by a variety of sources, including the words of the claims themselves, the specification, drawings, and prior art. Because applicant has the opportunity to amend the claims during prosecution, giving a claim its broadest reasonable interpretation will reduce the possibility that the claim, once issued, will be interpreted more broadly than is justified. In re Yamamoto, 740 F.2d 1569, 1571 (Fed. Cir. 1984)
Below are notes made by the examiner regarding claim interpretation of the most recent set of claims. Applicant is respectfully invited to comment on or dispute any of these statements.
Regarding claims 1-3 and 9-10, the recitations of “for sequencing library construction” and “for constructing a sequencing library” in the preamble are recitations of intended use of the instant claimed amplification primer and kit and 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. See also MPEP § 2111.02, citing In re Sinex, 309 F.2d 488, 492, 135 USPQ 302, 305 (CCPA 1962) (statement of intended use in an apparatus claim did not distinguish over the prior art apparatus), and MPEP § 2112.01 citing In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990) stating that “discovery of an unobvious property and use does not overcome the statutory restraint of section 102 when the claimed composition is known”.
Claim 8 recites the limitation of a “sequencing library constructed by the method for constructing a sequencing library according to claim 5” and is therefore a product-by-process claim. Note that as per MPEP § 2113, “product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps”. The same MPEP section states that “‘even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.’ In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). In the present case, the process steps imply the following structural limitations: amplified DNAs with a CA at the 3’-termini ligated to an adaptor containing a T sticky end. The specific process limitations of claim 8 do not distinguish the claimed invention from the prior art in accordance with MPEP § 2113. One of ordinary skill would expect the product to be the same no matter how it was synthesized and/or prepared.
Claims 18-21 are each drawn to kits comprising the amplification primer of claim 1, wherein the preamble of each claim recites the type of kit, namely a “mutation site detection kit”, a “chromosome ploidy detection kit”, a “gene fusion detection kit”, and a “pathogenic microorganism detection kit”, respectively. However, it is noted that as per MPEP 2111.02, "[A] claim preamble has the import that the claim as a whole suggests for it." Bell Communications Research, Inc. v. Vitalink Communications Corp., 55 F.3d 615, 620, 34 USPQ2d 1816, 1820 (Fed. Cir. 1995). "If the claim preamble, when read in the context of the entire claim, recites limitations of the claim, or, if the claim preamble is ‘necessary to give life, meaning, and vitality’ to the claim, then the claim preamble should be construed as if in the balance of the claim" citing Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165-66 (Fed. Cir. 1999). Further, the same section states that “During examination, statements in the preamble reciting the purpose or intended use of the claimed invention must be evaluated to determine whether the recited purpose or intended use results in a structural difference (or, in the case of process claims, manipulative difference) between the claimed invention and the prior art. If so, the recitation serves to limit the claim.” In the instant case, the limitation recited in the preamble provides nothing more than the intended use of the detection kit, and therefore cannot distinguish over the prior art if the prior art is reasonably able to be used in such a manner.
Claim Objections
Claim 15 is objected to because of the following informalities: the claim recites a “CD74-ROSI fusion gene”, which appears to be a typo for “CD74-ROS1 fusion gene”. Appropriate correction is required.
Claim Rejections – 35 U.S.C. 102
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 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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Smith et al.
Claims 1-2, 9-10, and 18-21 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Smith et al. (U.S. 6,110,710, issued 08/29/2000).
Regarding claim 1, Smith discloses an amplification primer for sequencing library construction comprising a primer sequence fragment complementary to a target fragment and a base G ligated to the 5' end of the primer sequence fragment, wherein the amplification primer and the target fragment are not complementary at the base G (e.g., as per col. 1, lines 55-67).
Regarding claim 2, Smith discloses the above primer, wherein the base G is directly ligated to the 5' end of the primer sequence fragment (e.g., as per col. 1, lines 55-67).
Regarding claims 9 and 18-21, Smith discloses the amplification primer of claim 1 (as detailed above) and the recitations of intended use in the preambles of these claims does not further limit the structural requirements of the primer(s) as detailed in the Claim Interpretation section, herein. Furthermore, since the primers of Smith can reasonably be used to prepare sequencing libraries from nearly any source of amplifiable DNA, they can reasonably be used in the intended uses as per the claims, absent factual evidence to the contrary.
Regarding claim 10, Smith further discloses a reagent for PCR amplification (e.g., Taq polymerase as per Example 1).
Claim Rejections – 35 U.S.C. 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 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.
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.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 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.
Fang et al. and Smith et al.
Claims 1-3, 5-11, and 18-22 are rejected under 35 U.S.C. 103 as being unpatentable over Fang et al. (U.S. PGPub 2016/0355870 A1, published 12/08/2016) in view of Smith et al. (U.S. 6,110,710, issued 08/29/2000).
Fang discloses “a method for generating ligation-ready DNA amplicons of a target DNA, comprising (i) contacting in a polymerase chain reaction (PCR) buffer said target DNA with at least one DNA polymerase, a dNTP mixture, and at least one PCR primer pair consisting of two target specific PCR primers, to obtain a reaction mixture, (ii) subjecting said reaction mixture to a PCR to generate a plurality of ligation-ready DNA amplicons of said target DNA, wherein at least one of said target specific PCR primers is 5'-phosphorylated” (e.g., as per para 0012). Further, Fang discloses TA cloning of the resulting amplification products in order to add Illumina® TruSeq sequencing adapters (e.g., as per the EXAMPLES).
Smith is relied on as above, however, it is noted that Smith is silent as to the limitation of ligating a G to the 5’-termini of the primers used if they do not already have a 5’-terminal G, or ligating or not ligating a G to the 5’-termini of the primers used if they do already have a 5’-terminal G, as required by claims 3, 5-8, 11, and 22.
It would have been prima facie obvious to a person of ordinary skill in the art prior to the effective filing date of the application to use an amplification primers with 5’-terminal G residues as per Smith in the amplification and cloning to construct a sequencing library as per Fang. One of ordinary skill in the art would have been motivated to do so since Smith explicitly discloses that adding a 5’-terminal G residue to the amplification primers and/or using a primer with an already-present 5’-terminal G residue promotes non-templated addition of a 3’-adenosine addition to a PCR product (e.g., as per the SUMMARY OF THE INVENTION section), thus increasing the efficiency of the TA ligation.
One of ordinary skill in the art would have had a reasonable expectation of success as of the application’s effective filing date in combining the teachings of the prior art references to arrive at the invention as presently claimed since it would merely require the modification of the 5’-terminal residue of the amplification primer(s), which was well within the reach of the skilled artisan.
Fang et al., Smith et al., and Milbury et al.
Claims 1-3, 5-13, and 18-22 are rejected under 35 U.S.C. 103 as being unpatentable over Fang et al. (U.S. PGPub 2016/0355870 A1, published 12/08/2016) in view of Smith et al. (U.S. 6,110,710, issued 08/29/2000) and further in view of Milbury et al. (Clinical Chemistry, 2012, 58(3):580-589).
Fang in view of Smith is relied on as above, however, it is noted that the references are silent as to the limitation of the sequencing method is used to perform mutation site detection, wherein the mutation site detection comprises intestinal cancer mutation sites, as set forth in claims 12-13.
Milbury discloses sequencing methods used to detect mutation sites in colorectal cancer (e.g., as per the METHODS section).
It would have been prima facie obvious to a person of ordinary skill in the art prior to the effective filing date of the application to perform the sequencing of colorectal cancer sequencing libraries as per Milbury using the amplification using 5’-phosphorylated G residue primers as per Fang in view of Smith. One of ordinary skill in the art would have been motivated to do so since Smith explicitly discloses that adding a 5’-terminal G residue to the amplification primers and/or using a primer with an already-present 5’-terminal G residue promotes non-templated addition of a 3’-adenosine addition to a PCR product (e.g., as per the SUMMARY OF THE INVENTION section), thus increasing the efficiency of the TA ligation, which would reasonably lead to increased sensitivity in the sequencing of Milbury.
One of ordinary skill in the art would have had a reasonable expectation of success as of the application’s effective filing date in combining the teachings of the prior art references to arrive at the invention as presently claimed since it would merely require the modification of the 5’-terminal residue of the amplification primer(s), which was well within the reach of the skilled artisan.
Fang et al., Smith et al., and Springer et al.
Claims 1-3, 5-11, 14, and 18-23 are rejected under 35 U.S.C. 103 as being unpatentable over Fang et al. (U.S. PGPub 2016/0355870 A1, published 12/08/2016) in view of Smith et al. (U.S. 6,110,710, issued 08/29/2000) and further in view of Springer et al. (eLife, 2018, 7:e32143).
Fang in view of Smith is relied on as above, however, it is noted that the references are silent as to the limitation of the sequencing method is used to perform chromosome ploidy of urothelial cancer and diagnosis, as set forth in claims 14 and 23.
Springer discloses sequencing methods used to perform chromosome ploidy of urothelial cancer and diagnosis (e.g., as per the UroSEEK: biomarkers in combination section on p. 14).
It would have been prima facie obvious to a person of ordinary skill in the art prior to the effective filing date of the application to perform the sequencing of urinary sequencing libraries as per Springer using the amplification using 5’-phosphorylated G residue primers as per Fang in view of Smith. One of ordinary skill in the art would have been motivated to do so since Smith explicitly discloses that adding a 5’-terminal G residue to the amplification primers and/or using a primer with an already-present 5’-terminal G residue promotes non-templated addition of a 3’-adenosine addition to a PCR product (e.g., as per the SUMMARY OF THE INVENTION section), thus increasing the efficiency of the TA ligation, which would reasonably lead to increased sensitivity in the sequencing of Springer.
One of ordinary skill in the art would have had a reasonable expectation of success as of the application’s effective filing date in combining the teachings of the prior art references to arrive at the invention as presently claimed since it would merely require the modification of the 5’-terminal residue of the amplification primer(s), which was well within the reach of the skilled artisan.
Fang et al., Smith et al., and Zheng et al.
Claims 1-3, 5-11, 15, and 18-22 are rejected under 35 U.S.C. 103 as being unpatentable over Fang et al. (U.S. PGPub 2016/0355870 A1, published 12/08/2016) in view of Smith et al. (U.S. 6,110,710, issued 08/29/2000) and further in view of Zheng et al. (Nature Medicine, 2014, 20(12):1479-1486).
Fang in view of Smith is relied on as above, however, it is noted that the references are silent as to the limitation of the sequencing method is used to perform gene fusion detection of TPM3-NTRK1 fusion gene, as set forth in claim 15.
Zheng discloses sequencing methods to detect TPM3-NTRK1 fusion gene products (e.g., as per the Abstract).
It would have been prima facie obvious to a person of ordinary skill in the art prior to the effective filing date of the application to perform the multiplex PCR as per Zheng using the amplification using 5’-phosphorylated G residue primers as per Fang in view of Smith. One of ordinary skill in the art would have been motivated to do so since Smith explicitly discloses that adding a 5’-terminal G residue to the amplification primers and/or using a primer with an already-present 5’-terminal G residue promotes non-templated addition of a 3’-adenosine addition to a PCR product (e.g., as per the SUMMARY OF THE INVENTION section), thus increasing the efficiency of the TA ligation, which would reasonably lead to increased sensitivity in the sequencing of Zheng.
One of ordinary skill in the art would have had a reasonable expectation of success as of the application’s effective filing date in combining the teachings of the prior art references to arrive at the invention as presently claimed since it would merely require the modification of the 5’-terminal residue of the amplification primer(s), which was well within the reach of the skilled artisan.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEREMY FLINDERS whose telephone number is (571)270-1022. The examiner can normally be reached M-F 10-6:00 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Heather Calamita can be reached on (571)272-2876. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JEREMY C FLINDERS/
Primary Examiner, Art Unit 1684
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