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 .
Election/Restrictions
Applicant’s election of Group II, claim 5 in the reply filed on 04/23/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1-4 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1-5 are pending and claim 5 is under examination on the merits.
Priority
This application 18/289,859 filed on 11/07/2023 is a 371 national phase of PCT/ US2022/028321filed on 05/09/2022, and claims the benefit of provisional U.S. Patent Application No. 63/185,678, filed on 05/07/2021.
The priority date of 5 is determined to be 05/07/2021, the filing date of provisional U.S. Patent Application No. 63/185,678.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," 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 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) 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") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) 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 of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specification
The use of terms which are trade names or marks used in commerce (including OligoAnalyzer™ and Thermo Fisher Scientific®), has been noted in this application. The term should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM, or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claim 5 is objected to because of the following informalities: The claim recites “a molecular beacon probe for detecting M. abscessus subsp. Bolletii reperesented by SEQ ID NO. 3”. The term “represented” appears to be a typographical error intended to be represented. Appropriate correction is required.
Claim Interpretation
Claim 5 recites primers and molecular beacon probes “represented by” SEQ ID NOs. For purposes of claim interpretation, “represented by” is broadly interpreted to include sequences that are not identical to the sequence in the SEQ ID NO, including mismatches and partial matches, as well as oligonucleotide sequences that have functional equivalence.
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.
Claim 5 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
35 U.S.C. § 101 requires that to be patent-eligible, an invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. M.P.E.P. § 2106. Regarding judicial exceptions, “[p]henomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972); see also M.P.E.P. § 2106, part II.
Based upon consideration of the claims as a whole, as well as consideration of elements/steps recited in addition to the judicial exception, the present claims fail to meet the elements required for patent eligibility.
Step 1
The claimed invention is directed to the statutory category of a products.
Step 2A, Prong One
The claim is taken to be directed to natural phenomena.
Claim 5 is directed to a product (an assay) comprising
“a forward primer for MAB2248 represented by SEQ ID NO. 1; a reverse primer for MAB2248 represented by SEQ ID NO. 2; a molecular beacon probe for detecting M. abscessus subsp. bolletii reperesented by SEQ ID NO. 3; a forward primer for MAB2830 represented by SEQ ID NO. 4; a reverse primer for MAB2830 represented by SEQ ID NO. 5; a molecular beacon probe for detecting M. abscessus subsp. abscessus represented by SEQ ID NO. 6; a molecular beacon probe for detecting M. abscessus subsp. massiliense represented by SEQ ID NO. 7; a forward primer for 23S rrl represented by SEQ ID NO. 8; a reverse primer for 23S rrl represented by SEQ ID NO. 9; a molecular beacon probe for detecting the wild type of 23S rrl represented by SEQ ID NO. 10;a forward primer for erm(41) A represented by SEQ ID NO. 11;a reverse primer for erm(41) A represented by SEQ ID NO. 12;a molecular beacon probe for erm(41) A represented by SEQ ID NO. 13;a forward primer for erm(41) T28C represented by SEQ ID NO. 14;a reverse primer for erm(41) T28C represented by SEQ ID NO. 15; and a molecular beacon probe for detecting erm(41) T28C represented by SEQ ID NO. 16.”
Claim 5 is directed to primers and probes. Such isolated nucleic acid molecules that are identical to fragments of naturally occurring nucleic acid molecules are not patent eligible subject matter. i.e. they are judicial exceptions. See MPEP 2106.04
Step 2A, Prong Two
The claims do not include additional elements that are sufficient to amount to add significantly more than the judicial exception for the reasons that follow.
A. The courts have identified the following concepts and products as examples of laws of nature or natural phenomena:
I. Isolated DNA, Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 589-91, 106 USPQ2d 1972, 1978-79 (2013);
IL. Single-stranded DNA fragments known as "primers", University of Utah Research Foundation v. Ambry Genetics Corp., 774 F.3d 755, 761, 113 USPQ2d 1241, 1244 (Fed. Cir. 2014) B. The claims encompass products that are not markedly different from products of nature for the following reasons:
Regarding claim 6, the claimed primers and probes comprising nucleotide sequences as set forth in SEQ ID NOs: 1-16 are all 100% identical to naturally occurring sequences in fragments or full length. These sequences are all directed to Mycobacteroides abscessus genomes as described in the specification and are identical to genome sequences in GenBank as shown below.
Because the naturally occurring counterpart of each of the claimed sequences and complementary nucleotide sequences thereof is a segment of a chromosome, the combination of the claimed nucleotide sequence and a complementary nucleotide sequence complementary to the claimed nucleotide sequence is not markedly different from the naturally occurring double-stranded DNA sequences found in the human genome. Alignments of each of the claimed capture sequences to their naturally-occurring counterparts follow below:
A sequence represented by SEQ ID NO. 1 is 100% identical to Genbank Accession MLCG01000006.1 Mycobacteroides abscessus ATCC 19977 WGS, submitted October 12, 2016:
PNG
media_image1.png
200
962
media_image1.png
Greyscale
A sequence represented by SEQ ID NO. 2 is 100% identical to Genbank Accession MLCG01000006.1 Mycobacteroides abscessus ATCC 19977 WGS, submitted October 12, 2016:
PNG
media_image2.png
206
963
media_image2.png
Greyscale
A sequence represented by SEQ ID NO. 3 is 100% identical to 100% identical to Genbank Accession NZ_CP065265.1 Mycobacteroides abscessus subsp. Bolletii strain G91 chromosome, complete genome, submitted November 21, 2020:
PNG
media_image3.png
434
1566
media_image3.png
Greyscale
A sequence represented by SEQ ID NO. 4 is 100% identical to Genbank Accession MLCG01000006.1 Mycobacteroides abscessus ATCC 19977 WGS, submitted October 12, 2016:
PNG
media_image4.png
205
959
media_image4.png
Greyscale
A sequence represented by SEQ ID NO. 5 is 100% identical to Genbank Accession MLCG01000006.1 Mycobacteroides abscessus ATCC 19977 WGS, submitted October 12, 2016:
PNG
media_image5.png
201
962
media_image5.png
Greyscale
A sequence represented by SEQ ID NO. 6 is 100% identical to Genbank Accession MLCG01000003.1 Mycobacteroides abscessus ATCC 19977 WGS, submitted October 12, 2016:
PNG
media_image6.png
232
794
media_image6.png
Greyscale
A sequence represented by SEQ ID NO. 7 is 100% identical to Genbank Accession JADWXL010000005.1 Mycobacteroides subsp. Massiliense strain GD60.5, whole genome shotgun sequence, submitted November 21, 2020:
PNG
media_image7.png
442
1690
media_image7.png
Greyscale
A sequence represented by SEQ ID NO. 8 is 100% identical to Genbank Accession MLCG01000002.1 Mycobacteroides abscessus ATCC 19977 WGS, submitted October 12, 2016:
PNG
media_image8.png
233
864
media_image8.png
Greyscale
A sequence represented by SEQ ID NO. 9 is 100% identical to Genbank Accession MLCG01000002.1 Mycobacteroides abscessus ATCC 19977 WGS, submitted October 12, 2016:
PNG
media_image9.png
235
787
media_image9.png
Greyscale
A sequence represented by SEQ ID NO. 10 is 100% identical to Genbank Accession MLCG01000002.1 Mycobacteroides abscessus ATCC 19977 WGS, submitted October 12, 2016:
PNG
media_image10.png
228
779
media_image10.png
Greyscale
A sequence represented by SEQ ID NO. 11 is 100% identical to Genbank Accession MLCG01000006.1 Mycobacteroides abscessus ATCC 19977 WGS, submitted October 12, 2016:
PNG
media_image11.png
237
875
media_image11.png
Greyscale
A sequence represented by SEQ ID NO. 12 (nucleotides 6-19) is 100% identical to Genbank Accession MLCG01000006.1 Mycobacteroides abscessus ATCC 19977 WGS, submitted October 12, 2016:
PNG
media_image12.png
234
894
media_image12.png
Greyscale
A sequence represented by SEQ ID NO. 13 (nucleotides 6-13 and 15-20) is 100% identical to Genbank Accession MLCG01000006.1 Mycobacteroides abscessus ATCC 19977 WGS, submitted October 12, 2016:
PNG
media_image13.png
159
792
media_image13.png
Greyscale
A sequence represented by SEQ ID NO. 14 is 100% identical to Genbank Accession MLCG01000006.1 Mycobacteroides abscessus ATCC 19977 WGS, submitted October 12, 2016:
PNG
media_image14.png
237
892
media_image14.png
Greyscale
A sequence represented by SEQ ID NO. 15 is 100% identical to Genbank Accession MLCG01000006.1 Mycobacteroides abscessus ATCC 19977 WGS, submitted October 12, 2016:
PNG
media_image15.png
223
876
media_image15.png
Greyscale
A sequence represented by SEQ ID NO. 16 is 100% identical to Genbank Accession MLCG01000006.1 Mycobacteroides abscessus ATCC 19977 WGS, submitted October 12, 2016:
PNG
media_image16.png
232
878
media_image16.png
Greyscale
Step 2B
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception. The claim does not add a specific limitation other than what is well-understood, routine, and conventional in the field.
Furthermore, the courts have recognized the following laboratory techniques as well-understood, routine, conventional activities in the life science arts when they are claimed in a merely generic manner or as insignificant extra-solution activity including:
i. Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014); and
ii. Hybridizing a gene probe, Ambry Genetics, 774 F.3d at 764, 113 USPQ2d at 1247.
For these reasons, the claims are rejected under section 101 as being directed to patent-ineligible subject matter.
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.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Sharma et al. (A real-time PCR assay for rapid identification of inducible and acquired clarithromycin resistance in Mycobacterium abscessus. 2020. BMC Infectious Diseases 20(1): 1-8, on IDS dated 11/07/2023) in view of CU458896.1 (Genbank Accession CU458896.1, Mycobacterium abscessus ATCC 19977 chromosome, complete sequence, submitted 10/29/2007), Tyagi et al. (US PGPub 20100120048), Macheras et al. (Multilocus Sequence Analysis and rpoB Sequencing of Mycobacterium abscessus (Sensu Lato) Strains. 2011. J Clin Microbiol 49 (2): 491-499), NZ_CP065265.1 (Genbank Accession NZ_CP065265.1, submitted 11/21/2020), and JADWXL010000005.1 (Genbank Accession JADWXL010000005.1, submitted 11/21/2020)
Regarding claim 5, Sharma teaches an assay for detecting genes in Mycobacterium abscessus (abstract) and, further, identifying Mycobacterium abscessus subspecies (p. 2, col. 1). Sharma teaches the assay uses primers and probes (p. 3, col. 2 and Table 2) for erm (41), erm (41) T28, and 23S rrl (Table 2).
23S rrl:
Regarding a forward primer for 23S rrl represented by SEQ ID NO. 8, Sharma teaches a 23S rrl primer “F PrimerR2058” (Table 2), which is 100% identical to a sequence represented by SEQ ID NO:8 as shown below:
PNG
media_image17.png
77
415
media_image17.png
Greyscale
Regarding a reverse primer for 23S rrl represented by SEQ ID NO. 9, Sharma teaches a 23S rrl primer “R PrimerR2058” (Table 2) that binds to the Mycobacterium abscessus rrl gene (CU458896.1 accession, coordinates 464208..1467319) at the positions of the gene shown below (2332-2311):
PNG
media_image18.png
64
438
media_image18.png
Greyscale
For comparison, the sequence of SEQ ID NO. 9 binds to the Mycobacterium abscessus rrl gene (CU458896.1 accession, coordinates 464208..1467319) at positions 2317-2298 of the gene:
PNG
media_image19.png
62
354
media_image19.png
Greyscale
Thus, the primer of Sharma would amplify the same target region as the primer of SEQ ID NO. 9 and is functionally equivalent.
Regarding a molecular beacon probe for detecting the wild type of 23S rrl represented by SEQ ID NO. 10, Sharma teaches the probe “23S_A2058” (Table 2), which is 88.9% identical to SEQ ID NO. 10 at nucleotides 2-19 as shown below:
PNG
media_image20.png
63
348
media_image20.png
Greyscale
It is also noted that, per the specification (p. 7, Table 1) the beginning and end sequences of SEQ ID NO. 10 are arm sequences of the molecular beacon probe.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Sharma and CU458896.1 to arrive at the instantly claimed invention for the detection of 23S rrl. Deciding which primer to use to amplify a given portion of a gene is a design choice. One of skill In the art would have been motivated to design a primer that prevented secondary structure formation and was specific to the gene of interest. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
erm(41) Δ:
Regarding a forward primer for erm(41) Δ represented by SEQ ID NO. 11, Sharma teaches an erm(41) primer “F PrimerTR” (Table 2), which is 100% identical to a sequence represented by SEQ ID NO:11 as shown below:
PNG
media_image21.png
72
390
media_image21.png
Greyscale
Regarding a reverse primer for erm(41) Δ represented by SEQ ID NO. 12, Sharma teaches an erm(41) primer “erm41–4” (Table 1), that binds to the Mycobacterium abscessus rrl gene (CU458896.1 accession, coordinates 2345955..2346476) at the positions of the gene shown (446-427) as shown below:
PNG
media_image22.png
70
358
media_image22.png
Greyscale
For comparison, the sequence of SEQ ID NO. 12 binds to the Mycobacterium abscessus erm(41) gene (CU458896.1 accession, coordinates 2345955..2346476) at positions 470-452 as shown below.
PNG
media_image23.png
67
360
media_image23.png
Greyscale
Thus, the primer of Sharma would amplify the same target region as the primer of SEQ ID NO. 12 and is functionally equivalent.
Regarding a molecular beacon probe for erm(41) Δ represented by SEQ ID NO. 13, Sharma teaches the probe “erm(41)_probe1” (Table 2), which binds to the Mycobacterium abscessus erm(41) (CU458896.1 accession, coordinates 2345955..2346476) gene as shown below:
PNG
media_image24.png
64
408
media_image24.png
Greyscale
For comparison, the sequence of SEQ ID NO. 13 binds to the Mycobacterium abscessus erm(41) gene (CU458896.1 accession, coordinates 2345955..2346476) as shown below:
PNG
media_image25.png
68
327
media_image25.png
Greyscale
Thus, the probe of Sharma would hybridize to the same target (erm(41)) as the probe of SEQ ID NO. 13 and is functionally equivalent. It is also noted that, per the specification (p. 7, Table 1) the beginning and end sequences of SEQ ID NO. 13 are arm sequences of the molecular beacon probe.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Sharma and CU458896.1 to arrive at the instantly claimed invention for the detection of erm(41) delta. Deciding which primer to use to amplify a given portion of a gene is a design choice. One of skill In the art would have been motivated to design a primer that prevented secondary structure formation and was specific to the gene of interest. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
erm(41) T28C:
Regarding a forward primer for erm(41) T28C represented by SEQ ID NO. 14, Sharma teaches the primer “F PrimerE28”(Table 2) binds to the Mycobacterium abscessus erm(41) gene (CU458896.1 accession, coordinates 2345955..2346476) as shown below (positions 388-406):
PNG
media_image26.png
84
376
media_image26.png
Greyscale
For comparison, the sequence of SEQ ID NO. 14 binds to the Mycobacterium abscessus erm(41) gene (CU458896.1 accession, coordinates 2345955..2346476) as shown below (positions 230-242):
PNG
media_image27.png
78
283
media_image27.png
Greyscale
Regarding a reverse primer for erm(41) T28C represented by SEQ ID NO. 15, Sharma teaches the primer “R PrimerE28” (Table 2) which binds to erm(41) (CU458896.1 accession, coordinates 2345955..2346476) at positions 93-75 as shown below:
PNG
media_image28.png
67
374
media_image28.png
Greyscale
For comparison, the sequence of SEQ ID NO. 15 binds to the Mycobacterium abscessus erm(41) gene (CU458896.1 accession, coordinates 2345955..2346476) as shown below (positions 111-92):
PNG
media_image29.png
61
342
media_image29.png
Greyscale
Thus, the probes of Sharma would amplify the same target region of (erm(41)) as the probe of SEQ ID NOs. 14 and 15 and are functionally equivalent.
Regarding a molecular beacon probe for detecting erm(41) T28C represented by SEQ ID NO. 16, Sharma teaches the probe “erm(41)T28” (Table 2), which binds to erm(41) (CU458896.1 accession, coordinates 2345955..2346476) at positions 24-33 as shown below:
PNG
media_image30.png
64
350
media_image30.png
Greyscale
For comparison, the sequence of SEQ ID NO. 16 binds to the Mycobacterium abscessus erm(41) gene (CU458896.1 accession, coordinates 2345955..2346476) as shown below (positions 20-35):
PNG
media_image31.png
70
327
media_image31.png
Greyscale
Thus, the probe of Sharma would hybridize to the same target (erm(41)) as the probe of SEQ ID NO. 13 and is functionally equivalent. It is also noted that, per the specification (p. 7, Table 1) the beginning and end sequences of SEQ ID NO. 16 are arm sequences of the molecular beacon probe.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Sharma and CU458896.1 to arrive at the instantly claimed invention for the detection of erm(41)T28C. Deciding which primer to use to amplify a given portion of a gene is a design choice. One of skill In the art would have been motivated to design a primer that prevented secondary structure formation and was specific to the gene of interest. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Sharma does not teach the probes are molecular beacon probes. However, the probes of Sharma (for example 23S_A2058: 5-6-FAM-CGGCAGGACGAAAAGACCC-BHQ1–3 in Table 2) have the structure of a molecular beacon.
Further, Tyagi teaches a method for identifying the nucleotide sequence of a short region of DNA or RNA using multiple probes for applications such as mutational analysis and pathogen identification (para 3), where probes are preferentially “molecular beacon probes” that form hairpins and have a fluorophore on one arm and a quencher on the other arm (para 8). Tyagi teaches a bacterial gene can be a Mycobacterium gene (para 12). Tyagi further teaches that molecular beacon probes have a number of advantages including assaying multiple targets simultaneously in the same assay and allele discrimination.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Sharma and Tyagi to arrive at the instantly claimed invention. The modification would have entailed designing the probes of Sharma in combination with primers as molecular beacon probes as taught by Tyagi. One would have been motivated by the added benefit of multiplexing potential and improved allele discrimination. In addition, the probes of Sharma share the structural requirements of a fluorophore on one end of the sequence and a quencher on the other end of the sequence. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
MAB2248
Regarding a forward primer for MAB2248 represented by SEQ ID NO. 1, Genbank Accession CU458896.1 (gene at 2,276,108..2,280,484) teaches the complete sequence of the MAB2248 which is 100% identical to SEQ ID NO:1, as shown below:
PNG
media_image32.png
69
352
media_image32.png
Greyscale
Regarding a reverse primer for MAB2248 represented by SEQ ID NO. 2, Genbank Accession CU458896.1 (gene at 2,276,108..2,280,484) teaches the complete sequence of the MAB2248 which is 100% identical to SEQ ID NO:2, as shown below:
PNG
media_image33.png
64
344
media_image33.png
Greyscale
MAB_2830
Regarding a forward primer for MAB2830 represented by SEQ ID NO. 4, Genbank Accession CU458896.1 (gene at complement 2881698..2883032) teaches the complete sequence of the MAB2830 which is 100% identical to SEQ ID NO: 4, as shown below:
PNG
media_image34.png
71
334
media_image34.png
Greyscale
Regarding a reverse primer for MAB2830 represented by SEQ ID NO. 5, Genbank Accession CU458896.1 (gene at complement 2881698..2883032) teaches the complete sequence of the MAB2830 which is 100% identical to SEQ ID NO: 5 at nucleotides 1-6 and 8-20, as shown below:
PNG
media_image35.png
62
356
media_image35.png
Greyscale
Regarding a molecular beacon probe for detecting M. abscessus subsp. abscessus represented by SEQ ID NO. 6, Genbank Accession CU458896.1 (gene at complement 2881698..2883032) which is 100% identical to SEQ ID NO: 5 at nucleotides 1-3 and 5-25, as shown below:
PNG
media_image36.png
69
421
media_image36.png
Greyscale
Neither Sharma nor Tyagi or teach primers or probes to MAB_2248 or MAB_2830.
Macheras teaches analysis to identify Mycobacterium abscessus strains. Macheras teaches that single locus analysis is inaccurate (p. 492, col. 1), and teaches the use of multilocus analysis to increase accuracy of identification (p. 2, col. 1-2).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Sharma, Tyagi, CU458896.1 with Macheras to arrive at the instantly claimed invention. The modification would have entailed designing primers and probes as taught by Sharma and Tyagi using the sequence of CU458896.1. One would have been motivated by teachings of Macheras to analyze additional loci for improved species identification. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Neither Sharma nor Tyagi or CU458896.1 teach a molecular beacon probe for detecting M. abscessus subsp. bolletii represented by SEQ ID NO. 3 or a molecular beacon probe for detecting M. abscessus subsp. massiliense represented by SEQ ID NO. 7.
M. abscessus subsp. Bolletii
Regarding a molecular beacon probe for detecting M. abscessus subsp. bolletii represented by SEQ ID NO. 3, Genbank Accession NZ_CP065265.1 (gene at positions 2263681..2268057) teaches the complete sequence of the M. abscessus subsp. Bolletii genome which is 100% identical to SEQ ID NO:3 nucleotides 7-24, as shown below:
PNG
media_image3.png
434
1566
media_image3.png
Greyscale
It is also noted that, per the specification (p. 7, Table 1) the beginning and end sequences of SEQ ID NO. 3 are arm sequences of the molecular beacon probe.
M. abscessus subsp. massiliense
Regarding a molecular beacon probe for detecting M. abscessus subsp. massiliense represented by SEQ ID NO. 7, Genbank Accession JADWXL010000005.1 (gene at positions 49453..51471) teaches the complete sequence of the M. abscessus subsp. Massiliense genome which is 100% identical to SEQ ID NO:7 nucleotides 1-13, as shown below:
PNG
media_image7.png
442
1690
media_image7.png
Greyscale
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Sharma and Tyagi with NZ_CP065265.1 and JADWXL010000005.1 to arrive at the instantly claimed invention of molecular beacon probes for detecting M. abscessus subsp. bolletii and M. abscessus subsp. massiliense. The modification would have entailed designing a molecular beacon sequence to bind to sequences of M. abscessus subsp. bolletii and M. abscessus subsp. Massiliense. The sequences were well known at the time of filing and one of skill in the art would have been motivated to design a probe that was specific to the species of interest. Sharma was directed to identification of subspecies of Mycobacterium abscessus and choosing a probe to bind a given species chromosome is a design choice considered routine and well-known to one of skill in the art. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JESSICA GRAY whose telephone number is (571)272-0116. The examiner can normally be reached Monday-Friday 8-5 with second Fridays off.
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, WINSTON 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.
/JESSICA GRAY/Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
Prosecution Insights