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 .
Application Status
The amended claims were filed on 5/19/2026, such that claims 53, 55, 56-66, and 125-140 are under examination in this Office action. Claims 1-52, 54, 67-124 were cancelled. The restriction of 12/4/2023, required species election for claims 53 and 125, where claims 53 and 125 are generic. Applicant responded on 1/30/2024, electing the transcript of N. gonorrhoeae gene with locus tag NG01812 and encoding major outer membrane protein (porB) where claims 53-66 and 125-130 encompassed the elected species.
Any rejection or objection not reiterated herein has been overcome by amendment.
Applicant’s amendments and arguments have been thoroughly reviewed but are not persuasive to place the claims in condition for allowance for reasons that follow.
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 disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (in mark-up specification of 8.23.21, at least at the following: [0040], [0064], [00107], [00117], [00301], Pg. 95 end of page, at ref 34).
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.
The disclosure is objected to because of the following informalities:
Trademarks (see below).
The use of the term Nanostring in the Specification including at least at [0056] and [00112], is a trade name or mark used in commerce, that has been noted in this application. The term, and any other trade mark or name, 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.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claims 139 and 140 are 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 pre-AIA the applicant, regards as the invention.
Claims 139 and 140 are indefinite in the recitation of “…wherein said transcript is a genetic variant of N. gonorrhoeae genes having a nucleotide sequence with at least 80% identity with any one of ” SEQ ID NO:28 -108 or 112-141. Without further clarity, it is not possible to establish the metes and bounds of these two claims, for a few reasons.
First, re: “said transcript is a genetic variant of said N. gonorrhoeae genes…” an issue that arises is that it is not conventional to refer to a transcript (which is an RNA molecule) as a genetic variant, since typically genetic variants differ in an aspect of their DNA sequence (such as a mutation, insertion, deletion, single nucleotide polymorphism, inversion, and more). So, the claim could intend for the transcript to vary (e.g. that there are mRNA variants), or it could intend instead for a gene to vary, or possibly both, but as written ‘genetic variant’ does not provide the clarity necessary to establish metes and bounds of the claims.
Next, the claim recites that “the transcript is a genetic variant of said N. gonorrhoeae genes having a nucleotide sequence with at least 80% identity with any one of SEQID
NO:28 to SEQ ID NO: 108 or SEQ ID NO: 112 to SEQ ID NO: 141.” Twenty-two locus tags are recited in claim 53 and 125. Thus, it is unclear how “said” genes comprise vastly more than 22 sequences. Further re: the genes, having a nucleotide sequence of the given SEQID NOs recited, it is shown below that not all of the SEQ ID NO’s recite DNA sequences. For example, SEQ ID NO: 33, 36, 39, 132, to name a few, disclose RNA sequences. SEQ ID NO: 33 is below, followed by SEQ ID NO:36, which self-indicate as RNA and depict “u’s” in sequences, indicative of RNA.
PNG
media_image1.png
180
504
media_image1.png
Greyscale
SEQ ID NO: 36
PNG
media_image2.png
246
511
media_image2.png
Greyscale
Therefore, 80% or more identity, as related to the disclosed sequences does not follow, when sequences may be DNA or RNA, and as such are not all genes.
Proper correction is required.
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 53, 55-58 are rejected under 35 U.S.C. 101 because the claimed invention is directed to the judicial exception of a law of nature or a natural phenomenon, and an abstract idea without significantly more. The judicial exception is not integrated into a practical application and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for reasons that follow.
The unpatentability of laws of nature was confirmed by the U.S. Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., No. 10-1150 (March 20, 2012).
The unpatentability of abstract ideas was confirmed by the U.S. Supreme court in Bilski v. Kappos, No. 08-964, 2010 WL 2555192 (June 28, 2010) and in Alice Corp. v. CLS Bank Int’l, 134 S. Ct. 2347, 2354 (2014).
Applicant’s attention is directed to MPEP 2106 “Patent Subject Matter Eligibility.”
Re: Step 1, the claims are directed to the statutory category of a process (a method).
Re: Step 2A, prong I, the claims are directed to a judicial exception, here a law of nature, or natural correlation between the transcript expression value of ’treated’ marker N. gonorrhoeae after contact with antibiotic for a period of time less than that of doubling time of the microbe and expression downshift, relative to untreated marker expression, and susceptibility to antibiotic of N. gonorrhoeae in sample. Stated more succinctly, the correlation of interest is between the marker transcript expression that downshifts rapidly, faster than microbe doubling time, and susceptibility of N.gonorrhoea sample to antibiotic.
Re: Step 2A, prong II, the claims recite the additional elements of the quantitative detection of transcript of RNA with antibiotic susceptibility and of comparing expression values to detect downshift in expression. Claim 55 articulates simply that untreated marker expression value is a control expression value and claim 56 repeats the procedural steps of claim 53 as relevant to control. Claim 57-58 recite normalization, as will be shown, a known conventional step for RNA transcript analysis.
The additional elements recited above do not integrate the judicial exception because the elements do not constitute significantly more, given the data below in sum recognizing well-understood, routine and/or conventional knowledge:
Quantitative detection of transcript as recited above is well-known as evidence below will show, and comparing expression values to detect downshift in expression is considered a mental process and as such, constitutes insignificant extra solution activity. Normalization is also known as discussed further below.
The quantitative detection of transcript is referenced in the specification in a manner indicative that such methods are generally well-understood, as is use of controls: The specification recites first that “the selected marker gene is therefore differentially expressed in the treated samples of the susceptible isolate or specimen compared with the resistant isolate or specimen, as will be understood by a skilled person.” (Specification, [008]), and ”Antibiotic susceptibility testing (AST) can be carried out as will be understood by a persons skilled in the art” [0038], where “differential expression of a gene can be detected in a microorganism following a different [difference] in one or more of these conditions as will be understood by a skilled person…Accordingly, differential expression analysis requires that gene expression values detected under the different conditions be compared and therefore that the expression of the genes be quantitatively detected.” ([0052]). Further, “quantitative detection of expression of a gene can be performed with various techniques such as by RNA-seq, qPCR, digital PCR and isothermal techniques such as LAMP … for RNA-seq data and additional nucleic acid quantification techniques identifiable to a skilled person…. In…such methods quantitative detection of expression of a gene is commonly combined with a reverse transcription step to convert the RNA sequence into a cDNA sequence which can be quantified by methods described herein and/or identifiable by a skilled person. ([0056]). Further, “An exemplary way to quantitatively detect differential expression…. used as a criterion to select…differentially expressed genes as will be understood by a person skilled in the art.” ([0055]). Finally, “The control transcripts and related method of identification described to identify markers…will be understood by a skilled person.” ([00217]).
References are cited in the specification, including the well-referenced overview of Conesa et al. (A survey of best practices for RNA-seq data analysis, Genome biol 2016, 17:13), addressing the important aspects of transcript identification and quantification of gene expression using RNA-seq, including differential gene expression analysis (Pg 1, left col para 1, Pg 4, end left to right col, and throughout).
Similarly, claims 57 and 58 address normalization. The specification references “normalization between” (cells in treated/control sample) “calculated from other measurements such as optical density” (and other methods recited) as will be understood by a skilled person.” ([0091]) and similarly “…DNA can be measured in the control and treated sample and used as normalization DNA measurement, as will be understood by a skilled person. ([00108]). Further, Nieto (BMC Mol Biol 2009, 10:63) had addressed gene expression and transcriptome analysis (Pg 1 para 1) and the need for normalization (Abstract) including through the use of one or more other genes and relative expression comparisons (Pg 2 right col, 2nd-3rd full para, Pg 5. Left col, final para and throughout). Further, Evans (Briefings in Bioinf, Feb 2017, 19 776-792) reviewed RNA-seq normalization used for comparative expression measurement work (Abstract).
Re: Step 2 B The additional elements do not amount to significantly more than insignificant extra solution activity in combination with the judicial exception since the claims employ well-understood, routine and conventional activity as described above, and do not provide additional elements that amount to an inventive concept such as functional improvements to computer functionality or technology, or applying the exception using a particular machine, or effecting a particular transformation of an article to a different thing. Rather, the activities are considered well-understood, routine, conventional activity (MPEP 2106.05).
Claims 53, 55-58 therefore constitute judicial exceptions that not integrated into practical application and as such are considered to be judicial exception without significantly more, making them patent ineligible under 35 § U.S.C. 101.
Response to Arguments
Addresses eligibility under 35 § U.S.C. 101, applicant points to amendments to claim 53 that now recite “contacting of the sample with an antibiotic for a time period shorter than a doubling time of the N. gonorrhoeae to obtain an antibiotic treated transcript expression value’. Applicant notes that the resulting combination of steps provide an ordered combination of features that integrated the natural correlation between expression of marker and antibiotic susceptibility into a rapid replication-independent molecular assay thus improving the technological field of testing and argues the claims should be eligible under 2A prong 2. In response, as addressed in the present Office action, the correlation involves detection of transcript after antibiotic contact for a time less than the doubling time of the bacteria, to obtain treated expression value of the susceptibility marker, where the period shorter than a doubling time is an agent that selects for what are natural markers that respond to the selection criterion of rapid evaluation, and thus constitute part of the judicial exception. Prong 2A 2 addresses additional features, which do not rise to that which is more than well understood activity as described above. The features recited beyond the judicial exception, where the judicial exception includes the rapid transcript responders, comprise transcript detection which is considered routine or insignificant activity and does not rise to the level of obviating the 101 under Prong 2B (also discussed in this Office action above).
Conclusion
Claims 53, 55-58, 139-140 are rejected.
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 Lisa Horth whose telephone number is (703)756-4557. The examiner can normally be reached Monday-Friday 8:30-4:30 EST.
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, Neil Hammell can be reached at (571) 270-5919. 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.
/LISA HORTH/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636
Prosecution Insights