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 .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12/15/2025 has been entered.
Applicant's election with traverse of Group II and the species of primer pair 1 (SEQ ID No. 1 and 2) and SEQ ID No. 7 in the reply filed on 4/14/2025 is acknowledged and has been previously been made final.
Claims 1-26 are pending.
Claims 1-18 have been withdrawn as being drawn to a nonelected invention. It is noted that claims 21 and 26 is withdrawn based upon the election of the species of Primer pair 1. Should the species elected be in condition for allowance, the examiner will move on to the next species.
The following rejections for claims 19-20, 22-25 are maintained. Response to arguments follows. It is noted that claim 21 is withdrawn as being dependent on claim 26 which is directed to a species that has not been elected.
This action is NONFINAL.
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 19-20, 22-25 are rejected under 35 U.S.C. 101 because the claimed invention is directed to product of nature without significantly more. The claim(s) recite(s) primers and probes which are products of nature as these oligonucleotides represent fragments of naturally occurring nucleic acids. This judicial exception is not integrated into a practical application. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the structures do not include anything other than a component that is found in nature.
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. The unpatentability of natural products was confirmed by the U.S. Supreme Court in Association for Molecular Pathology v. Myriad Genetics, Inc., 133 S. Ct. 2107, 2116, (2013).
The claimed invention is directed to naturally occurring fragments of a naturally occurring nucleic acids as the claims encompass fragments of the sequences which would include naturally occurring BARHL2. Further, the claims encompass naturally occurring water, bisulfite (reagents). There is no indication that these regents are different from those found in nature. This judicial exception is not integrated into a practical application because it conveys the same genetic information as the genes itself. These molecules are not patent eligible, whether isolated or not, pursuant to the Supreme Court decision in Association for Molecular Pathology v. Myriad Genetics Inc., US (June 13, 2013). The Supreme Court has made clear "separating [DNA] from surrounding genetic material is not an act of invention" Myriad, 133 S. Ct. at 2117. This judicial exception is not integrated into a practical application because they convey the same genetic information as their naturally occurring counterparts. In Myriad v. Ambry CAFC 2014-1361,1366, December 17, 2014, the CAFC further (regarding a claim directed to a pair of primers) stated “In fact, the naturally occurring genetic sequences at issue here do not perform a significantly new function. Rather, the naturally occurring material is used to form the first step in a chain reaction—a function that is performed because the probe or primer maintains the exact same nucleotide sequence as the relevant portion of the naturally occurring sequence. One of the primary functions of DNA’s structure in nature is that complementary nucleotide sequences bind to each other. It is this same function that is exploited here—the probe hybridizes to its complementary nucleotide sequence. Thus, just as in nature, probes utilize the innate ability of DNA to bind to itself.”
Response to Arguments
The reply traverses the rejection. A summary of the arguments is made below with response to the arguments following. The reply asserts that the applicant disagrees (p. 1) but does not provide any specific arguments.
These arguments have been reviewed but have not been found persuasive.
The claims still encompass a structure that is identical to a region of the naturally occurring gene. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the structures do not include anything other than a component that is found in nature. The mere fact that the primers are specific fragments, does not change the fact that these are still structures that are identical to a region of the naturally occurring gene. An argument that a primer would perform more than just hybridization, but require steps to “set the stage for PCR” is not sufficient as these components still bind to a section of identical nucleotides and therefore is functionally similar. With regard to bisulfite and a primer pair would not be routine and conventional, it is unclear how this arguments alters the rejection. First it is noted that bisulfite reagents and primer structures in the claim are both naturally occurring. Second the combination of these in a structure does not alter the structures of either to be something in addition to the naturally occurring structures.
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.
Claim(s) 19-20, 22-25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Liebenberg et al. (US Patent Application Publication 2009/0203011 August 13, 2009) in view of Hogan (US patent 6773882 Aug 10, 2004) , Diffenbach (PCR methods and Applications (1993) volume 3, pages S30-S37) and Roux et al (PCR Methods and Applications (1995) volume 4, pages s185-s194).
With regard to claims 19, Liebenberg et al. teaches an isolated nucleic acid (SEQ ID NO. 138) that encompasses primer pair 1. SEQ ID NO. 1 of primer pair 1 is identical to nucleotides 3683-3708 of Liebenberg et al. SEQ ID No. 138. SEQ ID NO. 2 of primer pair 1 is identical to nucleotides 3788-37664 of Liebenberg et al. SEQ ID No. 138. Liebenberg et al. teaches designing primers and probes of these regions (para 19-23). However, Liebenberg et al. does not specifically teaches SEQ ID NO. 1 or 2 as primers.
With regard to claim 20, 23, these claims do not require any other structures other than the structures of claim 19. As Liebenberg et al. teaches detection in lung adenocarcinoma and squamous cell carcinoma cancer patients (para 18, 9-21), the structures of Liebenberg et al. would be capable of using in the functionality.
With regard to claim 22, Liebenberg et al. teaches probes (para 19-23). SEQ ID NO. 7 is identical to nucleotides 3720-3748 of Liebenberg et al. SEQ ID No. 138.
With regard to claims 24-25, Liebenberg et al. teaches reagents for extracting DNA from tissue samples and using bisulfite (para 33, 48 and 92-94).
However, Liebenberg et al. does not specifically teaches SEQ ID NO. 1 or 2 as primers.
With regard to claims 19, 22, Diffenbach and Roux et al. teach constraints to designing oligonucleotides. Diffenbach teaches parameters and principles of promoter design include primer length, terminal nucleotide, GC content, melting temperature, PCR product length, and placement of target sequence (s30-s34). Diffenbach teaches PCR software was known (s35).
Roux teaches optimization of PCR by the presence of enhancing agents, Mg2+, annealing temperature, primer design, cycle number, hot start PCR (s185-s194).
The art of making probes from known target regions is well known in the art. Hogan et al. teaches the use of specific probes to amplify the 16S region of bacteria.
With regard to claims 19,22, Hogan et al. provides guidance for the selection of probes.
"Once the variable regions are identified, the sequences are aligned to reveal areas of maximum homology or 'match'. At this point, the sequences are examined to identify potential probe regions. Two important objectives in designing a probe are to maximize homology to the target sequence(s) (greater than 90% homology is recommended) and to minimize homology to non-target sequence(s) (less than 90% homology to non-targets is recommended). We have identified the following useful guidelines for designing probes with the desired characteristics.
First, probes should be positioned so as to minimize the stability of the probe: nontarget nucleic acid hybrid. This may be accomplished by minimizing the length of perfect complementarily to non-target organisms, avoiding G and C rich regions of homology to non-target sequences, and by positioning the probe to span as many destabilizing mismatches as possible (for example, dG:rU base pairs are less destabilizing than some others). Second, the stability of the probe: target nucleic acid hybrid should be maximized. This may be accomplished by avoiding long A and T rich sequences, by terminating the hybrids with G: C base pairs and by designing the probe with an appropriate Tm. The beginning and end points of the probe should be chosen so that the length and %G and %C result in a Tm about 2-10 ºC higher than the temperature at which the final assay will be performed. The importance and effect of various assay conditions will be explained further herein. Third, regions of the rRNA which are known to form strong structure inhibitory to hybridization are less preferred. Finally probes with extensive self complementarity should be avoided." (See Column 6 lines 66-67 and Column 7 lines 1-29).
Hogan et al. teaches, "while oligonucleotide probes of different lengths and base composition may be used, oligonucleotide probes preferred in this invention are between about 15 and about 50 bases in length" (see Column 10, lines 13-15). Hogan et al teaches labels that fluoresce can be used (column 12 lines 20-40).
Designing oligonucleotides to hybridize to specific targets, which are equivalents 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 Diffenbach and Roux and Hogan who teach selection of oligonucleotides that function as probes. 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 tested oligonucleotides from BARHL2 taught by Liebenberg et al. to obtain additional oligonucleotides that function to detect BARHL2 and identify oligonucleotides with improved properties for such detection. Thus, for the reasons provided above, the ordinary artisan would have designed additional oligonucleotides using the teachings in the art at the time the invention was made including oligonucleotides that comprise the recited sequences. As such the recited oligonucleotides are obvious over the cited prior art, absent secondary considerations
Response to Arguments
The reply traverses the rejection. A summary of the arguments is made below with response to the arguments following. The reply asserts that the applicant disagrees (p. 1) but does not provide any specific arguments.
The reply does not provide any specific arguetmsn. Prior arguetmsn asset a difference between cfDNA and genomic DNA, however, this arguetmsn does not provide that there is any difference in the claimed sequence structures and the teaching of the 35 USC 103. Furthermore, the arguetmsn does not point to any secondary considerations for the claimed structure.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE D SALMON whose telephone number is (571)272-3316. The examiner can normally be reached 9-530.
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, Wu Cheng (Winston) Shen can be reached on 5712723157. 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.
/KATHERINE D SALMON/Primary Examiner, Art Unit 1682