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 .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The IDS received on September 5, 2023 is proper and is being considered by the Examiner.
NPL #3 (Bagley et al.) was missing a proper publication information. The Office has filled in the necessary information.
Drawings
The drawings received on September 5, 2023 are acceptable.
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 1-6, 8-14, and 17 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 is indefinite for the following reasons.
Claim is directed to the preamble of diagnosing glioma and/or discrimination of a glioma with a mutation in the IDH1 gene, but the claim only contains an active step of “measuring the expression” of the three recited miRNAs. The wherein clause is a simple recitation of their natural correlation and therefore, the claim does not end with an active step that agrees back with the intent of the preamble. While minor details are not required in method/process claims, at least the basic steps must be recited in a positive, active fashion. See Ex parte Erlich, 3 USPQ2d, p. 1011 (Bd. Pat App. Int. 1986);
Claim recites an alternative embodiment of in vitro discrimination of a glioma with a mutation in IDH1 gene from a glioma with IDH1 wildtype gene, but the actual steps do not recite any steps that allow for this determination to be made; and
Claim employs “comprising or consisting of” in conjunction with another “and/or” alternative (for diagnosis vs discrimination) as a combination in a in a single claim. A combination of such and/or alternatives make the single claim embodiment vague and indefinite in determining the metes and bounds of the claim.
Claims 3 and 17 recite a Markush group of elements without a proper conjunction, thereby failing to properly define the group. For the purpose of prosecution, the conjunction, “and” has been assumed to be present between the members “urine sample” and “cerebrospinal fluid sample.”
Claims 6 and 11-14 recite limitation followed by the phrase, “such as”. Such a usage renders the limitation indefinite because it is unclear whether it is actively required or not. Removal of the phrase is required.
Additionally, claims 6 and 11-14 recite the limitations which are capitalized, rendering the limitations indefinite in whether they are trademarked techniques. As well, the term, “Next Generation Sequencing” is indefinite because what is considered “next generation” is ever evolving over time.
Claims 1-6 and 9-14 are indefinite by way of their dependency on claim 1.
Claim 8 is indefinite for the same reasons as discussed above, reciting multiple “and/or” combinations in a single claim.
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 1-6 and 8-14 are rejected under 35 U.S.C. 101 because the claimed invention is directed to the judicial exception (i.e., product of nature and natural phenomenon) without significantly more. The claims recite: 1) a natural correlation which exits between glioma and microRNA molecules and their levels; and 2) a combination of nucleotide sequences which are found in nature. This judicial exception is not integrated into a practical application because: 1) the natural correlation captured between the glioma and microRNA levels; and 2) the sequences found in nature are recited in a highly generic nature and fail to add a meaningful limitation to the judicial exceptions.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception based on the analysis under the current Patent Eligibility Guidelines (herein, “PEG”) as discussed below.
The rejection has two parts: A) a Kit; and B) a method.
Step 1 Inquiry under PEG
Step 1 inquiry under Patent Eligibility Guidelines (herein, “PEG”) determines whether or not the claimed invention is drawn to one of the recognized statutory classes of invention. Claims 1-7 and 9-14 satisfy the present inquiry as being drawn to a method; and claim 8 satisfy the inquiry as being drawn to a product.
Step 2A Inquiry under PEG
A recently revised PEG now performs step 2A inquiry under a 2-prong analysis, and the subject claims analyzed accordingly as follows:
Prong 1:
Prong-1 inquiry under step 2A determines whether the claims recite an abstract idea, a law of nature, or a natural phenomenon. As stated above, claims 1-7 and 9-14 recite a natural correlation which exist between glioma and the levels of microRNA molecules, miR-1-3p, miR-26-1-3p, and miR-487b-3p; and claim 8 simply captures the sequence of the miRNAs which exist in nature.
Therefore, claims recite a judicial exception.
Prong 2:
Prong-2 inquiry under step 2A determines whether or not the claims recite additional elements that integrate the judicial exception into a practical application in a manner that imposes a meaningful limit on the judicial exception.
A – The Kit:
Claim 8 recites a kit comprising primer pairs and/or probes that detects miR-1-3p, miR-26a-1-3p, and miR-487b-3p. While claim 8 recites the intent of the kit in the form of “diagnosing glioma” or “discriminating” IDH1 mutant from a wildtype counterpart, the intent does not physically alter the generically recited “primers and/or probes” which simply comprise nucleotide bases. Therefore, the claim does not recite any additional elements so as to integrate the judicial exception to impose a meaningful limit.
As to the primers and probe being a judicial exception, they are deemed a collection of nucleotide sequences that perfectly complements the microRNA sequences or an identical sequence as that of the miRNA sequences (if miRNA are converted to cDNA, and a primer/probe hybridizes thereto, then the primer/probe sequences are identical to miRNA).
To this end, it has long been settled that a combination of judicial exceptions does not render that combination patent eligible.
In Ambry, the court held that a primer pair [as well as probes, analogously as they are all nucleotide sequences] direct to an otherwise naturally existing gene were not patent eligible:
“The primer before us are not distinguishable from the isolated DNA found patent-ineligible in Myriad and are not similar to the cDNA found to be patent-eligible” (page 7)
The court found that the primers were not patent eligible because they contained the “identical sequence of the BRCA sequence directly opposite to the strand to which they are designed to bind” and that they were structurally identical to the ends of DNA strands found in nature” (page 7).
For example, in Ambry (citation omitted), one of the patents under suit was U.S. Patent 5,747,282, with specific claims 16 and 17:
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Claims 16 and 17 of the ‘282 patent was drawn to a pair of primers (see reproduced claim 16):
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Upon consideration of these pair of primers, the court stated the below:
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Also in Myriad (citation omitted), the court stated, “neither naturally occurring compositions of matter, nor synthetically created compositions that are structurally identical to the naturally occurring compositions, are patent eligible” (Id. At 2117)
Based on the precedence discussed above, the claimed kit comprising multiple primers and/or probes set of primers embraces fragments of naturally existing nucleotide molecules and even though may be presented as a collection, are nevertheless “not distinguishable” from the naturally exiting molecules and therefore, are deemed patent eligible.
B – The Method (Claims 1-6 and 9-14):
The claims directed to method is based on the natural correlation in the level of the three specifically recited microRNA molecules: miR-1-3p, miR-26a-1-3p, and miR-487b-3p and their correlation to glioma:
“it has now been found that glioma can be diagnosed in vitro by measuring the expression levels of combined serum miRNAs miR-1-3p, miR-26a-1-3p and miR-487b-3p in comparison to the expression levels thereof in healthy subjects.” (page 4, Specification)
Therefore, the claims recite and capture a judicial exception.
While claim 1 recites additional texts in the form of a “wherein clause”, the additional texts are simply reciting the inherent property of the miRNA expression levels and therefore, in sum, claim 1 does not recite any meaningful limitation other than this judicial exception itself.
Claims 2 and 3 recite the source of the biological sample. However, the judicial exception is present in the biological sample and the method of utilizing a sample is generically recited with no apparent innovation to the actual sample collection being performed. Therefore, simply identifying the source from which the judicial exception is observed also fails to add a meaningful limitation.
Claims 4-6 and 9-14 recite the additional limitation of the method being carried out using “one or more synthetic sequences complementary to at least a part of” the recited microRNA molecules; said synthetic sequences being in the form of a primers and/or probes; or utilizing PCR, digital PCR etc.
However, these additional elements are recited with highly general language which amounts to no more than “applying” the judicial exception.
As explained by the Supreme Court, in order to transform a judicial exception into a patent-eligible application, the additional element or combination of elements must do ‘more than simply stat[e] the [judicial exception] while adding the words ‘apply it’”. Alice Corp. v. CLS Bank, 573 U.S. __, 134 S. Ct. 2347, 2357, 110 USPQ2d 1976, 1982-83 (2014) (quoting Mayo Collaborative Servs. V. Prometheus Labs., Inc., 566 U.S. 66, 72, 101 USPQ2d 1961, 1965). Thus, for example, claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible. Alice Corp., 134 S. Ct. at 2358, 110 USPQ2d at 1983. See also 134 S. Ct. at 2389, 110 USPQ2d at 1984 (warning against a § 101 analysis that turns on “the draftsman’s art”) (MPEP 2106.05(f))
Recitation of judicial exception while employing a highly general language of using means which have been well-known to be employed, does not meaningfully limit the judicial exception.
Step 2B Inquiry under PEG
Step 2B inquiry of the PEG determines whether or not additional elements are provided and whether such elements amount to significantly more than the judicial exception in the claims.
A – The Kit:
As discussed above, the claim directed to the kit does not recite any additional elements and therefore fail to add any meaningful limitation.
B – The Method:
The additional elements recited for the method claims are in the form of the sample from which the judicial exception is observed. However, as discussed above, there is no apparent innovation to the sample being provided. Therefore, simply identifying the source from which the judicial exception is observed does not add any meaningful limitation to the judicial exception itself.
As to the claims that recite additional limitations in the form of using “one or more synthetic sequences complementary to at least a part of” the recited microRNA molecules; said synthetic sequences being in the form of a primers and/or probes; or utilizing PCR, digital PCR etc., the use of such primers and/or probes for determining the levels of microRNA molecules or nucleic acid molecules via real-time PCR, or via microarray has been well-established in the art of molecular diagnostics and therefore deemed to be no more than an application of a well-known, routine and conventional means to apply the judicial exception, failing to meaningfully apply the judicial exception.
Therefore, the present claims lack patent eligibility.
Claim Rejections - 35 USC § 102
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.
Claim 8 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Agilent Product Note (herein, “Agilent”, 2009, pages 1-4).
Claim 8 is directed to a kit directed to an embodiment of comprising three probes for miR-1-3p, miR-26a-1-3p, and miR-487b-3p, with the proviso that the kit does not comprise any other primers pair for detecting any other natural miRNAs.
The intended usage of the kit being for glioma diagnosis or discrimination of IDH1 mutant does alter the physical property of the kit itself.
In In re Haller (C.C.P.A. 73 USPQ 403, April 1997), the court expressed that in order for the article or composition of matter (i.e., product) be patentable, such must not only be useful and involve invention, but it also must be new. The court stated that if the product has no novelty, a patent cannot be granted on it regardless of its intended use (at 404). The court, citing In re Thomas J. Dixon, 18 C.C.P.A 711, 44 F.2d 881, 7 USPQ 209; In re Robert C. Russell, 18 C.C.P.A. 1184, 48 F.2d 668, 9 USPQ 181; In re Reeves, 20 C.C.P.A. 767, 62 F.2d 199, 16 USPQ 110; In re McKee, 20 C.C.P.A. 1018, 64 F.2d 379, 17 USPQ 293; and In re Hansen, 33 C.C.P.A. 979, 154 F.2d 684, 69 USPQ 332, expressed that, “[I]t is well settled that the application of particular printed matter to an old article cannot render the article patentable.” (at 405), concluding that the mere labeling of an old composition as an insecticide does not make it a new of different composition within the meaning of the patent statutes, the situation of which is analogous as that of In re Thuau, which attempted to patent an old product on the basis of a statement that it is intended for a new use. The court continued to express that such statement of intended use appearing in the claim or in a label on the product was immaterial so far as the question of patentability was concerned (at 405).
Since the miRNA microarray only comprises probes and not primers, the kit of microarray sold by Agilent meets this embodiment of the claim.
As well, the miRNA microarray of Agilent is disclosed as having approximately 15,000 features with 470, 723, and 866 miRNA probes (see miRNA Microarray Specifics & Ordering Details on page 4).
Therefore, absent evidence to the contrary, the Agilent’s kit of miRNA microarray comprising the probes of such numbers would necessarily comprise the probes to the three recited miRNAs with no primers to any other miRNAs.
As pointed out in In re Mott, 190 U.S.P.Q. 536 (CCPA 1975), "Claims must be given broadest reasonable construction their language will permit in ex parte prosecution, and applicant who uses broad language runs the risk that others may be able to support the same claim with a different disclosure."
Conclusion
Claims 1-6, 8-14, and 17 are rejected.
Claims 15 and 16 are allowable.
Claims 15-17 satisfy the patent eligibility requirement under 35 U.S.C. 101 because the claim is directed to a method of treatment of a glioma, wherein the determination is based on the judicial exception between the levels of the three specific miRNA markers (i.e., miR-1-3p, miR-26a-1-3p, and miR-487b-3p) and performing a specific treatment based on the diagnosis rendered.
Claims 1-6 and 9-17 are free of prior art because the prior art is silent on the use of the specific combination of the three specific miRNA markers and their levels for diagnosis of gliomas from subjects.
The specification combination appeared to provide a synergistic output over the usage of single markers alone or other potential combinations:
“Different combinations of the selected miRNAs have been subsequently considered to evaluate if they could provide an improvement of the diagnostic accuracy. As shown in Fig. 4A and B, ROC curves analyses indicate that the combination of miR-1-3p/miR-26a-1-3p/miR-487b-3p led to a substantial improvement in the diagnostic performance (AUC 0.9), compared to the single miRNAs of the signature (page 14)
Inquiries
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Young J. Kim whose telephone number is (571) 272-0785. The Examiner can best be reached from 7:30 a.m. to 4:00 p.m (M-F). The Examiner can also be reached via e-mail to Young.Kim@uspto.gov. However, the office cannot guarantee security through the e-mail system nor should official papers be transmitted through this route.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Gary Benzion, can be reached at (571) 272-0782.
Papers related to this application may be submitted to Art Unit 1681 by facsimile transmission. The faxing of such papers must conform with the notice published in the Official Gazette, 1156 OG 61 (November 16, 1993) and 1157 OG 94 (December 28, 1993) (see 37 CFR 1.6(d)). NOTE: If applicant does submit a paper by FAX, the original copy should be retained by applicant or applicant’s representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED, so as to avoid the processing of duplicate papers in the Office. All official documents must be sent to the Official Tech Center Fax number: (571) 273-8300. Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-1600.
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/YOUNG J KIM/Primary Examiner
Art Unit 1637 January 26, 2026
/YJK/