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 with traverse of species SCG3 and cg054 in the reply filed on 9/23/2025 is acknowledged. The traversal is on the ground(s) that searching the species does not present a burden. This argument has been thoroughly reviewed but was not found persuasive because the different genes do not share the same or corresponding special technical feature as they are structurally and functionally distinct. The requirement is still deemed proper and is therefore made FINAL.
Claims 1-3, and 8-19 are pending. Claims 8, 12, and 16 are withdrawn from consideration as being drawn to non-elected species. Claims 1-3, 9-11, 13-15, and 17-19 are examined herein.
Improper Markush Rejection
Claims 1-3, 9-10, 13-14, and 17-18 are rejected on the basis that they contain an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984).
A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements when the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. See MPEP § 2117 which provides guidance on the analysis of a proper Markush group.
Regarding the rejected claims, the Markush group in question is any alternatively recited combination comprising one or more of the structurally and functionally different genes or markers in the claims.
Regarding “single structural similarity”, the MPEP at 2117 IIA states that a recognized physical, chemical, or an art recognized class is a class where there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention. It is specifically stated that “Thus a Markush grouping is ordinarily proper if all the members for the group belong to a recognized class (whether physical, chemical, or art recognized) and are disclosed in the specification to possess at least one property in common which is mainly responsible for their function in the claimed invention, and it is clear from their very nature or from the prior art that all members possess this property (emphasis added)”.
Therefore, in analysis of whether a claim contains an improper Markush grouping, the MPEP states: A Markush claim contains an “improper Markush grouping” if either (emphasis added): (1) the members of the Markush group do not share a ‘single structural similarity’ or (2) the members do not share a common use.”
In the instant case, the genes and targets do not share any common structural element that is essential to the asserted utility of being associated with DLBCL or PCNSL. The different genes or targets are from different parts of the human genome and are composed of different nucleic acid sequences, and in the case of the genes, encoding functionally different proteins. Furthermore, the prior art does not teach, nor is it clear from their nature, that all of the functionally different genes and targets possess the property of being associated with DLBCL or PCNSL.
For example:
cg05491001 appears to refer to an array target ID located on chromosome 4, with no known function.
SCG3 is a gene which encodes a neuroendocrine secretory protein, and is located on chromosome 15. Diseases associated with SCG3 include parasagittal Meningioma.
The gene encoding GRIK1 is on chromosome 21, and encodes an Ionotropic glutamate receptor that functions as a gated ion channel. Diseases associated with GRIK1 include Temporal lobe epilepsy.
Therefore it is clear that when considering the different genes and targets, even in different combinations, recited in the alternative in the rejected claims, there does not appear to be any common structure related to the function of the genes or targets individually, or any particular combination, let alone an association with DLBCL or PCNSL.
Furthermore, the recited alternative species in the groups set forth here do not share a single structural similarity, as each method relies on detection of different gene combinations. The only structural similarity present is that all the genes are made up of nucleotides. However, comprising nucleotides per se does not support a conclusion that they have a common single structural similarity because the structure of comprising a nucleotide alone is not essential to the common activity of being correlated with DLBCL or PCNSL.
Following this analysis, the claims are rejected as containing an improper Markush grouping.
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 1-3, 9-11, 13-15, and 17-19 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural correlation/law of nature and an abstract idea without significantly more. This judicial exception is not integrated into a practical application and the claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons set forth below.
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. The unpatentability of abstract ideas was confirmed by the U.S. Supreme court in Bilski v. Kappos, 561 U.S. 593, 601 (June 28, 2010) and Alice Corp. Pty. Ltd. v. CLS Bank Int’l, 134 S. Ct. 2347, 2354 (2014). See also Myriad v Ambry, CAFC 2014-1361, -1366, December 17, 2014. The unpatentability of laws of nature was confirmed by the U.S. Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. 66, 71 (2012). “[L]aws of nature, natural phenomena, and abstract ideas” are not patentable. Dia-mond v. Diehr, 450 U. S. 175, 185 (1981); see also Bilski v. Kappos, 561 U. S. at 601 (2010).
Claims Analysis:
As set forth in MPEP 2106, the claims have been analyzed to determine whether they are directed to one of the four statutory categories (STEP 1).
The instant claims are directed to methods and therefore are directed to one of the four statutory categories of invention.
The claims are then analyzed to determine if they recite a judicial exception (JE) (STEP 2A, prong 1) [Mayo Collaborative Services v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1293 (2012), Alice Corp. Pry. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014)].
The claimed invention recites methods for identifying DLBCL or PCNSL by detecting methylation of CpG in different target sequences. However, this recitation is a natural correlation between the presence of methylated CpGs in the targets and DLBCL or PCNSL. With regard to the natural correlation, as in Mayo, the relationship is itself a natural process that exists apart from any human action. Additionally, the recitations of “identifying” in claims 1 and 3, as well as the comparing step in claims 1-3 are directed to abstract ideas because they encompass comparisons and conclusions which can occur entirely within the mind. It is therefore determined that the claims are directed to judicial exceptions.
The claims are then analyzed to determine whether they recite an element or step that integrates the JE into a practical application (STEP 2A, prong 2) [Vanda Pharmaceuticals Inc., v. West-Ward Pharmaceuticals, 887 F.3d 1117 (Fed. Cir. 2018)].
The claims recite steps of detecting the presence of hypermethylated CpG regions however this does not integrate the JE into a practical application because it is a mere data gathering step to use the correlation and does not add a meaningful limitation to the method.
In the absence of steps or elements that integrate the JE into a practical application, the additional elements/steps are considered to determine whether they add significantly more to the JE either individually or as an ordered combination, to “’transform the nature of the claim’ into a patent eligible application” [Mayo Collaborative Services v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1293 (2012), Alice Corp. Pry. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014)] (STEP 2B).
In the instant situation, the steps of “detecting the presence” of more or more hypermethylated regions or hybridizing nucleic acids with generally recited “QM-MSP” primers and probes for the regions set forth in the claims are recited with a high level of generality and do not provide any particular reagents that might be considered elements that transform the nature of the claims into a patent eligible application because no specific elements/steps are recited. This step is not only a mere data gathering step, but the general recitation of detection of known nucleic acids is well understood, routine, and conventional activity (See MPEP 2106.05(d)(II)). Applicant is reminded that in Mayo, the Court found that “[i]f a law of nature is not patentable, then neither is a process reciting a law of nature, unless that process has additional features that provide practical assurance that the process is more than a drafting effort designed to monopolize the law of nature itself." Further "conventional or obvious" "[pre]solution activity" is normally not sufficient to transform an unpatentable law of nature into a patent-eligible application of such a law”. Flook, 437 U. S., at 590; see also Bilski, 561 U. S., at ___ (slip op., at 14) (“[T]he prohibition against patenting abstract ideas ‘cannot be circumvented by’ . . . adding ‘insignificant post-solution activity’” (quoting Diehr, supra, at 191–192)). The Court also summarized their holding by stating “[t]o put the matter more succinctly, the claims inform a relevant audience about certain laws of nature; any additional steps consist of well understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.” Therefore these limitations/steps do not “‘transform the nature of the claim’ into a patent-eligible application.’” Alice, 134 S. Ct. at 2355 (quoting Mayo, 132 S. Ct. at 1297).
When viewed as an ordered combination, the claimed limitations are directed to nothing more than the determination that a natural correlation/phenomena exists. Any additional element consists of using well understood, routine and conventional activity, and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.
Accordingly, it is determined that the instant claims are not directed to patent eligible subject matter.
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.
Claims 1-3, 9-11, 13-15, and 17-19 rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
The claims recite the phrase “detecting the presence of one or more hypermethylated CpG regions”. However, it is not clear if the claim is intended to be directed to detecting hypermethylation in particular regions or to determine the presence of a region that is known to be hypermethylated. In the former situation, analysis of CpG hypermethylation is required, however in the latter situation, detection of a region, such as a gene itself, is encompassed. Accordingly the metes and bounds of the claims are unclear.
The claim recites “one or more genes”, however the designation of cg05491001 and cg25567674 do not appear to be directed any gene, nor is it clear from their recitation as to which nucleic acid sequence is encompassed by their recitation. While the specification appears to refer to them in the context of Array ID numbers, the specification does not teach which “gene” is encompassed by this designation. Furthermore, the reference to a particular chromosome position is indefinite without a clear definition as to what the chromosomal positions are in reference to. For example, as the genome has been updated over time, chromosomal positions for any particular nucleotide allele change as information is added or deleted from the chromosomal sequences. Therefore, the metes and bounds of the terms are unclear. Likewise, with regard to claims 2 and 3, without a clear indication as to the genomic regions encompassed by the recitation, the metes and bounds of primers and probes to these targets is also unclear.
The claims also refer to cg054 and cg255, however it is not clear if this is merely a shorthand designation for cg05491001 and cg25567674, respectively, or whether they refer to a structurally different target.
Claim 17 is indefinite in the recitation of “wherein at step identifying” as this is not grammatically complete. As such, metes and bounds of the recited limitations are unclear.
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 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by GSE92676 (NCBI, GEO, 2017).
GSE92676 teaches the methylation analysis of PCNSL samples using the Infinium HumanMethylation 450 BeadChip. As evidenced by the teachings of the specification, the Infinium HumanMethylation 450 BeadChip contains oligonucleotides for analysis of CpG of the claimed targets (see specification paragraph 0129). Furthermore, as evidenced by the specification, the data in this assay was used to test the performance of the claimed markers, therefore this assay inherently detected hypermethylation of the claimed targets. With regard to the recited element of “identifying the CpG regions… as hypermethylated”, this does not appear to be an active step requiring comparison but rather appears to define the metes and bounds of the relative limitation of encompassed by the term “hypermethylated”. Accordingly, the claim is anticipated by the prior art because the prior art appears to teach the active step recited in the claims.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to examiner Jehanne Sitton whose telephone number is (571) 272-0752. The examiner is a hoteling examiner and can normally be reached Mondays-Fridays from 8:00 AM to 2:00 PM Eastern Time Zone.
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/JEHANNE S SITTON/Primary Examiner, Art Unit 1682