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
The species election set forth in the office action dated 1/28/2026 is withdrawn.
Status of Claims
Currently, claims 1-24 are pending in the instant application.
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 11-16 and 19-23 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. The judicial exceptions are 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 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).
In Alice Corp, the Supreme Court reiterated the two step test devised in Mayo to determine patent eligibility for claims. “First, we determine whether the claims at issue are directed to one of those patent-ineligible concepts. If so, we then ask, ‘[w]hat else is there in the claims before us?’ To answer that question, we consider the elements of each claim both individually and ‘as an ordered combination’ to determine whether the additional elements ‘transform the nature of the claim’ into a patent-eligible application.” 134 S. Ct. at 2355 (citing and quoting 566 U.S. at 72-73, 76-78).
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 claims were 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 claims were 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)]. In the absence of a step(s) or element(s) that integrate the JE into a practical application, the additional elements/steps have been considered to determine whether they add significantly more to the JE (STEP 2B) [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)]. It was found that the present claims fail to meet the elements required for patent eligibility.
The instant claims are directed to diagnostic methods and therefore are directed to one of the four statutory categories of invention.
The claimed invention recites methods of determining if a human subject has a polymorphism in a 2:107,510,000-107,540,000 locus. However, this set is directed to an abstract idea because it encompasses reading a report. It is therefore determined that the claims are directed to a judicial exception.
In the instant situation, the additional element/step of administering a melatonin/5-HTlA receptor antagonist does not practically apply the judicial exception because it is conditional upon detection of a SNP. However, since the claim does not require detection of any particular allele or position, the administration step is not required in either the independent or dependent claims. .
The next step involves determining whether the remaining elements, either individually or as an ordered combination, are sufficient to “’transform the nature of the claim’ into a patent eligible application” Alice, 134 S. Ct. at 2355 (quoting Mayo, 132 S. Ct. at 1297). In the instant situation, the claims do not require any additional elements that transform the nature of the claim into a patent eligible application. Additionally, the general recitation of detection of known nucleic acids is well understood, routine, and conventional activity (see MPEP 2104.05(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.” No novel technique or inventive concept is added by these claims. 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).
The Supreme Court does acknowledge that it is possible to transform an unpatentable law of nature, but one must do more than simply state the law of nature while adding the words "apply it.” CLS BankInt’l, 134 S.Ct. at 2358; Prometheus, 132 S. Cl, at 1294. Further, general steps of “treating” a particular disease or disorder without any particular therapy recited is taken as instructions to apply the natural law.
When viewed as an ordered combination, the claimed limitations are directed to nothing more than the recitation of an abstract idea. Accordingly, it is determined that the instant claims are not directed to patent eligible subject matter.
Claim Rejections - 35 USC § 112
112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Written Description
Claims 11-23 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, at the time the application was filed, had possession of the claimed invention.
The claims are all directed towards methods which require detecting a SNP associated with treatment efficacy and/or adverse effect in subjects afflicted with dementia symptoms. In some instances the claims recite a 30kb locus, and others, a particular nucleotide position via an rs number. The specification states that the SNP detection can be achieved by directly detecting a particular position or indirectly with another nucleotide position in linkage disequilibrium. While the specification teaches 6 particular positions on chromosome 2, which had informative alleles associated with efficacy and response to piromelatine in AD patients, the claims more broadly encompass an undefined genus of structural variants that must have a particular functionality.
The term linkage disequilibrium refers to the preferential segregation of a particular polymorphic form with another polymorphic form at a different chromosomal location more frequently than expected by chance. Therefore the claims encompass detecting a potentially large genus of nucleic acids.
The specification teaches that conducting a GWAS analysis on AD patients being treated with piromelatine (page 24-25). The specification teaches conducting analysis in a 30 kb locus on chromosome 2 and detecting an association between a C allele of rs12328439, an A allele at rs62155556, an T allele at rs62155557, an A allele at rs62155558, a G allele at rs17033479, and an A allele at rs9789618 and paradoxical treatment efficacy. The specification teaches that these alleles were associated with significant enhancement over placebo in cNTB tests, but in deterioration of ADAS-Cog14 scores, indicative of worsening dementia (page 24). The specification teaches that further analysis revealed that 39% of non-carriers of the alleles taking 20 mg piromelatine (that is carriers of the alternate allele than those listed above) were associated with improvement in ADAS-Cog14 scores and were thus termed “responders” vs only 8% that were carriers of the alleles (table 2, pages 25-26). Conversely, the specification teaches that additional study with lower dosages of piromelatine (5mg) showed that AD carriers did not deteriorate on ADAS-Cog14 but that only the cNTB test showed improvement in scores for AD carriers. However, the specification does not teach the function of the SNP alleles or how they are associated with piromelatine treatment efficacy. Accordingly, the skilled artisan would not be able to predictably determine which other alleles of SNPs in the claimed locus or in sites farther away, are also associated with treatment.
Although the skilled artisan would be capable of determining SNPs in LD with the recited SNPs, the specification does not disclose all possible SNPs which meet the criteria set forth in the claims. Further, other than alleles recited above, the specification does not disclose which of the possible SNPs in the claimed locus can be reliably considered to be indicative of piromelatine treatment efficacy, and of these SNPs which are not identified, which of allele of the SNP is the one so associated. There is an implicit assertion on the record (as evidenced by the claims) that all SNP that are in linkage disequilibrium with the recited SNPs would meet this requirement. However, this assertion is not supported by general statistical knowledge which accepts that correlations are not transitive (Sotos et al.; Statistics Education Research Journal, 8(2) 33-55, 2009l cited in the IDS filed 9/27/2023).
While HapMap lists particular currently known SNPs, it is known that SNPs that are in LD can vary with different populations. These findings are supported by the teachings of Andiappan (BMC Genetics. 2010. 11: 36; cited in the IDS filed 9/27/2023). Further, Andiappan genotyped 20 candidate genes on 5q31-33 and through re-sequencing identified 237 SNPs, of which only 95 (40%) were in Hapmap (see abstract). The reference also discloses that HapMaps are provided for 4 reference populations and there is variability between the data for the different populations (e.g., p. 2, col. 1). Andiappan cites Mueller as reporting that, in a study of European populations spanning sequence regions of 750Kb, only two out of the four studied populations were well represented in the HapMap CEPH population (p. 2, col. 1). Accordingly, the HapMap cannot be relied up to establish possession of SNPs sharing any level of LD with recited SNPs and functionally associated as required.
The specification discloses only six markers which satisfy the claimed requirements. Examining these markers as disclosed in the specification, there is no common structural feature which would guide one attempting to practice the claimed invention in identifying other markers that would meet all of the functional requirements of the claimed methods. All members of the genus of markers useful in the claims have the same function, but no correlation between the naturally occurring allelic structures and their common properties is disclosed. While the skilled artisan may potentially identify these species using routine methods in the prior art, this is not a practical way to describe the full extent of the claimed subgenus of methods because finding naturally occurring alleles could be successful only empirically. The general knowledge in the art concerning alleles does not provide any indication of how the structure of one allele is representative of unknown alleles, as are currently embraced by most of the claims.
The nature of alleles is that they are variant structures, and in the present state of the art, the structure of one allele does not provide guidance to the existence or structure of other alleles. In other words, the existence and structure of other alleles are not predictable from the species of alleles described. The description given is not adequate to allow one of skill in the art to distinguish members used in the methods of the claimed subgenus from non members that are not within the scope of the claimed methods.
The written description issue applies to situations where the definition of the subject matter of the claims fails to provide description commensurate with the genus. Case law directly supports this rejection. As the District Court in University of Rochester v. G.D. Searle & Co., Inc. (2003 WL 759719 W.D.N.Y., 2003. March 5, 2003.) noted "In effect, then, the '850 patent claims a method that cannot be practiced until one discovers a compound that was not in the possession of, or known to, the inventors themselves. Putting the claimed method into practice awaited someone actually discovering a necessary component of the invention." This is similar to the current situation since the breadth of the current claims comprises the use of polymorphisms which the present inventors were not in the possession of, or which were not known to the inventors.
Since the specification does not disclose a representative number of SNPs in linkage disequilibrium with those recited or which reside within the claimed 30kb locus on chromosome 2 that are significantly associated with piromelatine treatment response in AD, or in any neurological disorder or intellectual ability, one of skill would conclude that Applicants were not in possession of the claimed genus of methods which utilize polymorphisms in linkage disequilibrium or in the recited locus because a description of only six members of this genus is not representative of the species in the genus and is insufficient to support the claims.
112(b)
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 11-23 are 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 phrases such as “determining if the human subject has a … SNP in a … locus” or “the SNP is … 2:107516926” or “ has a SNP selected from rs12328439”. The term SNP in the claims appears to be used to reference whether a particular nucleotide position in the genome is polymorphic, that is it can contain different alleles at the same position. However, the claims also recite a particular rs number without any contextual allele. It is noted that rs numbers are used to indicate a particular nucleotide position within the genome that is polymorphic and identifies the possible alleles at that position. It does not indicate any particular allele. Therefore, the metes and bounds of “if a subject has a SNP at” an rs number, a particular nucleotide position in a chromosome, or a broader locus is indefinite because it is not clear if the claim means to determine if a particular nucleotide position is polymorphic or whether it contains a specific allele.
The claims recite 2:107,510,000-107,540,000 to refer to a particular locus on chromosome 2. However the claim does not include a frame of reference as to what position 1 is. Since chromosomal positions change depending on the version of the genome reference assembly, without a reference or version number, the positions are arbitrary, rendering the metes and bounds of the claims unclear.
Double Patenting
Non-Statutory
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of US Patent application 11,840,731. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘731 patent are coextensive in scope with the claimed invention. As defined by the specification, the methods of the ‘731 claims are carried out on patients with not only AD, but dementia, ADHD, autism, and schizophrenia. Therefore, the claims are directed to genetic analysis of the same polymorphic loci, detecting the same alleles, and administering the same therapy in the same patients.
Claims 11-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of US Patent application 11,807,907. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘907 patent are anticipate the claimed invention. The claims are directed to genetic analysis of the same polymorphic loci, detecting the same alleles, and administering the same therapy in the same patients.
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