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 of the invention of Group 1 (claims 21-32, methods analysis) in the reply filed on 10/09/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 33 and 34 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/09/2025.
Claim Rejections - 35 USC § 112 – Failure to Limit
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 22 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 21 recites “at least one of the long alleles comprises > 24 consecutive CA dinucleotides”. The claim thus encompasses a method in which a long allele with 24, 25, 26, 27 …. consecutive CA dinucleotides is present (i.e.: 24 or any amount greater than 24). Claim 22 sets forth that “at least one of the long alleles comprises 24 consecutive CA dinucleotides”; because of the open nature of the transitional term “comprises” (i.e.: see MPEP 2111.03; inclusive of additional elements), the limitation does not set forth that the long allele is restricted to only 24 consecutive CA dinucleotides. The limitation in claim 22 appears to only set a lower limit (i.e.: 24) to the number of consecutive CA dinucleotides, but the allele may include (i.e.: may comprise) any number of CA dinucleotides in addition to the recited 24 consecutive CA dinucleotides. As such it is not clear that claim 22 is further limited than the requirements of claim 21.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 21-32 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exceptions including abstract ideas and natural phenomena without significantly more.
The claim(s) recite(s) methods where a subject is identified as having sporadic ALS where the presence of a particular genotype is indicative of the presence of sporadic ALS (e.g.: claim 21, step (e)), and the stratifying (i.e.: grouping or collating ) of subjects (claim 29, step (e)), which indicates that the claims are directed to an evaluation of data or information to reach a conclusion, make a judgment, or organize information, which is a mental process that is an abstract idea (see MPEP 2106.04(a) III).
Additionally, where claims recite a correlation between alleles and the presence of a pathology, the claim is directed to the natural association between genotype and phenotype, and thus is directed to a natural phenomenon (see MPEP 2106.04(b) I).
This judicial exception is not integrated into a practical application because the claims do not practically apply the judicial exception(s), as noted above, by including one or more additional elements that the courts have stated integrate the exception into a practical application:
An additional element reflects an improvement in the functioning of a computer, or an improvement to other technology or technical field;
An additional element that applies or uses a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition;
An additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim;
An additional element effects a transformation or reduction of a particular article to a different state or thing; and
An additional element applies or uses the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception.
Here it is noted that while the claims broadly recite steps of providing a treatment, the treatments are provided with such a high level of generality that the recited step is not considered to integrate the exception into a practical application (see MPEP 2106.04(d)(2). Additionally, where the treatment in claim 29 is applied in the same way to everyone (i.e.: regardless of stratification status), this treatment is not an integration of the judicial exception. Claim 29 does not specify which patients are treated, or only treat a specific patient population based upon their genetic composition. Thus, the claim is directed to a judicial exception.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the active step of the claims of measuring a CA dinucleotide repeat in STMN2 is well understood, routine and convention activity in the related prior art. For example, Submitted SNP(ss) Details: ss1583578618 (2015) and Submitted SNP(ss) Details: ss663873519 (2012) teach the identification of a CA dinucleotide repeat of polymorphic length that is in the same as the CA dinucleotides at position 30512 of SEQ ID NO: 1 as recited in the claims. Additional elements related to amplification of genomic DNA are field of use limitations (e.g.: MPEP 2106.05(h)), and primers used in a gene amplification are recited at a high level of generality and are thus related to insignificant extra-solution activity (e.g.: MPEP 2106.05(g).
For the reasons set forth above the claims are not directed to patent eligible subject matter.
Claim Rejections - 35 USC § 112 –Enablement
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 21-32 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for methods comprising stratifying human subjects on the basis of allele length of CA dinucleotide repeats at position 30512 SEQ ID NO: 1 in STMN2 gene, does not reasonably provide enablement for the use of allele length to identify a subject as having sporadic ALS (as recited in independent claim 21), or the stratification of any non-human subjects (as encompassed by independent claim 29). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Scope of the Claims/Nature of the Invention
The claims are directed to methods that encompass the identification of the presence of sporadic ALS in a subject based on allele length genotypes in STMN2 (CA dinucleotides in intron 3 at position 30512 of SEQ ID NO: 1), and encompass the diagnosis or stratification of any subject organism.
The nature of the invention requires knowledge of the required STMN2 alleles in any subject organism, as well as a robust and reliable correlation between STMN2 alleles and the presence of the sporadic ALS phenotype.
Teachings in the Specification and Examples
The specification (p.28-32) teaches the detection of a CA dinucleotide repeat with polymorphic length in intron 3 of the STMN2 gene at the position corresponding to position 30512 of SEQ ID NO: 1 in samples from human subjects. The specification teaches (p.29) that the alleles can be distinguished as short (S; <19 CA repeats) and long (L; >19 CA repeats) alleles. The specification teaches that in an analysis of ALS affected case subject and non-affected controls, the presence of a two long allele genotype (i.e.: L/L) was overrepresented in case subject (p.29; Table 1; p.30).
The specification does not teach the analysis of any non-human subjects.
The specification teaches only the analysis of two case:control populations.
State of the Art and the Unpredictability of the Art
While methods of detecting any known genetic content were known in the art, methods of correlating any genotypes with a phenotype (i.e.: the presence of sporadic ALS) are highly unpredictable.
Initially it is noted that the claims require the detection of alleles of a particular polymorphic repeat (i.e.: CA dinucleotide repeat in intron 3 of the STMN2 gene at the position corresponding to position 30512 of SEQ ID NO: 1), but generically encompass the analysis of any subject organism. Because the specification teaches only the analysis of human genetic material, it is relevant to point out that polymorphic content in a human gene may not be expected to be present in the homologous gene in any other subject organism. Such unpredictability is demonstrated by the teachings of Kaessmann, et al (2001), which teaches that in an analysis of a homologous portion of a chromosome in a variety of different primates, the level of genetic variation was different between the different subjects. As such it is unpredictable whether or not the particular alleles required by the claims would be applicable to any non-human subject.
Because the claims include the diagnostic association of alleles with a phenotype, it is relevant to point out the general unpredictability of such associations. In this regard Lucentini (2004) teaches that it is strikingly common for follow-up studies to find gene-disease associations wrong (left column, 3rd paragraph). Lucentini teaches that two studies found that typically when a finding is first published linking a given gene to a disease there is only roughly a one-third chance that the study will reliably confirm the finding (left column, 3rd paragraph). Lucentini teaches that bigger sample sizes and more family-based studies, along with revising statistical methods, should be included in the gene association studies (middle column, 1st complete paragraph).
More specially relevant to the instantly required association between STMN2 repeat alleles and the identification of sporadic ALS, the related are teaches that in attempts to replicate the finding in other populations, the association was not reproducible. Failure to reproduce the association is demonstrated by Monnakgotla et al (2023), Doronzio et al (2023), van Vugt et al (2025), Ross et al (2022), Nemati (2024), and Grima et al (2022). AS such it is highly unpredictably as to whether or not the L allele of the STMN2 intron polymorphism is overrepresented in ALS cases in typical human subject.
Quantity of Experimentation
The quantity of experimentation necessary is great, on the order of many man-years, and then with little if any reasonable expectation of successfully enabling the methods as claimed. The experimentation would require case:control analysis of any subject organism in an effort to establish a relationship between the STMN2 alleles of the claims and the presence of ALS, which is not established in the related post-filing art. Even if such extensive experimentation were to be performed, there is no indication that the associations required by the claims would be found.
Conclusion
Herein, although the level of skill in the art is high, given the particular disclosure in the specification and copious volume of related art that demonstrates the unpredictability of the art, it would require undue experimentation for one of skill in the art to make and use the invention as claimed.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEPHEN THOMAS KAPUSHOC whose telephone number is (571)272-3312. The examiner can normally be reached M-F, 8am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne Gussow can be reached at 571-272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Stephen Kapushoc
Primary Examiner
Art Unit 1683
/STEPHEN T KAPUSHOC/Primary Examiner, Art Unit 1683