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 without traverse of the species in claim 3 and 4 in the reply filed on 7/13/2016 is acknowledged.
Claims 1-20 are pending. Claims 5-8 and 14-20 have been withdrawn as being drawn to a nonelected species.
An action on the merits for claims 1-4 and 9-13 is set forth below.
Claim Objections
Claims 3-4, 12-13 are objected to because of the following informalities: In particular the abbreviations of the gene names would be spelled out for clarity. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1-4 and 9-13 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 specific correlations for increased risk of ALS-Glia based upon specific levels and genes in specific sample and species types, does not reasonably provide enablement for diagnosis of ALS based upon any level or activity in any sample or species. 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 or use the invention commensurate in scope with these claims.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 USC 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (CA FC 1988). Wands states at page 1404,
“Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.”
Breadth of the claims
The claims are drawn to method for diagnosing any subject as having ALS or a specific subtype based upon the increased or decreased of the level or activity of any the genes in table 3. The specification does not provide any examples or guidance of correlation diagnosis in any sample in any subject. Further, the art teaches that such associations are unpredictable.
When the claims are read in light of the specification, the specification discloses particular correlations, however, the specification does not provide the guidance of diagnosis of ALS any subtype based upon detection of any level or activity of the barkers in table 3 in any sample. Accordingly, the specification cannot be relied upon for providing support or enablement for the breadth of the method.
Nature of the Invention
The invention is in a class of invention which the CAFC has characterized as “the unpredictable arts such as chemistry and biology.” Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
Teachings in the Specification
The specification teaches measurement of particular subtypes and expression of RNA (p. 62). The specification provides that there are some correlations with particular subtypes and particular expression (p. 64-65), however, the specification has not provided the breadth of any expression in any sample from any species. Further, the specification has not provided guidance that detection of two of the recited genes provided diagnosis.
Further, as discussed below, such correlation are population and disease specific and require undue experimentation.
The predictability or unpredictability of the art and degree of experimentation
Further the claims are drawn to any sample type. The art of Cobb et al (Crit Care Med 2002 Vol. 30 p. 2711) teaches the unpredictability in analysis of gene expression in spleen and liver sample from septic mice. Notably, the reference teaches that, when compared to a non-septic sample, the relevant expression profiles of the septic mouse spleen and the septic mouse liver contain different nucleic acids at different levels (Table 1; p.2714, middle col., lns.2-8). As such the art teaches that expression levels of the same nucleic acids in different tissue samples differ. Therefore the art indicates that an association of expression level to a disease in one sample would not be correlative to an association to any other sample type. Therefore the art suggests the unpredictability of associating expression levels in one sample and other samples.
Enard et al. (Science 2002 Vol 296 p. 340) teaches that even between closely related species gene expression patterns differ (abstract). Enard et al. teaches that mRNA expression levels are different between humans, chimpanzees, orangutans and rhesus marcques (p. 340 1st column last sentence-2nd column 1st paragraph). Enard et al. teaches that there are a large number of quantitative differences in gene expression in closely related mammals (p. 342 2nd column last paragraph).
The art teach associations need to be confirmed by multiple large sampling sizes to determine a clear association. The art teaches that associations are population based and that it is difficult to reproduce expression studies. The art teaches that correlation between disease conditions and genetic expression is often irreproducible.
Therefore the skilled artisan would have to perform undue experimentation in order to diagnosis any patient in any sample increase or decrease of any combination of genes in table 3 to diagnosis.
Quantity of Experimentation
The quantity of experimentation in this area is extremely large since there are a significant number of parameters, which would have to be studied prior to being able to practice the claimed invention as broadly as written. The skilled artisan would have to determine the correlation of expression in any sample in any species. The skilled artisan would have to determine the association of either increased or decreased expression of any combination of genes in table 3 with an extremely large number of subtypes or ALS. This would require significant inventive effort, with each of the many intervening steps, upon effective reduction to practice, not providing any guarantee of success in the succeeding steps.
Level of Skill in the Art
The level of skill in the art is deemed to be high.
Conclusion
Case law has established that '(t)o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without 'undue experimentation.'" In re Wright 990 F.2d 1557, 1561. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) it was determined that '(t)he scope of the claims must bear a reasonable correlation to the scope of enablement provided by the specification to persons of ordinary skill in the art". The amount of guidance needed to enable the invention is related to the amount of knowledge in the art as well as the predictability in the art. Furthermore, the Court in Genetech Inc. v Novo Nordisk 42 USPQ2d 1001 held that '(I)t is the specification, not the knowledge of one skilled in the art that must supply the novel aspects of the invention in order to constitute adequate enablement".
In the instant case, the specification does not provide any examples or guidance to correlate increased or decreased expression any combination of the genes in table 3 any sample from any species with diagnosis. Further the art teaches that association studies are often irreproducible and that the associations are population specific. In view of this unpredictability, the specification has not established that the presently claimed method can be used to predict diagnosis.
Accordingly, in view of the unpredictability in the art, and the lack of disclosure in the specification and in the prior art and the unpredictability of the art, it would require undue experimentation for one of skill in the art to make and use the claimed invention.
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 1-4 and 9-13 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.
Claims 1-4 and 9-13 are indefinite over the use of “table 3” in Claim 1 and 10. MPEP 2173.05(s) addresses the use of such limitations in claims:
Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience."
In the instant case the claims may be amended to recite particular gene symbols from the relevant table as presented in the specification as originally filed.
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 1-4 and 9-13 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural correlation without significantly more. The claim(s) recite(s) a judicial exception of correlation of diagnosis of ALS or ALS subtype and an expression of two or more of the genes in table 3. This judicial exception is not integrated into a practical application because the claims require steps providing a sample and comparing level or activity and does not provide a step to integrate the 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 claims do not integrate the judicial exception to steps that are not considered routine and conventional steps.
These judicial exceptions are not integrated into a practical application because the claims only recite the natural correlation, wherein the step of comparing does not integrate the judicial expectation. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the steps are considered general and routine knowledge (as discussed below).
According to the 2019 Patent Eligibility Guidance an initial two step analysis is required for determining statutory eligibility.
Step 1. Is the claim directed to a process, machine, manufacture, or composition of matter? In the instant case the Step 1 requirement is satisfied as the claims are directed towards a process.
Step 2A Prong one. Does the claim recite a law of nature, a natural phenomenon or an abstract idea? Yes, a natural phenomenon.
The correlation of expression of the genes and diagnosis is considered a natural correlation. The step of providing a sample, determining the expression or alteration are considered a routine and conventional step.
Step 2A prong two. Does the claim recite additional elements that integrate the judicial exception into a practical application? The answer is no as the steps require only routine and convention steps and does not integrate the judicial exception to a practical application.
Step 2B. Does the claim recite additional elements that are significantly more than the judicial exceptions? No as the claims do not require any elements that integrate the judicial exception.
The steps that are not considered judicial expectations are the steps of diagnosing as it is considered the judicial exception itself. As noted in the specification the specificaoin uses known ALS cohorts, known genes using known expression assays (p. 5-7). The steps are recited at a high level of generality such that it amounts to insignificant pre-solution activity, e.g. mere data gathering steps necessary to determine response. When recited at this high level of generality, there is no meaningful limitation, such as a particular or unconventional machine or transformation of a particular article, in these steps that distinguish them from well-understood, routine and conventional data gathering activity engaged in by scientists prior to applicant’s invention and at the time the application was filed.
For those reasons, the claims are rejected under section 101 as being directed to non-statutory subject matter.
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.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu Cheng (Winston) Shen can be reached at 5712723157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KATHERINE D SALMON/ Primary Examiner, Art Unit 1682
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