DETAILED CORRESPONDENCE
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 .
This action is in response to the papers filed December 4, 2025. Currently, claims 1-20, 42 are pending. Claims 18-20 have been withdrawn as drawn to non-elected subject matter.
Election/Restrictions
Applicant's election without traverse of ADAMDEC1 and anti-TL1A antibody with CDRs comprising SEQ ID NO: 346-351, Claims 1-17, 42 in the paper filed December 4, 2025 is acknowledged.
The requirement is still deemed proper and is therefore made FINAL.
Priority
This application claims priority to
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Drawings
The drawings are acceptable.
Claim Objections
Claim 2 is objected to because the claim appears to be two claims merged together. Line 8 of Claim 2 starts “The method of claim 1 or 2” which is objected to. If this is a separate claim, Applicant is required to add a claim number.
Improper Markush Rejection
Claims 1-17 are rejected on the basis that it contains 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 in two situations. First, a Markush grouping is proper if 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. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
A Markush claim contains an “improper Markush grouping” if:
(1) the species of the Markush group do not share a “single structural similarity,” or (2) the species do not share a common use. Members of a Markush group share a “single structural similarity” when they belong to the same recognized physical or chemical class or to the same art-recognized class. Members of a Markush group share a common use when they are disclosed in the specification or known in the art to be functionally equivalent. See MPEP § 2117.
Here each species is considered to be each of the genes listed in Table 1A and 1B. Table 1A is found on pages 22-34 and comprises 201 biomarkers. Table 1B is page 35- 36 with about 40 markers.
The recited alternative species in the groups set forth here do not share a single structural similarity, as each different gene that could be detected is itself located in a separate region of the genome and has its own structure. The genes recited in the instant claims, do not share a single structural similarity since each consists of a different nucleotide sequences with different expression patterns. The only structural similarity present is that all detected positions are part of nucleic acid molecules. The fact that the markers comprise 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 CD-PBmu. Accordingly, while the different markers are asserted to have the property of being expressed in with CD-PBmu, they do not share a single structural similarity.
MPEP 2117 (II)(A) provides the following guidance as to what constitutes a physical, chemical, or art recognized class:
A recognized physical class, a recognized chemical class, or an art-recognized class is a class wherein “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. In other words, each member could be substituted one for the other, with the expectation that the same intended result would be achieved”
The recited genes do not belong to a recognized chemical class because there is no expectation from the knowledge in the art that the genes will behave in the same manner and can be substituted for one another with the same intended result achieved. In other words, there is no expectation from the knowledge in the art that each of the recited genes would function in the same way in the claimed method; it is only in the context of this specification that it was disclosed that all members of this group may behave in the same way in the context of the claimed invention. Further there is no evidence of record to establish that it is clear from their very nature that each of the recited genes possess the common property of being associated with CD-PBmu.
MPEP 2117 (II) further states the following:
Where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the compounds do not appear to be members of a recognized physical or chemical class or members of an art-recognized class, the members are considered to share a "single structural similarity" and common use when the alternatively usable compounds share a substantial structural feature that is essential to a common use. Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984).
The recited alternative species do not share a substantial common structure just because they all have a sugar phosphate backbone. The sugar phosphate backbone of a nucleic acid chain is not considered to be a substantial common structural feature to the group of genes being claimed because it is shared by ALL nucleic acids. Further, the fact that the genes all have a sugar phosphate backbone does not support a conclusion that they have a common single structural similarity because the structure of comprising a sugar phosphate backbone alone is not essential to the asserted common use of being associated with CD-PBmu.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
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 1-16, 42 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
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, part II.
Based upon consideration of the claims as a whole, as well as consideration of elements/steps recited in addition to the judicial exception, the present claims fail to meet the elements required for patent eligibility.
Question 1
The claimed invention is directed to a process that involves a natural principle and a judicial exception.
Question 2A Prong I
The claims are taken to be directed to an abstract idea, a law of nature and a natural phenomenon.
Claim 1 is directed to “a method of determining a Crohn’s Disease (CD) subtype status in a subject having CD” by detecting expression of a gene, determining the CD subtype status wherein an “increased level” compared to a reference “indicates status of CD-PBmu subtype”.
Claim 2 is directed to a method of selecting a treatment by determining a level of expression of a gene and detecting an expression profile comprising an increase in the level of expression of the gene, namely elected ADAMDEC1, and identifying the subject as a candidate for treatment.
Claim 42 is directed to processing or analyzing a biological sample by inputting data into a trained algorithm to generate a classification for a CD subtype and outputting a report.
Claims 1 and 2 are directed to a process that involves the judicial exceptions of an abstract idea (i.e. the abstract steps of “determining CD subtype status” “detecting expression of a gene” and “identifying a subject as a candidate for treatment”) and a law of nature/natural phenomenon (i.e. the natural correlation between the increased level of expression of ADAMDEC1 and CD-PBmu subtype).
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons that follow.
Herein, claim 1 involves the patent-ineligible concept of an abstract process. Claim 1 requires performing the step of “detecting expression of elected ADAMDEC1” “comparing a reference expression profile” and “determining CD subtype status”. Neither the specification nor the claims set forth a limiting definition for "detecting” or “determining" and the claims do not set forth how “detecting” or “determining” is accomplished. As broadly recited the detecting or determining step may be accomplished mentally by thinking about a subject’s gene expression level and assessing whether the subject has CD-PBmu subtype. Thus, the detecting and determining steps constitutes an abstract process idea.
Claim 2 is directed to identifying a subject as a candidate for treatment and selecting a treatment for a subject. The selection of a treatment or a patient is an abstract process that may be accomplished by mentally thinking about the expression profile.
The claims further recites a comparison between the expression level and a reference expression profile that is deemed an abstract idea (see MPEP 2106.04(a)(2)(III)(A); • claims to “comparing BRCA sequences and determining the existence of alterations,” where the claims cover any way of comparing BRCA sequences such that the comparison steps can practically be performed in the human mind, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 763, 113 USPQ2d 1241, 1246 (Fed. Cir. 2014)). Claims 4 and 12 are directed to an increase in the level of expression of at least 2-fold. Claims 5 and 13 limit the expression profile of the control.
With respect to Claim 42, the use of a trained algorithm is a mathematical concept. The trained algorithm is a “mathematical calculation” and falls into the “mathematical concepts” grouping of abstract ideas.
A correlation that preexists in the human is an unpatentable phenomenon. The association between expression levels such as elected ADAMDEC1 and CD-PBmu subtype is a law of nature/natural phenomenon. The "determining the CD subtype” and the preamble each tells users of the process to predict CD-PBmu in the sample, amounts to no more than an "instruction to apply the natural law". This determining step is no more than a mental step. Even if the step requires something more such as to verbalize the discovery of the natural law, this mere verbalization is not an application of the law of nature to a new and useful end. The "determining" step does not require the process user to do anything in light of the correlation. The "determining” step fails to provide the “practical assurance” sought by the Prometheus Court that the “process is more than a drafting effort designed to monopolize the law of nature itself.”
Question 2A Prong II
The exception is not integrated into a practical application of the exception. The claims do not recite any additional elements that integrate the exception into a practical application of the exception. While the claim recites detecting expression of one or more genes, namely elected ADAMDEC1, this is not an integration of the exception into a practical application. Instead, these elements are data gathering required to perform the method. Thus, the claim is “directed to” the exception.
With respect to Claim 2, the selection of a subject or the selection of a treatment is not a practical application. Even if the “selecting” is considered to be a step that is not an abstract idea, it does not integrate the abstract detection of expression profiles with increased levels relative to expression references or the natural phenomenon because it is merely an instruction regarding therapy but does not require the therapy be delivered or administered.
Claims 15-16 are directed to treating subject with a therapeutic agent based upon expression profiles. The exception is not integrated into a practical application of the exception. The claim recites “treating the subject with a therapeutic agent” or “administering to the subject a therapeutic agent”. This is not a treatment claim. This does not require additional elements that integrate the exception into a practical application of the exception. While the claim recites “treating the subject with a therapeutic agent” or “administering to the subject a therapeutic agent”, this is not an integration of the exception into a practical application. The limitation does not indicate how the patient is to be treated, or what the treatment is but instead covers any possible treatment that a doctor decides to administer to the patient. The claim does not require the treatment is related to Crohn’s disease, but could instead be a treatment for sleep deprivation or cancers. Even more the limitation is recited at such a high level of generality that it does not even require a doctor to take the calculation step’s outcome into account when deciding which treatment, making the limitation’s inclusion in the claim at best nominal. The recites “treating the subject with a therapeutic agent” or “administering to the subject a therapeutic agent” limitation fails to meaningfully limit the claim because it does not require any particular application of the recited calculation, and is at best the equivalent of merely adding the words “apply it” to the judicial exception.
Question 2B
The second step of Alice involves determining whether the remaining elements, either in isolation or combination with the other non patent ineligible elements, 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).
The claims are not sufficiently defined to provide a method which is significantly more from a statement of a natural principle for at least these reasons:
The claims do not include applying the judicial exception, or by use of, a particular machine. The claims do not tie the steps to a “particular machine" and therefore do not meet the machine or transformation test on these grounds. The use of machines generally does not impose a meaningful limit on claim scope.
The claims also do not add a specific limitation other than what is well-understood, routine and conventional in the field. The measuring expression is mere data gathering step that amounts to extra solution activity to the judicial exception. It merely tells the users of the method to determine the level of expression of genes in a sample without further specification as to how the sample should be analyzed. The claim does not recite a new, innovative method for such determination. The determining step essentially tells users to determine the markers through whatever known processes they wish to use.
The step of determining the expression levels was well known in the art at the time the invention was made. The prior art teaches that expression analysis using commercially available biochips and arrays that comprise the claimed genes. The steps are recited at a high level of generality. The claim merely instructs a scientist to use any expression analysis assay to determine the expression status. The claims do not require the use of any particular non-conventional reagents. When recited at this high level of generality, there is no meaningful limitation that distinguishes this step from well understood, routine and conventional activities engaged in by scientists prior to applicant’s invention and at the time the application was filed.
Additionally, the teachings in the specification demonstrate the well understood, routine, conventional nature of additional elements because it teaches that the additional elements were well known.
Further it is noted that the courts have recognized the following laboratory techniques as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity.
Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs., 818 F.3d at 1377; 118 USPQ2d at 1546;
Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014)
For these reasons the claims are rejected under section 101 as being directed to non-statutory subject matter.
Claim Rejections - 35 USC § 112- Second Paragraph
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 1-17 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 pre-AIA the applicant regards as the invention.
A) The claims refer to tables 1A and 1B (see Claims 1, 2, and 16). Claim 17 refers to Table 20B, 14, 15, 17A-B or 20A. MPEP 2173.05(s) states:
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.” Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).
Appropriate correction is required.
B) Claim 2 appears to be two claims merged together. It is unclear what is required by Claim 2 and how Claim 2 can depend on Claim 2. Correction is required.
C) Claim 2 further requires identifying a subject as a candidate for treatment of Crohn’s disease based upon the expression profile, however the preamble of the claim is directed to selecting a treatment. It is unclear whether the claim is directed to a method of selecting a treatment or a method of identifying a subject. Clarification is required.
D) Claims 8-11 are indefinite because it is unclear which Crohn’s disease is being referred to in Claim 1. Claim 1 requires a patient with Crohn’s disease and requires determining a subtype of Crohn’s disease. It is unclear whether the original subject has CD associated with perianal disease/fistula or whether the subtype is associated with perianal disease/fistula. Clarification is required.
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.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claim(s) 42 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Princen et al. (US 2015/0072879, March 12, 2015).
Princen teaches methods for improving inflammatory bowel disease (IBD) and subtypes such as UC and Crohn’s disease (CD) by detecting the level of markers. Princen teaches applying statistical classifier systems to level of IBD markers to diagnose or subtype samples (para 332). Princen teaches data was analyzed in relation to a reference database of samples (para 334). The samples are subjected to learning statistical classifier systems such as decision/classification trees, neural networks, random forests, for example (see para 335-340).
Double Patenting
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 1-17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim s 12, 14, 17, 19, 28 of copending Application No. 17/334, 109 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of ‘109 are directed to treating CD by administering to the subject a modulator or antagonist of TNF Superfamily Member 15 (TL1A) where the subject is identified as having CD-PBmu subtype where the expression profile was increased in ADAMDEC1. The instant claims are similarly directed to detecting expression of elected ADAMDEC1 and determining CD status of CD-PBmu. Instant Claim 16 is further directed at treating by administering a therapeutic agent, namely elected anti-TL1A ab.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims allowable.
The art made of record and not relied upon is considered pertinent to applicant's disclosure.
Gonsky et al. (Front. Gastroenterol, Vol 2, October 17, 2023) teaches a blood-based transcriptomic signature stratifies severe Crohn’s disease and defines potentially targetable therapeutic pathways. The research provides expression analysis for CD-PBmu subtyping.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANINE ANNE GOLDBERG whose telephone number is (571)272-0743. The examiner can normally be reached Monday-Friday 6am-3:30pm.
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/JEANINE A GOLDBERG/Primary Examiner, Art Unit 1682
January 26, 2026