DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. 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
2. Applicant’s election of Group I, drawn to a method for detecting a propensity to develop EoE, and the species of the SMAD3 locus and the co-morbid condition of allergies in the reply filed on 08 October 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)).
Claim Status
3. Claims 1-3, 5-10, 12-15, 17-18, and 20-24 are pending.
Claims 12-15 and 17-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 6, 8, 9, 23 and 24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Note that Applicant elected the locus of SMAD3 alone.
Claims 1-3, 5, 7, 10, and 20-22 read on the elected invention and have been examined herein to the extent that the claims read on methods wherein the locus is the SMAD3 locus; and claims 10 and 21 have been examined to the extent that the subject also suffers from the additional disease of allergies. Each of the claims encompass the non-elected species of the additionally recited loci and combinations thereof and claims 10 and 21 encompass non-elected comorbidities. Prior to the allowance of claims, any non-elected subject matter which has not been rejoined with the elected subject matter will be required to be removed from the claims.
Information Disclosure Statement
4. The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Objections
5. Claims 2 and 20-22 are objected to because of the following informalities:
Claim 2 recites “single nucleotide polymorphisms” and subsequently recites “said SNP.” Claim 2 should recite “single nucleotide polymorphisms (SNPs).”
Claims 20-22 recite “further comprising administration of an agent” (claim 20, line 1), whereas the claims should recite “further comprising administering an agent.”
Claim 21 recites “Chron’s disease” whereas the claim should recite “Crohn’s disease.”
Appropriate correction is required.
Claim Rejections - 35 USC § 101
6. 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, 5, 7, 10 and 20-22 are rejected under 35 U.S.C. 101 because the claimed invention is directed to the judicial exception of a law of nature / natural phenomenon, and/or an abstract idea without significantly more. The judicial exception is 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 that follow.
Applicant' s attention is directed to MPEP 2106 “Patent Subject Matter Eligibility” which discusses the Alice/Mayo two-part test for evaluating subject matter eligibility.
Regarding Step 1 of the subject matter eligibility test set forth at MPEP 2106III, the claims are directed to the statutory category of a process.
Regarding Step 2A, prong one, the claims recite the judicial exception of a law of nature. The claims recite the correlation between a genetic alteration in a gene sequence from a SMAD3 locus and propensity for developing EoE. In particular, the claims are drawn to a “method for detecting a propensity for developing eosinophilic esophagitis (EoE)” and require detecting a genetic alteration wherein “the presence of said genetic alteration indicating said patient has an increased risk for developing eosinophilic esophagitis” As in Mayo Collaborative Services v. Prometheus, the recited relationship is a natural phenomenon that exists apart from any human action. See also Cleveland Clinic Foundation v. True Health Diagnostic, LLC, 2018-1218 (Fed Cir. 2019) which states that “The re-phrasing of the claims does not make them less directed to a natural law.”
The claims also recite the judicial exception of an abstract idea and particularly mental processes.
MPEP 2106.04(a) states that the enumerated groupings of abstract ideas include:
“1) Mathematical concepts – mathematical relationships, mathematical formulas or equations, mathematical calculations (see MPEP § 2106.04(a)(2), subsection I);…
3) Mental processes – concepts performed in the human mind (including an observation, evaluation, judgment, opinion) (see MPEP § 2106.04(a)(2), subsection III).”
The claims require performing the step of “detecting in genotype information, the presence of at least one EoE associated genetic alteration” in a gene in a SMAD3 locus. As broadly recited, “detecting in genotype information” encompasses reading information in a database or report to thereby ascertain the presence of the genetic alteration. While claim 2 recites assays that can be performed to detect SNP, it is not clear from the claim that the method is one that includes performing one of the recited processes to accomplish the “detecting in genotype information” step. Similarly, it is unclear as to how the recitation in claim 5 of “wherein nucleic acids genetic alteration are obtained from an isolated cell of the human subject” is intended to relate to the step of “detecting in genotype information.” Accordingly, the step of ““detecting in genotype information” may be performed by critical thinking processes wherein genetic information is detected in a report or database. Thereby, this step is an abstract idea.
Regarding Step 2A, prong two, having determined that the claims recite a judicial exception, it is then determined whether the claims recite additional elements that integrate the judicial exception into a practical application.
Herein, the claims do not recite additional steps or elements that integrate the recited judicial exceptions into a practical application of the exception(s). Note that in claim 1, the administering step is optional and need not be performed. To the extent that claim 2 intends to recite an active step of performing one of the listed processes, the step of detecting a genetic alteration by one of the processes is part of the data gathering process necessary to observe the judicial exception. This step does not practically apply the judicial exception.
Regarding the administering step in claims 20-22, the claims recite the open claim language of “comprising” and the steps of the claims may be performed in any order, such that the claims encompass methods wherein the administering step is performed prior to the step of detecting genetic information. In this instance, the administering step is not a practical application of the judicial exception.
Applicant’s attention is directed to M.P.E.P. § 2106.04(d)(2)(c), which states:
“The treatment or prophylaxis limitation must impose meaningful limits on the judicial exception, and cannot be extra-solution activity or a field-of-use. For example, consider a claim that recites (a) administering rabies and feline leukemia vaccines to a first group of domestic cats in accordance with different vaccination schedules, and (b) analyzing information about the vaccination schedules and whether the cats later developed chronic immune-mediated disorders to determine a lowest-risk vaccination schedule. Step (b) falls within the mental process grouping of abstract ideas enumerated in MPEP § 2106.04(a). While step (a) administers vaccines to the cats, this administration is performed in order to gather data for the mental analysis step, and is a necessary precursor for all uses of the recited exception. It is thus extra-solution activity, and does not integrate the judicial exception into a practical application.”
Further, regarding claims 20 and 21, the administering step is recited at a high degree of generality encompassing administering any agent for the treatment of EoE, including agents that ameliorate only symptoms of allergies. Such general treatments constitute nothing more than an “apply it” limitation and are not considered to practically apply the judicial exception.
Regarding specific treatments, see MPEP 2106.04(d)(2):
When determining whether a claim applies or uses a recited judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition, the following factors are relevant.
a. The Particularity Or Generality Of The Treatment Or Prophylaxis
The treatment or prophylaxis limitation must be "particular," i.e., specifically identified so that it does not encompass all applications of the judicial exception(s). For example, consider a claim that recites mentally analyzing information to identify if a patient has a genotype associated with poor metabolism of beta blocker medications. This falls within the mental process grouping of abstract ideas enumerated in MPEP § 2106.04(a). The claim also recites "administering a lower than normal dosage of a beta blocker medication to a patient identified as having the poor metabolizer genotype." This administration step is particular, and it integrates the mental analysis step into a practical application. Conversely, consider a claim that recites the same abstract idea and "administering a suitable medication to a patient." This administration step is not particular, and is instead merely instructions to "apply" the exception in a generic way. Thus, the administration step does not integrate the mental analysis step into a practical application….
b. Whether The Limitation(s) Have More Than A Nominal Or Insignificant Relationship To The Exception(s)
The treatment or prophylaxis limitation must have more than a nominal or insignificant relationship to the exception(s). For example, consider a claim that recites a natural correlation (law of nature) between blood glucose levels over 250 mg/dl and the risk of developing ketoacidosis (a life-threatening medical condition). The claim also recites "treating a patient having a blood glucose level over 250 mg/dl with insulin". Insulin acts to lower blood glucose levels, and administering insulin to a patient will reduce the patient’s blood glucose level, thereby lowering the risk that the patient will develop ketoacidosis. Thus, in the context of this claim, the administration step is significantly related to the recited correlation between high blood glucose levels and the risk of ketoacidosis. Because insulin is also a "particular" treatment, this administration step integrates the law of nature into a practical application. Alternatively, consider a claim that recites the same law of nature and also recites "treating a patient having a blood glucose level over 250 mg/dl with aspirin." Aspirin is not known in the art as a treatment for ketoacidosis or diabetes, although some patients with diabetes may be on aspirin therapy for other medical reasons (e.g., to control pain or inflammation, or to prevent blood clots). In the context of this claim and the recited correlation between high blood glucose levels and the risk of ketoacidosis, administration of aspirin has at best a nominal connection to the law of nature, because aspirin does not treat or prevent ketoacidosis. This step therefore does not apply or use the exception in any meaningful way. Thus, this step of administering aspirin does not integrate the law of nature into a practical application.
Regarding Step 2B, the next question is whether the remaining elements/steps – i.e., the non-patent-ineligible elements/steps - either in isolation or combination, amount to significantly more than the judicial exception.
Herein, the claims as a whole are not considered to recite any additional steps or elements that amount to significantly more than routine and conventional activity and do not add something “significantly more” so as to render the claims patent-eligible. Claims 1-3, 5-7, 9 and 10 do not require performing any specific, non-conventional transformative active process steps. To the extent that claim 2 intends to encompass performing one of the recited processes to obtain the genetic information, the recited processes were well-known, routine and conventional in the prior art. This finding is evidenced by the teachings in the specification. For instance, para [0050] (note that paragraph numbering herein is with respect to the published application) teaches “Polymerase chain reaction (PCR) has been described in U.S. Pat. Nos. 4,683,195, 4,800,195, and 4,965,188, the entire disclosures of which are incorporated by reference herein. Further, para [0043] states “Appropriate conditions enabling specific hybridization of single stranded nucleic acid molecules of varying complementarity are well known in the art.” Further, Li et al (U.S. 20090162348; cited in the restriction requirement of 08 August 2025) teaches that methods for detecting SNPs, including sequencing and amplification methods and hybridization methods, were well known in the prior art (e.g., para [0120], [0161] and [0168]).
See also MPEP 2106.05(d) II which states 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.
i. Determining the level of a biomarker in blood by any means, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017);
ii. Using polymerase chain reaction to amplify and detect DNA, Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1377, 115 USPQ2d 1152, 1157 (Fed. Cir. 2015);
iii. Detecting DNA or enzymes in a sample, Sequenom, 788 F.3d at 1377-78, 115 USPQ2d at 1157); Cleveland Clinic Foundation 859 F.3d at 1362, 123 USPQ2d at 1088 (Fed. Cir. 2017);
iv. Immunizing a patient against a disease, Classen Immunotherapies, Inc. v. Biogen IDEC, 659 F.3d 1057, 1063, 100 USPQ2d 1492, 1497 (Fed. Cir. 2011);
v. Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs., 818 F.3d at 1377; 118 USPQ2d at 1546;
vi. Freezing and thawing cells, Rapid Litig. Mgmt. 827 F.3d at 1051, 119 USPQ2d at 1375;
vii. 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); and
viii. Hybridizing a gene probe, Ambry Genetics, 774 F.3d at 764, 113 USPQ2d at 1247.
Note that while the claims recite detecting genetic alteration in a particular gene, the identity of the gene or loci is part of the judicial exception and not something in addition to the recited judicial exceptions. The claims do not require using a particular non-conventional reagent, such as a particular, non-conventional probe or primer consisting of or comprising a specific nucleotide sequence to detect the genetic alteration so as to add something ‘significantly more’ to the recited judicial exceptions.
In Mayo v. Prometheus, the Supreme Court stated: "[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."
This is similar to the present situation wherein the additional steps and elements are recited at a high degree of generality and are all routine, well understood and conventional in the prior art. The recited steps and elements do not provide the inventive concept necessary to render the claims patent eligible. See also Genetic Technologies Ltd. v. Merial L.L.C. 818 F.3d at 1377, 1379 (Fed. Cir. 2016).
For the reasons set forth above, when the claims are considered as a whole, the claims are not considered to recite something significantly more than a judicial exception and thereby are not directed to patent eligible subject matter.
Improper Markush Grouping Rejection
7. Claims 1-3, 5, 7, 10 and 20-22 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.
The Markush groupings of the TMEM182, RAD50, SOX4, MATN2, PRKGI, RHOG, SHANK2, GPR12, RORA, SMAD3, GALNTI, CPNE4, URGCP, NAMPT, JAK2, and/or CCNY genes and combinations thereof are improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
It is first noted that MPEP 2117 states that “A Markush claim may be rejected under judicially approved "improper Markush grouping" principles when the claim contains an improper grouping of alternatively useable members. A Markush claim contains an "improper Markush grouping" if either: (1) the members of the Markush group do not share a "single structural similarity" or (2) the members do not share a common use. Supplementary Guidelines at 7166 (citing In re Harnisch, 631 F.2d 716, 721-22, 206 USPQ 300, 305 (CCPA 1980)). “ 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 (prong 1) and the members of a Markush group share a common function or use when they are disclosed in the specification or known in the art to be functionally equivalent (prong 2).
The phrase “significant structural element is shared by all of the alternatives” refers to cases where the compounds share a common chemical structure which occupies a large portion of their structures, or in case the compounds have in common only a small portion of their structures, the commonly shared structure constitutes a structurally distinctive portion in view of existing prior art, and the common structure is essential to the common property or activity.
A recognized physical class, a recognized chemical class, or an art-recognized class is a class wherein “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.” (see MPEP 2117IIA).
Herein, the recited alternative species do not share a single structural similarity, as each gene has a different chemical structure in that it consists of a different nucleotide sequence. The only structural similarity present is that all of the genes comprise nucleotides. The fact that the genes comprise nucleotides per se does not support a conclusion that they have a common single structural similarity because the structure of comprising nucleotides alone is not essential to the asserted common activity of comprising a genetic alteration that is correlated with EoE. Accordingly, while the different genes are asserted to have the property of comprising a genetic alteration that is correlated with EoE, they do not share a substantial structural similarity essential to this activity.
Further, the recited genes do not belong to a chemical or art-recognized class because there is no expectation from the knowledge in the prior art that the genes behave in the same manner and can be substituted for one another with the same intended result achieved. There is no evidence of record to establish that it is clear from their very nature that the recited genes possess the common property of comprising a genetic alteration that is correlated with EoE
Following this analysis, the claims are rejected as containing an improper Markush grouping.
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.
This rejection may be obviated by amendment of claim 1 to recite a “method for detecting a propensity for developing eosinophilic esophagitis (EoE) in a subject in need thereof, the method comprising: detecting in genotype information, the presence of at least one EoE associated genetic alteration in a SMAD3 gene” and reciting in a dependent claim that the method further comprises detecting the presence of a genetic alteration in one or more of the TMEM182, RAD50, SOX4, MATN2, PRKGI, RHOG, SHANK2, GPR12, RORA, GALNTI, CPNE4, URGCP, NAMPT, JAK2, and/or CCNY genes. Upon the allowance of independent claim 1, the additionally recited combination of genes in the dependent claim will be considered for rejoinder. See paragraph 10 in the restriction requirement of 08 August 2025.
Claim Rejections - 35 USC § 112(b) - Indefiniteness
8. 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 1-3, 5, 7, 10 and 20-22 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 1-3, 5, 7, 10 and 20-22 are indefinite over the recitation in claim 1 of “detecting in genotype information, the presence of at least one EoE associated genetic alteration in a target gene identified in said subject” because it is not clear as to what is identified in the subject - i.e., the target gene or the genetic alteration - and it is not clear as to whether the “identified in said subject” is part of the step of detecting, in genotype information, the presence of a genetic alteration or if the “identified in said subject” is a separate active step of the claim or is a property of the target gene or genetic information that they were previously identified in the subject.
Claims 1-3, 5, 7, 10 and 20-22 are indefinite over the recitation in claim 1 of “said patient” because this phrase lacks proper antecedent basis. While the claims previously refer to “a subject” and “said subject, the claims do not previously refer to a patient and do not set forth a nexus between the subject and the patient. Accordingly, “said patient” should be amended to read “said subject.”
Claim 2 is indefinite over the recitation of “the step of detecting the presence of said SNP” because this phrase lacks proper antecedent basis since the claim does not previously recite a step of detecting the presence of a SNP. Rather, the claim previously recites a step of “detecting in genotype information, the presence of at least one EoE associated genetic alteration in a target gene identified in said subject.” While claim 2 recites “wherein said loci comprise single nucleotide polymorphisms that indicate that the genetic alteration is present,” this is not equivalent to reciting that that the step of detecting in genotype information, the presence of at least one EoE association genetic alteration comprises detecting the presence of a SNP. Rather, this wherein clause indicates only that the loci comprises a SNP that indicates that the genetic information is present. This rejection may be obviated by amendment of claim 2 to recite “wherein said genetic alteration is a single nucleotide polymorphism (SNP) and wherein the step of detecting in genotype information, the presence of at least one EoE associated genetic alteration comprises performing a process selected from the group consisting of…”.
Claim 3 is indefinite over the recitation of “the target nucleic acid” because this phrase lacks proper antecedent basis sine the claim previously refers to only a target gene and not a target nucleic acid per se, which can be DNA or RNA. Further, it is unclear as to what is intended to be encompassed by “wherein in the target nucleic acid is DNA or RNA.”
Claim 5 is indefinite over the recitation of “wherein nucleic acids genetic alteration are obtained from an isolated cell of the human subject” because it is not clear as to how this limitation is intended to further limit the method of claim 1. First, claim 1 is drawn more generally to methods that detect a propensity for developing EoE in a subject and are not limited to a human subject. Accordingly, it is not clear as to whether claim 5 intends to limit the method of claim 1 to one in which the subject is a human subject. Secondly, the claim does not previously refer to “nucleic acids genetic alteration.” It is not clear as to whether claim 5 intends to encompass, for example, a method in which the genotype information was obtained from nucleic acids present in an isolated cell from a human subject or to a method which requires that the step of “detecting in genotype information, the presence of at least one EoE associated genetic alteration” comprises obtaining nucleic acids from an isolated cell of a human subject and detecting the genetic alteration in the nucleic acids.
Claim 22 is indefinite over the recitation of “said treatment is esophageal dilation, topical glucocorticoids, proton pump inhibitors, and corticosteroids” because it is unclear as to whether each of the “treatments” is required as is encompassed by “and” or if the claim intends to recite alternative treatments and agents. Claim 22 recites both treatments (esophageal dilation) and agents (topical glucocorticoids, proton pump inhibitors, and corticosteroids) and this further renders the claim indefinite.
Claim Rejections - 35 USC § 112 first paragraph – Written Description
9. 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 1-3, 5, 7, 10 and 20-22 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, 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, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a Written Description rejection.
In analyzing the claims for compliance with the written description requirements of 35 U.S.C. 112, first paragraph, a determination is made as to whether the specification contains a written description sufficient to show they had possession of the full scope of their claimed invention at the time the application was filed.
For claims drawn to a genus, MPEP § 2163 states:
“The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus (see i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. See Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021) ( "[T]he written description must lead a person of ordinary skill in the art to understand that the inventor possessed the entire scope of the claimed invention. Ariad, 598 F.3d at 1353–54 ('[T]he purpose of the written description requirement is to ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor's contribution to the field of art as described in the patent specification.' (internal quotation marks omitted).").”
MPEP § 2163 goes on to state:
“An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004).”
Herein, the claims are drawn to a “method for detecting a propensity for developing eosinophilic esophagitis (EoE) in a subject in need thereof, the method comprising: detecting in genotype information, the presence of at least one EoE associated genetic alteration in a target gene identified in said subject, the presence of said genetic alteration indicating said patient has an increased risk for developing eosinophilic esophagitis, wherein said genetic alteration is present in a gene sequence from the SMAD3 loci.
Claim 2 recites “wherein said loci comprise single nucleotide polymorphisms that indicate that the genetic alteration is present” and appears to include a step of detecting the presence of the SNP. Thereby, claim 2 encompasses methods that detect a SNP as indirectly indicative of the presence of a genetic alteration that is associated with EoE.
Claim 7 requires that “the genetic alteration is a sex-specific alteration.”
The claims do not define the genetic alteration or SNP that is indicative of the genetic alteration in terms of its complete structure or in terms of any other relevant structural characteristics.
The claims as broadly written encompass detecting a potentially large genus of genetic alterations, including single and multiple insertions, deletions, and substitutions, as well as rearrangements and fusions that are within a SMAD3 loci, as well as SNPs that indicate the presence of the genetic alterations, such as SNPs in linkage disequilibrium with the genetic alterations.
However, the specification teaches only the specific SNP in the SMAD3 gene of rs56062135T (minor allele) as being associated with EoE, as determined by genome wide association studies (GWAS).
Regarding claim 7, the rs56062135 is not disclosed in the specification as being a “sex-specific” alteration that is correlated with EoE. See Table 4 of the specification which discloses male-specific and female-specific SNPs associated with EoE.
No additional members of the claimed genus of SNPs associated with EoE or associated with other genetic alterations in the SMAD3 loci have been sufficiently described in terms of any other relevant identifying characteristics.
Thus, applicant has not established possession of a representative number of species within the claimed genus of genetic alterations in the SMAD3 gene or locus comprising the SMAD3 gene that are associated with EoE, including sex-specific genetic alterations, or SNPs indicative of the presence of a genetic alteration in the SMAD3 gene or locus that is associated with EoE.
It is noted that the specification teaches the general methodology for detecting genetic alterations and particularly SNPs. However, possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features.
As noted in Vas-Cath Inc. v. Mahurkar (19 USPQ2d 1111, CAFC 1991), the Federal Circuit concluded that:
"...applicant must also convey, with reasonable clarity to those skilled in art, that applicant, as of filing date sought, was in possession of invention, with invention being, for purposes of "written description" inquiry, whatever is presently claimed."
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. 112 is severable from its enablement provision.
With respect to the present invention, there is no record or description which would demonstrate conception of a representative number of genetic alterations in the SMAD3 gene or locus comprising the SMAD3 gene that are associated with EoE, including sex-specific genetic alterations, or SNPs indicative of the presence of a genetic alteration in the SMAD3 gene or locus that is associated with EoE required by the claimed methods. Therefore, the claims fail to meet the written description requirement because the claims encompass a significantly large genus of genetic alterations and SNPs which are not described in the specification.
Claim Rejections - 35 USC § 102
10. 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 (i.e., changing from AIA to pre-AIA ) 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.
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(s) 1-3, and 10 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pividori et al (Lancet Respir Med. 2019. 7(6): 509-522 and Supplementary Appendix, 66 pages) as evidenced by the present specification at Tables 2 and 3, and the UK Biobank (“Genome-wide genotyping” available via URL: <community.ukbiobank.ac.uk/hc/en-gb/articles/15468170680605-Genome-wide-genotyping>, printed on 10 December 2025).
Pividori teaches a method comprising detecting a T allele at rs56062135 in the SMAD3 locus in a nucleic acid (DNA) sample obtained from a human subject (e.g., abstract, p. 3 and Table 2 at p. 24; and p. 2 of Supplemental Information and Supplemental Table 4). Note that rs56062135 is a single nucleotide polymorphism, and the T allele is the minor allele, and the T allele at rs56062135 is considered to constitute a genetic alteration associated with EoE. The fact that the T allele at rs56062135 is an EoE associated genetic alteration is evidenced by the teachings in the specification in Tables 2 and 3 which show that the T allele / minor allele was found to be correlated with EoE. Note that the specification is cited only to establish what is inherent to the T allele at rs56062135.
Pividori teaches that that the T allele at rs56062135 of the SMAD3 locus is significantly associated with asthma (Table 2 and Supplemental Table 4).
Accordingly, Pividori teaches a method comprising: detecting in genotype information, the presence of at least one EoE associated genetic alteration in a target gene identified in the subject, the presence of the genetic alteration indicating said patient has an increased risk for developing eosinophilic esophagitis, wherein said genetic alteration is present in a gene sequence from the SMAD3 locus, and the genetic alteration is a T allele at the rs56062135 SNP.
Regarding the preamble of the claims, as set forth in MPEP 2111.02 II: “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction.” Herein, the preamble language is a statement of purpose and intended result and does not result in a manipulative difference in the method steps of the claims. Accordingly, the process steps are able to stand alone and the preamble limitation is not considered to materially distinguish the claimed method over the prior art. Further, regarding the recitation of “in a subject in need thereof,” as this relates to a diagnosis claim, all subjects would be in need of knowing if they have a propensity to develop EoE. Neither the specification nor the claims define a subject in need thereof in a manner that distinguishes such subjects over the subjects in the method of Pividori.
Regarding claims 2 and 3, Pividori teaches that genotyping of the SNPs was accomplished using an Affymetrix array, and thereby a process that includes specific hybridization (e.g., p. 7 of the Supplementary Appendix). This fact is also evidenced by the teachings of the UK Biobank, cited at p. 7 of the Supplementary Appendix, which states:
“Genome-wide genotyping data is available for approximately 488,000 UK Biobank participants. Genotype calling was performed by Affymetrix (now part of ThermoFisher Scientific) on two closely related purpose-designed arrays. 50,000 participants were run on the UK BiLEVE Axiom array and the remaining 450,000 were run on the UK Biobank Axiom array.”
Regarding claim 10, Pividori teaches that the subjects suffer from asthma (e.g., p. 3, Table 2 and Supplemental Table 4 ).
11. Claim(s) 1-3, 5, 10 and 20-22 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Rothenberg (U.S. 20170183719).
Rothenberg teaches a method for diagnosing EoE comprising detecting a marker allele associated with susceptibility for developing EoE (e.g., para [0074]). Rothenberg (para [0073]) states:
“As disclosed herein, particular marker alleles or haplotypes, and markers in linkage disequilibrium therewith, can be associated with EoE. In some embodiments, the marker allele or haplotype is one that confers a significant risk or susceptibility to developing EoE. In some embodiments, one or more marker alleles are selected from those listed in any of Tables 2-5 and 7-10. ...In some embodiments, one or more marker alleles are associated with atopy. In some embodiments, one or more marker associated with atopy is selected from Table 10.”
Table 10 of Rothenberg includes the SNP rs17228058 in the SMAD3 gene at Chr15:
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Accordingly, Rothenberg teaches a method for detecting a propensity for developing EoE in a subject in need thereof, the method comprising: detecting in genotype information, the presence of at least one EoE associated genetic alteration in a target gene identified in said subject, the presence of said genetic alteration indicating said patient has an increased risk for developing eosinophilic esophagitis, wherein said genetic alteration is present in a gene sequence from the SMAD3 gene locus (i.e., the minor allele of rs17228058).
Regarding claims 2 and 3, Rothenberg teaches that genotyping of the SNPs can be performed using specific (array) hybridization (e.g., para [0083]) using a sample of genomic DNA (e.g., para [0115]).
Regarding claim 5, Rothenberg teaches that the sample in which the SNP is detected may be cells isolated from a subject (e.g., para [0049]).
Regarding claim 10, Rothenberg teaches “Consistent with an allergic etiology, EoE frequently co-occurs with allergic diseases, including asthma, eczema, allergic rhinitis and food anaphylaxis” (para [0064]). Rothenberg teaches that the patients studied therein had atopy, which included a physician-documented history of positive skin-prick test, allergic rhinitis, allergic dermatitis/eczema, asthma, or food allergy (para [0151]).
Regarding claim 20, Rothenberg states “In some embodiments, a subject diagnosed with EoE is treated for EoE” (para [0074-0075]).
Further regarding claim 22, Rothenberg teaches administering a glucocorticoid to patients diagnosed as having EoE (para [0122-0123]).12. Claim(s) 1-3, 5 and 10 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhu et al (Nature Genetics. 2018. 50(6): 857-864 and Supplementary Information, 66 pages, 79 pages total), as evidenced by the present specification at Tables 2 and 3 and the UK Biobank (“Genome-wide genotyping” available via URL: <community.ukbiobank.ac.uk/hc/en-gb/articles/15468170680605-Genome-wide-genotyping>, printed on 10 December 2025).
Zhu teaches a method comprising detecting a T allele at rs56062135 in the SMAD3 locus in a nucleic acid (DNA) sample obtained from a human subject (e.g., p. 858, col. 2 to p. 859, col. 1 and Table 2; and p. 2 of Supplemental Information). Note that rs56062135 is a single nucleotide polymorphism, and the T allele is the minor allele, and the T allele at rs56062135 is considered to constitute a genetic alteration associated with EoE. The fact that the T allele at rs56062135 is an EoE associated genetic alteration is evidenced by the teachings in the specification in Tables 2 and 3 which show that the T allele / minor allele was found to be correlated with EoE. Note that the specification is cited only to establish what is inherent to the T allele at rs56062135.
Zhu teaches that rs56062135 at the SMAD3 locus is significantly associated with asthma and allergic diseases (p. 859, col. 1 and Table 2).
Accordingly, Zhu teaches a method comprising: detecting in genotype information, the presence of at least one EoE associated genetic alteration in a target gene identified in the subject, the presence of the genetic alteration indicating said patient has an increased risk for developing eosinophilic esophagitis, wherein said genetic alteration is present in a gene sequence from the SMAD3 locus, and the genetic alteration is a T allele at the rs56062135 SNP.
Regarding the preamble of the claims, as set forth in MPEP 2111.02 II: “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction.” Herein, the preamble language is a statement of purpose and intended result and does not result in a manipulative difference in the method steps of the claims. Accordingly, the process steps are able to stand alone and the preamble limitation is not considered to materially distinguish the claimed method over the prior art. Further, regarding the recitation of “in a subject in need thereof,” as this relates to a diagnosis claim, all subjects would be in need of knowing if they have a propensity to develop EoE. Neither the specification nor the claims define a subject in need thereof in a manner that distinguishes such subjects over the subjects in the method of Zhu.
Regarding claims 2 and 3, Zhu teaches that genotyping of the SNPs was accomplished using an Affymetrix array, and thereby a process that includes specific hybridization (e.g., p. 1 and 4 of “Supplementary Note”). This fact is also evidenced by the teachings of the UK Biobank, cited at p. 1 of “Supplementary Note”, which states:
“Genome-wide genotyping data is available for approximately 488,000 UK Biobank participants. Genotype calling was performed by Affymetrix (now part of ThermoFisher Scientific) on two closely related purpose-designed arrays. 50,000 participants were run on the UK BiLEVE Axiom array and the remaining 450,000 were run on the UK Biobank Axiom array.”
Regarding claim 5, Zhu (p. 11 of printout “Life Sciences Reporting Summary”) states that “For UK Biobank blood collection, DNA extraction and genotyping procedures, researchers are blinded to phenotype information.” Thus, the sample in which the SNP was detected was a blood sample. This is considered to be a sample that contains cells (blood cells). Thereby, the method of Zhu is one in which the nucleic acids used to detect the SNP/genetic alteration are present in a cell sample isolated from the human subject.
Regarding claim 10, Zhu teaches that the subjects suffer from asthma or allergies (e.g., . 858, col. 2 to p. 859, col. 1 and Table 2).
Claim Rejections - 35 USC § 103
13. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 5 and 20-22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Pividori et al (Lancet Respir Med. 2019. 7(6): 509-522 and Supplementary Appendix, 66 pages), as evidenced by the present specification at Tables 2 and 3 and UK Biobank (“Genome-wide genotyping” available via URL: <community.ukbiobank.ac.uk/hc/en-gb/articles/15468170680605-Genome-wide-genotyping>, printed on 10 December 2025), and further in view of Hakonarson et al (U.S. 20190153523).
The teachings of Pividori are presented above.
Regarding claim 5, Pividori does not teach the identity of the sample which is used to perform the genotyping assay to detect the T allele at rs56062135.
However, Hakonarson teaches methods for diagnosing asthma in a patient wherein the methods comprise detecting a SNP in a biological sample from a patient, including a sample that is a cell or cells isolated from a patient or a blood sample from the patient (e.g., para [0054] and [0056-0057]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Pividori so as to have specifically obtained genotype information regarding the rs56062135 SNP of a patient by assaying a cell or cells