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 .
Continued Examination Under 37 CFR 1.114
2. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 07 August 2026 has been entered.
3. Applicant's arguments and amendments to the claims presented in the reply of 07 August 2025 have been fully considered but do not place the application in condition for allowance. All rejections and objections not reiterated herein are hereby withdrawn.
In particular, the previous rejection of claims 1-3, 5, 10 and 21-22 under 35 U.S.C. 101 has been obviated by the amendment to the claims to require the final step of “treating said subject harboring said one or more SNPs using one or more of esophageal dilation, topical glucocorticoids, proton pump inhibitors, and corticosteroids.”
Claim Status
4. Claims 1-3, 5, 6, 8-10, 12-15, 17-18, 21 and 23-25 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Claims 12-15 and 17-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08 October 2025.
Claims 6, 8, 9, 23 and 24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim.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. Election was made without traverse in the reply filed on 08 October 2025.
Claims 1-3, 5, 10, 21 and 25 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.
New Claim Objections
5. Claims 1-3, 5, 10, 21 and 25 are objected to because of the following informalities:
Claims 1-3, 5, 10, 21 and 25 are objected to because the claims recite “said one or more SNPs” whereas the claims should recite “the at least one EoE associated SNP” or “said SNP.”
Claim 25 recites “administering to the subject with an siRNA, shRNA…” whereas the claim should recite “administering to the subject an siRNA, shRNA….”
Appropriate correction is required.
Maintained Improper Markush Grouping Rejection
6. Claims 1-3, 5, 10, 21 and 25 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 a C allele in rs887992 in TMEM182, an A allele in rs2106984 in RAD50, a T allele in rs1620996 in SOX4, a T allele in rs2513845 in MATN2, a T allele in rs185811602 in PRKG1, a T allele in rs147702004 in RHOG, a T allele in rs182139615 in SHANK2, an A allele in rs146034499 in GPR12, a G allele in rs2279293 in RORA, a T allele in rs56062135 in SMAD3, an A allele in rs5348565 in GALNT1, an A allele in rs143457388 in CPNE4, a C allele in rs188483654 in URGCP, an A allele in rs147307036 in NAMPT, a T allele inrs62541556 inJAK2, and/or a C allele in rs191051238 in CCNY 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 SNP gene has a different chemical structure in that it consists of a different nucleotide alteration and is flanked by a different nucleotide sequence. See the distinct nucleotide sequences presented in Fig. 10A for the recited SNPs. For example, the elected SNP rs56062135 has a structure that is distinct from rs887992, as shown in the partial sequence alignment of their sequences listed in Fig. 10A, as set forth below:
rs56062135:
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20
392
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rs887992:
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20
422
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The only structural similarity present is that all of the SNPs comprise nucleotides. The fact that the SNPs comprise nucleotides per se does not support a conclusion that they have a common single structural similarity because the structure of comprising nucleotides or of being a SNP is not essential to the asserted common activity of being associated with EoE or indicative of a subject having an increased risk of developing EoE. Accordingly, while the different SNPs are asserted to have the property of being associated with risk of developing EoE, they do not share a substantial structural similarity essential to this activity.
Further, the recited SNPs do not belong to a chemical or art-recognized class because there is no expectation from the knowledge in the prior art that the SNPs 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 SNPs possess the common property of being associated with the risk of developing 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 treating eosinophilic esophagitis (EoE) in a subject in need thereof, the method comprising: detecting in genotype information, the presence of at least one EoE associated SNP, wherein said SNP is a T allele in rs56062135 in SMAD3 gene” and reciting in a dependent claim that the method further comprises detecting the presence of one or more of additional SNPs selected from C allele in rs887992 in TMEM182….”. 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.
Response to Remarks:
The response states:
“where a Markush group includes only materials from a recognized scientific class of equivalent materials or from an art-recognized class, "the mere existence of such a group in an application tend[s] to prove the equivalence of its members ... in the absence of some convincing evidence of some degree of non- equivalency of one or more of the remaining members." In re Ruff, 256 F.2d 590, 598-99, 118 USPQ 340, 348 (CCPA 1958) (emphasis added). Accordingly, the failure of the prior art to previously establish that the recited SNPs would be indicative of a predisposition to EoE does not render the Markush grouping improper absent evidence of non-equivalency.”
These arguments have been fully considered but are not persuasive because Applicant has not established that the recited SNPs do belong to an art-recognized class. There is no requirement for the examiner to provide evidence of non-equivalency when the recited SNPs do not share a single structural similarity that is essential to the asserted common property or activity – i.e., of being indicative of / associated with EoE and there is no evidence of record to establish that the recited SNPs belong to an art-recognized class.
The response further states:
“Here, all members of claim 1 share a single structural similarity because they belong to the same art-recognized class of genetic alterations, more specifically, SNPs useful in identifying a subject with a predisposition for EoE. This class of equivalent materials, "EoE-associated SNP" or "EoE-associated specific marker" is identified in the specification as filed at page 7, lines 22-27. As the specification as filed includes this group, the equivalence of its members is satisfied absent some convincing evidence of some degree of non-equivalency of these members.
Furthermore, the data described by the specification as filed supports the equivalency of these SNPs. More specifically, Figures 4A-4C and Table 2 show that the meta-analysis conducted herein identified multiple EoE-associated SNPs, including a few previously identified SNPs (see, e.g., CLEC16A). Accordingly, these previously identified EoE-associated SNPs indicate that the prior art acknowledges the existence of the claimed group and the specification as filed teaches that each of the recited novel EoE-associated SNPs belong to this group.”
These arguments are not persuasive because it is only the specification which teaches that the recited SNPs have the property of being indicative of a predisposition to EoE. The prior art does not teach that the recited SNPs have the property of being useful for identifying a subject with a predisposition of EoE. Thus, the prior art has not established that the SNPs recited in claim 1 belong to the same art-recognized class of genetic alterations.
Regarding the arguments pertaining to Table 2 of the specification, this table indicates that the CLEC16A, TSLP/WDR36 and CAPN14 loci were “Previously identified loci.” The “**” / “Previously identified loci” designation is included in the column that lists gene names and not the column that lists the SNPs within the gene. Thus, Table 2 appears to indicate only that these 3 genes were previously identified as potentially linked to EoE. Most importantly, claim 1 does not include the CLEC16A, TSLP/WDR36 and CAPN14 SNPs. Thus, Table 2 does not establish that the SNPs required by claim 1, and dependent claims 2-3, 5, 10, 21 and 25, all belong to the same art-recognized class of SNPs/genetic alterations.
Note that MPEP 2173 provides the following example which emphasizes that an “art recognized class” is one in which the prior art teaches the equivalence of the members of the Markush grouping:
“In other words, each member could be substituted one for the other, with the expectation that the same intended result would be achieved. For example, in the context of a claim covering a disposable diaper, a limitation “the fastener selected from the group consisting of a pressure sensitive adhesive and complementary release material, a complementary hook and loop structure, a snap, and a buckle” would likely be considered an art recognized class because a review of the prior art would establish that it was well known that each member could be substituted for each other with the expectation that the intended result (repositionable and refastenable) would occur.” Emphasis added.
In the present application, Applicant does not point to any teachings in the prior art which establishes that it was well known that the recited SNPs could be substituted for each other with the expectation that the intended result – i.e., the SNPs of a C allele in rs887992 in TMEM182, an A allele in rs2106984 in RAD50, a T allele in rs1620996 in SOX4, a T allele in rs2513845 in MATN2, a T allele in rs185811602 in PRKG1, a T allele in rs147702004 in RHOG, a T allele in rs182139615 in SHANK2, an A allele in rs146034499 in GPR12, a G allele in rs2279293 in RORA, a T allele in rs56062135 in SMAD3, an A allele in rs5348565 in GALNT1, an A allele in rs143457388 in CPNE4, a C allele in rs188483654 in URGCP, an A allele in rs147307036 in NAMPT, a T allele inrs62541556 inJAK2, and a C allele in rs191051238 in CCNY.
Claim Rejections - 35 USC § 112(a) – Written Description
7. 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.
Claim 25 is 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).”
Claim 25 is drawn to a method for treating EoE in a subject in need thereof comprising detecting the presence of at least one EoE associated SNP, wherein the elected SNP is a T allele in rs56062135 in SMAD3, and treating the subject harboring the SNP using one or more of esophageal dilation, topical glucocorticoids, proton pump inhibitors, and corticosteroids, and further administering to the subject “an siRNA, shRNA, antisense oligonucleotides, peptides, or peptide/DNA complexes which alters mRNA or protein levels of a EoE associated gene harboring the EoE associated SNP.”
Accordingly, the claims require an agent that alters - i.e., either increases or decreases - the level of mRNA or protein of a SMAD3 gene harboring a T allele in rs56062135.
The specification defines an agent as follows:
“The terms “agent” and “compound” are used interchangeably herein and denote a chemical compound, a mixture of chemical compounds, a biological macromolecule, or an extract made from biological materials such as bacteria, plants, fungi, or animal (particularly mammalian) cells or tissues. Biological macromolecules include siRNA, shRNA, antisense oligonucleotides, peptides, peptide/DNA complexes, and any nucleic acid based molecule which exhibits the capacity to modulate the activity of the CNV or SNP-containing nucleic acids described herein or their encoded proteins.”
Accordingly, the claims encompass a significantly large genus of agents that have any of the contemplated diverse chemical structures and which have the functional property that they either increase or decrease the quantity of a mRNA or protein expressed by a SMAD3 gene having a T allele at rs56062135.
The claims do not define the agent in terms of their specific structure or in terms of other relevant structural properties.
The specification does not identify any agents that meet the limitations of the claims of an agent that increases or decreases the quantity of a mRNA or protein expressed by a SMAD3 gene having a T allele at rs56062135. Nor does the specification establish that a representative number of the diverse compounds encompassed by the claims of siRNA, shRNA, antisense oligonucleotides, peptides, or peptide/DNA complexes that increase or decrease the quantity of mRNA or protein expressed by a SMAD3 gene having a T allele at rs56062135, were known in the prior art.
The variation encompassed by the presently claimed genus of agents for treating EoE is large and there is no evidence of record to establish that the members of the claimed genus share a common structure. The disclosure therefore does not show that applicant was in possession of the necessary common attributes or features possessed by the members of the claimed genus of agents that are to be administered to subjects having the T allele at rs56062135 of SMAD3. Accordingly, the skilled artisan would not recognize that applicant was in possession of the invention as broadly claimed at the time the application was filed.
Note that the 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.” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)).
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 48 USPQ2d 1398 (CAFC 1997). The Federal Circuit has cautioned that, for claims reciting a genus of antibodies with particular functional properties, “[c]laiming antibodies with specific properties, e.g., an antibody that binds to human TNF-a with A2 specificity, can result in a claim that does not meet written description even if the human TNF-a protein is disclosed because antibodies with those properties have not been adequately described." Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875, 1877- 78 (Fed. Cir. 2011).
Additionally, Cf. University of Rochester v G.D. Searle & Co., Inc., Monsanto Company, Pharmacia Corporation, and Pfizer Inc., No. 03-1304, 2004 WL 260813 (Fed. Cir., Feb. 13, 2004) held that:
Regardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to that subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.
Also, 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."
With respect to the present invention, there is no record or description which would demonstrate conception of a representative number of the siRNA, shRNA, antisense oligonucleotides, peptides, and peptide/DNA complexes required by claim 25. Therefore, claim 25 fails to meet the written description requirement because the claim requires administering a genus of agents that increase or decrease the mRNA or protein level of a SMAD3 gene harboring the EoE associated SNP of a T allele at rs56062135 which are not described in the specification. Response to Remarks:
The response states:
“in the interest of advancing prosecution, the claims are amended to replace this feature with treatment using one or more of esophageal dilation, topical glucocorticoids, proton pump inhibitors, and corticosteroids. Support for this amendment can be found throughout the specification as filed including, without limitation, at pages 25, lines 1-28 of the application as filed. Accordingly, it is clear that each of the treatments are adequately described in view of this amendment.”
However, new claim 25 has been added which recites the same limitations that were previously recited in claim 1 – i.e., that the subject with EoE-associated SNP is administered an siRNA, shRNA, antisense oligonucleotides, peptides, or peptide/DNA complexes which alters mRNA or protein levels of a EoE associated gene harboring the EoE associated SNP. Claim 25 is rejected for the reasons set forth above.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CARLA J MYERS whose telephone number is (571)272-0747. The examiner can normally be reached M-Th 6:30-5:00 EST.
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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 on 571-272-0731. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CARLA J MYERS/Primary Examiner, Art Unit 1682
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