DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s election without traverse of group I and the species rs229527 and inhibitor of TL1A in the reply filed on 2/3/26 is acknowledged.
Claims 6, 8, 21, 23, and 37 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 2/3/26.
Drawings
The drawings filed on 5/31/23 and 10/18/23 are objected to because they are not fully legible (Figures 2B, 4, 6, 7B, 7C, 7D, 16-19, 23, and 26). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Improper Markush Rejection
Claims 1-5, 7, 9-15, 20, and 22 are rejected on the judicially-created 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). The improper Markush grouping includes species of the claimed invention that do not share both a substantial structural feature and a common use that flows from the substantial structural feature. The members of the improper Markush grouping do not share a substantial feature and/or a common use that flows from the substantial structural feature for the following reasons: The claims are directed to a large multitude of SNPs, each having a different location in the genome and different influences on gene activity.
In response to this rejection, Applicant should either amend the claim(s) to recite only individual species or grouping of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claims(s) in fact share a substantial structural feature as well as a common use that flows from the substantial structural feature. This is a rejection on the merits and may be appealed to the Board of Patent Appeals and Interferences in accordance with 35 U.S.C. 134 and 37 CFR 41.31(a)(1).
When the Markush grouping is for alternatives of chemical compounds, they shall be regarded as being of a similar nature where the following criteria are fulfilled:
(A) All alternatives have a common property or activity; and
(B) (1) A common structure is present, i.e., a significant structural element is shared by all of the alternatives; or
(B) (2) In cases where the common structure cannot be the unifying criteria, all alternatives belong to a recognized class of chemical compounds in the art to which the invention pertains.
In paragraph (B)(1), above, the words “significant structural element is shared by all of the alternatives” refer 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. The structural element may be a single component or a combination of individual components linked together.
In paragraph (B)(2), above, the words “recognized class of chemical compounds” mean that 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.
In order for the members of the Markush group to belong to “recognized class of chemical compounds” there must be an expectation that the members of the class will behave in the same way in the context of the claimed invention. In other words, each member of the class could be substituted one for the other with the expectation that the same intended result would be achieved. In the instant case, detection of any specific SNP is not representative of any other SNP. There is no expectation that any one of the SNPs as claimed can be substituted for any of the other with the expectation of the same outcome.
As set forth in MPEP2117, “Note that 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 and when one of them [is] anticipated the group [is] therefore rendered unpatentable, 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)("[A]ctual equivalence is not enough to justify refusal of a patent on one member of a group when another member is in the prior art. The equivalence must be disclosed in the prior art or be obvious within the terms of Section 103." Id. at 599, 118 USPQ at 348).”
In the instant case, art against any one SNP would not be evidence against any of the remaining members. Additionally, claim 5 is directed to a modulator of miR-155 or an inhibitor of TLA, which is a genus of compounds that have different structures and mechanisms. The miR-155 modulator can be a miR-155 mimic or antagomir, which have completely different structures than an antiTL1A antibody (instant claim 7), wherein each agent acts via different mechanisms.
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 1-5, 7, 9-15, 20, and 22 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more. The claim(s) recite(s) a natural correlation. This judicial exception is not integrated into a practical application because the steps at a high level of generality of detection of a naturally occurring marker and correlation to a disease state. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite administration of any therapeutic agent to trat any inflammatory or fibrotic disease or condition.
Analysis, step 1: The claims are directed to a method, which is a statutory category of invention.
Analysis, step 2A, prong 1: The claims recite a judicial exception, a natural phenomenon. The claims are directed to assaying for a SNP and correlating it with the presence of an inflammatory or fibrotic disease or condition. This is a natural correlation, and it existed in the body before people had discovered it. It is a natural phenomenon. In claims 1 and 15, the claims recites determining the presence or risk of an inflammatory or fibrotic disease or condition by mere detection of one of the instantly recited naturally occurring SNPs. This limitation sets forth a judicial exception because this type of correlation is a consequence of natural processes, similar to the naturally occurring correlation found to be a law of nature by the Supreme Court in Mayo. Additionally, the correlation could be performed by a human using mental steps or basic critical thinking, which are types of activities that have been found by the courts to represent abstract ideas (e.g., the mental comparison in Ambry Genetics, or the diagnosing an abnormal condition by performing clinical tests and thinking about the results in Grams). Thus, the claim is directed to at least one exception, which may be termed a law of nature, an abstract idea, or both.
Analysis, step 2A, prong 2: In instant case, the method steps of (a) obtaining a sample from a subject, and (b) detecting the presence of a SNP consist of well understood, routine, conventional activity already engaged in by the clinical community (e.g., see Zhao et al. (Human Molecular Genetics, 2013, Vol. 22, No. 16 3347–3362) that teaches detection of rs229527 in a biological sample). Collecting a sample and detecting the presence of the SNP are insignificant and amounts to mere data gathering.
Finally, the claims further recites an additional element of administering a therapeutically effective amount of any therapeutic agent for the treatment of the disease or condition. However, the treatment step is recited with such a high level of generality that it encompasses the administration of any known therapy at the time of the invention. Specifically, a variety of treatments for inflammatory bowel disease were routinely and conventionally used (e.g., Pithadia et al. (Pharmacological Reports 2011, 63, 629-642)). There are no meaningful constraints on the administering step such that a particular treatment consideration would apply because it is not limited to any particular manner or type of treatment of any specific condition. Therefore, the treatment step fails to meaningfully limit the claim because it does not require any particular application of the abstract idea and therefore amounts only to a generic instruction to apply the exception.
Thus, the claims as a whole do not integrate the recited judicial exception into practical application.
Analysis, step 2B: The claims recite detection at a high level of generality of a naturally occurring marker and correlation to a disease state, which amount to mere data gathering and routine laboratory techniques. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite administration of any therapeutic agent to trat any inflammatory or fibrotic disease or condition. The claims as a whole do not amount to significantly more than a generic instruction to “apply” the judicial exception. Thus ,the instant claims do not amount to significantly more than the judicial exception itself and do not qualify as patent eligible subject matter under 35 U.S.C. § 101.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 14, 15, 20, and 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.
Claim 14 recites the limitation "the CD" of claim 1. There is insufficient antecedent basis for this limitation in because claim 1 does not recite CD.
Claim 15 recites the limitation "the therapeutic agent" in part (b). There is insufficient antecedent basis for this limitation in the claim because the claim has no prior recitation of a therapeutic agent. Claims 20 and 22 are rejected because they depend from claim 15 and do not obviate the rejection.
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 1-5, 7, 9-15, 20, and 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are directed to administration of any therapeutic agent, which is a genus of agents that has not been adequately described in the specification. The specification does not adequately describe the structure required for the agent to be therapeutic. Without further description of the structure required for the function, one would not be able to readily envision which agents are therapeutic or which agents are excluded from the instantly recited genus.
For example, Wang et al. (International Society of Nephrology, 2013, 84, 45-53) teach that water is a therapeutic agent (abstract).
The specification teaches that miR-155 modulators or anti-TL1A antibodies are therapeutic agents. The specification does not adequately describe the structure required for the agent to modulate miR-155 in any manner. Without further description of the structure required for the function, one would not be able to readily envision which agents modulate miR-155 or inhibit TL1A or act as a therapeutic agent in any manner. The species of the specification are not representative of the entire claimed genus.
Additionally, claim 1 recites “a proxy polymorphism in linkage disequilibrium therewith as determined with an r2 of at least 0.85”, which is a genus of polymorphisms that have not been adequately described in the specification. Without further description of the structure required for the function, one would not be able to readily ascertain which polymorphisms meet the limitation of being a proxy polymorphism in linkage disequilibrium therewith as determined with an r2 of at least 0.85.
Claim 15 recites subjecting the biological sample to an assay “adapted to detect at least one polymorphism”. However, the specification does not adequately describe the parameters of adapting an assay to detect at least one polymorphism. Without further description of the method steps required, one would not be able to readily envision which assays have been adapted to detect at least one of the recited polymorphisms.
The MPEP states that for a generic claim, the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. See MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitute a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad genus. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618. Additionally, in Carnegie Mellon University v. Hoffman-La Roche Inc., Nos. 07-1266, -1267 (Fed. Cir. Sept. 8, 2008), the Federal Circuit affirmed that a claim to a genus described in functional terms was not supported by the specification’s disclosure of species that were not representative of the entire genus. Furthermore, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The claims are rejected under the written description requirement for failing to disclose adequate species to represent the claimed genus, the genus being agents that modulate miR-155 or inhibit TL1A or act as a therapeutic agent in any manner; or proxy polymorphisms in linkage disequilibrium therewith as determined with an r2 of at least 0.85.
The Guidelines for Examination of Patent Applications under the 35 USC § 112, first paragraph, “Written Description” Requirement”, published at Federal Register, Vol. 66, No. 4, pp. 1099-1111 outline the method of analysis of claims to determine whether adequate written description is present. The first step is to determine what the claim as a whole covers, i.e., discussion of the full scope of the claim. Second, the application should be fully reviewed to understand how applicant provides support for the claimed invention including each element and/or step, i.e., compare the scope of the claim with the scope of the description. Third, determine whether the applicant was in possession of the claimed invention as a whole at the time of filing.
Thus, having analyzed the claims with regard to the Written Description guidelines, it is clear that the specification does not disclose a representative number of species for agents within the instant enormous genus that function as claimed. Thus, one skilled in the art would be led to conclude that Applicant was not in possession of the claimed invention at the time the application was filed.
Claims 1-5, 7, 9-15, 20, and 22 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of detecting rs229527 and correlating to Crohn’s disease, does not reasonably provide enablement for a method of treating any inflammatory or fibrotic disease or condition via delivery of any therapeutic agent after detection of rs229527. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
Factors to be considered in a determination of lack of enablement include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)
The claims are directed to a method of treating any inflammatory or fibrotic disease or condition via delivery of any therapeutic agent via any means after detection of rs229527.
The specification demonstrates correlating specific SNPs to the presence of Crohn’s disease, as well as statistical analysis and prophetic screening for therapeutic agents.
The specification does not draw an adequate nexus between delivery of any possible therapeutic agent to treat any possible inflammatory or fibrotic disease or condition.
For example, Wang et al. (International Society of Nephrology, 2013, 84, 45-53) teach that water is a therapeutic agent (abstract). Certainly water alone would not treat any possible inflammatory or fibrotic disease or condition.
The specification does not draw an adequate nexus between detection of rs229527 and the predictable correlation to the presence of any inflammatory or fibrotic disease or condition. The specification has determined via statistical analysis that the presence of rs229527 is correlated to Crohn’s disease, which is not commensurate in scope with any inflammatory or fibrotic disease or condition.
The claims encompass a method of treating any inflammatory or fibrotic disease or condition via delivery of any possible therapeutic agent provided that rs229527 is detected, although rs229527 is not indicative of any inflammatory or fibrotic disease or condition; and certainly not any therapeutic agent would treat any inflammatory or fibrotic disease or condition.
Additionally, although TL1A inhibition is known to be involved in a variety of preclinical inflammatory disease models ( see Table 1 of Hsu et al. (Mucosal Immunology | VOLUME 4 NUMBER 4 | JULY 2011, 368-370), Hsu et al. teaches that how it mediates its effects, and which cells are the real targets, remains to be elucidated (page 370). The specification does not draw an adequate nexus between delivery of any TL1A inhibitor via any mode of delivery and the predictable outcome of treatment of any possible inflammatory or fibrotic disease or condition (instant claims 5 and 20).
Additionally, there is no guidance in the specification as filed that teaches how to deliver the instantly recited genus of inhibitors, each having different delivery challenges, and predictably treat any inflammatory or fibrotic disease or condition in vivo.
With regards to siRNAs, a single species of the instant inhibitors, the instant siRNAs are not required to have any specific structural relationship with any specific target sequence. Thee instant claims encompass targeting any target that has the effect of treating any inflammatory or fibrotic disease or condition.
Applicant is not enabled for mediating RNA interference in vivo by the broadly recited methods, as delivery and effective action therein is known in the art to be unpredictable with regards to dsRNA duplexes. Activity in vitro is not predictable of the in vivo therapeutic effect in the in vivo complex environment.
For example, Elbashir et al. (The EMBO Journal, Vol. 20, No. 23, pages 6877-6888, 2001) teaches that duplexes of 21-23 nt RNAs are the sequence specific mediators of RNAi and that even single mismatches between the siRNA duplex and the target mRNA abolish interference (abstract and page 6888).
Fujita et al. (Int. J. Mol. Sci. 2015, 16, 5254-5270) teach that two types of small RNA molecules, small interfering RNAs (siRNAs) and microRNAs (miRNAs), have a central function in RNAi technology. The success of RNAi-based therapeutic delivery may be dependent upon uncovering a delivery route, sophisticated delivery carriers, and nucleic acid modifications (page 5254). Fujita et al. teach that the success of an RNAi-based therapy in clinical trials rests on careful selection of target genes and miRNAs. Moreover, we suggest that a delivery route, sophisticated delivery carriers, chemical modification, and modified RNAi platforms are needed to enhance RNAi effects in cancer cells (pages 5262-5263).
Friedrich et al. (BioDrugs (2022) 36:549–571) teach that still, the development of siRNA therapeutics faces several challenges and issues, including the definition of optimal siRNAs in terms of target, sequence, and chemical modifications, siRNA delivery to its intended site of action, and the absence of unspecific off-target effects (Abstract). Friedrich et al. teach that the use of short siRNA is preferred because longer siRNAs can provoke an inflammatory antiviral immune response (page 551).
Friedrich et al. teach: As a basic parameter, the GC content of an siRNA is addressed by algorithms and its range should be between ~30 and 60%. Too low GC content can lead to weak or unspecific binding, whereas too high GC content may impede unwinding by helicase and incorporation in the RISC complex. Between nucleotides 9 and 14, however, low GC content is important to increase RISC function during mRNA cleavage. Sequences that could lead to secondary structures in the sense or antisense stand must be avoided (e.g., internal repeats, palindromes, CCC or GGG sequences). A proper duplex formation is essential for functional siRNA. Additionally, sequences that contain single nucleotide polymorphisms, miRNA seed matches, and known toxic motifs must be avoided (page 552).
Friedrich et al. teach: The 5′-untranslated region (and 3′-untranslated region) of mRNA as well as sequences close to the start codon are not recommended as siRNA targets, as the binding of regulatory proteins in this area may impede RISC binding and thus the silencing effect. Rather, selecting regions in the open reading frame about 50–100 nucleotides downstream of the start codon is recommended. Furthermore, siRNAs closer to the start codon seem to be more efficient than those further downstream (page 552). Friedrich et al. is evidence as to the delivery challenges, as well as the fact that not any siRNA inhibitor of a target would result in the desired therapeutic effect.
As outlined above, it is well known that there is a high level of unpredictability in the RNAi art (a single species of the instant inhibitors) for therapeutic in vivo applications and design. The scope of the claims in view of the specification as filed together do not reconcile the unpredictability in the art to enable one of skill in the art to make and/or use the claimed invention, namely a broad method of treating treat any inflammatory or fibrotic disease or condition via broad systemic delivery of a broad genus of agents that act via different mechanisms and have different levels of activity encompassing in vivo effects.
Additionally, instant claim 15 (preamble) is directed to a method of treating any inflammatory or fibrotic disease or condition but the recited outcome is treating the inflammatory bowel disease and part (a) requires for the subject to have an inflammatory bowel disease. Treating an inflammatory bowel disease would not predictably result in the treatment of any inflammatory or fibrotic disease or condition as recited in the preamble.
MPEP 2164.01
Any analysis of whether a particular claim is supported by the disclosure in an application requires a determination of whether that disclosure, when filed, contained sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use the claimed invention.
Also, MPEP 2164.01(a)
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
Given the teachings of the specification as discussed above, one skilled in the art could not predict a priori whether introduction of any therapeutic agent in vivo by the broadly disclosed methodologies of the instantly claimed invention, would result in successful treatment of any inflammatory or fibrotic disease or condition in vivo.
To practice the claimed invention, one of skill in the art would have to de novo determine; the stability of the molecule in vivo, delivery of the molecule to the whole organism, specificity to the target tissue in vivo, dosage and toxicity in vivo, and entry of the molecule into the cell in vivo and the effective action therein. Without further guidance, one of skill in the art would have to practice a substantial amount of trial and error experimentation, an amount considered undue and not routine, to practice the instantly claimed invention.
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation (see MPEP 2164.01(a)).
Claim Rejections - 35 USC § 103
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 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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) 1-5, 7, and 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhao et al. (Human Molecular Genetics, 2013, Vol. 22, No. 16 3347–3362), in view of Riley (Mayo Clin Proc, Dec 1972, Vol 47, 975-979), Kruidenier et al. (US 2020/0362025 A1), and Zheng et al. (J Clin Lab Anal. 2018;32:e22266, 1-7).
Zhao et al. teach that rs229527 is a statistically significant SNP in Graves’ disease (page 3350). Zhao et al. teach that the SNP is associated with autoimmune diseases and Graves’ disease (page 3355). Given that it was known that rs229527 is indicative of Graves’ disease, it would have been obvious to treat a patient after detecting this SNP with a therapeutic agent that treats Graves’ disease (instant claim 1).
Graves’ disease meets the instant limitation of an inflammatory disease or condition because Zhao et al. teach that the SNP rs229527 is located in the gene C1QTNF6 (Table 2) and that C1QTNF6 , which was reported to be associated with autoimmune disease, such as type1 diabetes, vitiligo, multiple sclerosis and Crohn’s disease, was independently associated with Graves’ disease in this study (page 3355) (instant claim 1).
Additionally, Riley teaches that an inflammatory infiltration, consisting predominantly of lymphocytes and plasma cells, is found in all orbital tissues including the lacrimal gland in Graves’ disease (page 975). Riley teaches that, in addition to inflammatory cells, fibroblasts were plentiful. In three cases in which we performed muscle biopsy at the time of surgical correction of ocular deviations due to extra-ocular muscle involvement, electron microscopy demonstrated disorganization of the myofibrillar structure of the muscle cells (page 976). Therefore, Graves’ disease meets the instant limitation of an inflammatory or fibrotic disease or condition.
Zhao et al. teaches detection of the polymorphism via quantitative RT-PCR (page 3359) (instant claim 2) from blood samples (page 3359) (instant claim 3).
Optimizing a therapeutic regimen via increasing or decreasing a dosage of the therapeutic agent is an obvious step to a treatment regimen and is routine to one of ordinary skill in the art (instant claim 4).
It would have been obvious for the therapeutic agent to be a TL1A inhibitor because Kruidenier et al. teach that Graves’ disease is mediated, at least in part, by TL1A signaling [0079]. Therefore, it would have been obvious to inhibit TL1A with the expectation of a treatment effect (instant claim 5). It would have been obvious for the TL1A inhibitor to be a TL1A-antibody because Kruidenier et al. teach that anti-TL1A antibodies are therapeutic agents to inhibit the expression of TL1A activity or expression (abstract) (instant claim 7).
It would have been obvious for the expression of miR-155 to be elevated because Zheng et al. teaches that serum miR-155 is elevated in Graves’ disease and can differentiate between Graves’ disease patients and healthy controls (page 1) (instant claim 9).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Amy R Hudson whose telephone number is (571)272-0755. The examiner can normally be reached M-F 8:00am-6:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at 571-270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/AMY ROSE HUDSON/Primary Examiner, Art Unit 1636
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