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 .
The preliminary amendment filed 1/4/2024 has been entered. Currently, claims 92, 95, 97, 101, 104-105, 107-108, 110, 113, and 116 are pending and under examination.
The IDS filed 10/4/2023 has been reviewed.
Claim Rejections - 35 USC § 112
112(a)
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.
Claims 92, 95, 97, 101, 104-105, 107-108, 110, 113, and 116 are rejected under 35 U.S.C. 112(a) 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, had possession of the claimed invention.
The claims are directed to administration of any IL-33 binding antagonist, ST2 binding antagonist, or an IL-1RAcP binding antagonist, or any of the large genus of therapeutics encompassed by claim 113, including any IL-13 binding antagonist, which must function to treat ANY IL-33 mediated disorder. This includes an enormous genus of drugs to treat an enormous genus of diseases, as evidenced by the disorders listed in claims 116, which include any inflammatory condition, any immune disorder, any eosinophilic disorder, any infection, any solid tumor, etc.
Relevant to the lack of particular structural limitations in the rejected claims , MPEP 2163 states:
The claimed invention as a whole may not be adequately described if the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional in the art or known to one of ordinary skill in the art.
Additionally, at 2163IIA3(a), the MPEP states:
“…describing a composition by its function alone typically will not suffice to sufficiently describe the composition. See Eli Lilly, 119 F.3 at 1568, 43 USPQ2d at 1406 (Holding that description of a gene’s function will not enable claims to the gene “because it is only an indication of what the gene does, rather than what it is.”); see also Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991)). 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) (The patent at issue claimed a method of selectively inhibiting PGHS-2 activity by administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product, however the patent did not disclose any compounds that can be used in the claimed methods. While there was a description of assays for screening compounds to identify those that inhibit the expression or activity of the PGHS-2 gene product, there was no disclosure of which peptides, polynucleotides, and small organic molecules selectively inhibit PGHS-2. The court held that “[w]ithout such disclosure, the claimed methods cannot be said to have been described.”).
In the case of the instant claims, the functionality of identifying a therapy comprising any IL-33 axis binding antagonist to treat any inflammatory condition, immune disorder, fibrotic disorder, infection, CNS disorder, tumor, etc is a critical feature of the claimed methods.
The specification defines “therapy” or “treatment” as clinical intervention which can be performed either for prophylaxis or during clinical pathology, and encompasses preventing the occurrence as well as alleviating symptoms, decreasing disease progression, etc. (specification page 28).
While the skilled artisan may be capable of developing inhibitors with the claimed functionality of being an antagonist as encompassed by the claims, 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. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895.
Further, while a particular agent may be an inhibitor of IL-33, IL-13, etc, there is no indication, teaching, guidance, or expectation that ALL inhibitors of the recited biomarkers would be capable of "treating" all of the enormous number of diseases and disorders as is broadly claimed.
The claims encompass a genus of structurally undefined compounds which require a specific functionality. However, the specification fails to teach how to distinguish members of the claimed genus of compounds which possess the claimed functionality (that is inhibiting the recited biomarkers AND treating any “IL 33 mediated disorder” from the large genus of disorders encompassed by the claims) from non-members.
For claims drawn to a genus, the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that “only describe[d] one type of structurally similar antibodies” that “are not representative of the full variety or scope of the genus.”). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615. Further, University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404, 1405 held that:
To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“ [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the invention, with all its claimed limitations, not that which makes it obvious,” and by using “such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.
Thus considering the breadth of the compounds required by the claimed methods, their specific required functionalities, and the teachings of the instant specification, it is the conclusion that the specification does not provide an adequate written description of the broadly claimed subject matter.
112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 92, 95, 97, 101, 104-105, 107-108, 110, 113, and 116 rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 92 is indefinite for the recitation “in a sample derived from” the patient because it is not clear if it refers to a sample that has been obtained from a patient, or if it includes samples that have been cultivated in vitro, such as cell lines.
The recitation of “reference level” in the context of comparing sST2 levels is unclear because neither the claim nor the specification define what type of sample this is. For example, it is not clear if it refers to a healthy control or to a patient with an IL-33 mediated disorder at a particular stage or severity of disease. The metes and bounds of the claim, therefore, cannot be determined.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 92, 95, 97, 104, 105, 110, and 116 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Levy (US 20130157290).
Levy teaches a method comprising determining level of sST2 level, including protein level (para 0045) in a biological sample from a subject and comparing it to a control level (para 0008-0011). Levy teaches the biological sample includes whole blood, plasma, or serum (para 0051). Levy teaches that sST2 levels that are higher than that of a normal control is indicative of poor prognosis. Levy teaches that the method can also monitor the efficacy of treatment of a disease (para 0020), including asthma. Levy teaches the treatment includes administering an sST2 antagonist (para 0022). Since Levy teaches all of the steps of the claimed methods, the teachings of Levy anticipate the claimed invention.
Claim Rejections - 35 USC § 103
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.
Claims 92, 95, 97, 104, 105, 110, and 116 are rejected under 35 U.S.C. 103 as being unpatentable over Hamzaoui (Hamzaoui et al; J Asthma. 2013 Oct; vol 50, pages 803-809; cited in the IDS dated 10/4/23) in view of Coyle (US 20100260770; cited in the IDS dated 10/4/23).
Hamzaoui teaches assessing the levels of sST2 and IL-33 in subjects with moderate as well as severe asthma (see page 2). Hamzaoui teaches that sST2 and IL-33 levels in induced sputum (IS) samples and serum were significantly higher in asthmatic children compared with healthy controls (see page 3, col 2) and that values of sST2 and IL-33 observed in IS were found to correlate with disease activity. Hamzaoui teaches that elevated IL-33 mRNA expression in IS was correlated with TNF-α mRNA levels and reflected the inflammatory process observed in the lung of young asthmatics (abstract).
Hamzaoui does not teach administering an IL-33 axis binding antagonist to a patient with levels of sST2 determined to be at or above a reference level, or assessing a treatment response of a patient treated with an IL-33 axis binding antagonist by determining the level of sST2 in a sample from the patient at a time point during the treatment. Coyle teaches that IL-33 activation induces various inflammatory mediators (para 0006, Fig. 2). Coyle teaches that expression of IL-33 in human asthmatic lung biopsies was increased (para 0027, Fig. 23) and that IL-33 specific binding polypeptides can be used to treat inflammatory disorders such as chronic inflammatory disorders including, among others, asthma, (para 0029, abstract). Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the invention to have administered asthma treatment as taught by Coyle to the patients taught by Hamzaoui for the obvious benefit of treating the patients for asthma, in view of the teachings of Hamzaoui and Coyle.
Claim 101 is rejected under 35 U.S.C. 103 as being unpatentable over Hamzaoui in view of Coyle, as applied to claims 92, 95, 97, 104, 105, 110, and 116 above, and further in view of Matsumoto (Allerg Int.; vol 63, pages 153-160. Epub 2014 Apr 25; cited in the IDS dated 10/4/23).
The teachings of Hamzaoui and Coyle are set forth above. Hamzaoui and Coyle do not teach further determining the level of periostin in a sample from the patient besides determining the level of sST2. Matsumoto teaches the use of periostin as a marker of pulmonary function decline and refractory Th2/eosinophilic inflammation in patients with asthma receiving long-term ICS treatment; and that serum periostin could be a companion diagnostic for targeted therapy against refractory Th2/eosinophilic inflammation (abstract, for example). Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to measure the levels of sST2 and periostin in a patient such as an asthmatic patient following the teachings of Hamzaoui and Matsumoto. The person of ordinary skill in the art would have been motivated to do so for better diagnosis and guided/targeted therapy. There would have been a reasonable expectation of success because Hamzaoui has demonstrated the significantly higher sST2 and IL-33 levels in IS and serum samples of asthmatic patients, which correlate with disease activity; and Matsumoto teaches the use of periostin as a marker of pulmonary function and inflammation in patients with asthma.
Claim 113 is rejected under 35 U.S.C. 103 as being unpatentable over Hamzaoui in view of Coyle, as applied to claims 92, 95, 97, 104, 105, 110, and 116 above, and further in view of Cairns (Pulmonary Pharmacology and Therapeutics, vol 18, pages 55-66, 2005; cited in the IDS dated 10/4/23).
The teachings of Hamzaoui and Coyle are set forth above. Hamzaoui and Coyle do not teach treatment with an IL-33 antagonist in combination with a tryptase-beta binding antagonist. Cairns teaches that a tryptase inhibitor could limit airway remodeling, a component of disease not addressed by current therapies including leukotriene antagonists; that tryptase has an acute dependence on its catalytic activity, providing a firm rationale that inhibitors directed at the enzymatic activity of tryptase will have some therapeutic benefit in asthma (page 57, 2nd column, 2nd paragraph); and that studies with the tryptase inhibitor from Axys, APC 366 (tryptase beta inhibitor) in the sheep and pig antigen models confirmed a role for mast cell tryptase beta in mediating airway hyperresponsiveness, which has advanced into human clinical trials for asthma (page 58, 2nd column, 2nd paragraph; and page 59, 1st column, 1st and 2nd paragraphs). Therefore, it would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to treat an asthma patient with an IL-33 specific binding polypeptide in combination with a tryptase beta inhibitor; and to measure the level of sST2 in a sample from said patient at a time point during the treatment following the teachings of Hamzaoui, Coyle, and Cairns. The person of ordinary skill in the art would have been motivated to do so in order to evaluate or assess the effectiveness of the treatment and to make better determination for the future therapy; and reasonably would have expected success because Hamzaoui has demonstrated that the significantly higher sST2 and IL-33 levels in IS and serum samples of asthmatic patients correlate with disease activity.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to examiner Jehanne Sitton whose telephone number is (571) 272-0752. The examiner is a hoteling examiner and can normally be reached Mondays-Fridays from 8:00 AM to 2:00 PM Eastern Time Zone.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Winston Shen, can be reached on (571) 272-3157. The fax phone number for organization where this application or proceeding is assigned is (571) 273-8300.
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/JEHANNE S SITTON/Primary Examiner, Art Unit 1682