DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-14 are pending.
Claims 7-14 have been withdrawn.
Claims 1-6 are currently under examination.
Objections to Specification withdrawn
The objections to the specification are withdrawn in view of Applicant’s arguments and the amendment to the Specification.
35 USC § 112(a) rejections withdrawn
The rejection of claims 1-6 for failing to comply with the enablement requirement are withdrawn in view of Applicant’s amendment to claim 1.
35 USC § 103 rejections maintained
The rejections of claims 1-4 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Orengo et al (US 2017/0096483, published April 6, 2017) in view of Burkett et a; (US 2022/0152148, published May 19, 2022, effective filing date March 18, 2019) are maintained.
The claims are drawn to a method of preventing anaphylaxis in a subject, comprising providing to the subject a composition comprising an inhibitor of SerpinA3 gene expression.
Orengo disclose that SerpinA3f is associated with IL-33 diseases (paragraphs 14, 71, 74; Table 4). Orengo discloses the treatment of IL-33 associated diseases with IL-33 antagonists which decrease levels of SerpinA3f, one of nine markers of IL-33-associated disease (paragraphs 14, 66, 71). While Orego does not disclose methods that inhibit SerpinA3f gene expression, Orengo discloses antagonist of IL-33 that lower the expression levels of SerpinA3f. Orengo disclose that IL-33 signaling has been implicated in anaphylaxix by mast cell activation and food allergies (paragraph 5, 63).
Orengo does not specifically disclose treating a subject with SerpinA3f siRNA.
Burkett identified a role for CLEC-2 in controlling the expression of IL-33 (paragraph 44, 45). Burkett disclose that SerpinA3f was upregulated upon deletion of CLEC-2. Burkett disclose that IL-33 is a critical regulator of allergic airway inflammation in the lung (Abstract; paragraphs 21, 44, 45). Burkett disclose that agents that are capable of modulating the expression, activity, and/or function of SerpinA3f include SerpinA3f siRNA (paragraphs 70-74, 112, 151, 215-220; claims 16, 17). Burkett disclose agents that modulate the expression, activity, and/or function of Serpina3f genes or gene products differentially expressed upon deletion of CLEC-2 in macrophages or absence of CLEC-2 in macrophages (paragraph 10).
One of ordinary skill in the art would have been motivated to apply Burkett’s method of using SerpinA3f siRNA to treat allergic responses to Orengo’s method of treating anaphylaxis with an IL-33 antagonist because both Burkitt and Orengo disclose methods for the treatment of IL-33-associated allergic responses with antagonists which decrease levels of SerpinA3f. As disclosed in Burkett these antagonists include SerpinA3f siRNA. It would have been prima facie obvious to combine Orengo’s method of preventing anaphylaxis with antagonists of IL-33 that lower levels of SerpinA3f with Burkett’s method of using SerpinA3f siRNA to treat allergic responses to have a method of treating anaphylaxis in a subject, comprising providing to the subject a composition comprising an inhibitor of SerpinA3 gene expression. One of ordinary skill in the art would have had a reasonable expectation of success given the methods of using siRNA for therapy were known in the art.
Applicant argues that Orengo is directed to methods of treating IL-33 mediated disorders and does not teach treating an IL-33 mediated disorder with an inhibitor of a SerpinA3 gene. Applicant argues that Orengo is directed to treating the IL-33 mediated disorder with an IL-33 antagonist. Applicant argues that anaphylaxis is not listed in Orengo as an IL-33 mediated disease or disorder to be treated.
Applicant further argues that the only context in which Orengo discusses SerpinA3f is as one of several biomarkers, e.g. that can be evaluated to monitor the treatment with the IL-33 antagonist. Applicant argues that Orengo teaches that treatment with the IL-33 antagonist can be evaluated by measuring one or more of "resistin-like alpha (RETNA); chemokine (C-C motif) ligand 8 (Ccl8); serum amyloid A 3 (Saa3); Gm1975 (BCl 17090); killer cell lectin-like receptor (Kirgl); stefin Al (Csta); membrane-spanning 4-domain (Ms4a8a); chemokine (C-C motif) ligand 11 (Ccll 1 ); and serine ( or cysteine) peptides (Serpina3f)". Applicant argues that Orengo provides no disclosure or suggestion that inhibiting a SerpinA3 gene would be sufficient to treat or prevent an IL-33 mediated disorder, and certainly does not disclose or suggest that inhibiting a SerpinA3 gene would be effective to prevent anaphylaxis as presently claimed.
In addition, Applicant argues that Burkett discloses methods of modulating Type 2 and/or Type 3 immune response by administering an agent capable of modulating CLEC-2 signaling. Applicant argues that Burkett is not directed to anaphylaxis, nor is anaphylaxis a Type 2 or Type 3 immune response. Applicant argues that Burkett does not disclose anaphylaxis anywhere throughout the application. Applicant disclose that Burkett does not disclose or suggest modulating any immune response by administering siRNA against SerpinA3f, but rather is directed to use of agents that modulate
CLEC-2 signaling, e.g. CLEC-2 agonists, with a particular focus on agents that disrupt CLEC- 2/PDPN interactions. Applicant argues that Burkett only discloses Serpina3f as one of at least 55 potential genes whose expression, activity, or function may be modulated by the agent that modulates CLEC-2 signaling. Applicant argues that Burkett discloses that the activity expression, or function of many potential genes may be effected as a result of administering the agent that modulates CLEC-2 signaling, e.g. a CLEC-2 agonist, to the subject. Applicant argues that Burkett does not disclose or suggest that targeting SerpinA3f would be sufficient to treat or prevent any allergic response in a subject, and certainly does not disclose or suggest siRNA against
SerpinA3f for treatment or prevention of anaphylaxis.
Applicant further argues that as described above the method of Burkett is not a method of "using SerpinA3f siRNA to treat allergic responses", but rather discloses a method of modulating CLEC-2 signaling, e.g. using a CLEC-2 agonist. Applicant further argues that Burkett simply does not teach or suggest that administering siRNA against SerpinA3f would be sufficient to treat or prevent an allergic response. Applicant argues that the method of Orengo is not a "method of treating anaphylaxis with antagonists of SerpinaA3f' but rather, Orengo discloses a method of treating an IL-33 mediated
disorder with an IL-33 antagonist. Applicant argues that Orengo does not disclose or suggest that inhibiting SerpinA3f would be sufficient for treatment or prevention of anaphylaxis.
Applicant’s argument have been considered but are not persuasive. In response to applicant's arguments against Orengo and Burkett individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Orengo disclose that SerpinA3f is associated with IL-33 diseases that includes anaphylaxis and food allergies (paragraphs 5, 14, 63, 71, 74; Table 4). Orengo discloses the treatment of IL-33 associated diseases with IL-33 antagonists which decrease levels of SerpinA3f, one of nine markers of IL-33-associated disease (paragraphs 14, 66, 71). While Orengo does not disclose methods that inhibit SerpinA3f gene expression, Burkett disclose that that agents that are capable of modulating the expression, activity, and/or function of SerpinA3f include SerpinA3f siRNA (paragraphs 70-74, 112, 151, 215-220; claims 16, 17). Burkett further disclose that IL-33 is a critical regulator of allergic airway inflammation in the lung (Abstract; paragraphs 21, 44, 45). Burkett disclose agents that modulate the expression, activity, and/or function of Serpina3f genes or gene products differentially expressed upon deletion of CLEC-2 in macrophages or absence of CLEC-2 in macrophages (paragraph 10). Burkett disclose that the subject is suffering from or at risk for an allergic inflammatory disease (paragraph 14). Burkett disclose that the allergic inflammatory disease may be allergic airway inflammation (Id). Burkett disclose that they have identified a role for CLEC-2 in regulating both alveolar macrophage function and allergic airway inflammation, in part by controlling expression of IL-33 and potentiating Th2 proliferation and differentiation. (paragraph 44). Burkett disclose that CLEC-2-/- mice develop spontaneous airway inflammation and have increased expression of IL-33 (paragraph 45). Given that both Orengo and Burkett identify Serpina3f as a marker of IL-33 mediated inflammatory responses while Burkett discloses treating a subject with IL-33 mediated inflammatory response with agents
modulate the expression, activity, and/or function of Serpina3f genes or gene products, while Orengo discloses IL-33 antagonists for treating IL-33 associated diseases, it would have been obvious to have a method of preventing anaphylaxis in a subject, comprising providing to the subject a composition comprising an inhibitor of SerpinA3f gene expression.
It is noted that a prior art reference is relevant for all its teachings, not only its examples. Merck & Co. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989) (holding that both preferred and unpreferred embodiments must be considered). In addition, Applicants point to narrow embodiments which are not the sum total of information conveyed by Orengo and Burkett. Art is art, not only for what it expressly teaches, but also for what it would reasonably suggest to the skilled artisan, including alternative or non-preferred embodiments. MPEP § 2123.
Both Orengo and Burkett disclose that elevated levels of IL-33 was involved in anaphylaxis and allergic inflammatory disease, respectively. Both Orengo and Burkett disclose that elevated levels of serpinA3f were found under conditions in which IL-33 was elevated. Burkett disclose agents, including siRNA, that modulate the expression, activity, and/or function of Serpina3f genes or gene products. Given the disclosures of Orengo and Burkett it would have been obvious to have a method of preventing anaphylaxis in a subject, comprising providing to the subject a composition comprising an siRNA of SerpinA3f.
Although neither Orengo nor Burkett disclose examples demonstrating that an inhibitor of SerpinA3f gene expression prevented anaphylaxis in a subject a "specification need not contain a working example if the invention is otherwise disclosed in such a manner that one skilled in the art will be able to practice it without an undue amount of experimentation." In re Borkowski, 422 F.2d 904, 908 (CCPA 1970). Furthermore, it is noted that the present specification does not demonstrate that SerpinA3f siRNA was capable of preventing anaphylaxis in a subject.
Claims 1-6 are rejected under 35 U.S.C. 103 as being unpatentable over Orengo et al (US 2017/0096483, published April 6, 2017) in view of Burkett et a; (US 2022/0152148, published May 19, 2022, effective filing date March 18, 2019) in further view of Londei et al (US 2019/0016795, published January 17, 2019).
Neither Orengo nor Burkett disclose that the composition is provided to the subject prior to exposure to a potential allergen in order to prevent anaphylaxis in the subject.
Londei disclose prevention of anaphylaxis by administering an anti-IL-33 inhibitor including an siRNA along with the food allergen (paragraphs 9-15, 70, 71).
It would have been obvious to apply Londei’s method for desensitizing an individual by prior treatment to an siRNA prior to exposure to a potential allergen in order to prevent anaphylaxis in the subject to Orengo and Burkett’s method for preventing anaphylaxis in a subject, comprising providing to the subject a composition comprising an inhibitor of SerpinA3f gene expression because Orengo, Burkett and Londei all disclose the importance if IL-33 for allergic responses while Orengo and Burkett disclose the importance of SerpinA3f in the induction of IL-33. Given that agents to SerpinA3f would affect the expression of IL-33 it would have been obvious to inhibit the expression of IL-33 to desensitize the subject to food allergens by inhibiting the gene expression of SerpinA3f. It would have been prima facie obvious to combine Orengo and Burkett’s method for preventing anaphylaxis in a subject, comprising providing to the subject a composition comprising an inhibitor of SerpinA3 gene expression with Londei’s method for desensitizing an individual by prior treatment to an siRNA prior to exposure to a potential allergen in order to prevent anaphylaxis to have a method for treating anaphylaxis in a subject, comprising providing to the subject a composition comprising an inhibitor of SerpinA3 gene expression.
Applicant argues that the deficiencies of Orengo and Burkett with regard to claim 1 are described above. Applicant argues that Londei does not compensate for the deficiencies of Orengo and Burkett, as Londei also does not disclose or suggest inhibition of SerpinA3 gene expression for prevention of anaphylaxis.
Thus, Applicant argues as set forth above. Thus, for the reasons set forth above and the reasons of record, the rejection is maintained.
Summary
Claims 1-6 stand rejected
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
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