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 .
Priority
This application was filed on March 29, 2022, and is a 371 application of PCT/US20/53566 filed on September 30, 2020, which claims benefit to the provisional application 62/908,525 filed on Sept. 30, 2019.
Status of Claims
In the response filed on May 4, 2026, Applicants have amended claims 1-2, 9; canceled claims 3, 5, 7-8, 10-15, 20, 22, 24-26, and 31; and filed new claims 32-33.
Applicant’s election without traverse of Group I (claims 1-2, 4, 6, and 9) in the reply filed on October 2, 2025, is acknowledged.
Currently, claims 1-2, 4, 6, 9, and 32-33 are under consideration.
Response to Traversal: Applicant notes that the Office Action summary page includes claim 6 as being withdrawn; however, the Office Action on page 2 discloses that claim 6 is under consideration. Applicant believes there was a typo and proceeded on the basis that claim 6 was under examination.
The Examiner is grateful for Applicants acknowledgment of the typo on the summary page. Applicant is correct regarding the typographical error, and that claim 6 is not withdrawn. Further, claim 6 was included in Group I of the restriction requirement sent on April 2nd, 2025. As discussed above, claims 6 is under consideration in this Office Action.
Withdrawn Objections & Rejections
Rejections and/or objections not reiterated from the previous office action are hereby withdrawn due to amendment. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 112
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 1-2, 4, and 6 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.
This rejection is a new rejection necessitated by amendments to the claims. However, since it is substantially similar to a rejection set forth in the non-final Official action mailed on Nov. 6, 2025, therefore any aspect of applicant's response considered relevant to the rejection as newly set forth is responded to following the statement of rejection.
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.
Independent Claim 1 recites "A method of treating arteriovenous malformation in a subject comprising administering a therapeutically effective amount of an inhibitor of Eph receptor/ephrinB2 signaling to the subject". However, the specification doesn't have adequate support in the disclosure for a generic inhibitor of Eph receptor/Ephrin signaling that characterizes any inhibitor of Eph receptor/ephrinB2 signaling that is administered to a subject for treating arteriovenous malformation.
As written in the claim, "an inhibitor" encompasses a broad genus that includes multiple classes of inhibitors and stimulators and given its broadest reasonable interpretation in light of the specification (i.e. polypeptide, small molecules, micro RNA, RNAi, or shRNA etc.), corresponding to any inhibitor of Eph receptor/Ephrin signaling that imparts the function of treating arteriovenous malformation.
Under the written description guidelines (see MPEP 2163), the Examiner is directed to determine whether one skilled in the art would recognize that the Applicant was in possession of the claimed invention as a whole at the time of filing. The following considerations are critical to this determination.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail so that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, 8. V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. An original claim may lack written description support when (1) the claim defines the invention in functional language specifying a desired result, but the disclosure fails to sufficiently identify how the function is performed, or the result is achieved or (2) a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en bane). The written description requirement is not necessarily met when the claim language appears in ipsis verbis in the specification. "Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement." Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002).
Accordingly, to satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.
In analyzing whether the written description requirement is met for the genus, "inhibitor", the specification is first assessed to determine whether a representative number of species have been described by their complete structure of the genus.
Independent claim 1 recites administering a therapeutically effective amount of an inhibitor of Eph receptor/ephrinB2 signaling in a subject in order to treat arteriovenous malformation. However, the specification doesn't have adequate support in the disclosure for the generic inhibitor that characterizes any inhibitor of Eph receptor/ephrin B2 signaling that treats arteriovenous malformation in a subject.
The specification discloses that the inhibitor of Eph receptor/Ephrin signaling could comprises an antibody, lipid, antigen binding fragment thereof, and wherein the antibody binds to a receptor or a ligand (specification para. 29-35). The specification discloses "In some embodiments, the Eph receptor is an EphB receptor, such as EphB1, EphB2, EphB3, EphB4, EphB5 or EphB6. In some embodiments, the Eph receptor is an Eph type-B receptor, such as Eph type-B receptor 4 (EphB4). In some embodiments, the inhibitor is soluble Eph type-B receptor 4. In some embodiments, the Eph type-B receptor is Eph type-B receptor 1 (EphBl), Eph type-B receptor 2 (EphB2), Eph type-B receptor 3 (EphB3), or Eph type-B receptor 6 (EphB6)" (specification para. 21). Further, the specification contemplates "modulators of an Eph receptor/ephrin that are partial or full-length Eph receptor or ephrin ligand, as well as sequence variants (no more than 10 amino acid changes, and preferably no more than three amino acid changes) and mimics of the wild-type Eph receptor or ephrin and variants may also comprise truncations of the wild type proteins" (Spec. Para. 31). However, the specification only discloses that the soluble extracellular domain of EphB4 (sEphB4) inhibits "cerebral hemorrhage and delays moribundity (Figs. 13, 14) and reduces AV shunting (Fig. 15) following Alk1 deletion in the mouse model disclosed herein, compared to control mice, and therefore completely inhibits EphB4 signaling in mice (Spec. para. 92, Example 6). Accordingly, the specification only teaches a method of treating arteriovenous malformation in a subject comprising administering a therapeutically effective amount of an inhibitor is EphB1, EphB2, EphB3, sEphB4, EphB5 or EphB6, of Eph receptor/ephrinB2 signaling in a subject. Therefore, the specification fails to identify any inhibitor Eph receptor/Ephrin signaling that when administered will treat arteriovenous malformation in the subject.
The method of making the claimed invention is not well established at the time of filling. However, one of skill in the art would neither expect nor predict the appropriate method of treating arteriovenous malformation in a subject by administering an inhibitor of Eph receptor/ephrinB2 signaling as claimed would be by using any inhibitor of Eph receptor/ephrinB2 signaling.
The teaching of Kertesz, et al. (2006, cited IDS 8/21/2023), teaches that the "soluble monomeric derivative of the extracellular domain of EphB4 (sEphB4) was designed as an antagonist of EphB4/EphrinB2 signaling" (see e.g. abstract). Further, Kertesz discloses that "sEphB4 blocks organization and migration of ECs to form tubules, which are the principal events leading to maturation of newly forming vessels. Importantly, sEphB4 exerts similar effects in angiogenesis models in vivo, and further, significantly inhibits tumor growth as well" (see e.g. 2336-2337). Therefore, Kertesz provides robust evidence that specifically, sEphB4, may inhibit integrin-matrix interaction by interrupting EphB4 signaling and thus reduce cell attachment and tube formation (see e.g. 2336-2337).
Additionally, the prior art of Murphy, et al. (2012, cited IDS 8/21/2023), discloses that soluble form of the EphB4 (sEphB4) receptor competitively inhibits EphB4 receptor signaling after repression of Notch4 (Fig. SB) and the sEphB4 receptor significantly reduced the diameter the AV shunt diameter (see e.g. page 5-8). Thus, Murphy provides further evidence that not any inhibitor of the Eph receptor/ephrinB2 signaling will treat arteriovenous malformation.
Therefore, with these additional evidence, the ordinary artisan cannot predictably identify that any inhibitor of Eph receptor/ephrinB2 signaling will treat arteriovenous malformation in a subject. Furthermore, functionally defined genus claims can be inherently vulnerable for lack of adequate written description, especially in highly unpredictable technology fields, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. See ABBVIE DEUTSCH LAND GMBH & 2 CO. v. JANSSEN BIOTECH, INC., Appeals from the United States District Court for the District of Massachusetts in Nos. 09-CV-11340-FDS, 10-CV-40003-FDS, and 10-CV-40004-FDS, Judge F. Dennis Saylor, IV. See also Ariad, 598 F.3d at 1351 ("[T]he level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology."); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1352 (Fed. Cir. 2011) (noting the technical challenges in developing fully human antibodies of a known human protein).
The Applicant has recited that "the soluble extracellular domain of EphB4 (sEphB4) inhibits cerebral hemorrhage and delays moribundity (Figs. 13, 14) and reduces AV shunting (Fig. 15)(i.e. treating arteriovenous malformation) following Alk1 deletion in the mouse model" (see Spec. para. 92, Example 6). Given the breadth of any "inhibitor" that the claims embrace, a description of one species, soluble Eph type-B receptor 4 (EphB4), fails to provide a representative number of species that teaches the complete structure of the genus (i.e. any inhibitor). Consequently, any inhibitor of Eph receptor/ephrinB2 signaling is not apparent to one of ordinary skill in the art from the description present in the specification. Therefore, an artisan of ordinary skill could not envision all the embodiments encompassed by the breadth of the claims. Accordingly, the specification doesn't have adequate support in the disclosure for the generic inhibitor that can characterize any inhibitor of Eph receptor/ephrinB2 signaling to treat arteriovenous malformation in a subject. Similarly, the disclosure doesn't identify a generic inhibitor that characterizes any inhibitor of Eph receptor/ephrinB2 signaling that will treat arteriovenous malformation in a subject. Therefore, the claimed recitation of any inhibitor doesn't have adequate written description. Furthermore, neither the specification nor the art indicates the ability to identify a generic inhibitor that characterizes any inhibitor of Eph receptor/ephrinB2 signaling to treat arteriovenous malformation in a subject.
Therefore, it concludes that the claimed recitation of any inhibitor of Eph receptor/ephrinB2 signaling to treat arteriovenous malformation in a subject doesn't have an adequate written description. Specifically, the specification does not identify the generic inhibitor of Eph receptor/ephrinB2 to characterize any inhibitor of Eph receptor/ephrinB2 signaling that can be administered to treat arteriovenous malformation in a subject. It concludes that a skilled artisan would find the specification inadequately described. Therefore, the Applicant did not sufficiently possess the broader invention as claimed.
Response to Traversal:
Applicant argues that amended claim 1 of reciting "an inhibitor of Eph receptor/ephrinB2 signaling" in place of "a modulator," directly addresses the Office's concern about the breadth of the genus "modulator"(Remarks, page 7). Applicant asserts that the instant application teaches two distinct inhibitory approaches with actual experimental data, therefore under M.P.E.P. § 2163, the written description requirement for a claimed genus is met (Remarks, page 7).
Applicant arguments are acknowledged, have been fully considered, and have been deemed unpersuasive.
Contrary to Applicants assertion, the specification only teaches one pharmacological inhibitor sEphB4 (see Remarks, page 7 and spec, para. 85). Therefore, the genus for any inhibitor does not have adequate written description. It is acknowledged that under M.P.E.P. § 2163, the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species, or by disclosure of relevant identifying characteristics such as functional characteristics coupled with a known or disclosed correlation between function and structure (Remarks, page 7). In the instant case, Applicant’s specification specifically discloses that the inhibitor is soluble Eph type-B receptor 4, and in some embodiments, the Eph type-B receptor is Eph type-B receptor 1 (EphBl), Eph type-B receptor 2 (EphB2), Eph type-B receptor 3 (EphB3), or Eph type-B receptor 6 (EphB6)" (specification para. 21). As discussed above, the claimed recitation of any inhibitor (e.g. polypeptide, small molecules, micro RNA, RNAi, or shRNA etc.) of Eph receptor/ephrinB2 signaling to treat arteriovenous malformation in a subject doesn't have an adequate written description.
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.
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.
Claims 1-2, 4, 6, 9, and 32-33 is rejected under 35 U.S.C. 103 as being unpatentable over Wang et al., (US2011/0195901A1, published 2005, hereinafter as “Wang”, prior art of record), in view of Wang, Hai U., and David J. Anderson. (Neuron 18.3: 383-396, published 1997, hereinafter as “Wang (1997)”), Kertesz N, et al., (Blood. Mar 15;107(6):2330-8., published 2006, cited IDS 8/21/2023; hereinafter as “Kertesz”), and Frisen and Holmberg (US2005/0049194 A1, cited IDS 8/21/2023, hereinafter as “Frisen”, prior art of record).
This rejection is a new rejection necessitated by amendments to the claims. However, since it is substantially similar to a rejection set forth in the non-final Official action mailed on Feb. 3, 2026, therefore any aspect of applicant's response considered relevant to the rejection as newly set forth is responded to following the statement of rejection.
Regarding claim 1 and 32-33, Wang discloses a method of treating arteriovenous malformation in a subject (see e.g. para 34, 47, 60-65), comprising administering a therapeutically effective amount of an inhibitor (e.g. agonist, agent or drug) of Eph receptor/ephrinB2 signaling to the subject (see e.g. abstract, para. 45-50, 60-65, claim 31, Example 13). Further, Wang discloses wherein the Eph type-B receptor is Eph type-B receptor 4 (EphB4)(see e.g. para. 60-66, Examples 1-7, claims 16-29, see Table in para. 21-22). Further, Wang discloses “an aqueously soluble polypeptide having the amino acid sequence of the extracellular domain of EphB4” (see e.g. para. 60), which reads on the claimed soluble Eph type-B receptor 4 (see specification para. 92).
Wang does not explicitly disclose wherein the inhibitor of EphB4 is soluble Eph type-B receptor 4.
However, Wang cites the prior art of Wang (1997), for disclosing that an EphB4 hybrid protein in which the extracellular domain of the membrane protein that is fused to the Fc domain of human IgG can be used as a soluble agonist (see e.g. para. 66). Additionally, the prior art of Kertesz discloses that the “soluble monomeric derivative of the extracellular domain of EphB4 (sEphB4) was designed as an antagonist of EphB4/EphrinB2 signaling” and that sEphB4 is thus a therapeutic candidate for vascular proliferative diseases (see e.g. abstract).
Accordingly, prior to the effective filing date of the instant claimed invention, it would have been prima facie to obvious for a person of ordinary skill in the art to have modified the method of treating arteriovenous malformation in a subject, as taught of Wang, and incorporate the soluble Eph type-B receptor 4 inhibitor as taught by Wang (1997) and Kertesz, with a reasonable expectation of success because one of ordinary skill in the art would know that the extracellular domain of EphB4 (sEphB4) was designed as an antagonist of EphB4/EphrinB2 signaling (as taught by Wang (1997) and Kertesz, see e.g. abstracts, respectively).
Regarding claim 2, Wang discloses wherein the inhibitor inhibits Eph receptor/ephrin B2 signaling (see e.g. abstract, para. 60-65, claim 31).
Regarding claim 4 and 6, Wang discloses arteriovenous malformation (i.e. AVM)(see e.g. para. 34, 47, 60-65).
Wang does not explicitly state wherein the subject has hereditary hemorrhagic telangiectasia or wherein the AVM is in the brain.
However, the prior art of Frisen discloses a method for alleviating a symptom of Rendu-Osler-Weber syndrome (i.e. hereditary hemorrhagic telangiectasia (HHT)) with administering an ephrin inhibitor (see e.g. claims 22-26, para. 196). Further, Frisen discloses that a targeted tissue may be a region of the brain damaged by a disease (i.e. HHT).
Accordingly, prior to the effective filing date of the instant claimed invention, it would have been prima facie to obvious for a person of ordinary skill in the art to have modified the method of treating arteriovenous malformation in a subject, as taught of Wang, and incorporate wherein the AVM is in the brain and the subject has hereditary hemorrhagic telangiectasia (HHT) in the brain, as taught by Frisen, with a reasonable expectation of success because one of ordinary skill in the art would know that administering an ephrin inhibitor alleviating a symptoms of HHT (as taught by Frisen, see e.g. claims 22-26, para. 196). Furthermore, both Wang and Frisen disclose treating arteriovenous malformation and using modulators of Eph receptor/ephrinB2 signaling for therapeutic use (see e.g. Wang para. 34,69 and Frisen para. 151, 196). Thus, providing a reasonable expectation of success.
Regarding claim 9, as stated supra, Wang discloses wherein the Eph receptor is soluble an Eph type-B receptor(see e.g. para. 60-65, claim 31).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Response to Traversal:
Applicant argues that Wang is directed to assessing the in vivo activity of screened drug candidates and does not disclose a method of treating AVM by administering a therapeutically effective amount of an inhibitor of Eph receptor/ephrinB2 signaling to a subject (Remarks, page 9). Applicant asserts that Wang is directed to gene identification and drug target discovery, not to a method of treating AVM by administering an inhibitor of Eph receptor/ephrinB2 signaling (Remarks, page 9-10).
Applicant arguments are acknowledged, have been fully considered, and have been deemed partially persuasive.
Applicant’s arguments with respect to the previous rejection of the claims as rejected as being anticipated by Wang et al., have been fully considered and are persuasive in view of the amendments to the claims. However, upon further consideration, a new ground(s) of obviousness rejections are made in view of Wang et al., Wang (1997), Kertesz N, et al., and Frisen.
In response to applicant's argument that Wang does not disclose a method of treating AVM by administering a therapeutically effective amount of an inhibitor of Eph receptor/ephrinB2 signaling to a subject, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). As discussed above, Wang discloses blocking the function (i.e., inhibit binding of ephrin-B2 to its receptors) can be used as potential anti-angiogenic agents (see e.g. Example 13). Further, Wang discloses a reduction in EphB2-Fc binding to the ephrin-B2 (see e.g. fig. 2), therefore providing a therapeutically effective amount of an inhibitor of ephrin B2 signaling. It is noted that the claim recites “Eph receptor/ephrinB2 signaling”, which is interpreted as “Eph receptor and/or ephrin B2 signaling”.
Applicant’s arguments rely on language solely recited in preamble recitations in claim(s), specifically “treating”. When reading the preamble in the context of the entire claim, the recitation of treating is not limiting because the body of the claim describes a complete invention, and the language recited solely in the preamble does not provide any distinct definition of any of the claimed invention’s limitations. Thus, the preamble of the claim(s) is not considered a limitation and is of no significance to claim construction. See Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See MPEP § 2111.02. As discussed above, Wang discloses an Eph receptor agonist “can be used to treat a disease or disorder characterized by undesirable or excessive vascularization or vascular permeability (i.e. arteriovenous malformation, AVM)(see e.g. claim 82-84). Further, Wang discloses “a method can comprise administering the drug to a mouse (e.g., embryo, neonate, juvenile, adult, a wound site, tumor, ischemic lesion or arteriovenous malformation in any of the preceding) having an indicator gene inserted in a gene specifically expressed in arteries, and observing the effect of the drug on the growth of the arteries, compared to the effect in a suitable control mouse having an indicator gene, not treated with the drug, but maintained under identical conditions”(para. 34). Therefore, it is unclear how Wang only discloses a drug screening.
Further, it is noted that MPEP 2111.04 states “The broadest reasonable interpretation of a method (or process) claim having contingent limitations requires only those steps that must be performed and does not include steps that are not required to be performed because the condition(s) precedent are not met.” In the instant case, the claim does not disclose the steps of treatment besides administering a therapeutically effecting amount of an inhibitor of Eph receptor or ephrinB2 signaling to a subject.
Applicant argues that Wang in view of Frisen does not disclose each element of claim 4 and that the Office has not established a reasonable expectation of success (Remarks, page 11).
Applicant arguments are acknowledged, have been fully considered, and have been deemed partially persuasive.
Applicant’s arguments with respect to the previous rejection of the claims as rejected as being anticipated by Wang et al., have been fully considered and are persuasive in view of the amendments to the claims. However, upon further consideration, a new ground(s) of obviousness rejections are made in view of Wang et al., Wang (1997), Kertesz N, et al., and Frisen.
In response to applicant's argument that Wang does not provide treatment, a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. As discussed above, Wang discloses a reduction in EphB2-Fc binding to the ephrin-B2 (see e.g. fig. 2). Further, it is noted that the claim recited “an inhibitor of Eph receptor and/or ephrinB2 signaling to the subject”. Thus, inhibition of EphB2 binding is a subject is discloses by Wang, as discussed above.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, both Wang and Frisen disclose treating arteriovenous malformation and using modulators (i.e. inhibitors) of Eph receptor/ephrinB2 signaling for therapeutic use (see e.g. Wang para. 34,69 and Frisen para. 151, 196). Thus, providing a reasonable expectation of success.
In response to applicant's argument that the prior art of Wang in view of Frisen does not disclose each element of claim 4, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). It is noted that claim 4 recites “wherein the subject has “hereditary hemorrhagic telangiectasia or the subject is at risk of, or has had, a hemorrhagic stroke”. Thus, it is unclear how the prior art does not disclose each element of claim 4.
In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/JOSEPHINE GONZALES/ Examiner, Art Unit 1631
/JAMES D SCHULTZ/ Supervisory Patent Examiner, Art Unit 1631
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