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.
Election/Restrictions
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.
Claims 16-19, 21, 23, 27-30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 Oct. 2, 2025.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)).
Election/Restrictions
In the response filed on Oct. 2, 2025, Applicants have amended claims 4, 9, 16, 19, 23, and 30, and canceled claims 3, 5, 7-8, 10-15, 20, 22, 24-26, and 31.
Currently, claims 1-2, 4, 6, and 9 are under consideration.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on August 21, 2023, are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Applicant is reminded that the listing of references in the specification are not a proper information disclosure statements (see e.g. page 20-23). 37 CFR 1.98(b) requires a lists of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
The disclosure is objected to because it contains an embedded hyperlinks (see e.g. https://ghr.nlm.nih.gov/), located on page 20 (see e.g. ref. 11-12). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
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. 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 a modulator of Eph receptor/ephrinB2 signaling to the subject”. However, the specification doesn't have adequate support in the disclosure for a generic modulator of Eph receptor/Ephrin signaling that characterizes any modulator of Eph receptor/ephrinB2 signaling that is administered to a subject for treating arteriovenous malformation.
As written in the claim, “a modulator” 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, microRNA, RNAi, or shRNA etc.), corresponding to any modulator 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, B.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 banc). 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, “modulator”, 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 a modulator 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 modulator that characterizes any modulator of Eph receptor/ephrin B2 signaling that treats arteriovenous malformation in a subject.
The specification discloses that the modulator 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 (EphB1), 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 the inhibitory modulator, sEphB4, of Eph receptor/ephrinB2 signaling in a subject. Therefore, the specification fails to identify any modulator 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 a modulator of Eph receptor/ephrinB2 signaling as claimed would be by using any modulator 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 modulate 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. 5B) 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 modulator of the Eph receptor/ephrinB2 signaling will treat arteriovenous malformation.
Therefore, with these additional evidence, the ordinary artisan cannot predictably identify that any modulator 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 DEUTSCHLAND 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 “modulator” 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. modulator). Consequently, any modulator 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 modulator that can characterize any modulator of Eph receptor/ephrinB2 signaling to treat arteriovenous malformation in a subject. Similarly, the disclosure doesn’t identify a generic modulator that characterizes any modulator of Eph receptor/ephrinB2 signaling that will treat arteriovenous malformation in a subject. Therefore, the claimed recitation of any modulator doesn’t have adequate written description. Furthermore, neither the specification nor the art indicates the ability to identify a generic modulator that characterizes any modulator of Eph receptor/ephrinB2 signaling to treat arteriovenous malformation in a subject.
Therefore, it concludes that the claimed recitation of any modulator 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 modulator of Eph receptor/ephrinB2 to characterize any modulator 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.
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, 4, and 6 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 treating arteriovenous malformation in a murine subject comprising administering a therapeutically effective amount of an inhibitory modulator of Eph receptor/ephrinB2 signaling in the murine subject, does not reasonably provide enablement for the following: a method of treating arteriovenous malformation in any subject comprising administering a therapeutically effective amount of any modulator of Eph receptor/ephrinB2 signaling to the subject.
(1) any modulator for treating arteriovenous malformation; and
(2) any subject with arteriovenous malformation.
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 use the invention commensurate in scope with these claims.
While determining whether a specification is enabling, one considers whether the claimed invention provides sufficient guidance to make and use the claimed invention, if not, whether an artisan would require undue experimentation to make and use the claimed invention and whether working examples have been provided. When determining whether a specification meets the enablement requirements, some of the factors that need to be analyzed are: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill, the level of predictability in the art, the amount of direction provided by the inventor, the existence of working examples, and whether the quantity of any necessary experimentation to make and use the invention based on the content of the disclosure is “undue”.
Nature of the Invention: Claims are drawn to a method of treating arteriovenous malformation in a subject comprising administering a therapeutically effective amount of a modulator of Eph receptor/ephrinB2 signaling to the subject (See claim 1).
Breadth of the Claims: The claimed invention encompasses a method of treating arteriovenous malformation in any subject comprising administering a therapeutically effective amount of any modulator of Eph receptor/ephrinB2 signaling to the subject. Thus, the claims are drawn to a method for treating arteriovenous malformation in any subject (i.e. mammal or non-mammal), comprising administering a therapeutically effective amount of any modulator (i.e. antagonist, inhibitor or stimulator) of Eph receptor/ephrinB2 signaling to the subject (i.e. mammal or non-mammal). As such, the claim is vastly broad encompassing embodiments contemplated and not contemplated by the specification.
Specification Guidance/Working Examples: The specification teaches the following:
(1) [85] “The soluble extracellular domain of EphB4 (sEphB4) completely inhibits EphB4 signaling in
mice. sEphB4 is injected intraorbitally into Slco1c1-CreERT2 ;Alk1tx/tx mice to test its ability
to prevent and treat BAVMs.” (page 19, para. 85).
[83] Example 6 Determining whether ephrinB2 or EphB4 is required for BAVM formation in Alk1 mutant mice: The Lacz reporters described herein are knockins (i.e., one copy of ephrinB2 or
EphB4 is knocked out by the LacZgene). Experiments will reveal whether having heterozygous ephrinB2 or EphB4 affects the BAVM phenotype in mice lacking Alk1. The data show that Slco1c1-CreERT2 ; Alk1fx/fx;EphBLacZ/+ mice treated with TAM from P13 show reduced BAVM formation and hemorrhage and delayed moribundity compared to Slco1c1 -CreERT2 ;Alk1fX/fx mice (Figures 13 and 14).
(2) [85] To determine if sEphB4 prevents BAVM formation, at P12 a cranial window is implanted and also begin daily injections of sEphB4 (about 4mg/kg) into Slco1c1-CreERT2 ;Alk1fx/fx mice are begun (page 19, para. 85).
[62] Example 1 Engineering a mouse model of HHT2: Alk1 was specifically from brain ECs, avoiding the lethal complications of whole body Alk1 deletion, using the Slco1c1-CreERT2 allele, a temporally inducible Cre under the control of the Slco1c1 promoter, which is a promoter active specifically in brain endothelium. Deletion of Alk1 from postnatal day (P) 13 with tamoxifen (TAM) in this Slco1c1-CreERT2 ;Alk1fxlfx model led to 100% BAVM and intracranial hemorrhages, without detectable defects elsewhere in the body.” (page 11, para. 62).
As such, the specification fails to provide specific guidance to a method of treating arteriovenous malformation in any subject comprising administering a therapeutically effective amount of any modulator of Eph receptor/ephrinB2 signaling to the subject. Therefore, the specification only enables treating arteriovenous malformation in a murine model comprising administering a therapeutically effective amount of an inhibitory modulator of Eph receptor/ephrinB2 signaling to the murine model.
State of the Art: Regarding any subject and any modulator for treating arteriovenous malformation, the prior art of Adams (2000, Trends in cardiovascular medicine 10.5:183-188) discloses that is was well known that an “important role for ephrinB2 and EphB4 in vascular development was confirmed by genetic experiments in the mouse and that the mutant animals lacking ephrinB2 and EphB4 die before day 11 of embryonic development (E11) displaying various cardiovascular defects (see e.g. page 184-185). Further, the prior art of Kertesz (2006, cited IDS 8/21/2023) teaches that “EphrinB2 is the only ligand for EphB4 receptor and both proteins are essential for the development of the cardiovascular system. EphrinB2 is expressed in angioblasts destined to mature into arterial ECs and perivascular smooth muscle cells, whereas EphB4 defines venous lineage at the same step” (page 2336-2337). Further, Kertesz teaches that the soluble monomeric derivative of the extracellular domain of EphB4 (sEphB4) was designed as an antagonist of EphB4/EphrinB2 signaling, where sEphB4 blocks activation (i.e. inhibits) of EphB4 and EphrinB2; suppresses endothelial cell migration, adhesion, and tube formation in vitro (see e.g. abstract. Page 2336-2337). Additionally, Kertesz discloses that “sEphB4 exerts similar effects in angiogenesis models in vivo, and further, significantly inhibits tumor growth as well, and that another recombinant protein, CF2, which lacks the globular ligand-binding domain, was also tested, but does not inhibit ligand binding” (page 2336-2337). Therefore, the prior art before the effective filing date provides robust evidence that not all modulations of Eph receptor/ephrinB2 signaling have a common core structure and act in the same manner. Furthermore, the prior art of Yang (2016, Angiogenesis 19.3: 297-309) reviews the critical role of the B family of Ephs and Ephrins, especially EphrinB2/EphB4, and suggests that further investigations should be focused on the precise mechanisms of temporal–spatial regulation, the potential therapies targeting the genes or the molecules of the Eph family members and the development of specific Eph/Ephrin interfering compounds (see e.g. page 305). Thus, the state of the art at the time of the invention suggests that the designing of an antagonist of EphB4/EphrinB2 signaling, and that specific compounds should be developed for EphB4/EphrinB2 signaling.
Furthermore, the prior art before the effective filing date Murphy (2012, cited IDS 8/21/2023), discloses that by studying and “exploiting the tractable brain arteriovenous malformation (AVM) mouse model system will provide important clues into the cellular and molecular regulation of AVMs in general” (see e.g. abstract, pages 1 and 9). Additionally, Murphy discloses that the AVM murine model demonstrated “a complete and safe normalization of dangerous high-flow AV shunts in animals may spur development of molecular therapeutic strategies to induce the regression of these dangerous high-flow vessels and treat these devastating diseases” (see e.g. page 9). Thus, the prior art before the effective filing date discloses that not all models for AVM were considered safe and effective for studying and developing molecular therapeutic strategies.
Accordingly, the prior art does not provide guidance to any modulator of Eph receptor/ephrinB2 signaling for treating arteriovenous malformation in any subject. Further, the state of the art teaches that a murine model system will be important for studying the cellular and molecular regulation of arteriovenous malformation (AVM) and thus, treating AVMs. Accordingly, the state of the art does not provide specific guidance to treating arteriovenous malformation in any subject. Thus, the breadth of treating arteriovenous malformation comprising administering a therapeutically effective amount of any modulator of Eph receptor/ephrinB2 signaling fails to predictably treat arteriovenous malformation in any subject as claimed. As such, similar to the specification, the art teaches that the claimed treating arteriovenous malformation comprising administering a therapeutically effective amount of any modulator of Eph receptor/ephrinB2 signaling fails to predictably treat arteriovenous malformation in any subject.
Thus, the art at the time of the invention teaches that any modulator of Eph receptor/ephrinB2 signaling fails to treat arteriovenous malformation in any subject as claimed. Thus, the breadth of the claims to treating arteriovenous malformation by administering a therapeutically effective amount of any modulator of Eph receptor/ephrinB2 signaling fails to predictably treat any subject as claimed. As such, similar to the specification, the art teaches that the claimed treating arteriovenous malformation comprising administering a therapeutically effective amount of any modulator of Eph receptor/ephrinB2 signaling fails to predictably treat arteriovenous malformation in any subject.
Thus, in conclusion, the breadth of the claims to a method of treating arteriovenous malformation with any modulator of Eph receptor/ephrinB2 signaling is not enabled for treating any subject with arteriovenous malformation, as discussed above. The specification solely provides specific guidance to a method of treating arteriovenous malformation in a mouse comprising administering a therapeutically effective amount of an inhibitory modulator of Eph receptor/ephrinB2 signaling to the mouse, see Example 6, and fails to describe treating with any modulator of Eph receptor/ephrinB2 signaling to any subject with arteriovenous malformation, as discussed above.
Therefore, at the time of filing the skilled artisan would need to perform an undue amount of experimentation without a predictable degree of success to implement the invention as claimed.
The prior art rejections listed below are directed to the scope that is enabled: The treating arteriovenous malformation in a murine model comprising administering a therapeutically effective amount of an inhibitory modulator of Eph receptor/ephrinB2 signaling embodiment.
Claim Rejections - 35 USC § 102
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 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 1-2 and 9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hai U. Wang et al., (US 2011/0195901 A1, published 2005, hereinafter as “Wang”).
Regarding claim 1, Wang discloses a method of treating arteriovenous malformation in a subject (i.e. selective modulation (inhibition)) of formation, growth and survival of arteries and/or veins)(see e.g. para 34, 47, 60-65) comprising administering a therapeutically effective amount of a modulator of Eph receptor/ephrinB2 signaling to the subject (i.e. EphB4)(see e.g. abstract, para. 60-65, claim 31).
Regarding claim 2, as stated supra, Wang discloses wherein the modulator inhibits Eph receptor/ephrin B2 signaling (see e.g. abstract, para. 60-65, claim 31).
Regarding claim 9, as stated supra, Wang discloses wherein the Eph receptor is soluble Eph type-B receptor 4 (EphB4)(see e.g. para. 60-65, claim 31).
Therefore, Wang anticipates the instant claims.
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 th e 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 4 is rejected under 35 U.S.C. 103 as being unpatentable over Hai U. Wang et al., (US2011/0195901A1, published 2005, hereinafter as “Wang”), as applied to claims 1-2 and 9 above, and in further view of Frisen and Holmberg (US2005/0049194 A1, cited IDS 8/21/2023, hereinafter as “Frisen”).
The teachings of Wang apply here as indicated above.
Regarding claim 4, as stated supra, Wang discloses arteriovenous malformation (see e.g. para. 34, 47, 60-65).
Wang does not explicitly state wherein the subject has hereditary hemorrhagic telangiectasia.
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).
Accordingly, it would have been obvious for a person of ordinary skill in the art to have combined the method of administering a modulator of Eph receptor/ephrinB2 signaling as taught by Wang with treating hereditary hemorrhagic telangiectasia in a subject as taught by Frisen because Wang discloses treating arteriovenous malformation (See e.g. para. 34). 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. Furthermore, an artisan of ordinary skill in the art of (i.e. Eph receptor/ephrinB2 signaling) has good reason to pursue the known options within his or her technical grasp (KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (US 2007).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 4 and 6 is rejected under 35 U.S.C. 103 as being unpatentable over Hai U. Wang et al., (US 2011/0195901 A1, published 2005, hereinafter as “Wang”), as applied to claims 1-2 and 9 above, and in further view of Murphy, et al. (Sci Transl Med 4, 117ra118, published 2012, cited IDS 8/21/2023).
The teachings of Wang apply here as indicated above.
Regarding claims 4 and 6, as stated supra, Wang discloses arteriovenous malformation (see e.g. para. 34, 47, 60-65).
Wang does not explicitly state wherein the subject is at risk or has had a hemorrhagic stroke, and the arteriovenous malformation is in the brain.
However, the prior art of Murphy discloses arteriovenous malformation (AVM) in the brain (see e.g. abstract, figs. 1-3 and 6). Further, Murphy discloses that AVMS often result in a stroke (see e.g. abstract, page 978-979).
Accordingly, it would have been obvious for a person of ordinary skill in the art to have modified the methods of Wang and incorporate arteriovenous malformation (AVMs) in the brain as taught by Murphy because Murphy discloses that it was known in the art that AVMS are particularly problematic in the brain (see e.g. abstract). Furthermore, given that Wang teaches treating arteriovenous malformation comprising administering a modulator of Eph receptor/ephrin82 signaling, and that Murphy teaches brain arteriovenous malformations can cause hemorrhagic stroke (abstract), which shows increased expression of ephrinB2 (fig. 7), page 978-979), it would have been obvious to one of ordinary skill in the art to have attempted Wang's method of administering a modulator of Eph receptor/ephrinB2 signaling to a subject wherein the subject is at risk of, or has had, a hemorrhagic stroke as taught by Murphy. Thus, having a reasonable expectation of success. Furthermore, an artisan of ordinary skill in the art of (i.e. methods regarding vascular abnormalities) has good reason to pursue the known options within his or her technical grasp (KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (US 2007).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPHINE GONZALES whose telephone number is (571)272-1794. The examiner can normally be reached M-Th: 9AM - 5:00PM (EST).
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JOSEPHINE GONZALES
Examiner
Art Unit 1631
/JOSEPHINE GONZALES/Examiner, Art Unit 1631
/JAMES D SCHULTZ/Supervisory Patent Examiner, Art Unit 1631