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 .
DETAILED ACTION
2. The election without traverse filed 12/19/2025 in response to the Office Action of 09/19/2025 is acknowledged and has been entered.
Applicant has elected Group I, claims 1-12, drawn to a construct comprising, in combination: a ligand that binds to EphA2, EphA3, and EphB2; and at least one effector molecule.
Additionally, Applicant has elected (A) a mutant of eA5 as the ligand; (B) a chemotherapeutic agent; (C) a lysosomal localization element as the subcellular compartment localization signal element; and (D) A B-C-D-E as the formula.
Upon review and reconsideration, eA5 and an EphA2, EphA3 and EphB2 binding fragment will be rejoined with a mutant of eA5 for examination; a nuclear localization element will be rejoined with a lysosomal localization element for examination.
3. Claims 1-18 are pending in the application. Claims 13-18 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/19/2025.
Claims 1-12 are currently under prosecution.
Priority
5. Applicant’s claim under 35 U.S.C. §§ 119(e) and/or 121, or 365(c) for benefit of the earlier filing date of applications, is acknowledged.
6. 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 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.
Claim Rejections - 35 USC § 102
7. 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.
8. Claims 1-10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Debinski et al. (US 20090123371, published on May 14, 2009, IDS).
Claims 1-10 are herein drawn to a construct comprising, in combination: a ligand that binds to EphA2, EphA3 and EphB2; and at least one effector molecule, wherein said at least one effector molecule comprises a Pseudomonas exotoxin A.
Debinski et al. teach ligands of the Eph receptors (e.g. EphA2, EphA3, and EphB2) include ephrins (e.g. ephrinA1 or ephrinA5 also known as eA5); see entire document, e.g. [0054-0057], [0089].
For claim 2, Debinski et al. teach ephrinA1 in monomeric form is conjugated to a therapeutic agent; see claim 12, [0014-0017].
For claim 4, Debinski et al. teach glycosylation; see [0069].
For claims 5 and 10, Debinski et al. teach wherein said therapeutic agent comprises a Pseudomonas exotoxin; see claim 14.
For claims 6-7, Debinski et al. teach dimeric ephrinA1-Fc; see [0045]. Fc of Debinski et al. meets the limitations of the instant claimed a cytosol localization element and a subcellular compartment.
For claims 8-9, Debinski et al. teach ephrinA1 fused to Fc via a polypeptide linker; see [0090].
Claim Rejections - 35 USC § 103
9. 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 of this title, 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.
10. The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
11. Claims 1 and 3-4 are rejected under 35 U.S.C. 103 as being unpatentable over Debinski et al. (US 20090123371, published on May 14, 2009, IDS) and in view of Carvalho et al. (Nature Neuroscience, 2006, 9(3): 322-330, IDS).
Claims 3-4 are herein drawn to the construct of claim 1, wherein said ligand is a mutant of eA5.
The teachings of Debinski et al. have been set forth in the above rejection of claims 1-10 under 35 U.S.C. 102(a)(1).
Although Debinski et al. teach ligands of the Eph receptors (e.g. EphA2, EphA3, and EphB2) include ephrinA5 (also known as eA5), Debinski et al. do not teach a mutant of ephrinA5.
However, this deficiency is remedied by Carvalho et al.
Carvalho et al. teach a method of introduction of point mutations in ephrinA5 at position 125, 126 and 129; see entire document, e.g. sixth paragraph of left col. on page 328.
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 combine the teachings of the references so as to make a mutant of ephrinA5 as a ligand of EphA2, EphA3 and EphB2. One would have been motivated to do so because Debinski et al. teach ephrinA5 as a ligand of EphA2, EphA3 and EphB2; Carvalho et al. teach a method of introduction of point mutations in ephrinA5. Thus, one of ordinary skill in the art would have a reasonable expectation of success that by combining the teachings of the references so as to make a mutant of ephrinA5 as a ligand of EphA2, EphA3 and EphB2 to arrive claimed invention of having point mutations in ephrinA5, because a method of introduction of point mutations in ephrinA5 as taught by Carvalho et al.
12. Claims 1 and 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Debinski et al. (US 20090123371, published on May 14, 2009, IDS) and in view of Maithal et al. (WO 2007057922, 24 May 2007).
Claim 11 is herein drawn to the construct of claim 10, wherein E is (KLAKLAK)2(SEQ ID NO:1).
Claim 12 is herein drawn to the construct of claim 8, wherein D is a nuclear localization element and wherein E is a chemotherapeutic agent.
The teachings of Debinski et al. have been set forth in the above rejection of claims 1-10 under 35 U.S.C. 102(a)(1).
Debinski et al. do not teach E is (KLAKLAK)2(SEQ ID NO:1), and D is a nuclear localization element.
However, this deficiency is remedied by Maithal et al.
Maithal et al. teach that peptide “KLAKLAKKLAKLAK" is selectively toxic to angiogenic endothelial cells and showed anti-cancer activity; see entire document, e.g., page 4 lines 13-15.
The peptide “KLAKLAKKLAKLAK" of Maithal et al., should be produced in nuclear; thus, the peptide is a nuclear localization element.
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 combine the teachings of the references so as to have a construct comprises ephrinA1-linker-Fc-KLAKLAKKLAKLAK. One would have been motivated to do so because Debinski et al. teach ephrinA1-linker-Fc- chemotherapeutic agent; Maithal et al. teach that peptide “KLAKLAKKLAKLAK" is selectively toxic to angiogenic endothelial cells and showed anti-cancer activity. Thus, one of ordinary skill in the art would have a reasonable expectation of success that by combining the teachings of the references so as to substitute the therapeutic agent of Debinski et al. for another therapeutic agent (KLAKLAKKLAKLAK) of Maithal et al., because simple substitution of the therapeutic agent of Debinski et al. for another therapeutic agent (KLAKLAKKLAKLAK) of Maithal et al. would obtain predictable results.
Given the examination guidelines for determining obviousness under 35 U.S.C. 103 in view of the Supreme Court decision in KSR International Co. V. Teleflex Inc. 82 USPQ2d 1385 (2007) and the Examination Guidelines set forth in the Federal Register (Vol. 72, No. 195, October 10, 2007) and incorporated recently into the MPEP (Revision 9, March 2014), the following rationales to support rejection under 35 U.S.C. 103(a) are noted:
A) Combining prior art elements according known methods to yield predictable results.
B) Simple substitution of one known element for another to obtain predictable results.
C) Use of known technique to improve similar devices (methods, or products) in the same way.
D) Applying known technique to a known device (method, or product) ready for improvement to yield predictable results.
E) “Obvious to try” --- choosing form a finite number of identified, predictable solutions, with a reasonable expectation of success.
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art.
G) Some teachings, suggestion, or motivation in the prior art that would lead to one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
In this case, simple substitution of the therapeutic agent of Debinski et al. for another therapeutic agent (KLAKLAKKLAKLAK) of Maithal et al. would obtain predictable results.
Obviousness is not the result of a rigid formula disassociated from the consideration of the facts of a case. Indeed, the common sense of those skilled in the art demonstrates why some combinations would have been obvious where others would not. See KSR International Co. V. Teleflex Inc. 82 USPQ2d 1385 (2007). From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention.
Double Patenting
13. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the claims at issue are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
14. Claims 1-5 and 10 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 9,974,830.
Although the conflicting claims are not identical, they are not patentably distinct from each other because for the following reasons:
Claims 1-5 and 10 are herein drawn to a construct comprising, in combination: a ligand that binds to EphA2, EphA3 and EphB2; and at least one effector molecule, wherein said at least one effector molecule comprises a Pseudomonas exotoxin A.
Claims 1-7 of U.S. Patent No. 9,974,830 are drawn to a method comprising ephrinA1 is coupled to a therapeutic agent, wherein said therapeutic agent comprises a Pseudomonas exotoxin.
In Pfizer, Inc., v. Teva Pharamaceutical USA, inc. (Fed. Cir, 2008), the Court concluded that the safe harbor of section 121 is limited to divisional applications only. The instant application is not filed as a result of a restriction requirement of U.S. Patent No. 9,974,830. The fusion protein claimed in the claims of the patent is the same as the instantly claimed fusion protein.
Conclusion
15. No claim is allowed.
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/YAN XIAO/Primary Examiner, Art Unit 1642