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 .
Claim status
To expedite the compact prosecution, the Examiner is pursuing the amended claims dated 11 June 2024, in which applicant; amended claims 3-8, 11-13; and added claim 14. Therefore, claims 1-14 are pending in the application.
Priority
This application was filed 06/11/2024 and is a 371 application of PCT/EP2022/086770 filed on 12/19/2022, which claims benefit to the foreign application 22193585.1, filed on 09/02/2022 and 21216348.9, filed on 12/21/2021. Thus, the earliest possible priority for the instant application is 12/21/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07/30/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner and the signed and initialed PTO Forms 1449 are mailed with this action.
Title Objection
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. See MPEP 606.01
The following title is suggested:
"An adenovirus vector comprising a designed ankyrin repeat domain and a trimerization domain."
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
Claim 1-8, and 10-14 rejected under 35 U.S.C. 102(a)(1) as being anticipated by Schmid et al. (Nature Comm. vol. 9, 2018, pages 1-16, XP055704946; cited in IDS filed 07/30/2024; hereinafter “Schmid”).
Claim interpretation: Examiner interpreted that the term ''protein scaffold" means a protein with exposed surface areas in which amino acid insertions, substitutions or deletions are highly tolerable, therefore, the protein scaffold could be selected from the group consisting of a polypeptide, an antibody fragment and a scFv (SPEC p. 7, last ¶ - page 8, first ¶). Therefore, to expediting the prosecution Examiner interpreted any polypeptide, scFv falls under the definition of a protein scaffold.
[AltContent: textbox ([img-media_image1.png]
Fig. 1 of Schmid et al. )]Regarding claims 1-4, 6-7, Schmid discloses adapter polypeptides for retargeting of adenovirus vectors (i.e., adenovirus serotype 5 (HADV5, Fig. 1)) in animal tumor models (abstract, results, discussion). The adapter polypeptides comprise as first module a Designed Ankyrin Repeat Protein (DARPin) binding to the knob of an adenovirus and a trimerization domain derived from the capsid protein SHP of lambdoid phage 21 (limitation of claim 7) and as second module a retargeting DARPin binding to specific cell-surface receptors, (e.g. a HER2-binding DARPin (e.g., a protein scaffold)). The adapter consists of a central fiber knob-binding DARPin fused on one side to the phage protein SHP, which mediates extremely stable trimerization and thus formation of a highly stable complex of the DARPins and fiber knob (p. 2 Right hand col. 1st ¶, Fig. 1). The HER2-binding DARPin is fused via a long flexible linker to the N-terminus of the knob-binding DARPin (See Fig. 1a). Therefore, the protein scaffold is not DARPin.
Regarding claim 5, Schmid discloses constructed a trimeric scFv by fusing a highly stable trimerization domain, SHP of lambdoid phage 2143, to the carboxy-terminus of the scFv (Supplementary Fig. 4c, d). (e.g., recombinant protein comprises from the N- to the C-terminus), therefore recombinant protein comprises, wherein said recombinant protein comprises from the N- to the C-terminus a) a protein scaffold; b) a flexible linker, c) a DARPin which binds to the knob of an adenovirus, d) a short linker (glycine–serine linker), and e) trimerization domain (p. 2 Right hand col. 1st ¶, Fig. 1 and 5).
Regarding claims 8-9 and 11-12, Schmid demonstrates a massive coverage of the virion surface through the hexon shielding scFv fragment, trimerized to exploit the hexon symmetry and gain avidity, wherein the shielded particles are equipped with adaptor proteins, the virions deliver their payload genes into human cancer cells (i.e., A431 cells, eukaryotic cell (Fig. 1 caption)) expressing HER2 or EGFR (abstract, p. 2 Right hand col. 2nd ¶, Fig. 1). Therefore, Schmid anticipates protein scaffold is an antibody fragment (i.e., scFv) and the delivery system of the adenoviral comprising the adenovirus.
Regarding claims 13-14, Schmid demonstrates that no increase in tumor targeting by the retargeting adapter was detected after intravenous administration, compared with the knob-blocking adapter, although the tumor-to-liver ratio of payload expression was significantly increased by a factor of around 170 in the EGFR+ tumor model and by 25-fold in the HER2+ tumor model (Fig. 4c, d), compared to the naked HAdV5HVR7. Therefore, Schmid anticipated the method for treating a patient administering a eukaryotic cell comprising the adenovirus comprising recombinant protein as discloses above to a patient in need thereof.
Accordingly, Schmid anticipates the instant claims 1-8, and 10-14.
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 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.
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.
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 1-8, 9, and 10-14. are rejected under 35 U.S.C. 103 as being unpatentable over Schmid et al. (Nature Comm. vol. 9, 2018, pages 1-16, XP055704946; cited in IDS filed 07/30/2024; hereinafter “Schmid”), in view of Tamaskovic et al. (US10093740B2; cited in PTO892; hereinafter “Tamaskovic”).
As discussed previously, regarding claims 1-8, and 10-14 Schmid discloses adapter polypeptides for retargeting of adenovirus vectors (i.e., adenovirus serotype 5 (HADV5, Fig. 1)) in animal tumor models (abstract, results, discussion). The adapter polypeptides comprise as first module a Designed Ankyrin Repeat Protein (DARPin) binding to the knob of an adenovirus and a trimerization domain derived from the capsid protein SHP of lambdoid phage 21 (limitation of claim 7) and as second module a retargeting DARPin binding to specific cell-surface receptors, (e.g. a HER2-binding DARPin (e.g., a protein scaffold)). The adapter consists of a central fiber knob-binding DARPin fused on one side to the phage protein SHP, which mediates extremely stable trimerization and thus formation of a highly stable complex of the DARPins and fiber knob (p. 2 Right hand col. 1st ¶, Fig. 1). The HER2-binding DARPin is fused via a long flexible linker to the N-terminus of the knob-binding DARPin (See Fig. 1a).
Although regarding claim 9, Schmid does not specifically teach scFv comprises the amino acid sequence of SEQ ID NO: 4. However, such was known in the prior art.
Regarding claim 9, Tamaskovic teaches the cytotoxic activity of bispecific HER2 binding agents constructed from antibody fragments, bispecific constructs of the type scFv1-linker-scFv2; DARPin-linker-scFv; and scFv-linker-DARPin constructs were constructed. Here, in each fusion protein, one of the units (scFv1, scFv2, scFv or DARPin) binds to domain 1, the other one binds to domain 4, wherein scFv comprises SEQ ID NO: 68, which is 100% identical to instant SEQ ID NO: 4 (see the ABSS result filed 06/05/2026) (Col. 38 example 5, lns 38-47; Col. 39 lns 10-17; col 9 lns 60-61 of Tamaskovic).
Accordingly, it would have been obvious to practice the adenovirus of Schmid and include the scFv comprises SEQ ID NO: 68 as taught by Tamaskovic with a reasonable expectation of success. The POSITA would have been motivated at the time of filing to do so as taught by Tamaskovic because the HER2 binding agents comprising one or two antibody fragments are able to trigger apoptosis of the targeted cell much better than trastuzumab (Col. 43 lns 13-16 of Tamaskovic). The POSITA would have had a reasonable expectation of success in combining the teachings of Schmid and Tamaskovic because each of these teachings both successfully generated Vectors for scFv/DARPin Fusion Proteins. Therefore, the products and method as taught by Schmid et al. in view of Tamaskovic et al. would have been prima facie obvious over the products and method of the instant application. In regard to the reasonable expectation of success in doing so, include the scFv comprises SEQ ID NO: 68 of Tamaskovic had a reasonable expectation of success since the steps thereof required no more than recombinant DNA and cell culture technology.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MASUDUR RAHMAN whose telephone number is 571-272-0196. The examiner can normally be reached M-F 8-5 (EST).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached on (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/MASUDUR RAHMAN/ Patent Examiner, Art Unit 1633
/JEREMY C FLINDERS/ Primary Examiner, Art Unit 1684
Prosecution Insights