DETAILED ACTION
Status of the Claims
Claims 1-18, 20-33 are pending
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A preliminary amendment filed on 03/07/2024 cancelling claim 19 and adding claims 25-33 is acknowledged.
A preliminary amendment filed on 04/21/2026 amending claims 22 and 27 is acknowledged.
Applicant’s election with traverse of Group 20 (drawn in part to a fusion protein that comprises two-RING domains and a protein targeting domain, wherein the RING domains are both TRIM21 in the reply filed on 04/21/2026 is acknowledged. However, Group 20 is drawn in part to a fusion protein, wherein the RING domains were derived from TRIM21 and TRIM25. Group 19 is drawn to a fusion protein where the RING domains are derived from TRIM21. Both groups consist of the same claims (2-10, 16, and 25-26). Applicant’s election with traverse of an antibody fragment for the protein target domain and VHH fragments for the antibody fragment in the reply filed on 04/21/2026 is acknowledged. The traversal is on the grounds that claims 1-18, 20-24 and 26-33 are generic and all pending claims read on the elected group and all pending claims read on the elected species. This is not found persuasive because Applicant’s response does not establish a common special technical feature.
The requirement is still deemed proper and is therefore made FINAL.
Claims 11-15, 17-18, 20-24, 27-33 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 04/21/2026.
Claims 1-10, 16, and 25-26 are under consideration and are being examined herein.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119
(a)-(d). The certified copy has been filed in parent Application No. GB2102471.6 filed on 02/22/2021. The instant application is a 371 national stage application of PCT/EP2022/054370
filled on 02/22/2022.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 08/18/2023 and 01/23/2026 are acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. 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. See pages 1, 23 and 32.
Claim Objections
Claims 1, 4, 5, 7, 8, 10 and 25 are objected to because of the following informalities: Claims 1, 4, 5, 7, 8, 10 and 25 contain the acronym RING. RING should be defined the first time it is used in the claims. Appropriate correction is required.
Claims 5, 6, 7 and 25 are objected to because of the following informalities: Claims 5, 6, 7 and 25 contain the acronym TRIM. TRIM should be defined the first time it is used in the claims. Appropriate correction is required.
Claims 2, 3, 4, 5, 6, 7, 8, 9, and 25 are objected to because of the following informalities: Claims 2, 3, 4, 5, 6, 7, 8, 9, and 25 are missing a comma before “wherein”. The claims should read “claim x, wherein”. Appropriate correction is required.
Claim 4 is objected to because of the following informalities: Claim 4 recites “herein”. The claim should be amended to recite “wherein”. Appropriate correction is required.
Claims 4, 5, 8, 9, 10 and 16 are objected to because of the following informalities: Claims 4, 5, 8, 9, 10 and 16 recites “claims 1”. The claims should read “claim 1”. Appropriate correction is required.
Claim 26 is objected to because of the following informalities: Claim 26 recites “,wherein , wherein”. The claim should be amended to remove “wherein ,”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 4, 5-7, and 25 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 4 is indefinite in the recitation of “the protein targeting domain is located at the C-terminal domain end of the first and second RIND domains” for the following reason. It is unclear if there is a protein targeting domain located at the C-terminus of the first RING domain and a protein targeting domain at the C-terminus of the second RING domain or just at the C-terminus of the second RING domain. The claim is interpreted as every domain of the fusion protein has its own N- and C-terminus and are arranged sequentially with the C-terminus of the first RING links to the N-terminus of the second RING and the protein targeting domain is linked to the C-terminus of the second RING domain. Correction is required.
Claims 5-7 and 25 are indefinite in the recitation of “RING domain are derived from TRIM polypeptides”, “RING domain are derived from the same TRIM polypeptide” and “RING domain are derived from TRIM21”. It is unclear which interpretation should be taken: whether the term “derived” is intended to mean that some modification is made to the TRIM polypeptides or simply indicate that the domains are the RING domains of the TRIM polypeptides, or if there is some other intention. Correction is required.
Claim Rejections - 35 USC § 112(a) Written Description
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 (2-10, 16, 25 and 26 dependents thereon) 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.
As stated in MPEP 2111.01, during examination, the claims must be interpreted as broadly as their terms reasonably allow. Claim 1 is directed in part to a fusion protein comprising a first RING domain; a second RING domain; and a protein targeting domain. The RING domains can be from any protein that has a RING domain and the protein targeting domain can be any molecule that targets a protein. Claim 5 is directed to the fusion protein according to claim 1, wherein the first RING domain and second RING domain are derived from TRIM polypeptides. Claim 6 is directed to the fusion protein according to claim 5, wherein the TRIM polypeptides are selected from the group consisting of TRIM5, TRIM7, TRIM19, TRIM21, TRIM25, TRIM28 and TRIM 32. Claim 7 is directed to the fusion protein according to claim 6, wherein the first RING domain and second RING domain are derived from the same TRIM polypeptide.
The specification discloses support for a fusion protein (R-R-PS) composed of linked two RING domains of TRIM21 with a PRYSPRY domain further bound to the C-terminus thereof is capable of efficient formation of TRIM21 anchored ubiquitin chains (see Example 3), efficient degradation of GFP-Fc (see Example 4), and degradation of endogenous Iκκα via rabbit αIκκ IgG (see Example 6). The specification as filed, only describes fusion proteins with the RING domains derived from TRIM21 and show that the RING domain of TRIM5α is also suitable for inclusion in the fusion proteins of the invention (see Example 5). Claim 1 exceeds what is actually described in the specification and does not convey that the applicants were in possession of any “fusion protein comprising RING domains from any protein that has a RING domain and a domain that is any molecule that targets a protein.
The specification does not disclose a TRIM ‘genus” such that the RING domains can be derived from any TRIM polypeptide, nor does it provide structural or functional guidance that would demonstrate possession of fusion proteins using RING domains from TRIM family members generally, beyond the specifically described TRIM21 and TRIM5α. The disclosure of TRIM21 and TRIM5α are insufficient to demonstrate that the inventors were in possession of the broader genus of “TRIM polypeptides” recited in claim 5.
Claim 6 further limits the subject matter to a list of TRIM polypeptides (“TRIM5, TRIM7, TRIM19, TRIM21, TRIM25, TRIM28 and TRIM 32”). The specification, however, does not describe fusion proteins comprising RING domains from TRIM7, TRIM19, TRIM25, TRIM28 or TRIM 32. The presence of TRIM21 and TRIM5α in the examples and proposing that the mechanism presented in Example 5 (see pg. 33) is likely found more widely within the realm of RING E3 ligases does not provide written description support for fusion proteins derived from TRIM7, TRIM19, TRIM25, TRIM28 or TRIM 32. The specification does not reasonably convey to those skilled in the art that the inventors had possession, at filing, of fusion proteins derived from these particular TRIM proteins, opposed to TRIM21 and TRIM5α. Accordingly, claim 6 lacks adequate written description support.
Claim 7 further limits claim 6 wherein both RING domains are derived from the same TRIM21 polypeptide. The specification only describes constructs using TRIM21 and TRIM5α and does not reasonably convey possession of constructs I which both RING domains are derived from other TRIM polypeptides. Thus, claim 7 is not adequately supported in its full breadth.
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.
Claim 1-2, 5-9, 16, 25 and 26 are rejected under 35 U.S.C. 102(a)(1)(a)(2) as being anticipated by James et al. (WO2012/010855A1, Pub. 01/26/2012; Applicant-Cited Prior Art in IDS dated 08/18/2023; B1).
Claim 1 is directed in part to a fusion protein comprising: a first RING domain; a second RING domain; and a protein targeting domain. Claim 2 is directed to the fusion protein of claim 1, wherein the fusion protein does not comprise a domain selected from a coiled-coil domain and a B-box domain. This is interpreted as the fusion protein can have a coiled-coil domain but not a B-box domain or can have a B-box domain and not a coiled-coil domain.
Claim 5 is directed to the fusion protein according to claim 1, wherein the first RING domain and second RING domain are derived from TRIM polypeptides. Claim 6 is directed to the fusion protein according to claim 5, wherein the TRIM polypeptides are selected from the group consisting of TRIM5, TRIM7, TRIM19, TRIM21, TRIM25, TRIM28 and TRIM 32. Claim 7 is directed to the fusion protein according to claim 6, wherein the first RING domain and second RING domain are derived from the same TRIM polypeptide. Claim 8 is directed to the fusion protein according to claim 1, wherein the fusion protein comprises two RING domains. Claim 9 is directed to the fusion protein according to claim 1, wherein the protein targeting domain is a PRYSPRY domain, an antibody or antibody fragment thereof, or antibody mimetic. Claim 16 is directed to a pharmaceutical composition comprising a fusion protein according to claim 1, and a pharmaceutically acceptable carrier and/or excipient. Claim 25 is directed to the fusion protein according to claim 6, wherein the first RING domain and second RING domain are derived from TRIM21.Claim 26 is directed to the fusion protein of claim 9, wherein, wherein the antibody fragment is selected from the group consisting of a Fab, Fab', F(ab')2, scFab, Fv, scFV, dAB, VL fragments thereof, VH fragments thereof and VHH fragments thereof.
James et al. teaches a compound comprising a ligand which binds, directly or indirectly, specifically to an antigen of a pathogen provided that said ligand is not the PRYSPRY domain of TRIM21; and a RING domain and/or an inducer of TRIM21 expression (see pg. 57, claim 1). James et al. teaches the RING domain is derived from a TRIM polypeptide (see pg. 57, claim 8). James et al. teaches that the TRIM polypeptide is selected from the group consisting of TRIM5α, TRIM19, TRIM21 and TRIM28 (see pg. 57, claim 9). James et al. teaches that the compound may contain two or more RING domains (see pg. 57, claim 10 and pg. 4, lines 23-24). James et al. teaches that the RING domain used in the invention has an E3 ligase activity (see pg. 22, Lines 6-9 and pg. 57, claim 7). James et al. teaches that another domain such as the B-box domain or coiled-coil domain can be also be added (see pg. 4, Lines 15-22) and also a pA-R fusion protein that is a protein A and RING domain without the B-box and coiled-coil domain (see pg. 54, Line 16). James et al. teaches that the immunoglobulin molecule that is in the compound can be VHH (see pg. 57, claim 3). James et al. teaches that the compounds of the invention can be utilized in purified form together with pharmacologically appropriate carriers (see pg. 37, Lines 3-10). Therefore, the teachings of James et al. anticipate the instant claims as written/interpreted.
Claims 1, 3-4 and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Fletcher et al. (Cell Host and Microbe 24, 761-775, published 12/12/2018, Applicant-Cited Prior Art in IDS dated 08/18/2023; C4).
Claim 1 is directed in part to a fusion protein comprising: a first RING domain; a second RING domain; and a protein targeting domain.
Claim 3 is directed in part to the fusion protein of claim 1, wherein the fusion protein does not comprise a coiled-coil domain and does not comprise a B-box domain.
Claim 4 is directed to a fusion protein according to claim 1, wherein the protein targeting domain is located at the C-terminal domain end of the first and second RING domains.
Fletcher et al. teaches a tandem RING protein with a genetically installed non-hydrolyzable Ub at its N terminus, and a FLAG tag at the C terminus (UbRRFLAG) (see pg. 772, left column, second paragraph). A FLAG tag can be interpreted as a protein targeting domain as it binds to an anti-FLAG antibody. See interpretation of claim 4 in Claim Rejections - 35 USC § 112(b). Therefore, the teachings of Fletcher et al. anticipate claims 3 and 4 as written/interpreted.
Claim 10 is directed to the fusion protein according to claim 1, further comprising linker sequences between the first and second RING domains and/or the second RING domain and the protein targeting sequence.
Fletcher et al. teaches a recombinant tandem RING protein, connected by a two-residue linker, including sufficient RING residues to form the “four-helix bundle” that allows RING dimerization (see pg. 772, left column, first paragraph). Therefore, the teachings of Fletcher et al. anticipate claim 10 as written/interpreted.
Double Patenting
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 conflicting claims 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) 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 www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-10, 16, and 25-26 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7-10 and 15 of copending Application No. 18/877,919 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the set of claims pertain to a fusion protein comprising a first RING domain, a second RING domain, and protein targeting domain (adapter domain is a protein targeting domain (see pg. 14 of the specification of 18/877,919), wherein the second RING domain is between the first RING domain and the protein targeting domain.
Claims 1-10, 16 and 25-26 of the instant application as interpreted are directed in part to a fusion protein comprising a first RING domain; a second RING domain; and a protein targeting domain, wherein the fusion protein of claim 1 does not comprise a domain selected from a coiled coil domain and a B-box domain, wherein the fusion protein of claim 1 does not comprise a coiled-coil domain and does not comprise a B-box domain, wherein the protein targeting domain of the fusion protein of claim 1 is located at the C-terminal domain end of the first and second RING domains, wherein the first and second RING domains of the fusion protein of claim 1 are derived from TRIM polypeptides, wherein the TRIM polypeptides of the fusion protein of claim 5 are selected from a group consisting of TRIM5, TRIM7, TRIM19, TRIM21, TRIM25, TRIM28 and TRIM32, wherein the first and second RING domains of the fusion protein of claim 6 are derived from the same TRIM polypeptide, wherein the fusion protein of claim 1 comprises two RING domains, wherein the protein targeting domain of the fusion protein of claim 1 is a PRYSPRY domain, an antibody or antibody fragment thereof, or antibody mimetic, wherein the fusion protein of claim 1 has a linker between the first and second RING domains and/or the second RING domain and the protein targeting domain, wherein a pharmaceutical composition comprises the fusion protein of claim 1, and a pharmaceutically acceptable carrier and/or excipient, wherein both RING domains of the fusion protein of claim 6 are derived from TRIM21, and wherein the antibody fragment of claim 9 is selected from the group consisting of a Fab, Fab', F(ab')2, scFab, Fv, scFV, dAB, VL fragments thereof, VH fragments thereof and VHH fragments thereof.
Claims 1-10, 16, and 25-26 of the instant application are patentably indistinct from claims 1, 7-10 and 15 of copending Application No. 18/877,919. Claims 1, 7-10 and 15 of copending application No. 18/877,919 are directed to a fusion protein comprising: - at least a first RING domain; and an adaptor domain that is capable of localizing the RING domain with a substrate, and wherein the fusion protein is incapable of N-terminal autoubiquitination, wherein the fusion protein of claim 1 comprises a second RING domain, wherein the second RING domain is between the first RING domain and the adaptor domain; does not comprise a coiled-coil domain and/or B-box domain; and/or comprises a linker sequence between the RING domain and the adapter sequence, wherein the RING domains of claim 1 are derived from TRIM polypeptides, wherein the TRIM polypeptides of the fusion protein of claim 8 are selected from TRIM5, TRIM7, TRIM19, TRIM21, TRIM25, TRIM28 and TRIM32, preferably TRIM21, wherein the adaptor sequence of the fusion protein of claim 1 is a protein targeting domain selected from PRYSPRY domain, an antibody or antibody fragment thereof, or antibody mimetic, wherein the antibody fragment is preferably selected from the group consisting of Fab, Fab', F(ab')2, scFab, Fv, scFV, dAB, VL fragments thereof, VH fragments thereof and VHH fragments thereof, and a pharmaceutical composition comprising the fusion protein of claim 1 and a pharmaceutically acceptable carrier and/or excipient.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are in condition for allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DALTON EDWARD KIEFER whose telephone number is (571)272-1235. The examiner can normally be reached M-F 7:30-5 EST.
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/DALTON EDWARD KIEFER/Examiner, Art Unit 1652
/ROBERT B MONDESI/Supervisory Patent Examiner, Art Unit 1652
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