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
The instant application, filed on 09/14/2022, claims priority to the US Provisional application 63/243843, filed on 09/14/2021. The claimed priority cannot be granted because new matter (SEQ IDs 4 and 7) was introduced in the instant application and the new matter is recited as a limitation to all the instant independent and dependent claims. Also, the diagrams submitted on 09/14/2022 includes Fig. 1 and Fig. 3A-3D which are not present in the US Provisional application 63/243843. Applicant is advised the instant claims will be examine with a priority date of 09/14/2022.
Status of the Claims/Application
Claims 3-10, 12, 15-18, 21-23, 27-46, 51, 54 and 56-57 are canceled. Claims 1 and 2 are currently amended. Claims 1-2, 11, 13-14, 19-20, 24-26, 47-50, 52-53 and 55 are pending and are herein under examination on the merits.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 01/16/2026 is acknowledged and is in compliance with the provisions of 37 CRF 1.97. It has been considered by the examiner.
Withdrawn Rejections
As per applicant amendment/remarks filed on 01/16/2026, claims 1 and 2 are amended to not include SEQ ID NOs 3, therefore rendering the rejections submitted on 10/22/2025 under 35 USC 101, 35 USC 102 and 35 USC 35 103 moot. Therefore, the rejections under 35 USC 101, 35 USC 102 and 35 USC 35 103 submitted on 10/22/2025 are withdrawn.
New Grounds for Rejections
In view of the applicants remarks/amendments to instant claims 1 and 2 filed on 01/16/2026 in response to the office action submitted on 10/22/2025, the examiner establishes new grounds for rejections in view of the amendments of independent claims 1 and 2 from which all the other claims depend.
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.
Claims 1-2, 11, 13, 19-20, 24-26, 47-50, 52-53 and 55 are rejected under 35 U.S.C. 102 as being anticipated by WO 2020/069398 A1, herein further referred to as Karow.
The applied reference has a common applicant and joint inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(1).
Regarding claims 1, 2, 11, 13, 20 and 24, Karow teaches;
a.) a masked cytokine comprising of (Karow Abstract, para 0040 and Fig 3A) to be masked by a masking moiety at one or more receptor sites of the cytokine or a functional fragment thereof, wherein the cytokine becomes activated by a protease at the target site and wherein the half-life of the cytokine is also extended,b.) a first polypeptide chain comprising a masking moiety such as CD122 (Karow para 225 and 247) for capable of binding or inhibit the cytokine from binding to its cognate receptor, and the cytokine only becomes active at the target site after protease cleavage of the linker at the target site, and wherein the masking moiety is linked to a first half-life extension moiety such as a heavy chain of the Fc domain for extending the half-life of the cytokine (Karow para 0308-0309) via a first linker; and (Karow para 0040, and Fig. 3A)
c.) a second polypeptide chain comprising a cytokine moiety such as IL-2 (Karow para 0592) which can be the therapeutic component for targeting a tumor, thereof linked to a second half-life extension moiety (also a heavy chain of an Fe domain) via a second linker (Karow para 0040 and Fig. 3A),
i.) wherein the first half-life extension moiety is associated with the second half-life extension moiety through a disulfide bond to form the Fe domain for half-life extension (Karow para 0040 and Fig. 3A), and
ii.) wherein at least the first linker or the second linker comprises a polypeptide.
Karow teaches that this construct is used to address the issue that there is a need for developing cytokine therapeutics that effectively target tumors without the side effects associated with systemic immune activation (Karow para 5). Karow also teaches that a linker that comprises the amino acid sequence having about or at least 85-95 % sequence identity to an amino acid sequence selected from SEQ ID NO: 356-555 can be used as a proteolytically cleavable peptide linker in the polypeptide construct (Karow para 0268-0269). Karow teaches that SEQ ID NO: 379 (IPVSLRSGRSNAQRLE) an amino acid of 16 amino acids in length (Karow Tab. 1). SEQ ID NO: 379 has an 89.% match to SEQ ID NO 1 (PVSLRSGS) with a “best locality similarity” of 100% at PVSLRSG which includes the known cleavage sites for MMP-2 as evidenced by US’6154’s SEQ ID NOs: 36 and 37 (US’6154 col 8 Tab. 2).
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Regarding claim 14, and incorporating the analysis of claim 2 above, KAROW teaches that the linkers (1CP and 2CP) are between the making moiety, cytokine, and the half-life extension domain (Karow Fig. 3A). Regarding "carrier moiety" in claim 14, the specification indicates that "carrier" includes immunoglobulins (Specification, para. 0238). Karow teach that the half-life extension domain includes the Fc domain (Karow para 0311).
Regarding claim 19, and incorporating the analysis of claim 2 above, Karow teaches a masked IL-2 polypeptide construct comprising a masking moiety. Karow teaches that a masking moiety refers to a peptide capable of binding to, or otherwise exhibiting an affinity for a cytokine or functional group (Karow para 0570). Karow teaches exemplary masking moieties including can be IL-2R or IL-2 receptor that comprises IL-2Rα, IL-2Rß and IL-2Rγ, and IL-2Rα is an extracellular domain of the IL-2 receptor that binds to IL-2 (Karow para 0571).
Regarding claims 25 and 26 and incorporation the analysis of claims 1 and 24, Karow teaches that the masked cytokines may be constructed such that either of the linkers can be a cleavable or non-cleavable linker (Karow para 0592) so as to construct an activated or nonactivated construct upon cleavage or non-cleavage of the linker. Karow Table 4 teaches exemplary constructs wherein the first linker is cleavable and the second linker is non-cleavable and vice versa.
Regarding claim 47, and incorporating the above analysis of claim 1, Karow
teaches that upon proteolytic cleavage of the cleavable linker at the target site, the cytokine becomes activated and is capable of binding to its cognate receptor or protein of interest (Karow Abstract).
Regarding claim 48, and incorporating the above analysis of claim 1 above, US'3298 teaches a nucleic acid encoding a polypeptide (Karow para 0028 and 0459-0460).
Regarding claim 49, and incorporating the above analysis of claim 48 above, Karow teaches a vector comprising a nucleic acid (Karow para 0028 and para 0459-0460).
Regarding claim 50, and incorporating the above analysis of claim 49 above, Karow teaches a host cell comprising a vector (Karow para 0028 and para 0459-0460).
Regarding claims 52, and incorporating the above analysis of claim 2 above, Karow teaches a pharmaceutical composition comprising the polypeptide construct and a pharmaceutically acceptable salt (Karow para 0034-0035). Regarding claim 53, and incorporating the above analysis of claim 52 above, KAROW teaches a kit comprising a pharmaceutical composition as in claim 52 (KAROW Col. 5, lines 53-54).
Regarding claim 55, and incorporating the above analysis of claim 13 above, KAROW teaches a method for treating or preventing cancer in a subject, (Karow para 0036), the method comprising administering to the subject an effective amount of a masked IL-2 polypeptide construct (Karow para 0592). IL-2 is approved for the treatment of metastatic renal carcinoma and melanoma (Karow para 0005).
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 24 and 26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 17 /995159 in view Karow herein further referred to as US’5159. Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of the copending application recites a masked cytokine that comprises all the limitations of claims 24 and 26 of the instant application. Claim 1 of the copending does not specifically recite the amino acid sequence as claimed in claims 24 and 26 but recites a broad genus of linkers.
Karow teaches that a linker that comprises the amino acid sequence having about or at least 85-95 % sequence identity to an amino acid sequence selected from SEQ ID NO: 356-555 can be used as a proteolytically cleavable peptide linker in the polypeptide construct (Karow para 0268-0269). KAROW teaches that SEQ ID NO: 379 (IPVSLRSGRSNAQRLE) an amino acid of 16 amino acids in length (Karow Tab. 1). SEQ ID NO: 379 has an 89.% match to SEQ ID NO 1 (PVSLRSGS) with a “best locality similarity” of 100% at PVSLRSG which includes the known cleavage sites for MMP-2.
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Therefore, it would have been obvious for a skilled before the effective filing date for a skilled artisan to modify the teachings of US’5159 in view Karow with a reasonable high degree of predictable success to use a proteolytically cleavable peptide with amino acid such as that of Karow to construct the masked cytokine as claimed in instant claims 24 and 26.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 24-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 9 and 19 of copending Application No. 17/995162 in view Karow, herein further referred to as US’5163. Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1 and 9 of the copending application, US’5163 all the limitations of the masked cytokine as claimed in the instant application. Claims 1 and 9 of US’5163 does not specifically recite the amino acid sequence as claimed in claims 24 and 26 but recites a broad genus of linkers that can be used in the construct.
Karow teaches that a linker that comprises the amino acid sequence having about or at least 85-95 % sequence identity to an amino acid sequence selected from SEQ ID NO: 356-555 can be used as a proteolytically cleavable peptide linker in the polypeptide construct (Karow para 0268-0269). Karow teaches that SEQ ID NO: 379 (IPVSLRSGRSNAQRLE) an amino acid of 16 amino acids in length (Karow Tab. 1). SEQ ID NO: 379 has an 89.% match to SEQ ID NO 1 (PVSLRSGS) with a “best locality similarity” of 100% at PVSLRSG which includes the known cleavage sites for MMP-2.
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Therefore, it would have been obvious for a skilled before the effective filing date for a skilled artisan to modify the teachings of US’5162 in view Karow with a reasonable high degree of predictable success to use a proteolytically cleavable peptide with amino acid such as that of Karow to construct the masked cytokine as claimed in instant claims 24 and 26.
Response to Arguments
Applicant’s arguments/amendments, see Remarks pg. 5-9, filed 01/16/2026, with respect to the rejections of claims 1, 2 and 48 under 35 USC 101, claims 1-2, 11 and 13 under 35 USC 102(a)(1) and/or 102(a)(2), claims 1, 2, 14, 19-20, 24-26, and 47-50, 52-53 and 55 under 35 USC 103, and claims 1-2, 24, 26, 35 and 52-53 under NSDPs have been fully considered and are persuasive in view of the applicant amendments. Therefore, the rejections have been withdrawn. However, upon further consideration, a new ground of double patent rejections are made in view of the amendments.
Conclusion
No Claims Allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMMANUEL LED YOUTCHOM PENDIE whose telephone number is (571)272-6313. The examiner can normally be reached Mon - Fri: 8AM - 5PM CST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanna Hama can be reached at (571) 272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/EMMANUEL LED YOUTCHOM PENDIE/ Examiner, Art Unit 1647
/JOANNE HAMA/ Supervisory Patent Examiner, Art Unit 1647