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
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on June 9, 2026 has been entered.
RESPONSE TO AMENDMENT
Status of Application/Amendments/claims
3. Applicant’s amendment filed June 9, 2026 is acknowledged. Claims 2-21 are cancelled. Claims 1 and 22-28 are pending in this application. Election was made without traverse in the reply filed on May 22, 2023.
4. Claims 1 and 22-28 are under examination with respect to a p75NTR neurotrophin binding protein (NBP)-Fc fusion protein in this office action.
5. Applicant’s arguments filed on June 9, 2026 have been fully considered but they are not deemed to be persuasive for the reasons set forth below.
Claim Rejections/Objections Withdrawn
6. The provisional rejection of claims 1 and 22-28 on the ground of nonstatutory double patenting as being unpatentable over claims 24, 27-28, 33, 36 and 38 of copending Application No. 17/659991, claims 1, 12-15 and 21-30 of copending Application No. 18/975908 is withdrawn in response to Applicant’s approved terminal disclaimer.
Claim Rejections/Objections Maintained
In view of the amendment filed on June 9, 2026, the following rejections are maintained.
Double Patenting
7. 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 and 22-28 stand rejected on the ground of nonstatutory double patenting as being unpatentable over claims 5-6 and 9 of US9764000, claims 5-6, 9 of US10751389, claims 5-6 of US12201672 in view of He et al. (Science, 2004; 304:870-875) and Ying et al. (J. Biol. Chem., 2012; 287:19399-19408). The rejection is maintained for the reasons of record and the reasons set forth below.
The p75NTR (NBP) fusion protein recited in the claims or used in the method recited in the claims of the US976400 (the ‘000 patent), the US10751389 (‘the ‘389 patent), or the US12201672 (the ‘672 patent) comprises the p75NTR(NBP) connected to IgG Fc and wherein the p75NTR (NBP) fusion protein comprises instant SEQ ID NO:3. Thus, The p75NTR (NBP) fusion protein recited in the claims of the ‘000, the ‘389 and the ‘672 patents meets the limitation “the fusion protein comprising instant SEQ ID NO:3 “ recited in instant claims.
While the claims of the ‘000, the ‘389 and the ‘672 patents do not recite the limitation “dimer” or “two monomers linked by a disulfide bond” recited in claims 1 and 22-28, He et al. and Ying et al. teach these limitations and provide motivation and an expectation of success in generation of a fusion protein dimer comprising the sequence of instant SEQ ID NO:3 because:
i) the claimed fusion protein dimer comprises a p75NTR(NBP) fusion protein that comprises a p75NTR(NBP) and a IgFc, and also comprises the instant SEQ ID NO:3;
ii) an Ig-Fc-fusion automatically forms a dimer as evidenced by Ying et al. (see p. 19399, 2nd col., 2nd-3rd para.)
iii) the p75NTR or p75NTR(NBP) automatically forms a homodimer via a disulfide bond on the cell surface, and NGF forms a homodimer via a disulfide bond and complexed with a p75NTR or p75NTR(NBP) dimer to execute their activity and downstream intracellular signaling as taught by He (see p.873, col. 3, paragraph 3 to p. 875); and
iv) an Ig Fc fusion protein monomer is more soluble and does not affect binding or activity of the fusion protein as taught by Ying (see p.19399, abstract).
A person of ordinary skill in the art would have recognized that selecting and applying the known features of forming a homodimer by the p75NTR(NBP) fusion protein or p75NTR(NBP)-IgFc fusion protein and the known technique disclosed by He and Ying to the p75NTR (NBP) fusion protein comprising instant SEQ ID NO:3 of the ‘000, the ‘389 and the ‘672 patents would have yielded the predictable result of generation of a fusion protein dimer comprising instant SEQ ID NO:3, wherein the fusion protein dimer comprises two monomers and each monomer comprises instant SEQ ID NO:3 and linked through a disulfide bond, and resulted in an improved product.
Using the known features of forming a homodimer by p75NTR(NBP) and/or IgFc via a disulfide bound to the p75NTR (NBP) fusion protein comprising instant SEQ ID NO:3 of the ‘000, the ‘389 and the ‘672 patents would generate a fusion protein dimer comprising instant SEQ ID NO:3, wherein the fusion protein dimer comprises two monomers and each monomer comprises instant SEQ ID NO:3 and linked through a disulfide bond, and expand application of the p75NTR (NBP) fusion protein comprising instant SEQ ID NO:3 of the ‘000, the ‘389 and the ‘672 patents in therapeutic and pharmaceutical purposes, and would increase patient’s satisfaction with treatment using the p75NTR (NBP) fusion protein comprising instant SEQ ID NO:3 because the activity of NGF and p75NTR(NBP) form a homodimer complex to execute their activity and downstream intracellular signaling.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known features of forming a homodimer by p75NTR(NBP) fusion protein or p75NTR(NBP)-IgFc fusion protein and the known technique disclosed by He and Ying to the p75NTR (NBP) fusion protein comprising instant SEQ ID NO:3 of the ‘000, the ‘389 and the ‘672 patents, and yield the predictable result of a fusion protein dimer comprising instant SEQ ID NO:3, wherein the fusion protein dimer comprises two monomers and each monomer comprises instant SEQ ID NO:3 and linked through a disulfide bond. Therefore, instant claims are not patentably distinct from the claims of the ‘000, the ‘389 and the ‘672 patents because instant claims are obvious over the claims of the ‘000, the ‘389 and the ‘672 patents in view of He and Ying.
Response to Arguments
On p. 4-5 of the response, Applicant argues that: i) instant claims are patentably distinct from a fusion protein recited the claims of the issued patents because the instant claims require a dimer of a fusion protein having instant SEQ ID NO:3, and none of the patents claim a fusion dimer; ii) different fusion proteins with different linkers showed different functional characteristics and immunogenicity but SEQ ID NO:3 had no immunogenicity.
Applicant's arguments have been fully considered but they are not found persuasive. Contrary to Applicant's arguments, the examiner asserts that based on MPEP §804, MPEP §2141, MPEP2141-I, rationales identified by the Court in KSR (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, 82 USPQ2d 1385 (2007)), MPEP2141-II, the basic factual inquires of Graham v. John Deere Co.(Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966)),and MPEP §2141.01-2147.03, the cited references do render the claimed invention obvious because:
i. The p75NTR (NBP) fusion protein recited in the claims or used in the method recited in the claims of the US976400 (the ‘000 patent), the US10751389 (‘the ‘389 patent), or the US12201672 (the ‘672 patent) comprises the p75NTR(NBP) connected to IgG Fc, and comprises the instant SEQ ID NO:3.
ii. an Ig-Fc-fusion automatically forms a dimer as evidenced by Ying et al. (see p. 19399, 2nd col., 2nd-3rd para.).
iii. the p75NTR or p75NTR(NBP) also automatically forms a homodimer via a disulfide bond on the cell surface, and NGF forms a homodimer via a disulfide bond and complexed with a p75NTR or p75NTR(NBP) dimer to execute their activity and downstream intracellular signaling as taught by He (see p.873, col. 3, paragraph 3 to p. 875).
While the claims of the ‘000, the ‘389 and the ‘672 patents do not recite the limitation “dimer” or two monomers linked by a disulfide bond recited in claims 1 and 22-28, the p75NTR (NBP) fusion protein recited in the claims of the ‘000 patent, the ‘389 patent, or the ‘672 patent comprises the p75NTR(NBP) connected to IgG Fc, and comprises the instant SEQ ID NO:3, which meets the limitation “a fusion protein dimer comprising the sequence of instant SEQ ID NO:3” recited in instant claims.
In addition, He teaches that p75NTR or p75NTR(NBP) forms a homodimer via a disulfide bond on the cell surface, and NGF forms a homodimer via a disulfide bond and complexed with a p75NTR or p75NTR(NBP) dimer to execute their activity and downstream intracellular signaling (see p.873, col. 3, paragraph 3 to p. 875) and Ying teaches that an Ig-Fc-fusion automatically forms a dimer (see p. 19399, 2nd col., 2nd-3rd para.); and an IgFc fusion protein monomer is more soluble and does not affect binding or activity of the fusion protein (see p.19399, abstract).
A person of ordinary skill in the art would have recognized that selecting and applying the known features of forming a homodimer by the p75NTR(NBP) fusion protein or p75NTR(NBP)-IgFc fusion protein and the known technique disclosed by He and Ying to the p75NTR (NBP) fusion protein comprising instant SEQ ID NO:3 of the ‘000, the ‘389 and the ‘672 patents would have yielded the predictable result of generation of a fusion protein dimer comprising instant SEQ ID NO:3, wherein the fusion protein dimer comprises two monomers and each monomer comprises instant SEQ ID NO:3 and linked through a disulfide bond, and resulted in an improved product because the activity of NGF and p75NTR(NBP) form a homodimer complex to execute their activity and downstream intracellular signaling and an Fc fusion protein automatically forms a dimer and does not affect the activity of the fusion protein.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known features of forming a homodimer by p75NTR(NBP) fusion protein or p75NTR(NBP)-IgFc fusion protein and the known technique disclosed by He and Ying to the p75NTR (NBP) fusion protein comprising instant SEQ ID NO:3 of the ‘000, the ‘389 and the ‘672 patents, and yield the predictable result of a fusion protein dimer comprising instant SEQ ID NO:3, wherein the fusion protein dimer comprises two monomers and each monomer comprises instant SEQ ID NO:3 and linked through a disulfide bond.
Therefore, instant claims are not patentably distinct from the claims of the ‘000, the ‘389 and the ‘672 patents because instant claims are obvious over the claims of the ‘000, the ‘389 and the ‘672 patents in view of He and Ying.
Accordingly, the rejection of claims 1 and 22-28 on the ground of nonstatutory double patenting as being unpatentable over claims 5-6 and 9 of US9764000, claims 5-6, 9 of US10751389, claims 5-6 of US12201672 in view of He and Ying is maintained.
Double Patenting
8. Claims 1 and 22-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9-22 of copending Application No. 19/294032, claims 1-9 of copending Application No. 19/397512, claims 1-9 of copending Application No. 19/397514 or claims 1-23 of copending Application No. 19/706179 in view of He et al. (Science, 2004; 304:870-875) and Ying et al. (J. Biol. Chem., 2012; 287:19399-19408). The rejection over Application No. 19/706179 is necessitated by an update search of inventor name. The rejection is maintained for the reasons of record and the reasons set forth below.
The p75NTR (NBP) fusion protein recited in the claims or used in the method recited in the claims of the ‘032, the 512, the ‘514 and the ‘179 Applications comprises the p75NTR(NBP) connected to IgG Fc and wherein the p75NTR (NBP) fusion protein comprises instant SEQ ID NO:3. Thus, The p75NTR (NBP) fusion protein recited in the claims of the ‘000, the ‘389 and the ‘672 patents meets the limitation “the fusion protein comprising instant SEQ ID NO:3 “ recited in instant claims.
While the claims of the ‘032, the 512, the ‘514 and the ‘179 Applications do not recite the limitation “dimer” or two monomers linked by a disulfide bond recited in claims 1 and 22-28, He et al. and Ying et al. teach these limitations and provide motivation and an expectation of success for the reasons set forth above.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known features of forming a homodimer by p75NTR(NBP) fusion protein or p75NTR(NBP)-IgFc fusion protein and the known technique disclosed by He and Ying to the p75NTR (NBP) fusion protein comprising instant SEQ ID NO:3 of the ‘032, the 512, the ‘514 and the ‘179 Applications, and yield the predictable result of a fusion protein dimer comprising instant SEQ ID NO:3, wherein the fusion protein dimer comprises two monomers and each monomer comprises instant SEQ ID NO:3 and linked through a disulfide bond.
Therefore, instant claims are not patentably distinct from the claims of t the ‘032, the 512, the ‘514 and the ‘179 Applications because instant claims are obvious over the claims of the ‘032, the 512, the ‘514 and the ‘179 Applications in view of He and Ying.
Response to Arguments
On p.5 of the response, Applicant argues that the rejection is moot and should be withdrawn because none of the cited applications have issued. Applicant requests the rejections be held in abeyance.
In response, the provisional rejection of claims 1 and 22-28 on the ground of nonstatutory double patenting as being unpatentable over claims 9-22 of copending Application No. 19/294032, claims 1-9 of copending Application No. 19/397512, claims 1-9 of copending Application No. 19/397514 or claims 1-23 of copending Application No. 19/706179 in view of He and Ying is maintained of record and until a terminal disclaimer is filed.
Conclusion
9. NO CLAIM IS ALLOWED.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHANG-YU WANG whose telephone number is (571)272-4521. The examiner can normally be reached Monday-Thursday, 7:00am-5:00pm EST.
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Chang-Yu Wang
June 26, 2026
/CHANG-YU WANG/Primary Examiner, Art Unit 1675
Prosecution Insights