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 .
Acknowledgments and Claim Status
The Examiner acknowledges receipt of the amendment filed 4/8/2026 wherein claim 29 was amended; claims 2-7, 11-13, 15, 23, 24, 26, and 28 were canceled; and claims 39-41 were added. In addition, the Examiner acknowledges the amendment filed 2/13/2026.
Note(s): Claims 1, 8-10, 14, 16-22, 25, 27, and 29-41 are pending.
The Examiner acknowledges receipt of the 37 CFR 1.132 declaration filed 2/13/2026 by Tingdong Li, PhD. The declaration was considered, but deemed non-persuasive to overcome the rejection for reasons set forth in the written description (112 first paragraph) rejection below.
Priority and Priority Document
This application is a 371 of PCT/CN2020/101424 filed 7/10/2020 which claims benefit to CHINA CN201910624609.9 filed 7/11/2019.
Note(s): The earliest effective filing date is 7/11/2019 because the priority document fully supports the pending invention.
The Examiner acknowledges receipt of the certified document required by 37 CFR 1.55 filed 1/11/2022. In addition, the Examiner acknowledges receipt of the English translation of the priority document filed 8/26/2025.
Applicant’s Election
Once again, Applicant's election with traverse of Group I filed 4/3/2025 is acknowledged. The traversal is on the grounds that amended independent claim 1 reads on all the groups as they require the fusion protein of amended claim 1. This is found non-persuasive because lack of unity was shown for the claims that were presented for examination as detailed in the office action mailed 2/4/2025. A document (Wadia et al, Nature Medicine, 2004, Vol. 10, No. 3, pages 310-315) was made of record to illustrate that Applicant’s pending independent claim 1 at that time, the claim limitations were met. Thus, independent claim 1 was found to lack a special technical feature distinguished over the prior art. Hence, the restriction requirement was deemed proper and made FINAL.
Once again, in the response filed 4/3/2025, Applicant elected the following species for initial examination: cell penetrating peptide (Tat-derived peptide); pH-sensitive fusogenic peptide (INF7); furin recognition sequence (SEQ ID NO: 4); cathepsin L recognition sequence (SEQ ID NO: 6); specific binding sequence (leucine zipper peptide); and fusion protein (SEQ ID NO: 14). Group I comprises pending claims 1, 8, 9, 29-31, and 37-41.
Note(s): Initially, Applicant’s elected species was searched. No prior art was found to reject the claims. The search was extended over the full scope of Group I. While no prior art was found to reject the claims, Applicant must address and overcome the written description and double patenting rejections below.
Withdrawn Claims
Claims 10, 14, 16-22, 25, 27, and 32-36 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Response to Applicant’s Amendment and/or Arguments
The Applicant's arguments and/or amendment filed 2/13/2026 and 4/8/2026 to the rejection of claims 1, 8, 9, 28-31, 37, and 38 made by the Examiner under 35 USC 112 first paragraph and/or double patenting have been fully considered and deemed non-persuasive for the reasons record and those set forth below.
Double Patenting Rejection
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, 8, 9, 29-31, and 37-41 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 10, 13-15, 21, 26, 29, 32-35 of copending Application No. 17/758,234 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to a fusion protein/polypeptide comprising furin, cathepsin L, a cell penetrating peptide, and a pH sensitive fusogenic peptide (see, for example, copending claims 1 and 15). Thus, the inventions disclose overlapping components. Note(s): Copending SEQ ID Nos: 8 and 10 correspond to pending SEQ ID Nos. 4 and 6, respectively.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
APPLICANT’S ASSERTIONS
In summary, Applicant has requested that the provisional rejection be held in abeyance until allowable subject matter is determined.
EXAMINER’S RESPONSE
Applicant’ request to hold the rejection is duly noted. The rejection is still deemed proper.
Written Description Rejection
Note(s): The rejection was modified to include SEQ ID Nos, 16, 17, and 21 which are present in specification, page 24, Table 2.
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, 8, 9, 29-31, 37, 38, 40, and 41 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.
Applicant is reminded that an inventor is entitled to a patent to protect his work only if he/she produces or has possession of something truly new and novel. The invention being claimed must be sufficiently concrete so that it can be described for the world to appreciate the specific nature of the work that sets it apart from what was before. The inventor must be able to describe the item to be patented with such clarity that the reader is assured that the inventor actually has possession and knowledge of the unique composition that makes it worthy of patent protection. The pending application does not sufficiently describe the invention as it relates to cathepsin L recognition sequences other than sequences comprising or consisting of NNTHDLVGDVRLAGV (SEQ ID NO: 6), NNTHDLVGDVGLAGV (SEQ ID NO: 21), ARAYGFRGPGPQLRRGWRPSS (SEQ ID NO: 16), and EEDNRDSSMKLSFRARAYGFRGPG (SEQ ID NO: 17). Thus, what the reader gathers from the instant application is a desire/plan/first step for obtaining a desired result. While the reader can certainly appreciate the desire for achieving a certain end result, establishing goals does not necessarily mean that an invention has been adequately described.
While compliance with the written description requirements must be determined on a case-by-case basis, the real issue here is simply whether an adequate description is necessary to practice an invention described only in terms of its function and/or based on a disclosure wherein a description of the components necessary in order for the invention to function are lacking. In order to satisfy the written description requirement, the specification must describe every element of the claimed invention in sufficient detail so that one of ordinary skill in the art would recognize that the inventor possessed the claimed invention at the time of filing. In other words, the specification should describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that the inventor created what is the claimed. Thus, the written description requirement is lacking in the instant invention since the various terms as set forth above are not described in a manner to clearly allow persons of ordinary skill in the art to recognize that Applicant invented what is being claimed.
APPLICANT’S ASSERTIONS
In summary, Applicant makes reference to the remarks and declaration filed 2/13/2026 as reasons why the written description rejection should be withdrawn. In particular, it is asserted that (1) the based on the teachings regarding SEQ ID NOs: 6, 16, 17, and 21 in combination with general knowledge in the field, a skilled artisan would be capable of selecting a specific CTSL cleavage site sequence for constructing the delivery system of the pending application. (2) Applicant asserts that cathepsin L (CTSL) cleavage sites (N, Na, and Nb) are derived from human Chromogranin A and would be capable of enhancing delivery efficiency and cellular fluorescence to varying degrees. (3) Applicant asserts that other CTSL cleavage sites are well known and published were published before the filing date of the current application.
EXAMINER’S RESPONSE
First, it should be noted that the written description rejection sets forth that SEQ ID NOs: 6, 16, 17, and 21 have adequate written description. Second, As stated supra, the declaration under 37 CFR 1.132 was considered and deemed non-persuasive for the following reasons.
In regards to (1) and (3), Table 2 (page 24, see excerpt below) is made of record. The amino acid sequences which have adequate written description are SEQ ID NO: 6 NNTHDLVGDVRLAGV; SEQ ID NO: 21 NNTHDLVGDVGLAGV; SEQ ID NO: 16 ARAYGFRGPGPQLRRGWRPSS; and SEQ ID NO: 17 EEDNRDSSMKLSFRARAYGFRGPG. Both SEQ ID NOs: 6 and 21 have all amino acid residues overlapping, except in position 11, SEQ ID NO: 6 has a Arg (R) and SEQ ID NO: 21 has a Gly (G). Arginine and glycine are not conservative amino acid substitutions and as such are not obvious variants of one another. SEQ ID NOs: 16 and 17 both contain the amino acid subsequence ARAYGFRGPG. Thus, the four sequences do not support all cathepsin L sequences in general which may be structural different from those comprising ARAYGFRGPG (see SEQ ID NOs 16 and 17) or NNTHDLVGDV{RG}LAGV (see SEQ ID NOs: 6 and 21). The pending application sets forth an adequate description for the designated cathepsin L species in combination with a cell penetrating peptide, a pH sensitive fusogenic peptide, a protease recognition sequence comprising R-X1-X2-R wherein X1 is any amino acid and X2 is K or R.
In addition, it is noted that the written description statute requires that the specification be written in a full, clear, concise, and exact manner. The disclosure lacks a representative number of species which would lead one skilled in the art to conclude that Applicant was in possession of a multitude of CTSL species that were compatible with the pending invention as the four species used both SEQ ID NOs: 6 and 21 have all amino acid residues overlapping, except in position 11, SEQ ID NO: 6 has a Arg (R) and SEQ ID NO: 21 has a Gly (G) and SEQ ID NOs: 16 and 17 both contain the amino acid subsequence ARAYGFRGPG. Other random species are not present in the disclosure nor is there language to indicate that any CTSL in general would yield the same results. While the number of species required to represent a genus will vary, depending upon the level of skill and knowledge in the art as well as the variability among the claims genus, the disclosure does not support such a genus. Also, it is noted that the disclosure does not set forth a core of CTSL substances (other than SEQ ID NOs: 6, 16, 17, and 21) that are required to ensure that the fusion protein would behave in a certain manner. Likewise, the disclosure does not set forth how to differentiate between CTSL substance to differentiate, without testing which ones(s) is/are compatible with the pending invention.
In regards to (2), it should be noted that the written description rejection was modified to include SEQ ID NOs: 6, 16, 17, and 21 which encompasses recognition sites N, Na, Nb, and mutant N. Thus, the Examiner has indicated that adequate written description is present for those species and made modifications to the rejection.
Page 24, Table 2:
PNG
media_image1.png
254
607
media_image1.png
Greyscale
Information Disclosure Statement
The information disclosure statement filed 2/13/2026 was considered.
Comments/Notes
It should be noted that no prior art is cited against the pending invention. Specifically, the prior art neither anticipates nor renders obvious the particular fusion protein component arrangement from the N-terminus to C-terminus. The closest art is Wadia et al (Nature Medicine, 2004, Vol. 10, No. 3, pages 310-315) which was previously cited in a 103 rejection. The rejection was overcome as detailed in the response filed 8/19/2025.
In the art it is recognized that the order of a fusion protein is critical because it affect a protein’s function, expression level, and folding, for example. See Sino Biological, 2007-2025, https://www.sinobiological.com/resource/protein-review/fusion-protein, pages 1-15.
Conclusion
Claims 1, 8, 9, 29-31, and 37-41 are rejected. Claims 10, 14, 16-22, 25, 27, and 32-36 are withdrawn.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Future Correspondences
Any inquiry concerning this communication or earlier communications from the examiner should be directed to D L Jones whose telephone number is (571)272-0617. The examiner can normally be reached M-F.
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, Michael G. Hartley can be reached at (571)272-0616. 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.
/D. L. Jones/
Primary Patent Examiner
Art Unit 1618
June 2, 2026
Prosecution Insights