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 .
Status of the Claims
1. Claims 1-20 are the original claims filed 8/4/2023. In the Reply filed 3/5/2026, Claims 1, 9, 15 and 20 are amended. In the Response of 8/5/2026, Claims 1-2, 4-9, 11, 13, and 20 are amended, claims 3 and 10 are canceled, and new claim 21 is added.
Claims 1-2, 4-9, 11-21 are of the claims.
Claims 15-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 3/5/2026.
Claims 1-2, 4-9, 11-14 and 20-21 are of the claims under examination.
Applicants’ amendment of the claims raises new grounds for rejection. The Office Action is final.
Priority
2. USAN 18/365,239, filed 08/04/2023, is a Continuation of PCT/CN2022/074716, filed 01/28/2022, and claims foreign priority to CN 202110164375.1, filed 02/05/2021. Receipt is acknowledged of a certified copy of papers for CN 202110164375.1 as required by 37 CFR 1.55.
Information Disclosure Statement
3. As of 9/27/2026, a total of one (1) IDS is filed for this application: 8/4/2023. The corresponding initialed and dated 1449 form is considered and of record.
Withdrawal of Objections
Specification
4. The objection to the disclosure because of informalities is withdrawn.
a) The specification is amended to rectify the deficiencies for figure legends to include labeled panels.
b) The specification is amended to rectify the deficiencies to include sequence identifiers for the peptide sequences > 4 amino acids in length at [0040; 0043; 0094; 0096] and pursuant to 37 CFR 1.812-1.825.
c) The specification is amended to rectify the deficiencies for the improper use of the term Microfuge, SnapGene, CutSmart, which is a trade name or a mark used in commerce.
Claim Objections
5. The objection to Claims 1-14 and 20 because of informalities is moot for the canceled claims (claims 3 and 10) and withdrawn for the pending claims.
b) Claim 1 is amended to replace “being composed of” with “comprising”.
c) Claims 1-14 and 20 are amended in claim 1 to replace “being composed of” with “comprising”.
d) Claims 1-14 and 20 are amended to delete the phrase recite the phrase “has an ability to specifically” in claim 1.
f) Claim 3 is canceled.
g) Claim 6 is amended for consistency to use parentheses around the peptide sequences.
h) Claim 7 is amended to delete the species “VL-VH-AC, VL-VH-AN, VH-VL-AC, VH-VL-AN”.
i) Claim 8 is amended to recite “wherein he nano-assembly comprises at least two recombinant fusion proteins.
j) Claim 13 is amended to recite “7,200” and “110,000”.
k) Claim [15] actually, claim 20 is amended into a pharmaceutical composition comprising an active ingredient of the nano-assembly of claim 1 and a drug specific for a tumor, an autoimmune disease, an inflammatory disease or an infection.
Withdrawal of Rejections
Claim Rejections - 35 USC § 112(b)
6. The rejection of Claims 1-14 and 20 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is moot for the canceled claims (claims 3 and 10) and withdrawn for the pending claims.
a) Applicants have made a bona fide effort the amend the claims to conform with current U.S. practice.
b) Claims 1-14 and 20 are amended to delete the limitation "or the fusion proteins with the intact hydrophobic domains which derived through substitution, deletion, and/or addition of one or more amino acids " in claim 1.
c) Claim 5 is amended to delete the phrase “wherein the VL is an antibody light chain variable regionthe VH is an antibody heavy chain variable region
d) Claim 6 is amended to recite a sequence identifier for the peptide sequences > 4 amino acids in length.
e) Claims 8-9 are amended to recite the limitation "
f) Claim 9 is amended to recite the phrase “wherein the nano-assembly fusion proteins.”
g) Claim 11 is amended to recite the broad recitation “polylactide”, and to delete “and an end group of the polylactide is at least one of ester, carboxyl, and hydroxyl groups.”
h) Claim 11 is amended to clarify the conjunctive element for the claim.
Claim Rejections - 35 USC § 103
7. The rejection of Claims 1-2, 5, 8-14 and 20 under 35 U.S.C. 103(a) as being unpatentable over Marquette et al (US 20160090415; filed 2014-05-21) as evidenced by Feige et al (Trends Biochem Sci. 2009 Dec 21;35(4):189–198) is moot for the canceled claims and withdrawn for the pending claims.
8. The rejection of Claim(s) 1 and 4 under 35 U.S.C. 103 as being unpatentable over Marquette et al (US 20160090415; filed 2014-05-21) as evidenced by Feige et al (Trends Biochem Sci. 2009 Dec 21;35(4):189–198) and as applied to claim 1 above, and further in view of Irvine et al (US 20140377334; filed 2014-06-19) is withdrawn for the pending claims.
9. The rejection of Claims 1-14 and 20 under 35 U.S.C. 103 as being obvious over U.S. Patent No. 11957764 (filed 2020/10/21) in view of Marquette et al (US 20160090415; filed 2014-05-21) is moot for the canceled claims and withdrawn for the pending claims.
The rejections are obviated in view of the claims to recite a nano-assembly comprised of at least one fusion protein comprising an antigen-binding scFv (single-chain antibody fragment) and a hydrophobic region, where the hydrophobic region is albumin and comprises at least 5 hydrophobic domains, and where the fusion protein is in combination through hydrophobic interaction with an aliphatic polyester of at least one of polylactide, polyglycolide, poly(glycolide-co-lactide) and polycaprolactone.
Notably, none of the references teach or suggest the hydrophobic region of the fusion protein is albumin and that comprises “at least 5 hydrophobic domains.” Hydrophobic domains of albumin are interpreted as being distinguishable from the albumin protein region, thus suggests the hydrophobic region is an engineered albumin protein.
Applicants allege in the Response of 8/5/2026 the special technical feature is:
“the specific configuration allows the hydrophobic domain of the fusion protein (albumin) and the hydrophobic polyester to entangle and self-assemble purely through hydrophobic interactions via simple physical mixing. This eliminates the need for harsh or complex manufacturing processes, maintaining antibody activity while easily achieving "multivalent" and "multispecific" effects with excellent stability”;
“the nano-assembly formed through spontaneous hydrophobic interactions between specific components”; and
“[to] structurally modify an antibody into a fusion protein with an albumin anchor to achieve spontaneous self-assembly.”
Double Patenting
10. The rejection of Claims 1-14 and 20 on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 11957764 is moot for the canceled claims and withdrawn for the pending claims.
The rejection is obviated in view of the claims to recite a nano-assembly comprised of at least one fusion protein comprising an antigen-binding scFv (single-chain antibody fragment) and a hydrophobic region, where the hydrophobic region is albumin and comprises at least 5 hydrophobic domains, and where the fusion protein is in combination through hydrophobic interaction with an aliphatic polyester of at least one of polylactide, polyglycolide, poly(glycolide-co-lactide) and polycaprolactone.
Notably, the reference patent claims do not teach or suggest the hydrophobic region of the fusion protein is albumin and that comprises “at least 5 hydrophobic domains.” Hydrophobic domains of albumin (the hydrophobic region) are interpreted as being distinguishable from the albumin region, thus suggesting the hydrophobic region is an engineered albumin protein.
11. The provisional rejection of Claims 1-14 and 20 on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of copending Application No. 18/363,747 (reference application US 20240083976) is moot for the canceled claims and withdrawn for the pending claims.
The rejection is obviated in view of the claims to recite a nano-assembly comprised of at least one fusion protein comprising an antigen-binding scFv (single-chain antibody fragment) and a hydrophobic region, where the hydrophobic region is albumin and comprises at least 5 hydrophobic domains, and where the fusion protein is in combination through hydrophobic interaction with an aliphatic polyester of at least one of polylactide, polyglycolide, poly(glycolide-co-lactide) and polycaprolactone.
Notably, the reference claims do not teach or suggest the hydrophobic region of the fusion protein is albumin and that comprises “at least 5 hydrophobic domains.” Hydrophobic domains of albumin (the hydrophobic region) are interpreted as being distinguishable from the albumin region, thus suggesting the hydrophobic region is an engineered albumin protein.
Objections Maintained
Claim Objections
12. The objections to Claims 1-2, 4-9, 11-14 and 20-21 because of informalities are maintained.
a) In the Office Action of 5/12/2026, the original grounds for objection to Claims 1-2, 4-9, 11-14 and 20-21 are the deficiencies noted for grammatical and idiomatic errors. Applicants have not responded by way of amendments. The response is incomplete.
b) In the Office Action of 5/12/2026, the original ground for objection to Claim 2 is that the listed proteins are an antigen to which a single-chain antibody fragment bind. The proteins/antigens listed in claim 2 are not the names of a single-chain antibody fragment or scfv. Amend the claim to a single-chain antibody fragment that binds to a protein or antigen recited in claim 2.
New Grounds for Rejection
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
13. Claims 2 and 5 are rejected under 35 U.S.C. 101 because the claimed invention lacks patentable utility. Claim 2 is drawn to a “single chain antibody fragment of humans.” The single chain antibody fragment is not naturally occurring in a human. The single chain antibody fragment is an engineered antibody fragment. For the single chain antibody fragment to be from a human, the human would need to be engineered to express and produce the single chain antibody fragment.
Claim Rejections - 35 USC § 112
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.
Written Description
14. Claims 1-2, 4-9, 11-14 and 20-21 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.
Claim interpretation
The claims are drawn to a nano-assembly comprised of at least one fusion protein comprising an antigen-binding scFv (single-chain antibody fragment) and a hydrophobic region, where the hydrophobic region is albumin and comprises at least 5 hydrophobic domains, and where the fusion protein is in combination through hydrophobic interaction with an aliphatic polyester of at least one of polylactide, polyglycolide, poly(glycolide-co-lactide) and polycaprolactone.
The hydrophobic region of the fusion protein is albumin and that comprises “at least 5 hydrophobic domains.”
“hydrophobic domain”: the specification provides a specific definition for the meaning of a hydrophobic domain for an albumin protein.
[0048] In some preferred embodiments, the protein is derived from human serum albumin with at least three or four hydrophobic domains. The protein with hydrophobic domains is derived from human serum albumin with at least five hydrophobic domains, or above-mentioned proteins with complete hydrophobic domains through substitution, deletion, and/or addition of one or more amino acids; more preferably, proteins from human serum albumin with six or seven hydrophobic domains.
The specification does not teach or suggest examples of what “at least 5 hydrophobic domains” of albumin comprise much less having mutated amino acids.
The POSA could reasonably conclude that hydrophobic domains of albumin (the hydrophobic region) are distinguishable from the albumin region, per se, thus suggesting the hydrophobic region is an engineered albumin protein. Key features of albumin hydrophobic domains are
Fedotova (PTO 892) teaches the structure of serum albumin contains 11 distinct hydrophobic binding domains nested within its larger structural subdomains. The primary hydrophobic pockets are in subdomains IIA and IIIA (also known as Sudlow's sites I and II).
The POSA could conclude that if the albumin region contains fewer than 11 hydrophobic domains, then it is engineered albumin region.
The POSA could conclude that if the albumin contains “at least 5 hydrophobic domains” and more than 11 hydrophobic domains are present, then it is engineered albumin region.
The POSA cannot reasonably ascertain what the examples nor the corresponding amino acid sequences are for a hydrophobic domain of albumin that are envisaged by Applicants, and that are commensurate in scope with the claims.
Applicants allege in the Response of 8/5/2026 the special technical feature is:
“the specific configuration allows the hydrophobic domain of the fusion protein (albumin) and the hydrophobic polyester to entangle and self-assemble purely through hydrophobic interactions via simple physical mixing. This eliminates the need for harsh or complex manufacturing processes, maintaining antibody activity while easily achieving "multivalent" and "multispecific" effects with excellent stability”;
“the nano-assembly formed through spontaneous hydrophobic interactions between specific components”; and
“[to] structurally modify an antibody into a fusion protein with an albumin anchor to achieve spontaneous self-assembly.”
Applicants have failed to show examples of appropriate hydrophobic domains for the hydrophobic region, albumin, that can be accommodated in numbers of “at least 5” within the albumin region much less within the fusion protein, and that facilitate the “spontaneous” self-assembly of the nano-assembly.
The Court has held that the disclosure of screening assays and general classes of compounds was not adequate to describe compounds having the desired activity: without disclosure of which peptides, polynucleotides, or small organic molecules have the desired characteristic, the claims failed to meet the description requirement of § 112. See University of Rochester v. G.D. Searle & Co., lnc., 69 USPQ2d 1886,1895 (Fed. Cir. 2004).
There is insufficient guidance and direction as to the written description of the claimed nano-assembly, as broadly encompassed by the claimed invention. One of skill in the art would conclude that the specification fails to disclose a representative number of species much less a single species to describe the claimed genera.
Conclusion
15. No claims are allowed.
16. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
17. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN A. BRISTOL whose telephone number is (571)272-6883. The examiner can normally be reached Mon-Fri 9 AM-5 PM.
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, Wu Julie can be reached at 571-272-5205. 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.
/LYNN A BRISTOL/Primary Examiner, Art Unit 1643
