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
2. This Office Action is responsive to Applicant’s Amendment and Remarks, filed March 4, 2026. The amendment, filed March 4, 2026, is entered, wherein claims 1 – 2, 4, 9, and 13 are amended, claims 14 – 16 are new, and claims 3, 7 – 8, and 10 – 12 are canceled.
Claims 1 – 2, 4 – 6, 9, and 13 – 16 are pending in this application.
Priority
3. This application is a domestic application, filed March 6, 2023, which claims benefit of foreign priority document CN202211485727.4, filed November 24, 2022.
Election/Restrictions
4. Newly submitted claims 14 and 16 directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: Applicant’s provisional election of “a single and specific heterobifunctional linker”, as set forth in the Non-Final Rejection, mailed December 11, 2025, is drawn to “N-hydroxysuccinimide ester”. However, the newly submitted claims 14 and 16 recite “heterobifunctional linker comprising maleimidocaproyl-L-valine-L-citrulline-p-aminobenzyl alcohol p-nitrophenyl carbonate (Mc-Val-Cit-PABC-PNP)”, which is different from “N-hydroxysuccinimide ester”.
Since Applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 14 and 16 are withdrawn from consideration as being directed to a non-elected species. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, Applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should Applicant traverse on the ground that the inventions are not patentably distinct, Application should submit evidence of identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art. The evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention. Thus, claims 1 – 2, 4 – 6, 9, 13, and 15 are currently examined.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/04/2026 was filed after the mailing date of the previous Office Action on December 11, 2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Withdrawn Objections
6. The objection of claims 1 and 13 in the previous Office Action, mailed December 11, 2025, is withdrawn in view of the amended claims 1 and 13.
Withdrawn Rejections
7. The rejection of claims 1 – 7 and 9 in the previous Office Action, mailed December 11, 2025, under 35 U.S.C. 102(a)(1) as being anticipated by Ehrlich et al. with evidence provided by Novozymes Biopharma US Inc. has been fully considered and is withdrawn in view of the amended claim 1.
The rejection of claims 1 – 9 and 13 in the previous Office Action, mailed December 11, 2025, under 35 U.S.C. 103 as being unpatentable over Ehrlich et al. with evidence provided by Novozymes Biopharma US Inc. in view of Gurudevan et al. has been fully considered and is withdrawn in view of the amended claim 1.
The rejection of claims 1, 3, and 5 – 9 in the previous Office Action, mailed December 11, 2025, on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, and 5 of copending Application No. 19/132,453 has been considered. As terminal disclaimer is filed on March 4, 2026 and is approved on March 24, 2026, the rejection is withdrawn.
The following are modified / new grounds of rejection necessitated by Applicant’s Amendment and Remarks, filed March 4, 2026, wherein claims 1 – 2, 4, 9, and 13 are amended, claims 14 – 16 are new, claims 3, 7 – 8, and 10 – 12 are canceled, and claims 14 and 16 are withdrawn. Previously and newly cited references have been used to establish the modified / new grounds of rejection.
New Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 4 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 4 depends from claim 1. Claim 1 requires that the rHSA be generated by expressing a nucleic acid encoding the rHSA in a plant cell. Claim 4 recites expression in yeast cell. The yeast cell alternative is not included in the “plant cell” limitation of claim 1 because yeast cell is not considered as plant cell. Therefore, claim 4 does not properly depend from claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Modified / New Claim Rejections - 35 USC § 103
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 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
i. Determining the scope and contents of the prior art.
ii. Ascertaining the differences between the prior art and the claims at issue.
iii. Resolving the level of ordinary skill in the pertinent art.
iv. Considering objective evidence present in the application indicating obviousness or
nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1 – 2, 4 – 6, 9, 13, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Ehrlich et al. (Bioconjugate Chemistry, 2013, Vol. 24, Issue 12, page 2015 – 2024, cited in the previous Office Action mailed December 11, 2025) in view of Zhang et al. (Journal of Zhejiang University SCIENCE B, 2013, Vol. 14, Issue 10, page 867 – 874, Reference included with PTO-892), Gurudevan et al. (European Journal of Pharmaceutical Sciences, 2018, Vol. 115, page 167 – 174, Reference included with PTO-892), and Derdák et al. (Chemical Physics Letters, 2019, Vo. 724, page 13 – 17, Reference included with PTO-892).
a. Regarding claims 1 – 2, 4 – 6, 9, 13, and 15, Ehrlich et al. teach rHSA conjugates of a 15-amino-acid truncated peptide YY (PYY) analogue using heterobifunctional linker comprising 6-maleimidohexanoic acid N-hydroxysuccinimide ester (MHS). The conjugation involves (1) reaction of succinimidyl ester on linker with ɛ-amine of Lys2 on the peptide and (2) reaction of maleimide on peptide linker with free thiol of cysteine 34 (Cys34) on albumin (Abstract). The rHSA are purchased from Novozymes (page 2016, Right Col., para. 1).
However, Ehrlich et al. do not teach that the rHSA is generated by expressing a nucleic acid encoding the rHSA in a plant cell and the therapeutic drug molecule is amphotericin B (AmB).
Zhang et al. teach that HSA is widely utilized for medical purposes and biochemical research and transgenic rice has proved to be an attractive bioreactor for mass production of rHSA. Zhang et al. conduct study to develop a selectively terminable transgenic rice line expression HSA in rice seeds and a simple process for recovery and purification of rHSA for economical manufacture. An HSA expression cassette is inserted into a T-DNA vector encoding an RNA interference (RNAi) cassette suppressing the CYP81A6 gene. A transgenic rice line, HSA-84, is obtained with stable expression of rHSA of up to 0.72% of the total dry weight of the dehusked rice seeds. The line also demonstrates high sensitivity to bentazon, and thus could be killed selectively by a spray of bentazon. A two-step chromatography purification scheme is established to purify the rHSA from rice seeds to a purity of 99% with a recovery of 62.4%. The study provides an alternative strategy for large-scale production of HSA with a built-in transgene safety control mechanism (Abstract). Rice-derived rHSA does not require sophisticated equipment, unlike traditional yeast fermentation, and could be scaled up simply by planting a large acreage of transgenic rice. Rice seeds also offer a low hydrolytic condition for storage of rHSA, which can overcome the limitation of protein stability within the microbial expression system (page 872, Right Col., para. 2). Zhang et al. also prove that the rHSA produced by transgenic rice is identical to native protein from blood in terms of its N-terminal amino acid sequence, molecular mass as measured by MALDI-TOF. Previous research has shown that rHSA is identical to native protein in biological activity. Therefore, the rHSA protein produced by transgenic rice is also biological identical to its native protein (page 873, Left Col., para. 2).
Derdák et al. disclose the interaction of AmB with HSA by using fluorescence polarization technique to determine complex stabilities. The study demonstrate the formation of highly stable albumin-drug complexes, suggesting the significant role of serum albumins regarding the plasma protein binding of AmB (Abstract).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute the rHSA purchased from Novozymes as taught by Ehrlich et al. with rHSA obtained from transgenic rice line because Zhang et al. teach that rice-derived rHSA does not require sophisticated equipment and may be scaled up simply by planting more transgenic rice and Zhang et al. teach that such rice-derived rHSA retains the biological activity of the native protein. One would have been motivated to substitute the rHSA purchased from Novozymes as taught by Ehrlich et al. with rHSA obtained from transgenic rice line because Zhang et al. teach that rice seeds offer a low hydrolytic condition for storage of rHSA, which can overcome the limitation of protein stability within the microbial expression system as well as other benefits. Such substitution will yield predictable and improved product. One of ordinary skill in the art would have had a reasonable expectation of success to substitute the rHSA purchased from Novozymes as taught by Ehrlich et al. with rHSA obtained from transgenic rice line because Zhang et al. teach the benefit of using rHSA obtained from rice seeds, which retains the biological activity of the native protein.
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute the PYY analogue in the rHSA conjugate as taught by Ehrlich et al. with AmB in view of Derdák et al. because both Ehrlich et al. and Derdák et al. address conjugation strategies involving HSA to improve the properties, such as stability, of attached molecules. Ehrlich et al. teach the conjugation of peptides, such as PYY to rHSA using a heterobifunctional linker system to improve stability and half-life. Derdák et al. disclose the conjugation of AmB to HSA for the purpose of enhancing AmB’s stability. One would have been motivated to substitute the PYY analogue in the rHSA conjugate as taught by Ehrlich et al. with AmB in view of Derdák et al. because both conjugation strategies aim to improve properties through albumin conjugation. Ehrlich et al. demonstrate a method of covalently linking molecules to HSA using linker, which could reasonably be adapted for use with AmB. Therefore, one of ordinary skill in the art would have had a reasonable expectation of success to substitute the PYY analogue in the rHSA conjugate as taught by Ehrlich et al. with AmB in view of Derdák et al. because the conjugation chemistry used in Ehrlich et al. is known in the art and widely applicable, including for drug, such as AmB, thereby, yielding predictable outcome.
Responses to Applicant’s Remarks:
Applicant’s Remarks, filed March 4, 2026, have been fully considered and are found to be not persuasive.
Regarding the rejection, Applicant argues that neither Ehrlich et al. nor Gurudevan et al. teach use of rHSA that is generated by expressing a nucleic acid encoding the rHSA in a plant cell. One of skill in the art would have found nothing in Gurudevan et al. that would have motivated one of skill to modify one of skill to modify Ehrlich et al. to teach this claimed invention, as amended, to incorporate use of a rHSA that is generated by expressing a nucleic acid encoding the rHSA in plant cell. However, the arguments are moot because the new grounds of rejection are no longer based on the combination of Ehrlich et al. and Gurudevan et al. The new grounds of rejection rely upon the teachings of Ehrlich et al. in view of Zhang et al. and Derdák et al., wherein Ehrlich et al. teach the conjugate of rHSA and PYY, Zhang et al. teach that rice-derived rHSA, which retains the same biological activity as native protein, does not require sophisticated equipment and may be scaled up simply by planting more transgenic rice, and Derdák et al. teach that AmB is known to conjugate with HSA for the enhanced stability. The combination of references renders the claimed invention obvious because the substitutions as discussed above yield predictable and improved products.
Conclusion
No claim is found to be allowable.
Applicant's amendment necessitated the modified / 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.
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/H.Y.L./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693
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