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
Application status
Claims 16-33 are pending in this application.
Priority
The instant application is the 371 national stage entry of PCT/JP2022/011580 filed on 03/15/2022. Acknowledgment is made of applicant's claim for foreign priority under 35 U.S.C. 119(a)-(d) to a foreign patent application JAPAN JP2021-042220 without English translation on 03/16/2021.
Election
Applicant's election without traverse of Group I, Claims 16-31 in the response filed on 04/10/2026, is acknowledged.
Claims 32-33 are withdrawn from further consideration by the Examiner, 37 CFR 1.142(b) as being drawn to a non-elected invention.
For the reasons provided above, this restriction requirement is deemed proper, and therefore, it is made final.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 04/10/2024 and 05/16/2025 are acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Objections to the Specification
This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 through 1.825; Applicants’ attention is directed to the final rulemaking notice published at 55 FR 18230 (May 1, 1990), and 1114 OG 29 (May 15, 1990). To be in compliance, Applicants should identify nucleotide sequences of at least 10 nucleotides and amino acid sequences of at least 4 amino acids in the specification by a proper sequence identifier, i.e., “SEQ ID NO:” (see MPEP 2422.01). If these sequences have not been listed in the computer readable form and paper copy of the sequence listing, applicant must provide an initial computer readable form (CRF) copy of the “Sequence Listing”, an initial paper copy of the “Sequence Listing”, as well as an amendment directing its entry into the specification, and a statement that the content of the paper and CRF copies are the same and, where applicable, include no new matter as required by 37 C.F.R. 1.821(e) or 1.821(f) or 1.821(g) or 1.821(b) or 1.825(d). See particularly paragraph [0023] of the specification containing an amino acid sequence, and therefore, this sequence should be represented by proper sequence identifier number, i.e. SEQ ID NO: 1.
It is noted by the Examiner that the instant specification is missing a “Sequence Listing” paragraph stating an incorporation by reference statement with the date of creation, sequence file name and size in bytes. – See also MPEP 2422.
Appropriate correction is required.
Claim Rejections - 35 U.S.C. § 112
The following is a quotation of 35 U.S.C. 112(b):
(B) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 16-31 are rejected under 35 U.S.C. § 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claim 16 (17-31 dependent therefrom) recites “at least cysteine at position 73” which is unclear. It is unclear what “at least” means since there could be a single cysteine at a single position. In the interest of advancing prosecution, the noted phrase is interpreted as “cysteine at position”.
Claim 16-18 and 28 (19-27 and 29-31 dependent therefrom) is unclear and confusing in the recitation of the phrase, “cysteine at position ## from N-terminal of the amino acid sequence thereof or located at a position equivalent there to”. It is unclear where the cysteine position is located because there is no reference SEQ ID NO which is recited “amino acid sequence” corresponds to. The Examiner suggests inserting a SEQ ID NO where the corresponding position of cysteine can be found. To add to this confusion, the only SEQ ID NO, i.e., SEQ ID NO: 1, disclosed in this application does not have a Cys at position 73 (the Examiner notes that position 73 of SEQ ID NO: 1 is Lys). In the interest of advancing prosecution, claim 16 is interpreted as “a modified serum albumin-thioredoxin fusion body, the modified serum albumin-thioredoxin fusion body comprising a serum albumin and thioredoxin, wherein the serum albumin and the thioredoxin are fused, and the thioredoxin is a modified form in which a cysteine is substituted by another amino acid”.
Claims 22-27 and 29 are indefinite and confusion in the recitation of “the cysteine” in claim 17, 18 and 28, all of which depend from claim 16. However, it is unclear which cysteine “the cysteine” is referring to since there are more than one cysteine recited in claim 17, 18 and 28, all of which depend from claim 16. For instance, claim 17 recites cysteines at position 62 and/or position 69 of thioredoxin but claim 16 also recites cysteine at position 73. Similar issues are present in all of claims 22-27 and 29. In the interest of advancing prosecution, “the cysteine” is interpreted as referring to any one of the cysteines recited in claims 16-18 and 28.
The following is a quotation 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.
Claims 16-31 are rejected under 35 U.S.C. § 112(a), written description, 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(s), at the time the application was filed, had possession of the claimed invention.
The instant claims are directed to a modified serum albumin-thioredoxin fusion body, the modified serum albumin-thioredoxin fusion body comprising a serum albumin and thioredoxin, wherein the serum albumin and the thioredoxin are fused, and the thioredoxin is a modified form in which a cysteine is substituted by another amino acid (see above 112(b) rejections for the claim interpretation).
To satisfy the written description aspect of 35 U.S.C. § 112(a) for a claimed genus of [compositions or methods], it must be clear that: (1) the identifying characteristics of the claimed [compositions or methods] have been disclosed, e.g., structure, physical and/or chemical characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or a combination of these; and (2) a representative number of species within the genus must be disclosed.
The Court of Appeals for the Federal Circuit has recently held that a “written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as be structure, formula [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials.” University of California v. Eli Lilly and Co., 1997 U.S. App. LEXIS 18221, at *23, quoting Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993) (bracketed material in original). To fully describe a genus of genetic material, which is a chemical compound, applicants must (1) fully describe at least one species of the claimed genus sufficient to represent said genus whereby a skilled artisan, in view of the prior art, could predict the structure of other species encompassed by the claimed genus and (2) identify the common characteristics of the claimed molecules, e.g., structure, physical and/or chemical characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or a combination of these (paraphrased from Enzo Biochemical Inc. v. Gen-Probe Inc. (CAFC (2002) 63 USPQ2d 1609).
The specification discloses only a single representative species of serum albumin-thioredoxin fusion protein as set forth in SEQ ID NO: 1 with a few different combinations of substitutions: HAS Cys34Ala and Trx Cys62Ala/Cys69Ala/Cys73Ala (see Figures 1-3). However, this single disclosed species fails to provide adequate written description for a genus of modified serum albumin-thioredoxin fusion bodies, the modified serum albumin-thioredoxin fusion bodies comprising any orthologs of serum albumins from any species and any orthologs of thioredoxin from any species, wherein the serum albumin and the thioredoxin are fused, and the thioredoxin is a modified form in which any cysteine is substituted by any of 19-non-cysteine amino acids.
In this case, the specification fails to describe any identification of structural characteristics or properties of the genus of modified serum albumin-thioredoxin fusion bodies, the modified serum albumin-thioredoxin fusion bodies comprising any orthologs of serum albumins from any species and any orthologs of thioredoxin from any species, wherein the serum albumin and the thioredoxin are fused, and the thioredoxin is a modified form in which any cysteine is substituted by any of 19-non-cysteine amino acids (italicized for added emphasis). While M.P.E.P. section 2163 acknowledges that a single species can describe a genus, it also acknowledges that for a genus that encompasses widely variant species, disclosure of a single species within the genus fails to adequately describe all members of the genus. Please refer to the M.P.E.P. section 2163.05 [R-7.2022] under I, B for more details with respect to sufficient number of representative species that should be disclosed to describe a widely variant genus.
Given the lack of additional representative species of a genus of modified serum albumin-thioredoxin fusion bodies, the modified serum albumin-thioredoxin fusion bodies comprising any orthologs of serum albumins from any species and any orthologs of thioredoxin from any species, wherein the serum albumin and the thioredoxin are fused, and the thioredoxin is a modified form in which any cysteine is substituted by any of 19-non-cysteine amino acids, as encompassed by the claim, Applicants have failed to sufficiently describe the claimed invention, in such full, clear, concise, and exact terms that a skilled artisan would recognize Applicants were in possession of the claimed invention.
Applicant is referred to the revised guidelines concerning compliance with the written description requirement of U.S.C. 112(a) published in the Official Gazette and also available at www.uspto.gov.
Claim Rejections - 35 USC § 103
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 16-31 are rejected under 35 U.S.C. 103 as being unpatentable over Furukawa et al. (Human serum albumin–thioredoxin fusion protein with long blood retention property is effective in suppressing lung injury, Journal of Controlled Release Volume 154, Issue 2, 5 September 2011, Pages 189-195) in view of Forman-Kay et al. (1H and15N resonance assignments and secondary structure of the human thioredoxin C62A, C69A, C73A mutant, Journal of Biomolecular NMR, 2 (1992) 431-445), McCurdy et al. (A covalently linked recombinant albumin dimer is more rapidly cleared in vivo than are wild-type and mutant C34A albumin, Journal of Laboratory and Clinical Medicine, Volume 143, Issue 2, February 2004, Pages 115-124), and an evidentiary reference of Ikuta et al. (Albumin fusion of thioredoxin — The production and evaluation of its biological activity for potential therapeutic applications, Journal of Controlled Release, Volume 147, Issue 1, 1 October 2010, Pages 17-23, see IDS).
The instant claims are drawn to a modified serum albumin-thioredoxin fusion body, the modified serum albumin-thioredoxin fusion body comprising a serum albumin and thioredoxin, wherein the serum albumin and the thioredoxin are fused, and the thioredoxin is a modified form in which a cysteine is substituted by another amino acid (see above 112(b) rejections for the claim interpretation).
Furukawa et al. teach that a recombinant human albumin-thioredoxin fusion protein (see abstract). Furukawa et al. further teach recombinant expression, purification, beneficial longer half-life, and therapeutic use/pharmaceutical composition of said recombinant human albumin-thioredoxin fusion protein (see page 190-193 entirely; and page 194, left column, 2nd para). The evidentiary reference of Ikuta et al. teach that said recombinant human albumin-thioredoxin fusion protein is connected by a linker, (GGGGS)2 (see page 18, right column, last sentence of the 1st para; and Fig. 1).
Furukawa et al. do not teach any substitutions in said recombinant human albumin-thioredoxin fusion protein.
Forman-Kay et al. teach human thioredoxin comprising C62A/C69A and C73A substitutions (see summary on page 431). Forman-Kay et al. further teach that these substitutions are used to prevent intermolecular disulfide bridge and aggregation (see page 432, 3rd para).
McCurdy et al. teach a recombinant serum albumin comprising C34A substitution, which eliminates disulfide bond mediated dimerization (see abstract).
It would have been obvious to a person of ordinary skill in the art (POSITA) prior to the effective filing date of the instant application to make and use the modified serum albumin-thioredoxin fusion protein comprising C62A/C69A and C73A substitutions in thioredoxin and C34A substitution in serum albumin as taught by Furukawa et al., Forman-Kay et al. and McCurdy et al. A POSITA would have been motivated to make and use such composition because such substitutions can prevent dimerization, oxidative inactivation, short half-life, and/or aggregation as taught by Furukawa et al., Forman-Kay et al. and McCurdy et al. as noted above. A POSITA would have had a reasonable expectation of success to make and use such composition because all of the required biochemical reagents and techniques were readily available and rampantly used as evidenced by Furukawa et al., Forman-Kay et al. and McCurdy et al. prior to the filing of the instant application.
For the reasons provided herein, the invention as claimed is prima facie obvious over the combined teachings of the prior art.
Conclusion
Claims 16-31 are rejected for the reasons as stated above. Applicants must respond to the objections/rejections in this Office action to be fully responsive in prosecution.
The instant Office action is non-final.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAE W LEE whose telephone number is (571)272-9949. The examiner can normally be reached on M-F between 9:00-6:00.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached on (571)272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JAE W LEE/
Examiner, Art Unit 1656
/MANJUNATH N RAO/Supervisory Patent Examiner, Art Unit 1656
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