DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 January 16, 2026, has been entered.
Claim Disposition
3. Claims 1-20, 23 and 25 have been cancelled. Claims 21-22, 24 and 26-38 are pending and are under examination.
Information Disclosure Statement
4. The Information Disclosure Statements filed on July 11, 2025, January 16, 2026, January 26, 2026 and February 3, 2026, have been received and entered. The references cited on the PTO-1449 Form have been considered by the examiner and a copy is attached to the instant Office action. Note that references have been lined through because they have an improper date citation.
Abstract objection
5. The abstract is objected to for the following informalities:
The abstract is objected to because it appears on a page with the amendments to the abstract.
The abstract of the disclosure does not commence on a separate sheet in accordance with 37 CFR 1.52(b)(4) and 1.72(b). A new abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text.
Correction is required.
Claim objection
6. Claims 21-22, 24 and 26-38 are objected to for the following informalities:
For clarity it is suggested that claim 21 is amended to delete “muscle”. In addition, claim 21 should be amended to read, “……wherein expression of the at least two different recombinant vertebrate animal muscle proteins is driven….and wherein (a) multiple copies of the expression…..”. The dependent claims hereto are also included.
For clarity and consistency it is suggested that claim 22 is amended to spell out the acronyms.
For clarity it is suggested that claim 24 is amended to read, “….wherein [[each recombinant vertebrate animal muscle protein of ]] the at least two different recombinant vertebrate animal muscle proteins [[comprises and an amino acid sequence of any one of SEQ ID NOS]] comprise the amino acid sequence selected from the group consisting of SEQ ID NOs: 1-57, 61-99….”.
Appropriate correction is required.
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.
7. Claims 21-22, 24 and 26-38 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AlA), 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.
The claimed invention is directed to a composition comprising a yeast cell (S. cerevisiae) transformed with an expression vector having genes encoding at least two different recombinant vertebrate animal muscle proteins wherein expression of the at least two different recombinant vertebrate animal muscle proteins is driven by fungi promoters (see claim 21 in its entirety). The claimed composition encompasses a host cell transformed with an expression vector driven by fungi promoters with multiple copies of the expression vector integrated into the genome of the yeast host cell and the two different recombinant proteins are not from the yeast host cell. Any foreign gene encoding two different animal muscle proteins with any fungi promoters is the scope of claim 21 which encompasses a large variable genus. The claimed invention is devoid of any structural limitations. The claimed invention encompasses a large variable genus of structures not adequately described for the recited genes encoding at least two different recombinant vertebrate animal muscle proteins. It is well established in the art that several different genes can encode the same protein. The art also acknowledges that for example, actin is not exactly the same in all organisms. For instance actin from a human and a protist share 61% identity, claim 21 is very broad and doesn’t specify the source of the muscle proteins. Human muscle proteins are not excluded from claim 21. It is noted that dependent claim 24 recites structural limitations, however, independent claim 21 has to stand on its own. Further, the invention of claim 21 has approximately 56 muscle proteins recited and dependent claim 24 recites that the structures are comprised in approximately 157 sequences. Thus there is no one to one correspondence between the muscle proteins and the structures provided. The ordinary skilled worker does not have a glimpse of the gene that will be expressed to produce the desired results. The specification at paragraph [0024] discloses that “the recombinant animal proteins may be full-length proteins…... The sequences of the recombinantly expressed proteins may be modified……. The modifications may improve the yield of protein produced by the organism that has been engineered to express the protein, e.g., by improving the efficiency of transcription and/or translation of the protein, by improving the stability of the protein, by altering the rate at which the protein is secreted by the organism, or by changing the activity of the protein so any deleterious effects of expression of the protein on the recombinant host cell are minimized”.
At paragraph [0027] of the specification it is disclosed that
“ It is well known that expression of mammalian and avian cytoskeletal proteins, such as actin and tubulin, in microbial hosts can be toxic to those hosts, thus limiting expression levels. This is due to the biological activity of these proteins interfering with the metabolism of the host cell. The nutritional properties of these animal derived proteins will remain essentially unchanged regardless of the biological activity of the protein. Expression levels of toxic recombinant animal proteins can be increased by decreasing their host toxicity via targeted mutagenesis (to decrease the biological activity responsible for the protein's toxicity, for example). Examples are provided herein for improving expression of actin, but these examples should not be construed as limiting. Similar methodology can be used for other proteins”. The claimed invention is not adequately described because there is no indicia in the claims that the proteins recited in the list are modified as stated above to ensure that they are no producing the toxic levels disclosed in the specification. The claim language recites “recombinant” however, there are no indicia to inform the ordinary skilled worker of what modifications were done to the gene or the protein to get the desired effects.
However, the claimed invention is not limited to the disclosure in the specification and is much broader. The scope of the claims far exceed the disclosure in the specification with respect to the genes, the protein structures (see recitation of “an amino acid in claim 24) and what is required to get expression of the foreign proteins in the yeast cells. The below paragraphs further demonstrate that the invention as claimed is broader than the instant specification which specifically discloses the proteins, conditions, genes and gene manipulation.
[0069] The genes and the proteins encoded by the genes may also be truncated in order to yield a high expression and fast cell growth. Modifications of the gene sequence (e.g., the addition or removal of certain amino acids) will, in some cases, increase cell viability and increase the rate of cell division. Proteins that are too large to overexpress efficiently will be truncated in order to increase the expression level.
[0071] The expression vector pNZ8152 (MoBiTec GmbH, Gottingen, Germany) is a Gram-positive broad host range vector. Taking advantage of the nisA promoter, it allows intracellular recombinant protein expression via induction with nisin. The vector pNZ8152 also contains the selectable marker alanine racemase gene alr, which restores auxotrophy to D-alanine caused by a deletion of the host cell copy of alr. The vector is linearized using HindIIII restriction enzyme (New England Biolabs, Ipswich, MA) and dephosphorylated using established molecular cloning methods [1]. Linearized vector is separated using agarose gel electrophoresis. An agarose gel section containing linearized vector is collected and the linearized plasmid is purified from the agarose using a commercially available DNA purification kit, e.g. the QIAquick Gel Extraction Kit (Qiagen, Germantown, MD).
[0072] The gene sequence for chicken myosin regulatory light chain 2, skeletal muscle isoform, (MYLPF) can be obtained from UniProt.org under accession number P02609. The double-stranded DNA is constructed through chemical gene synthesis from either ATUM (Newark, CA), Genscript (Piscataway, NJ), or IDT (Coralville, Iowa). It is supplied in a vector of choice. The DNA sequence can also be obtained via amplification of cDNA generated directly from a mRNA of a biological sample, such as a tissue or a blood sample from a chicken donor. The gene sequence is modified to aid in cloning, gene expression, or enhance production. It is “codon optimized”, i.e. triplet DNA sequences that are not commonly used in the expression host are changed to those that are commonly used.
[0073] The codon optimized myosin regulatory light chain 2, skeletal muscle isoform, gene (MYLPF), containing exons, but no introns, is ligated to the linearized and purified pNZ8152 vector via enzymatic ligation to generate a vector capable of being inserted into a host organism. The method used is known in the art and the protocol can be obtained from a molecular cloning manual [1].
The dependent claims hereto recite some of the missing information in claim 21, however, claim 21 needs to stand on its own (thus no structure-function correlation is made). The claimed invention encompasses a large variable genus of products that are not adequately described. Further, the claims are read in light of the specification, but the limitations of the specification cannot be read into the claims.
The claims also recite multiple different recombinant proteins (see claim 21 that are encoded by the multiple genes, for example). The instant specification fails to provide adequate description for the large genus encompassed in the claims. The specification fails to provide a representative number of species for the claimed genus to show that applicant was in possession of the claimed genus. A representative number of species means that the species, which are adequately described, are representative of the entire genus. Therefore, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of the proteins and variants thereof.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), states that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed" (See page 1117). The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed" (See Vas-Cath at page 1116). The skilled artisan cannot envision the detailed chemical structure of the encompassed genus of polypeptides, and therefore, conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993).
Therefore, for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that the applicant had possession of the claimed invention at the time the instant application was filed.
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
8. Claim 24 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 24 is indefinite for the recitation of “each recombinant vertebrate animal muscle proteins comprises an amino acid sequence of any one of SEQ ID NOs:1-57, 61-99, 101-139 or 141-165” because the structures are far more than the recited proteins. How can each of the listed proteins correspond to so many structures (approximately 56 proteins with approximately 157 structures). Clarification is needed.
Appropriate correction is required.
Response to Arguments
9. Applicant’s comments have been considered in full. Withdrawn objections/rejections will not be discussed herein as applicant’s comments are moot. Note that new rejections and objections have been instituted for the reasons stated above. The terminal disclaimer filed has been received and accepted.
Conclusion
10. No claims are presently allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HOPE A ROBINSON whose telephone number is (571) 272-0957. The examiner can normally be reached 9-5pm on Monday to Friday.
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/HOPE A ROBINSON/Primary Examiner, Art Unit 1652
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