DETAILED ACTION
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 .
Claims 1-16 are pending as originally filed and are considered herein.
Specification
The specification is objected to.
Page 77 extended into actual page 78 of the specification, page 78 go on for 2 actual pages, page 79 occupies two pages and part of a third page, and page 8 is 2 pages long. Thus, the page numbering does not match the pages the subject matter is on. Please correct the page numbering accordingly.
Drawings
Figures 1-3, 5-9, and 11 are objected to.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Figure 2 is objected to. Figure 2 carries a sequence meeting the requirements for a sequence identifier, and the sequence is not present in the drawing, nor is it present in the brief description of the drawings. See also PTO-2301, attached.
Claim Rejections - 35 USC § 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.
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.
Claims 1-2 and 10 are 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 1 recites “… producing a multimeric polypeptide …” in the preamble, and recites “cultivating a mammalian cell, … and which comprises one or more nucleic acids encoding the multimeric polypeptide”, and “recovering the multimeric polypeptide from the cells or the cultivation medium”. There is a disconnect here, in that the claims appear to be concerned with the XBP1 and provides no production of the polypeptide so-encoded in step a, while it is somehow recovered in step b. I.e., there is no requirement in the claims for production of the polypeptide. The claim seems to be lacking in essential elements providing the production of the polypeptide. It is not clear how the polypeptide is recovered, if it is not required to be produced.
Claim 2 also has the issue of reciting the polypeptide encoded without requiring its production, and thus, it is again not clear how it is so-recovered.
Claim 10 is rejected. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 10 recites the broad recitation “at least about 75%”, and the claim also recites “at least about [80, 90, 95, or 100%]”, which are the narrower statements of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
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.
Claims 1-16 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.
The claims are generic for a sequence encoding a multimeric protein (e.g., Claim 1, step a). As seen by the rejection for clarity, it is simply not known how merely encoding it, will produce a recoverable multimeric protein.
The specification teaches that an antisense oligonucleotide may be used for exon skipping of exon 4, in the pre-mRNA of XBP1 to produce the variant XBP1[delta]4, (AKA XBP1s or XBP1p), the variant being transcriptionally active, causing expression of particular genes. Here this is utilized to increase the expression of a recombinant protein, i.e., expressing a coding sequence placed into the cell (pp. 1-2). The Examples demonstrate the production of and screening of antisense sequences for the fourth exon of XBP1, in hamster, mouse and human cells, and documents the amount of XBP1s relative to non-exon skipped mRNA for XBP1. Then the examples demonstrate fed-batch production with the LNA added for recombinant protein production.
While Applicant’s description does not state the elements required for production of mRNA encoding coding the protein of interest contains a promoter and response element that is utilized by XBP1s, does recognize the requirement for promoters for expression (e.g., pp. 18-19). In addition, it is well known in the art, for XBP1s to act to increase transcription of these stress-responses, it binds to an ERSE or UPRE element for the promoter of the coding region (e.g., Kaufman (2002) “Orchestrating the unfolded protein response in health and disease”, The Journal of Clinical Investigation, 110(10): 1389-98, see page 1391).
Thus, given the breadth, not requiring anything, and purpose of producing increased expression of the coding sequence, the Artisan would not have understood Applicant to have been in possession of more than the coding region minimally linked to a promoter and ERSE or UPRE element.
Claims Free of the Art
Similar to the ISR and written opinion in PCT/EP2021/086382 (of record, other-reference, dated 6/22/23, 12 pages long), the Examiner finds the claims free of the Art. To wit, the Art demonstrates a knowledge of stress response, but did not recognize the problem of linking this to increased recombinant protein production, through the use of exon skipping with an antisense oligonucleotide. It should be noted that a rejection for enablement was considered, as suggested by the same written opinion, but was deemed in appropriate. Applicant has shown many successful sequences in their screens (varying levels, but still successful), and the present claims are to a method, not a composition. Thus, contrary to the written description, the Examiner does not believe there is an issue with enablement or written description here.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT M KELLY whose telephone number is (571)272-0729. The examiner can normally be reached M-F: 8a-5p.
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ROBERT M. KELLY
Examiner
Art Unit 1638
/ROBERT M KELLY/ Primary Examiner, Art Unit 1638