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
This action is in response to the papers filed on June 29, 2022. Claims 1-10 are currently under examination.
Priority
This application is claiming the benefit under 35 U.S.C. 119(e) of prior -filed U.S. provisional 62/957,047 filed on January 3, 2020, filed prior to PCT application, PCT/US2020/067682 on December 31, 2020.
Thus, the earliest possible priority for the instant application is January 3, 2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/06/2022 is acknowledged. The submissions are in compliance with the provisions of 37 CPR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Specification Objection
The disclosure is objected to because of the following informalities: The specification references color drawings, See ([0008]; [0010]; [0024]). Necessary correction is required. Applicant may obviate the objection by filing the petition for color drawings.
Additionally, the disclosure is objected to because of the following informalities: The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. See [0043]. Appropriate correction is required.
Drawings Objection
The drawings are objected to under 37 CFR 1.83(a) because they fail to show color designated and as described in the specification, see Fig. 1A. Additionally, multiple figures are poorly rendered, such as Fig. 5, 11, 13A. The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawings 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).
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 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:
Additionally, any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim interpretation
Claim 1 recites “a model of protein folding”. The term “model of protein folding” is given its broadest reasonable interpretation consistent with the specification and encompasses any biological system suitable for studying protein folding, misfolding, or chaperone-client interactions in vivo. Under this interpretation, a transgenic mammal expressing an epitope-tagged product of the Hspa5 gene constitutes a model of protein folding because BiP, the protein encoded by Hspa5, is an endoplasmic reticulum chaperone whose native function is to bind unfolded or misfolded client proteins during protein folding. Hence, the ordinary artisan would recognize expression of epitope-tagged BiP implicitly provides a system for evaluating protein folding and necessarily results in the formation of epitope-tagged BiP-client complexes in vivo, regardless of whether such complexes are expressly isolated or characterized.
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 6-10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as failing to set forth 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 6-10 contains the trademark/trade name FLAG™. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a fusion/epitope tag and, accordingly, the identification/description is indefinite. The claim does not clearly define the amino acid sequence, length, composition, or structural boundaries of the claimed tag.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mimura et al. (Cell Death Differ. 2007 Aug;14(8):1475-85. Epub 2007 Apr 20).
Regarding claims 1-6, Mimura discloses the use of homologous recombination to produce mammalian transgenic mutant BiP mice containing a HA-tag (pg. 1476, column 1, para. 3). The ordinary artisan would have recognized the terms heat shock 78 kDA protein 5 (Hspa5), Glucose-Regulated Protein 78 (GRp78), and the binding immunoglobin protein (BiP) are terms conventionally used to refer to the synonymous locus or gene, as supported by the instant specification [0006] and [0025].
***
Claims 1-3, 5-7, and 9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Colbert et al. (WO 2008/121385 A2, see IDS).
Regarding claims 1-3, 5-7, and 9, Colbert discloses a transgenic rat with a transgene comprising an epitope tag, specifically FLAG-tag, in the Hspa5/BiP gene. Colbert discloses the transgenic rats express the BiP-Flag protein ([0128-0129]). Colbert discloses Immunoglobulin Binding Protein (BiP) is an ER chaperone also known as Glucose Regulated Protein of 78 kDa (Grp78), and Hspa5 ([0055]). Furthermore, Colbert discloses the generation of stable transgenic founders that transmit the BiP-FLAG transgene through the germline ([0077]; [0128]). Thus, the claimed product-by-process recitation of ‘homologous recombination’ does not distinguish the claimed transgenic animal from the transgenic animal disclosed by Colbert.
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 factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-10 are rejected under 35 U.S.C. 103 as being unpatentable over Mimura et al. (Cell Death Differ. 2007 Aug;14(8):1475-85. Epub 2007 Apr 20), in view of Preissler et al. (Elife. 2015 Oct 16:4:e08961.) and Hernan et al. (Biotechniques. 2000 Apr;28(4):789-93.).
Regarding claims 1-6, Mimura discloses the use of homologous recombination to produce mammalian transgenic mutant BiP mice containing a HA-tag (pg. 1476, column 1, para. 3). The ordinary artisan would have recognized the terms heat shock 78 kDA protein 5 (Hspa5), Glucose-Regulated Protein 78 (GRp78), and the binding immunoglobin protein (BiP) are terms conventionally used to refer to the synonymous locus or gene, as defined by the instant specification [0006] and [0025].
Regarding claims 7-10, while Mimura teaches the inclusion of the HA-tag epitope component, Mimura does not specifically teach a FLAG-tag, 3xFLAG, or a tag comprising at least three flag sequences.
However, the ordinary artisan would have recognized that the use of FLAG-tags and multimerized FLAG tags was well known in the prior art, in view of the teachings of Preissler and Hernan.
Preissler teaches the BiP-3xFLAG constructs for studying BiP interactions and functions, demonstrating that multiple FLAG sequences may be fused to BiP without disrupting activity (Fig. 6). Additionally, Hernan further teaches the general utility of FLAG epitope tags and explains that increasing the number of FLAG sequences enhances detection and immunoprecipitation efficiency (Abstract, pg. 793, column 1, para. 1-2).
Thus, before the effective filing date of the instant application, the ordinary artisan would have found it obvious to substitute the HA-tagged BIP component, as taught by Mimura, with a FLAG-tagged BiP, including a tag comprising at least three FLAG sequences, as taught by Preissler and Hernan, in order to obtain the predictable result of producing a transgenic animal comprising the BiP-3xFLAG, or FLAG-tagged BiP-client complexes. The ordinary artisan would have been motivated to make such a substitution by the well-recognized advantage of improved detection and recovery of BiP and associated protein complexes, with a reasonable expectation of success.
***
Claims 1-10 are rejected under 35 U.S.C. 103 as being unpatentable over Colbert et al. (WO 2008/121385 A2), in view of Preissler et al. (Elife. 2015 Oct 16:4:e08961.) and Hernan et al. (Biotechniques. 2000 Apr;28(4):789-93.).
Regarding claims 1-3, 5-7, and 9, Colbert discloses a transgenic rat with a transgene comprising an epitope tag, specifically FLAG-tag, in the Hspa5/BiP gene. Colbert discloses the transgenic rats express the BiP-Flag protein, or FLAG-tagged BiP-client complexes ([0128-0129]). Colbert discloses Immunoglobulin Binding Protein (BiP) is an ER chaperone also known as Glucose Regulated Protein of 78 kDa (Grp78), and Hspa5 ([0055]). Furthermore, Colbert discloses the generation of stable transgenic founders that transmit the BiP-FLAG transgene through the germline ([0077]; [0128]). Thus, the claimed product-by-process recitation of ‘homologous recombination’ does not distinguish the claimed transgenic animal from the disclosed transgenic animal.
Regarding claim 4, Colbert discloses a transgenic mammalian animal expressing epitope-tagged BiP, specifically teaching transgenic rats expressing FLAG-tagged BiP ([0128-0129]). Before the effective filing date, the ordinary artisan would have reasonable understood mice and rats are both well-established and conventional laboratory organisms routinely used interchangeably as genetic models for studying conserved cellular processes. For instance, Colbert teaches mice models ([0006]).
Regarding claims 8 and 10, Colbert does not specifically teach a 3xFLAG, or a tag comprising at least three flag sequences.
However, the ordinary artisan would have recognized that the use of multimerized FLAG tags was well known in the prior art, in view of the teachings of Preissler and Hernan.
Preissler teaches the BiP-3xFLAG constructs for studying BiP interactions and functions, demonstrating that multiple FLAG sequences may be fused to BiP without disrupting activity (Fig. 6). Additionally, Hernan further teaches the general utility of FLAG epitope tags and explains that increasing the number of FLAG sequences enhances detection and immunoprecipitation efficiency (Abstract, pg. 793, column 1, para. 1-2).
Thus, before the effective filing date of the instant application, the ordinary artisan would have found it obvious to modify the FLAG-tagged BiP, as taught by Colbert, to comprise at least three FLAG sequences, as taught by Preissler and Hernan, to improve detection of BiP and associated complexes, with a reasonable expectation of success.
Conclusion
Claims 1-10 are rejected. No claims are allowed.
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/J.D.L./Examiner, Art Unit 1633
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699