DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant's election without traverse of Mycobacterium tuberculosis-derived nanocarrier protein in the reply filed on 08/10/2026 is acknowledged. The requirement is still deemed proper and is therefore made FINAL.
Claims 1-11 and Mycobacterium tuberculosis-derived nanocarrier protein are under consideration in this Office Action.
Claim Rejections - 35 USC § 112(b) or 35 U.S.C. 112 (pre-AIA ) 2nd Paragraph
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 4, 8, 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 pre-AIA the applicant regards as the invention.
Claim 4 recites the phrase “the Flag tag affinity chromatography purification comprises first elution and second elution that are conducted sequentially; a first eluent for the first elution comprises 2-[4-(2-hydroxyethyl) piperazin-1-yl]ethanesulfonic acid (HEPES), NaCl, and a detergent; and a second eluent for the second elution comprises the HEPES, the NaCl, and a 1×Flag peptide”. There is insufficient antecedent basis for this limitation in the claim.
Claim 8 recites the phrase “a third eluent for the gel exclusion chromatography purification comprises HEPES and NaCl”. There is insufficient antecedent basis for this limitation in the claim.
Claim 10 recites the phrase “a method for preparing the Escherichia coli total protein solution comprises the following steps: cloning a fusion gene of the Mycobacterium-derived nanocarrier protein into a pETDuet-1 plasmid to obtain a recombinant plasmid; transferring the recombinant plasmid into Escherichia coli to allow prokaryotic expression to obtain an Escherichia coli engineered strain; and resuspending the Escherichia coli engineered strain with a resuspension reagent, and collecting a resulting supernatant after solid-liquid separation to obtain the Escherichia coli total protein solution”. There is insufficient antecedent basis for this limitation in the claim.
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 of this title, 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.
Claims 1-11 are rejected under 35 U.S.C. 103 as being unpatentable over US20240084310 (2024-03-14; PTO 892) in view of Tang et al. (PNAS 118 (16) e2025658118. April 14, 2021; PTO 892), Contreras et al. (J Biol Chem. 2014 Jun 27;289(26):18279-89; PTO 892), US20070275416 (2007-11-29; PTO 892), US20240093159 (2024-03-21; PTO 892)
US20240084310 teaches encapsulin protein and a fusion protein comprising the same, and more specifically to a recombinant expression vector for vaccine production, and a preparation method therefor. US20240084310 teaches methods comprising cloning encapsulin gene into E.coli expression vector, transforming the expression vector into E. coli to produce the encapsuling, lysing the E.coli cells, collecting the soluble supernatant for nickel affinity chromatography and gel-filtration column chromatography using Superose 6 increase 10/300. See entire publication and claims especially paragraphs [0009]- [0033], [0083]-[0091]; Examples 1-3; and claims 1-10, 14-20.
The teachings of the reference differ from the claims in that the reference does not teach the claimed purification method of a Mycobacterium-derived nanocarrier protein.
Contreras et al. teach recombinant expression of Mycobacterium tuberculosis derived protein Mt-Enc (CFP29/Rv078C) in E.coli including Hit-tag variants using pET vectors with His-tag, cell lysis, supernatant recovery of the expressed protein, purification of Mt-Enc by nickel-nitrilotriacetic acid affinity chromatography and gel filtration including purification of cargo proteins Dyp, BrfB, FolB. See entire publication and abstract especially MATERIALS AND METHODS section, RESULTS section, and pages 18280-87)
Tang et al. teach purification of native Mycobacterium smegmatis DyP-loaded encapsuling where the native encapsulin protein was successfully purified by nickel-nitrilotriacetic acid (Ni-NTA) affinity chromatography and gel filtration (Fig. 1A) using Superose 6 increase 10/300 (see entire publication and abstract especially Results and Discussion section, Materials and Methods section, and pages 1-6).
US20070275416 teaches an affinity marker comprising a FLAG-domain, which contains at least one FLAG-tag, and a Streptavidin-binding domain (Strep-domain), which contains at least two Strep-tags, a protein containing this affinity marker, a nucleic acid which codes for it, a vector or a cell containing the affinity marker, method for the purification of a protein produced in a cell using this affinity marker, and the use of the affinity marker for the purification of a protein produced in a cell (see entire publication and claims especially paragraphs [0024]- [0090]). US20070275416 teaches the following in the claims:
1. An affinity marker comprising a FLAG-domain which contains at least one FLAG-tag, and
a Streptavidin-binding domain (Strep-domain) which contains at least two Strep-tags.
2. The affinity marker as claimed in claim 1, wherein the FLAG-domain contains or consists of at least 1, 2 or 3 FLAG-tags.
3. The affinity marker as claimed in claim 1, wherein the FLAG-tag contains or consists of at least one sequence selected from the group consisting of DYKD, DYKDDDDK, DFKDDDK, DYKAFDNL, DYKDHDG, MDFKDDDK, MDYKAFDNL, DYKDHDI and DYKDHDGDYKDHDIDYKDDDDK.
4. The affinity marker as claimed in claim 1, wherein the Strep-domain contains at least 3, 4, 5 or 6 Strep-tags.
5. The affinity marker as claimed in claim 1, wherein the Strep-tags contain an amino acid sequence selected from the group consisting of histidine-proline-glutamine, histidine-proline-asparagine, histidine-proline-methionine and WSHPQFEK.
6. The affinity marker as claimed in claim 1, wherein the Strep-domain contains exactly 2 Strep-tags and the FLAG-domain contains exactly 1 or exactly 3 FLAG-tags.
7. The affinity marker as claimed in claim 1, wherein there is a cleavable linkage between the FLAG-domain and the Strep-domain.
8. The affinity marker as claimed in claim 1, wherein the affinity marker contains or consists of an amino acid sequence selected from the group consisting of SEQ ID NO.30, 31, 32 and 33.
9. A protein containing an affinity marker as claimed in claim 1.
10. A nucleic acid coding for an affinity marker as claimed in claim 1.
11. A method for the purification of a protein expressed in a cell, comprising the steps:
a) preparation of a protein as claimed in claim 9;
b) purification of the protein by means of affinity purification using the FLAG-domain; and
c) purification of the purified protein from step b) by means of affinity purification using the Strep-domain.
12. A method for the purification of a protein expressed in a cell, comprising the steps:
a) preparation of a protein as claimed in claim 9;
b) purification of the protein by means of affinity purification using the Strep-domain; and
c) purification of the purified protein from step b) by means of affinity purification using the FLAG-domain.
13. The method as claimed in claim 11 or 12, wherein the cell is a eukaryotic cell.
US20240093159 teaches virus-like particles and methods of production thereof where
constructs built on pET-Duet-1 expression plasmids were used for producing virus-like proteins and fusion proteins (see entire publication and claims especially paragraphs [0336], [0536]-[0588] and Examples 1-4.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify and/or combine the reference teachings to arrive at the claimed invention by cloning the Mycobacterium tuberculosis derived proteins of Contreras et al. and/or Tang et al. into the pET-Duet-1 expression plasmids of US20240093159 fused to 1×Flag tag as taught by US20070275416; transforming the plasmid into the E.coli of US20240084310, recombinantly express and purify the Mycobacterium tuberculosis derived proteins using affinity chromatography and gel filtration chromatography as taught by US20240093159 and all of the above cited references to obtain the purified Mycobacterium tuberculosis derived proteins. One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do this in order to obtain a simple method for expressing, producing, and purifying Mycobacterium tuberculosis derived proteins. It would have been obvious in view of the above reference teachings to incorporate any of the recited the chromatography method steps, components at recited concentrations, and method step conditions as routine experimentation and/or as desired for purification of the Mycobacterium tuberculosis derived proteins. Hence, the claimed invention as a whole is prima facie obvious.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP §§ 706.02(l)(1) - 706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of copending Application 18826473, claims 1, 3, 5-21 of copending Application 18437991. Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons.
The claims and/or specification of the copending application teach purification method of a Mycobacterium-derived nanocarrier protein, comprising the following steps: providing an Escherichia coli total protein solution, wherein the Escherichia coli total protein solution comprises a Mycobacterium-derived nanocarrier protein, and the Mycobacterium-derived nanocarrier protein is fused with a 1×Flag tag at a C-terminus of a subunit; subjecting the Escherichia coli total protein solution to Flag tag affinity chromatography purification to obtain a crude extract of the Mycobacterium-derived nanocarrier protein; and subjecting the crude extract of the Mycobacterium-derived nanocarrier protein to gel exclusion chromatography purification to obtain a pure product of the Mycobacterium-derived nanocarrier protein. Thus, the teachings anticipate the claimed invention. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Christian L Fronda whose telephone number is (571)272-0929. The examiner can normally be reached Monday-Thursday and alternate Fridays between 9:00AM - 5:00PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Robert Mondesi can be reached on (408)918-7584. The fax phone number for the organization where this application or proceeding is assigned is (571)273-8300.
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/CHRISTIAN L FRONDA/Primary Examiner, Art Unit 1652
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