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 .
Election/Restrictions
Applicant’s election without traverse of Group I (Claims 1-8 and 15-20; drawn to a method of enhancing at least one BAT-like expression level in an individual) in the reply filed on October 27, 2025, is acknowledged.
Claims 9-14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention (Group II), there being no allowable generic or linking claim.
Applicant further elected the following species:
a. Plasmid as the expression vector
In light of the Applicant’s elected species, claims 4-5 and 17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
DETAILED ACTION
The claims filed on January 30, 2023, have been acknowledged. In light of the Applicant’s elected invention and species, claims 4-5, 9-14, and 17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 1-3, 6-8, 15-16, and 18-20 are pending and examined on the merits.
Priority
The applicant claims domestic priority from U.S. provisional application No. 63/305,299, filed on February 1, 2022. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Claims 1-3, 6-8, 15-16, and 18-20 receive domestic benefit from U.S. provisional application No. 63/305,299, filed on February 1, 2022.
Information Disclosure Statement
The information disclosure statement (IDS) filed on September 24, 2024, has been considered.
Claim Objections
Claims 1, 8, and 20 are objected to because of the following informalities:
In regard to Claims 1 and 8, instant claims use the abbreviations “BAT” and “WAT”, respectively, which has not been spelled out upon first use. Although claims are allowed abbreviations, if an abbreviation is not spelled out upon first use in a claim, MPEP §2429 states that Applicant only use abbreviations that are specifically defined in "WIPO Standard ST.25 (1998)" or that are well known and would be clear to someone who had not read the invention description.
In regards to claims 8 and 20, “wherein contracting” should read “wherein contacting”.
Appropriate correction is required.
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 6-8 and 18-20 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.
Claims 6 and 18 recite the limitation “the vector” in line 1 while claim 1 and claim 15 recite the term “an expression vector” and claims 3 and 16 recite “the expression vector”. There is insufficient antecedent basis for this limitation in the claims. As the Applicant uses different terms between claims (“the expression vector” and “the vector”), it is unclear whether “the vector” have proper antecedent basis and whether “the vector” is the same as “an expression vector” of claims 1 and 15. Applicant is recommended to use one set of terminology (an expression vector and the expression vector or a vector and the vector) for all the relevant claims.
Claims 8 and 20 recite the limitation "contracting the cell" in line 1, respectively, and claims 7 and 19 recite the limitation “the cell” in line 1 while claims 1 and 15 recite “contacting at least one cell”. There is insufficient antecedent basis for this limitation in the claims. As claims 1 and 15 recite “at least one cell”, the claims can be interpreted to require contacting a single cell or multiple cells. Therefore, it is unclear whether contacting the cell of claims 8 and 20 involves contacting a single cell or multiple cells and whether the cell of claims 7 and 19 refers to a single cell or multiple cells, thus, rendering the claims indefinite.
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 1-3, 6-8, 15-16, and 18-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by United States Patent Application No. 20110060034 (Harding).
Regarding claims 1-2, 8, 15, and 20, Harding teaches a method of treating a subject diagnosed with obesity (i.e. identifying an individual in need) by transforming a portion of the white adipose tissue cells into brown adipose tissue cells (i.e. contacting at least one cell with the expression vector) of the subject by administering an expression vector that includes a nucleotide sequence encoding HB-EGF operatively linked to an adipose-tissue specific promoter and a nucleotide sequence encoding ADAM 12S operatively linked to an adipose-tissue specific promoter (i.e. providing an expression vector encoding ADAM 12S) (paragraphs 0009-0017 and 0061 and Figure 5).
Regarding the increase in BAT-like expression level limitation of claim 1 and the functional changes of claims 8 and 20, as the expression vector transforms white adipose tissue into brown adipose tissue, this would result in an increase in the number of brown adipose tissue (BAT) which would increase the expression of BAT genes and markers. For example, Harding teaches that their transformed BAT cells have increased expression of PGC-1α compared to brown fat and decreased expression of C/EBPα, AKT-1, and PPARγ compared to white adipose tissue (Figure 8).
Regarding claims 3 and 16, Harding teaches that the expression vector carrying the polynucleotide sequences encoding HB-EGF and ADAM 12S can be plasmids (paragraph 0061 and Figure 5).
Regarding claims 6 and 18, Harding teaches that separate expression vectors can be used to provide HB-EGF and ADAM 12S (paragraphs 0055-0056).
Regarding claims 7 and 19, Harding teaches that gene transfer may more easily be performed under ex vivo conditions. Ex vivo treatment refers to the isolation of cells from an animal (such as a human subject), the delivery of a nucleic acids into the cells in vitro, and then the return of the modified cells back into an animal. This may involve the surgical removal of tissue/organs from an animal or the primary culture of cells and tissues (paragraphs 0041 and 0074). As Harding teaches that their method involves transforming white adipose tissue to brown adipose tissue, the primary culture would be human white adipose tissue adipocytes.
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 § 2146 et seq. 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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 1-3, 6-8, 15-16, and 18-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 8455191 in view of United States Patent Application No. 20110060034 (Harding).
Regarding claims 1-2, 8, 15, and 20, ‘191 claims a method for converting animal cells into brown adipose tissue cells, comprising transforming the animal cells using an expression vector comprising a nucleotide sequence encoding HB-EGF operatively linked to a promoter and a nucleotide sequence encoding ADAM 12S operatively linked to a promoter; wherein the animal cells are converted in vitro (claims 1-2).
‘191 does not teach identifying an individual in need of increased expression of a BAT-like marker.
However, Harding teaches a method of treating a subject diagnosed with obesity (i.e. identifying an individual in need) by transforming a portion of the white adipose tissue cells into brown adipose tissue cells (i.e. contacting at least one cell with the expression vector) of the subject by administering an expression vector that includes a nucleotide sequence encoding HB-EGF operatively linked to an adipose-tissue specific promoter and a nucleotide sequence encoding ADAM 12S operatively linked to an adipose-tissue specific promoter (i.e. providing an expression vector encoding ADAM 12S) (paragraphs 0009-0017 and 0061 and Figure 5).
Harding teaches that gene transfer may more easily be performed under ex vivo conditions. Ex vivo treatment refers to the isolation of cells from an animal (such as a human subject), the delivery of a nucleic acids into the cells in vitro, and then the return of the modified cells back into an animal. This may involve the surgical removal of tissue/organs from an animal or the primary culture of cells and tissues (paragraphs 0041 and 0074).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the in vitro method of converting animal cells into brown adipose tissue cells of ‘191 with the method of treating obesity using ex vivo modification of adipose tissue of Harding to arrive at the instantly claimed invention. One of ordinary skill in the art would have a reason to combine with a reasonable expectation of success because ‘191 and Harding are both interested in transforming cells into brown adipose tissue using vectors encoding ADAM12S and Harding directly identifies the potential for modifying cells ex vivo (an in vitro method) by contacting the cells with vectors encoding ADAM12S and HB-EGF to generate BAT-like cells. Therefore, it would have been obvious that the method of ‘191 could be used as part of an ex vivo modification of cells to treat obesity, as identified by Harding. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Regarding the increase in BAT-like expression level limitation of claim 1 and the functional changes of claims 8 and 20, as the expression vector transforms white adipose tissue into brown adipose tissue, this would result in an increase in the number of brown adipose tissue (BAT) which would increase the expression of BAT genes and markers. For example, Harding teaches that their transformed BAT cells have increased expression of PGC-1α compared to brown fat and decreased expression of C/EBPα, AKT-1, and PPARγ compared to white adipose tissue (Figure 8).
Regarding claims 3 and 16, ‘191 claims that the expression vector is a plasmid (claim 4).
Regarding claims 6 and 18, Harding teaches that separate expression vectors can be used to provide HB-EGF and ADAM 12S (paragraphs 0055-0056). Harding teaches that using separate expression vectors with different selection markers in the expression vectors for HB-EGF and ADAM 12S is preferable because it allows one to select the transformed cells independently and together (paragraph 0066).
Therefore, it would have been obvious to deliver the HB-EGF gene and the ADAM 12S gene on separate expression vectors because it allows one to select the transformed cells independently and together before delivery to a subject.
Regarding claims 7 and 19, Harding, as stated supra, teaches that gene transfer may more easily be performed under ex vivo conditions. Ex vivo treatment refers to the isolation of cells from an animal (such as a human subject), the delivery of a nucleic acids into the cells in vitro, and then the return of the modified cells back into an animal. This may involve the surgical removal of tissue/organs from an animal or the primary culture of cells and tissues (paragraphs 0041 and 0074). Furthermore, ‘191 claims that the target cell type is a white adipose cell (claim 9).
As Harding teaches that their method involves transforming white adipose tissue to brown adipose tissue and ‘191 identifies their target cells as a white adipose cell, the primary culture for ex vivo modification would be human white adipose tissue adipocytes.
Claim 1-3, 6-8, 15-16, and 18-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 8835112 in view of United States Patent Application No. 20110060034 (Harding).
Regarding claims 1-2, 8, 15, and 20, ‘112 claims a method for converting animal cells into brown adipose tissue cells, comprising transforming the animal cells using an expression vector comprising a nucleotide sequence encoding HB-EGF operatively linked to a promoter and a nucleotide sequence encoding ADAM 12 operatively linked to a promoter; wherein the animal cells are converted ex vivo (claims 1-2 and 7).
‘112 does not teach identifying an individual in need of increased expression of a BAT-like marker.
However, Harding teaches a method of treating a subject diagnosed with obesity (i.e. identifying an individual in need) by transforming a portion of the white adipose tissue cells into brown adipose tissue cells (i.e. contacting at least one cell with the expression vector) of the subject by administering an expression vector that includes a nucleotide sequence encoding HB-EGF operatively linked to an adipose-tissue specific promoter and a nucleotide sequence encoding ADAM 12S operatively linked to an adipose-tissue specific promoter (i.e. providing an expression vector encoding ADAM 12S) (paragraphs 0009-0017 and 0061 and Figure 5).
Harding teaches that gene transfer may more easily be performed under ex vivo conditions. Ex vivo treatment refers to the isolation of cells from an animal (such as a human subject), the delivery of a nucleic acids into the cells in vitro, and then the return of the modified cells back into an animal. This may involve the surgical removal of tissue/organs from an animal or the primary culture of cells and tissues (paragraphs 0041 and 0074).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the ex vivo method of converting animal cells into brown adipose tissue cells of ‘112 with the method of treating obesity using ex vivo modification of adipose tissue of Harding to arrive at the instantly claimed invention. One of ordinary skill in the art would have a reason to combine with a reasonable expectation of success because ‘112 and Harding are both interested in transforming cells into brown adipose tissue using vectors encoding ADAM12S ex vivo and Harding directly identifies the potential for modifying cells ex vivo by contacting the cells with vectors encoding ADAM12S and HB-EGF to generate BAT-like cells to treat obesity. Therefore, it would have been obvious that the method of ‘112 could be used as part of an ex vivo modification of cells to treat obesity, as identified by Harding. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Regarding the increase in BAT-like expression level limitation of claim 1 and the functional changes of claims 8 and 20, as the expression vector transforms white adipose tissue into brown adipose tissue, this would result in an increase in the number of brown adipose tissue (BAT) which would increase the expression of BAT genes and markers. For example, Harding teaches that their transformed BAT cells have increased expression of PGC-1α compared to brown fat and decreased expression of C/EBPα, AKT-1, and PPARγ compared to white adipose tissue (Figure 8).
Regarding claims 3 and 16, ‘112 claims that the expression vector is a plasmid (claim 4).
Regarding claims 6 and 18, Harding teaches that separate expression vectors can be used to provide HB-EGF and ADAM 12S (paragraphs 0055-0056). Harding teaches that using separate expression vectors with different selection markers in the expression vectors for HB-EGF and ADAM 12S is preferable because it allows one to select the transformed cells independently and together (paragraph 0066).
Therefore, it would have been obvious to deliver the HB-EGF gene and the ADAM 12S gene on separate expression vectors because it allows one to select the transformed cells independently and together before delivery to a subject.
Regarding claims 7 and 19, Harding, as stated supra, teaches that gene transfer may more easily be performed under ex vivo conditions. Ex vivo treatment refers to the isolation of cells from an animal (such as a human subject), the delivery of a nucleic acids into the cells in vitro, and then the return of the modified cells back into an animal. This may involve the surgical removal of tissue/organs from an animal or the primary culture of cells and tissues (paragraphs 0041 and 0074). Furthermore, ‘112, as stated supra, claims that the conversion can occur ex vivo (claim 7).
As Harding teaches that their method involves transforming white adipose tissue to brown adipose tissue, it would have been obvious that the combined method of ‘112 and Harding could also target white adipose tissue to transform it into brown adipose tissue. Therefore, the primary culture for ex vivo modification would be human white adipose tissue adipocytes.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KEENAN A BATES whose telephone number is (571)270-0727. The examiner can normally be reached M-F 7:30-5:00.
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/KEENAN A BATES/Examiner, Art Unit 1631