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Claims 9-14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention (Group II), there being no allowable generic or linking claim.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In light of the Applicant’s elected species, claims 4-5 and 17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.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 May 4, 2026, have been acknowledged. Claims 1-2, 6-8, 15, and 18-20 were amended. In light of the Applicant’s elected invention and species, claims 4-5, 9-14, and 17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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.
Notice of Non-responsive Amendment
The reply filed on May 4, 2026, is not fully responsive to the prior Office Action because of the following omission(s) or matter(s): the claims are not considered to be in compliance with 37 CFR § 1.121, recited here:
§ 1.121(c) Manner of making amendments in applications.
Amendments to a claim must be made by rewriting the entire claim with all changes (e.g., additions and deletions) as indicated in this subsection, except when the claim is being canceled. Each amendment document that includes a change to an existing claim, cancellation of an existing claim or addition of a new claim, must include a complete listing of all claims ever presented, including the text of all pending and withdrawn claims, in the application. The claim listing, including the text of the claims, in the amendment document will serve to replace all prior versions of the claims, in the application. In the claim listing, the status of every claim must be indicated after its claim number by using one of the following identifiers in a parenthetical expression: (Original), (Currently amended), (Canceled), (Withdrawn), (Previously presented), (New), and (Not entered).
(1) Claim listing. All of the claims presented in a claim listing shall be presented in ascending numerical order. Consecutive claims having the same status of "canceled" or "not entered" may be aggregated into one statement (e.g., Claims 1–5 (canceled)). The claim listing shall commence on a separate sheet of the amendment document and the sheet(s) that contain the text of any part of the claims shall not contain any other part of the amendment.
(c)(2) When claim text with markings is required. All claims being currently amended in an amendment paper shall be presented in the claim listing, indicate a status of “currently amended,” and be submitted with markings to indicate the changes that have been made relative to the immediate prior version of the claims. The text of any added subject matter must be shown by underlining the added text. The text of any deleted matter must be shown by strike-through except that double brackets placed before and after the deleted characters may be used to show deletion of five or fewer consecutive characters. The text of any deleted subject matter must be shown by being placed within double brackets if strike-through cannot be easily perceived. Only claims having the status of “currently amended,” or “withdrawn” if also being amended, shall include markings. If a withdrawn claim is currently amended, its status in the claim listing may be identified as “withdrawn— currently amended.”
The claim amendment submitted May 4, 2026, lists claim 15 as an original claim while claim 15 has been amended and should be identified as currently amended. While it would be appropriate to reject entry of the present amendment for noncompliance with 37 CFR § 1.121, applicant is instead respectfully reminded to properly note the status of each claim submitted in order to avoid the issuance of a Notice of Non-Compliant Amendment, which would delay prosecution and potentially have an adverse effect on any patent term adjustment should the claims proceed to issue.
Withdrawn Claim Rejections - 35 USC § 112
The prior rejection of claims 6-8 and 18-20 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 is withdrawn in light of Applicant’s amendments to claims 6 and 18 to recite the expression vector and to claims 7-8 and 19-20 to recite the at least one cell.
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). This a new rejection made in response to Applicant’s amendments to claims that is substantially similar to a previous rejection. Applicant’s traversal has been fully considered but is moot in response to the new rejection of record.
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). Harding teaches that co-expression of ADAM 12S and HB-EGF stimulates adipogenesis in multiple cell types which leads to increased lipid droplet accumulation (paragraphs 0003-0026 and 0048-0059 and Examples 5 and 10)
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. Regarding the lipid droplet accumulation, Harding teaches that white adipose tissue is composed primarily of white fat cells that contain a large lipid droplet surrounded by a layer of cytoplasm while brown adipose tissue is composed primarily of brown fat cells that have considerable cytoplasm, with lipid droplets scattered throughout (paragraphs 0025-0026). Therefore, converting a white adipose tissue adipocyte to a brown adipose tissue adipocyte would lead to an increase in the number of lipid droplets as white adipocytes have one large lipid droplet while brown adipose tissue has multiple lipid droplets.
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). This a new rejection made in response to Applicant’s amendments to claims that is substantially similar to a previous rejection. Any aspect of Applicant’s traversal that is relevant to the rejection as newly written is addressed below.
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 the increase in lipid accumulation, Harding teaches that co-expression of ADAM 12S and HB-EGF stimulates adipogenesis in multiple cell types which leads to increased lipid droplet accumulation (paragraphs 0003-0026 and 0048-0059 and Examples 5 and 10). Furthermore, Harding teaches that white adipose tissue is composed primarily of white fat cells that contain a large lipid droplet surrounded by a layer of cytoplasm while brown adipose tissue is composed primarily of brown fat cells that have considerable cytoplasm, with lipid droplets scattered throughout (paragraphs 0025-0026). Therefore, converting a white adipose tissue adipocyte to a brown adipose tissue adipocyte would lead to an increase in the number of lipid droplets as white adipocytes have one large lipid droplet while brown adipose tissue has multiple lipid droplets.
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.
Response to Arguments
Applicants respectfully request that the Examiner hold this rejection in abeyance pending notification of allowable subject matter. Applicant’s argument(s) has been fully considered, but is not persuasive. The rejection cannot be held in abeyance, and it is maintained for the reasons of record until the aforementioned issues are resolved.
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). This a new rejection made in response to Applicant’s amendments to claims that is substantially similar to a previous rejection. Any aspect of Applicant’s traversal that is relevant to the rejection as newly written is addressed below.
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 the increase in lipid accumulation, Harding teaches that co-expression of ADAM 12S and HB-EGF stimulates adipogenesis in multiple cell types which leads to increased lipid droplet accumulation (paragraphs 0003-0026 and 0048-0059 and Examples 5 and 10). Furthermore, Harding teaches that white adipose tissue is composed primarily of white fat cells that contain a large lipid droplet surrounded by a layer of cytoplasm while brown adipose tissue is composed primarily of brown fat cells that have considerable cytoplasm, with lipid droplets scattered throughout (paragraphs 0025-0026). Therefore, converting a white adipose tissue adipocyte to a brown adipose tissue adipocyte would lead to an increase in the number of lipid droplets as white adipocytes have one large lipid droplet while brown adipose tissue has multiple lipid droplets.
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.
Response to Arguments
Applicants respectfully request that the Examiner hold this rejection in abeyance pending notification of allowable subject matter. Applicant’s argument(s) has been fully considered, but is not persuasive. The rejection cannot be held in abeyance, and it is maintained for the reasons of record until the aforementioned issues are resolved.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Doug Schultz can be reached at (571) 272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KEENAN A BATES/Examiner, Art Unit 1631
/PETER PARAS JR/Supervisory Patent Examiner, Art Unit 1632
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