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 .
Status of Claims
Claims 1, 2, 4-20, 22-27, 29-41, 43-62 are currently pending.
Claims 1, 4, 19, 20, 22-27, 29, 36, 38, 39, 41, 43-45, 49-54, 58 and 59 have been amended.
Claims 1, 2, 4-20, 22-27, 29-41, 43-62 are currently under examination on the merits.
Priority
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. The U.S. effective filing date of all claims under examination is set at 03/02/2021 based on the provisional application 63/200,343 (filed 03/02/2021).
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 04/11/2024 is being considered by the examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Drawings
The drawings are objected to because:
Figs. 10, 11 and 12 are plotted with lines that are depicted in shades that are difficult to differentiate between each of the tested constructs.
Fig. 13 is illustrated with “Kidney Capsule” and “Sac” which have not been described or explained in the specification “Brief Description of The Drawings” for Fig. 13 and as such is unclear what this term refers to in the figure.
Figs. 15, 17, 19, 22 and 31 are labeled with “Insulin” on the bottom left of the micrographs and “Glucagon” on the bottom right of the micrographs. It is unclear what or where these refer to on the micrographs in these figures.
Fig. 29 is plotted with lines that are depicted in shades that are difficult to differentiate between “2hD6-28a (DPP6) CAR” and “No T cells”.
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.
Specification
The disclosure is objected to because of the following informalities:
Pg. 9 line 10 appears to have a typographical error. The word “and” should be amended to “an”
For the “Brief Description of The Drawings”, it is suggested that figures that show “Kidney Capsule”, for example Figs. 13, 14, 16 and 18, the description in the specification should include the description that transplanted islet cells were placed under the kidney capsule (as is disclosed on Pg. 90 line 34).
Appropriate correction is required.
Claim Objections
Claims 20, 22, 36 and 46 are objected to because of the following informalities:
Claim 20 appears to have a typographical error in line 7. The term “DPPP6” should be amended to “DPP6”.
Claim 22 appears to have a typographical error in line 2. The punctuation “:” should be inserted after “SEQ ID NO”.
Claim 36 appears to have an unnecessary phrase in line 2 after the amendment of the claim. The phrase “selected from the group” should be deleted because the claim does not recite any group.
Claim 46 appears to have a typographical error in line 3. The last word in the line “a” should be amended to “an” because “islet” begins with a vowel sound.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 2 and 27 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AlA), 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-AlA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 2 and 27 contain the trademark/trade name "nanobody" in line 2 of each of the claims. 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 “single variable domain heavy chain antibody” also known as “VHH” (see instant specification Pg. 35 lines 9-11 and 14-15) and, accordingly, the identification/description is indefinite.
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 46-51 and 58-62 are rejected under 35 U.S.C. 103 as being unpatentable over Rottman (WO 2020191358 A1 Date Published 2020-09-24) in view of Wang et al. (Cancer Immunol Res (2014) 2 (2): 154–166), Gross et al. (US 20200261499 Date Published 2020-08-20; provided in the IDS submitted on 04/11/20124), Busek et al. (Histochem Cell Biol 143, 497–504; 2015) and Duggleby et al. (Front. Immunol. 9:252, Pages 1-13, 2018).
Rottman teaches adoptive cell therapies for the treatment of cancer (Abstract). Rottman teaches the generation of CAR-T cells specific for target antigens including tumor associated antigens such as fibroblast activation protein (FAP) (Pg. 2 lines 19-25, Pg. 4 lines 27-31, Pg. 5 line 7 and Pg. 6 lines 10-19) to be used in nonhuman primate models of cancer by using T cells from cynomolgus macaques and subsequently treating the same animal with modified cells (Pg. 49 lines 17-22).
Rottman also teaches that that the cancer can be pancreatic islet cell tumor. Rottman further teaches a method of treating a cancer in a subject comprising administering to the subject an effective amount of human immune effector cells encoding an engineered antigen receptor (Pg. 2 lines 19 and 23-25), wherein the immune effector cells are autologous to the subject (Pg. 3 line 4) and comprise T cells that are CD4+ (Pg. 3 lines 5-7). They teach the CAR comprises: a CD28 transmembrane domain, a CD28 costimulatory domain, and a CD3ζ primary signaling domain (Pg. 7 lines 1-3).
Rottman also teaches that the method of treating a cancer in a subject comprises administering to the subject a second cell comprising a CAR that is specific for a second antigen (Pg. 2 lines 19-25). They teach that the cells can be administered intravenously (Pg. 26 line 27).
Rottman does not specifically teach a method of generating a non-human primate model of type 1 diabetes comprising administering an effective amount of a modified T cell comprising a chimeric antigen receptor (CAR) having an affinity for an islet cell antigen, or wherein the CAR has an affinity for DPP6, or wherein the method further comprises administering a second modified T cell comprising a CAR having affinity for a different islet cell antigen, wherein the different islet cell antigen is DPP6. They also do not specifically teach a non-human primate animal model of diabetes made by the method of administering to a non-human primate subject an effective amount of a modified T cell comprising a chimeric antigen receptor (CAR) having an affinity for an islet cell antigen.
Rottman further does not specifically teach a method of treating type 1 diabetes in a subject in need thereof, comprising administering to the subject a modified regulatory T cell comprising a chimeric antigen receptor (CAR) having affinity for FAP, wherein the CAR comprises an FAP binding domain, a CD28 transmembrane domain, a CD28 costimulatory domain, and a CD3( intracellular domain, or wherein the modified cell is an autologous cell, or wherein the modified cell is derived from a human.
However, these deficiencies are made up in the teachings of Wang et al., Gross et al. and Busek et al.
Wang et al. teaches CAR-T cells specific for mouse fibroblast activation protein (FAP) that selectively inhibited tumor growth by targeting tumor stroma that is high in FAP expression in mice (Abstract). Wang et al. also teaches that FAP expression was also seen in the pancreas (Pg. 155 column left lines 16-17 and Pg. 163 column right lines 10-18).
Gross et al. teaches effector immune cells comprising CARs and methods for treatment of cancer comprising administering said effector immune cells in mouse models (Abstract, paragraphs [0411] and [0412]). Gross et al. also teaches that the CAR can target FAP or DPP6 (paragraphs [0189] and [0214]).
Busek et al. teaches that fibroblast activation protein (FAP) and dipeptidyl peptidase-IV (DPP-IV) are co-expressed in adult human Langerhans islet cells (Abstract). They teach that FAP has been suggested to be involved in the regulation of glucose and lipid metabolism (Pg. 498 column left lines 22-23). They also teach that DPP6 is able to cleave several biologically active protein substrates that have impact on type 1 diabetes (Pg. 497 column right lines 25-27, Pg. 498 column right lines 1-2 and Pg. 502 column right lines 8-13). Therefore, Busek et al. teaches that FAP and DPP6 are islet cell antigens.
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method of generating a non-human primate model of cancer comprising administering an effective amount of CAR-T cells specific for FAP to non-human primates as a model for cancer treatment as taught by Rottman because Wang et al. teaches that CAR-T cells specific for FAP can selectively inhibit tumor growth in mouse and that FAP expression was also seen in the pancreas (Abstract, Pg. 155 column left lines 16-17 and Pg. 163 column right lines 10-18) and Gross et al. teaches that CAR specific for FAP can be used for cancer treatment in a mouse model (Abstract, paragraphs [0189], [0411] and [0412]). Noting Busek et al. teaches that FAP is expressed in adult human Langerhans islet cells and may be involved in the regulation of glucose and lipid metabolism (Abstract and Pg. 498 column left lines 22-23), such administering is equivalent to the recited steps of methods of generating a type 1 diabetes model, as recited by instant claims 46 and 48. Regarding instant claim 60, such administering is equivalent to “prophylactic” treatment. This is an example of (A) Combining prior art elements according to known methods to yield predictable results; and (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Further, it is obvious to perform a combined method of generating a non-human primate model of cancer comprising administering an effective amount of CAR immune cells specific for DPP6 as taught by Gross et al. wherein the CAR-T cells are administered to non-human primates as a model for cancer treatment as taught by Rottman since Gross et al. teaches CARs for treating cancer can target FAP or DPP6 (paragraphs [0189] and [0214]). Noting Busek et al. teaches that DPP6 is expressed in adult human Langerhans islet cells and has implications in type 1 diabetes (Abstract, Pg. 497 column right lines 25-27, Pg. 498 column right lines 1-2 and Pg. 502 column right lines 8-13), such administering is equivalent to the recited steps of methods of generating a type 1 diabetes model of instant claims 46-47. Regarding instant claim 60, such administering is equivalent to “prophylactic” treatment.
With regards to claims 49-50, it is obvious to perform a combined method of generating a non-human primate model of cancer comprising administering an effective amount of CAR-T cells specific for FAP to non-human primates as a model for cancer treatment as taught by Rottman and further comprising administering to the non-human primate subject an effective amount of a second modified T cell comprising a CAR having an affinity for a different islet cell antigen that is DPP6 as taught by Wang et al. and by Gross et al. because Rottman et al. teaches administering a first cell and a second cell for the treatment of cancer wherein each of the cells comprise CARs that are targeted to different antigens (Pg. 2 lines 19-25). Noting Gross et al. teaches that immune cells comprising CAR specific for DPP6 can be used for treating cancer in a mouse model (Abstract and paragraphs [0214], [0411] and [0412]) and Busek et al. teaches that DPP6 is expressed in adult human Langerhans islet cells and has implications in type 1 diabetes (Abstract, Pg. 497 column right lines 25-27, Pg. 498 column right lines 1-2 and Pg. 502 column right lines 8-13), such administering is equivalent to generating the type 1 diabetes model of instant claims 49-50.
With regards to claim 51, it is obvious to perform a combined method of generating a non-human primate model of cancer comprising administering an effective amount of CAR-T cells specific for FAP or DPP6 to non-human primates as a model for cancer treatment as taught by Rottman and Gross et al. respectively as described above, wherein the modified T cells are administered intravenously as taught by Rottman et al. (Pg. 26 line 27). Noting Busek et al. teaches that FAP is expressed in adult human Langerhans islet cells and may be involved in the regulation of glucose and lipid metabolism (Abstract and Pg. 498 column left lines 22-23), and that DPP6 is expressed in adult human Langerhans islet cells and has implications in type 1 diabetes (Abstract, Pg. 497 column right lines 25-27, Pg. 498 column right lines 1-2 and Pg. 502 column right lines 8-13), such administering is equivalent to the recited steps of methods of generating a type 1 diabetes model, as recited by instant claims 46 and 51.
With regards to claims 58 and 59, it is obvious to perform a combined method of generating a non-human primate model of cancer comprising administering an effective amount of CAR-T cells specific for FAP or DPP6 to non-human primates as a model for cancer treatment as taught by Rottman and Gross et al. respectively as described above, wherein the subject is a cynomolgus macaques as taught by Rottman (Pg. 49 lines 17-22). Noting Busek et al. teaches that FAP is expressed in adult human Langerhans islet cells and may be involved in the regulation of glucose and lipid metabolism (Abstract and Pg. 498 column left lines 22-23), and that DPP6 is expressed in adult human Langerhans islet cells and has implications in type 1 diabetes (Abstract, Pg. 497 column right lines 25-27, Pg. 498 column right lines 1-2 and Pg. 502 column right lines 8-13), such administering is equivalent to the recited steps of methods of generating a type 1 diabetes model, as recited by instant claims 46-48 and 58. Further, since the recited steps of methods of generating a type 1 diabetes model have been made obvious wherein the subject is a cynomolgus macaques as taught by Rottman (Pg. 49 lines 17-22), it is therefore obvious to perform the combined method to arrive at a non-human primate animal model of diabetes when using the said steps of the said methods, thus meeting the limitations of claim 59.
With regards to claims 60-62, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method of treating cancer in a subject in need thereof, comprising administering to the subject a modified T cell that is CD4+ and comprising a CAR having affinity for FAP as taught by Rottman and wherein the CAR comprises a CD28 transmembrane domain, a CD28 costimulatory domain, and a CD3ζ intracellular domain as taught by Rottman, because Wang et al. teaches that CAR-T cells specific for FAP can selectively inhibit tumor growth in mouse and that FAP expression was also seen in the pancreas (Abstract, Pg. 155 column left lines 16-17 and Pg. 163 column right lines 10-18) and Gross et al. teaches that CAR specific for FAP can be used for cancer treatment in a mouse model (Abstract, paragraphs [0189], [0411] and [0412]). Noting Busek et al. teaches that FAP is expressed in adult human Langerhans islet cells and may be involved in the regulation of glucose and lipid metabolism (Abstract and Pg. 498 column left lines 22-23), such administering is equivalent to “prophylactic” treatment of type 1 diabetes in a subject in need thereof. In addition, Rottman teaches that the immune effector cells encoding CAR specific for FAP can be human immune cells (Pg. 2 lines 19 and 23-25), can be autologous to the subject (Pg. 3 line 4) and can comprise T cells that are CD4+ (Pg. 3 lines 5-7). As taught by Duggleby et al., regulatory T cells are CD4+ T cells (Abstract), thus confirming that administering the CD4+ T cells comprising CAR with a binding domain to FAP as taught by Rottman meet the limitation of instant claim 60 of administering a modified regulatory T cell to the subject in need thereof.
Claim Rejections - 35 USC § 103 (second)
Claims 46-52 and 58-62 are rejected under 35 U.S.C. 103 as being unpatentable over Rottman (WO 2020/191358 A1 Date Published 2020-09-24), Wang et al. (Cancer Immunol Res (2014) 2 (2): 154–166), Gross et al. (US 20200261499 Date Published 2020-08-20; provided in the IDS submitted on 04/11/20124) and Busek et al. (Histochem Cell Biol 143, 497–504; 2015) as applied to claims 46-51 and 58-62 above and further in view of NCT02850536 (Record History Version 9 Date submitted 2020-10-29).
The combined teachings of Rottman, Wang et al., Gross et al. and Busek et al. render obvious instant claims 46-51 and 58-62 as discussed above in the first 103 which is incorporated here in its entirety.
However, Rottman, Wang et al., Gross et al. and Busek et al. do not specifically teach that the modified T cells comprising a CAR having an affinity for an islet cell antigen are administered via the splenic artery.
However, these deficiencies are made up in the teachings of NCT02850536.
NCT02850536 teaches administration of CAR-T for CEA-expressing liver metastases or pancreas cancer (Title). They teach that anti-CEA CAR-T cell infusions were delivered via the hepatic artery or splenic vein using the Surefire Infusion System (SIS) (Brief Summary)
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the administration of generated CAR-T cells with affinity for islet cell antigen FAP as taught by the combined methods of Rottman et al., Wang et al., Gross et al. and Busek et al. described in the first 103 above, via the splenic artery because NCT02850536 teaches that CAR-T cells targeting CEA can be delivered to liver metastasis and pancreas that express CEA through hepatic artery or splenic vein administration in a phase Ib trail (Brief Summary). This is an example of (A) Combining prior art elements according to known methods to yield predictable results; and (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Rejections - 35 USC § 103 (third)
Claims 46-51, 54-62 are rejected under 35 U.S.C. 103 as being unpatentable over Rottman (WO 2020191358 A1 Date Published 2020-09-24), Wang et al. (Cancer Immunol Res (2014) 2 (2): 154–166), Gross et al. (US 20200261499 Date Published 2020-08-20; provided in the IDS submitted on 04/11/20124) and Busek et al. (Histochem Cell Biol 143, 497–504; 2015) as applied to claims 46-51 and 58-62 above and further in view of Su et al. (OncoImmunology 2017, VOL. 6, NO. 1, e1249558, 15 pages) and Feng et al. (PNAS Vol. 117 No. 39, Pages 24022–24031, September 29, 2020).
The combined teachings of Rottman, Wang et al., Gross et al., and Busek et al. render obvious instant claims 46-51 and 58-62 as discussed above in the first 103 which is incorporated here in its entirety.
However, Rottman, Wang et al., Gross et al., and Busek et al. do not specifically teach the method of instant claim 46 further comprises administering an effective amount of an immune-modulating agent to the non-human primate subject, wherein the immune-modulating agent is a CRISPR-based system that disrupts the expression of an immune checkpoint protein that is selected from the group consisting of PD-1, CTLA-4, TIM3, GITR, BTLA, LAG3, and any combination thereof.
However, these deficiencies are made up in the teachings of Su et al. and Feng et al.
Su et al. teaches the generation of PD-1-disrupted cytotoxic T lymphocytes (CTL) by CRISPR-Cas9 system wherein PD-1 is an immune cell checkpoint inhibitor (Abstract). They teach that said PD-1-disrupted CTLs demonstrate enhanced immune response to Epstein-Barr virus (EBV)-LMP2A antigen and superior cytotoxicity to EBV-positive gastric cancer cells (Abstract). Therefore, Su et al. teaches a CRISPR-based system that is an immune-modulating agent since it can modulate the immune checkpoint inhibitor of PD-1.
Feng et al. teaches CRISPR/Cas system for generating genetically modified nonhuman primate (NHP) models for basic science and disease research (Abstract). They teach that regional genetic manipulations in utero or postnatally can be achieved by local injection of adeno-associated virus (AAV) to deliver the CRISPR/Cas system (Pg. 24023 column left paragraph second).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of generating a non-human primate model of cancer comprising administering CAR-T cells with affinity for islet cell antigen FAP as taught by the combined methods of Rottman et al., Wang et al., Gross et al. and Busek et al. described in the first 103 above, further comprising administering an effective amount of immune-modulating agent of CIRSPR/Cas9 as taught by Su et al. and Feng et al. wherein the CRISPR-Cas9 system disrupts the immune checkpoint of PD-1 as taught by Su et al. because Su et al. teaches that PD-1-disrupted CTLs demonstrate enhanced immune response and cytotoxicity (Abstract) and Feng et al. teaches that delivery of CRISPR/Cas system by postnatal injection of adeno-associated virus (AAV) can be used for generating genetically modified nonhuman primate models for disease research (Abstract and Pg. 24023 column left paragraph second). This is an example of (A) Combining prior art elements according to known methods to yield predictable results; and (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Allowable Subject Matter
The first CDR region comprising an amino acid sequence set forth in SEQ ID NO: 35; a second CDR region comprising an amino acid sequence set forth in SEQ ID NO: 36; and a third CDR region comprising an amino acid sequence set forth in SEQ ID NO: 37, and the variable region comprising the amino acid sequence set forth in SEQ ID NO: 33 are free of prior art.
Claims 1, 4-19, 26, 29-35, 37-41, and 43-45 are allowed.
Claim Objection
Claim 53 is objected due to its dependency on rejected independent claim 46.
Claims 23-25 are objected to for being dependent upon an objected claim.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Yie-Chia Lee (Tonya) whose telephone number is (571)272-0123. The examiner can normally be reached Monday - Friday 7.30a - 3.30p Eastern Time Zone.
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, Samira Jean-Louis can be reached on 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/YIE-CHIA LEE (TONYA)/Examiner, Art Unit 1642
/SEAN E AEDER/Primary Examiner, Art Unit 1642