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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 2/27/2026 has been entered.
Claims 1-28 are pending and have been considered on the merits herein.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 1 and its therefore dependent claims 2-28 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Specifically, the amendment “…wherein the T-cell population…comprises unique T cell clones” introduces new matter, which is not described in the specification as originally filed. The specification (0014-0017) describes a T cell population with high clonality and low diversity, and wherein diversity refers to a unique rearrangement (unique receptor gene rearrangements) and (0087-0089) describes expanded clones being new or existing clones; however, it is not clear and there is no support for “unique T cell clones”. Therefore, the amendment changes the scope of the claims and applicants’ invention for which no support is provided. This is a new matter rejection.
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.
Claim 1 and its therefore dependent claims 2-28 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.
As stated above, applicant has amended claim 1 to include “wherein the T-cell population…comprises unique T cell clones”; however, it is not clear what is meant by “unique T cell clones” as the specification only teaches diversity to be defined as the number of unique gene rearrangements and the expansion of new or existing clones but no direction as to what a “unique T cell clones” refers to.
Claim Rejections - 35 USC § 103
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 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.
Claim(s) 1-28 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO2015/070323 (IDS) in view of Rajani et al. (Am. Soc., Gene and Cell Ther., 2015, p. 166-174) and ClinicalTrial.gov NCT02620423 (IDS) in further view of Kirsch et al. (Mol. Onc., 2015, IDS), Samson et al. (Sci. Transl. Med., vol. 10, 2018, p. 1-12) and Tumeh et al. (Nature, 2014, IDS).
WO323 teaches a method of treating cancer in a subject comprising administering to the subject one or more doses of an oncolytic virus (0002, 0004, Ex. 1 and 2).
Regarding claim 6, the cancer is disclosed to be breast cancer, pancreatic cancer and includes “ all types of cancer, proliferative disorders, neoplasia, or malignant tumors found in mammals, including lymphomas, leukemias, blastomas, germ cell tumors, carcinomas and sarcomas. Exemplary cancers include cancer of the brain, breast, cervix, colon, head and neck, liver, kidney, lung, non-small cell lung, melanoma, mesothelioma, ovary, sarcoma, stomach, uterus and medulloblastoma. Optionally, the cancer is a neoplasm. Optionally, the cancer is head and neck cancer. Optionally, the cancer is lung cancer, liver cancer, lymphoma, pancreatic cancer, melanoma, kidney cancer or ovarian cancer” (0009, 0010, Ex. 1 and 2).
Regarding claims 7-9, approximately 10 to 1012 PFU or 108-1012 TCID50 of the oncolytic virus is administered (0056, 0068).
Regarding claim 10, the oncolytic virus is administered as an intravenous infusion (0048, 0054, 0055, 0060, see Ex. 1 and 2).
Regarding claim 11, additional therapeutic agents are administered to the subject including chemotherapeutic agents (0004, 0006, Ex. 1 and 2)
Regarding claim 13, the additional agent is an aromatase inhibitor (0045).
Regarding claims 17-23, the oncolytic virus is selected from reovirus, a Newcastle disease virus (NDV), a vesicular stomatitis virus (VSV), an adenovirus, a vaccinia virus, a parapox orf virus, a Sindbis virus, and a herpes simplex virus and particularly reovirus serotype 3 Dearing strain reovirus and may be a human reovirus (0011, 0021, 0022, 0067).
Regarding claim 23, the reovirus is deposited as IDAC Accession No. 190907-01 (0067).
Regarding claims 24, 25, the reovirus comprises a lambda-3 polypeptide having one or more amino acid modifications and specifically a Val at residue 214 (0031, 0067).
Regarding claim 26, the reovirus comprises a L1 genome segment having a nucleic acid modification consisting of a T at position 660 (0032, 0067).
Regarding claims 27 and 28, the reovirus is a recombinant or modified (0023, 0025, 0067, for example).
WO323 differs from the claimed invention in that they do not teach the limitations of claims 14-15.
Regarding claims 14-15, ClinicalTrials.gov ID NCT02620423 teaches a trial to investigate intravenous administration of Reolysin® (Reovirus serotype 3-Dearing strain at a dose of 4.5x1010 TCID50) in combination with additional therapeutic agents, i.e. the immune checkpoint inhibitor pembrolizumab, and a chemotherapeutic agent. The drugs are administered to subject having advanced pancreatic adenocarcinoma. Reovirus combined with chemotherapy leads to increased viral replication and oncolysis in Ras activated tumors, with an immunogenic response further enhanced by the checkpoint inhibitor pembrolizumab (P. 2, whole page, p. 6).
Rajani teaches that reovirus has oncolytic activity against many tumor types and that antitumor activity is directly associated with immune activation by virus replication in tumors. Immune therapy includes innate immune activation against virally infected tumor cells and generation of adaptive antitumor immune responses as a result of in vivo priming against anti-tumor associated antigens (abstract). Rajani administers the combination of reovirus therapy with immune checkpoint inhibition, i.e. the administration of anti-PD-1 antibody, which enhances survival of mice compared to each therapy alone. “In vitro immune analysis demonstrated that checkpoint inhibition improved the ability of NK cells to kill reovirus-infected tumor cells, reduced Treg activity, and increased the adaptive CD8+ T-cell-dependent antitumor T-cell response” (abstract, p. 167, 1st full parag.-p. 168). PD-1 blockade also enhanced the antiviral immune response but through effector mechanisms which overlapped with but also differed from those affecting the antitumor response (abstract). Rajani teaches that when anti-PD-1 antibody was administered starting 7 days after the first i.t. virus treatment, combining both treatments significantly prolonged survival of mice (P < 0.001 compared to i.t. reovirus), and cured ~40% of mice. Cured mice were tumor free for >100 days (p. 167, PD-1 blockade with reovirus prolongs survival section). The combined administration significantly enhanced survival compared to either therapy alone (p. 167, 1st full parag.) and tumors treated with the combination therapy showed increased CD8 T cells within the tumor (Fig. 5d).
Thus, before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to have used an immune checkpoint inhibitor, specifically those of claims 14 and 15, as an additional therapeutic agent in combination with an oncolytic virus, specifically reovirus, given the teachings of Rajani and ClinicalTrial.gov because the prior art references teach that the combined therapy is more effective than each therapy alone and the treatment significantly prolonged survival in the cancer patients. Therefore, a posita would have had a reasonable expectation of successfully treating cancer when administering the combination therapy in view of the teachings of the prior art references.
The references differ from the claimed invention in that they do not teach selecting a subject with a T-cell population exhibiting high peripheral clonality after treatment with the one or more doses on the oncolytic virus and administering a subsequent dose of the virus. The references also do not teach the limitations of claims 2-4 and 16.
Kirsch teaches a general overview of immunosequencing technology used to assess the level and distribution of clonal lymphocytes in a sample and to track single or multiple clones of interest over time within a given patient. Immunosequencing is an important analytical tool in the field of immune-oncology including residual disease post therapy in malignancies, prediction of response to immunotherapeutics of tumors containing infiltrating lymphocytes, the identification of clonal responses to vaccination, disease, and responses to certain exposures or interventions (abstract). Kirsch teach that “The adaptive immune system generates a remarkable breadth of diversity in antigen‐specific TCRs and Igs by combinatorial recombination of gene segments in lymphocytes. For example, the TCR is composed of two peptide chains, one encoded by the TCRA or TCRD genes, and the second encoded by the TCRB or TCRG genes, respectively. There are thus two types of T‐cell receptors…that differ both by the TCR heterodimer type and their immune function, with the vast majority of T‐cells carrying an αβ TCR. The existence of multiple V, D and J gene segments at these T‐cell loci permits a large combinatorial diversity in receptor composition; while the non‐templated insertion and/or deletion of nucleotides at the V‐J, V‐D, and D‐J junctions further adds to the potential diversity of receptors that can be encoded. The antigenic specificity of T‐cells is in large part determined by the amino acid sequence of the hypervariable complementarity‐determining region 3 (CDR3) of the T‐cell receptor (which, for most T‐cells, consists of a heterodimer formed by an alpha (A) and a beta (B) chain). Because of the potential diversity of receptors, it is highly improbable to randomly converge on the same TCRA or TCRB nucleotide CDR3 sequence, effectively making each CDR3 sequence a unique tag for a T‐cell clone… Immunosequencing is a multiplex PCR‐based based method that amplifies rearranged CDR3 sequences for a given immune receptor locus, and exploits the capacity of high‐throughput sequencing (HTS) technology to enumerate and quantify hundreds of thousands of CDR3 sequences simultaneously. Thus, the immunosequencing assay captures both specific individual clones as well as the full repertoire. The technology provides a highly accurate and standardized method for assessment of lymphoid clonality in healthy, diseased, or malignant tissues, and for identifying and tracking the presence and frequency of common and rare clones within the total adaptive immune system (section 2). Section 3.1 describes clonality and diversity.
Kirsch teaches “Having identified a particular sequence or sequences of interest through immunosequencing, the behavior of the associated clones can be tracked throughout the body, over time, or in different individuals. For example, a V(D)J sequence that arises in a lymphocyte that subsequently undergoes malignant transformation becomes a unique marker of that leukemia, lymphoma, or myeloma. Quantitative assessment of its frequency in response to therapeutic intervention can be of important prognostic significance to the patient undergoing treatment and the clinical management of that patient… In tumors, identification of the sequence repertoire overlap between the systemic circulation and the tumor‐infiltrating lymphocytic (TIL) population can provide information on the basic immunogenicity of the tumor as well as the likelihood of toxicity or response to an immunotherapeutic drug. ” (section 3.3).
“With the advent of immunotherapy for cancer, over the past five years there has been an increasing focus on the identification of biomarkers that can be used to determine whether lymphoid infiltrates are correlated with prognosis, and whether the quality of those infiltrates can be somehow predictive of tumors that will respond to modulation of the resident tumor infiltrating lymphocyte population. The TCR repertoire from circulating peripheral blood mononuclear cells has been profiled prior to and following administration of an anti‐CTLA4 blocking antibody. In response to this therapeutic intervention, there was a marked increase in both the “richness” (number of unique TCRB sequences) of circulating T‐cells and the diversity of the T‐cell population. The analysis of tumor‐infiltrating lymphocytes in the tumors of patients with melanoma has been an important precedent in the development of the field of immunotherapy. In one notable study biopsies of skin lesions from patients with metastatic melanoma were obtained and subjected to TCRB immunosequencing analysis before treatment with anti‐PD1 blocking monoclonal antibody. Patients whose tumors had the highest number of T‐cells and the more clonal T‐cell repertoire were most likely to respond to this therapy. Conversely, all of those patients whose total T‐cell number and clonality measure fell below the median for each of these parameters had progressive disease. Moreover, biopsies obtained more than three weeks following the initiation of the anti‐PD‐1 therapy showed that patients whose tumors showed significant expansion of pre‐existing T‐cell clones in response to the therapy were most likely to have demonstrated a clinical response (section 4.2).
Samson teaches that oncolytic virus immunotherapy selectively kill tumor cells and promote tumor-directed innate and adaptive immune responses (intro, 1st parag.). Samson teaches that the treatment of tumors with oncolytic reovirus leads to increases in cytotoxic T cell tumor infiltration (compared to patients not treated with the virus) priming the tumor immune microenvironment for immune-mediated therapy within combined with PD-1 blockade (Intro 2nd col., 1st parag.). Tumors treated with reovirus contained increased amounts of tumor-infiltrating cytotoxic T cells (CD8 cells) which are critical for PD-1 immunotherapy (p. 4, whole page, p. 6, last parag.-p. 7, 1st parag., p. 7, last parag. ).
Tumeh teach treating cancer patients with PD-1 immune checkpoint inhibitors, specifically pembrolizumab, and analyzing TCR sequencing using immunosequencing. Tumeh find not only an increase of CD8 cells, but immunosequencing showed uniquely rearranged, variable TCR beta chain regions, reflecting a T-cell population that was less diverse in repertoire and more clonal in nature, significantly correlating with clinical response to pembrolizumab treatment. Further, regarding TCR clonality, responders had more than 10 times as many clones expanded after anti-PD-1 therapy (p. 42nd full parag., p. 7, Next gen. seq. section). Regarding claim 2, Fig. 3d and Fig. 6a shows clonality greater than 0.06.
Thus, before the effective filing date of the claimed invention, the use of immunosequencing as an important analytical tool in the field of immune-oncology to analyze clonality and diversity, track response to cancer treatments including residual disease post therapy in malignancies, predict the of response to immunotherapeutics of tumors was known and disclosed by Kirsch and Tumeh. The references teach that the behavior of associated clones can be tracked throughout the body, over time, or in different individuals and that quantitative assessment of their frequency in response to therapeutic intervention can be of important prognostic significance to the patient undergoing treatment and the clinical management of that patient. Therefore, although the references do not specifically correlate clonality and diversity to oncolytic virus treatment, the tool is used to assess tumors having high numbers of T‐cells and tumor-infiltrating cytotoxic T cells in response to reovirus treatment and the adaptive immune response, as well as PD-1 immune checkpoint inhibitors, and tumors having the highest number of T‐cells and the more clonal T‐cell repertoire were most likely to respond to known cancer treatments including PD-1 immune checkpoint inhibitors. Therefore, given that both reovirus and PD-1 inhibitor treatments lead to increased T-cell infiltration, and an adaptive immune response, which is used for immunosequencing to show uniquely rearranged, variable TCR beta chain regions, reflecting a T-cell population that was less diverse in repertoire and more clonal in nature, and significantly correlating with clinical response to treatment, it would have been obvious to use immunosequencing with the oncolytic virus therapy of WO323 and in combination with the known combined cancer treatments of oncolytic viral treatment with PD-1 immune checkpoint inhibitors or additional therapeutic agents with a reasonable expectation of successfully determining responders as well as survival outcome. The art teaches that high clonality and low diversity significantly correlate with response to treatment and prognosis.
Response to Arguments
Applicant's arguments filed 2/27/2026 have been fully considered but they are not persuasive. Applicants argue that Coffey (WO323) does not teach a therapy where subjects are selected for displaying a T-cell population exhibiting high peripheral clonality after oncolytic virus treatment, but instead teachings first-line treatment comprising administering an oncolytic virus and a chemotherapeutic agent.
Applicant argues that the reference does not teach a subject with a T-cell population exhibiting high peripheral clonality after oncolytic virus treatment. Applicant argues that Coffey, Kirsch and Tumeh, alone or in combination do not teach the claimed invention. Applicants argue that Kirsch and Tumeh are drawn to checkpoint inhibitors as first-line therapy, yet do not contemplate T-cell clonality for selecting a patient for oncolytic virus therapy, nor a relationship between T-cell diversity and oncolytic virus treatment.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant argues that a posita would not have been motivated to apply clonality observations of Kirsch and Tumeh in context of first-line PD-1 blockade to the entirely different immunological context of reovirus therapy and that there is no evidence suggesting that T-cell clonality patterns for PD-1 therapy would arise or have the same significance in reovirus treatment.
Applicants argue that Fig. 8 and parag. (0088-0089) demonstrate a high level of clone turnover following viral treatment, accompanied by clonal expansion which were undetectable prior to treatment, while Tumeh teaches existing clones present at baseline that undergo expansion after treatment, rather than newly arising clones, thus failing to teach the emergence of unique T cell clones following reovirus therapy.
Applicant’s arguments directed at unique T cell clones; i.e. newly arising clones is not commensurate in scope with the claimed invention because as seen above in the 112 rejections, unique T cell clones is not clearly defined or claimed as newly arising clones.
Applicants provide additional studies directed to treatment with reovirus and paclitaxel showing clonal expansion however in contrast, patients treated with paclitaxel alone did not exhibit clonal expansion and thus, the results demonstrate that the clonal expansion is attributable to the oncolytic virus.
First, it should be noted that paclitaxel is neither a checkpoint inhibitor or aromatase inhibitor according to claims 13-15. The rejection is based upon teachings in the art which demonstrate that reovirus is an oncolytic virus which has antitumor activity directly associated with innate and adaptive immune responses and a priming against tumor associated antigens. Reovirus administration to tumors with immune checkpoint inhibitors significantly enhanced survival , improved the ability of NK cells to kill reovirus infected tumor cells and increased adaptive CD8+ T-cell-dependent antitumor T cell response. Reovirus activates innate and adaptive antitumor immune effector cells and their combination with a checkpoint inhibitor boost developing T-cells responses against the tumor (See Rajani Intro. whole 1st page). Thus, reovirus (and checkpoint inhibitor) administration activates the adaptive immune response. Kirsch teach that “The adaptive immune system generates a remarkable breadth of diversity in antigen‐specific TCRs and Igs by combinatorial recombination of gene segments in lymphocytes. Quantitative assessment of its frequency in response to therapeutic intervention can be of important prognostic significance to the patient undergoing treatment and the clinical management of that patient… In tumors, identification of the sequence repertoire overlap between the systemic circulation and the tumor‐infiltrating lymphocytic (TIL) population can provide information on the basic immunogenicity of the tumor as well as the likelihood of toxicity or response to an immunotherapeutic drug(section 3.3). With the advent of immunotherapy for cancer, over the past five years there has been an increasing focus on the identification of biomarkers that can be used to determine whether lymphoid infiltrates are correlated with prognosis, and whether the quality of those infiltrates can be somehow predictive of tumors that will respond to modulation of the resident tumor infiltrating lymphocyte population. The TCR repertoire from circulating peripheral blood mononuclear cells has been profiled prior to and following administration of an anti‐CTLA4 blocking antibody. In response to this therapeutic intervention, there was a marked increase in both the “richness” (number of unique TCRB sequences) of circulating T‐cells and the diversity of the T‐cell population. Patients whose tumors had the highest number of T‐cells and the more clonal T‐cell repertoire were most likely to respond to this therapy. Conversely, all of those patients whose total T‐cell number and clonality measure fell below the median for each of these parameters had progressive disease. Moreover, biopsies obtained more than three weeks following the initiation of the anti‐PD‐1 therapy showed that patients whose tumors showed significant expansion of pre‐existing T‐cell clones in response to the therapy were most likely to have demonstrated a clinical response (section 4.2)”. See also Tumeh who teach treating cancer patients with PD-1 immune checkpoint inhibitors, specifically pembrolizumab, and analyzing TCR sequencing using immunosequencing. Tumeh find not only an increase of CD8 cells, but immunosequencing showed uniquely rearranged, variable TCR beta chain regions, reflecting a T-cell population that was less diverse in repertoire and more clonal in nature, significantly correlating with clinical response to pembrolizumab treatment. Further, regarding TCR clonality, responders had more than 10 times as many clones expanded after anti-PD-1 therapy (p. 42nd full parag., p. 7, Next gen. seq. section). Regarding claim 2, Fig. 3d and Fig. 6a shows clonality greater than 0.06.
Thus, it is the Examiners position that the references teach that the behavior of associated clones can be tracked throughout the body, over time, or in different individuals and that quantitative assessment of their frequency in response to therapeutic intervention can be of important prognostic significance to the patient undergoing treatment and the clinical management of that patient. Although the references do not specifically correlate clonality and diversity to oncolytic virus treatment, the tool is used to assess tumors having high numbers of T‐cells and tumor-infiltrating cytotoxic T cells in response to reovirus treatment and the adaptive immune response, as well as PD-1 immune checkpoint inhibitors, and tumors having the highest number of T‐cells and the more clonal T‐cell repertoire were most likely to respond to known cancer treatments including PD-1 immune checkpoint inhibitors. Therefore, given that both reovirus and PD-1 inhibitor treatments lead to increased T-cell infiltration, and an adaptive immune response, which is used for immunosequencing to show uniquely rearranged, variable TCR beta chain regions, reflecting a T-cell population that was less diverse in repertoire and more clonal in nature, and significantly correlating with clinical response to treatment, it would have been obvious to use immunosequencing with the oncolytic virus therapy of WO323 and in combination with the known combined cancer treatments of oncolytic viral treatment with PD-1 immune checkpoint inhibitors or additional therapeutic agents with a reasonable expectation of successfully determining responders as well as survival outcome. The art teaches that high clonality and low diversity significantly correlate with response to treatment and prognosis.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIFFANY MAUREEN GOUGH whose telephone number is (571)272-0697. The examiner can normally be reached M-Thu 8-5.
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, Melenie Gordon can be reached at 571-272-8037. 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.
/TIFFANY M GOUGH/ Examiner, Art Unit 1651
/MELENIE L GORDON/Supervisory Patent Examiner, Art Unit 1651