DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. 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
2. Applicant’s election of Group I in the reply filed on Dec. 19, 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Applicant’s election without traverse of Group I in the reply filed on Dec. 19, 2025 is acknowledged.
Information Disclosure Statement
3. The information disclosure statement (IDS) submitted on April 26, 2023 was filed. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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.
4. Claim 1 is 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. Claim 1 recites the limitation "the respiratory capacity" in the claim. There is insufficient antecedent basis for this limitation in the claim.
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.
5. Claims 1, 4-5, 7, 10, 12, 16, 21, 24-25 and 27-28 are rejected under 35 U.S.C. 102(a)(1) and/or 102(a)(2) as being anticipated by Bedoya et al., (WO2017015427 published July 2017; priority to July 2015).
The claims are drawn to a method for manufacturing immune effector cells, comprising: (a) activating a population of immune effector cells; (b) transducing the immune effector cells with a vector comprising a polynucleotide encoding an engineered antigen receptor, and (c) culturing the transduced immune effector cells to proliferate;
wherein any one or more of steps (a)-(c) is performed in the presence of one or more metabolic enhancers selected from the group consisting of: pyruvate dehydrogenase kinase 1 (PDHK1) inhibitors, pyruvate dehydrogenase phosphatase (PDP) activators, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) polypeptides or variants thereof, and PGC1α agonists; and wherein the respiratory capacity of the transduced immune effector cells is increased by at least 10% relative to transduced T cells cultured in the absence of the one or more of the metabolic enhancers.
Bedoya et al., disclose a method for manufacturing immune effector cells [See abstract; page78, lines10-13]. The method comprises: (a) activating a population of immune effector cells [page 37, lines 24-29]; b) transducing the immune effector cells with a vector comprising a polynucleotide encoding an engineered antigen receptor which is transduced with a viral vector encoding a CAR [page 37, lines12-18 and page 38, lines 28-32]; and c) culturing the transduced immune effector cells for proliferation [page 6, lines 12-21; page 40, lines 19-21; page 48, line 29 and page 49, line 3]. The cell from the population of immune effector cells, is transduced with a vector within one day after population of immune effector cells are obtained from a blood sample from a subject [para 68]. Bedoya et al., describe immune effector cells transduced with a nucleic acid encoding a CAR, are expanded in culture for a period of several hours.
In certain contexts, including hypoxia, PDK1 inhibits the decarboxylation of pyruvate and entry of glucose derivatives into the tricarboxylic acid (TCA) cycle . PDK1 are induced to significantly higher levels in 28z cells relative to BBz cells at day 7 (Figure 34E). Increased expression levels of PDK1, coupled with the earlier finding of increased ECAR, is consistent with enhanced glycolysis in CAR T cells in comparison to their BBz counterparts. Bedoya et al., disclose inclusion of 4-1BB, a member of the TNF receptor family in the CAR architecture, promotes the outgrowth of CD8 central memory T cells that had significantly enhanced respiratory capacity, increased fatty acid oxidation and enhanced mitochondrial biogenesis [para 1019]. The PDK1 are induced to significantly higher levels in 28z cells relative to BBz cells at day 7 (FIG. 34E). Increased expression levels of Glut1 and PDK1, coupled with the earlier finding of increased ECAR, is consistent with enhanced glycolysis in 28z CAR T cells in comparison to their BBz counterparts [para 1019]. Two important enzymes involved in the breakdown of glucose during the ATP-generating step of the glycolytic pathway are phosphoglycerate kinase (PGK) and glucose-6-phosphate dehydrogenase (G6PD). PGK transfers a phosphate group to ADP in order to facilitate ATP generation, whereas G6PD, an NADP+-dependent enzyme, catalyzes the oxidative phase of the pentose phosphate pathway (PPP). Given that these enzymes have an important role in glycolysis, their expression levels in CAR T cells were investigated on Day 7. Their levels were elevated in 28z CAR T cells [para 1020].
FIG. 13 are graphs depicting cytotoxicity as a percent lysis of CD19 expressing K562 cells treated with PMBCs that have been stimulated with anti-CD3 and CD28 beads, and left either unmanipulated (UTD) or transduced with a CD19 CAR (CD19.BBz), de-beaded, and then harvested at Day 5 and D9 [para 199]. Thus teaching claims 4, 10 and 17. The CAR-expressing cell described herein may be used in a treatment regimen in combination with a kinase inhibitor, e.g., a CDK4 inhibitor, a BTK inhibitor, an MNK inhibitor, an mTOR inhibitor, an ITK inhibitor, etc. In one embodiment, the subject is a complete responder, and the subject is administered a treatment regimen that includes administration of a CAR-expressing cell described herein in combination with a kinase inhibitor, e.g., a kinase inhibitor described herein, e.g., at a dose or dosing schedule [para 890]. Cytokines have important functions related to T cell expansion, differentiation, survival and homeostasis. One of the most important cytokine families for clinical use is the common γ-chain (γc) family cytokines, which includes interleukin (IL)-2. The administration of IL-2 is limited by side effects and a propensity for expansion of regulatory T cells and the effect of activated induced cell death (AICD) [para 910]. In one embodiment, the CAR expressing immune effector cells and the ligand (e.g., antigen) coated beads are present and the reaction mixture further comprises one or more factors for enhancing proliferation and/or viability, including serum, e.g., one, two, three, four, five or more of: interleukin-2 (IL-2), insulin or any other additives for the growth of cells [para 75-76]. Thus teaching claim 16. Inclusion of 4-1BB, a member of the TNF receptor family in the CAR architecture, promotes the outgrowth of CD8 central memory T cells that had significantly enhanced respiratory capacity, increased fatty acid oxidation and enhanced mitochondrial biogenesis. In contrast, CAR T cells with CD28 domains yielded effector memory cells with a genetic signature consistent with enhanced glycolysis. These results provide, at least in part, a mechanistic insight into the differential persistence of CAR-T cells expressing 4-1BB or CD28 signaling domains in clinical trials and inform the design of future CAR T cell therapies [para 970]. Adoptive immunotherapy based on the infusion of genetically redirected autologous T cells has demonstrated promise for the treatment of both hematologic malignancies and solid tumors. Accordingly, multiple gain-of-function strategies to endow T cells with desired antigen receptors, based on either T cell receptors (TCRs) or chimeric antigen receptors (CARs) have been described [para 971]. Example 6. Basal OCR levels, basal OCR/ECAR ratio, maximum respiratory levels (FIG. 34F), and basal ECAR levels measured at Day 7 and Day 21 [para 220].
Therefore, Bedoya et al., anticipate the rejected claims.
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.
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.
6. Claims 1, 4-5, 7, 10, 12, 16-17, 21, 24-25 and 27-28 are rejected under 35 U.S.C. 103 as being unpatentable over Bedoya et al., (WO2017015427 published July 2017; priority to July 2015) in view of Delgoffe (WO 2017223557 published 2017-12-28; priority to June 24, 2016).
Bedoya et al., has been discussed as teaching a method for manufacturing immune effector cells, comprising: (a) activating a population of immune effector cells;
(b) transducing the immune effector cells with a vector comprising a polynucleotide encoding an engineered antigen receptor, and (c) culturing the transduced immune effector cells to proliferate; wherein any one or more of steps (a)-(c) is performed in the presence of one or more metabolic enhancers selected from the group consisting of: pyruvate dehydrogenase kinase 1 (PDHK1) inhibitors, pyruvate dehydrogenase phosphatase (PDP) activators, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) polypeptides or variants thereof, and PGC1α agonists; and
wherein the respiratory capacity of the transduced immune effector cells is increased by at least 10% relative to transduced T cells cultured in the absence of the one or more of the metabolic enhancers. However Bedoya et al., does not teach the PGC1α polypeptide or variant thereof.
Delgoffe teach recombinant T cells that include a vector encoding one or more of peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1-alpha (PGC1α). Such recombinant T cells can also include a chimeric antigen receptor (CAR) or a recombinant T cell receptor (TCR). Also provided are kits and compositions that can be used with such methods [abstract]. Delgoffe provides recombinant T cells containing a vector that encodes one or more of peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1-alpha (PGC1α), mitochondrial transcription factor A (Tfam), GA binding protein transcription factor alpha subunit GABPA), and estrogen-related receptor alpha (ERRα ). Expression of the vector in the T cell results in increased expression of one or more of these genes, and thus increased activity of these proteins. In some examples, the PGC1α, Tfam, GABPA, and/or ERRα expressed from the vector is a variant sequence that encodes a protein that is resistant to negative regulation [para 9]. Such methods can include introducing the vector encoding one or more of PGC1α, Tfam, GABPA, and ERRα (which may also encode a CAR or TCR), into a T cell, thereby generating the recombinant T cell. In some examples, a separate vector encoding a CAR or TCR is introduced into the T cell, thereby generating the recombinant T cell. Such methods can further include culturing or growing the transformed recombinant T cells under conditions that permit expression of one or more of PGC1α, Tfam, GABPA, and ERRα (and in some examples also a CAR or TCR). In some examples, the recombinant T cells are incubated or culture in the presence of interleukin 2 (IL-2). In some examples, the recombinant T cells are cultured for a period of days or weeks (such as at least 1 week, at least 2 weeks, at least 3 weeks, at least 4 weeks, or at least 6 weeks). In some examples, the method includes monitoring the recombinant T cells, for example determining the number of cells, determining or measuring the mitochondrial activity and/or mass of the recombinant T cells, and/or determining or measuring expression of one or more of PGC1α, PD-1, PGC1α, CAR, and TCR [para 12]. Chimeric antigen receptor (CAR): Artificial, engineered T cell receptors, which graft an arbitrary specificity onto an immune effector cell. Typically, these receptors are used to graft the specificity of a monoclonal antibody onto a T cell; with transfer of their coding sequence facilitated by vectors. Using adoptive cell transfer, CARs can be useful. For example, T cells (obtained from the patient or from a donor) are modified so that they express receptors [para 40]. An exogenous gene supplied by a vector. In one example, a transgene includes one or more PGC1α, coding sequences, for example in combination with a CAR or TCR coding sequence [para 69]. Example 1 describe mononuclear cells were recovered and immediately used for experiments, Human PBMC Isolation from Peripheral Blood [para 153-154]. The composition or kits include recombinant T cells and/or vectors disclosed herein, for example in combination with a pharmaceutically acceptable carrier. In one example, the kit, further includes one or more of a transfection reagent, culture medium, antibiotic, IL2, IL15, IL7, anti-CD3, and anti-CD28 (e.g., anti-CD3/anti-CD28 stimulatory beads) [para 14]. Thus teaching claims 27-28.
Therefore, it would have been prima facie obvious at the time of applicants’ invention to apply PGC1α polypeptide or variant thereof as taught by Delgoffe et al.,
to Bedoya’s method for manufacturing immune effector cells, comprising an activation step; transducing step and culturing step performed in the presence of one or more metabolic enhancers selected from the group consisting of: pyruvate dehydrogenase kinase 1 (PDHK1) inhibitors, pyruvate dehydrogenase phosphatase (PDP) activators, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) polypeptides or variants thereof, and PGC1α agonists; further comprising the PGC1α polypeptide or variant thereof in order to provide a vector that encodes peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) which permits expression resulting in general increases in mitochondrial function. One of ordinary skill in the art would have a reasonable expectation of success by incorporating PGC1α t produce beneficial desired therapeutic results. Furthermore, no more than routine skill would have been required to incorporate the PGC1α of Delgoffe et al., when Bedoya et al., teach promoting the outgrowth of CD8 central memory T cells which significantly enhanced respiratory capacity, increased fatty acid oxidation and enhanced mitochondrial biogenesis.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses combining prior art elements according to known methods to yield predictable results, thus the combination is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "The combination of familiar element according to known methods is likely to be obvious when it does no more than yield predictable results". It is well known to take a method of manufacture, where there is no change in the respective function of the components and the steps are well known, thus the combination would have yielded a reasonable expectation of success along with predictable results to one of ordinary skill in the art at the time of the invention. Therefore, it would have been obvious to a person of ordinary skill in the art to combine prior art elements according to known methods that is ready for improvement to yield predictable results. The claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Claim Rejections - 35 USC § 103
7. Claims 13 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Bedoya et al., (WO2017015427 published July 2017; priority to July 2015) and Delgoffe (WO 2017223557 published 2017-12-28) as applied to claims 1, 4-5, 7, 10, 12, 16-17, 21, 24-25 and 27-28 above, and further in view of Menk et al., (Cell Rep. 22(6): 1509-1521. 2018).
Bedoya et al., has been discussed as teaching a method for manufacturing immune effector cells, comprising: (a) activating a population of immune effector cells;
(b) transducing the immune effector cells with a vector comprising a polynucleotide encoding an engineered antigen receptor, and (c) culturing the transduced immune effector cells to proliferate; wherein any one or more of steps (a)-(c) is performed in the presence of one or more metabolic enhancers selected from the group consisting of: pyruvate dehydrogenase kinase 1 (PDHK1) inhibitors, pyruvate dehydrogenase phosphatase (PDP) activators, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) polypeptides or variants thereof, and PGC1α agonists; and
wherein the respiratory capacity of the transduced immune effector cells is increased by at least 10% relative to transduced T cells cultured in the absence of the one or more of the metabolic enhancers. Delgoffe et al., teach performing one or more of steps (a)-(c) further comprising transducing the immune effector cells with a vector comprising a polynucleotide encoding an engineered antigen receptor and a polynucleotide encoding a biologically active PGC1α polypeptide fragment selected from the group consisting of amino acids 1-270 of PGC1α, amino acids 1-290 of PGC1α, no more than about the first (N-terminal) 270 amino acids of PGC1α, or no more than about the first (N-terminal) 290 amino acids. Variants of a native PGC1α, Tfam, GABPA, or ERRα protein or coding sequences (such as a protein (or coding sequence thereof) with increased resistance to negative regulation) are typically characterized by possession of at least about 80%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity counted over the full length alignment with the amino acid sequence using the NCBI Blast 2.0, gapped blastp set to default parameters. For comparisons of amino acid sequences of greater than about 30 amino acids, the Blast 2 sequences function is employed using the default BLOSUM62 matrix set to default parameters, (gap existence cost of 11, and a per residue gap cost of 1). When aligning short peptides (fewer than around 30 amino acids), the alignment should be performed using the Blast 2 sequences function, employing the PAM30 matrix set to default parameters (open gap 9, extension gap 1 penalties) [para 61]. Such variant peptides are produced by manipulating the nucleotide sequence encoding a peptide using standard procedures such as site-directed mutagenesis or PCR. Such variants can also be chemically synthesized [para 92].
However neither Bedoya et al., nor Delgoffe et al., teach the PDHK1 inhibitors comprise dichloroacetic acid (DCA).
Menk et al., teach to fulfill bioenergetic demands of activation, T cells perform aerobic glycolysis, a process common to highly proliferative cells in which glucose is fermented into lactate rather than oxidized in mitochondria [abstract]. Menk et al., show T cell activation rapidly induces glycolysis independent of transcription, translation, CD28, and Akt and not involving increased glucose uptake or activity of glycolytic enzymes. Rather, TCR signaling promotes activation of pyruvate dehydrogenase kinase 1 (PDHK1), inhibiting mitochondrial import of pyruvate and facilitating breakdown into lactate. Inhibition of PDHK1 reveals this switch is required acutely for cytokine synthesis but dispensable for cytotoxicity [abstract]. Using both naive and previously activated, rested (PA-R) CD4+ and CD8+ T cells, T cells were activated for 6 hr in vitro with plate-bound anti-CD3 and anti-CD28, and oxidative metabolism were measured. Consistent with previous findings, PA-R and naive T cells switch metabolic states within 6 hr of activation [results]. A prominent form of pyruvate dehydrogenase (PDH) regulation is modification by phosphorylation by the glycolytic gatekeeper pyruvate dehydrogenase kinase 1 resulting in inhibition of PDH function, blocking pyruvate flow into mitochondria, and facilitating lactic acid conversion. Tyrosine phosphorylation of PDHK1 was rapidly induced upon TCR ligation and in a CD28-independent manner in T cells (Figure 3C; Figure S2C). Menk et al., employed dichloroacetate (DCA), a specific inhibitor of PDHK1, to block activity of PDHK1 in the presence of TCR signals. Inhibition of PDHK1 with DCA prevented the initiation of glycolysis in PA-R T cells, shown both using Seahorse ECAR and direct lactate measurements (Figures 3D and 3E). The activity of PDHK1, read out by its phosphorylation of PDH, was also increased upon T cell activation and inhibited by DCA treatment (Figure S2D). Furthermore, DCA treatment of T cells already undergoing rapid activation-induced glycolysis reduced ECAR to preactivation levels (Figure 3F). [Rapid Activation-Induced Glycolysis Is Mediated by PDHK1 in a Manner Independent of Transcription, Translation, and Glucose Flux].
Consistent with these reports, at high doses, DCA-mediated PDHK1 inhibition had effects on proliferation after 96 hr (Figure S4A). Because this pathway is induced minutes after activation, its major importance may be to support the early-immediate, rapid effector function of T cells competent to produce cytokines. DCA treatment also inhibited cytokine production in overnight activation, suggesting that although this switch is induced quickly upon activation, it is used later into the activation phase to facilitate cytokine synthesis and secretion (Figure 5C). PDHK1 inhibition by DCA was not toxic to the cells (Figure S4C). [Rapid Activation-Induced Glycolysis Regulates Distinct Acute Effector Functions].
Therefore, it would have been prima facie obvious at the time of applicants’ invention to apply DCA as taught by Menk et al., to Bedoya and Delgoffe’s method for manufacturing immune effector cells in order to provide a PDHK1 inhibitor which rapidly caused rapid effector function of T cells competent to produce cytokines and facilitate cytokine synthesis and secretion. One of ordinary skill in the art would have a reasonable expectation of success by employing DCA to block activity of PDHK1 in the presence of TCR signals. Furthermore, no more than routine skill would have been required to incorporate the DCA and PDHK1 inhibition was not toxic to the cells and employees reversible inhibition of aerobic glycolysis via DCA and DCA allowed for maximal respiratory values.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses combining prior art elements according to known methods to yield predictable results, thus the combination is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "The combination of familiar element according to known methods is likely to be obvious when it does no more than yield predictable results". It is well known to take a method of manufacture, where there is no change in the respective function of the components and the steps are well known, thus the combination would have yielded a reasonable expectation of success along with predictable results to one of ordinary skill in the art at the time of the invention. Therefore, it would have been obvious to a person of ordinary skill in the art to combine prior art elements according to known methods that is ready for improvement to yield predictable results. The claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Pertinent Art
8. The prior art made of record and not relied upon is considered pertinent to applicant’s disclosure: WO2019084234 teach chimeric receptor that targets CD33 and allows activation of the co-stimulatory pathway without binding the natural ligand. The application also relates to polynucleotides that encode the chimeric receptor, vectors, and host cells comprising the chimeric receptor. The application also relates to methods for preparing host cells comprising a chimeric antigen receptor in order to improve the in vivo persistence of the chimeric antigen receptor host cells.
WO2019084288 teach methods of making CAR-expressing immune effector cells (e.g., T cells, or NK cells), and compositions and reaction mixtures comprising the same. The disclosure further provides methods of using said CAR-expressing immune effector cells.
WO2019178421 teach methods and compositions related to the modification of immune effector cells to increase therapeutic efficacy. In some embodiments, immune effector cells modified to reduce expression of one or more endogenous target genes, or to reduce one or more functions of an endogenous protein to enhance effector functions of the immune cells are provided. In some embodiments, immune effector cells further modified by introduction of transgenes conferring antigen specificity, such as exogenous T cell receptors (TCRs) or chimeric antigen receptors (CARs) are provided.
Michelakis ED, Webster L, Mackey JR. Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer. Br. J. Cancer. 2008;99:989–994.
Dichloroacetate and cancer: new home for an orphan drug? Biochim. Biophys. Acta. 2014;1846:617–629.
Conclusion
9. No claims allowed.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JA-NA A HINES whose telephone number is (571)272-0859. The examiner can normally be reached Monday thru Thursday.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor Dan Kolker, can be reached on 571-272-3181. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JANA A HINES/Primary Examiner, Art Unit 1645