DETAILED CORRESPONDENCE
Status of the Application
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 06/23/2025 has been entered.
Claims 1-2, 4-5, 8-19, 22, and 26 are pending in this application.
Applicant’s amendment to the claims filed 06/23/2025 is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Applicant’s amendment to the specification filed 06/23/2025 is acknowledged.
Applicant’s remarks filed on 06/23/2025 in response to the final rejection mailed on 03/21/2025 is acknowledged and has been fully considered.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Election
The elected subject matter is
Group I, corresponding to claims 1-2, 4-5, 8-13, 22 and 26, drawn to the technical feature of a method of cell culture comprising (i) providing cells in a cell culture medium to start a cell culture process, wherein the cells are modified to reduce the level of synthesis of growth or productivity inhibitors by the cell, wherein the inhibitors are formate or glycerol,
elected without traverse in the reply filed 07/23/2024.
New claim 26 is drawn to the method of claim 2, and is therefore considered part of the elected invention of Group I set forth above.
Claims 14-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 1-2, 4-5, 8-13, 22 and 26 are being examined on the merits.
Objections to Specification
The objection to the specification are withdrawn in view of the amendments to address the typo in the trademark SMIPTM.
Claim Rejections - 35 USC § 112(b)
Claims 2, 4-5, 8-9, 12-13 and 26 are newly ejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 2 (claims 4-5, 8-9, 12-13 and 26 dependent therefrom) is indefinite for the recitation of “The method of claim 1, wherein the one or more inhibitors is formate and wherein the one or more genes is SHMT2”. As amended, claim 1 limits the one or more genes to PGP and limits the inhibitor to glycerol, thus excluding formate as the inhibitor and SHMT2 as the one or more genes as recited in claim 2 and rendering the scope of claims 1 and 2 unclear to one of skill in the art. It is suggested that applicant clarify the meaning of claim 2.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 2, 4-5, 8-9, 12-13 and 26 are rejected under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, and for failing to include all the limitations of the claim upon which it depends. As amended, claim 1 limits the one or more genes to PGP and limits the inhibitor to glycerol, thus excluding formate as the inhibitor and SHMT2 as the one or more genes as recited in claim 2. As such, claim 2 (claims 4-5, 8-9, 12-13 and 26 dependent therefrom) fails to further limit claim 1 and additionally does not include all of the limitations of the claim upon which it depends. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
The rejection of claims 1-2, 4-5, 8-13 and 22 under 35 U.S.C. 103 as being unpatentable over Pfizer in view of Perry et al. (Arch Biochem Biophys, 2007, 462:21; cited on the IDS submitted 06/02/2021; herein referred to as Perry), and
the rejection of claim 3 under 35 U.S.C. 103 as being unpatentable over Pfizer and Perry, and further in view of Possik et al. (Biochimie, 2017, 143:18; cited on the Form PTO-892 mailed 03/21/2025; herein referred to as Possik),
are withdrawn in view of the amendment to claim 1 to recite “wherein the one or more genes is phosphoglycolate phosphatase (PGP), and wherein the one or more inhibitors is glycerol”.
Claims 1, 10-11 and 22 are newly rejected under 35 U.S.C. 103 as being unpatentable over Pfizer in view of Possik.
As amended, claim 1 is drawn to a method of cell culture comprising (i) providing CHO cells in a cell culture medium to start a cell culture process, wherein expression of one or more genes is modified in the cells to reduce a level of synthesis of one or more growth or productivity inhibitors by the cells as compared to a level of synthesis of one or more growth or productivity inhibitors by corresponding unmodified cells,
wherein the one or more genes is phosphoglycolate phosphatase (PGP), and
wherein the one or more inhibitors is glycerol.
Pfizer discusses cells and methods of cell culture [title].
Regarding claim 1, Pfizer discloses a method of cell culture where cells are modified to reduce the level of synthesis of growth and/or productivity of inhibitors by the cell [abstract], wherein the expression of one or more genes is modified to reduce the level of synthesis of cell growth and/or productivity inhibitors [claim 2] in CHO cells [claim 63].
Pfizer additionally discloses a scenario where proteins are increasingly important diagnostic and therapeutic agents, commonly produced commercially in cell culture wherein the cells have been engineered to produce unusually high levels of a protein of interest, and therefore discloses the importance of optimizing culture conditions to address inefficient mammalian cell metabolism that normally results in the consumption of nutrients for the production of byproducts that accumulate over the course of the culture in order to facilitate the successful production of target proteins [p 1, ln 15-24]. Therefore Pfizer indicates the importance of reducing byproduct formation that can inhibit or contend with target protein production in mammalian cell culture.
Pfizer does not teach the limitations regarding modifying expression of PGP to reduce a level of synthesis of glycerol.
Possik relates to glycerol-3-phosphate phosphatase and PGP and their roles in intermediary metabolism [title], and discloses a previously unknown mammalian enzyme phosphoglycolate phosphatase (PGP) can function as a glycerol-3-phosphate (Gro3P) phosphatase (G3PP) to regulate metabolite levels [abstract].
Regarding claim 1, Possik discloses that Gro3P can be formed from DHAP and taken away from glycolysis through the “Gro3P shuttle”, where it is further dephosphorylated by G3PP activity to form glycerol [Figure 1]. As Possik discloses that PGP also acts as a G3PP enzyme, PGP is indicated to influence the production of glycerol that is inversely tied to glycolysis, since the originating DHAP molecule is shunted to the glycerol pathway at the expense of its progression through glycolysis. Possik further discloses that removal of G3PP activity in rat cells resulted in increased O2 consumption and ATP production, but the overexpression of proteins with G3PP activity had the reverse effect [p 21, col 1, para 3], indicating that lower G3PP activity reduces glycerol production while increasing activity through the glycolytic pathway based on the pathway displayed in [Figure 1].
In view of Pfizer and Possik, one of ordinary skill in the art would have recognized that lowering the expression of PGP would thereby lower the production of glycerol and instead shift metabolism towards O2 consumption and ATP production, which is interpreted to correspond to increased growth and activity, and would have been motivated to do so as Pfizer discloses the importance of reducing the consumption of nutrients used for production of byproducts in order to facilitate the successful production of target molecules.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine Pfizer and Possik to modify the method of Pfizer by lowering expression of PGP to reduce the accumulation of glycerol, as taught by Possik, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the method of Pfizer by lowering PGP expression because Pfizer teaches the importance of reducing the consumption of nutrients used for production of byproducts in order to facilitate the successful production of target molecules, and Possik teaches lowering the expression of PGP lowers the production of glycerol and shifts metabolism towards O2 consumption and ATP production. One of ordinary skill in the art would have had a reasonable expectation of success because Pfizer relates to methods of optimizing metabolism in cells through regulating metabolite levels, and Possik relates to the enzyme PGP and its ability to regulate metabolite levels.
Regarding claim 10, Pfizer discloses the use of a pH sensor to monitor pH of the cell culture, and in response to a rise above a predetermined pH value, glucose is fed to the cell culture [claim 27].
Regarding claim 11, Pfizer discloses the cell culture is a fed batch culture [claim 28].
Regarding claim 22, Pfizer discloses the method wherein cell growth and/or productivity are increased as compared to a control culture, said control culture being identical except comprises unmodified cells [claim 66].
Therefore, the invention of claims 1, 10-11 and 22 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claims 2, 4-5, 8-9, 12-13 and 26 are newly rejected under 35 U.S.C. 103 as being unpatentable over Pfizer in view of Possik as applied to claims 1, 10-11 and 22 above, and further in view of Perry.
Claim 2 is drawn to the method of claim 1, wherein the one or more inhibitors is formate and wherein the one or more genes is SHMT2.
SHMT2 is referred to in the specification as mitochondrial serine hydroxymethyltransferase [p 2].
In view of the rejection of claim 2 and its dependents under 35 USC 112(d) as not further limiting claim 1 as well as not reciting all of the limitations of claim 1, and in view of the indefiniteness under 35 USC 112(b) of claim 2 and its dependents as set forth above, for the sake of compact prosecution, claim 2 is being examined with the interpretation that it is drawn to the method steps of claim 1 but instead replaces the one or more genes of PGP with SHMT2, and replaces the one or more inhibitor of glycerol with formate.
The teachings of Pfizer and Possik as applied to claims 1, 10-11 and 22 are discussed above. Additionally, Pfizer discloses a method of cell culture where cells are modified to reduce the level of synthesis of growth and/or productivity of inhibitors by the cell [abstract], wherein the expression of one or more genes is modified to reduce the level of synthesis of cell growth and/or productivity inhibitors [claim 2] in CHO cells [claim 63], wherein the modified gene encodes an enzyme that catalyzes the synthesis of formate [claim 4] which inhibits the growth of cells [p 8, ln 17-23].
These references do not teach the one or more genes is SHMT2.
Perry discusses the effect of vitamin B6 availability on serine hydroxymethyltransferase (SHMT) in MCF-7 cells [title], and discloses that formate is a major source of one-carbon units for cytoplasmic one-carbon metabolism that is generated in the mitochondria from serine [p 21, col 2, para 2].
Regarding claim 2, Perry teaches the modification of MCF-7 cells to generate PLP-deficient cells to reduce the expression and activity of serinehydroxymethyltransferase [p 24, col 1, para 3, p 22, col 1, final paragraph, and Figure 2b], and that serinehydroxymethyltransferase is responsible for the conversion of serine to formate [Figure 1]. As such, one of skill in the art would have reasoned that the modification of a cell to reduce the expression of SHMT would result in reduced production of formate as well.
In view of Perry, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of Pfizer and Possik by reducing the expression of SHMT, as taught by Perry, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the combined method of Pfizer and Possik because Pfizer teaches a method of modifying the expression of genes that produce formate which inhibits the growth of cells, and Perry indicates that reduction of SHMT expression will reduce the production of formate from serine. One of ordinary skill in the art would have had a reasonable expectation of success because both Pfizer and Perry discuss methods that regulate production of the metabolite formate.
Regarding claim 4, Pfizer teaches the modification of genes to decreases gene expression to reduce the level of synthesis of growth and/or productivity inhibitors by the cell [claim 58] for use in a method to reduce the level of inhibitory metabolites that include formate [abstract and p 8, ln 17-23], and Perry teaches that serinehydroxymethyltransferase is responsible for the conversion of serine to formate [Figure 1]. Therefore one of skill in the art would be motivated to modify the gene encoding SHMT to reduce the production of formate.
Regarding claim 5, Pfizer discloses maintaining formate at a specific concentration below a reference concentration [claim 13], which is below 2 mM [claim 14].
Regarding claim 8, Pfizer discloses measuring the concentration of formate and when that measured concentration is above a predefined value, that concentration is decreased by reducing the amount of precursor provided to the cells [claim 15], wherein the predefined value of formate is disclosed as 2 mM [claim 14].
Regarding claim 9, Pfizer discloses measuring the concentration by NMR, HPLC or UPLC [claim 16].
Regarding claim 12, Pfizer discloses the method comprises a growth phase and a production phase and step (ii) is applied during the growth phase, wherein step (ii) comprises a step of measuring a concentration of formate [claim 29].
Regarding claim 13, Pfizer discloses modifying the expression of one or more genes comprises gene deletion, disruption, substitution, point mutation, multiple point mutation, insertion mutation or frameshift mutation of the gene, or introduction of one or more nucleic acids comprising the one or more genes into the cell, optionally as an expressible construct or expressible vector construct [claim 40].
Regarding claim 26, Pfizer discloses the method wherein cell growth and/or productivity are increased as compared to a control culture, said control culture being identical except comprises unmodified cells [claim 66].
Therefore, the invention of claims 2, 4-5, 8-9, 12-13 and 26 would have been obvious to one of ordinary skill in the art before the effective filing date.
Response to remarks: beginning p 7 of Applicant’s response to rejections under 35 USC 103; Applicant in summary contends Pfizer does not teach PGP, SHMT2, or glycerol as a growth or productivity inhibitory, which is not remedied by Perry, and thus the amended claim 1 is not obvious over the combination of Pfizer and Perry; Applicant further contends there is no reasonable expectation from Possik that modifying the PGP gene would result in decreased glycerol, and the teachings of Possik regarding the G3PP activity of rat cells are not relevant to the recited method of reducing inhibitor synthesis in CHO cells; Applicant further contends Possik does not teach or suggest how or why one would modify the PGP gene in CHO cells to reduce the level of synthesis of glycerol, and thus one of skill in the art would not modify the PGP gene to reduce glycerol synthesis as PGP plays a role in four different critical metabolic pathways.
Applicant’s remarks are considered and found not convincing.
As stated in the rejection above, Pfizer teaches a method of culturing CHO cells modified to reduce the level of synthesis of growth and/or productivity of inhibitors by the cell comprising modifying the expression of one or more genes to reduce the level of synthesis of cell growth and/or productivity inhibitors. Pfizer additionally discusses the importance of proteins as diagnostic and therapeutic agents, commonly produced commercially in cell culture wherein the cells have been engineered to produce unusually high levels of a protein of interest, and therefore discloses the importance of optimizing culture conditions to address inefficient mammalian cell metabolism that normally results in the consumption of nutrients for the production of byproducts that accumulate over the course of the culture in order to facilitate the successful production of target proteins. Therefore Pfizer indicates the importance of reducing byproduct formation that can inhibit or contend with target protein production in mammalian cell culture. Possik discloses the function of PGP, and connects that function to glycerol synthesis in mammalian animals (rats), wherein lowering of said activity increased markers associated with increased glycolytic activity and thus lower glycerol, and that increasing said activity had the opposite effect. One of ordinary skill in the art would have recognized that lowering the expression of PGP would thereby lower the production of glycerol based on the teachings of Possik, and following the method of Pfizer of modifying the gene to reduce the production of glycerol would have arrived at the claimed invention.
Regarding the assertion that the teachings of Possik are not relevant to the claimed method, it is common in the field to consider developments in mammalian animal studies as being applicable in other mammalian animals, as CHO cells are understood to be a mammalian animal-derived cell line. As such one of skill in the art would have a reasonable expectation of success in modifying the method of Pfizer by altering the PGP enzyme activity as taught by Possik considering the known overlap in the central carbon metabolism of mammalian organisms.
Regarding the assertion that Possik does not teach or suggest how or why one would modify the PGP gene in CHO cells to reduce the level of synthesis of glycerol, Possik teaches the modification of PGP and its effects on glycerol and cellular metabolism, while Pfizer teaches the method of modifying target genes to reduce the production of inhibitors or other byproducts that might inhibit or contend with target protein production. One of skill in the art could therefore use the method of Pfizer to modify the PGP of CHO cells based on the motivation provided by Possik of the effects on cellular metabolism, as well as the motivation provided by Pfizer to reduce byproduct formation with the intent of optimizing culture conditions to enhance the desired cellular productivity. Regarding Applicant’s assertion that one of skill in the art would not modify the PGP gene to reduce glycerol synthesis as PGP plays a role in four different critical metabolic pathways, Possik discloses no evidence that altering PGP critically disrupted the metabolic pathways, and in contrast reported that the lowering of said PGP activity, understood to result in lower glycerol production, increased ATP production and O2 consumption that is associated with increased central carbon metabolism.
Double Patenting
The rejection of claims 1-2, 4-5, 8-13 and 22 on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5 of U.S. Patent No. 10,544,395 (cited on the Form PTO-892 mailed 10/28/2025) in view of Pfizer and Perry, and
the rejection of claim 3 on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 10,544,395 in view of Pfizer, and further in view of Possik
are withdrawn in view of the amendment to claim 1 to recite “wherein the one or more genes is phosphoglycolate phosphatase (PGP), and wherein the one or more inhibitors is glycerol”.
Claims 2, 4-5, 8-9, 12-13 and 26 are newly rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5 of U.S. Patent No. 10,544,395 (cited on the Form PTO-892 mailed 10/28/2025; herein “patent”) in view of Pfizer and Perry.
Instant claim 2 is drawn to the method of instant claim 1,
wherein instant claim 1 recites a method of cell culture comprising (i) providing CHO cells in a cell culture medium to start a cell culture process, wherein expression of one or more genes is modified in the cells to reduce a level of synthesis of one or more growth or productivity inhibitors by the cells as compared to a level of synthesis of one or more growth or productivity inhibitors by corresponding unmodified cells,
wherein the one or more genes is phosphoglycolate phosphatase (PGP), and
wherein the one or more inhibitors is glycerol,
however it is noted that instant claim 2 recites wherein the one or more inhibitors is formate and wherein the one or more genes is SHMT2.
In view of the rejection of instant claim 2 and its dependents under 35 USC 112(d) as not further limiting instant claim 1 as well as not reciting all of the limitations of claim 1, and in view of the indefiniteness under 35 USC 112(b) of instant claim 2 and its dependents as set forth above, for the sake of compact prosecution, instant claim 2 is being examined with the interpretation that it is drawn to the method steps of instant claim 1 but instead replaces the one or more gene of PGP with SHMT2, and replaces the one or more inhibitor of glycerol with formate.
Claim 1 of the patent recites a method of cell culture comprising maintaining at least one metabolite below a specific concentration in cell medium, and claim 5 of the patent recites the metabolite is formate.
The claims of the patent do not recite expression of one or more genes is modified in the cells to reduce a level of synthesis of one or more growth or productivity inhibitors by the cells as compared to a level of synthesis of one or more growth or productivity inhibitors by corresponding unmodified cells, wherein the one or more genes is SHMT2.
Pfizer discusses cells and methods of cell culture [title].
Regarding instant claim 2, Pfizer discloses a method of cell culture where cells are modified to reduce the level of synthesis of growth and/or productivity of inhibitors by the cell [abstract], wherein the expression of one or more genes is modified to reduce the level of synthesis of cell growth and/or productivity inhibitors [claim 2] in CHO cells [claim 63], wherein the modified gene encodes an enzyme that catalyzes the synthesis of formate [claim 4] which inhibits the growth of cells [p 8, ln 17-23].
Perry discusses the effect of vitamin B6 availability on serine hydroxymethyltransferase (SHMT) in MCF-7 cells [title], and discloses that formate is a major source of one-carbon units for cytoplasmic one-carbon metabolism that is generated in the mitochondria from serine [p 21, col 2, para 2].
Regarding instant claim 2, Perry discloses the modification of MCF-7 cells to generate PLP-deficient cells to reduce the expression and activity of serinehydroxymethyltransferase [p 24, col 1, para 3, p 22, col 1, final paragraph, and Figure 2b], and that serinehydroxymethyltransferase is responsible for the conversion of serine to formate [Figure 1]. As such, one of skill in the art would reason the modification of a cell to reduce the expression of SHMT would result in reduced production of formate as well.
In view of Pfizer and Perry, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the claims of the patent by reducing the expression of SHMT, as disclosed by Perry, to lower the production of the inhibitor formate, as disclosed by Pfizer, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the claims of the patent by lowering the production of formate through reducing the expression of SHMT, because Pfizer discloses a method of modifying the expression of genes that produce formate which inhibits the growth of cells, and Perry discloses that reduction of SHMT expression will reduce the production of formate from serine. One of ordinary skill in the art would have had a reasonable expectation of success because the patent and Pfizer discuss methods for growing cells and maintaining low levels of formate, and Pfizer and Perry discuss methods that regulate production of the metabolite formate.
Regarding instant claim 4, Pfizer discloses the modification of genes to decreases gene expression to reduce the level of synthesis of growth and/or productivity inhibitors by the cell [claim 58].
Regarding instant claim 5, Pfizer discloses maintaining formate at a specific concentration below a reference concentration [claim 13], which is below 2 mM [claim 14].
Regarding instant claim 8, Pfizer discloses measuring the concentration of formate and when that measured concentration is above a predefined value, that concentration is decreased by reducing the amount of precursor provided to the cells [claim 15], wherein the predefined value of formate is disclosed as 2 mM [claim 14].
Regarding instant claim 9, Pfizer discloses measuring the concentration by NMR, HPLC or UPLC [claim 16].
Regarding instant claim 12, Pfizer discloses the method comprises a growth phase and a production phase and step (ii) is applied during the growth phase, wherein step (ii) comprises a step of measuring a concentration of formate [claim 29].
Regarding instant claim 13, Pfizer discloses modifying the expression of one or more genes comprises gene deletion, disruption, substitution, point mutation, multiple point mutation, insertion mutation or frameshift mutation of the gene, or introduction of one or more nucleic acids comprising the one or more genes into the cell, optionally as an expressible construct or expressible vector construct [claim 40].
Regarding instant claim 22, Pfizer discloses the method wherein cell growth and/or productivity are increased as compared to a control culture, said control culture being identical except comprises unmodified cells [claim 66].
Response to remarks: beginning p 10 of applicants response to double patenting rejections; Applicant in summary contends the amendments to the claims renders the double patenting rejections no longer applicable.
Applicant’s response is considered and found not convincing. For the reasons stated above, claims 2, 4-5, 8-9, 12-13 and 26 are rejected as being unpatentable over claims 1 and 5 of U.S. Patent No. 10,544,395 in view of Pfizer and Perry, which is a new rejection necessitated by the instant claim amendments.
Conclusion
Status of the Application:
Claims 1-2, 4-5, 8-19, 22, and 26 are pending.
Claims 14-19 are withdrawn.
Claims 1-2, 4-5, 8-13, 22 and 26 are rejected.
No claim is in condition for allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH SPANGLER whose telephone number is (571)270-0314. The examiner can normally be reached M-F 7:30 am - 4:30 pm.
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, Manjunath Rao can be reached at (571) 272-0939. 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.
/JOSEPH R SPANGLER/
Examiner
Art Unit 1656
/David Steadman/Primary Examiner, Art Unit 1656