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 .
Detailed Action
This action is in response to the papers filed on May 18, 2023. Claims 1-20 are currently pending. Claims 1 and 16 are independent claims. Therefore, claim 1-20 are under examination to which the following grounds of rejection are applicable.
Priority
This application is claiming the benefit under 35 U.S.C. 119(e) of prior-filed provisional application 63/343,814 filing date 05/19/2022.
Thus, the earliest possible priority for the instant application is May 19, 2022.
Drawings
The replacement drawings received on August 16, 2023 are objected to. Applicant submitted only the sheets that had changes/corrections. However, 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.
Thus, Applicant should submit corrected drawings which include all drawings as originally submitted 5/18/2023.
Specification Objection
The use of the term True gel 3D, Agilent and CELLINK, which is a trade name or a mark used in commerce, has been noted in this application. Said Trade The term should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
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.
Claims 1-20 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 applicant regards as the invention.
Claims 1 and 16 recite “cells adhere to one another via the biomaterial matrix thereby forming the cell spheroids” and “the clusters of cells adhering to one another
thereby forming the cell spheroids”, respectively. It is unclear how “cells embedded in a biomaterial matrix” can adhere to one another to form spheroids. The specification does not provide any definition as to what is meant by “cells adhere to one another” and “the clusters of cells adhering to one another”. It is unclear if cells are removed from the biomaterial matrix to adhered to each other or if the biomaterial matrix containing cell adhere to biomaterial matrix. Although it is acknowledged the specification some flow conditions that are considered by applicant to form clusters and attach together (¶ [0069], ¶ [0102] of the published application), these are merely exemplary and non-limiting. The metes and bounds of the claims are unclear particularly since adhesion of cells without a biomaterial matrix would vary depending on secretion of adhesion molecules on the surface of the cells, type of cells and other conditions. As such, the metes and bounds of the claims cannot be determined.
Claims 1, 5, and 16 are indefinite in their recitation of “generating vortices”, “vortices with acoustic vibrations” and “using acoustic vibration to generate vortices”, respectively, in a fluidic mixture within a fluidic system. It is unclear how acoustic waves which only carry orbital angular momentum (OAM), are essentially scalar pressure fields and are generally considered spinless (see post filing art by Li et al., Communications Physics | ( 2024) 7:188,pp. 1-10) are able to generate acoustic vortices into a flowing suspension comprising a mixture including cells embedded in a biomaterial matrix. Moreover, a Google® search of prior art for terms comprising “acoustic vibration to generate vortices within a channel to a spheroid and organoid does not give any hit which demonstrates that these terms are not commonly used terms. Thus, the recitation of “generating vortices” “vortices with acoustic vibrations” and “using acoustic vibration to generate vortices” to generate spheroid and organoids in claims 1, 5 and 16 is unclear. Though paragraphs [0059]-[0060] describe how acoustic mixer 10 is configured to incorporate two mechanisms i.e., bubble and sharp edges as illustrated in Figures 2 and 3 these are merely exemplary and non-limiting.
Claims 2 and 17 are indefinite in their recitation of “acoustic microstreams in the mixture”. The phrase " acoustic microstreams in the mixture " is not defined by the claims, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Appropriate action is required.
Claims 3 and 18 are indefinite in their recitation of “sharp edges”. The recitation of term “sharp edges” is a relative term and renders the claim indefinite. The term " sharp " is not defined by the claim. Applicant must describe what number of edges are considered “sharp” as the art depends on the individual situation as well as the person making the determination. Although it is acknowledged the specification some edges that are considered by applicant to be " sharp” (¶ [0059], ¶ [0060] of the published application), these are merely exemplary and non-limiting. The metes and bounds of the claims are unclear particularly since sharp would vary depending on how much volume needs to be sequestered between two edges of a vortex (see Figure 3), pulsing parameters with a piezo transducer, components of the biomatrix containing cells and others. As such the metes and bounds of the claims are indefinite.
Claim 10 is indefinite in its recitation of “injecting the mixture having a cell concentration of from 0.3 to 2 million cells per millilitre” as the cells are embedded in a biomaterial and not a fluid, the unit of “cells per millilitre” is unclear.
Claims 3 and 18 are rejected because the recitation of “a piezo transducer”. The term " a piezo transducer " is not defined by the claim. The Specification does not have a closed definition of what is meant by “ a piezo transducer ". Thus, the metes and bounds of the claims are indefinite. For the sake of compact prosecution, the term " a piezo transducer " is interpreted as any other suitable vibration generating device, such as acoustic vibrator (paragraph [0061] of the published application).
Claims 4, 6-9 and 11-15 are indefinite insofar as they depend from claim 1. Claims 19-20 are indefinite insofar as they depend from claim 16.
35 U.S.C. 112, (d)
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.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], 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.
Claim 7 and by dependency claims 8-9 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 7 depends from claim 1. Claim 1 requires that the cells are embedded in a biomaterial matrix. Claim 7 broadens the scope of the claimed biomaterial matrix as it also requires the cells to be embedded in a collagen mixture.
Applicant may cancel the claim, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
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.
Claim 1 recites a method for forming spheroids within a fluidic system comprising: injecting a mixture including cells embedded in a biomaterial matrix into a channel; generating vortices in the mixture flowing within the channel; trapping the cells using the vortices to form clusters of cells until the cells of the clusters of cells adhere to one another via the biomaterial matrix thereby forming the cell spheroids; and retrieving the cell spheroids from the channel.
Claims 1-3, 7-12, and 16-18 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (Lab Chip, 2016,16, 2636-2643) in view of Suresh et al. ((2017) US 20190031999 A1) , Jeong et al ((2016)PloS one, 11(7), e0159013) and Le ((2020) Lab on a Chip, 20(3), 582-591).
PNG
media_image1.png
322
414
media_image1.png
Greyscale
Regarding claims 1 and 16, Chen et al. teaches a method for forming cell spheroids in a microfluidic channel (Introduction), generating vortices within the mixture flowing within the channel, trapping cells using vortices until cells aggregate, and retrieval of cell spheroids from the channel via 3D acoustic tweezers (Abstract, Fig. 1 and Spheroid Formation).
Chen et al. achieves this by applying Surface acoustic wave (SAWs) based cell manipulation that caused microstreaming to adjacent medium (the suspended cells) that trap the cells at pressure nodes and form cell spheroids (see Spheroid Formation, Fig 1 & 2).
PNG
media_image2.png
222
317
media_image2.png
Greyscale
PNG
media_image3.png
462
719
media_image3.png
Greyscale
Chen’s microfluidic device for forming spheroids flows a suspension of cells within a channel while applying acoustic waves to cause mircostreams that trap and aggregate cells into cell spheroids. By injecting fluid after stopping the vibrations of the channel, the spheroids are ejected and retrieved for downstream applications (page, 2638, col. 1, para. 1).
Regarding independent claim 16, and the recitation of “using acoustic vibration”, the 3D acoustic tweezers of Chen is a three-dimensional (3D) acoustic tweezers device as taught by Suresh et al. Suresh et al teaches Figure 1A a three-dimensional (3D) acoustic tweezers device used to generate volumetric nodes, surrounding a microfluidic experimental area (paragraph [0041]). Moreover, Suresh teaches three-dimensional (3D) acoustic tweezers which use surface acoustic waves to create 3D trapping nodes for the capture and manipulation of particles (e.g., microparticles and cells) along three mutually orthogonal axes (para. [0052]). The generation of three mutually orthogonal axes standing waves (from acoustic wave generators) would necessarily generate the vortices as recited in claim 16. Therefore, tweezers are functionally the same as acoustic vibrations. Additionally, Suresh teaches that a cell substrate can be modified by suitable surface-modifying substances including collagen, fibronectin, an RGD peptide, and/or other extracellular matrix (ECM) proteins or growth factors can be coated onto the cell substrate, e.g., to elicit an appropriate biological response from cells, (para [0125]).
However, Chen and Suresh fail to explicitly teach cells embedded in a biomaterial matrix.
However, Jeong at al. demonstrates that embedding the cells or spheroids within a biomaterial (collagen) matrix, within a microfluidic channel, will promote adhesion and improve spheroid integrity (page 3, para. 3 & 4, under Materials and Methods (“Fabrication if PDMS on a microfluidic chip” and “Culture of cell-hydrogel mixture in a microfluidic channel”)). Jeong recites “microfluidic channels were then coated with poly-dopamine solution (2 mg/mL) to promote type I collagen adhesion” (page 3, para 3) and “cell suspension was mixed with the type I collagen solution at a 1:9 ratio and 3.5×103 of HT-29 cells” (page 3, para 4).
Therefore, in view of the benefits of improving cell adhesion and spheroid integrity using a collagen matrix, it would have been obvious for a person with ordinary skill in the art to modify Chen’s spheroid-formation method to incorporate the embedding of cells in a biomaterial matrix comprising collagen to promote the aggregation of cell spheroids in a microfluidic channel via 3D acoustic tweezers since they both share the same goal of forming spheroids within a microfluidic channel. In addition, it would have been obvious to the ordinary artisan that the known techniques of Jeong at al. could have been applied to the method of Chen et al and Suresh with predictable results because the known techniques of Chen et al predictably results in methods useful to promote the aggregation of cell spheroids in a microfluidic channel.
A rationale to support a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 (2007) (see MPEP §§ 2143, A. and 2143.02).
Regarding claims 2 and 17, the combined teachings of Chen, Suresh, Jeong render obvious claims 1 and 16. Moreover, Chen’s microfluidic device produces microstreams that trap and aggregate cells into cell spheroids (abstract, “Our method used drag force from microstreaming to levitate cells in the vertical direction, and used radiation force from Gor'kov potential to aggregate cells in the horizontal plane”).
Regarding claims 3 and 18, the combined teachings of Chen, Suresh, Jeong render obvious claims 1 and 16-17. Moreover, Chen discloses a piezoelectric substrate, on which two orthogonal pairs of interdigital transducers (IDTs) were deposited (Fig. 1A). (page 2637, column 1, last paragraph, bridging to column 1, first paragraph) and Suresh teaches one or more surface acoustic wave generators to generate one or more surface acoustic waves (paragraphs [0068]) and two mutually orthogonal pairs of interdigital transducers (IDTs) that produce SSAWs (para [0132]).
However, the combined teachings of Chen and Suresh do not teach that two mutually orthogonal pairs of interdigital transducers (IDTs) that produce SSAWs induce vibrations of sharp edges via a piezo transducer.
Le et al. teaches a microfluidic chip that uses a piezoelectric transducer attached to the chip that induces the vibration of a sharp internal edge creating vortices within the microfluidic chip (page 585, col 1 para. 3 bridging into col. 2; page 587, col 1, para. 1 bridging into col. 2). Furthermore, Le discloses that a piezoelectric transducer coupled with a sharp internal edge efficiently perturbs the fluid flow and mixes the fluids (see page 583, column 1, para. 4 bridging into column 2.).
Therefore, a person with an ordinary skill in the art would have been motivated to substitute the sharp-edge piezo transducer actuation discussed in Le et al. for pairs of interdigital transducers of Chen and Suresh to make localized vibrations with sharp edges to trap and aggregate. There would be a reasonable expectation of success on improved fluid flow and increasing of generated vortices with sharp edges.
Regarding claim 7, the combined teachings of Chen et al. Suresh and Jeong et., render obvious claim 1. Moreover, Jeong teaches collagen matrices (page 3, para. 3 & 4).
Regarding claim 8, the combined teachings of Chen et al. Suresh and Jeong et., render obvious claim 1. Moreover, Jeong teaches type-1 collagen matrices (page 3, para. 3 & 4).
Regarding claim 9, the combined teachings of Chen et al. Suresh and Jeong et., render obvious claim 1. Moreover, Jeong teaches preparing acid-soluble collagen by neutralizing acid soluble collagen with sodium hydroxide (see page 3, under Materials and Methods “Collagen gel solution (2 mg/mL) was prepared by mixing collagen type I (rat tail, BD Biosciences, San Jose, CA) with phenol red-containing PBS with pH adjusted to 7.4 using 0.5 N NaOH.”).
Regarding claim 10, the combined teachings of Chen et al., Suresh et al. and Jeong et al., render obvious claim 1. Moreover, Chen teaches injecting the mixture with a cell concentration of from 0.3 to 2 million cells per millilitre (see page 2638, col.1, para 2 , “HepG2 spheroids were fabricated in our acoustic tweezers platform with input cell density of 8 × 10^6 cells per ml, then collected and cultured in Petri dishes.”). Therefore, a person of ordinary skill would have been motivated to optimize the amount of cells per millimeter in order to advantageously reach optimal stability. It is not inventive to find optimal workable ranges by routine experimentation. See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).Regarding claim 11, the combined teachings of Chen et al. Suresh and Lee et., render obvious claim 1. Moreover, Chen teaches retrieving the cell spheroids includes flowing the cell spheroids out of the channel by injecting a fluid into the channel to push the cell spheroids towards an outlet of the channel (page 2638, col. 1, para 1, under Spheroid formation and long-time culture, “Mature spheroids were washed through an outlet and collected in a Petri dish for further biological experiments or drug testing”).
Regarding claim 12, the combined teachings of Chen et al. Suresh and Lee et., render obvious claim 1 and claim 11. Moreover, Chen teaches a fluid containing Dulbecco’s modified essential medium for a spheroid cell suspension (see page 2637, col. 2, para. 1, under Cell preparation, “HepG2 (ATCC, USA), a human hepatocellular carcinoma cell line, was cultured in Eagle's Minimum Essential Medium (ATCC, USA) with 10% fetal bovine serum”).
***
Claims 4-6 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al., Suresh et al. and Jeong et al., as applied to Claims 1 and 16 above, and in further view of Collins et al. (Lab Chip, 2017,17, 1769-1777). Claim 19 is also rendered obvious and is rejected under 35 U.S.C 103 as being unpatentable over Chen, Suresh, Jeong and Le, as applied to claims 16-18, and in further view of Collins et al. (Lab Chip, 2017,17, 1769-1777).
With regard to claim 1, the combined teachings of Chen, Suresh and Jeong render obvious the claimed methodology, as iterated above in the 103 rejection the content of which is incorporated in claim 1.
Regarding claims 16-18, the combination of Chen, Suresh, Jeong and Le render obvious to claims 16-18.
However, Chen, Suresh, Jeong and Le fail to teach trapping cells using a continuous flow while spheroids are being formed, as recited in claims 4 and 19.
PNG
media_image4.png
200
400
media_image4.png
Greyscale
Collins teaches a method for cell capture and trapping of cells using acoustic streaming generated by a surface acoustic wave (see Abstract). Additionally, Collins et al. discusses a method for trapping cells in a continuous flow using acoustic streaming (see Title, Abstract, and Fig 1.). Collins recites “we maximize the effect of acoustic streaming in a continuous flow using a highfrequency (381 MHz), narrow-beam focused surface acoustic wave. This results in rapid fluid streaming, with velocities orders of magnitude greater than that of the lateral flow, to generate fluid vortices that extend the entire width of a 400 μm wide microfluidic channel.” (Abstract).
It would have been obvious for a person with ordinary skill in the art to apply the continuous-flow mechanism taught by Collins to the spheroid-forming system taught by Chen, Suresh, Jeong and Le since all Chen, Suresh, Jeong and Collins utilize acoustic trapping mechanism (via surface acoustic waves) to confine particles or cells. Collins also demonstrates that acoustic vortices can localize and trap cell-sized particles in recirculated flow regions of the microfluidic.
Implementation of the continuous-flow conditions in Collins would predictably result in increased automation of forming spheroids, since Collins emphasizes that the flow results in rapid fluid streaming and increased velocities greater than lateral flow.
Regarding claim 5, the combined teachings of Chen, Suresh, Jeong, Le and Collins render obvious the claimed methodology of claim 4. Moreover, Suresh teaches acoustic vortices using acoustic vibrations (para [0052, 0134-0136]).
Regarding claim 6, the combined teachings of Chen, Suresh, Jeong, Le and Collins. render obvious claims 4 and 5. Moreover, Chen teaches stopping the vibrations once cell spheroids reach a desired size, allowing them to flow down an outlet (page 2639, col. 1, para 1, “Finally, we turned off the SAWs and re-injected the cell suspension into the chamber”).
***
Claims 13-15 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al., Suresh et al. and Jeong et al., as applied to claim 1 above, and in further view of Corrado et al. ( (2019) Biotechnology and bioengineering, 116(5), 1152–1163). Claim 20 is also rendered obvious and is rejected under 35 U.S.C 103 as being unpatentable over Chen, Suresh, and Jeong, as applied to claim 16 above, and in further view of Corrado et al. ((2019) Biotechnology and bioengineering, 116(5), 1152–1163).
With regard to claim 1, the combined teachings of Chen, Suresh and Jeong render obvious the claimed methodology, as iterated above in the 103 rejection the content of which is incorporated in claim 1.
Regarding claim 16, the combination of Chen, Suresh, Jeong renders obvious to claims 16.
However, the combined teachings of Chen, Suresh, Jeong and Le fail to teach the injecting of methylcellulose into the mixture, as recited in claims 13 and 20.
Corrado et al. teaches a microfluidic device that develops spheroids within a microfluidic device using Eagle’s minimum essential medium supplemented by methylcellulose (page 1154, paragraph 1, col 1, under Hep-G2 spheroid-formation, “This was then diluted to cells per ml in Eagle’s minimum essential medium supplemented with 20% of 0.24% methylcellulose and seeded in round‐bottom 96‐well plates (Falcon, Milan, Italy) at a seeding density of 3000 cells per well.”).
It would have been obvious to integrate Corrado’s EMEM supplemented with methylcellulose with Chen’s method for forming spheroids in a fluidic system using a mixture of Eagle’s Minimal Essential Medium with collagen to suspend cells within the microfluidic. This combination is achieved because both Chen’s mixture and Corrado’s mixture for spheroid culture support the formation of spheroids in a fluidic model. Such integration of methylcellulose into the cell suspension would predictably result in the aggregation of cells and formation of spheroids, as it was used in the formation of Corrado’s spheroids.
Regarding claims 14 and 15, the combined teachings of Chen et al., Jeong et al., Suresh et al., and Corrado et al. render obvious claim 1 and 13. Moreover, Corrado et al. teaches supplementing methylcellulose into the mixture, which entails adding methylcellulose before and after the injection of the channel ((page 1154, paragraph 1, col 1, under Hep-G2 spheroid-formation, “This was then diluted to cells per ml in Eagle’s minimum essential medium supplemented with 20% of 0.24% methylcellulose and seeded in round‐bottom 96‐well plates (Falcon, Milan, Italy) at a seeding density of 3000 cells per well.”).
Conclusion
Claims 1-20 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Katriel B Kasayan whose telephone number is (571)272-1402. The examiner can normally be reached 7:30a-5p.
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, Maria G Leavitt can be reached at (571) 272-1085. 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.
/KATRIEL BARCELLANO KASAYAN/ Examiner, Art Unit 1634
/MARIA G LEAVITT/ Supervisory Patent Examiner, Art Unit 1634