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 .
Summary
Claims 1-5, 7, 9, 12, 17-18, 25-26, 28-29, 32-34, 36, and 41-42 are pending in this office action. Claims 6, 8, 10-11, 13-16, 19-24, 27, 30-31, 35, 37-40 are cancelled. All pending claims are under examination in this application.
Priority
The current application was filed on March 1, 2024 is a 371 of PCT/US2022/042198 filed August 31, 2022, which in turn claims domestic priority to provisional patent applications 63/244,035 and 63/239,863 filed September 14, 2021 and September 1, 2021, respectively.
Information Disclosure Statement
Receipt of the Information Disclosure Statements filed on August 21, 2024 and March 1, 2024 are acknowledged. A signed copy of the two documents are attached to this office action.
Claim Objections
Claim 5 is objected to because of the following informality:
Claim 5 has the text “4-(oxy)phenoxy)acetyl moiety,…”. Please ensure the parentheses match within the name (there should be four not three). Appropriate correction is required.
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.
Claim 18 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 18 has the following text within the wherein clause:
R2 and R3 are H;
R3 is -L-PTM, -NH-(CH2-CH2-O)m-CH3, or -CONH-(CH2-CH2-O)m-CH3, and R2 is H;
R2 is -L-PTM, -NH-(CH2-CH2-O)m-CH3, or -CONH-(CH2-CH2-O)m-CH3, and R3 is H; or each subscript m is independently 1 or 2.
There is no conjunction indicating additive or alternative substituents (and/or). Therefore, the text is unclear and indefinite.
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 non-obviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-5, 7, 9, 12, 17-18, 25-26, 28-29, 32-34, 36, and 41-42 are rejected under 35 U.S.C. 103 as being unpatentable over Crew et al. (US2015/0291562A1) in view of Chamberlain et al. (Drug Discovery Today, 2019), Tan et al. (Nature, 2007), Man et al. (US2011/0196150A1), and Parry (WO2004/031379A1) as evidenced by Lupas et al. (PLOS Computational Biology, 2015).
[The Examiner is going to introduce each new reference and then combine them where appropriate to reject the instant claims.]
1. Crew et al.
Crew et al. is considered the closest prior art as it teaches imide-based modulators of proteolysis and associated methods of use (see title). In addition, Crew et al. disclose that the description relates to imide-based compounds, including bifunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the description provides compounds, which contain on one end a ligand which binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type (see abstract).
2. Chamberlain et al.
Chamberlain et al. teach cereblon modulators: Low molecular weight inducers of protein degradation (see title). In addition, Chamberlain et al. disclose that targeted protein degradation has become an exciting new paradigm in drug discovery with the potential to target new protein families for therapeutic intervention. In 2010, Hiroshi Handa and colleagues discovered that the drug thalidomide binds to the protein cere-blon, a component of the CRL4CRBN E3 ubiquitin ligase. In contrast to the heterobifunctional small molecule degraders reported in the literature, thalidomide is of very low molecular weight ( ~258Da) with molecular properties (solubility, metabolic stability, permeability etc) that readily support pharmaceutical dosing. It was subsequently shown that thalidomide and the analogues lenalidomide and pomalidomide are able to de-grade the transcription factors Ikaros and Aiolos. CK1a and GSPT1 were subsequently identified as substrates for specific ligands, indicating that this molecular class could be tuned for selective protein degradation. Structural studies showed that the thalidomide analogues bind to a shallow hydrophobic pocket on the surface of cereblon, and scaffold a protein-protein interaction with target proteins. Target proteins do not need any affinity for the cereblon modulators, and as such undruggable, or even unligandable, proteins can be targeted for degradation. A similar mechanism of action was subsequently identified for the clinical molecule indisulam, indicating that low molecular weight degraders are not unique to cereblon. The groundbreaking work on cereblon represents a case study for the discovery and characterization of low molecular weight protein degraders for other ligases (see abstract).
3. Tan et al.
Tan et al. teach mechanism of auxin perception by the TIR1 ubiquitin ligase (see title). In addition, Tan et al. disclose that auxin is a pivotal plant hormone that controls many aspects of plant growth and development. Perceived by a small family of F-box proteins including transport inhibitor response 1 (TIR1), auxin regulates gene expression by promoting SCF ubiquitin-ligase-catalysed degradation of the Aux/IAA transcription repressors, but how the TIR1 F-box protein senses and becomes activated by auxin remains unclear. Here we present the crystal structures of the Arabidopsis TIR1–ASK1 complex, free and in complexes with three different auxin compounds and an Aux/IAA substrate peptide. These structures show that the leucine-rich repeat domain of TIR1 contains an unexpected inositol hexakisphosphate co-factor and recognizes auxin and the Aux/IAA polypeptide substrate through a single surface pocket. Anchored to the base of the TIR1 pocket, auxin binds to a partially promiscuous site, which can also accommodate various auxin analogues. Docked on top of auxin, the Aux/IAA substrate peptide occupies the rest of the TIR1 pocket and completely encloses the hormone-binding site. By filling in a hydrophobic cavity at the protein interface, auxin enhances the TIR1–substrate interactions by acting as a ‘molecular glue’. Our results establish the first structural model of a plant hormone receptor (see abstract).
4. Man et al.
Man et al. teach arylmethoxy isoindoline derivatives and compositions comprising and methods of using the same (see title). In addition, Man et al. disclose that provided are 4'-arylmethoxy isoindoline compounds, and pharmaceutically acceptable salts, solvates, clathrates, stereoisomers, and prodrugs thereof. Methods of use, and pharmaceutical compositions of these compounds are disclosed (see abstract).
5. Parry
Parry teaches proteins having polysaccharidase activity (see title). In addition, Parry discloses pharmaceutical, or agrochemical composition or kit of parts comprising: a micro-particle or micro-capsule; and a protein which comprises a first binding domain which is a carbohydrate binding domain and a second binding domain which is capable of selective binding, wherein the first or second binding domain is capable of binding to said microcapsule or microparticle and the protein exhibits polysaccharidase activity. (see abstract).
Combination of Crew et al., Chamberlain et al., and Tan et al. as evidenced by Lupas et al.
Regarding instant claim 1, Crew et al., Chamberlain et al., and Tan et al. as evidenced by Lupas et al. teach a method for controlling the level of a target protein in a plant cell. The necessary citations of Crew et al., Chamberlain et al., and Tan et al. as evidenced by Lupas et al. that pertain to instant claim 1 are presented in Table I.
Table I
Instant Claim 1
Crew et al., Chamberlain et al., and Tan et al. as evidenced by Lupas et al. Citations
A method for controlling the level of a target protein in a plant cell, the method comprising contacting the plant cell with an effective amount of a compound according to Formula I:
Crew et al. disclose a compound of formula PTM-L-CLM wherein PTM is a protein target moiety, L the covalent linker and CLM is an imide structure that can be an N-substituted 1,3-oxoisoindolinyl moiety (see claims 1, 3, 7, 11, table 1 within Crew et al.). The compound can be used in a method of recruiting endogenous proteins to a ubiquitin ligase for degradation (see abstract within Crew et al.). The target protein comprises the structure, control, hormone, enzyme, genetic, immunological, shrinkage, storage, transportation, and any signaling proteins and peptides having biological function or activity (see paragraphs [0127-0228] within Crew et al.) disclose possible targeting moieties, all related to human cells.
Despite the Crew et al. disclosure focusing on human cells, the incorporation of plant cells (agrochemical use) into the three-domain structure of PTM-L-LTM can be realized from the Chamberlain et al. and Tan et al. citations.
Chamberlain et al. disclose low molecular weight Cereblon modulators (see title and abstract within Chamberlain et al.). Cereblon is a component of an E3 ubiquitin ligase and thalidomide can induce protein degradation by interaction with a ligase, hence it can control the level of target proteins in the cell (see abstract within Chamberlain et al.). The same property is common to further derivatives called imminomodulatory imide drugs such as iberodimide (CC-220). CC-220 exhibits more than an order of magnitude improved affinity towards cereblon than thalidomide, lenalidomide, or pomalidomide, and consequently exhibits far more potent degradation of Ikaros and Aiolos. The crystal structure of iberdomide revealed that increased potency correlates with more extensive interactions with the surface of cereblon (see page 32, left column, paragraph 3 within Chamberlain et al.). [CC-220 has a similar structure to the claimed LTM]. In the plant world this mechanism of molecular glues has been identified for auxin and jasmonate (see page 32, left column, paragraph 2 within Chamberlain et al.).
Tan et al. describes how auxin regulates gene expression by promoting the ubiquitin-ligasecatalysed degradation of Aux/lAA transcription repressors (see title and abstract within Tan et al.).
PTM-L-LTM (I), or a salt or hydrate thereof, wherein: PTM is a targeting moiety that binds the target protein; L is a covalent bond or linker moiety; and LTM is a ubiquitin ligase binding moiety that binds a plant ubiquitin ligase.
Obviousness Rationale
Structures based on three domains that promote the interaction of a protein of interest with a ubiquitin ligase are known from Crew et al. and the treatment of disease within the human cell.
This molecule has formula PTM-L-CLM. CLM is a N-substituted 1,3-dioxoisoindolininyl moiety. Many of the CLM moieties have activity as an LTM. [Lupas et al. confirms the homologous nature of human and plant cereblon (see page 3, left column, paragraph 2 within Lupas et al.)]. This type of mechanism to target proteolysis is known from the human cell and has been used to treat diseases by formulating molecules wherein the moiety interacting with the protein had a different structure according to the protein whose level needs to be regulated in the cell. In principle, the methodology is known and the fact of changing from CLM to LTM to interact with different protein of interest appears as an obvious measure that the skilled artisan (POSITA; person of ordinary skill in the art) would apply in order to control the level of different proteins. This is especially relevant based on the homologous structures which bind. Further LTMs are also known and could be applied in combination with the claimed PTM.
Therefore, a skilled artisan (POSITA) would consult the disclosures of Crew et al., Chamberlain et al., and Tan et al. to teach all the elements of instant claim 1.
The remainder of the instant claims which are either directly or indirectly dependent on claim 1 are taught in full by the combination of Crew et al., Chamberlain et al., and Tan et al.
Regarding instant claim 2, Crew et al., Chamberlain et al., and Tan et al. as evidenced by Lupas et al. teach wherein controlling the level of the target protein comprises targeted degradation of the target protein. Crew et al. disclose the term "protein target moiety" or PTM is used to describe a small molecule which binds to a target protein or other protein or polypeptide of interest and places/presents that protein or polypeptide in proximity to an ubiquitin ligase such that degradation of the protein or polypeptide by ubiquitin ligase may occur (see paragraph [0128] within Crew et al.).
Regarding instant claim 3, Crew et al., Chamberlain et al., and Tan et al. as evidenced by Lupas et al. teach wherein the target protein is selected from the group consisting of hydroxyphenylpyruvate dioxygenase, acetolactate synthase, or acetyl CoA carboxylase. Crew et al. disclose target proteins include Acetyl-CoA carboxylase (see paragraph [0125] within Crew et al.).
Regarding instant claim 4, Crew et al., Chamberlain et al., and Tan et al. as evidenced by Lupas et al. teach wherein the plant ubiquitin ligase is a plant cereblon. Chamberlain et al. disclose the structure of cereblon in complex with lenalidomide and CK1a (human) (see page 32, left column, paragraph 2 within Chamberlain et al.). There is significant structural overlap between the core binding from human to plant cereblon [Lupas et al. confirms the homologous nature of human and plant cereblon (see page 3, left column, paragraph 2 within Lupas et al.)]. Thus, indicating that the human E3 ubiquitin ligases protein degraders shown within Figure I would also have plant binding activity.
Figure I
PNG
media_image1.png
200
400
media_image1.png
Greyscale
Combination of Crew et al., Chamberlain et al., Tan et al., and Parry as evidenced by Lupas et al.
Regarding instant claims 5, 33, and 34, Crew et al., Chamberlain et al., Tan et al., and Parry as evidenced by Lupas et al. indirectly teach wherein PTM is N-(5,8-dimethoxy-[1,2,4]triazolo[1,5-c]pyrimidin-2-yl)-6-(trifluoromethyl)benz-2-yl- sulfonamide moiety. Parry discloses use of the agrochemical penoxsulam having this core motif (see pape 24, line 22 within Parry). Moreover, Parry discloses use of protein targeting moieties (see page 41, line 32 within Parry). Penoxsulam targets the plant enzyme Acetolactate Synthase (ALS) (also called AHAS), inhibiting its function, leading to plant death, making ALS its primary protein target site for herbicidal action (see PTO-892 NPL W). This PTM candidate would use its herbicidal activity to enhance the three-domain molecule (PTM-L-LTM). A skilled artisan (POSITA) would use penoxsulam or a derivative as a PTM to target plant cells.
Regarding instant claim 9, Crew et al., Chamberlain et al., Tan et al., and Parry as evidenced by Lupas et al. teach a compound according to Formula I: PTM-L-LTM (I), or a salt or hydrate thereof, wherein: PTM is a targeting moiety that binds with a protein in a plant cell; L is a covalent bond or linker moiety; and LTM is a ubiquitin ligase binding moiety that binds a plant ubiquitin ligase. Please see the discussion and citations within instant claims 1 and 5 for the necessary rejection text.
Regarding instant claim 32, Crew et al., Chamberlain et al., Tan et al., and Parry as evidenced by Lupas et al. teach wherein the protein targeting moiety targets a plant protein. Please see the discussion and citations within instant claim 4. Cereblon is a protein (see PTO-892 NPL 2U).
Regarding instant claim 36, Crew et al., Chamberlain et al., Tan et al., and Parry as evidenced by Lupas et al. teach wherein an agriculturally acceptable carrier is added to the formulation (see page 28, lines 7-32 within Parry). Also, please see the discussion and citations within instant claim 9.
Regarding instant claim 41, Crew et al., Chamberlain et al., Tan et al., and Parry as evidenced by Lupas et al. teach a plant cell comprising the compound of instant claim 9, or a salt or hydrate thereof. Please see the discussion and citations within instant claims 1 and 9 for the necessary rejection text.
Regarding instant claim 42, Crew et al., Chamberlain et al., Tan et al., and Parry as evidenced by Lupas et al. teach the plant cell of instant claim 41, wherein the compound is present in the plant cell in an amount sufficient to cause degradation of a protein of interest. Please see the discussion and citations within instant claims 2 and 41 for the necessary rejection text.
Combination of Crew et al., Chamberlain et al., Tan et al., and Man et al.
Regarding instant claim 7, Crew et al., Chamberlain et al., Tan et al., and Man et al. as evidenced by Lupas et al. teach an LTM having an N-substituted 1,3-dioxoisoindolinyl moiety of formula II. Man et al. disclose the molecule shown within Figure II (see page 23, left column).
Figure II
PNG
media_image2.png
9
400
media_image2.png
Greyscale
This compound is not used part of a three-domain molecule (PTM-L-LTM). However, once a skilled artisan (POSITA) has identified small-molecules (see instant claim 4) that bind to plant cereblon (like CC-220), the Man et al. disclosure will be consulted. As disclosed within instant claim 7 the -L-PTM moiety could be attached meta to the amide of the fused 5,6-ring system within the central core.
Regarding instant claim 12, Crew et al., Chamberlain et al., Tan et al., and Man et al. as evidenced by Lupas et al. teach the compound of instant claim 9, with an LTM having an N-substituted 1,3-dioxoisoindolinyl moiety of formula II. Please see the discussion and citations within instant claim 7 and 9 for the necessary rejection text.
Regarding instant claim 17, Crew et al., Chamberlain et al., Tan et al., and Man et al. as evidenced by Lupas et al. teach wherein one and only one of R1a and R2-R7 is -L-PTM. Crew et al. disclose a substituent, Rn, off the aromatic portion of the isoindoline moiety (see for example page 10, right column within Crew et al.). This group Rn is equivalent to R1a of instant claim 17. Therefore, R2-R7 would be H or a selected group in-line with the claim limitation, but not -L-PTM. A skilled artisan (POSITA) could ensure only one -L-PTM is attached to the LTM (for example see Figure III where the arrow points to the meta aromatic position).
Figure III
[AltContent: arrow][-L-PTM]
PNG
media_image2.png
9
400
media_image2.png
Greyscale
Regarding instant claim 18, Crew et al., Chamberlain et al., Tan et al., and Man et al. as evidenced by Lupas et al. teach the necessary substituents for the LTM. [The Examiner interpreted instant claim 18 to have an “and” after wherein substituents 1 and 2 are cited, and an “or” after wherein substituents 3 and 4 are cited.] Please see the discussion and citations within instant claim 7 and 12 for the necessary rejection text.
Regarding instant claim 25, Crew et al., Chamberlain et al., Tan et al., and Man et al. as evidenced by Lupas et al. teach the necessary substituents for the LTM. Man et al. disclose the structure within Figure IV, which matches the instant claim 25 limitations (see page 5, left column within Man et al.).
Figure IV
PNG
media_image3.png
200
400
media_image3.png
Greyscale
Regarding instant claim 26, Crew et al., Chamberlain et al., Tan et al., and Man et al. as evidenced by Lupas et al. teach the necessary substituents for the LTM. Man et al. disclose the structure within Figure IV, which matches the instant claim 25 limitations. A synthetic organic chemist (skilled artisan; POSITA) could design a -L-PTM moiety at position R4 under routine experimental conditions (see Figure V).
Figure V
[AltContent: arrow]
PNG
media_image3.png
200
400
media_image3.png
Greyscale
-L-PTM
Regarding instant claims 28 and 29, Crew et al., Chamberlain et al., Tan et al., and Man et al. as evidenced by Lupas et al. teach the necessary substituents for the LTM. Man et al. disclose the structure within Figure VI, which matches the instant claim 25 limitations (see page 24, left column within Man et al.).
Figure VI
Analogous Art
The Crew et al., Chamberlain et al., Tan et al., Man et al., and Parry as evidenced by Lupas et al. references are directed to the same field of endeavor as the instant claims, that is, a method for controlling the level of a target protein in a plant cell disclosed within instant claim 1.
Obviousness Analysis
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method for controlling the level of a target protein disclosed by Crew et al., using the plant biology teachings of Chamberlain et al. and Tan et al. as evidenced by Lupas et al. The additional claim-specific features described in Man et al. and Parry for the LTM and PTM, respectively, allow a skilled artisan (POSITA) to arrive at the subject matter of the instant claims.
The Crew et al., Chamberlain et al., Tan et al., Man et al., and Parry as evidenced by Lupas et al. references all have considerable application for a skilled artisan (POSITA) to control the level of a target protein within a plant cell. In this instance, both Chamberlain et al. and Tan et al. as evidenced by Lupas et al. supply the plant biology necessary for the primary reference of Crew et al., while Man et al. and Parry supplies the claim-specific features for the LTM and PTM, respectively. All references are directed to controlling the level of a target protein in a plant cell and therefore constitute analogous art under MPEP §2141.01(a). A POSITA would have reasonably consulted the five references when seeking to improve or adapt a method for controlling the level of a target protein in a plant cell.
Starting with Crew et al., the skilled person only had to try the necessary claim limitations disclosed by Chamberlain et al., Tan et al., Man et al., and Parry as evidenced by Lupas et al. The combination of Crew et al., Chamberlain et al., Tan et al., Man et al., and Parry as evidenced by Lupas et al. would allow one to arrive at the present application without employing inventive skill. This combination of the method for controlling the level of a target protein taught by Crew et al. along with the use of the necessary claim limitations taught by Chamberlain et al., Tan et al., Man et al., and Parry as evidenced by Lupas et al. would allow a research and development scientist (POSITA) to develop the invention taught in the instant application. It would have only required routine experimentation to modify the method for controlling the level of a target protein disclosed by Crew et al. with the use of the necessary claim limitations taught by Chamberlain et al., Tan et al., Man et al., and Parry as evidenced by Lupas et al. Incorporating the disclosure of Crew et al. into the plant biology presented by Chamberlain et al. and Tan et al. as evidenced by Lupas et al. represents a predictable use of prior art elements according to their established functions, consistent with MPEP §2143 and KSR. Also, the additional claim-specific features for the LTM and PTM described in Man et al. and Parry, respectively, follow a similar pattern for a skilled artisan (POSITA) to develop the PTM-L-LTM three-domain molecule.
Furthermore, the additional claim limitations taught by Chamberlain et al., Tan et al., Man et al., and Parry as evidenced by Lupas et al. would have been viewed by a POSITA as routine design optimizations or known modifications to control the level of a target protein in a plant cell. Implementing these features in Crew et al.’s method for controlling the level of a target protein would not require more than ordinary skill or routine experimentation.
Accordingly, the combination of Crew et al., supplemented by Chamberlain et al., Tan et al., Man et al., and Parry as evidenced by Lupas et al. provides all the elements of the claimed invention. The resulting method for controlling the target protein in a plant cell constitutes no more than the predictable outcome of combining familiar prior art components, and therefore the claimed subject matter would have been obvious to a POSITA prior to the effective filing date of the invention.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN W LIPPERT III whose telephone number is (571)270-0862. The examiner can normally be reached Monday - Thursday 9:00 AM - 5:00 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, Robert A Wax can be reached on 571-272-0623. 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.
/JOHN W LIPPERT III/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615