DETAILED ACTION
Response to Amendment
Applicant’s response to the office action filed on December 22, 2025 has been entered. The claims pending in this application are claims 1-3, 6-14, 17-26, and 76 wherein claims 7, 8, 11, 12, 18, 19, 22-26, and 76 have been withdrawn in the office action mailed on April 15, 2024. The objection not reiterated from the previous office action is hereby withdrawn in view of applicant’s amendment filed on December 22, 2025. Claims 1-3, 6, 9, 10, 13, 14, 17, 20, and 21 will be examined.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Scope of Enablement
Claims 1-3, 6, 9, 10, 13, 14, 17, 20, and 21 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for contacting a sample comprising a permeabilized cell comprising the two or more target nucleic acids with a set of probes, does not reasonably provide enablement for performing multiplex detection of a plurality of target nucleic acids in a permeabilized cell using the methods recited in claims 1-3, 6, 9, 10, 13, 14, 17, 20, and 21. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 USC 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (CA FC 1988). Wands states at page 1404,
“Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.”
The Nature of The Invention
The claims are drawn to a method for multiplex detection of two or more target nucleic acids in a permeabilized cell. The invention is a class of invention which the CAFC has characterized as “the unpredictable arts such as chemistry and biology.” Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
The Breadth of The Claims
Claims 1-3, 6, 9, 10, 13, 14, 17, 20, and 21 encompass a method for multiplex detection of two or more target nucleic acids in a permeabilized cell, comprising:(A) contacting a sample comprising a permeabilized cell comprising the two or more target nucleic acids with a set of probes, wherein the set of probes comprises subsets of probes comprising a plurality of detectable labels that provide a unique identifiable signal for at least one of the two or more target nucleic acids, wherein the unique identifiable signal is generated from a unique combination of two or more detectable labels, a different number of at least one detectable label, or a combination thereof in the subset of probes; (B) detecting a signal from each of the detectable labels bound to the two or more target nucleic acids; and (C) determining the identity of the two or more target nucleic acids based on a predefined code of unique combinations of signals from two or more detectable labels, signals from different numbers of at least one detectable label, or a combination thereof for each target nucleic acid of the two or more target nucleic acids.
Working Examples
Although the specification provides one working example (see page 31 of US 2022/0119870 A1, which is US publication of this instant case), the specification provides no working example for performing multiplex detection of a plurality of target nucleic acids in a permeabilized cell using the methods recited in claims 1-3, 6, 9, 10, 13, 14, 17, 20, and 21.
The Amount of Direction or Guidance Provided and The State of The Prior Art
The specification provides one working example (see page 31 of US 2022/0119870 A1, which is US publication of this instant case). However, the specification provides no working example for performing multiplex detection of a plurality of target nucleic acids in a permeabilized cell using the methods recited in claims 1-3, 6, 9, 10, 13, 14, 17, 20, and 21. Furthermore, there is no experimental condition and/or experimental data in the specification to support the claimed invention. During the process of the prior art search, the examiner has not found any prior art which is related to perform multiplex detection of a plurality of target nucleic acids in a permeabilized cell using the methods recited in claims 1-3, 6, 9, 10, 13, 14, 17, 20, and 21.
Level of Skill in The Art, The Unpredictability of The Art, and The Quantity of Experimentation Necessary
While the relative skill in the art is very high (the Ph.D. degree with laboratory experience), there is no predictability whether multiplex detection of a plurality of target nucleic acids in a permeabilized cell can be performed using the methods recited in claims 1-3, 6, 9, 10, 13, 14, 17, 20, and 21.
Since the specification teaches that “[ F]IG. 4C illustrates another embodiment of sub-SGC implementation, where the SGC ID code is implemented on the LP molecule. In this embodiment, LP molecules binding to the same SGC can be mixtures of LPs each conjugated to a different label according to a predefined code book. For example, as shown in FIG. 4C, SGC5 LPs are a mixture of LPs conjugated to three different labels, creating the ID code 1101, corresponding to labels 4, 3 and 1. The advantage of this embodiment is that the ‘coloring’ of the SGC complex by the LPs will be completely randomized, which can further help to reduce coding errors. A partial LP mixing code book is shown on the right of FIG. 4C, with 7 different exemplary SGC codes shown using 4 labels”, “[F]IG. 4C illustrates yet another embodiment of sub-SGC implementation, where the SGC ID code is implemented on the LP molecule. In previously described methods, the LP sequences bound to a single SGC all carry the same label. The embodiment of FIG. 3 also utilizes the same labels on a given SGC. In the embodiment depicted in FIG. 4C, LP molecules binding to the same SGC can be a mixture of LPs each conjugated to a different label according to a predefined code book. For example, as shown in FIG. 4C, SGC5 LPs are a mixture of LPs conjugated to three different labels, creating the ID code 1011. The advantage of this embodiment is that the ‘coloring’ of the SGC complex by the LPs will be completely randomized, which can further help to reduce coding errors. Since the SGC ID codes are not hard coded in the SGCs, this scheme provides the flexibility to assign different ID codes to different SGCs in different assay configurations simply by devising a different code book on the fly. In addition, the mixing of LPs can be made in unequal amounts to normalize the labeling intensities across the N labels, which again can help in reducing encoding/ decoding errors. Furthermore, the mixing of LPs can be made according to predefined ratios of different labels such that each label can encode >1 bit of information. For example, a 1010 ID code could be distinguished from a 101’0 ID code where the 1’ refers to a specific label being present at a higher or lower concentration (and therefore providing a different relative signal intensity) than a 1. Each color can be provided at up to M relative concentrations such as 1, 1’, 1’’, 1’’’, etc., which will be limited by the number of distinct levels that can be reliably detected by the signal detection system and the number of available LA sites in each SGC (the higher the total number of LA sites, the larger the number of distinct levels can be detected). The disadvantage of this embodiment is that MN-1 LP and LA sequences will be required to uniquely encode and decode each SGC. In comparison, in the embodiment shown in FIG. 4A, only N unique LPs and LAs are required”, “[A]s shown in FIG. 4C, the SGC ID code is implemented on the LP molecule. In this embodiment, LP molecules binding to the same SGC can be mixtures of LPs each conjugated to a different label according to a predefined code book. For example, as shown in FIG. 4C, SGC5 LPs are a mixture of LPs conjugated to three different labels, creating the ID code 1101, corresponding to labels 4, 3 and 1. The advantage of this embodiment is that the ‘coloring’ of the SGC complex by the LPs will be completely randomized, which can further help to reduce coding errors. A partial LP mixing code book is shown on the right of FIG. 4C, with 7 different exemplary SGC codes shown using 4 labels”, “[F]IG. 4D shows an embodiment of FIG. 4C in more detail. As depicted in FIG. 4D, for each SGC, a specific label anchor (LA, the binding site on the amplifier for the label probe) is assigned so that each SGC for a particular target nucleic acid has a plurality of the same LAs on the amplifier. The level at which combinatorial labeling can be provided is with the label probes (LPs). In this case, SGC5 is illustrated showing that the amplifiers comprise a plurality of identical LAs, labeled ‘E.’ As shown in FIG. 4D, SGC5 is coded with 3 ID codes (1101) corresponding to 3 distinct label probes (4, 3 and 1), all of which have the same binding site for the plurality of ‘E’ LAs on the corresponding amplifiers. Therefore, all three label probes (4, 3 and 1) are bound to the amplifiers of SGC5, thereby labeling the SGC5 target nucleic acid with the label code 1101”,
“[F]IG. 4E shows an embodiment of FIG. 4C in more detail. The SGC5 of FIG. 4D is shown bound to its respective target nucleic acid, with the label probes having an ‘E’ binding site bound to the respective ‘E’ LAs of the SGC5 amplifiers (as in FIG. 4D). Also shown are two additional exemplary SGCs bound to their respective target nucleic acids. SGC1, coded as shown in FIG. 4D, comprises a plurality of identical LAs, labeled ‘A.’ SGC1 is coded with 1 ID code (0001) corresponding to a label probe (1), which has the binding site for the plurality of ‘A’ LAs of the SGC1 amplifiers. Therefore, the label probe ‘1’ is bound to the amplifiers of SGC1, thereby labeling the SGC1 target nucleic acid with the label code 0001. SGC3, coded as shown in FIG. 4D, comprises a plurality of identical LAs, labeled ‘C.’ SGC3 is coded with 2 ID probes (0011) corresponding to 2 distinct label probes (2 and 1), both of which have the same binding site for the plurality of ‘C’ LAs on the corresponding SGC3 amplifiers. Therefore, both label probes (2 and 1) are bound to the amplifiers of SGC3, thereby labeling the SGC3 target nucleic acid with the label code 0011”, “[F]IG. 4F shows an embodiment of FIG. 4C in more detail. FIG. 4F
illustrates that, once an SGC for a particular target nucleic acid has been designed, the actual coding for the target nucleic acid can be readily modified simply by changing the labels on the label probes that bind to the amplifiers of a particular SGC. For example, in FIG. 4D, SGC2 comprises amplifiers with ‘B’ LAs and is coded as 0010 using label 2. In FIG. 4F, the same SGC assembly can be used with respect to the target probes, pre-amplifier, and amplifiers with ‘B’ LAs, but instead of using ‘B’ LA-binding label probes with only label 2 as in FIG. 4B, ‘B’ LA-binding label probes can be used that have a mixture of labels 3 and 2 such that SGC2 is now coded with both labels (0110). Thus, labels 3 and 2 (0110) are bound to ‘B’ LAs on the SGC2 amplifiers. Similarly, SGC5 comprising amplifiers with ‘E’ LAs is now coded in FIG. 4F as 1110 by using label probes with ‘E’ LA-binding label probes that have a mixture of labels 4, 3 and 2 (1110), instead of labels 4, 3 and 1 (1101) as shown in FIG. 4D”, “[F]IG. 4G shows an embodiment of FIG. 4C in more detail. In FIG. 4G, an additional ‘coding’ can be implemented by using different ratios of label probes. As shown in FIG. 4G, rather than binding the distinct label probes in equivalent amounts, the ratio of distinct label probes bound to the corresponding amplifiers can be varied such that not only the presence of a particular label but also the relative amount of a particular label can be used as another way to provide a distinct label. As shown in FIG. 4G, SGC2 is coded as 0110 with labels 3 and 2, whereas SGC2’ can be used to code a different target nucleic acid using the code 011’0 and the same labels 3 and 2, but where the ratio of label 2 to label 3 bound to SGC2’ is different than the ratio of label 2 to label 3 bound to SGC2. The two target nucleic acids are labeled with the same label probes, but the target nucleic acids can be distinguished based on the relative amounts of the two label probes bound to the respective target nucleic acids” and “[A]s described herein, in some embodiments, an SGC for different target nucleic acids will have a different number of labels in the code (e.g., 1000, 1100, 1110 and 1111) (see FIGS. 4C and 4D). In this situation and in the case where the number of LAs on the respective SGCs is the same, if the number of label probes are added to the SGCs, the SGC coded 1000 will have a higher number of bound labels (label 4 probes) than the number of label 4 probes bound to an SGC coded 1111, since label probe 4 can bind to all of the sites on one of the SGCs but on ¼ of the sites on the other SGC. In some embodiments of the invention, it can be desirable to normalize the amount of label bound to different SGCs coded by different numbers of distinct labels. In an exemplary embodiment as shown in FIG. 4H, two target nucleic acids are shown with two bound SGCs, SGC2 and SGC5. SGC2 is coded as 0110 with labels 3 and 2, and SGC5 is coded as 1110 with labels 4, 3 and 2. In this case, where all of the label probes bind to the respective LAs, ‘B’ LAs in the case of SGC2 and ‘E’ LAs in the case of SGC5, and assuming that the SGC2 and SGC5 have approximately the same number of LAs in the respective SGCs, the number of respective labels that can bind to SGC2 will be higher than the number of respective labels that bind to SGC5 (i.e., the 2 distinct labels for SGC2 (labels 3 and 2) and the 3 distinct labels for SGC5 (labels 4, 3 and 2) will be bound to the same number of sites, resulting in a higher number of labels 3 and 2 being bound to SGC2 than SGC5 since some of the SGC5 sites are occupied by label 4). If desired, the number of labels (and therefore intensity of signal) can be normalized by including ‘blank’ label probes, i.e., probes having a binding site for the respective LAs (in this case ‘B’ for SGC2 and ‘E’ for SGC5) but without a label. For example, if it is desired to compare SGC2 and SGC5 with equal intensity signals for the respective labels, ⅓ “blank” label probes can be included with the mixture of ‘B’ LA-specific probes so that the intensity of labels 3 and 2 will be the same on both SGCs (i.e., ⅓ of SGC2 occupied by ‘blank’ label probes and ⅓ of SGC5 occupied by label 4). In another example, if a multiplex assay is being performed where some SGCs include 4 labels, then the assay can be performed so that the same proportion of ‘blank’ label probes are included in the label probe sets using less than 4 labels, for example, ½ ‘blank’ label probes can be included with the SG2-specific label probes coded by 2 distinct labels (0110) and ¼ ‘blank’ label probes can be included with the SGC5-specific label probes coded by 3 distinct labels (1110) so that the amount of each distinct label probe, 4, 3, 2 and 1, bound to the respective SGCs is the same on each SGC. Using such ‘blank’ label probes can also be utilized in combination with distinct label probes to provide for a desired proportion of respective labels, such as a desired ratio of label probes on an SGC” (see paragraphs [0011], [0048] to [0053], and [0057], and Figures 4C to 4H of US 2022/0119870 A1, which is US publication of this instant case), the specification clearly shows that one of labeled signal generating complexes (SGCs) produced by step (A) of claim 1 is differentiated from another of the labeled signal generating complexes (SGCs) based on a 4 number predefined coding system. For example, in the 4 number predefined coding system, 0110 means that a SGC has labels 2 and 3, 1110 means that a SGC has labels 2, 3, and 4, and 1111 means a SGC has labels 1, 2, 3, and 4. However, the scope of the claims is much broader than the scope of the specification because the claims do not indicate how a predefined code works. Since claim 1 does not indicate how to generate a predefined code of unique combinations of signals from two or more detectable labels for each target nucleic acid of the two or more target nucleic acids and how to generate an unique identifiable signal from different numbers of at least one detectable label or a combination thereof for each target nucleic acid of the two or more target nucleic acids, how the detectable labels bound to the target nucleic acids in step (B) is correlated with a predefined code in step (C), and how two or more labeled signal generating complexes (SGCs) are differentiated from each other using the predefined code, it is unpredictable how the identity of the two or more target nucleic acids can be determined based on a predefined code of unique combinations of signals from two or more detectable labels, signals from different numbers of at least one detectable label, or a combination thereof for each target nucleic acid of the two or more target nucleic acids such that multiplex detection of a plurality of target nucleic acids in a permeabilized cell cannot be performed using the methods recited in claims 1-3, 6, 9, 10, 13, 14, 17, 20, and 21.
Case law has established that “(t)o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation’.” In re Wright 990 F.2d 1557, 1561. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) it was determined that “[T]he scope of the claims must bear a reasonable correlation to the scope of enablement provided by the specification to persons of ordinary skill in the art”. The amount of guidance needed to enable the invention is related to the amount of knowledge in the art as well as the predictability in the art. Furthermore, the Court in Genentech Inc. v Novo Nordisk 42 USPQ2d 1001 held that “[I]t is the specification, not the knowledge of one skilled in the art that must supply the novel aspects of the invention in order to constitute adequate enablement”.
In view of above discussions, the skilled artisan will have no way to predict the experimental results. Accordingly, it is concluded that undue experimentation is required to make the invention as it is claimed. These undue experimentation at least includes to test whether multiplex detection of a plurality of target nucleic acids in a permeabilized cell can be performed using the methods recited in claims 1-3, 6, 9, 10, 13, 14, 17, 20, and 21.
Conclusion
In the instant case, as discussed above, the level of unpredictability in the art is high, the specification provides one with no guidance that leads one to claimed methods. One of skill in the art cannot readily anticipate the effect of a change within the subject matter to which the claimed invention pertains. Thus given the broad claims in an art whose nature is identified as unpredictable, the unpredictability of that art, the large quantity of research required to define these unpredictable variables, the lack of guidance provided in the specification, the absence of any working example related to claimed invention and the no teaching in the prior art balanced only against the high skill level in the art, it is the position of the examiner that it would require undue experimentation for one of skill in the art to perform the method of the claim as broadly written.
Response to Arguments
In page 13, fourth paragraph bridging to page 16, second paragraph of applicant’s remarks, applicant argues that “[W]ithout acquiescing to the basis of the rejection and solely to advance prosecution, claim 1 is amended to recite methods comprising steps (B) detecting a signal from each of the detectable labels bound to the two or more target nucleic acids; and (C) determining the identity of the two or more target nucleic acids based on a predefined code of unique combinations of signals from two or more detectable labels, signals from different numbers of at least one detectable label, or a combination thereof for each target nucleic acid of the two or more of target nucleic acids. Thus, these amendments indicate how detectable labels bound to the target nucleic acids in step (B) are correlated with a predefined code in step (C), and how two or more labeled signal generating complexes (SGCs) are differentiated from each other using a predefined code. As such, the claims indicate how a predefined code works. Additionally, all the subparts of FIG. 4 outline various exemplary codes for labeling different target nucleic acids with different detectable labels using different combinations and numbers of the labels to detect a each of the target nucleic acids based on the ID code. Thus, Applicant respectfully submits that the specification clearly provides direction or guidance for multiplex detection of target nucleic acids using a predefined code. The Examiner appears to concede this point by stating that ‘the specification clearly shows that one of labeled signal generating complexes (SGCs) produced by step (A) of claim 1 is differentiated from another of the labeled signal generating complexes (SGCs) based on a 4 number predefined coding system.’ Office Action, page 9, emphasis added. As such, the specification clearly shows the nature of a predefined coding system and demonstrates how the identity of two or more target nucleic acids can be predicted and determined based on the predefined code. The Examiner further argues that ‘there is no direction or guidance to show that multiplex detection of a plurality of target nucleic acids in a permeabilized cell can be performed using the methods (Office Action page 3), ‘there is no predictability whether multiplex detection of a plurality of target nucleic acids in a permeabilized cell can be performed using the methods’ (Office Action, page 4), and that ‘undue experimentation at least includes to test whether multiplex detection of a plurality of target nucleic acids’ (Office Action page 10). Although a working embodiment is not required for enablement, Applicant respectfully directs the Examiner to Example 1 and corresponding FIG. 8, which demonstrate successful multiplex detection of a plurality of target nucleic acids using the method as outlined in FIG. 4C, which as described above the Examiner specifically highlighted as showing label differentiation and use of a predefined coding system. Example 1 is directed to multiplex detection of four target nucleic acids using three fluorescent dyes. As recited in [00198], ‘configuration of the assay [in example 1] is essentially as described in FIG. 4C.’ The description of FIG. 4C in [0011] states ‘LP molecules binding to the same SGC can be mixtures of LPs each conjugated to a different label according to a predefined code book.’ The description of FIG. 8 and Example 1 recites that the ‘zoomed image was processed with the Richardson-Lucy spatial deconvolution algorithm in MATLAB (Mathworks; Natick, Mass.), signal dots were detected (exemplary signal dots shown with arrows labeled 801-804), and colors were decoded to individual targets and shown in FIGS. 8C-8F,’ see [0020] and [00199]. As such, the specification clearly demonstrates that the claimed methods are suitable for multiplex detection of target nucleic acids and one of skill can extrapolate the expected results when using the claimed methods” and “[T]he application outlines a number of configuration for probes (FIGS. 1-2), describes multiplex detection using an ID code for differences in combination and number of detectable labels (FIGS. 3-5), outlines configurations to reduce chances of miscoding (FIGS. 6-7), and provides a specific working example based on the provided methods for multiplex detection. Applicant respectfully submits that one of skill in the art engaging in detection of target nucleic acids in a permeabilized cell would find the disclosed specification enabling to make and use the full scope of the claimed invention without undue experimentation”.
The above arguments have been fully considered but they are not persuasive toward the withdrawal of the rejection. Although applicant argues that “the specification clearly provides direction or guidance for multiplex detection of target nucleic acids using a predefined code”, “the specification clearly demonstrates that the claimed methods are suitable for multiplex detection of target nucleic acids and one of skill can extrapolate the expected results when using the claimed methods”, and “one of skill in the art engaging in detection of target nucleic acids in a permeabilized cell would find the disclosed specification enabling to make and use the full scope of the claimed invention without undue experimentation”, since claim 1 does not indicate how to generate a predefined code of unique combinations of signals from two or more detectable labels for each target nucleic acid of the two or more target nucleic acids and how to generate an unique identifiable signal from different numbers of at least one detectable label or a combination thereof for each target nucleic acid of the two or more target nucleic acids, how the detectable labels bound to the target nucleic acids in step (B) is correlated with a predefined code in step (C), and how two or more labeled signal generating complexes (SGCs) are differentiated from each other using the predefined code, it is unpredictable how the identity of the two or more target nucleic acids can be determined based on a predefined code of unique combinations of signals from two or more detectable labels, signals from different numbers of at least one detectable label, or a combination thereof for each target nucleic acid of the two or more target nucleic acids such that multiplex detection of a plurality of target nucleic acids in a permeabilized cell cannot be performed using the methods recited in claims 1-3, 6, 9, 10, 13, 14, 17, 20, and 21.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Frank Lu, Ph. D., whose telephone number is (571)272-0746. The examiner can normally be reached Monday to Friday, 9 AM to 5 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, Anne Gussow, Ph.D., can be reached at 571-272-6047. 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.
/FRANK W LU/
Primary Examiner, Art Unit 1683
February 26, 2026