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 .
Status of the Application
1. Claims 1-15 are pending and subject to examination on the merits. Claim 15 is withdrawn from consideration as being drawn to non-elected subject matter. Claims 1-14 are currently under examination.
Election/Restrictions
2. Claim 15 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention II, there being no allowable generic or linking claim. Election of group I (Claims 1-14), Species I (protein kinase) of Abl1, and Species 2 (inhibitor) Abl1 ATP site inhibitor (i.e. dasatinib and/or imatinib) was made without traverse in the reply filed on 15 May 2026.
Priority
3. Acknowledgment is made for the Applicant’s claim for domestic priority based on the US provisional application PRO 63/378,686 filed 07 October 2022.
Drawings
4. The drawings are objected to because although Fig. 2A and 2B have a clear designation of time for the x-axis, it is unclear if the same applies down the column or across for the remaining sub-figures (i.e. Figs. 2C-2L). It is recommended to add the time/distance key to each of the subsequent sub-figures. 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.
Specification
5. The use of the term Digidata™ (p. 31, line 16), which is a trade name or a mark used in commerce, has been noted in this application. 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.
6. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (p. 23, line 23). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
7. Claim 1 objected to because of the following informalities: ClyA should be defined before the abbreviation is used. Appropriate correction is required.
8. Claim 3 is objected to because of the following informalities: “is tyrosine kinase” should be “is a tyrosine kinase” to improve grammar.
9. Claim 5 is objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim should refer to other claims in the alternative only. Claim 7 can be dependent on claim 5, which can be dependent on any claims 1-3. See MPEP § 608.01(n).
10. Claim 7 is objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim should refer to other claims in the alternative only. Claim 7 can be dependent on claim 5, which can be dependent on any claims 1-3. See MPEP § 608.01(n).
11. Claim 9 is objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim should refer to other claims in the alternative only. Claim 9 can be dependent on claim 7, which can be dependent on any claims 1-5. Additionally, claim 9 can be dependent on claim 5, which can be dependent on any claims 1-3. See MPEP § 608.01(n).
12. Claim 11 is objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim should refer to other claims in the alternative only. Claim 11 can be dependent on claim 9, which can be dependent on any claims 1-7. Additionally, Claim 11 can be dependent on claim 7, which can be dependent on any claims 1-5. Finally, Claim 11 can be dependent on claim 5, which can be dependent on any claims 1-3.See MPEP § 608.01(n).
13. Claim 13 is objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim should refer to other claims in the alternative only. Claim 13 can be dependent on claim 11, which can be dependent on claim 5, 7, or 9, which can be dependent on any claims 1-3, claims 1-5, or claims 1-7, respectively. See MPEP § 608.01(n).
Claim Interpretation
14. Claims 5, 7, 9, 11, and 13 will be examined; however, they will be interpreted to be dependent upon claim 1 only.
Claim Rejections - 35 USC § 112(a)
15. 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.
Written Description:
16. Claims 8, 10, and 12-14 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 8, 10, and 12-14 are drawn to the nanopore tweezer system comprising: (i) an ionic fluid filled compartment separated by a membrane into two chambers, (ii) a ClyA nanopore disposed in the membrane with a cis pore of 7nm and a trans pore of 3nm, (iii) a protein kinase in the lumen of the ClyA nanopore, and (iv) electrodes facilitating electrical potential difference across the membrane, and wherein the protein kinase is has an active site that is blocked; and, wherein the membrane is a micelle, bacteria, or eukaryotic cell.
MPEP 2163(1):
35 U.S.C. 112(a) and the first paragraph of pre-AIA 35 U.S.C. 112 require that the "specification shall contain a written description of the invention ...." This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en bane); Vas-Gath, Inc. v. Mahurkar, 935 F.2d 1555, 1560, 19 USPQ2d 1111, 1114 (Fed. Cir. 1991); see also Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920-23, 69 USPQ2d 1886, 1890-93 (Fed. Cir. 2004) (discussing the history and purpose of the written description requirement); In re Curtis, 354 F.3d 1347, 1357, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004) ("conclusive evidence of a claim's enablement is not equally conclusive of that claim's satisfactory written description"). The written description requirement has several policy objectives. "[T]he 'essential goal' of the description of the invention requirement is to clearly convey the information that an applicant [inventor] has invented the subject matter which is claimed." In re Barker, 559 F.2d 588, 592 n.4, 194 USPQ 470, 473 n.4 (CCPA 1977). Another objective is to convey to the public what the applicant claims as the invention. See Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1566, 43 USPQ2d 1398, 1404 (Fed. Cir. 1997), cert. denied, 523 U.S. 1089 (1998). "The 'written description' requirement implements the principle that a patent must describe the technology that is sought to be patented; the requirement serves both to satisfy the inventor's obligation to disclose the technologic knowledge upon which the patent is based, and to demonstrate that the patentee [inventor] was in possession of the invention that is claimed." Capon v. Eshhar, 418 F.3d 1349, 1357, 76 USPQ2d 1078, 1084 (Fed. Cir. 2005). Further, the written description requirement promotes the progress of the useful arts by ensuring that patentees adequately describe their inventions in their patent specifications in exchange for the right to exclude others from practicing the invention for the duration of the patent's term.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Gath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. However, a showing of possession alone does not cure the lack of a written description. Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 969-70, 63 USPQ2d 1609, 1617 (Fed. Cir. 2002). For example, it is now well accepted that a satisfactory description may be found in originally-filed claims or any other portion of the originally-filed specification. See In re Koller, 613 F.2d 819, 204 USPQ 702 (CCPA 1980); In re Gardner, 475 F.2d 1389, 177 USPQ 396 (CCPA 1973); In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). However, that does not mean that all originally-filed claims have adequate written support. The specification must still be examined to assess whether an originally-filed claim has adequate support in the written disclosure and/or the drawings.
17. The claims are drawn to a nanopore tweezer system comprising: (i) an ionic fluid filled compartment separated by a membrane into two chambers, (ii) a ClyA nanopore disposed in the membrane with a cis pore of 7nm and a trans pore of 3nm, (iii) a protein kinase in the lumen of the ClyA nanopore, and (iv) electrodes facilitating electrical potential difference across the membrane, and wherein the protein kinase is has an active site that is blocked; and, wherein the membrane is a micelle, bacteria, or eukaryotic cell encompassing a very large and variable genus of different membrane preparations. All of the individual membrane groups, i.e. micelle vs. bacteria vs. eukaryotic cell, are large a variable. Specifically, a eukaryotic membrane is not the same as a bacterial cell membrane, and neither of these living membranes the same a circular polar lipid micelle. The specification does not describe any utilization of micelles, bacterial cells, or eukaryotic cells. At most, the specification describes the utilization of a completely different membrane system entirely, a DPhPC planar lipid bilayer. This working example does not sufficiently provide support for any living membrane or even a synthetic circular membrane. Here the specification is incomplete and it mandates that those skilled in the art must then figure out how to use the aimed invention. Thus, the claims do not find adequate support in any place in the specification to show that possession of a nanopore tweezer system capable of utilizing a micelle, eukaryotic, or bacterial cell as the membrane. The courts have established:
Novozymes A/S v. DuPont Nutrition Biosciences APS, 723 F.3d 1336 (Fed. Cir. 2013):
A patent, however, "is not a reward for the search, but compensation for its successful conclusion." Ariad, 598 F.3d at 1353 (quoting University of Rochester, 358 F.3d at 930 n.10). For that reason, the written description requirement prohibits a patentee from "leaving it to the ... industry to complete an unfinished invention.” Id.
Claim Rejections - 35 USC § 112(b)
18. 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.
19. Claims 1-14 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.
20. The term “about” in claim 1 is a relative term which renders the claim indefinite. The term “about” (part ii) is not defined by the claim, 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. It is unclear what the range is above and below the recited values for the pore lumen sizes, i.e. a 10% difference above and below or 1%, etc. Claims 2-14 are included in the instant rejection, since they do not mitigate the issue.
21. Claim 1 (part iii) recites the limitation "the lumen of the ClyA nanopore" in part iii. It is unclear if “the lumen of the ClyA nanopore” is referring to “a cis pore lumen” or “a trans pore lumen” in part ii. It is unclear which lumen “the lumen” is referring to. Claims 2-14 are included in the instant claims, since they do not mitigate the issue.
22. Claim 2 recites the limitation "wherein protein kinase" in line 1. it is unclear if “wherein protein kinase” is referring to “the protein kinase” recited in claim 1, part iii or any protein kinase. To mitigate this issue, amend the claim to read “the protein kinase” to clearly define the claimed protein kinase.
23. Claim 7 recites the limitation "the membrane preparation" in lines 1-2. There is insufficient antecedent basis for this limitation in the claim because there is no instance of “a membrane preparation” in the proceeding claims. To mitigate this issue, amend the claim to read “the protein kinase” to clearly define the claimed protein kinase.
24. Claim 8 recites the limitation "the membrane preparation" in lines 1-2. There is insufficient antecedent basis for this limitation in the claim because there is no instance of “a membrane preparation” in the proceeding claims. To mitigate this issue, amend the claim to read “the protein kinase” to clearly define the claimed protein kinase. Claims 10 and 12-14 are included in the instant rejection, since they do not mitigate the issue.
25. Claim 11 recites “has the amino acid sequence SEQ ID NO: 1,” which renders the claim indefinite because, it is unclear whether this is supposed to interpreted as comprising or consisting of SEQ ID NO: 1 is being claimed to make up the ClyA pore. To mitigate this issue, it is recommended to amend the claim to utilize the conventional claim language “consisting of” or “comprising.” See MPEP 2111.03(IV).
26. Claim 14 recites “has the amino acid sequence SEQ ID NO: 2 or SEQ ID NO: 3,” which renders the claim indefinite because, it is unclear whether this is supposed to interpreted as comprising or consisting of SEQ ID NO: 2 or SEQ ID NO: 3 is being claimed to make up the ClyA pore. To mitigate this issue, it is recommended to amend the claim to utilize the conventional claim language “consisting of” or “comprising.” See MPEP 2111.03(IV).
Claim Rejections - 35 USC § 102
27. 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.
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
28. Claims 1-7 and 9-13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Li et al (Li et al., 2022, Nature Comm—cited herein) and as evidenced by “Recombinant ABL1 (229-500) protein” (“Recombinant ABL1 (229-500) protein,” 2026, downloaded 01 July 2026 from <https://www.activemotif.com/catalog/details/81334/recombinant-abl1-229-500-protein> --cited herein) and as evidenced by Soskine et al (Soskine et al., 2013, J Am Chem Soc—cited herein). Regarding claim 1, drawn to a nanopore tweezer system comprising: (i) an ionic solution fluid-filled compartment separated by a membrane, comprising a planar lipid bilayer (claim 7), into a first and second chamber; (ii) a ClyA nanopore disposed in the membrane with a cis pore lumen of about 7nm and trans pore lumen of about 3nm; (iii) a protein kinase, wherein said kinase is a tyrosine kinase (claim 3) with a molecular weight in the range of 15-70kDa (claim 2), specifically Abl1 (claim 4), in the lumen; and (iv) electrodes configured for generating an electrical potential difference across the membrane to facilitate ionic flow through the ClyA nanopore, wherein the protein kinase has an active site that is blocked with a tyrosine kinase inhibitor (claim 3), wherein said inhibitor is an ATP-active site inhibitor (claim 5), and wherein said inhibitor is imatinib (claim 6), Li et al. teaches the utilization of nanopore tweezers to assess the conformational dynamics of Abl kinase domain (abstract), where specifically a ClyA-AS nanopore, wherein said ClyA-AS nanopore has a cis lumen size of 7nm and a trans lumen size of 4nm as evidenced by Soskine et al (p. 10, Fig. 1), was inserted into a DPhPC planar lipid bilayer separating two chambers, filled with 300uL of buffer (150mM NaCl, 100mM TrisHCl, pH 7.5), where the current generated by the ions flow through the nanopore was monitored, and the Abl kinase studied is Abl1, consisting of residues 229-512, (Figure 4 and Methods, “Mutagenesis, expression, and purification of Abl kinase,” lines 1-3), which is 32.8 kDa, as evidenced by “Recombinant ABL1 (229-500) protein” (p. 2, line 6), where the inhibitor used is imatinib (Figure 4). Regarding claim 9, drawn to the protein kinase modified with a N-terminal positively charged peptide SEQ ID NO: 12 (KRKKSGG) (claim 10), Li et al. teaches the utilization of N4posAbl, where the N4pos tag is KRKKSGG (p. 2, Results and discussion, paragraph 3). Regarding claim 12, drawn to the ClyA nanopore having at least one substitution of C87A, Li et al. teaches the utilization of ClyA-AS, which has a C87A, as evidenced by Soskine et al (p. 3, lines 23-24; p. 10, Fig. 1). Regarding claim 13, drawn to the ClyA nanopore having additional substitutions at L99, E103, F166, and K294, LI et al. teaches the utilization of ClyA-AS, which has the following substitutions C87A, L99Q, E103G, F166A, and K294R, as evidenced by Soskine et al (p. 10, Fig. 1).
Conclusion
29. All claims are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CIARA A MCKNIGHT whose telephone number is (703)756-4791. The examiner can normally be reached M-F 8:00am-4:30pm.
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/CIARA A MCKNIGHT/Examiner, Art Unit 1656
/SUZANNE M NOAKES/Primary Examiner, Art Unit 1656
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