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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 05/12/2022 has been considered by the examiner.
Election/Restrictions
Applicant's election of Group I and Species A, Claims 21, 24-28 and 41-54, without traverse in the reply filed on 09/22/2025 is acknowledged.
Claim Objections
Claims 25, 44, 50 are objected to because of the following informalities:
Claim 25, line 1: please amend “first portion” to –first portion of the molecule—for purposes of consistency.
Claim 25, line 3: please amend “second portion” to – second portion of the molecule—for purposes of consistency.
Claim 44, line 1: please amend “first portion” to –first portion of the molecule—for purposes of consistency.
Claim 44, line 3: please amend “second portion” to – second portion of the molecule—for purposes of consistency.
Claim 50, line 1: please amend “first portion” to –first portion of the molecule—for purposes of consistency.
Claim 50, line 3: please amend “second portion” to – second portion of the molecule—for purposes of consistency.
Appropriate correction is required.
Applicant is advised that should claims 49-53 be found allowable, claims 21, 24-28, 41, and 43-47 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
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 21, 24-28 and 41-54 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 the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 21, claim 21 recites “the first portion and the second portion are portions of a single molecule” in lines 7-8. However, it is unclear if “a single molecule” is the same as “the molecule” [claim 21 previously recited a first portion of a molecule and a second portion of the molecule] or if it is a different, newly recited molecule. Therefore, the scope of claim 21 is indefinite. Claims 24-28 and 41-42 are further rejected by virtue of its dependence upon and because it fails to cure the deficiencies of claim 21. The Examiner suggests if “a single molecule” is the same as “the molecule”, to amend to recite “the first portion and the second portion are portions of the molecule” or alternatively to replace the limitation with “wherein the molecule is a single molecule”.
Regarding claim 27, the term “substantially” in lines 1-2 is a relative term which renders the claim indefinite. The term “substantially” 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 how close to planar or parallel the membrane should be in order to meet the claimed “substantially planar” and “substantially parallel”. The metes and bounds of the claim are not clearly defined. Therefore, the scope of claim 27 is indefinite.
Regarding claim 43, the term “substantially” in lines 5-6 is a relative term which renders the claim indefinite. The term “substantially” 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 how close to planar or parallel the membrane should be in order to meet the claimed “substantially planar” and “substantially parallel”. The metes and bounds of the claim are not clearly defined. Therefore, the scope of claim 43 is indefinite. Claims 44-48 are further rejected by virtue of its dependence upon and because it fails to cure the deficiencies of claim 43.
Regarding claim 43, claim 43 recites “the first portion and the second portion are portions of a single molecule” in lines 8-9. However, it is unclear if “a single molecule” is the same as “the molecule” [claim 43 previously recited a first portion of a molecule and a second portion of the molecule] or if it is a different, newly recited molecule. Therefore, the scope of claim 43 is indefinite. Claims 44-48 are further rejected by virtue of its dependence upon and because it fails to cure the deficiencies of claim 43. The Examiner suggests if “a single molecule” is the same as “the molecule”, to amend to recite “the first portion and the second portion are portions of the molecule” or alternatively to replace the limitation with “wherein the molecule is a single molecule”.
Regarding claim 49, claim 49 recites “the first portion and the second portion are portions of a single molecule” in lines 7-8. However, it is unclear if “a single molecule” is the same as “the molecule” [claim 49 previously recited a first portion of a molecule and a second portion of the molecule] or if it is a different, newly recited molecule. Therefore, the scope of claim 49 is indefinite. Claims 50-54 are further rejected by virtue of its dependence upon and because it fails to cure the deficiencies of claim 49. The Examiner suggests if “a single molecule” is the same as “the molecule”, to amend to recite “the first portion and the second portion are portions of the molecule” or alternatively to replace the limitation with “wherein the molecule is a single molecule”.
Regarding claim 52, the term “substantially” in lines 1-2 is a relative term which renders the claim indefinite. The term “substantially” 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 how close to planar or parallel the membrane should be in order to meet the claimed “substantially planar” and “substantially parallel”. The metes and bounds of the claim are not clearly defined. Therefore, the scope of claim 52 is indefinite.
Claim Rejections - 35 USC § 102/103
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(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.
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.
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.
Claim(s) 21, 24-28, 43-46, and 49-52 is/are rejected under 35 U.S.C. 102(a)(1) as anticipated by Gershow et al. (Recapturing and trapping single molecules with a solid-state nanopore, 2007, Nature Nanotechnology, 2, 775-779 and Supplemental Information of Gershow et al.) or, in the alternative, under 35 U.S.C. 103 as obvious over Gershow et al. (Recapturing and trapping single molecules with a solid-state nanopore, 2007, Nature Nanotechnology, 2, 775-779 and Supplemental Information of Gershow et al.) in view of Aksimentiev et al. (US20140360876A1).
Regarding claim 21, a method (Gershow teaches a method for capturing and recapturing individual molecules through a nanopore [see e.g., Abstract, Title, Fig. 1 and Fig. 1 caption]) comprising:
detecting by a processing system including a processor a first entry, into a first pore located in a membrane, of a first portion of a molecule (Gershow teaches a single DNA molecule is detected translocating a pore located in a SiN membrane in the forward direction by an ionic current blockage [B in Fig. 1], which is detected, monitored, digitized and continuously recording the output to disk using a pClamp software and the voltage is controlled by a custom Labview software [Supplemental Information: Page 1 last paragraph continued to next page and Page 2, last paragraph; Fig. 1 and Fig. 1 caption, Page 775, Col. 1, Para. 2-3; Page 775, Col. 2, Paras. 1-3; Abstract]. One of ordinary skill in the art would recognize that the software and “recording to disk” would inherently include a processing system with a processor wherein the software is stored and installed for facilitating/executing the software’s programmed instructions, thus detecting by a processing system including a processor a first entry of a first portion of a molecule [the entire DNA molecule including all portions including a first portion, such as a first nucleotide, a front end/portion or a first base pair, is detected translocating in the forward direction as outlined above and necessarily includes a first entry of a first portion of the DNA molecule] into the nanopore located in the SiN membrane.), wherein the membrane has a first side and a second side (Gershow teaches the ∼20-nm-thick SiN membrane has a first side [e.g., left, top side] and a second side [e.g., right, bottom side] [Fig. 1 and Fig. 1 caption, Page 775, Col. 1, last paragraph]), and wherein the first pore extends from the first side of the membrane to the second side of the membrane (Gershow teaches the first nanopore extends from the first side [left, top side] to the second side [right, bottom side], and the nanopore joins two reservoirs on the left and right as seen in Fig. 1 [Fig. 1 and Fig. 1 caption, Page 775, Col. 1, last paragraph continued to next page]);
detecting by the processing system a second entry, into the first pore, of a second portion of the molecule (Gershow teaches a single DNA molecule is detected translocating the pore located in the SiN membrane in the forward direction by an ionic current blockage [B in Fig. 1], which is detected, monitored, digitized and continuously recording the output to disk using a pClamp software and the voltage is controlled by a custom Labview software [Supplemental Information: Page 1 last paragraph continued to next page and Page 2, last paragraph; Fig. 1 and Fig. 1 caption, Page 775, Col. 1, Para. 2-3; Page 775, Col. 2, Paras. 1-3; Abstract]. One of ordinary skill in the art would recognize that the software and “recording to disk” would inherently include a processing system with a processor wherein the software is stored and installed for facilitating/executing the software’s programmed instructions, thus detecting by a processing system including a processor a second entry of a second portion of the molecule [the entire DNA molecule including all portions including a second portion, such as a second nucleotide, a middle or back end/portion or a second base pair, is detected translocating in the forward direction as outlined above and necessarily includes a second entry of a second portion of the DNA molecule] into the nanopore located in the SiN membrane.), wherein the first portion and the second portion are portions of a single molecule (Gershow teaches a single DNA molecule is detected translocating the pore located in the SiN membrane in the forward direction by an ionic current blockage [B in Fig. 1], and thus necessarily teaches the first portion and the second portion are portions of a single DNA molecule as the captured single DNA molecule includes all portions, including the first and second portion, as outlined in the rejection above [Title, Fig. 1 and Fig. 1 caption, Page 775, Col. 1, Para. 2-3; Page 775, Col. 2, Paras. 1-3]); and
responsive to detecting the first entry into the first pore and the second entry into the first pore, facilitating by the processing system a first movement of the first portion of the molecule back out of the first pore and a second movement of the second portion of the molecule back out of the first pore (Gershow teaches after a molecule was detected entering the pore [corresponding to responsive to detecting the first entry into the first pore and the second entry in the first pore as the entire DNA molecule translocating the pore includes a first entry of a first portion of the molecule and a second entry of a second portion of the molecule], the forward voltage was maintained for a programmed time before a reverse voltage of -120 mV was applied and maintained for 500 ms, which is facilitated and controlled by the custom Labview software. One of ordinary skill in the art would recognize that a software, such as a custom Labview software, would inherently include a processing system with a processor wherein the software is stored and installed for facilitating/executing the software’s programmed instructions. With the voltage reversed by the software and processing system, the molecule is seen to translocate the pore in the reverse direction [Fig. 1E], made evident by a second current blockage ([E] as seen in Fig. 1F), thus facilitating by the processing system a first movement of the first portion of the molecule back out of the first pore and a second movement of the second portion of the molecule back out of the first pore by reversing the voltage, as the entire single DNA molecule [which includes all portions] translocates the pore in the reverse direction [Fig. 1 and Fig. 1 caption, Page 775, Col. 1, Para. 2-3; Page 775, Col. 2, Paras. 1-3; Supplemental Information: Page 2, last paragraph].)
As outlined above, Gershow teaches the software used for controlling the voltage, measuring/detecting the current, digitizing and continuously recording the output to disk using software [such as pClamp software and custom Labview software] [Supplemental Information: Page 1 last paragraph continued to next page and Page 2, last paragraph]. One of ordinary skill in the art would recognize that the software would inherently include a processing system with a processor wherein the software is stored and installed for facilitating/executing the software’s programmed instructions. Gershow therefore anticipates the limitations of claim 21 above. However, Gershow does not expressly teach the software includes a processing system including a processor for facilitating/executing the software’s programmed instructions, and thus for purposes of compact prosecution, claim 21 is further rejected under 35 U.S.C. 103 over Gershow in view of Aksimentiev as outlined below.
Aksimentiev discloses a method for controlling materials such as DNA through a through-hole/nanopore, including, but not limited to, applying an electrical potential to an electrolyte solution to apply a transport force on the molecular strand to displace a section of the molecular strand into the nanopore and measuring a signal at the nanopore to identify the section of the molecular strand with reversible stepping of DNA through the membrane system such as a one-nucleotide or larger displacement of the DNA strand through the nanopore [see e.g., Title, Abstract, Figs. 9-10 and 7, Paras. 0046-0047]. Aksimentiev further teaches a machine in the form of a computer system 1100 which a set of instructions (e.g., software), when executed, may cause the machine/computer system to perform any one or more of the methods and operations, such as, applying a potential to the solution to apply a transport force on the molecular strand to displace a section of the molecular strand into the through-hole and measuring the signal at the through-hole to identify the section of the molecular strand and the computer system/processing system can be combined with an apparatus including a membrane comprising a through-hole, a first voltage source to apply a first potential to a surface of the membrane, a second voltage source to apply a second potential to a solution having conductive properties, a sensor to measure a signal at the through-hole, and a memory to store instructions; the computer system 1100/processing system includes a processor and also stores one or more sets of instructions (e.g., software) that the computer system is capable of executing and in response to executing the instructions, can perform operations as mentioned above [see e.g., Fig. 11 and Paras. 0051-0058].
Gershow and Aksimentiev are considered analogous art to the claimed invention because they are in the same field of nanopore sensors [Abstract of Gershow and Aksimentiev]. It would have been obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Gershow which includes the software that detects and facilitates in response to detecting, as outlined in the rejection above, to add a processing system including a processor wherein the software is installed and stored, and which executes the software’s programmed instructions and in response to executing the instructions/software, performs the operations, as taught by Aksimentiev, since Aksimentiev teaches it would be beneficial for providing a computer system within which a set of instructions, when executed, may cause the machine to perform any one or more of the methods and operations such as applying a potential to the solution to apply a transport force on the molecular strand to displace a section of the molecular strand into the through-hole and measuring the signal at the through-hole to identify the section of the molecular strand and can be combined with an apparatus including a membrane comprising a through-hole, a first voltage source to apply a first potential to a surface of the membrane, a second voltage source to apply a second potential to a solution having conductive properties, a sensor to measure a signal at the through-hole, and a memory to store instructions [see e.g., Fig. 11 and Paras. 0051-0058 of Aksimentiev]. Furthermore, the claimed limitations are obvious because 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 yielded nothing more than predictable results, MPEP 2143[I][A].
Regarding claim 24, the method of claim 21, wherein the first movement of the first portion of the molecule back out of the first pore and the second movement of the second portion of the molecule back out of the first pore results from adjusting a first physical characteristic in a vicinity of the first pore to cause the first portion of the molecule to be backed out of the first pore and the second portion of the molecule to be backed out of the first pore (Gershow teaches after a molecule was detected entering the pore, the forward voltage was maintained for a programmed time before a reverse voltage of -120 mV was applied and maintained for 500 ms. With the voltage and field reversed, the molecule is seen to translocate the pore in the reverse direction [Fig. 1E], made evident by a second current blockage ([E] as seen in Fig. 1F), corresponding to a first movement of the first portion of the molecule back out of the first pore and a second movement of the second portion of the molecule back out of the first pore, as the entire single DNA molecule [which includes all portions] translocates the pore in the reverse direction. The movement of the molecule [which necessarily includes a first movement and second movement of a first and second portion of the molecule, respectively, as outlined in the rejections above] back out of the first pore in the reverse direction results from adjusting the electric field “physical characteristic” in the reservoirs from being biased at +120 mV to adjusting the bias voltage to -120 mV, i.e., reversing the voltage and the electric field to cause the molecule [which necessarily includes the first and second portion of the molecule as outlined in the rejections above] to be backed out of the first pore/translocate in the reverse direction, and this adjusting of the electric field “physical characteristic” is in a vicinity of the first pore, because the voltage bias is applied to the reservoirs through the electrodes, and the nanopore joins the two reservoirs, and thus is in a vicinity of/near the pore as seen in Fig. 1 [Fig. 1 and Fig. 1 caption, Page 775, Col. 1, Para. 2-3; Page 775, Col. 2, Paras. 1-3; Supplemental Information: Page 2, last paragraph]. The examiner notes the electric field is the same physical characteristic disclosed in the instant specification [see e.g., Para. 000123 of the instant specification which states a physical characteristic in a vicinity of a pore can be an electric field that is changed near the pore]).
Regarding claim 25, the method of claim 21, wherein the first entry of the first portion into the first pore is from the first side of the membrane and wherein the second entry of the second portion into the first pore is from the first side of the membrane (Gershow teaches the single DNA molecule passes through the nanopore in the forward direction as seen in Fig. 1, from left to right, and thus the molecule’s entry into the nanopore is from the first side [left, top side] of the membrane. The molecule is detected passing through the pore in the forward direction and includes a first entry of a first portion of the molecule and a second entry of the second portion of molecule as it includes all portions of the molecule entering the nanopore when the entire molecule translocates, therefore, both the first and second entry of the first and second portion, respectively, into the nanopore is from the first side [left, top side] of the membrane [Fig. 1 and Fig. 1 caption, Page 775, Col. 2, Paras. 1-3; Page 775, Col. 1, Para. 2-3, see rejection above])
Regarding claim 26, the method of claim 21, wherein the molecule comprises DNA (Gershow teaches the molecule is DNA [Abstract, Page 775, Col. 1, Para. 1; Page 775, Col. 2, Paras 1-3 and Fig. 1 with Fig. 1 Caption]).
Regarding claim 27, the method of claim 21, wherein the membrane is substantially planar and wherein the first side of the membrane is substantially parallel to the second side of the membrane (Gershow teaches the ∼20-nm-thick SiN membrane is planar as seen in Fig. 1 and the first side [e.g., left, top side] of the membrane is parallel to the second side [e.g., right, bottom side] of the membrane [Fig. 1 and Fig. 1 caption, Page 775, Col. 1, last paragraph]).
Regarding claim 28, the method of claim 21, wherein the membrane is a solid-state membrane that comprises SiN (Gershow teaches a ∼20-nm-thick SiN membrane and is solid-state with a solid-state nanopore [Title, Abstract, Fig. 1 and Fig. 1 caption, Page 775, Col. 1, Paras. 2-3]).
Regarding claim 43, a method (Gershow teaches a method for capturing and recapturing individual molecules through a nanopore [see e.g., Abstract, Title, Fig. 1 and Fig. 1 caption]) comprising:
detecting by a processing system including a processor a first entry, into a first pore located in a membrane, of a first portion of a molecule (Gershow teaches a single DNA molecule is detected translocating a pore located in a SiN membrane in the forward direction by an ionic current blockage [B in Fig. 1], which is detected, monitored, digitized and continuously recording the output to disk using a pClamp software and the voltage is controlled by a custom Labview software [Supplemental Information: Page 1 last paragraph continued to next page and Page 2, last paragraph; Fig. 1 and Fig. 1 caption, Page 775, Col. 1, Para. 2-3; Page 775, Col. 2, Paras. 1-3; Abstract]. One of ordinary skill in the art would recognize that the software and “recording to disk” would inherently include a processing system with a processor wherein the software is stored and installed for facilitating/executing the software’s programmed instructions, thus detecting by a processing system including a processor a first entry of a first portion of a molecule [the entire DNA molecule including all portions including a first portion, such as a first nucleotide, a front end/portion or a first base pair, is detected translocating in the forward direction as outlined above and necessarily includes a first entry of a first portion of the DNA molecule] into the nanopore located in the SiN membrane.), wherein the membrane has a first side and a second side (Gershow teaches the ∼20-nm-thick SiN membrane has a first side [e.g., left, top side] and a second side [e.g., right, bottom side] [Fig. 1 and Fig. 1 caption, Page 775, Col. 1, last paragraph]), wherein the first pore extends from the first side of the membrane to the second side of the membrane (Gershow teaches the first nanopore extends from the first side [left, top side] to the second side [right, bottom side], and the nanopore joins two reservoirs on the left and right as seen in Fig. 1 [Fig. 1 and Fig. 1 caption, Page 775, Col. 1, last paragraph continued to next page]),
wherein the membrane is substantially planar, and wherein the first side of the membrane is substantially parallel to the second side of the membrane (Gershow teaches the ∼20-nm-thick SiN membrane is planar as seen in Fig. 1 and the first side [e.g., left, top side] of the membrane is parallel to the second side [e.g., right, bottom side] of the membrane [Fig. 1 and Fig. 1 caption, Page 775, Col. 1, last paragraph]);
detecting by the processing system a second entry, into the first pore, of a second portion of the molecule (Gershow teaches a single DNA molecule is detected translocating the pore located in the SiN membrane in the forward direction by an ionic current blockage [B in Fig. 1], which is detected, monitored, digitized and continuously recordingthe output to disk using a pClamp software and the voltage is controlled by a custom Labview software [Supplemental Information: Page 1 last paragraph continued to next page and Page 2, last paragraph; Fig. 1 and Fig. 1 caption, Page 775, Col. 1, Para. 2-3; Page 775, Col. 2, Paras. 1-3; Abstract]. One of ordinary skill in the art would recognize that the software and “recording to disk” would inherently include a processing system with a processor wherein the software is stored and installed for facilitating/executing the software’s programmed instructions, thus detecting by a processing system including a processor a second entry of a second portion of the molecule [the entire DNA molecule including all portions including a second portion, such as a second nucleotide, a middle or back end/portion or a second base pair, is detected translocating in the forward direction as outlined above and necessarily includes a second entry of a second portion of the DNA molecule] into the nanopore located in the SiN membrane), wherein the first portion and the second portion are portions of a single molecule (Gershow teaches a single DNA molecule is detected translocating the pore located in the SiN membrane in the forward direction by an ionic current blockage [B in Fig. 1], and thus necessarily teaches the first portion and the second portion are portions of a single DNA molecule as the captured single DNA molecule includes all portions, including the first and second portion, as outlined in the rejection above [Title, Fig. 1 and Fig. 1 caption, Page 775, Col. 1, Para. 2-3; Page 775, Col. 2, Paras. 1-3]); and
responsive to detecting the first entry into the first pore and the second entry into the first pore, facilitating by the processing system a first movement of the first portion of the molecule back out of the first pore and a second movement of the second portion of the molecule back out of the first pore (Gershow teaches after a molecule was detected entering the pore [corresponding to responsive to detecting the first entry into the first pore and the second entry in the first pore as the entire DNA molecule translocating the pore includes a first entry of a first portion of the molecule and a second entry of a second portion of the molecule], the forward voltage was maintained for a programmed time before a reverse voltage of -120 mV was applied and maintained for 500 ms, which is facilitated and controlled by the custom Labview software. One of ordinary skill in the art would recognize that a software, such as a custom Labview software, would inherently include a processing system with a processor wherein the software is stored and installed for facilitating/executing the software’s programmed instructions. With the voltage reversed by the software and processing system, the molecule is seen to translocate the pore in the reverse direction [Fig. 1E], made evident by a second current blockage ([E] as seen in Fig. 1F), thus facilitating by the processing system a first movement of the first portion of the molecule back out of the first pore and a second movement of the second portion of the molecule back out of the first pore by reversing the voltage, as the entire single DNA molecule [which includes all portions] translocates the pore in the reverse direction [Fig. 1 and Fig. 1 caption, Page 775, Col. 1, Para. 2-3; Page 775, Col. 2, Paras. 1-3; Supplemental Information: Page 2, last paragraph].),
wherein the first movement of the first portion of the molecule back out of the first pore and the second movement of the second portion of the molecule back out of the first pore results from adjusting a first physical characteristic in a vicinity of the first pore to cause the first portion of the molecule to be backed out of the first pore and the second portion of the molecule to be backed out of the first pore (Gershow teaches after a molecule was detected entering the pore, the forward voltage was maintained for a programmed time before a reverse voltage of -120 mV was applied and maintained for 500 ms. With the voltage and field reversed, the molecule is seen to translocate the pore in the reverse direction [Fig. 1E], made evident by a second current blockage ([E] as seen in Fig. 1F), corresponding to a first movement of the first portion of the molecule back out of the first pore and a second movement of the second portion of the molecule back out of the first pore, as the entire single DNA molecule [which includes all portions] translocates the pore in the reverse direction. The movement of the molecule [which necessarily includes a first movement and second movement of a first and second portion of the molecule, respectively, as outlined in the rejections above] back out of the first pore in the reverse direction results from adjusting the electric field “physical characteristic” in the reservoirs from being biased at +120 mV to adjusting the bias voltage to -120 mV, i.e., reversing the voltage and the electric field to cause the molecule [which necessarily includes the first and second portion of the molecule as outlined in the rejections above] to be backed out of the first pore/translocate in the reverse direction, and this adjusting of the electric field “physical characteristic” is in a vicinity of the first pore, because the voltage bias is applied to the reservoirs through the electrodes, and the nanopore joins the two reservoirs, and thus is in a vicinity of/near the pore as seen in Fig. 1 [Fig. 1 and Fig. 1 caption, Page 775, Col. 1, Para. 2-3; Page 775, Col. 2, Paras. 1-3; Supplemental Information: Page 2, last paragraph]. The examiner notes the electric field is the same physical characteristic disclosed in the instant specification [see e.g., Para. 000123 of the instant specification which states a physical characteristic in a vicinity of a pore can be an electric field that is changed near the pore]).
As outlined above, Gershow teaches the software used for controlling the voltage, measuring/detecting the current, digitizing and continuously recording the output to disk using software [such as pClamp software and custom Labview software] [Supplemental Information: Page 1 last paragraph continued to next page and Page 2, last paragraph]. One of ordinary skill in the art would recognize that the software would inherently include a processing system with a processor wherein the software is stored and installed for facilitating/executing the software’s programmed instructions. Gershow therefore anticipates the limitations of claim 43 above. However, Gershow does not expressly teach the software includes a processing system including a processor for facilitating/executing the software’s programmed instructions, and thus for purposes of compact prosecution, claim 43 is further rejected under 35 U.S.C. 103 over Gershow in view of Aksimentiev as outlined below.
Aksimentiev discloses a method for controlling materials such as DNA through a through-hole/nanopore, including, but not limited to, applying an electrical potential to an electrolyte solution to apply a transport force on the molecular strand to displace a section of the molecular strand into the nanopore and measuring a signal at the nanopore to identify the section of the molecular strand with reversible stepping of DNA through the membrane system such as a one-nucleotide or larger displacement of the DNA strand through the nanopore [see e.g., Title, Abstract, Figs. 9-10 and 7, Paras. 0046-0047]. Aksimentiev further teaches a machine in the form of a computer system 1100 which a set of instructions (e.g., software), when executed, may cause the machine/computer system to perform any one or more of the methods and operations, such as, applying a potential to the solution to apply a transport force on the molecular strand to displace a section of the molecular strand into the through-hole and measuring the signal at the through-hole to identify the section of the molecular strand and the computer system/processing system can be combined with an apparatus including a membrane comprising a through-hole, a first voltage source to apply a first potential to a surface of the membrane, a second voltage source to apply a second potential to a solution having conductive properties, a sensor to measure a signal at the through-hole, and a memory to store instructions; the computer system 1100/processing system includes a processor and also stores one or more sets of instructions (e.g., software) that the computer system is capable of executing and in response to executing the instructions, can perform operations as mentioned above [see e.g., Fig. 11 and Paras. 0051-0058].
Gershow and Aksimentiev are considered analogous art to the claimed invention because they are in the same field of nanopore sensors [Abstract of Gershow and Aksimentiev]. It would have been obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Gershow which includes the software that detects and facilitates in response to detecting, as outlined in the rejection above, to add a processing system including a processor wherein the software is installed and stored, and which executes the software’s programmed instructions and in response to executing the instructions/software, performs the operations, as taught by Aksimentiev, since Aksimentiev teaches it would be beneficial for providing a computer system within which a set of instructions, when executed, may cause the machine to perform any one or more of the methods and operations such as applying a potential to the solution to apply a transport force on the molecular strand to displace a section of the molecular strand into the through-hole and measuring the signal at the through-hole to identify the section of the molecular strand and can be combined with an apparatus including a membrane comprising a through-hole, a first voltage source to apply a first potential to a surface of the membrane, a second voltage source to apply a second potential to a solution having conductive properties, a sensor to measure a signal at the through-hole, and a memory to store instructions [see e.g., Fig. 11 and Paras. 0051-0058]. Furthermore, the claimed limitations are obvious because 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 yielded nothing more than predictable results, MPEP 2143[I][A].
Regarding claim 44, the method of claim 43, wherein the first entry of the first portion into the first pore is from the first side of the membrane and wherein the second entry of the second portion into the first pore is from the first side of the membrane (Gershow teaches the single DNA molecule passes through the nanopore in the forward direction as seen in Fig. 1, from left to right, and thus the molecule’s entry into the nanopore is from the first side [left, top side] of the membrane. The molecule is detected passing through the pore in the forward direction and includes a first entry of a first portion of the molecule and a second entry of the second portion of molecule as it includes all portions of the molecule entering the nanopore when the entire molecule translocates, therefore, both the first and second entry of the first and second portion, respectively, into the nanopore is from the first side [left, top side] of the membrane [Fig. 1 and Fig. 1 caption, Page 775, Col. 2, Paras. 1-3; Page 775, Col. 1, Para. 2-3, see rejection above])..
Regarding claim 45, the method of claim 43, wherein the molecule comprises DNA (Gershow teaches the molecule is DNA [Abstract, Page 775, Col. 1, Para. 1; Page 775, Col. 2, Paras 1-3 and Fig. 1 with Fig. 1 Caption]).
Regarding claim 46, the method of claim 43, wherein the membrane is a solid-state membrane (Gershow teaches a ∼20-nm-thick SiN membrane and is solid-state with a solid-state nanopore [Title, Abstract, Fig. 1 and Fig. 1 caption, Page 775, Col. 1, Paras. 2-3]).
Regarding claim 49, a method (Gershow teaches a method for capturing and recapturing individual molecules through a nanopore [see e.g., Abstract, Title, Fig. 1 and Fig. 1 caption]) comprising:
detecting by a processing system including a processor a first entry, into a first pore located in a membrane, of a first portion of a molecule (Gershow teaches a single DNA molecule is detected translocating a pore located in a SiN membrane in the forward direction by an ionic current blockage [B in Fig. 1], which is detected, monitored, digitized and continuously recording the output to disk using a pClamp software and the voltage is controlled by a custom Labview software [Supplemental Information: Page 1 last paragraph continued to next page and Page 2, last paragraph; Fig. 1 and Fig. 1 caption, Page 775, Col. 1, Para. 2-3; Page 775, Col. 2, Paras. 1-3; Abstract]. One of ordinary skill in the art would recognize that the software and “recording to disk” would inherently include a processing system with a processor wherein the software is stored and installed for facilitating/executing the software’s programmed instructions, thus detecting by a processing system including a processor a first entry of a first portion of a molecule [the entire DNA molecule including all portions including a first portion, such as a first nucleotide, a front end/portion or a first base pair, is detected translocating in the forward direction as outlined above and necessarily includes a first entry of a first portion of the DNA molecule] into the nanopore located in the SiN membrane.), wherein the membrane has a first side and a second side (Gershow teaches the ∼20-nm-thick SiN membrane has a first side [e.g., left, top side] and a second side [e.g., right, bottom side] [Fig. 1 and Fig. 1 caption, Page 775, Col. 1, last paragraph]), wherein the first pore extends from the first side of the membrane to the second side of the membrane (Gershow teaches the first nanopore extends from the first side [left, top side] to the second side [right, bottom side], and the nanopore joins two reservoirs on the left and right as seen in Fig. 1 [Fig. 1 and Fig. 1 caption, Page 775, Col. 1, last paragraph continued to next page]), and
wherein the membrane is a solid-state membrane (Gershow teaches a ∼20-nm-thick SiN membrane and is solid-state with a solid-state nanopore [Title, Abstract, Fig. 1 and Fig. 1 caption, Page 775, Col. 1, Paras. 2-3]);
detecting by the processing system a second entry, into the first pore, of a second portion of the molecule (Gershow teaches a single DNA molecule is detected translocating the pore located in the SiN membrane in the forward direction by an ionic current blockage [B in Fig. 1], which is detected, monitored, digitized and continuously recordingthe output to disk using a pClamp software and the voltage is controlled by a custom Labview software [Supplemental Information: Page 1 last paragraph continued to next page and Page 2, last paragraph; Fig. 1 and Fig. 1 caption, Page 775, Col. 1, Para. 2-3; Page 775, Col. 2, Paras. 1-3; Abstract]. One of ordinary skill in the art would recognize that the software and “recording to disk” would inherently include a processing system with a processor wherein the software is stored and installed for facilitating/executing the software’s programmed instructions, thus detecting by a processing system including a processor a second entry of a second portion of the molecule [the entire DNA molecule including all portions including a second portion, such as a second nucleotide, a middle or back end/portion or a second base pair, is detected translocating in the forward direction as outlined above and necessarily includes a second entry of a second portion of the DNA molecule] into the nanopore located in the SiN membrane.), wherein the first portion and the second portion are portions of a single molecule (Gershow teaches a single DNA molecule is detected translocating the pore located in the SiN membrane in the forward direction by an ionic current blockage [B in Fig. 1], and thus necessarily teaches the first portion and the second portion are portions of a single DNA molecule as the captured single DNA molecule includes all portions, including the first and second portion, as outlined in the rejection above [Title, Fig. 1 and Fig. 1 caption, Page 775, Col. 1, Para. 2-3; Page 775, Col. 2, Paras. 1-3]); and
responsive to detecting the first entry into the first pore and the second entry into the first pore, facilitating by the processing system a first movement of the first portion of the molecule back out of the first pore and a second movement of the second portion of the molecule back out of the first pore (Gershow teaches after a molecule was detected entering the pore [corresponding to responsive to detecting the first entry into the first pore and the second entry in the first pore as the entire DNA molecule translocating the pore includes a first entry of a first portion of the molecule and a second entry of a second portion of the molecule], the forward voltage was maintained for a programmed time before a reverse voltage of -120 mV was applied and maintained for 500 ms, which is facilitated and controlled by the custom Labview software. One of ordinary skill in the art would recognize that a software, such as a custom Labview software, would inherently include a processing system with a processor wherein the software is stored and installed for facilitating/executing the software’s programmed instructions. With the voltage reversed by the software and processing system, the molecule is seen to translocate the pore in the reverse direction [Fig. 1E], made evident by a second current blockage ([E] as seen in Fig. 1F), thus facilitating by the processing system a first movement of the first portion of the molecule back out of the first pore and a second movement of the second portion of the molecule back out of the first pore by reversing the voltage, as the entire single DNA molecule [which includes all portions] translocates the pore in the reverse direction [Fig. 1 and Fig. 1 caption, Page 775, Col. 1, Para. 2-3; Page 775, Col. 2, Paras. 1-3; Supplemental Information: Page 2, last paragraph].),
wherein the first movement of the first portion of the molecule back out of the first pore and the second movement of the second portion of the molecule back out of the first pore results from adjusting a first physical characteristic in a vicinity of the first pore to cause the first portion of the molecule to be backed out of the first pore and the second portion of the molecule to be backed out of the first pore (Gershow teaches after a molecule was detected entering the pore, the forward voltage was maintained for a programmed time before a reverse voltage of -120 mV was applied and maintained for 500 ms. With the voltage and field reversed, the molecule is seen to translocate the pore in the reverse direction [Fig. 1E], made evident by a second current blockage ([E] as seen in Fig. 1F), corresponding to a first movement of the first portion of the molecule back out of the first pore and a second movement of the second portion of the molecule back out of the first pore, as the entire single DNA molecule [which includes all portions] translocates the pore in the reverse direction. The movement of the molecule [which necessarily includes a first movement and second movement of a first and second portion of the molecule, respectively, as outlined in the rejections above] back out of the first pore in the reverse direction results from adjusting the electric field “physical characteristic” in the reservoirs from being biased at +120 mV to adjusting the bias voltage to -120 mV, i.e., reversing the voltage and the electric field to cause the molecule [which necessarily includes the first and second portion of the molecule as outlined in the rejections above] to be backed out of the first pore/translocate in the reverse direction, and this adjusting of the electric field “physical characteristic” is in a vicinity of the first pore, because the voltage bias is applied to the reservoirs through the electrodes, and the nanopore joins the two reservoirs, and thus is in a vicinity of/near the pore as seen in Fig. 1 [Fig. 1 and Fig. 1 caption, Page 775, Col. 1, Para. 2-3; Page 775, Col. 2, Paras. 1-3; Supplemental Information: Page 2, last paragraph]. The examiner notes the electric field is the same physical characteristic disclosed in the instant specification [see e.g., Para. 000123 of the instant specification which states a physical characteristic in a vicinity of a pore can be an electric field that is changed near the pore]).
As outlined above, Gershow teaches the software used for controlling the voltage, measuring/detecting the current, digitizing and continuously recording the output to disk using software [such as pClamp software and custom Labview software] [Supplemental Information: Page 1 last paragraph continued to next page and Page 2, last paragraph]. One of ordinary skill in the art would recognize that the software would inherently include a processing system with a processor wherein the software is stored and installed for facilitating/executing the software’s programmed instructions. Gershow therefore anticipates the limitations of claim 49 above. However, Gershow does not expressly teach the software includes a processing system including a