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 .
Claims 1-10, 12-17 and 19 are pending in this application, Claim 19 is acknowledged as withdrawn, Claims 1-10 and 12-17 were examined on their merits.
The rejection of Claim 1 under 35 U.S.C. § 102(a)(1) as being anticipated by
Yonekawa (JP2010172231A), translation, cited in the IDS, has been withdrawn due to the Applicant’s amendment to the claim filed 04/10/2026.
The rejection of Claim(s) 1-4, 12, 16 and 17 under 35 U.S.C. § 102(a)(2) as being anticipated by Moriyama et al. (WO2020/196635A1), cited in the IDS, has been withdrawn in view of the statement by Applicant pursuant to 35 U.S.C. § 102(b)(2)(C) that the prior art reference was commonly owned and is not prior art.
The rejection of Claim(s) 1-4, 5-10 and 12, 13-15, 16 and 17 under 35 U.S.C. § 103 as being unpatentable over Moriyama et al. (WO2020/196635A1), cited in the IDS, has been withdrawn in view of the statement by Applicant pursuant to 35 U.S.C. § 102(b)(2)(C) that the prior art reference was commonly owned and is not prior art.
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 5-10 and 12-14 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.
Claim 5 recites, "preparing a flow channel having an inner diameter corresponding to a
magnitude of a force to be applied to the organism".
It is unclear what the relationship/correspondence is between the diameter of the flow channel and the magnitude of the organism applied force. The Examiner notes that at Pg. 3, Paragraph [0064] of the published application there is a description of a Figure;
"illustrating a relationship among the inner diameter of the nozzle 49, the distance between the end portion 254 of the nozzle 49 and the bottom portion 25a of the vessel 25, the curvature radius of the gas-liquid interface 255, the maximum value of the force applied to the cell to be the manipulation target 35, the magnitude of a force (compression force) of a downward component, the magnitude of a force (separating force) of a lateral component, the area of the gas-liquid interface 255 on which the cell to be the manipulation target 35 can be attached".
However, this description is not limited to the sole relationship between the flow
channel diameter and the magnitude of force, contains other variables and is drawn to
specifics not found in the instant claims. For purposes of examination, the Examiner
has interpreted the claim as any change in the flow channel diameter having a
corresponding effect on any force magnitude applied.
Claim 6 recites, "wherein the controlling the vector includes controlling the
magnitude of the force applied from the gas-liquid interface to the organism by
controlling a curvature radius of a portion of the gas-liquid interface in contact with the
organism". It is unclear what the relationship/correspondence is between the magnitude
of applied force at the gas-liquid interface and the curvature radius of the portion of the
gas-liquid interface contacting the organism. The Examiner notes that at Pg. 3,
Paragraph [0064] of the published application there is a description of a Figure;
"illustrating a relationship among the inner diameter of the nozzle 49, the distance between the end portion 254 of the nozzle 49 and the bottom portion 25a of the vessel 25, the curvature radius of the gas-liquid interface 255, the maximum value of the force applied to the cell to be the manipulation target 35, the magnitude of a force (compression force) of a downward component, the magnitude of a force (separating force) of a lateral component, the area of the gas-liquid interface 255 on which the cell to be the manipulation target 35 can be attached".
However, this description is not limited solely to the relationship between the
magnitude of applied force and curvature radius of the gas-liquid interface, contains
other variables and is drawn to specifics not found in the instant claims.
For purposes of examination, the Examiner has interpreted the claim as any change in the curvature radius of the gas-liquid interface having a corresponding effect on any applied force magnitude.
Claim 7 recites, "wherein the controlling the vector includes controlling the
magnitude of the force applied from the gas-liquid interface to the organism by
controlling a surface tension between the gas and the liquid". It is unclear what the
relationship/correspondence. is between the magnitude of applied force at the gas-liquid
interface to the organism and the surface tension between the gas and liquid. The Examiner notes that at Pgs. 23-24, Paragraph [0295] of the published application states;
"The following Mathematical Formula 1 is a mathematical formula for explaining the
method 914 of controlling the internal pressure of the bubble 256 by the curvature radius of the gas-liquid interface 255 and the method 915 of controlling the internal pressure by the interface free energy E2 of the gas-liquid interface 255. In the following Mathematical Formula 1, Pin represents the internal pressure of the bubble 256, Pout represents a liquid pressure, P represents the absolute value of a difference between the internal pressure of the bubble 256 and the liquid pressure, E2 represents the interface free energy (surface tension) of the gas-liquid interface 255, and r represents the curvature radius of the gas-liquid interface 255. When Pout is constant, the last equation of Mathematical Formula 1 is obtained".
However, the citation does not indicate or explain how exactly the interface free
energy (surface tension) of the gas-liquid interface (presumably the surface tension
between the gas and the liquid) correlates in any way with the magnitude of force
applied to the organism.
For purposes of examination, the Examiner has interpreted the
claim as any change in the surface tension of the gas-liquid interface having a
corresponding effect on any applied force magnitude.
Claim 8 recites, "the controlling the vector includes controlling the magnitude of
the force applied from the gas-liquid interface to the organism by controlling a
movement acceleration of the gas-liquid interface" and Claim 9 recites, "the controlling
the vector includes controlling the movement acceleration of the gas-liquid interface by
controlling a movement acceleration of the flow channel".
It is unclear what the relationship/correspondence is between the magnitude of applied force at the gas-liquid interface to the organism and the movement acceleration of the gas-liquid interface/flow channel. The Examiner notes that at Pg. 25 of the published application states:
"The force applied to the manipulation target 35 is a product of the mass of the manipulation
target 35 and the movement acceleration of the gas-liquid interface 255 to which the manipulation target 35 is attached. That is, the force applied to the manipulation target 35 attached to the gas-liquid interface 255 is proportional to the movement acceleration of the gas-liquid interface 255 to which the manipulation target 35 is attached. Therefore, the magnitude of the force applied from the gas-liquid interface 255 to the manipulation target 35 can be controlled by controlling the movement acceleration of the gas-liquid interface 255".
However, the citation does not indicate or explain exactly what the
relationship/correspondence is between the magnitude of applied force at the gas-liquid
interface to the organism and the movement acceleration of the gas-liquid interface/flow
channel. The description is not limited to the sole relationship between the magnitude
of force and movement acceleration of the gas-liquid interface, contains other variables,
does not mention the flow channel at all, and is drawn to specifics not found in the
instant claims. For purposes of examination, the Examiner has interpreted the claim as
any change in the movement acceleration of the flow channel/gas-liquid interface
having a corresponding effect on any magnitude of force applied to the organism.
Claim 10 recites, "the controlling the vector includes controlling the movement
acceleration of the gas-liquid interface by controlling a pressurization acceleration of the
pump". It is unclear what the relationship/correspondence is between pressurization
acceleration and the movement acceleration of the gas-liquid interface/flow channel.
The Examiner notes that at Pg. 25, Paragraph [0310] of the published application
states,
"In the method 917 of controlling the pressurization acceleration of the syringe pump, the movement acceleration of the gas-liquid interface 255 is controlled by controlling the acceleration of the gas supply from or gas intake to the syringe pump. In this case, the pressure generation unit 47 of the bubble forming unit 200 controls the plunger to control the acceleration at which gas is supplied from the syringe pump or the acceleration at which gas is taken into the syringe pump. Accordingly, the movement acceleration of the gas-liquid interface 255 is controlled by controlling the pressurization acceleration of the bubble 256 formed at the end portion 254 of the nozzle 49"
However, the citation does not indicate or explain exactly what the
relationship/correspondence is between the movement acceleration of the gas-liquid
interface and the pressurization acceleration of the pump. The description is not limited
to the sole relationship between pump pressurization acceleration and movement
acceleration of the gas-liquid interface and contains other variables, such as a bubble,
syringe pump and nozzle not found in the instant claims. For purposes of examination,
the Examiner has interpreted the claim as any change in the pump pressure having a
corresponding effect on movement acceleration of the gas-liquid interface.
Claim 12 recites, "controlling the direction of the force applied from the gas-liquid
interface to the organism by controlling a direction and a moving direction of a surface
of a portion of the gas-liquid interface in contact with the organism" and Claim 13
recites, "controlling the direction of the surface of the portion of the gas-liquid interface
in contact with the organism by controlling a curvature radius of the portion of the gas-
liquid interface in contact with the organism". It is unclear what the
relationship/correspondence is between the direction of the force applied from the gas-
liquid interface to the organism and the moving direction of a surface of the gas-liquid
interface in contact with the organism or the curvature radius of the portion of the gas-
liquid interface in contact with the organism.
The Examiner notes that at Pg. 26, Paragraph [0315] of the published application states;
"As illustrated in FIG. 19(a), when the nozzle 49a having the large inner diameter R1 is used, the curvature radius r at the contact point P of the bubble 256 becomes large, and the straight line connecting with the center point Q of the circle becomes relatively downward. Therefore, the gas-liquid interface 255 comes into contact with the manipulation target 35 from a slightly upper direction. Thus, when the gas-liquid interface 255 moves from the gas toward the liquid side, the direction in which the gas-liquid interface 255 applies a force to the manipulation target 35 is the direction D1. In this case, as illustrated in the experimental image in the lower diagram of FIG. 19(a), the manipulation target 35 enters under the bubble 256 without separation and is compressed. On the other hand, as illustrated in FIG. 19(b), when the nozzle 49b having the small inner diameter R2 is used, the curvature radius r at the contact point P of the bubble 256 becomes small, and the straight line connecting with the center point Q of the circle becomes relatively lateral. Therefore, the gas-liquid interface 255 comes into contact with the manipulation target 35 from a slightly lateral direction. Thus, when the gas-liquid interface 255 moves from the gas toward the liquid side, the direction in which the gas-liquid interface 255 applies a force to the manipulation target 35 is the direction D2. In this case, as shown in the experimental image in the lower diagram of FIG. 19(b), the manipulation target 35 is separated from the bottom portion 25a of the vessel 25. Note that the direction of the force of the gas-liquid interface 255 pushing the manipulation target 35 is also determined by the magnitude relationship between the inner diameter of the nozzle 49 and the diameter of the manipulation target 35, and for example, when the inner diameter of the nozzle 49 and the diameter of the manipulation target 35 are substantially the same, the direction of the force of the gas-liquid interface 255 pushing the manipulation target 35 is a relatively lateral direction.'
However, the citation does not indicate or explain exactly what the
relationship/correspondence is between the direction of force applied by the gas-liquid
interface to the organism and the moving direction of the surface of the portion of the
gas-liquid interface in contact with the organism or the curvature radius thereof. The
description is not limited to the sole relationship between the direction of the gas-liquid
interface and the direction of applied force or the curvature radius of the portion of the
gas-liquid interface contacting the organism and contains other variables, such as a
nozzle not found in the instant claims. For purposes of examination, the Examiner has
interpreted the claim as any change in the direction/curvature radius of the gas-liquid
interface having a corresponding effect on the direction of applied force from the gas-
liquid interface to the organism.
Claim 14 recites, "the controlling the vector includes controlling the direction of
the surface of the portion of the gas-liquid interface in contact with the organism by
controlling a distance between the end portion and a bottom of a vessel accommodating
the liquid". It is unclear what the relationship/correspondence is between the direction of a surface of the gas-liquid interface in contact with the organism and the distance
between the portion and the bottom portion of the vessel containing the liquid.
The Examiner notes that at Pg. 24, Paragraph [0300] of the published application
states;
"FIG. 17 illustrates an example of a schematic diagram illustrating a relationship between the distance between the end portion 254 of the nozzle 49 and the bottom portion 25a of the vessel 25 and the curvature radius r of the gas-liquid interface 255 in the present embodiment. FIG. 17(a) illustrates a case where a distance L1 between the end portion 254 of the nozzle 49 and the bottom portion 25a of the vessel 25 is long, and FIG. 17(b) illustrates a case where a distance L2 between the end portion 254 of the nozzle 49 and the bottom portion 25a of the vessel 25 is short. As illustrated in FIG. 17(a), when the distance L1 is long, the bubble 256 formed at the end portion 254 of the nozzle 49 is not sufficiently crushed, so that the curvature radius r of the gas-liquid interface 255 is large, and as illustrated in FIG. 17(b), when the distance L2 is short, the bubble 256 formed at the end portion 254 of the nozzle 49 is sufficiently crushed, so that the curvature radius r of the gas-liquid interface 255 is small. Note that when the distance L2 between the end portion 254 of the nozzle 49 and the bottom portion 25a of the vessel 25 is short, a relationship between the distance L2 and the curvature radius r of the gas-liquid interface 255 may be measured in advance and stored in the recording unit 190".
However, the citation does not indicate or explain exactly what the
relationship/correspondence is between the direction of the surface of the portion of the
gas-liquid interface with the organism and the distance between the end portion and a
bottom of the liquid containing vessel. The citation description is not limited to the sole relationship between the direction of the surface of the portion of the gas-liquid interface with the organism and the distance between the end portion and a bottom of the liquid containing vessel and contains other variables, such as a curvature radius and nozzle not found in the instant claims.
For purposes of examination, the Examiner has interpreted the claim as any
change in the direction of the surface of the gas-liquid interface in contact with the
organism having a corresponding effect on the distance between the end portion and
the bottom of the liquid containing vessel.
Claim 15 recites, "preparing a flow channel having an inner diameter
corresponding to a direction of a force to be applied to the organism". It is unclear what
the relationship/correspondence is between the diameter of the flow channel and the
direction of applied force. The Examiner notes that at Pg. 3, Paragraph [0064] of the
published application there is a description of a Figure;
"illustrating a relationship among the inner diameter of the nozzle 49, the distance between the end portion 254 of the nozzle 49 and the bottom portion 25a of the vessel 25, the curvature radius of the gas-liquid interface 255, the maximum value of the force applied to the cell to be the manipulation target 35, the magnitude of a force (compression force) of a downward component, the magnitude of a force (separating force) of a lateral component, the area of the gas-liquid interface 255 on which the cell to be the manipulation target 35 can be attached"
However, this description is not limited to the sole relationship between the flow
channel diameter and the direction of force and contains other variables and is drawn to
specifics not found in the instant claims. For purposes of examination, the Examiner has interpreted the claim as any change in the flow channel diameter having a corresponding effect on any applied force direction.
Claim 12 recites, "controlling a direction and a moving direction of a surface
portion of the gas-liquid interface in contact with the organism". It is unclear if the
"direction" and the "moving direction" refer to the same thing or if they refer to two
distinct directions. Claims 13-14 are rejected as being dependent upon rejected Claim
12.
Claim Rejections - 35 USC § 102
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.
Claims 1, 4, 12, 16 and 17 are newly rejected under 35 U.S.C. § 102(a)(1) as being anticipated by Jordan et al. (1994), cited in the IDS.
Jordan et al. teaches forming a freshly produced bubble (gas-liquid interface) at the end of a flow channel (micropipette) immersed in a culture medium comprising adherent cells and bringing the bubble (i.e. controlling the direction of the force applied from a gas side to a liquid side of the gas-liquid interface into contact with the cells) with the force and direction of the application being controlled by a micromanipulator (Pg. 449, Fig. 3 and Pg. 450, Column 2, Lines 3-20 and Pg. 451, Column 1 and Fig. 7), and reading on Claim 1, 12, 16 and 17.
That is, the gas bubble or gas-liquid interface (gas side) at the end of the micropipette immersed into the liquid media (liquid side) is brought into contact with the cells adhered to the bottom of a well (thus the direction of application is controlled) with sufficient force to attach the cells to the bubble;
and wherein a syringe pump is used to generate bubbles which controls the gas flow (Pg. 448, Column 1, Lines 1-5), and reading on Claim 4.
Claim Rejections - 35 USC § 103
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.
Claims 1, 2, 3, 4, 5-10, 12, 13-15, 16 and 17 are newly rejected under 35 U.S.C. § 103 as being unpatentable over Jordan et al. (1994), cited in the IDS.
The teachings of Jordan et al. were discussed above.
Jordan et al. did not teach a method wherein the magnitude of the force applied from the gas-liquid interface to the organism is controlled, as required by Claim 2;
wherein the magnitude of the force applied from the gas-liquid interface to the organism is controlled by controlling a gas pressure of the gas at the gas-liquid interface, as required by Claim 3;
wherein controlling the vector includes preparing a flow channel having an inner diameter corresponding to a magnitude of a force to be applied to the organism, as required by Claim 5;
wherein controlling the vector includes controlling the magnitude of the force
applied from the gas-liquid interface to the organism and controlling the direction of the
surface of the portion of the gas-liquid interface in contact with the organism;
by controlling a curvature radius of the portion of the gas-liquid interface in
contact with the organism, as required by Claims 6 and 13;
wherein controlling the vector includes controlling the magnitude of the force
applied from the gas-liquid interface to the organism by controlling a surface tension
between the gas and the liquid, as required by Claim 7;
wherein controlling the vector includes controlling the magnitude of the force
applied from the gas-liquid interface to the organism by controlling a movement
acceleration of the gas-liquid interface, as required by Claim 8;
or wherein controlling the vector includes controlling the movement acceleration
of the gas-liquid interface by controlling the movement acceleration of the flow channel,
as required by Claim 9;
wherein controlling the vector includes controlling the movement acceleration of
the gas-liquid interface by controlling a pressurization acceleration of the pump, as
required by Claim 10;
wherein controlling the vector includes controlling the movement acceleration of
the gas-liquid interface by controlling a pressurization acceleration of the pump, as
required by Claim 14;
and wherein controlling the vector includes preparing a flow channel having an
inner diameter corresponding to a direction of a force to be applied to the organism, as
required by Claim 15.
It would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Jordan et al. of contacting cell with a gas bubble produced by a syringe-pump to control the gas pressure of the gas introduced/discharged from the syringe pump to the bubble because this would also have an effect on the pressure applied by the bubble to the organism. Those of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to make this modification in order to control the gas volume in the produced bubble and therefore the pressure the bubble will provide to the contacted cells. There would have been a reasonable expectation of success in making this modification because the reference already teaches contacting cells with bubbles produced by pressure from a syringe-pump.
While the Jordan et al. reference does not specifically teach the limitation of Claim 5, wherein controlling the vector includes preparing a flow channel having an inner diameter corresponding to a magnitude of a force to be applied to the organism, one of ordinary skill in the art would recognize that the inner diameter of the flow channel from which the bubble originates is a result-effective optimizable variable. Those of ordinary skill in the art would have recognized that a small diameter flow channel will produce a small diameter bubble and a large diameter flow channel will produce a large diameter bubble, each with different corresponding magnitudes of force when applied to adherent cells.
This is motivation for someone of ordinary skill in the art to practice or test the flow channel parameter values widely to find those that are functional or optimal to apply sufficient force to remove adherent cells which then would be inclusive or cover the instantly claimed values. Absent any teaching of criticality by the Applicant concerning the diameter of the flow channel, it would be prima facie obvious that one of ordinary skill in the art would recognize this limitation is an optimizable variable which can be met as a matter of routine optimization (see MPEP § 2144.05 (II)(B). Those of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to make this modification in order to obtain a flow channel capable of providing the desired magnitude of force to remove adherent cells. There would have been a reasonable expectation of success in making this modification because the Jordan reference is not particularly limited to a flow channel (micropipette) with any particular diameter.
While the Jordan et al. reference does not specifically teach the limitation of Claim 6, wherein controlling the vector includes controlling a curvature radius of the portion of the gas-liquid interface in contact with the organism, one of ordinary skill in the art would recognize that the inner diameter of the flow channel from which the bubble originates will directly affect the curvature radius of the bubble portion in contact with the adherent cells, as a result-effective optimizable variable. Those of ordinary skill in the art would have recognized that a small diameter flow channel will produce a small diameter bubble and a large diameter flow channel will produce a large diameter bubble, each with different corresponding curvature radii when applied to adherent cells.
This is motivation for someone of ordinary skill in the art to practice or test the flow channel parameter values widely to find those that are functional or optimal to apply sufficient curvature radii to remove adherent cells which then would be inclusive or cover the instantly claimed values. Absent any teaching of criticality by the Applicant concerning the diameter of the flow channel (and therefore the corresponding curvature radius of the produced bubble), it would be prima facie obvious that one of ordinary skill in the art would recognize this limitation is an optimizable variable which can be met as a matter of routine optimization (see MPEP § 2144.05 (II)(B). Those of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to make this modification in order to obtain a flow channel capable of providing the desired magnitude of force to remove adherent cells. There would have been a reasonable expectation of success in making this modification because the Jordan reference is not particularly limited to a flow channel (micropipette) with any particular diameter.
While the Jordan et al. reference does not specifically teach the limitation of
Claim 7, controlling the magnitude of the force applied from the gas-liquid interface to
the organism by controlling a surface tension between the gas and the liquid, one of
ordinary skill in the art would recognize that the surface (interfacial) tension between a
gas and a liquid is a result-effective optimizable variable. Those of ordinary skill in the
art would have recognized that the interfacial tension is a function of the characteristic
properties of the liquid and the gas. This is motivation for someone of ordinary skill in the art to practice or test the interfacial tension parameter values widely to find those that are functional or optimal to apply sufficient force to remove adherent cells which then would be inclusive or cover the instantly claimed values. Absent any teaching of criticality by the Applicant concerning the diameter of the flow channel, it would be prima facie obvious that one of ordinary skill in the art would recognize this limitation is an optimizable variable which can be met as a matter of routine optimization (see MPEP § 2144.05 (II)(B). Those of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to make this modification in order to obtain a surface tension capable of providing the desired magnitude of force to remove adherent cells. There would have been a reasonable expectation of success in making this modification because the Jordan reference is not particularly limited to any particular surface tension parameter.
The Examiner notes, as discussed above, and with regard to Claim 9, that Jordan et al. teaches forming a gas-liquid interface (bubble) between a liquid and a gas at the end portion of a flow channel after arranging/placing/immersing the end portion in a liquid so that the bubble comes into contact with adherent cells (a predetermined organism) cultured on a surface (e.g., controlling the direction of the force applied from the gas-liquid interface in contact with the cells from a gas side to the liquid side of the gas-liquid interface) (Pg. 449, Fig. 3 and Pg. 450, Column 2, Lines 3-20 and Pg. 451, Column 1 and Fig. 7).
While the Jordan et al. reference does not specifically teach the limitation of Claims 8 and 9, controlling the magnitude of the force applied from the gas-liquid interface to the organism by controlling a movement acceleration of the gas-liquid interface by controlling the movement acceleration of the flow channel, one of ordinary skill in the art would recognize that the movement acceleration of the gas-liquid interface of the bubble produced by the movement acceleration of the flow channel to the adherent cells is a result-effective optimizable variable. Those of ordinary skill in the art would have recognized that the magnitude of force on an object is equal to the objects mass times the acceleration. This is motivation for someone of ordinary skill in the art to practice or test the gas-liquid interface/flow channel movement acceleration parameter values widely to find those that are functional or optimal to apply sufficient magnitude of force to remove adherent cells which then would be inclusive or cover the instantly claimed values.
Absent any teaching of criticality by the Applicant concerning the movement
acceleration of the gas-liquid interface/flow channel, it would be prima facie obvious that
one of ordinary skill in the art would recognize this limitation is an optimizable variable
which can be met as a matter of routine optimization (see MPEP § 2144.05 (II)(B).
Those of ordinary skill in the art before the effective filing date of the claimed invention
would have been motivated to make this modification in order to obtain a gas-liquid
interface/flow channel movement acceleration capable of providing the desired
magnitude of force to remove adherent cells.
There would have been a reasonable expectation of success in making this modification because the Jordan reference is not particularly limited to any movement acceleration parameter.
The Examiner notes as discussed above, and with regard to Claim 10, that Jordan et al. teaches forming a gas-liquid interface (bubble) between a liquid and a gas at the end portion of a flow channel after arranging/placing/immersing the end portion in a liquid so that the bubble comes into contact with adherent cells (a predetermined organism) cultured on a surface (i.e., controlling the direction of the force applied from the gas-liquid interface in contact with the cells from a gas side to the liquid side of the gas-liquid interface) (Pg. 449, Fig. 3 and Pg. 450, Column 2, Lines 3-20 and Pg. 451, Column 1 and Fig. 7).
While the Jordan et al. reference does not specifically teach the limitation of Claim 10, controlling the vector includes controlling the movement acceleration of the gas-liquid interface by controlling a pressurization acceleration of the pump, one of ordinary skill in the art would recognize that the pressurization acceleration of the pump and its resultant movement acceleration of the gas-liquid interface of the produced bubble on the adherent cells is a result-effective optimizable variable. Those of ordinary skill in the art would have recognized that the pump's pressurization acceleration would directly result in the movement acceleration (e.g. such as expansion) of the gas-liquid interface (bubble). This is motivation for someone of ordinary skill in the art to practice or test the pump pressurization acceleration/gas-liquid interface movement acceleration parameter values widely to find those that are functional or optimal to apply sufficient magnitude of force to remove adherent cells which then would be inclusive or cover the instantly claimed values. Absent any teaching of criticality by the Applicant concerning the pump pressurization acceleration/gas-liquid interface movement acceleration, it would be prima facie obvious that one of ordinary skill in the art would recognize this limitation is an optimizable variable which can be met as a matter of routine optimization (see MPEP § 2144.05 (II)(B). Those of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to make this modification in order to obtain a pump pressurization acceleration/gas-liquid interface movement acceleration capable of providing the desired magnitude of force to remove adherent cells. There would have been a reasonable expectation of success in making this modification because the Moriyama reference is not particularly limited to any pump pressurization acceleration/gas-liquid interface movement acceleration parameter.
The Examiner notes as discussed above, and with regard to Claim 14, that Jordan et al. teaches forming a gas-liquid interface (bubble) between a liquid and a gas at the end portion of a flow channel after arranging/placing/immersing the end portion in a liquid so that the bubble comes into contact with adherent cells (a predetermined organism) cultured on a surface (i.e., controlling the direction of the force applied from the gas-liquid interface in contact with the cells from a gas side to the liquid side of the gas-liquid interface) (Pg. 449, Fig. 3 and Pg. 450, Column 2, Lines 3-20 and Pg. 451, Column 1 and Fig. 7).
While the Jordan et al. reference does not specifically teach the limitation of Claim 14, controlling the vector includes controlling the direction of the surface of the portion of the gas-liquid interface in contact with the organism by controlling a distance between the end portion and a bottom of a vessel accommodating the liquid, one of ordinary skill in the art would recognize that the positioning/distance of the end portion and the vessel containing the liquid including the cells is a result-effective optimizable variable. Those of ordinary skill in the art would have recognized that the distance of the bubble producing end portion from the liquid vessel bottom will affect how and to what degree the produced bubble contacts the vessel bottom. This is motivation for someone of ordinary skill in the art to practice or test the end portion/vessel bottom distance parameter values widely to find those that are functional or optimal to apply sufficient force vector to remove adherent cells on the vessel bottom which then would be inclusive or cover the instantly claimed values.
Absent any teaching of criticality by the Applicant concerning the end portion to
vessel bottom distance, it would be prima facie obvious that one of ordinary skill in the
art would recognize this limitation is an optimizable variable which can be met as a
matter of routine optimization (see MPEP § 2144.05 (II)(B). Those of ordinary skill in
the art before the effective filing date of the claimed invention would have been
motivated to make this modification in order to obtain an end portion to vessel bottom
distance capable of providing the desired force vector to remove adherent cells. There
would have been a reasonable expectation of success in making this modification
because the Jordan reference is not particularly limited to any end portion to vessel
bottom distance.
The Examiner notes as discussed above, and with regard to Claim 15, that Jordan et al. teaches forming a gas-liquid interface (bubble) between a liquid and a gas at the end portion of a flow channel after arranging/placing/immersing the end portion in a liquid so that the bubble comes into contact with adherent cells (a predetermined organism) cultured on a surface (i.e., controlling the direction of the force applied from the gas-liquid interface in contact with the cells from a gas side to the liquid side of the gas-liquid interface) (Pg. 449, Fig. 3 and Pg. 450, Column 2, Lines 3-20 and Pg. 451, Column 1 and Fig. 7).
While the Jordan et al. reference does not specifically teach the limitation of Claim 15, wherein controlling the vector includes preparing a flow channel having an inner diameter corresponding to a direction of a force to be applied to the organism, one of ordinary skill in the art would recognize that the inner diameter of the flow channel is a result-effective optimizable variable. Those of ordinary skill in the art would have recognized that a small diameter flow channel will produce a small diameter bubble and a large diameter flow channel will produce a large diameter bubble, each with different corresponding directions of force when applied to adherent cells. This is motivation for someone of ordinary skill in the art to practice or test the flow channel parameter values widely to find those that are functional or optimal to apply sufficient force to remove adherent cells which then would be inclusive or cover the instantly claimed values. Absent any teaching of criticality by the Applicant concerning the diameter of the flow channel, it would be prima facie obvious that one of ordinary skill in the art would recognize this limitation is an optimizable variable which can be met as a matter of routine optimization (see MPEP § 2144.05 (II)(B). Those of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to make this modification in order to obtain a flow channel capable of providing the desired magnitude of force to remove adherent cells. There would have been a reasonable expectation of success in making this modification because the Jordan reference is not particularly limited to a flow channel with any diameter.
Response to Arguments
Applicant’s arguments, see Remarks, filed 04/10/2026, with respect to the withdrawn rejections of Claims 1-10 and 12-17 under 35 U.S.C. § 102(a)(1), 35 U.S.C. § 102(a)(2) and 35 U.S.C. § 103 have been fully considered and are persuasive.
Applicant's remaining arguments have been fully considered but they are not persuasive.
The Applicant argues that with respect to Claim 5, the Specification references the flow channel in a nozzle and Paragraph [0298]-[0299] describe a relationship between an inner diameter of a flow nozzle (containing the flow channel) and the curvature radius of the gas-liquid interface. Applicant asserts that [0299] indicates that controlling the inner diameter of the nozzle enables control of the pushing force applied by the gas-liquid interface to the target (Remarks, Pg. 7, Lines 1-8).
This is not found to be persuasive for the following reasons, the cited paragraphs [0298]-[0299] are only drawn to a specific example/embodiment of the relationship between the inner diameter of the nozzle (not found in the claims) and the curvature radius r of the gas-liquid interface. Furthermore, as discussed above, the description in the Specification is not limited to the sole relationship between the flow channel diameter and the magnitude of any applied force, contains other variables and is drawn to specifics not found in the instant claims.
Thus, it remains unclear what the relationship/correspondence is between the diameter of the flow channel and the magnitude of the organism applied force as claimed.
The Applicant argues that the rationale set forth above with regard to Claim 5 is the same as applied to Claim 6 (Remarks, Pg. 7, Lines 9-12).
This is not found to be persuasive for the reasoning provided above with regard to Claim 5.
The Applicant argues with regard to Claim 7 that Paragraphs [0289]-[0296] describe how to control the interface free energy (surface tension) of the gas-liquid interface at the contact point of the gas-liquid interface with a manipulation target and Paragraph [0291] describes how controlling internal pressure of a bubble controls a maximum value of force applied in the direction in which the gas-liquid interface pushes the manipulation target (Remarks, Pg. 7, Lines 13-19).
This is not found to be persuasive for the following reasons, the cited paragraphs are drawn to specific examples/embodiments which contain other variables and are drawn to specifics not found in the instant claims. Thus, it remains unclear what the
relationship/correspondence is between the magnitude of applied force at the gas-liquid
interface to the organism and the surface tension between the gas and liquid as claimed.
With regard to Claim 8, the Applicant argues that the Examiner quoted citation specifically states that the magnitude of applied force can be controlled by controlling the movement acceleration of the gas-liquid interface and cites other teachings in the disclosure of controlling movement acceleration of the gas-liquid interface and flow channel (Remarks, Pg. 7, Lines 20-27).
This is not found to be persuasive for the following reasons, the citations do not indicate or explain exactly what the relationship/correspondence is between the magnitude of applied force at the gas-liquid interface to the organism and the movement acceleration of the gas-liquid interface/flow channel. The description is not limited to the sole relationship between the magnitude of force and movement acceleration of the gas-liquid interface, contains other variables, do not mention the flow channel at all in some embodiments, and are drawn to specifics not found in the instant claims. Thus, it remains unclear what the relationship/correspondence is between the magnitude of applied force at the gas-liquid interface to the organism and the movement acceleration of the gas-liquid interface/flow channel.
With regard to Claim 10, the Specification cited by the Examiner describes the bubble formed at the end portion of the nozzle and Paragraphs [0289]-[0310] of the published application describe in detail how to control the bubble in various ways, including controlling acceleration at which gas is supplied to or removed from the syringe pump.
Applicant notes that such acceleration will change pressurization of the bubble at the end portion of the nozzle (containing the flow channel) (Remarks, Pg. 7, Lines 28-30 and Pg. 8, Lines 1-6).
This is not found to be persuasive for the following reasons, the citations do not indicate or explain exactly what the relationship/correspondence is between the movement acceleration of the gas-liquid interface and the pressurization acceleration of the pump. The descriptions are not limited to the sole relationship between pump pressurization acceleration and movement acceleration of the gas-liquid interface and contains other variables, such as a bubble, syringe pump and nozzle not found in the instant claims. Thus, it remains unclear what the relationship/correspondence is between pressurization acceleration and the movement acceleration of the gas-liquid interface/flow channel.
With regard to Claims 12 and 14, the Applicant argues that “direction” and “moving direction” are two different things and the Specification indicates regarding the direction of the surface in contact with the organism, crushing of the bubble can change direction of the point P which contacts the manipulation target while moving direction of the surface is a function of how the gas-liquid interface is moving. Applicant asserts that the Specification and figures describe numerous way the interface can move noting that when it moves, P also moves but that movement is not necessarily in the same direction as the direction P itself (Remarks, Pg. 8, Lines 7-15 and Pg. 9, Lines 1-2).
This is not found to be persuasive for the following reasons, the citations do not indicate or explain exactly what the relationship/correspondence is between the direction of the force applied from the gas-liquid interface to the organism and the moving direction of a surface of the gas-liquid interface in contact with the organism or the curvature radius of the portion of the gas-liquid interface in contact with the organism or what the relationship/correspondence is between the direction of a surface of the gas-liquid interface in contact with the organism and the distance between the portion and the bottom portion of the vessel containing the liquid. The citations do not indicate or explain exactly what the relationship/correspondence is between the direction of force applied by the gas-liquid interface to the organism and the moving direction of the surface of the portion of the gas-liquid interface in contact with the organism or the curvature radius thereof. The description is not limited to the sole relationship between the direction of the gas-liquid interface and the direction of applied force or the curvature radius of the portion of the gas-liquid interface contacting the organism or the sole relationship between the direction of the surface of the portion of the gas-liquid interface with the organism and the distance between the end portion and a bottom of the liquid containing vessel and contains other variables, such as a nozzle and curvature radius not found in the instant claims. Thus, the claims remain unclear for reasons of record set forth in the prior action and above.
Conclusion
No claims are allowed.
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.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to PAUL C MARTIN whose telephone number is (571)272-3348. The Examiner can normally be reached Monday-Friday 12pm-8pm EST.
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, Sharmila G Landau can be reached at (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL C MARTIN/Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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