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 .
Response to Amendment
Applicant’s amendment filed on 03/25/26 has been entered. Claim 11 is cancelled. Claims 15-21 remain withdrawn. Claims 1-10, 12, and 14 are pending and examined herein. Applicant’s remark and amendment have overcome each and every objection set forth in Office Action mailed on 12/29/2025.
Status of Rejection and Objection
The objection of claim 5 is withdrawn in light of Applicant’s amendment.
The rejection of claim 11 is obviated by Applicant’s cancellation.
The 103 rejections of claims 1-10, 12, and 14 are maintained.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 1-6, 8, 9, 12, and 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Endo (US 4749270 A) in view of El-Badry (Micromanipulators and Micromanipulation, 1963) as cited in previous Office Action.
Regarding claim 1 and 4, Endo discloses a bio-manipulator (Fig. 2), comprising:
a displacement hydraulic controller (joystick of Fig 2 and 9 (also known as hydraulic operator 26, Fig. 9) connected to the hydraulic drive mechanism 17 in Fig. 2, 6 and 7;) comprising a housing (hard rest 60, Fig. 9), an internal sealing assembly comprising a sealing assembly housing (housing surrounded the piston rod 45, Fig. 7 and a screw (the piston rod is securely secured by screws, secured to the piston rod 45 by a set screw. Col. 8, ln 38-39), a piston-style actuator (piston rod 45, Fig. 7), and screws to hold the assembled controller together (screw 12b, Fig. 6 and 7);
a junction box (28 and 30, Fig 12, along with portion of holder 35 above transparent disc 75 extending to connection with tube 19, "annular support frame 28", col 4 In 25, and "feed frame 33", col 4 In 30-31), wherein a portion of the junction box is optically transparent ("FIGS. 11 and 12 show another form of needle carrier 15A. Instead of being carried by the holder frame 33 as shown in FIGS. 4 and 5, in this instance, a transparent disc 75 is fitted in the feed frame 30", col 9 In 54-57);
an extrusion head (portion of holder 35 below transparent disc 75, Fig 11; "holder 35", col 9 In 60) in fluidic communication with the junction box (portion of holder 35 above transparent disc 75 and portion of holder 35 below transparent disc 75 are in fluid communication to allow fluid from tube 19 to provide pressure for glass needle), displacement controller ("Accordingly, it is possible to oscillate the joystick 70 within the slot 60a in a direction indicated by a double-ended arrow B about the articulation member, thus causing the slider 66 to slide in either of the directions indicated by the arrow A, acting through the ball 66a." col 8 In 10-15; "The other end of the piston rod 65 is connected to the slider 66 which is slidable on the base 59 in the horizontal direction, as indicated by a double-ended arrow A" col 7 In 61-64; see fig 10; see fig 10, piston rod 65 is fluidly coupled with hydraulic drive mechanism 17 which communicates with holder 35 through support frame 28), and macro-hydraulic controller("so that the rotation of the knob 74 causes an axial movement of the piston rod 73." col 8 In 24-26, piston rod 73 is fluidly coupled with hydraulic drive mechanism 17 which communicates with holder 35 through support frame 28); and
an adapter (12a, Fig 2; "dovetail 12a") configured to mechanically couple the extrusion head to the optical axis of a microscope ("a stage 12 is detachably mounted relative to the body 10 through a translational structure including a dovetail 12a and a dovetail groove 10a" col 3 In 52-54, Stage 12 includes holder 35 and body 10 is a microscope, "As shown, the microscope includes a body 10," col 3 In 47 -48. The translational structure is designed to move the extrusion head to the optical axis of the microscope, "The glass needle is carried by an annular needle holder in the direction of the optical axis" col 2 In 56-58);
wherein the hydraulic controller comprises a piston-style actuator (The threaded shaft 55 is threadably engaged with the hydraulic cylinder 54 which is threadably engaged with the head 50, and the piston rod 58 is fitted into a central axial bore therein which is coaxial with the transmission shaft 51. Col. 6 lines 48-52) consisting a shaft (hydraulic cylinder 54) having a threaded portion (threaded shaft 55, Fig. 8) and a non-threaded portion (piston rod 58, Fig. 8).
The embodiments of Endo only show a configuration with one hydraulic controller instead of two. Furthermore, Endo does not explicitly disclose hydraulic controller of Endo comprises a gasket to prevent fluid leakage.
Regarding installing a gasket in the hydraulic controller, El-Badry discloses it is typical for capillaries/cylinders to be inserted into a holder/housing firmly and sealed by means of rubber gasket (A long polyethylene tubing of about 0.4-mm internal diameter connects the microinjector to an angle-type micropipet holder designed for use with the micromanipulator. Capillaries inserted in the holder are firmly sealed by means of neoprene rubber gaskets. The microinjection unit may be used separately, and the holder may be, page 65, para. 4).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date to have utilized gasket to firmly secured the cylinders (cylinders 41, Fig. 7) inside of hydraulic controller of Endo as taught by El-Badry. Doing so allows the components of device be securely sealed inside the housing of the controller.
Regarding having a second displacement hydraulic controller and a threaded shaft of one of the controllers having a larger diameter than the other, Endo discloses the device can be further modified with multiple hydraulic drive mechanism connected together (Col. 2, ln 61-66) for coarse and/or fine adjustment motion (Fig. 9 and 14)(In particular, claims 34 and 35 state “where one of said second and third hydraulic drive mechanisms provides for a coarse adjustment of the needle” and wherein the remaining one of said second and third drive mechanisms provides for a fine adjustment of said needle).
El-Badry discloses a micromanipulator (Fig. 13, page 40) comprising two pistons (two perpendicularly intersected piston on the left-hand side of Fig. 13), wherein the one of the pistons have a larger diameter than the other (Operation depends on the displacement of hydraulic fluid by one of the two pistons. The larger piston, the coarse volumetric control, has a diameter of about 0.4 mm, while the smaller piston, providing fine displacement, is about 0.125 mm in diameter. Page 40, para. 1). It would have been obvious to one of ordinary skill in the art before the effective filing date to have modified the two hydraulic controllers of the device of Modified Endo based on the design of El-Badry to derive the claimed invention. Having two controllers with different piston diameters allows the operator a more delicate control to volume displacement of the fluid (The larger piston, the coarse volumetric control, has a diameter of about 0.4 mm, while the smaller piston, providing fine displacement. Page 40, para. 1).
Regarding claim 2, Modified Endo discloses the claimed invention as discussed above in claim 1. Endo discloses the extrusion head further comprises an adapter configured to receive interchangeable tip (clamp screw 36, Fig 12; "having a clamp screw 36 which is used to secure the glass needle 16" col 4 In 35-36).
Regarding claim 3, Modified Endo discloses the claimed invention as discussed above in claim 2. Endo discloses the adapter configured to receive interchangeable tips is a tapered nozzle (see fig 5, clamp screw 36 is shown to be in the shape of a nozzle with a tapered end) configured to receive micropipette tips, a tapered nozzle with an orifice configured to receive a glass capillary, or a sealed adapter configured to receive a luer-lock syringe needle (clamp screws are capable of receiving and securing any of the above devices).
Regarding claim 5-6 and 9, Modified Endo discloses the claimed invention as discussed above in claim 1. Endo discloses the two displacement hydraulic controllers (after modification as discussed above in claim 1) are in fluidic communication with the junction box through tubing (hydraulic transmission tube 25 and 27; Fig 3) filled with a first fluid, wherein the first fluid is a non-biocompatible fluid (oil, col. 6, ln 12-26), and
The extrusion head and junction box are in fluidic communication through tubing filled with a second fluid (col. 5, ln 4-23), where in the second fluid different than the first fluid (liquid chemical; col. 5, ln 15-23), wherein the second fluid is a bio-compatible fluid (the liquid chemical is being deposited to the stage of the microscope station, and therefore, it needs to be bio-compatible to the biological sample being analyzed).
Regarding claim 8, Modified Endo discloses the claimed invention as discussed above in claim 5. Endo discloses the second fluid forms an immiscible layer with the first fluid in the junction box (whereby by filling the tube 19 with a silicone oil or the like, pressure can be applied to a liquid chemical contained within the glass needle 16 to displace it from the needle tip. col. 5, ln 15-23; the silicone oil in the tube is used to push the liquid chemical out to the stage, which can only work if the two fluids are immiscible).
Regarding claim 12, Modified Endo discloses the claimed invention as discussed above in claim 1. Neither Endo nor El-Badry explicitly discloses the threaded rods specification for the macro-displacement hydraulic controller.
As the displaced volumes of fluid are variables that can be modified, among others, by adjusting the diameter of the piston rod, with volume displaced both increasing as the rod diameter is increased, the precise rod diameter would have been considered a result effective variable by one having ordinary skill in the art before the effective filing date of the invention. As such, without showing unexpected results, the claimed rod diameter cannot be considered critical. Accordingly, one of ordinary skill in the art before the effective filing date of the invention would have optimized, by routine experimentation, the rod diameter in the Endo to obtain the desired balance between displaced volume as taught by El-Badry (In re Boesch, 617 F.2d. 272, 205 USPQ 215 (CCPA 1980)), since it has been held that where the general conditions of the claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. (In re Aller, 105 USPQ 223). “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.). “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.).
Regarding claim 14, Modified Endo discloses the claimed invention as discussed above in claim 1. Endo discloses each hydraulic controller comprises a dial (coarse motion knob 74, Fig. 2) capable of being operated independently of the other
Claim(s) 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Endo in view of El-Badry as applied to claim 5 above, and further in view of Walsh (Formation of droplet interface bilayers in a Teflon tube, 2016) as cited in previous Office Action.
Regarding claim 7, Modified Endo discloses the claimed invention as discussed above in claim 5. Neither Endo nor El-Badry specifically discloses the first fluid is Novec-7500.
In an analogous art, Walsh discloses gas in the tubing system is problematic as it is compressible and therefore when the syringe pump starts/stops the fluid motion in the tube does not start/stop as rapidly as when no gas is present (in the context of Modified Endo, this may interfere with precise amount of fluid being displaced). To reduce/minimize bubble formation, fluorocarbon with low viscosity/partial pressure such as HFE 7500/Novec-7500 can be utilized (Forming fluidic architectures, para. 1). Therefore, it would have been obvious to one of ordinary skill in the art to have considered and adopted Novec-7500 as the first fluid in order to reduce/minimize unwanted bubble formation (Walsh, Forming fluidic architectures, para. 1).
Claim(s) 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Endo in view of El-Badry as applied to claim 5 above, and further in view of Doe (Generating CRISPR/Cas9-Derived Mutant Mice by Zygote Cytoplasmic Injection Using an Automatic Microinjector, 2018) as cited in previous Office Action.
Regarding claim 10, Modified Endo discloses the claimed invention as discussed above in claim 5. Neither Endo nor El-Badry specifically discloses the second fluid is PBS.
Phosphate buffered saline (PBS) are generally used for analyzing or preserving the cellular/biological sample under microscope. In an analogous art, Doe discloses PBS are used for storing the cellular sample (3.1, Zygote Preparation, step 4; Fig. 4).
Therefore, it would have been an obvious to one of ordinary skill in the art before the effective filing date to have utilize liquid chemicals such as PBS as the second fluid for application of analyzing cellular sample using microscope and micromanipulators as demonstrated by art like Doe.
Response to Arguments
Applicant's arguments filed 03/25/26 have been fully considered but they are not persuasive. Applicant’s remark is directed to the Office Action failing to provide construction or technical detail of the device of El-Badry that would have been incorporated to the device of Endo to derive the claimed invention (Remark Page 7, para. 3).
The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
In this case, Endo has already disclosed incorporating an additional hydraulic mechanism/controller with one for coarse motion and one for fine motion (claims 34 and 35 state “where one of said second and third hydraulic drive mechanisms provides for a coarse adjustment of the needle” and wherein the remaining one of said second and third drive mechanisms provides for a fine adjustment of said needle). However, Endo does not explicitly state or mention the difference in the shaft diameter between the coarse and fine motion handle. In this case, El-Badry disclosed that it is common for a coarse and fine motion handle of a micromanipulator to have two different diameters for more precision in controlling the hydraulic displacement (The larger piston, the coarse volumetric control, has a diameter of about 0.4 mm, while the smaller piston, providing fine displacement. El-Badry Page 40, para. 1). As a result, it would have been obvious to one of ordinary skill in the art that hydraulic drive incorporating a second hydraulic mechanism/controller for a coarser/finer rotary motion would have required a different shaft diameter compared to the shaft of the first hydraulic mechanism based on the teaching of El-Badry even when El-Badry does not sufficiently provide technical details or guidance to achieve the claimed invention.
Applicant’s second argument that “what Endo actually says is that a plurality of hydraulic drive mechanisms can be connected together through hydraulic transmission tubes for coupling them together in a simple manner” have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. In summary, Endo discloses hydraulic drive mechanism can be used for coarse rotary motion (Fig. 2, coarse motion rotary knob 74, hydraulic operator 26, and hydraulic transmission tube) and fine motion knob utilizing similar hydraulic drive mechanism (Fig. 13-14, knob 76), and fine/coarse needle adjustment (claims 34-35). El-Badry discloses utilizing two drive mechanisms with pistons of different size for fine and coarse motion control by adjusting the precise amount of hydraulic fluid used (a micromanipulator (Fig. 13, page 40) comprising two pistons (two perpendicularly intersected piston on the left-hand side of Fig. 13), wherein the one of the pistons have a larger diameter than the other (Operation depends on the displacement of hydraulic fluid by one of the two pistons. The larger piston, the coarse volumetric control, has a diameter of about 0.4 mm, while the smaller piston, providing fine displacement, is about 0.125 mm in diameter. Page 40, para. 1). Hence, as both arts utilize hydraulic drive mechanism for motion and volumetric control, one of ordinary skill in the art would have established nexus between El-Badry and Endo to derive the claimed invention of claim 1 as discussed in the rejection of claim 1 above.
For the reason above, the rejection is maintained.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/M.H./ Examiner, Art Unit 1758
/MARIS R KESSEL/ Supervisory Patent Examiner, Art Unit 1758
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