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 .
Drawings
The drawings are objected to under 37 CFR 1.83(a). The drawings must show every feature of the invention specified in the claims. Therefore, the “deposition head moving device” (Claim 14), “vibration device” (Claim 27), “blotting device” (Claim 27), “screw drive” (Claim 31), “piezoelectric drive” (Claim 31), and “sensor” (Claim 32) must be shown or the feature(s) canceled from the claim(s). No new matter should be entered.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier.
Such claim limitations are:
“a liquid depositing device configured to deposit” as in Claim 14.
“a liquid removing device configured to remove” as in Claim 14.
“a deposition head moving device configured to move” as in Claim 14.
“a vibration device operable to vibrate” as in Claim 27.
“a blotting device operable to extract” as in Claim 27.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
“a pipette or a syringe...[or]...a series of through-channels, extending from a rear of the deposition head to spaces between the pads” as in Paras. [0139-0140] of Applicant’s instant pre-grant publication US 2024/0393215 A1, and equivalents thereof.
“a vibration device operable to vibrate the array of pad and a blotting device operable to extract liquid...a series of through-channels in the deposition head that connect to spaces between the pads” as in Paras. [0141-0142] of Applicant’s instant pre-grant publication US 2024/0393215 A1, and equivalents thereof.
“a linear motion stage” as in Para. [0144] of Applicant’s instant pre-grant publication US 2024/0393215 A1, and equivalents thereof.
“a solenoid, a magnet and coil, a piezoelectric device such as a tube scanner, and/or a linear translation stage” as in Para. [0040] of Applicant’s instant pre-grant publication US 2024/0393215 A1, and equivalents thereof.
“glass fiber filter paper” as in Para. [0078] of Applicant’s instant pre-grant publication US 2024/0393215 A1, and equivalents thereof.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
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 17-18, 23-25, and 33 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 17, the term “an electron-microscope-imaging-accessible area” is a relative term which renders the claim indefinite. The term “an electron-microscope-imaging-accessible area” 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. The area size may be different depending on the particular electron microscope and distance from the electron beam and/or detector. Thus, one of ordinary skill in the art would not possibly determine without ambiguity the metes and bounds of the claimed electron-microscope-imaging-accessible area. Claim 18 is thereby further rejected by virtue of dependence on Claim 17.
Regarding Claim 25, the claim recites “wherein the liquid depositing device includes a pipette or a syringe”; however, the liquid depositing device is not provided with a structural or functional description so as to link the pipette/syringe to said liquid depositing device, and thereby amounts to a mere parts listing. As such, the metes and bounds of the position/function of the pipette/syringe within the system is unclear.
Regarding Claims 23-24 and 33, the claims recite “per unit area” appearing to refer to particular regions/areas of the foil onto which sample is deposited. However, the claims fail to particularly point out what is meant by “unit area” as claim 14 fails to establish sectioning of the foil into unit areas, or some other recitation establishing the sought meaning. By this, the metes and bounds of the “per unit area” designation provided in Claims 23-24 and 33 are unclear as the “unit area” is arbitrarily introduced without structural or functional linkage to the foil and/or stamping system.
Claim Rejections - 35 USC § 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 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.
Claims 14-15, 17-25, 27-28, 30, and 34-35 are rejected under 35 U.S.C. 103 as being unpatentable over Ho et al. (Ho, Cheng-En; et al.; “Micro-Stamp Systems for Batch-Filling, Parallel-Spotting, and Continuously Printing of Multiple Biosample Fluids”, SLAS Technology, Volume 13, Issue 4, August 2008, Pages 187-197.), hereinafter “Ho”, in view of Carragher et al. (US 2014/0360286 A1), hereinafter “Carragher”.
Regarding Claim 14, Ho teaches a system for depositing a sample-containing liquid onto a sample support (See Fig. 6 showing the glass sample support. See also Fig. 1.), the system comprising:
a deposition head including an array of pads lying within a first plane (See Ho Fig. 1 showing the “PDMS micro stamper array”; and Fig. 6 showing an array of the “PDMS stamp(s)” corresponding to the claimed array of pads, and wherein the blue outer frame supporting the microchannels holding the PDMS pads is the deposition head. – See also page 188, the “System Introduction” section: “Among various micro printing schemes, most of which can deal with very limit types of proteins at one time; yet the back filling of a micro-stamp chip including reservoirs with PDMS stamps can parallelly print 4-10 proteins simultaneously.”);
a liquid depositing device (See Abstract and page 189: “the filling chip”.) configured to deposit a volume of the sample- containing liquid on top of the array of pads (See Abstract and page 189, the “System Introduction” section: “This system consists of a filling chip and a stamping chip. The filling chip can simultaneously transfer tens of proteins into the stamping chip...” – See also Figs. 5 and 6 showing the filling chip loading sample onto the stamping chip.);
a liquid removing device configured to remove an amount of the sample-containing liquid and thereby leave isolated drops of the sample-containing liquid on each pad in the array of pads (See Fig. 1 showing the “micro-channel” array connecting to each PDMS stamper, the microchannel array being the liquid removing device, commensurate with the Claim Interpretation under 35 USC 112(f) discussed in the section above. See also Abstract: “Different proteins can be dispensed into the corresponding channels and driven into the tips of the micro stamps.” – See also Fig. 6 showing the “micro vertical channel(s)”, and the “System Introduction” section on page 188.); and
Further regarding Claim 14, Ho does not specifically teach the system discussed above as used in a cryo-electron microscopy process, the sample support including a support grid and a foil, nor a deposition head moving device configured to move the array of pads with the drops of the sample-containing liquid into contact with the foil of the sample support to thereby transfer the sample-containing liquid from each of the pads to the foil, as in Claim 14.
However, Carragher teaches a respective bioanalyte printing system ([0014, 0024]) used in a cryo-electron microscopy process ([0025] and Examples 1-4) wherein the bioanalyte liquid is deposited on a sample support including a support grid and a foil (See para. [0042]: “dispensed onto continuous carbon and holey carbon grids” and note that the present specification paras. [0066, 0091, 0118] expressly treat the foil as a carbon foil as in Carragher.). Further, Carragher teaches a deposition head moving device (linear motor/actuator) configured to move the array of pads (See para. [0034]: “During the dispense phase, the stack assembly position is maintained static, while the grid is driven downwards by the motor.”. -- See further paras. [0032-0033].) with the drops of the sample-containing liquid into contact with the foil of the sample support to thereby transfer the sample-containing liquid from each of the pads to the foil (See Carragher Claim 3.). Therein, this automated arrangement provides a controlled and repeatable means for depositing biological samples for analysis, ensuring consistent stamping across runs, and wherein carbon foil is a common substrate for cryo EM analysis.
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the system of as used in a cryo-electron microscopy process, the sample support including a support grid and a foil, nor a deposition head moving device configured to move the array of pads with the drops of the sample-containing liquid into contact with the foil of the sample support to thereby transfer the sample-containing liquid from each of the pads to the foil, such as suggested by Carragher, as H0 achieves the same desired result of samples including protein samples deposited in a controlled manner on a surface and would thereby be an obvious substitution for the similarly structured contact pins of Carragher, wherein H0 would enjoy the benefits of automated dispensing of Carragher including improved consistency between runs.
The modification merely applies the known automatic contact printing system (as provided by the deposition head moving device) of Carragher to provide precise repeatable movement to the known pad array contact print head of Ho for standardized controlled contact between the stamp array of Ho and the foil, thereby representing a reasonable expectation of success regarding the combination. Additionally, as the stamping system of Ho achieves the identical result of Carragher of printing a fluid array on a sample holding surface, one skilled in the art would recognize Ho as applicable to a cryo EM process identically utilizing such sample deposition.
Further note that, while Examiner has provided the rejection above including the cryo EM process and the sample support/foil, the recitation “for depositing a sample-containing liquid onto a sample support used in a cryo-electron microscopy process” merely describes a capability of and/or intended use of the claimed device given the term “for” indicating a use of the system. Applicant may wish to amend the claim to recite something on the order of “for depositing a sample-containing liquid used in a cryo-electron microscopy process, the system comprising a sample support including a support grid and a foil...” so as to positively claim and require the sample support/foil. However, in the absence of particular structure of specific functionality related thereto, the system being used for preparing a sample for a cryo EM process remains a mere intended use: Limitations based on the intended use of a structure do not confer patentability if the prior art is capable of performing the same function – see MPEP 2111.02(II). When an apparatus is claimed, its patentability is based on the structure of the apparatus and not on the function it performs or the field in which it is applied. In this case, whether the system is used for preparing a sample for a cryo EM process or some other different type of analysis is immaterial, as the function of depositing small-volume arrays of biological samples for analysis remains the same.
Regarding Claim 15, the prior art meets the limitations of Claim 14 as discussed above. Further, Ho teaches the system discussed above wherein the deposition head is covered with the pads, and wherein the pads are substantially flat (See Fig. 1a showing the PDMS stamps as being substantially flat and covering bottom portions of the deposition head (horizontal yellow rectangle) to form the print surface.), as in Claim 15.
Regarding Claim 17, the prior art meets the limitations of Claim 14 as discussed above. Further, Ho teaches the system discussed above wherein a diameter of the array of pads is approximately equal to an electron-microscope-imaging-accessible area of the support grid of the sample support (See Fig. 2a showing an electron micrograph of the PDMS stamp array, thereby being approximately equal to an electron-microscope-imaging-accessible area of the support grid of the sample support as the support grid corresponds to the individual stamps of the stamp array. – See further the 35 USC 112 section above.), as in Claim 17.
Further regarding Claim 17, Ho does not specifically teach the system discussed above wherein the array of pads is arranged within a circle on the deposition head, as in Claim 17.
However, this recitation is interpreted as merely requiring the array of pads be arranged in a circular orientation about the deposition head, such as seen through Fig. 11 showing the deposition head 800 having a circle of space surrounding the pads and channels, and is thereby a mere alternative arrangement to the pads arranged within a rectangle on the deposition head of Ho, the pads merely being arranged in a rectangular configuration instead of being bound by a circular head shape. Mere change in orientation or position of elements absent any criticality or unexpected result is an obvious matter of design choice – see MPEP 2144.04(VI)(C). Herein, one of ordinary skill in the art would find it obvious that the device having the claimed relative arrangement of pads within a circle as claimed would not perform differently than the prior art device of Ho having pads within a rectangle (Fig. 1), absent evidence of criticality, non-obviousness, or unexpected results associated with the position of the claimed pads within a circle. Further note that the “a circle” may also be interpreted as a mere spatial designator not having actual structure within the system. Applicant may wish to amend the claim to provide a structural element such as “a circular groove” or “a circular ridge” if a surrounding structure about the pads is what is desired.
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the system of Ho wherein the array of pads is arranged within a circle on the deposition head, as a mere obvious matter of design choice not impacting the stamping function of the pads, and thus has a reasonable expectation of success.
Regarding Claim 18, the prior art meets the limitations of Claim 17 as discussed above. Further, Ho does not specifically teach the system discussed above wherein the diameter of the array of pads is about 2 mm to about 2.5 mm, as in Claim 18.
However, as discussed above regarding Claim 14, one of ordinary skill in the art would find it obvious to substitute the stamping arrangement of Hu in the cryo EM application discussed by Carragher achieving the identical purpose of the printhead in Carragher of disposing droplets of biological sample onto a surface. Therein Carragher, the grid area is 2 mm diameter ([0037]).
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious that, when modifying the system of Ho, to provide the 2 mm diameter grid area of Carragher as a typical grid size for cryo EM. Given this modification, one skilled in the art would find it obvious to provide the diameter of the array of pads as about 2 mm so as to utilize the complete area of the grid of the cryo EM application in Carragher.
Regarding Claim 19, the prior art meets the limitations of Claim 14 as discussed above. Further, Ho teaches the system discussed above wherein each of the pads has a diameter of between about 2 μm and about 50 μm (See page 188, the “Manufacturing and Printing Results” section: “inner hole diameter [of the stamp]: 50 μm”. Satisfies the “a diameter” of the pad. Applicant may wish to specify the outer diameter in the claim if this is desired.) and is configured to support thereon a drop volume of the drops of the sample-containing liquid of between about 0.1 femtoliters and about 10 picoliters (Given the commensurate arrangement of Ho as in Claim 14 and stamping diameter of about 50 μm as claimed herein, Ho would be commensurately expected to be fully capable of and configured to commensurately support drops of the sample-containing liquid of between about 0.1 femtoliters and about 10 picoliters; no structural distinction preventing Ho from handling similarly sized droplets is present. Further, one of ordinary skill in the art would find it obvious to optimize via routine experimentation the volumes capable of being supported by a respective stamp pad for the volume requirements of a particular assay or limited sample at hand.), as in Claim 19.
Regarding Claim 20, the prior art meets the limitations of Claim 14 as discussed above. Further, Ho teaches the system discussed above wherein top surfaces of the pads are hydrophilic or are covered with a hydrophilic material (See page 188, the “Manufacturing and Printing Results” section: “Before stamping, O2 plasma treatment was used to transform the SU8 channels and PDMS stamps hydrophilic.”), as in Claim 20.
Regarding Claim 21, the prior art meets the limitations of Claim 14 as discussed above. Further, Ho teaches the system discussed above wherein a surface of the deposition head between the pads is hydrophobic or is covered with a hydrophobic material (In Hu, the deposition head having the microchannels passing therethrough (Fig. 6, horizontal yellow rectangle) is formed of SU-8 polymer, normally hydrophobic, wherein Ho describes transforming the PDMS stamps and the SU-8 microchannels hydrophilic by plasma treatment (page 188: “Before stamping, O2 plasma treatment was used to transform the SU8 channels and PDMS stamps hydrophilic.”); however, Ho does not discuss treating the SU-8 spaces between the pads. Thus, Ho reasonably suggests that the surface of the deposition head between the pads is hydrophobic being made of untreated SU-8 polymer.), as in Claim 21.
Regarding Claim 22, the prior art meets the limitations of Claim 14 as discussed above. Further, Ho teaches the system discussed above wherein the pads are made with a compliant material, the compliant material including a polydimethylsiloxane (PDMS) and/or an SU-8 epoxy-based photoresist (See page 188, the “Manufacturing and Printing Results” section: “The stamp was fabricated by the incorporation of SU8 lithography and PDMS molding.”), as in Claim 22.
Regarding Claim 23, the prior art meets the limitations of Claim 14 as discussed above. Further, Ho teaches the system discussed above wherein an areal density of the pads, a diameter of the pads, and a liquid contact angle on the pads corresponds to a predefined final average liquid thickness across a full area of the foil (The foil being provided by Carragher as discussed above regarding Claim 14.) to be contacted by the array of pads and to a predefined average liquid volume per unit area (Given that the areal density of pads and the diameter of pads in Hu correspond to the spotted diameter and density of spots, and the contact angle corresponds to an amount of liquid on the pads, such parameters commensurately correspond to a predefined final average liquid thickness spotted across a full area of the foil, the thickness being in direct relation to the amount of liquid deposited. – See Fig. 6f.), as in Claim 23.
Regarding Claim 24, the prior art meets the limitations of Claim 14 as discussed above. Further, Ho does not specifically teach the system discussed above wherein the predefined final average liquid thickness is between about 5 nm and about 150 nm and the average liquid volume per unit area is between about 10 pL and about 150 pL per square millimeter, as in Claim 24.
However, it would have been obvious to one of ordinary skill in the art to optimize the amount of sample deposited per unit area and thickness thereof according to the requirements and constraints of the particular assay being performed. Such as in the case of cryo EM when combined with Carragher, the film thickness must be sufficiently thin for electron transmission while still containing an adequate amount of sample for imaging. In mixing and reaction cases, the volume of sample is tuned for the particular assay reagent ratios, and in optical analysis the sample thickness may be tuned to an optimal range for optical analysis to avoid over/under-saturation effects (Hook/Prozone).
The deposited volume therefore constitutes a known result-effective variable which would have been routinely adjusted by a skilled artisan based on factors such as assay type, sample concentration, grid area, and desired imaging quality, with a reasonable expectation of success obtaining a suitable film, including the claimed thickness and volume-per-area ranges, given the commensurately scaled pads of Ho. See (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).
Further, Carragher teaches a sample thickness range of about 50 nm to about 500 nm ([0025]: “Ideally the vitrified layer should be just slightly thicker than the diameter of the particle (50-500 nm)”) wherein one skilled in the art would find it obvious to utilize this range in Ho for the cryo EM application of Carragher so as to provide a suitable sample thickness meeting the thickness constraints of cryo EM. As Ho's teaching of range about 50 nm to about 500 nm overlaps with the instant claimed range of about 5 nm to about 150, a prima facie case of obviousness exists in view of In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990), absent contrary evidence of criticality or non-obviousness of the claimed range. Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to select the overlapping portion of the range so as to maximally achieve the optimal sample thickness for cryo EM in the combination of Ho and Carragher.
Regarding Claim 25, the prior art meets the limitations of Claim 14 as discussed above. Further, Ho teaches the system discussed above wherein the liquid depositing device includes a pipette or a syringe (See page 190, the “System Operation” section: “Different protein solutions were loaded into the reservoirs of the micro-filling chip using a pipette, as depicted in Figure 6a.”), as in Claim 25.
Regarding Claim 27, the prior art meets the limitations of Claim 14 as discussed above. Further, Ho teaches the system discussed above wherein the liquid removing device includes a vibration device operable to vibrate the array of pads and/OR a blotting device operable to extract liquid from the array of pads (See Fig. 1 showing a blotting device (bottom grey rectangle) extracting liquid from the pad array (and thereby being an equivalent thereof the disclosed glass fiber filter paper – see the Claim Interpretation section above) to produce the bio-sample array. – As Applicant has provided an alternative-type “or” recitation, only one of the alternatives of the vibration device or the blotting device is required to be taught by the prior art. Herein, Ho teaches the blotting device, Ho does not appear to teach a vibration device.), as in Claim 27.
Regarding Claim 28, the prior art meets the limitations of Claim 14 as discussed above. Further, Ho teaches the system discussed above wherein the liquid removing device includes a series of through-channels in the deposition head that connects to spaces between the pads (See Fig. 1 showing the “micro channel(s)” through the deposition head and Fig. 6A showing the PDMS stamp pads connecting to the “micro vertical channel”.), wherein the series of through-channels is configured to withdraw the sample-containing liquid in the spaces between the pads through the rear of the deposition head (See Abstract: “Different proteins can be dispensed into the corresponding channels and driven into the tips of the micro stamps.”. – See also Page 193: “By the capillary force, protein solutions flowed into the micro channel of the stamper chip (Fig. 12b) in seconds.”.), as in Claim 28.
Regarding Claim 30, the prior art meets the limitations of Claim 14 as discussed above. Further, Ho is modified in view of Carragher, as discussed above regarding Claim 14, so as to provide the deposition head moving device to ensure consistency in sample deposition between replicate runs. Therein Carragher, the deposition head moving device includes a linear motion stage configured to move the deposition head and the array of pads ([0034]: “During the dispense phase, the stack assembly position is maintained static, while the grid is driven downwards by the motor.” – See also paras. [0019], [0032-0033]: “X-Y-Z stage”.), as in Claim 30.
Regarding Claim 34, the prior art meets the limitations of Claim 14 as discussed above. Further, Ho teaches the system discussed above wherein a contact angle of the sample-containing liquid on each of the pads is between about 0° and 30° (Given the commensurate arrangement of the pad array of Ho as in Claim 14, one of ordinary skill in the art would expect the pad array of Ho to commensurately display or be capable of a contact angle of the sample-containing liquid on each of the pads between about 0° and 30°. Further, the liquid sample is not a positively claimed element of the presently claimed system; thus, particulars to the contact angle of such liquid sample hold no patentable weight. Applicant may wish to amend the claim to provide the desired contact angles as configurations of the pads rather than prospective behavior of a prospective sample liquid. Additionally, as the contact angle relates to the amount of sample dispensed, with a greater contact angle indicating a greater volume of sample, one of ordinary skill in the art would find it obvious to optimize through routine experimentation the sample liquid contact angle with the pad so as to achieve a desired amount/volume of deposited liquid for a particular assay at hand.), as in Claim 34.
Regarding Claim 35, the prior art meets the limitations of Claim 14 as discussed above. Further, Ho teaches the system discussed above wherein the deposition head includes a series of through-channels extending from a rear of the deposition head to spaces between the pads (See Fig. 1 showing the “micro channel(s)” through the deposition head and Fig. 6A showing the PDMS stamp pads connecting to the “micro vertical channel”.), the series of through-channels configured to receive therethrough the sample-containing liquid to be deposited on the pads by injecting the sample-containing liquid from the rear of the deposition head into the spaces between the pads and onto tops of the pads (See Abstract: “Different proteins can be dispensed into the corresponding channels and driven into the tips of the micro stamps.”. – See also Page 193: “By the capillary force, protein solutions flowed into the micro channel of the stamper chip (Fig. 12b) in seconds.”.), as in Claim 35.
Claim 29 is rejected under 35 U.S.C. 103 as being unpatentable over Ho in view of Carragher, as applied to Claims 14-15, 17-25, 27-28, 30, and 34-35 above, and in further view of Tisone et al. (US 2008/0227663 A1), hereinafter “Tisone”.
Regarding Claim 29, the prior art meets the limitations of Claim 14 as discussed above. Further, Ho in view of Carragher does not specifically teach the system discussed above wherein the deposition head connects to a syringe and a syringe pump collectively configured to inject the sample-containing liquid into and/or onto the deposition head and remove the sample-containing liquid from the deposition head, as in Claim 29.
However, Tisone teaches a respective system for printing small-volume biological sample arrays for analytical testing ([0003]: “systems and methods for high speed array printing”, [0077]: “desirable tools for automated ultra-low volume liquid handling of biological samples”) wherein the print/deposition head connects to a syringe and a syringe pump collectively configured to inject the sample-containing liquid into and/or onto the deposition head (See Fig. 2F showing the syringe pump 520 connected to the deposition head (printing manifold) 509 for supplying a continuous supply of sample/reagent liquid – see para. [0232].) and remove the sample-containing liquid from the deposition head ([0130]: “In another embodiment, the fluid or liquid 530 (FIG. 2C) comprises a system fluid or backing reagent, such as distilled water, and the dispensing apparatus 508 operates in a “suck-and-spit” mode. In this embodiment, the dispenser 528 is used to aspirate a predetermined amount of fluid, liquid or reagent from a source receptacle or microtiter plate and the like and then dispense the aspirated reagent onto or into the target 511. As the skilled artisan will appreciate, reagent is aspirated by retracting or decrementing the pump piston 518 with the valve 545 b open to create a reduced pressure or partial vacuum to draw source reagent into the dispenser 528 via a suitable tip or nozzle thereon.”, [0175]: “to set the pressure to a predetermined and/or steady state aspirate pressure, the syringe plunger 518 (FIGS. 2C and 2L) is typically decremented (or possibly incremented) by a predetermined amount”). Therein, such continuous dispensing allows for an increase in throughput over the pipette-filled well and transfer arrangement of Ho.
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the system of Ho wherein the deposition head connects to a syringe and a syringe pump collectively configured to inject the sample-containing liquid into and/or onto the deposition head and remove the sample-containing liquid from the deposition head, such as suggested by Tisone, so as to increase throughput via continuous reagent delivery rather than the filling steps required of Ho, and wherein such modification does not change the fundamental operation of Ho for printing liquid and merely instead provides an obvious alternative means for delivering sample to the deposition head, thereby representing a reasonable expectation of success.
Claims 31-32 are rejected under 35 U.S.C. 103 as being unpatentable over Ho in view of Carragher, as applied to Claims 14-15, 17-25, 27-28, 30, and 34-35 above, and in further view of Mirkin et al. (US 2015/0286148 A1), hereinafter “Mirkin”.
Regarding Claim 31, the prior art meets the limitations of Claim 30 as discussed above. Further, Ho in view of Carragher does not specifically teach the system discussed above wherein the linear motion stage includes a screw drive OR a piezoelectric drive configured to move the deposition head and the array of pads in positional steps with an accuracy of about 10 micrometers or better, as in Claim 31.
However, Mirkin teaches a respective system for printing/stamping aliquots of an organic species of biological sample onto a substrate surface by contacting a tip/pad with the substrate (See Fig. 10a and Mirkin Claim 16: “the tips deposit the patterning composition onto the substrate when selective lowered into contact or closer contact with the substrate”. – See also [0232-0234]: “The patterning composition is coated on the tip array...Patterning compositions can include materials such as...organic species (e.g., moieties comprising a carbon-carbon bond, such as small molecules, polymers, polymer precursors, proteins, antibodies, and the like), polymers (e.g., both non-biological polymers and biological polymers such as single and double stranded DNA, RNA, and the like), polymer precursors, dendrimers, nanoparticles, and combinations thereof.”). Therein, an actuation mechanism for contacting (or nearly contacting) the tip array to the substrate comprises a piezoelectric driver ([0009]: “the system including a tip array coupled to an actuator comprising a piezo driver”, [0170]: “the microscopic, preferably pyramidal, tips can be made to deform with successively increasing amounts of applied pressure, which can be controlled by simply extending the piezo in the vertical direction (z-piezo)”, see also Fig. 17 showing the piezo scanner.) configured to move the tip array in positional steps ([0226]) with an accuracy of about 10 micrometers or better ([0224]: “The features that can be patterned range from sub-100 nm to 1 mm in size or greater, and can be controlled by altering the exposure time and/or the contacting pressure of the tip array 10.” – As Mirkin discloses sub-100 nm feature size (width as controlled by the insertion/compression depth/degree given the tips are pyramidal) by controlling the pressure exerted by the piezo driver to compress the tips against the substrate, the piezo drive of Mirkin must have an accuracy of about 10 micrometers or better to achieve such sub-100 nm accuracy. – See also Fig. 18 and [0170] discussing the deformability of the tips, acting as compressible stamp pads.), thereby allowing for high-definition sample features to be accurately delivered to a substrate for better repeatability and consistency between runs.
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the system of Ho in view of Carragher wherein the linear motion stage includes a piezoelectric drive configured to move the deposition head and the array of pads in positional steps with an accuracy of about 10 micrometers or better, such as suggested by Mirkin, so as to provide for enhanced printing accuracy for better repeatability and consistency between runs; and wherein such a system would have a reasonable expectation of success in Ho/Carragher given the similar scale of micro-scale deposition and requiring necessary accuracy for consistency given by Ho/Carragher as discussed above.
Regarding Claim 32, the prior art meets the limitations of Claim 31 as discussed above. Further, Ho in view of Carragher does not specifically teach the system discussed above wherein the linear motion stage includes a sensor operable to detect contact of the deposition head with the foil and the grid, as in Claim 32.
However, Mirkin teaches a respective system for printing/stamping aliquots of an organic species of biological sample onto a substrate surface by contacting a tip/pad with the substrate (See Fig. 10a, Mirkin Claim 16, and [0234].) wherein the device comprises a sensing arrangement for determining the contact of the tips to the substrate ([0227]: “The intensity of light reflected from the tips 14 of the tip array 10 increases upon contact with the substrate surface (e.g., the internal surfaces of the tip array 10 reflect light differently upon contact). By observing the change in reflection of light at each tip, the tip array 10 and/or the substrate surface can be adjusted to effect contact of substantially all or all of the tips 14 of the tip array 10 to the substrate surface.”). Therein, such an arrangement allows for confirmation of sample deposition, thereby reducing errors relating to sample failing to be deposited.
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the linear motion stage for contacting the deposition head with the foil and the grid of Ho in view of Carragher wherein the linear motion stage includes a sensor operable to detect contact of the deposition head with the foil and the grid, such as suggested by Mirkin, so as to allow for confirmation of sample deposition, thereby reducing errors relating to sample failing to be deposited (undetected misfire), and would have a reasonable expectation of success therein Ho/Carragher as the system thereof similarly depends on successful contact of microprinting elements with a substrate.
Claim 33 is rejected under 35 U.S.C. 103 as being unpatentable over Ho in view of Carragher, as applied to Claims 14-15, 17-25, 27-28, 30, and 34-35 above, and in further view of Foncy et al. (Foncy, Julie; et al.; “Dynamic inking of large-scale stamps for multiplexed microcontact printing and fabrication of cell microarrays”; August 23, 2018; PLOS ONE 13(8): e0202531.), hereinafter “Foncy”.
Regarding Claim 33, the prior art meets the limitations of Claim 14 as discussed above. Further, Ho in view of Carragher does not specifically teach the system discussed above wherein the array of pads contains pads of different diameters in different regions to deposit different amounts of the sample-containing liquid per unit area on the foil to thereby produce liquid films of different average thickness on different regions of the foil, as in Claim 33.
However, Foncy teaches a respective system for microcontact printing/stamping of biological samples (See page 14, the “Conclusion” section: “This manufacturing process can thus be implemented for extensive analysis applications in biology and pharmacology such as drug screening, tissue engineering and statistically relevant fundamental studies of some cell mechanisms.” – See also Fig. 1A showing manufacturing of the PDMS stamp, and Fig. 1B showing operation of the PDMS stamp.) wherein an array of pads contains pads of different diameters in different regions (See page 3, the “Magnetic stamp design and fabrication” section: “Magnetic PDMS stamps were structured with a variety of feature sizes (from 10 to 150 μm) and forms (squares, lines, spots and triangles).”. See also the “Cell microarray conception” section: “PDMS stamps were structured with various features (squares, lines, spots and triangles) with sizes and spacing ranging from 10 μm to 50 μm.”. See also Figs. 4A and B.) to deposit different amounts of the sample-containing liquid per unit area on the foil to thereby produce liquid films of different average thickness on different regions of the foil (Given the differing diameters of the stamp pads seen through Foncy, one would commensurately expect different amounts of the sample-containing liquid per unit area on the foil as different sized stamp pads hold different amounts of stamp liquid over a differing area, and thereby commensurately produce films of different average thickness.). Therein, such arrangement provides for a multiplexed printhead capable of supplying different amounts/arrangements of sample for different assays, such as specifically discussed by Foncy (See page 2, the “Introduction” section.), thereby increasing the utility of the system.
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the system of Ho in view of Carragher wherein the array of pads contains pads of different diameters in different regions to deposit different amounts of the sample-containing liquid per unit area on the foil to thereby produce liquid films of different average thickness on different regions of the foil, such as suggested by Foncy, so as to provide for a multiplexed printhead capable of supplying different amounts/arrangements of sample for different assays, such as specifically discussed by Foncy (See page 2, the “Introduction” section.), thereby increasing the utility of the system, and wherein the teachings of Foncy would have a reasonable expectation of success in Ho/Carragher as one need only change the manufacturing size of the PDMS stamp mold of Ho.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BENJAMIN KASS whose telephone number is (703)756-5501. The examiner can normally be reached Monday - Friday from 9:00 A.M. to 5:00 P.M. EST. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Charles Capozzi, can be reached at telephone number (571)270-3638. The fax phone number for the organization where this application or proceeding is assigned is (571)273-8300.
Per updated USPTO Internet usage policies, Applicant and/or applicant’s representative is encouraged to authorize the USPTO examiner to discuss any subject matter concerning the above application via Internet e-mail communications. See MPEP 502.03. To approve such communications, Applicant must provide written authorization for e-mail communication by submitting the following statement via EFS Web (using PTO/SB/439) or Central Fax (571-273-8300):
“Recognizing that Internet communications are not secure, I hereby authorize the USPTO to communicate with the undersigned and practitioners in accordance with 37 CFR 1.33 and 37 CFR 1.34 concerning any subject matter of this application by video conferencing, instant messaging, or electronic mail. I understand that a copy of these communications will be made of record in the application file.”
Written authorizations submitted to the Examiner via e-mail are NOT proper. Written authorizations must be submitted via EFS-Web (using PTO/SB/439) or Central Fax (571-273-8300). A paper copy of e-mail correspondence will be placed in the patent application when appropriate. E-mails from the USPTO are for the sole use of the intended recipient, and may contain information subject to the confidentiality requirement set forth in 35 USC § 122. See also MPEP 502.03.
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 https://www.uspto.gov/patents/uspto-automated-interview-request-air-form.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center; and visit https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you need assistance from a USPTO Customer Service Representative, call (800) 786-9199 (IN USA OR CANADA) or (571) 272-1000.
/B.J.K./Examiner, Art Unit 1798
/P. Kathryn Wright/Primary Examiner, Art Unit 1798
Prosecution Insights