DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 22 December 2025 has been entered.
Response to Arguments
Applicant's arguments filed 22 December 2025 have been fully considered but they are not persuasive.
Rejections under 35 USC 103: Kotani as evidenced by Naito
The remarks take the position that the claimed invention is a sample support optimized for DESI which requires high mechanical strength, which is fundamentally different from MALDI. It is noted that claim 1 does not require a DESI plate, therefore the BRI covers any sample plate for ionizing a sample.
With respect to Kotani, the remarks take the position that:
1) Kotani’s support is optimized for a wicking method;
2) the method of Kotani does not require the high mechanical strength need for the claimed invention and
3) adopting the claimed joint diameter to increase the density of the particle aggregate could impede the smooth wicking of the sample which is the primary purpose of Kotani.
With respect to the first point, while Kotani does disclose movement of sample through the substrate, the instant specification also teaches diffusion of the sample into the substrate ([0007] and [0038] of the published application). Thus, it is interpreted that the instant substrate is optimized for diffusion (i.e. wicking).
With respect to the second point, Kotani teaches a porosity of 40% to 50 % ([0024]). As evidenced by US pgPub 2025/003843 to Ikeda such a porosity is sufficient for DESI (see paragraphs [0037] and [0078] respectively). Therefore, Kotani does have the mechanical strength needed for DESI (note again DESI is not required in claim 1).
With respect to the third point, the instant specification also discloses diffusion into the porous structure ([0007] and [0038] of the published application).
Therefore, since it was known that increasing the bond diameter increases the strength, it would have been obvious to one of ordinary skill in the art to have a bond diameter equal to or greater than 1/10 because determining the optimal bond diameter to achieve optimal strength would be routine to one of ordinary skill in the art.
Lastly, upon further consideration Kotani also teaches porosity of porous sponge-like glass is approximately 56% the average pore diameter is approximately 1.45 nm ([0056]).
That is, while Kotani does not teach the pore size of the sintered glass beads, Kotani recognized that an average pore size of 1.45 nm would result in a porosity of 56 % ([0056]). Therefore, for a smaller porosity of 40-50% ([0024]), the pore size would be smaller than 1.45 nm for the sintered glass beads. Since the glass beads have an average diameter of 50 microns ([0025]), the bond area would inherently be greater than 1/10 in order to achieve a pore size (i.e. void between sintered particles) three orders of magnitude smaller than the size of the microbeads. Therefore, alternatively claims 1 and 6-7 are rejected under 35 USC § 102(a)(1).
With respect to claims 8-11, the remarks take the generic position that the applied art fails to disclose the claimed features. This has been found unpersuasive. The amendments are addressed herein below.
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.
Claim(s) 1 and 6-7 are rejected under 35 U.S.C. 102(a)(a) as being anticipated by Kotani et al. (WO2019155741)(submitted with IDS) (national stage application US pgPub 20210050201 is used as the translation) (first interpretation).
Regarding claim 1, Kotani teaches a sample support (fig. 2, 1) for ionizing a sample (intended use), comprising: a substrate (2) that includes:
a first surface (either 2a or 2b) having an electrical insulating property ([0024]-[0025] sintered glass beads), wherein the electrical insulating property is exposed to an outside of the sample support (2a prior to being coated with conductive layer 4);
wherein the first surface of the substrate is not provided with a conductive layer (prior to application of conductive layer the surface 2a is not coted), and
wherein the first surface of the substrate is a surface onto which the sample is transferred (a sample can be placed on the uncovered surface 2a prior to coating. MPEP 2114 (II) recites: “"[A]pparatus claims cover what a device is, not what a device does." Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990) (emphasis in original). A claim containing a "recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus" if the prior art apparatus teaches all the structural limitations of the claim. Ex parte Masham, 2 USPQ2d 1647 (Bd. Pat. App. & Inter. 1987)”. Here, transferring a sample on the surface is a manner of operating the apparatus and thus does not structurally distinguish the claimed invention over the uncovered surface 2a of Kotani);
a second surface opposite to the first surface (the other of either 2a or 2b); and
an irregular porous structure that opens to at least the first surface ([0024])
wherein the porous structure is formed by an aggregate of a plurality of particles ([0053]);
wherein the particles are made of glass, a metal oxide, or an insulation-coated metal ([0024]).
an average diameter of a joint between adjacent particles is 1/10 or more of an average diameter (see discussion in response to arguments above) and less than the average diameter of the particles (because the glass beads are sintered ([0045]) and retain a spherical shape as evident by the average diameter shape ([0025])), the joint must inherently be less than the diameter because fusing the beads greater than the diameter would suggest a loss of the spherical shape. In otherwords, in order to have beads with an average diameter after sintering, the joint or fuse between beads must inherently be far less than the diameter of the beads themselves. Alternatively, [0024] teaches a porosity of the sintered body of glass beams being 40-50% and the porous structure distributed in three-dimensions. Porosity is the ratio of voids to entire volume, therefore in order for a three-dimensional porous volume to have a 40-50% porosity, the bonding between sintered beads would inherently have to be less than the diameter of the beads. That is, the volume of the porous substrate is the void + beads. The porosity is therefore void/(void+beads). For a 50% porosity the void space of pores must equal the bead space, therefore the sintered beads cannot be joined more than diameter of the beads because a 50% porosity would not be possible (i.e. joints of equal or greater diameter between beads in a three-dimensional irregular structure would result in voids much less than 50% because the voids would be filled with the joints. ).
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 and 6-7 are rejected under 35 U.S.C. 103 as being unpatentable over Kotani et al. (WO2019155741)(submitted with IDS) (national stage application US pgPub 20210050201 is used as the translation) (second interpretation) as evidenced by Naito et al. (WO 2019107063).
Regarding claim 1, Kotani teaches a sample support (fig. 2, 1) for ionizing a sample (intended use), comprising: a substrate (2) that includes:
a first surface (either 2a or 2b) having an electrical insulating property ([0024]-[0025] sintered glass beads), wherein the electrical insulating property is exposed to an outside of the sample support (2a prior to being coated with conductive layer 4);
wherein the first surface of the substrate is not provided with a conductive layer (prior to application of conductive layer the surface 2a is not coted), and
wherein the first surface of the substrate is a surface onto which the sample is transferred (a sample can be placed on the uncovered surface 2a prior to coating. MPEP 2114 (II) recites: “"[A]pparatus claims cover what a device is, not what a device does." Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990) (emphasis in original). A claim containing a "recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus" if the prior art apparatus teaches all the structural limitations of the claim. Ex parte Masham, 2 USPQ2d 1647 (Bd. Pat. App. & Inter. 1987)”. Here, transferring a sample on the surface is a manner of operating the apparatus and thus does not structurally distinguish the claimed invention over the uncovered surface 2a of Kotani);
a second surface opposite to the first surface (the other of either 2a or 2b); and
an irregular porous structure that opens to at least the first surface ([0024])
wherein the porous structure is formed by an aggregate of a plurality of particles ([0053]);
wherein the particles are made of glass, a metal oxide, or an insulation-coated metal ([0024]).
an average diameter of a joint between adjacent particles is less than the average diameter of the particles (because the glass beads are sintered ([0045]) and retain a spherical shape as evident by the average diameter shape ([0025])), the joint must inherently be less than the diameter because fusing the beads greater than the diameter would suggest a loss of the spherical shape. In otherwords, in order to have beads with an average diameter after sintering, the joint or fuse between beads must inherently be far less than the diameter of the beads themselves. Alternatively, [0024] teaches a porosity of the sintered body of glass beams being 40-50% and the porous structure distributed in three-dimensions. Porosity is the ratio of voids to entire volume, therefore in order for a three-dimensional porous volume to have a 40-50% porosity, the bonding between sintered beads would inherently have to be less than the diameter of the beads. That is, the volume of the porous substrate is the void + beads. The porosity is therefore void/(void+beads). For a 50% porosity the void space of pores must equal the bead space, therefore the sintered beads cannot be joined more than diameter of the beads because a 50% porosity would not be possible (i.e. joints of equal or greater diameter between beads in a three-dimensional irregular structure would result in voids much less than 50% because the voids would be filled with the joints. ).
Kotani fails to expressly teach the average diameter of a joint between adjacent particles is one tenth or more of an average diameter of the particles.
However, Naito is evidence that increasing the bonding thickness between spherical glass beads improves the bonding strength ([0130]).
Therefore, one of ordinary skill in the art would have recognized that the bonding thickness to be a result effective variable. That is, less bonding thickness results in weaker bonding strength, vs. increased bonding thickness results in stronger bonding strength. It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention for the average diameter of a joint between adjacent particles is one tenth or more of an average diameter of the particles, since it has been held that where the general conditions of a 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 233.
Regarding claim 6, Kotani teaches wherein the particles are glass beads ([0024]).
Regarding claim 7, Kotani teaches wherein the porous structure is formed so as to communicate the first surface and the second surface ([0024]).
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 8-11 are rejected under 35 U.S.C. 103 as being unpatentable over Kotani et al. as evidenced by Naito et al. (WO 2019107063) in view of Takats (Takats et al., “mass Spectrometry Sampling Under Ambient Conditions with Desorption Electrospray Ionization” Science, 2004) as evidenced by Knapp (US pgPub 2008/0087811) and Naito et al. (Naito et al., “A novel laser desorption/ionization method using through hole porous alumina membranes”, Rapid Communications in in mass spectrometry (2018)) or alternatively in view of Takats (US pgPub 2009/0302211).
Regarding claim 8, Kotani et al. teach an ionization method (0033) including:
a first step of preparing a sample support (fig. 2, 1) that includes a substrate (2) including a first surface (either 2a) having an electrical insulating property (glass beads [0024]), a second surface opposite to the first surface (2B opposite 2a), and an irregular porous structure that opens to at least the first surface ([0024]), wherein the electrical insulating property is exposed to an outside of the sample support (prior to application of conductive layer. Paragraph [0028] teaches a conductive layer is provided on the first surface, therefore requiring the first surface to be in a state without a conductive layer prior to the application), wherein the first surface of the substrate is not provided with a conductive layer (prior to application the first surface is not provided with a conductive layer)
wherein the porous structure is formed by an aggregate of a plurality of particles ([0053]);
wherein the particles are made of glass, a metal oxide, or an insulation-coated metal ([0024]).
an average diameter of a joint between adjacent particles is less than the average diameter of the particles (because the glass beads are sintered ([0045]) and retain a spherical shape as evident by the average diameter shape ([0025])), the joint must inherently be less than the diameter because fusing the beads greater than the diameter would suggest a loss of the spherical shape. In otherwords, in order to have beads with an average diameter after sintering, the joint or fuse between beads must inherently be far less than the diameter of the beads themselves. Alternatively, [0024] teaches a porosity of the sintered body of glass beams being 40-50% and the porous structure distributed in three-dimensions. Porosity is the ratio of voids to entire volume, therefore in order for a three-dimensional porous volume to have a 40-50% porosity, the bonding between sintered beads would inherently have to be less than the diameter of the beads. That is, the volume of the porous substrate is the void + beads. The porosity is therefore void/(void+beads). For a 50% porosity the void space of pores must equal the bead space, therefore the sintered beads cannot be joined more than diameter of the beads because a 50% porosity would not be possible (i.e. joints of equal or greater diameter between beads in a three-dimensional irregular structure would result in voids much less than 50% because the voids would be filled with the joints. ).
Kotani fails to expressly teach the average diameter of a joint between adjacent particles is one tenth or more of an average diameter of the particles.
However, Naito is evidence that increasing the bonding thickness between spherical glass beads improves the bonding strength ([0130]).
Therefore, one of ordinary skill in the art would have recognized that the bonding thickness to be a result effective variable (note the instant specification suggests no criticality to the join relative the average diameter of the particles). That is, less bonding thickness results in weaker bonding strength, vs. increased bonding thickness results in stronger bonding strength. It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention for the average diameter of a joint between adjacent particles is one tenth or more of an average diameter of the particles, since it has been held that where the general conditions of a 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 233.
Kotani teaches only discloses laser desorption ionization and a conductive coating and therefore fails to disclose the second step of transferring a sample to the first surface; and a third step of ionizing the transferred component of the sample by irradiating the first surface with a charged microdroplet, and sucking the ionized component. As evidenced by Knapp an electrically conductive layer is required for LDI for non-silicon surfaces ([0031)). Therefore, Kotani requires the conductive coating. However, Naito is evidence that the conductive coating is not desirable because it results in a loss of the high hydrophilic property of the alumina surface (page 1853, first paragraph in left column), therefore negatively effecting the impregnation of the solution into the through holes.
However, Takats teaches an exposed insulating outside surface and a step of ionizing the transferred component of the sample by irradiating the first surface with a charged microdroplet and sucking the ionized component (fig. 1, shows a DESI source and right column teaches an insulating sample or analyte deposited on an insulating surface, thus both first and second surfaces are exposed and insulating. Further figure 1 shows atmospheric inlet of mass spectrometer. In order for the desorbed ions to enter the inlet of the MS, they must inherently be drawn or sucked by the vacuum of the open inlet to the MS because MS inherently occurs under vacuum conditions).
Takats modifies Kotani by teaching the substitution of laser desorption ionization for DESI, therefore allowing the support to be insulative without a conductive coating.
While laser desorption ionization requires a conductive layer (see discussion in Knapp above) and the conductive layer is not desirable in Naito due to its hydrophobic nature for capillary transfer of sample components (see Naito discussion above), Takats teaches that using DESI does not require the support to have a conductive coating. Therefore, it would have been obvious to one of ordinary skill in the art to adopt the DESI source of Takats instead of the laser in Kotani because it would allow the through hole support to be without the conductive layer, improving the hydrophilic properties of the support and thus the sample transfer as evidenced by Naito. In other words, since both inventions are directed towards desorption ionization, it would have been obvious to one of ordinary skill in the art to substitute the laser of Kotani for the electrospray nozzle of Takats because DESI does not require the metal coating as the LDI taught by Naito (see evidence discussed above). Therefore, the substitution of the DESI source for the laser of Kotani allows for a porous substrate without the conductive layer. Thus, the substitution results in the insulative porous substrate that is more hydrophilic, improving the capillary transfer of the sample components to the first surface as evidenced by Naito. Moreover, DESI has the advantage over MALDI in that under ambient conditions DESI can be used for the spatial analysis of native surfaces (see page 472 of Takats, right column last paragraph). Therefore, it would be obvious to substitute the laser of Kotani for the electrospray source of Takats such that spatial analysis may be performed for a given sample by lifting the requirements of a vacuum chamber or a fixed sample stage (see page 472 of Takats, right column last paragraph).
Alternatively, Takats teaches first and second surfaces exposed during sample mounting ([0096]) and irradiating the first surface being externally exposed with charged-droplets ([0015]) and sucking the ionized components (as seen in figure 1).
Takats modifies Kotani by suggesting substitution of charged droplets for a laser (laser of prior art [0009]) and preferentially using an insulating substrate.
While laser desorption ionization requires a conductive layer (see discussion in Knapp above) and the conductive layer is not desirable in Naito due to its hydrophobic nature for capillary transfer of sample components (see Naito discussion above), Takats teaches that using a charged liquid stream of charged particles does not require the support to be conductive. Therefore, it would have been obvious to one of ordinary skill in the art to adopt the charged particle liquid jet (i.e. droplets) of Takats instead of the laser in Kotani because it would allow the through hole support to be without the conductive layer, improving the hydrophilic properties of the support and thus the sample transfer as evidenced by Naito. Moreover, the insulative sample support has the advantage of resisting the applied liquid jet ([0096]).
Regarding claim 9, Kotani in view of Takats as evidenced by Naito teaches in the second step, the component of the sample is held on a surface of one or more of the particles ([0039] component that is moved to the first surface 2a is remained on the first surface 2a by a surface tension, when modified by Takats the component would be held by the beads as evidenced by Naito which teaches hydrophilic properties of insulative materials).
Regarding claim 10 Kotani in view of Takats teaches wherein in the third step, an irradiated area of the charged microdroplets is relatively moved with respect to the first surface (figure in takats on page 471 showing freely moving sample stage in air).
Claim 11 is taught as discussed above in claim 8. Kotani further teaches a method of mass spectrometry ([0023]).
Conclusion
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/MICHAEL J LOGIE/Primary Examiner, Art Unit 2881