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 .
Claim Objections
Claims 1-2, 5-6, and 8-10 are objected to because of the following informalities:
Claim 1 recites “A method for desorbing and ionizing of sample material…”, which is grammatically erroneous and should read ‘A method for desorbing and ionizing sample material’ or ‘A method for desorption and ionization of sample material’;
Claim 1 recites “…and triggering of local desorption…”, which is grammatically erroneous and should read ‘…and triggering local desorption…’;
Claim 1 recites “…and triggering of ionization and/or increasing a degree of ionization of…”, which is grammatically erroneous and should read ‘…and triggering ionization and/or increasing a degree of ionization of…’;
Claim 1 recites “…substantially perpendicular to a surface normal of the sample support…”, which is grammatically erroneous and should read ‘…substantially perpendicular to a surface normal to the sample support…’;
Claim 1 recites “…a focus position and/or beam waist position…”, which should read ‘…a focus position and/or a beam waist position…’;
Claim 1 recites “…a current impingement point at the sample material…”, which should read ‘…a current impingement point on the sample material…’;
Claim 2 recites “…relative to a surface normal of the sample support.”, which is grammatically erroneous and should read ‘…relative to a surface normal to the sample support.’;
Claim 5 recites “…comprises a glass plate, metal plate or ceramic plate.”, which should read ‘…comprises a glass plate, a metal plate, or a ceramic plate.’;
Claim 6 recites “…a pulse laser.”, which should read ‘…a pulsed laser.”;
Claim 7 recites “…wherein the position of the first energetic radiation and/or the direction of propagation of the second energetic radiation relative to the sample support is…”, however, in the case of ‘and’, the verb ‘is’ does not agree in number with the subject, and thus this limitation should read ‘…wherein the position of the first energetic radiation and/or the direction of propagation of the second energetic radiation relative to the sample support are/is…’;
Claim 8 recites “…a mobility analyzer, mass analyzer, or a coupled mobility-mass analyzer.”, which should read ‘…a mobility analyzer, a mass analyzer, or a coupled mobility-mass analyzer.’;
Claim 9 recites “…the focus position and/or beam waist position…”, which should read ‘…the focus position and/or the beam waist position…’;
Claim 10 recites “…the focus position and/or beam waist position…”, which should read ‘…the focus position and/or the beam waist position…’;
Claim 10 recites “…the desorption device, the ionization device, the first adjustment device and the second adjustment device…”, which should read ‘…the desorption device, the ionization device, the first adjustment device, and the second adjustment device…’.
Appropriate correction is required.
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 1-10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites “A method for desorbing and ionizing of sample material which is deposited on a sample support…”. It is unclear whether ‘which is deposited on a sample support’ is intended to be part of the method, or is merely describing the initial state of the sample material and sample support when the method starts. As such, it is not possible to adequately determine the metes and bounds of the claim, rendering it indefinite. Based on Examiner’s reading of Applicant’s specification, it appears that the method is not intended to include depositing sample material on a sample support. Accordingly, for purposes of examination, this limitation is interpreted as ‘A method for desorbing and ionizing of sample material disposed on a sample support…’.
Claim 1 recites “…while varying a position of the first energetic radiation relative to the sample support…”. It is unclear what is intended by ‘a position of the first energetic radiation’, as one could reasonably read this as limiting the position of the source of the radiation or as limiting the impingement position of the radiation on the sample. However, ‘a position of the first energetic radiation’ does not make sense in context, as the energetic radiation will have a plurality of positions at any given time, due to the energetic radiation naturally propagating and diffusion. As such, it is not possible to adequately determine the metes and bounds of the claim, rendering it indefinite. Applicant’s specification appears to only support changing an angle of incidence of the first energetic radiation such that the impingement locations on the sample support change. Accordingly, for purposes of examination, this limitation is interpreted as ‘…while varying an impingement position of the first energetic radiation relative to the sample support…’.
Claim 1 recites “…and aiming at a plurality of impingement points on the sample material on the sample support…”. However, it appears that the aiming would necessarily occur prior to each instance of impacting of the sample material with a first energetic radiation. Additionally, it is unclear which portions of this step are intended to be repeatedly performed, as it would appear based on Examiner’s reading of Applicant’s specification that each of ‘locally impacting’, ‘triggering local desorption’, and ‘varying a position’ are performed repeatedly. As such, it is not possible to adequately determine the metes and bounds of the claim, rendering it indefinite. Examiner suggests rephrasing this whole limitation to clearly indicate the correspondence of each of these sub-steps. Accordingly, for purposes of examination, this limitation is interpreted as ‘…locally impacting sample material on the sample support at a plurality of impingement points on the sample material using a first energetic radiation which triggers local desorption of sample material into a gas phase above the sample support, while varying an impingement position of the first energetic radiation to each of the plurality of impingement points on the sample material on the sample support’.
Claim 1 recites “…with a focus position and/or beam waist position of the second energetic radiation being aligned such that it is positioned substantially opposite a current impingement point at the sample material on the sample support…”. It is unclear what is intended by ‘being aligned such that it is positioned substantially opposite a current impingement point’, as ‘substantially opposite’ does not clearly indicate the required positioning of the impingement point. Additionally, the term ‘current impingement point’ is ambiguous, as ‘current’ could also reasonably be interpreted as ‘electrical current’. As such, it is not possible to adequately determine the metes and bounds of the claim, rendering it indefinite. For purposes of examination, this limitation is interpreted as ‘…with a focus position and/or a beam waist position of the second energetic radiation being controllably aligned above each respective impingement point at the sample material on the sample support…’.
Claim 3 recites “…wherein the sample material has been prepared using a light-absorbent matrix substance.” It is unclear whether this is intended to be an additional method step, as it appears to be limiting actions taken before the start of the method. As such, it is not possible to adequately determine the metes and bounds of the claim, rendering it indefinite. Based on Examiner’s reading of Applicant’s specification, it appears that the method is not intended to include preparing the sample material using the recited matrix substance, and is merely intended to limit the state of the sample material prior to the method starting, and separate from any particular method steps. Accordingly, for purposes of examination, this limitation is interpreted as ‘…wherein the sample material is interspersed in a light-absorbent matrix substance.’
Claim 7 recites “…the position of the first energetic radiation…”, which is indefinite for similar reasons to those discussed in regards to claim 1, and is interpreted similarly as ‘…the impingement position of the first energetic radiation…’.
Claim 7 recites “…wherein the position of the first energetic radiation and/or the direction of propagation of the second energetic radiation relative to the sample support is…”. It is unclear whether ‘relative to the sample support’ is intended to refer to both ‘the position’ and/or ‘the direction of propagation’, or whether this is intended to solely limit ‘the direction of propagation’. As such, it is not possible to adequately determine the metes and bounds of the claim, rendering it indefinite. Based on Examiner’ reading of Applicant’s specification, it appears this is intended to limit both ‘the position’ and ‘the direction of propagation’, in accordance with claim 1. Accordingly, for purposes of examination, this limitation is interpreted as ‘…wherein the position of the first energetic radiation relative to the sample support and/or the direction of propagation of the second energetic radiation relative to the sample support are/is…’.
Claim 9 recites “wherein the focus position and/or beam waist position of the second energetic radiation is aligned (i) perpendicularly to and/or (ii) along the direction of propagation of the second energetic radiation”. It is unclear what is intended by the focus position/beam waist position being ‘aligned perpendicularly to the direction of propagation of the second energetic radiation’. Additionally, it is unclear how the focus position/beam waist position can be both ‘aligned perpendicularly to the direction of propagation and aligned along the direction of propagation’. As such, it is not possible to adequately determine the metes and bounds of the claim, rendering it indefinite. Based on Examiner’s reading of Applicant’s specification, this appears to be attempting to limit the lateral and vertical adjustment of the focus position/beam waist position and the longitudinal adjustment of the focus position/beam waist position, however, the phrasing ‘is aligned’ does not properly convey this. Accordingly, for purposes of examination, this limitation is interpreted as ‘wherein the focus position and/or beam waist position of the second energetic radiation is adjusted (i) perpendicularly to and/or (ii) along the direction of propagation of the second energetic radiation’.
Claim 10 is indefinite because it is unclear whether the claim depends on claim 1. The claim recites “a method according to Claim 1”, which makes it unclear whether the method steps required in ‘the method according to Claim 1’ are required by claim 10. However, because claim 10 pertains to a device, requiring the claim to depend on claim 1 would be indefinite, as the claim would thus be requiring method steps in an apparatus claim. See MPEP 2173.05(p).II. As such, it is not possible to adequately determine the metes and bounds of the claim, rendering it indefinite. Accordingly, for purposes of examination, this limitation is interpreted as not depending on claim 1, and only being required to be capable of performing the method of claim 1 (i.e., having the necessary structures and capabilities thereof); in other words, ‘a guidance system that communicates with and is programmed to coordinate with the desorption device, the ionization device, the first adjustment device, and the second adjustment device.’.
Claim 10 recites the terms “the first energetic radiation”, “the second energetic radiation”, “the position of the first energetic radiation”, “the focus position of the second energetic radiation”, and “the beam waist position of the second energetic radiation”, each of which lacks antecedent basis in the claim, and are each interpreted as ‘a [term]’.
Claim 10 recites “…which is deposited on a sample support…”, which is indefinite for similar reasons to those discussed in regards to claim 1, and is interpreted similarly as ‘A device for desorbing and ionizing sample material disposed on a sample support…’.
Claim 10 recites “…the position of the first energetic radiation…”, which is indefinite for similar reasons to those discussed in regards to claim 1, and is interpreted similarly as ‘…an impingement position of the first energetic radiation…’.
Claims that depend on the above rejected claims are also rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph.
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.
Claims 1-10 are rejected under 35 U.S.C. 103 as being unpatentable over Bossmeyer (U.S. PGPub. No. US 20180174815 A1) in view of Haase (U.S. PGPub. No. US 20220397551 A1).
Examiner notes that Bossmeyer is Applicant provided prior art via the IDS dated 11/29/2023.
Regarding claim 1, as best understood in view of the 35 U.S.C. 112(b) issues identified above, Bossmeyer teaches a method for desorbing and ionizing of sample material which is deposited on a sample support (Abstract; [0001]; [0068]), comprising:
- [locally impacting sample material on the sample support ;
- impacting locally desorbed sample material using a pulsed second energetic radiation, which is aimed into the locally desorbed sample material, and triggering of ionization and/or increasing a degree of ionization of the locally desorbed sample material (See Fig. 6, beam 26 irradiating plume of ions 6; [0008]; [0068]), with a direction of propagation of the second energetic radiation being in a plane that is substantially perpendicular to a surface normal of the sample support and positioned above the sample support (See Fig. 6, beam 26 propagating perpendicular to surface normal to sample support 5, and above beam 26 propagating above the sample support 5), and [; and
- transferring ionized sample material, originating from the locally desorbed sample material which has been impacted with the second energetic radiation, into an ion-processing device (See Fig. 6, plume 6 being directed to ion funnel 7, into subsequent ion analysis stages such as 8, 9-11, an 11-16; [0008]-[0009]).
Bossmeyer does not teach [locally impacting sample material on the sample support at a plurality of impingement points on the sample material using a first energetic radiation which triggers local desorption of sample material into a gas phase above the sample support, while varying an impingement position of the first energetic radiation to each of the plurality of impingement points on the sample material on the sample support] (Emphases added by Examiner) and does not explicitly teach [with a focus position and/or a beam waist position of the second energetic radiation being controllably aligned above each respective impingement point at the sample material on the sample support].
However, Examiner notes that focusing a laser beam to a particular location is well represented in the prior art and an ordinarily skilled artisan would be reasonably apprised of the basic use of lenses to control a focus position to a particular location along the propagation of the beam (i.e., not lateral to the beam propagation). This does not necessarily mean that controllably aligning the focus position/the beam waist position above each of a plurality of impingement points on the sample would be known or obvious absent some teaching, suggestion, or motivation.
Nevertheless, Haase teaches [locally impacting sample material on the sample support at a plurality of impingement points on the sample material using a first energetic radiation which triggers local desorption of sample material into a gas phase above the sample support, while varying an impingement position of the first energetic radiation to each of the plurality of impingement points on the sample material on the sample support] (See Fig. 1, optical elements 6-12; [0006]; [0037]; [0040]).
Haase additionally teaches [with a focus position and/or a beam waist position of the elements being used for a second beam, and for controlling the focus to be above the impingement points.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Bossmeyer to include the teachings of Haase of the controllable optical elements varying beam focus positions in a MALDI system to achieve [locally impacting sample material on the sample support at a plurality of impingement points on the sample material using a first energetic radiation which triggers local desorption of sample material into a gas phase above the sample support, while varying an impingement position of the first energetic radiation to each of the plurality of impingement points on the sample material on the sample support] (Emphases added by Examiner) and [with a focus position and/or a beam waist position of the second energetic radiation being controllably aligned above each respective impingement point at the sample material on the sample support].
Doing so represents combining known prior art elements according to known methods in order to yield predictable results, and would allow one, as taught by Haase, to controllably vary the focus position of a laser beam in a MALDI system, which would allow one to improve the system of Bossmeyer by allowing for impingement on multiple sample positions without moving the sample stage, which is indicated by Haase as undesirable in [0004] due to oscillation and vibrations in the stage setup, and which would be avoided by applying the optical elements of Haase to the desorption laser of Bossmeyer. Furthermore, applying these optical elements in a similar manner to the second laser beam of Bossmeyer also represents combining known prior art elements according to known methods in order to yield predictable results, namely, by allowing one to control the position of the beam focus of the second beam to correspond with the modified positions of the ion plume caused by the different impingement points.
Examiner notes that galvanometric mirror systems are generally known within the prior art, and in particular for changing the position of lasers. For example, see prior art cited below.
Regarding claim 2, as best understood in view of the 35 U.S.C. 112(b) issues identified above, Bossmeyer in view of Haase teaches the method according to Claim 1.
Haase further teaches wherein a direction of incidence of the first energetic radiation is changed relative to a surface normal of the sample support ([0006]; [0037]; [0040]).
Regarding claim 3, as best understood in view of the 35 U.S.C. 112(b) issues identified above, Bossmeyer in view of Haase teaches the method according to Claim 1.
Bossmeyer further teaches wherein the sample material has been prepared using a light-absorbent matrix substance ([0016]; [0019]; [0040]).
Regarding claim 4, as best understood in view of the 35 U.S.C. 112(b) issues identified above, Bossmeyer in view of Haase teaches the method according to Claim 1.
Bossmeyer further teaches wherein the sample material comprises a plurality of spot preparations or a two-dimensional tissue section ([0001]; [0003]; [0006]; [0012]; [0019]; [0028]; [0040]).
Regarding claim 5, as best understood in view of the 35 U.S.C. 112(b) issues identified above, Bossmeyer in view of Haase teaches the method according to Claim 1.
Bossmeyer further teaches wherein the sample support comprises a glass plate, metal plate or ceramic plate ([0019]).
Regarding claim 6, as best understood in view of the 35 U.S.C. 112(b) issues identified above, Bossmeyer in view of Haase teaches the method according to Claim 1.
Bossmeyer further teaches wherein the first energetic radiation and/or the second energetic radiation is delivered by a pulse laser ([0007]; [0010]; [0016]-[0017]; [0037]).
Regarding claim 7, as best understood in view of the 35 U.S.C. 112(b) issues identified above, Bossmeyer in view of Haase teaches the method according to Claim 1.
Haase further teaches wherein the position of the first energetic radiation and/or the direction of propagation of the second energetic radiation relative to the sample support is changed or re-aligned using one or more mirrors and/or one or more lenses (See Fig. 1, items 7-12).
Regarding claim 8, as best understood in view of the 35 U.S.C. 112(b) issues identified above, Bossmeyer in view of Haase teaches the method according to Claim 1.
Bossmeyer further teaches wherein the ion-processing device comprises a mobility analyzer, mass analyzer, or a coupled mobility-mass analyzer (See Fig. 6; Abstract; [0004]-[0010]; [0057]; [0065]).
Regarding claim 9, as best understood in view of the 35 U.S.C. 112(b) issues identified above, Bossmeyer in view of Haase teaches the method according to Claim 1.
Bossmeyer in view of Haase further teaches wherein the focus position and/or beam waist position of the second energetic radiation is aligned (i) perpendicularly to and/or (ii) along the direction of propagation of the second energetic radiation (See Bossmeyer Fig. 6; See Haase Fig. 1, optical elements 6-12; [0006]; [0037]; [0040]; Examiner notes that applying the adjustment of the focus of the laser beam of Haase to the second beam of Bossmeyer would inherently include modifying the focus position and/or the beam waist position laterally and/or longitudinally).
Regarding claim 10, as best understood in view of the 35 U.S.C. 112(b) issues identified above, Bossmeyer teaches a device for desorbing and ionizing sample material which is deposited on a sample support (Abstract; [0001]; [0068]), comprising:
- a desorption device for generating and guiding the first energetic radiation (See Fig. 6, beam 25 from laser system 24 desorbing plume of ions 6; [0008]; [0017]; [0047]; [0068]);
- an ionization device for generating and guiding the second energetic radiation (See Fig. 6, beam 26 from laser system 24 desorbing plume of ions 6; [0008]; [0017]; [0047]; [0068]);
-
-
- [.
Bossmeyer does not teach a first adjustment device for setting and changing the position of the first energetic radiation relative to the sample support; - a second adjustment device for setting and aligning the focus position and/or beam waist position of the second energetic radiation and does not explicitly teach [a guidance system that communicates with and is programmed to coordinate with the desorption device, the ionization device, the first adjustment device, and the second adjustment device].
However, it is typical in the art for a laser system and/or a mass spectrometry system such as those disclosed by Bossmeyer to have some form of controller or processing device in order to function as intended, as would be understood by one of ordinary skill in the art. Typically, this is in the form of a computer system (having a processor and software) coupled to the mass spectrometry system, as would be known by an ordinarily skilled artisan.
Nevertheless, Haase teaches a (See Fig. 1, optical elements 6-12; [0006]; [0037]; [0040];); and [a guidance system that communicates with and is programmed to coordinate with the desorption device, the ionization device, the
Examiner notes that the adjustment device of Haase could be equivalently applied to the second laser of Bossmeyer in a similar fashion, but because Haase is a single laser system, it lacks disclosure of such optical elements being used for a second beam.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Bossmeyer to include the teachings of Haase of the controllable optical elements varying beam focus positions in a MALDI system to achieve a first adjustment device for setting and changing the position of the first energetic radiation relative to the sample support; - a second adjustment device for setting and aligning the focus position and/or beam waist position of the second energetic radiation and [a guidance system that communicates with and is programmed to coordinate with the desorption device, the ionization device, the first adjustment device, and the second adjustment device].
Doing so represents combining known prior art elements according to known methods in order to yield predictable results, and would allow one, as taught by Haase, to controllably vary the focus position of a laser beam in a MALDI system, which would allow one to improve the system of Bossmeyer by allowing for impingement on multiple sample positions without moving the sample stage, which is indicated by Haase as undesirable in [0004] due to oscillation and vibrations in the stage setup, and which would be avoided by applying the optical elements of Haase to the desorption laser of Bossmeyer. Additionally, applying these optical elements in a similar manner to the second laser beam of Bossmeyer also represents combining known prior art elements according to known methods in order to yield predictable results, namely, by allowing one to control the position of the beam focus of the second beam to correspond with the modified positions of the ion plume caused by the different impingement points. Finally, controlling the elements of the system using a programmed guidance system (e.g., a control unit) also represents combining known prior art elements according to known methods in order to yield predictable results, and would allow one to control the optical elements of the system of Bossmeyer in view of Haase using conventional control elements.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Pertaining to galvanometric mirror systems:
Cottrell (US 5461235 A);
Willoughby (US 20050056776 A1);
Haase’282 (US 20090039282 A1);
Clem (US 20130168545 A1);
Loboda (US 20210239707 A);
Corkum (see IDS dated 11/29/2023);
Sandkuijl (US 20210333173 A1);
Otherwise relevant prior art:
Haase’142 (US 20220285142 A1);
Niehaus (DOI: 10.1038/s41592-019-0536-2);
Bednarik (DOI: 10.1002/anie.201806635);
Ellis (DOI: 10.1039/C7CC02325A);
Woods (DOI: 10.1021/pr301004w);
Bien (DOI: 10.1007/s00216-020-03070-0).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTOPHER J GASSEN whose telephone number is (571)272-4363. The examiner can normally be reached M-F 9-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, ROBERT H KIM can be reached at (571)272-2293. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHRISTOPHER J GASSEN/ Examiner, Art Unit 2881
/ROBERT H KIM/ Supervisory Patent Examiner, Art Unit 2881