DEVICE, APPARATUS AND METHOD FOR MINIBEAM RADIATION THERAPY

§103 §112

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 - Warning Applicant is advised that should claim 13 be found allowable, claim 15 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Claim 15 repeats most of the claim limitations of parent claim 13 verbatim and contains no additional limitations. 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 limitation(s) is/are: “a beam source arranged to generate an incident beam of charged particles that exhibits: • an energy superior or equal to 10 and/or less than or equal to 1000 MeV, and • a divergence less than 15 milliradian, and/or • an absolute value of a correlation coefficient between a size of the incident beam and the divergence of the incident beam superior or equal to 0.8 and/or less than or equal to 1” in claims 13-15 and “a beamline of a medical facility arranged to emit an incident beam of charged particles” in claims 16-17 & 19. 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. The corresponding structure for both is an accelerator and beam transportation magnets (see “The beam source comprises a proton accelerator, such as a cyclotron, and a beam transport system comprising magnets and being arranged to convey an incident proton beam 6 from the proton accelerator to the nozzle 2.” Instant application) 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(b) 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 1-9, 18, and 20 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. The claims recite a method that includes a step of providing a volume “along which a full width at half maximum of the focused beam is less than or equal to 2mm”. It is unclear what action is being claimed, as the limitation contains neither an action nor a function, but only a desired result. That is, the limitation states that it is desired that the method should result in a beam that has a specific property within the volume (a full width at half maximum of less than or equal to 2mm) but does not specify any steps for modifying the beam to give it the claimed distribution. Other limitations of the claim suggest that the beam will be modified to have the claimed distribution if the focal lengths of the quadrupoles are set to specific parameters (see “setting the focal point of the first quadrupole and the focal point of the second quadrupole at a distance from each other that is less than or equal to 50 cm, for providing the volume extending between the focal point of the first quadrupole and the focal point of the second quadrupole, along which the full width at half maximum (FWHM) of the focused beam is less than or equal to 2 mm,”). Therefore, examiner will treat the recitation of “providing a volume … along which a full width at half maximum of the focused beam is less than or equal to 2mm” as being fulfilled if the step of setting the focal lengths as claimed is present. Claims 1-9, 18, and 20 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted steps are: generating or providing an incident beam of charged particles. The claims recite a method for generating a minibeam, “the minibeam being generated from an incident beam of charged particles” but fails to recite a method step of generating or providing an incident beam. Without the incident beam being generated or provided, it is not possible to perform the remaining steps of the claim, such as “focusing the incident beam” which requires that the incident beam first be generated or provided. Claims 4 & 9 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 claims 4 & 9, the entirety of the claims relate to wherein clauses that describe the output beam. It is unclear if the wherein clauses recite an intended result of the previously recited steps or if additional steps or constraints are required to cause the output beam to take these forms. If they are an intended result of the previously recited steps, they carry no patentable weight. If applicant is of the opinion that the beam distribution is not a result of the prior recited steps, they may amend the claims to recite whatever additional steps or constraints are required to achieve the claimed beam distribution. For the purposes of examination, the claims will be treated as claiming a desired result of the previously recited steps. Claim 19 is 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 19, the claim recites “wherein the beam source arranged to generate an incident beam of charged particles that exhibits a dose rate superior to 40 Gray per second and an irradiation time lower than 500 milliseconds.” It is unclear how the beam source must be “arranged” to generate such an incident beam. The claim appears to be a recitation of an intended use (using the beam source for generating an incident beam of charged particles that exhibits a dose rate superior to 40 Gray per second and an irradiation time lower than 500 milliseconds) rather than an actual arrangement of the beam source. For the purposes of examination, the limitation will be treated as intended use. Claim Rejections - 35 USC § 112(d) The following is a quotation of 35 U.S.C. 112(d): (d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph: Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. Claim 3 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to include all the limitations of the claim upon which it depends. Claim 3 broadens the claim. The parent claim specifies that the distance d5 be in the range 2-50cm, and claim 3 broadens the range to the universe of real numbers (“wherein a distance from an end of the vacuum environment to the focal point of the second quadrupole is equal to or greater than 10 centimeters and/or is less than or equal to 50 cm.” where all real numbers are at least one of greater than 10 and less than 50). It is suggested applicant amend the claim to remove the “or” option, so that the limitation reads “wherein a distance from an end of the vacuum environment to the focal point of the second quadrupole is equal to or greater than 10 centimeters and 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. Claim(s) 1-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over “Measurements of in-air spot size of pencil proton beam for various air gaps in conjunction with a range shifter on a ProteusPLUS PBS dedicated machine and comparison to the proton dose calculation algorithms” (Rana et al.). Regarding claim 1, Rana et al. discloses a method for generating a minibeam, the minibeam being generated from an incident beam of charged particles that exhibits: • an energy comprised between 10 and 1000 MeV, and • a divergence less than 15 milliradian, and/or • an absolute value of a correlation coefficient between a size of the incident beam and the divergence of the incident beam comprised between 0.8 and 1, the method comprising the steps consisting of: - focusing the incident beam, through a first quadrupole according to a first direction (“A set of two focusing quadrupole magnets focus the proton beam at the isocenter.”); - focusing the incident beam, through a second quadrupole according to a second direction orthogonal to the first direction (“A set of two focusing quadrupole magnets focus the proton beam at the isocenter.”); - deflecting the incident beam, through a third magnet according to a third direction (fig. 1, “Vertical Scanning Magnets”); - deflecting the incident beam through a fourth magnet according to a fourth direction different from the third direction (fig. 1, “Horizontal Scanning Magnets”); and - setting a focal length of the first quadrupole and respectively a focal length of the second quadrupole (“A set of two focusing quadrupole magnets focus the proton beam at the isocenter.”), for decreasing a size of the focused beam to a full width at half maximum (FWHM) that is less than or equal to 2 mm along the volume extending between the focal point of the first quadrupole and the focal point of the second quadrupole (intended result, non-limiting), and - setting the focal point of the first quadrupole and the focal point of the second quadrupole at a distance from each other that is less than or equal to 50 cm (“A set of two focusing quadrupole magnets focus the proton beam at the isocenter.”, both are set to same focal point (the isocenter) so distance between the focal points approximately zero), for providing the volume extending between the focal point of the first quadrupole and the focal point of the second quadrupole, along which the full width at half maximum (FWHM) of the focused beam is less than or equal to 2 mm (intended result, non-limiting), and - setting the focal point of the second quadrupole at a distance between 2.0 cm and 50 cm from an exit plane of the nozzle (fig. 3, focal point is isocenter which is 6.5 – 41.5 cm from nozzle exit when range shifter is in use, and 0-35 cm from nozzle exit when not using a range shifter). Rana et al. does not disclose whether the focal lengths of are set to a value between 60 and 250 cm and a value between 50 and 200 cm. It is generally known how to set the focal lengths as needed. It would have been obvious to a person having ordinary skill in the art at the time the application was filed to place the isocenter at least 50 and 60 cm away from the quadrupoles to provide sufficient room for the scanning magnets. It would further have been obvious to place the isocenter within 200 and 250 cm, respectively, to reduce the overall nozzle size and maintain a small air gap, where a small air gap in particular is desired, as disclosed in Rana et al. (“The air gap increases the in-air spot size at the isocenter due to the angular distribution of a pencil proton beam after traversing the range shifter and translation of angular distribution into a geometric spread of proton beam’s cross-section at the detector/patient surfaces as a function of distance [7, 8].”). Regarding claim 2, Rana et al. discloses the method according to claim 1, comprising the step consisting of arranging the beam, the first and second quadrupoles and the third and fourth magnets in a vacuum environment (fig, 1, “nozzle”), said vacuum environment extending over a distance higher than 50 cm (must be to enclose two focusing magnets, two scanning magnets, and an ionization chamber). Rana et al. does not disclose whether the vacuum environment extends over a distance lower than 200 cm. It would have been obvious to a person having ordinary skill in the art at the time the application was filed to make the nozzle extend over a distance lower than 200 cm to reduce the overall size of the nozzle. Regarding claim 3, Rana et al. discloses the method according to claim 2, wherein a distance from an end of the vacuum environment to the focal point of the second quadrupole is equal to or greater than 10 centimeters and/or is less than or equal to 50 cm (fig. 3, focal point is isocenter which is 6.5 – 41.5 cm from nozzle exit when range shifter is in use, and 0-35 cm from nozzle exit when not using a range shifter). Regarding claim 4, Rana et al. discloses the method according to claim 1, wherein a full width at half maximum (FWHM) of the beam distribution at the target plane perpendicular to an axis of the incident beam is less than 50 mm (intended result, non-limiting, also fig. 6). Regarding claim 5, Rana et al. discloses the method according to claim 1, wherein a distance separating the first quadrupole from the second quadrupole is less than 15 cm (fig. 1). Regarding claim 6, Rana et al. discloses the method according to claim 1, wherein the incident beam of charged particles exits from a beamline of a medical facility (“Our proton center is equipped with ProteusPLUS (Ion Beam Applications, Louvain-la-Neuve, Belgium), which includes PBS in all three gantries.”). Regarding claim 7, Rana et al. discloses the method according to claim 1, wherein the charged particles are ions (“proton beam”). Regarding claim 8, Rana et al. discloses the claimed method except it is not specified if the operational frequencies of the third and fourth magnets are superior or equal to 1 Hz and/or are less than or equal to 200 Hz. It would have been obvious to a person having ordinary skill in the art at the time the application was filed to use frequencies in this range as a matter of routine optimization, as it is not disclosed that these frequencies are critical. Regarding claim 9, Rana et al. discloses the method according to claim 1, wherein a minibeam distribution at the target plane perpendicular to an axis of the minibeam exhibits a horizontal full width at half maximum (hFWHM) less than or equal to 2 mm and a vertical FWHM (vFWHM) equal to or less than the hFWHM of the minibeam (intended result, non-limiting). Regarding claim 10, Rana et al. discloses a harged particles minibeam Radiation Therapy scanning nozzle (MRTSN), the MRTSN comprising, along a beam path of the charged particles inside the nozzle: - a first quadrupole arranged to focus the incident beam according to a first direction (fig. 1, “Focusing Quadrupole Magnets”); - a second quadrupole arranged to focus the incident beam according to a second direction orthogonal to the first direction (fig. 1, “Focusing Quadrupole Magnets”); - a third magnet arranged to deflect the incident beam according to a third direction (fig. 1, “Vertical Scanning Magnets”); and - a fourth magnet arranged to deflect the incident beam according to a fourth direction different from the third direction (fig. 1, “Horizontal Scanning Magnets”); the first quadrupole and respectively the second quadrupole being arranged to have: • focal lengths (inherent, a lens must have a focal length) for decreasing a size of the focused beam of the focused beam to a full width at half maximum (FWHM) that is less than or equal to 2 mm along a volume extending between a focal point of the first quadrupole and a focal point of the second quadrupole (intended use, non-limiting), • a distance between the focal point of the first quadrupole and the focal point of the second quadrupole that is less than or equal to 50 cm (“A set of two focusing quadrupole magnets focus the proton beam at the isocenter.”, both are set to same focal point (the isocenter) so distance between the focal points approximately zero), for providing the volume extending between the focal point of the first quadrupole and the focal point of the second quadrupole, along which the full width at half maximum (FWHM) of the focused beam to be less than or equal to 2 mm (intended use, non-limiting), the second quadrupole being further arranged to have a focal point at a distance between 2.0 cm and 50 cm from an exit plane of the nozzle (fig. 3, focal point is isocenter which is 6.5 – 41.5 cm from nozzle exit when range shifter is in use, and 0-35 cm from nozzle exit when not using a range shifter). Rana et al. does not disclose whether the focal lengths comprise between 60 and 250 cm and between between 50 and 200 cm. It is generally known how to set the focal lengths as needed. It would have been obvious to a person having ordinary skill in the art at the time the application was filed to place the isocenter at least 50 and 60 cm away from the quadrupoles to provide sufficient room for the scanning magnets. It would further have been obvious to place the isocenter within 200 and 250 cm, respectively, to reduce the overall nozzle size and maintain a small air gap, where a small air gap in particular is desired, as disclosed in Rana et al. (“The air gap increases the in-air spot size at the isocenter due to the angular distribution of a pencil proton beam after traversing the range shifter and translation of angular distribution into a geometric spread of proton beam’s cross-section at the detector/patient surfaces as a function of distance [7, 8].”). Regarding claim 11, Rana et al. discloses the MRTSN according to claim 10, comprising a vacuum chamber wherein the first and second quadrupoles and the third and fourth magnets are arranged (fig. 1, “nozzle”). Regarding claim 12, Rana et al. discloses the MRTSN according to claim 11, wherein a distance between an exit face of the vacuum chamber and the focal point of the second quadrupole is less than 50 cm (fig. 3, focal point is isocenter which is 6.5 – 41.5 cm from nozzle exit when range shifter is in use, and 0-35 cm from nozzle exit when not using a range shifter). Regarding claim 13, Rana et al. discloses charged particles minibeam radiation therapy system comprising: - a beam source arranged to generate an incident beam of charged particles that exhibits: • an energy superior or equal to 10 and/or less than or equal to 1000 MeV, and • a divergence less than 15 milliradian, and/or • an absolute value of a correlation coefficient between a size of the incident beam and the divergence of the incident beam superior or equal to 0.8 and/or less than or equal to 1 (“Our proton center is equipped with ProteusPLUS (Ion Beam Applications, Louvain-la-Neuve, Belgium), which includes PBS in all three gantries.”), - a minibeam scanning nozzle (MSN) arranged to generate a minibeam of charged particles comprising, along a beam path of the charged particles inside the nozzle: • a first quadrupole arranged to focus the incident beam according to a first direction fig. 1, “Focusing Quadrupole Magnets”); • a second quadrupole arranged to focus the incident beam according to a second direction orthogonal to the first direction fig. 1, “Focusing Quadrupole Magnets”); • a third magnet arranged to deflect the incident beam according to a third direction (fig. 1, “Vertical Scanning Magnets”); and • a fourth magnet arranged to deflect the incident beam according to a fourth direction different from the third direction (“Horizontal Scanning Magnets”); the first quadrupole and respectively the second quadrupole being arranged to have: - focal lengths (inherent, a lens must have a focal ength) for decreasing a size of the focused beam to a full width at half maximum (FWHM) that is less than or equal to 2 mm along a volume extending between a focal point of the first quadrupole and a focal point of the second quadrupole (intended use, non-limiting), - a distance between the focal point of the first quadrupole and the focal point of the second quadrupole that is less than or equal to 50 cm (“A set of two focusing quadrupole magnets focus the proton beam at the isocenter.”, both are set to same focal point (the isocenter) so distance between the focal points approximately zero), for providing the volume extending between the focal point of the first quadrupole and the focal point of the second quadrupole, along which the full width at half maximum (FWHM) of the focused beam to be less than or equal to 2 mm (intended use, non-limiting), the second quadrupole being further arranged to have a focal point at a distance between 2.0 cm and 50 cm from an exit plane of the nozzle (fig. 3, focal point is isocenter which is 6.5 – 41.5 cm from nozzle exit when range shifter is in use, and 0-35 cm from nozzle exit when not using a range shifter). Rana et al. does not disclose whether the focal lengths comprise between 60 and 250 cm and between 50 and 200 cm. It is generally known how to set the focal lengths as needed. It would have been obvious to a person having ordinary skill in the art at the time the application was filed to place the isocenter at least 50 and 60 cm away from the quadrupoles to provide sufficient room for the scanning magnets. It would further have been obvious to place the isocenter within 200 and 250 cm, respectively, to reduce the overall nozzle size and maintain a small air gap, where a small air gap in particular is desired, as disclosed in Rana et al. (“The air gap increases the in-air spot size at the isocenter due to the angular distribution of a pencil proton beam after traversing the range shifter and translation of angular distribution into a geometric spread of proton beam’s cross-section at the detector/patient surfaces as a function of distance [7, 8].”). Regarding claim 14, Rana et al. discloses the system according to claim 13, wherein the beam source comprises a beamline of a medical facility 1 (“Our proton center is equipped with ProteusPLUS (Ion Beam Applications, Louvain-la-Neuve, Belgium), which includes PBS in all three gantries.”). Regarding claim 15, Rana et al. discloses the system according to claim 13, wherein the MSN is a charged particles minibeam Radiation Therapy scanning nozzle (MRTSN), the MRTSN comprising, along a beam path of the charged particles inside the nozzle: - a first quadrupole arranged to focus the incident beam according to a first direction; - a second quadrupole arranged to focus the incident beam according to a second direction orthogonal to the first direction;- a third magnet arranged to deflect the incident beam according to a third direction; and - a fourth magnet arranged to deflect the incident beam according to a fourth direction different from the third direction (fig. 1); the first quadrupole and respectively the second quadrupole being arranged to have: - a focal length comprised between 60 and 250 cm and respectively a focal length comprised between 50 and 200 cm (obvious for the reasons discussed above with respect to parent claim 13), for decreasing a size of the focused beam to a full width at half maximum (FWHM) that is less than or equal to 2 mm along a volume extending between a focal point of the first quadrupole and a focal point of the second quadrupole (intended result, non-limiting), - a distance between the focal point of the first quadrupole and the focal point of the second quadrupole that is less than or equal to 50 cm (“A set of two focusing quadrupole magnets focus the proton beam at the isocenter.”, both are set to same focal point (the isocenter) so distance between the focal points approximately zero), for providing the volume extending between the focal point of the first quadrupole and the focal point of the second quadrupole, along which the full width at half maximum (FWHM) of the focused beam to be less than or equal to 2 mm (intended result, non-limiting), the second quadrupole being further arranged to have a focal point at a distance between 2.0 cm and 50 cm from an exit plane of the nozzle (fig. 3, focal point is isocenter which is 6.5 – 41.5 cm from nozzle exit when range shifter is in use, and 0-35 cm from nozzle exit when not using a range shifter). Regarding claim 16, Rana et al. discloses a charged particles minibeam radiation therapy system comprising : - a beamline of a medical facility arranged to emit an incident beam of charged particles (“Our proton center is equipped with ProteusPLUS (Ion Beam Applications, Louvain-la-Neuve, Belgium), which includes PBS in all three gantries.”), - a minibeam scanning nozzle (MSN) arranged to generate a minibeam of charged particles from the incident beam of charged particles, the MSN comprises, along a beam path of the charged particles inside the nozzle: • a first quadrupole arranged to focus the incident beam according to a first direction (fig. 1, “Focusing Quadrupole Magnets”); • a second quadrupole arranged to focus the incident beam according to a second direction orthogonal to the first direction (fig. 1, “Focusing Quadrupole Magnets”); • a third magnet arranged to deflect the incident beam according to a third direction (fig. 1, “Vertical Scanning Magnets”); and • a fourth magnet arranged to deflect the incident beam according to a fourth direction different from the third direction (fig. 1, “Horizontal Scanning Magnets”); the first quadrupole and respectively the second quadrupole being arranged to have: - a focal length (inherent, a lens must have a focal length) for decreasing a size of the focused beam to a full width at half maximum (FWHM) less than or equal to 2 mm along a volume extending between a focal point of the first quadrupole and a focal point of the second quadrupole (intended use, non-limiting), - a distance between the focal point of the first quadrupole and the focal point of the second quadrupole that is less than or equal to 50 cm (“A set of two focusing quadrupole magnets focus the proton beam at the isocenter.”, both are set to same focal point (the isocenter) so distance between the focal points approximately zero), for providing the volume extending between the focal point of the first quadrupole and the focal point of the second quadrupole, along which the full width at half maximum (FWHM) of the focused beam to be less than or equal to 2 mm (intended use, non-limiting), the second quadrupole being further arranged to have a focal point at a distance between 2.0 cm and 50 cm from an exit plane of the nozzle fig. 3, focal point is isocenter which is 6.5 – 41.5 cm from nozzle exit when range shifter is in use, and 0-35 cm from nozzle exit when not using a range shifter). Rana et al. does not disclose whether the focal lengths comprise between 60 and 250 cm and between 50 and 200 cm. It is generally known how to set the focal lengths as needed. It would have been obvious to a person having ordinary skill in the art at the time the application was filed to place the isocenter at least 50 and 60 cm away from the quadrupoles to provide sufficient room for the scanning magnets. It would further have been obvious to place the isocenter within 200 and 250 cm, respectively, to reduce the overall nozzle size and maintain a small air gap, where a small air gap in particular is desired, as disclosed in Rana et al. (“The air gap increases the in-air spot size at the isocenter due to the angular distribution of a pencil proton beam after traversing the range shifter and translation of angular distribution into a geometric spread of proton beam’s cross-section at the detector/patient surfaces as a function of distance [7, 8].”). Regarding claim 17, Rana et al. discloses the system according to claim 16, wherein the MSN is arranged downstream of the beamline in a path of the incident beam of charged particles (“Our proton center is equipped with ProteusPLUS (Ion Beam Applications, Louvain-la-Neuve, Belgium), which includes PBS in all three gantries.”). Regarding claim 18, Rana et al. discloses the claimed method except it is does not specify whether the focal length of the first quadrupole and respectively of the second quadrupole are set by adjusting a magnetic field gradient generated by the first quadrupole and respectively by the second quadrupole. Focusing quadrupoles work by adjust either a magnetic field gradient or an electric field gradient, and it would have been obvious to a person having ordinary skill in the art at the time the application was filed to use a magnetic field gradient because magnetic quadrupoles have a stronger focusing effect. Regarding claim 19, Rana et al. discloses the system according to claim 16, wherein the beam source arranged to generate an incident beam of charged particles that exhibits a dose rate superior to 40 Gray per second and an irradiation time lower than 500 milliseconds (intended use). Regarding claim 20, Rana et al. discloses the claimed method except it does not specify whether the wherein values of magnetic field gradients generated by the first and second quadrupoles are greater than or equal to 0 or are less than or equal to 1.6 T.cm-1. It would have been obvious to use magnetic field gradients for the reasons discussed above, and the gradient must have a value greater than 0 for it to perform focusing. Regarding the upper limit of 1.6 T.cm-1, applicants have not suggested that this value is critical and it would have been obvious to use a value below this limit if it was sufficient to achieve the desired level of focus. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELIZA W OSENBAUGH-STEWART whose telephone number is (571)270-5782. The examiner can normally be reached 10am - 6pm Pacific Time M-F. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert 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. 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 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 would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /ELIZA W OSENBAUGH-STEWART/Primary Examiner, Art Unit 2881