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 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.
Claim 8 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.
Claim 8 recites the limitation "the ion optics". There is insufficient antecedent basis for this limitation in the claim. Suggested correction: make claim 8 dependent on claim 6.
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) 64-65, 71, and 79-82 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 2011/0204219 (Stein).
Regarding claim 64, Stein discloses a method of sequencing a biopolymer, comprising:
ionizing a biopolymer contained within a fluid (“In some embodiments, the sample chamber 6 contains an aqueous solution in which candidate molecules are dissolved.” P 26) into ions or ion clusters (“In one set of embodiments, the method includes acts of passing a polymer through a pore having a diameter of less than about 1 micrometer, sequentially cleaving the polymer as it passes through the pore to produce a plurality of fragments, and ionizing one or more of the fragments.” P 7);
passing the ions or ion clusters through a magnetic mass filter (“In some embodiments, a property of at least one subunit of a polymer is determined using mass spectrometry.” P 16, wherein “Monomer 12 can be accelerated through mass spectrometer 19 using a magnetic field created by magnetic region 10, before impinging on a detector 11, from which an output can be recorded.”);
directing the ions or ion clusters to an array of detectors (“t the far end of the mass spectrometer, a single ion detector array 11 registers the location of each ion impingement.” P 38); and
determining a sequence of the biopolymer by determining the ions or ion clusters with the array of detectors (“For example, in the case of biopolymer sequencing, the mass of each monomer, or the mass of a fragment that corresponds to a monomer, and the order of detection of the monomers or fragments of monomers are sufficient to determine the sequence of the polymer.”).
Regarding claim 65, Stein discloses the method of claim 64, wherein the biopolymer is a protein (“Non-limiting examples of biopolymers include a polynucleotide (e.g. DNA, RNA, etc.), a polypeptide (e.g. a protein, a hormone, etc.), a polysaccharide, (e.g. heparin, hyaluronic acid, glycogen, cellulose, chitin, etc.), or the like, as well as combinations of these.” P 17).
Regarding claim 71, Stein discloses the method of claim 64, wherein the ions or ion clusters have at an overall ion transmission efficiency of greater than or equal to about 0.8 (“In some instances, efficiency may be defined as the number of molecules detected by a mass spectrometer divided by the number of molecules entering the mass spectrometer … the efficiency of the mass spectrometer may be … at least about 80%, at least about 90%, at least about 95%, at least about 98%, or even at least about 99%.” P 39).
Regarding claim 79, Stein discloses the method of claim 64, wherein the ions or ion clusters may be detected at a time resolution of better than 100 nanoseconds (“detectors that are capable of counting ions with high efficiency, in some cases greater than 95% efficiency, and at a high rate, in some instances exceeding 100 million Hertz.” P 38).
Regarding claim 80, Stein discloses the method of claim 64, wherein ionizing a biopolymer contained within a fluid into ions or ion clusters comprises ionizing the biopolymer into single ions (“In some embodiments, a single ion (which may be a subunit of a polymer, or an ion based on another species) can be isolated in a mass spectrometer and a signal generated from the single ion.” P 16).
Regarding claim 81, Stein discloses the method of claim 64, wherein passing the ions or ion clusters through a magnetic mass filter comprises passing single ions through a magnetic mass filter (“In some embodiments, a single ion (which may be a subunit of a polymer, or an ion based on another species) can be isolated in a mass spectrometer and a signal generated from the single ion.” P 16).
Regarding claim 82, Stein discloses the method of claim 64, wherein directing the ions or ion clusters to an array of detectors comprises directing the single ions to an array of detectors (“At the far end of the mass spectrometer, a single ion detector array 11 registers the location of each ion impingement.” P 38).
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) 1-3, 5-10, and 63 is/are rejected under 35 U.S.C. 103 as being unpatentable over “The nanopore mass spectrometer” (Bush et al.) in view of US 2011/0204219 (Stein).
Regarding claim 1, Bush et al. discloses a mass spectrometer, comprising:
an ion source (fig. 2, “nanopore ion source”) comprising a capillary (“capillary nanotips”) and an electrode proximate the capillary (“extraction electrode”) wherein the capillary comprises an opening having a cross-sectional dimension of less than 125 nm (“Figures 5(c) and 5(d) show scanning electron micrographs of a nanotip with an inner diameter of 60 nm.”)
a magnetic mass filter downstream of the ion source (fig. 2, “Quadrupole mass filed”); and
a detector downstream of the magnetic mass filter (fig. 2, “channel detector”, also fig. 2 “faraday cup”).
Bush does not disclose an array of detectors. Stein discloses a nanopore mass spectrometer with an array of detectors (multiple figures, element 11). It would have been obvious to a person having ordinary skill in the are to substitute the array of detectors from Stein for the single detector in Bush et al. so that the mass spectrum could be measured more efficiently, as more detectors means measuring a larger number of ions over a great mass to charge window at any given time.
Regarding claim 2, Bush et al. in view of Stein disclose the mass spectrometer of claim 1, further comprising a vacuum chamber housing the ion source (“vacuum chamber”).
Regarding claim 3, Bush et al. in view of Stein disclose the mass spectrometer of claim 2, wherein the vacuum chamber has a pressure of no more than 100 mPa (intended use, also “The pressure inside the chamber rises to about 10-6 mbar with the introduction of a nanopore containing liquid sample. The safe operation of the mass filter and the ion detector requires a chamber pressure in the lower part of the 10-6 mbar range.”).
Regarding claim 5, Bush et al. in view of Stein disclose the claimed invention except for the magnetic mass filter comprising a permanent magnet. The use of permanent magnets in magnetic mass filters is well-known in the art. It would have been obvious to a person having ordinary skill in the art to substitute a permanent magnet for the quadrupole mass filter of Bush so that power would not be required to operate the mass filter.
Regarding claim 6, Bush et al. in view of Stein disclose the mass spectrometer of claim 1, further comprising an ion optics downstream of the ion source and upstream of the magnetic mass filter (fig. 2, ion lens 1 and ion lens 2).
Regarding claim 7, Bush et al. in view of Stein disclose the mass spectrometer of claim 1, furthering comprising an ion bender configured to deflect ions exiting the mass filter to the detector (fig. 2, ion bender).
Regarding claim 8, Bush et al. in view of Stein disclose the mass spectrometer of claim 7, wherein the ion optics comprises at least one Einzel lens (“The ions travel through a circular hole in the center of the extractor and then through an electrostatic einzel lens that focuses their trajectories onto the main axis of the mass spectrometer.”).
Regarding claim 9, Bush et al. in view of Stein disclose the mass spectrometer of claim 1, wherein the mass spectrometer has a temporal resolution of less than or equal to 1 microsecond (as per MPEP 2112.01, when the structure recited in the reference is substantially identical to that the claims, claimed properties are presumed to be inherent, it is noted that at least the array of detectors is capable of this rate, Stein, “The detector array may comprise, for instance, a set of Channeltron (Burle Industries, Inc., Lancaster, Pa.) single ion detectors that are capable of counting ions with high efficiency, in some cases greater than 95% efficiency, and at a high rate, in some instances exceeding 100 million Hertz.”).
Regarding claim 10, Bush et al. in view of Stein disclose the mass spectrometer of claim 1, wherein the array of detectors comprises an electron multiplier (“The detector array may comprise, for instance, a set of Channeltron (Burle Industries, Inc., Lancaster, Pa.) single ion detectors” P 38).
Regarding claim 63, Bush et al. in view of Stein disclose the mass spectrometer of claim 1, wherein the detector is a single-ion detector (channeltrons are known to be single-ion detectors).
Claim(s) 66, 72-73 is/are rejected under 35 U.S.C. 103 as being unpatentable over Stein as applied to claims 65-65 above.
Regarding claim 66, Stein discloses the claimed method except it is silent as to whether ionizing amino acids of the protein is done at a rate of at least 1 amino acid per microsecond. The process steps in Stein are the same as in the claimed method, and applicant has not shown that any particular settings, parameters, or additional steps are necessary to achieve the claimed ionization rate. Therefore, this appears to be merely a rate found to be achievable through routine experimentation. It would have been obvious to a person having ordinary skill in the art at the time the application was filed to ionize the amino acids at as high rate is reasonably achievable to improve efficiency.
Regarding claim 72, Stein discloses the claimed method except it is silent as to whether the ions or ion clusters are produced at a rate of greater than or equal to 1 ion or ion cluster/microsecond to 100 ions or ion clusters/microsecond. The process steps in Stein are the same as in the claimed method, and applicant has not shown that any particular settings, parameters, or additional steps are necessary to achieve the claimed ionization rate. Therefore, this appears to be merely a rate found to be achievable through routine experimentation. It would have been obvious to a person having ordinary skill in the art at the time the application was filed to ionize the biopolymer at as high rate is reasonably achievable to improve efficiency.
Regarding claim 73, Stein discloses the claimed method except it is silent as to whether he time interval between a molecule exiting as ions or ion clusters proximate the opening and detection of the ions or ion clusters at the array of detectors is greater than or equal to 10 microseconds and less than or equal to 100 microseconds. The time interval is dependent on the length of the travel path and the strength of the extraction voltage and any acceleration voltages applied. Therefore, a person having ordinary would now how to set the time interval as desired, and the particular range given appears to choose through routine optimization or experimentation, as applicant has not stated that the range solves any particular problem or has any unexpected effect.
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