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 .
Information Disclosure Statement
The information disclosure statements (IDS) submitted on November 29, 2023 are being considered by the examiner. Two of the information disclosure statements submitted on November 29, 2023 were crossed out and not considered due to being duplications. Non-Patent Literature (NPL) citation 10, Davidson et al. was not considered and lined through because it was not submitted.
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 carbohydrate.” There is insufficient antecedent basis for this limitation in the claim. Claim 7, upon which claim 8 depends on mentions that the sample is a glycan. There is no prior mention of a carbohydrate sample. “The glycan sample” mentioned in claim 7 corresponds to “a glycan sample” mentioned in claim 1, which it is dependent on.
For examination purposes examiner has interpreted “the carbohydrate sample” as “the glycan sample.” For claim 8, it would be advised to change “the carbohydrate sample” to “the glycan sample” to match the prior claims. Further, if this change is made, “the carbohydrate sample” in claim 10 should be changed to “the glycan sample”, since it would no longer have antecedent basis to the terminology of claim 8.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-6, 12-13, are rejected under 35 U.S.C. 103 as being unpatentable over Lapadula et al. (“Lapadula”) (US 2011/0137570 A1) in view of MtoZ Biolabs (How Can Relative Abundance Be Calculated?).
Regarding claim 1, Lapadula discloses a method of analyzing the structure of a glycan sample (paragraph 0006), the method comprising: receiving data indicative of one or more spectra of mass-to-charge ratio (m/z) versus relative abundance of the glycan sample from a mass spectrometer (MS) instrument (paragraphs 0006-0009; paragraph 0079 defines that fragmentation pattern is represented by m/z peaks; Figs. 1-2 show relative abundance versus m/z);
While Lapadula discloses that the relative abundance is used, Lapadula does not explicitly disclose the formula for calculating the relative abundance. Examiner is interpreting “generate a ratio according to the following equation:
a
a
+
b
wherein a is a magnitude of one or more first peaks in the one or more spectra and b is the magnitude of one or more second peaks in the one or more spectra;” as the calculation of relative abundance.
MtoZ Biolabs discloses how to calculate relative abundance by dividing one peak height/area/intensity by the total of the peak heights/areas/intensities (step 5). In step 5, MtoZ Biolabs teaches calculating relative abundance for two peaks.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to calculate the relative abundance in Lapadula, by the method disclosed by MtoZ Biolabs, as this is disclosed as being a known formula for calculating relative abundance. As set forth in MPEP §2143(I)(A), “The rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art.”
Determine that the ratio is within a range of a predetermined ratio; based on determining that the ratio is within the range of the predetermined ratio determining that a predetermined structural characteristic is present in the glycan sample; and outputting an indication of the predetermined structural characteristic in the glycan sample (Lapadula discloses that the relative abundance of isomers can be used to weight the scoring method (paragraph 0515). The scoring method is used to compare the predicted fragmentation of a glycan/substructure with an experimental fragmentation pattern and assign a value to the glycan/substructure that is then used to determine whether the proposed glycan is acceptable (paragraph 0100).)
Regarding claim 2, Lapadula discloses the glycan sample comprises a protonated glycan comprising an oligosaccharide (paragraphs 0152-0156).
Regarding claim 3, the protonated glycan comprises an O-glycan, an N-glycan or a sialylated glycan (paragraph 0082, N-glycan and O-glycan).
Regarding claim 4, Lapadula discloses the glycan comprises an oligosaccharide (paragraph 0082), and wherein the monosaccharides of the oligosaccharide are linked through O-glycosidic linkages (paragraphs 0123-0124; Scheme 3 shows monosaccharides linked via o-glycosidic linkages).
Regarding claim 5, Lapadula discloses the predetermined structural characteristic comprises: an identity of the one or more monosaccharides or oligosaccharides of the glycan; a connectivity of the O-glycosidic linkages of the one or more oligosaccharides of the glycan; or the configuration of anomeric carbons in the one or more monosaccharides or oligosaccharides of the glycan (paragraph 0123).
Regarding claim 6, Lapadula discloses determining the range of the predetermined ratio based on a number of ion counts associated with the one or more spectra (paragraph 0159).
Regarding claim 12, Lapadula discloses the one or more first peaks are defined at an m/z of 138 and the one or more second peaks are defined at an m/z of 144 in an MSn spectrum derived from fragmentation of a portion of the sample corresponding to m/z 204 in an MSn-1 spectrum, wherein the predetermined ratio is 0.37, 0.81, or 0.73 and wherein the predetermined structural characteristic comprises: the presence of an isomer in the glycan sample, the isomer comprising N- acetylgalactosamine (GalNAc), N-acetylglucosamine (GlcNAc), or N-acetylmannosamine (ManNAc); or the presence at the reducing end of an oligosaccharide in the glycan sample, of GalNAc or GlcNAc (paragraphs 0120, 0124; scheme 3).
The structures (material) would have the same properties and therefore would have the same m/z and ratios that are being claimed.
Regarding claim 13, Lapadula discloses the one or more first peaks are defined at an m/z of 84 and 126 and the one or more second peaks are defined at an m/z of 138, 144, 168, and 186 in an MSn spectrum derived from fragmentation of a portion of the sample corresponding to m/z 204 in an MSn-1 spectrum, wherein the predetermined ratio is 0.21, 0.20, or 0.42 and wherein the predetermined structural characteristic comprises: a type of a O-glycosidic linkage between two monosaccharides in a disaccharide portion of the glycan sample, the type of the O-glycosidic linkage being 1-3, 1-4, or 1-6 linkage (paragraph 0124 shows 1-4 linkage).
The structures (material) would have the same properties and therefore would have the same m/z and ratios that are being claimed.
Claims 7-11, 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Lapadula et al. in view of MtoZ Biolabs as applied to claim 1 above, and further in view of Deguchi et al. (“Deguchi”)(US 2008/0048110 A1) and Kozhinov et al. (“Kozhinov”) (WO 2017/168389 A1).
Regarding claim 7, modified Lapadula does not disclose how the MS instrument is set up.
Deguchi discloses by the MS instrument, the one or more spectra by passing the glycan sample through the MS instrument, and generating, by one or more analog-to-digital converters (ADCs), the data indicative of one or more spectra (paragraph 0047; Figs 10, 13-14 one of ordinary skill in the art at the time of the invention would know that a converter would be needed to convert the data from the detector16 into digital format so that the data analyzer can process, and interpret it).
Deguchi discloses that the configuration in Figs. 10, 13-14 is a time-of-flight, a Fourier transform (FT) ion-cyclotron resonance (ICR), or an Orbitrap mass spectrometer (paragraph 0056).
Deguchi does not explicitly mention the use of a converter with MS instrument.
Kozhinov discloses an invention for the acquisition of digitized signals and corresponding mass spectra from an analog signal. (Fig. 1A, 17 ADC) that can be used in conjunction with FT ICR or Orbitrap mass spectrometers (pg. 1 Field of Invention; pgs. 5-6 Data acquisition systems and Reference to Fig. 1A).
It would have been obvious to one having ordinary skill in the art before the effective
filing date of the claimed invention to use an analog-to-digital converter to convert in real time the conditioned analog signal into a digital data stream (Kozhinov, pg. 19). As set forth by MPEP §2143(I)(D).
Regarding claim 8, modified Lapadula discloses obtaining by MS instrument, the one or more spectra comprises: obtaining by the MS instrument, a first MS spectrum (MS1 spectrum) by passing the glycan sample through the MS instrument the first time; obtaining a portion of the carbohydrate sample corresponding to one or more peaks of the MS1 spectrum; and obtaining by MS instrument, a second MS spectrum (MS2 spectrum) by passing the portion of the carbohydrate sample through the MS instrument the second time (paragraphs 0008-0016, 0177).
Regarding claim 9, modified Lapadula discloses the portion of the glycan sample is a first portion of the glycan sample, and wherein obtaining by the MS instrument the one or more spectra further comprises: obtaining a second portion of the glycan sample corresponding to one or more peaks of the MS2 spectrum; and obtaining by the MS instrument a third MS spectrum (MS3 spectrum) by passing the second portion of the glycan sample through the MS instrument a third time (paragraphs 0015-0016, 0165).
Regarding claim 10, modified Lapadula discloses obtaining by MS instrument the one or more spectra further comprises: obtaining a third portion of the carbohydrate samples corresponding to one or more peaks of the MS3 spectrum; and obtaining by the MS instrument a fourth MS spectrum (MS4 spectrum) by passing the third portion of the glycan sample through the MS instrument a fourth time (paragraphs 0015-0016, 0165).
Regarding claim 11, modified Lapadula discloses that the glycan mixture may optionally be separated by LC (liquid chromatography) or similar techniques (paragraph 0155).
Lapadula does not disclose the use of liquid chromatography prior to performing MS.
Deguchi discloses prior to obtaining by the MS instrument the one or more spectra by passing the glycan sample through the MS instrument, the glycan sample is passed through a liquid chromatograph (LC) instrument to generate a liquid chromatogram (fig. 10, liquid chromatograph 11), and wherein obtaining by the MS instrument the one or more spectra by passing the glycan sample through the MS instrument the first time comprises passing through the MS instrument (fig. 10, mass spectrometer 15) a portion of the glycan sample corresponding to a particular peak in the liquid chromatogram (paragraphs 0026, 0047).
It would have been obvious to one having ordinary skill in the art before the effective
filing date of the claimed invention to use liquid chromatography to reduce the number of glycan structures examined at one time (Lapadula, paragraph 0155).
Regarding claim 17, modified Lapadula discloses that sequential mass spectrometry is often implemented using an ion trap (IT-MS). Lapadula does not disclose that an ion trap was used.
Deguchi discloses a MS instrument with an ion trap (paragraphs 0039, 0055; fig. 13, CID/ECD cell 17).
It would have been obvious to one having ordinary skill in the art before the effective
filing date of the claimed invention to use an ion trap with sequential mass spectrometry (IT-MS) to allow the operator to select peaks from a spectrum, fragment them and record the resulting product ions in another spectrum (Lapadula, paragraph 0165)
Regarding claim 18, modified Lapadula discloses collision-induced dissociation (CID) (paragraphs 0073, 0642 claim 12).
Claims 14-16 are rejected under 35 U.S.C. 103 as being unpatentable over Lapadula et al. in view of MtoZ Biolabs as applied to claim 1 above, and further in view of Walsh et al. (“Walsh”)(US 2022/0013197 A1).
Regarding claim 14, modified Lapadula discloses a disaccharide (paragraph 0127, scheme 4A) but does not disclose the linkage.
Walsh discloses the predetermined structural characteristic comprises: a type of a O-glycosidic linkage between two monosaccharides in an oligosaccharide portion of the glycan sample, the type of the O-glycosidic linkage being 1-3, 1-4, or 1-6 linkage (pg. 23 shows a disaccharide lactose with 1-4 linkage).
While Walsh does not explicitly disclose the “one or more first peaks are defined at an m/z of 138 and 168, and the one more second peaks are defined at an m/z of 126, 144, and 186 in an MSn spectrum derived from fragmentation of a portion of the sample corresponding to an m/z of 366 or an m/z of 350 in an MSn-1 spectrum, wherein the predetermined ratio is wherein the predetermined ratio is 0.621, 0.843, or 0.536,” the structures (material) would have the same properties and therefore would have the same m/z and ratios that are being claimed. See MPEP §2112.01(II).
It would have been obvious to one having ordinary skill in the art before the effective
filing date of the claimed invention to combine prior art elements according to known methods to yield predictable results. See MPEP §2143(I)(A).
Regarding claim 15, modified Lapadula does not disclose glycosidic linkages being (α2-6) or an (α2-3) linkage.
Walsh discloses the predetermined structural characteristic comprises: a type of O-glycosidic linkage between two monosaccharides of a disaccharide portion of the glycan sample, the type of the glycosidic bond linkage being an (α2-6) or an (α2-3) linkage (pg. 26 shows glycans with 2-3 linkages).
While Walsh does not explicitly disclose the “one or more first peaks are defined at an m/z of 186 and 204, and the one or more second peaks are defined at an m/z of 256, 274, 292, 454, and 495 in an MSn spectrum derived from fragmentation of a portion of the carbohydrate sample corresponding to an m/z of 657 in an MSn-1 spectrum; wherein the predetermined ratio is 0.426 or 0.219”, the structures (material) would have the same properties and therefore would have the same m/z and ratios that are being claimed. See MPEP §2112.01(II).
It would have been obvious to one having ordinary skill in the art before the effective
filing date of the claimed invention to combine prior art elements according to known methods to yield predictable results. See MPEP §2143(I)(A).
Regarding claim 16, modified Lapadula does not disclose the type of O-glycosidic linkages.
Walsh discloses the predetermined structural characteristic comprises: a type of O-glycosidic linkage between Neu5Ac and Gal in a disaccharide portion of the glycan sample, the type of the glycosidic linkage being an (α2-6) or an (α2-3) linkage; a type of O-glycosidic linkage between Gal and GlcNAc in a tetrasaccharide portion of the glycan sample, the type of the glycosidic linkage being a (β1-4) or an (β1-3) linkage, the tetrasaccharide being Neu5Ac(α2-3)GalGlcNAc(β1-3)Glc; or a type of O-glycosidic linkage between Gal and GlcNAc-OH in a disaccharide portion of the glycan sample, the type of the glycosidic linkage being a (β1-3), (β1-4) or a (β1-6) linkage (pg. 29 shows glycans with Neu5Ac and Gal linkages with (α2-3) linkages).
While Walsh does not explicitly disclose the “one or more first peaks are defined at an m/z of 204 and 366, and the one or more second peaks are defined at an m/z of 274, 292, 454, 472 and 495 in an MSn spectrum derived from fragmentation of a portion of the carbohydrate sample corresponding to an m/z of 657 in an MSn-1 spectrum, wherein the predetermined ratio is 0.867, 0.758, 0.685, 0.536, 0.531, 0.403, or 0.234”, the structures (material) would have the same properties and therefore would have the same m/z and ratios that are being claimed. See MPEP §2112.01(II).
It would have been obvious to one having ordinary skill in the art before the effective
filing date of the claimed invention to combine prior art elements according to known methods to yield predictable results. See MPEP §2143(I)(A).
Claims 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Walsh et al. (“Walsh”) (US 2022/0013197 A1) in further view of MtoZ Biolabs (How Can Relative Abundance Be Calculated?).
Regarding claim 19, Walsh discloses a system comprising at least one processor; and receiving data indicative of one or more spectra of mass-to-charge ratio (m/z) versus relative abundance of a glycan sample from a mass spectrometer (MS) instrument (paragraphs 0049-0051; fig. 4); determining that the ratio is within a range of a predetermined ratio; based on determining that the ratio is within the range of the predetermined ratio, determining that a predetermined structural characteristic is present in the glycan sample; and outputting an indication of the predetermined structural characteristic in the glycan sample (paragraphs 0013-0015).
While Walsh discloses that the relative abundance is used, Walsh does not explicitly disclose the formula for calculating the relative abundance.
MtoZ Bio labs discloses how to calculate relative abundance as mentioned in response to claim 1. See supra.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to calculate the relative abundance in Walsh, by the method disclosed by MtoZ Biolabs, as this is disclosed as a being a known formula for calculating relative abundance. As set forth in MPEP 2143 I A, “The rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art.”
Regarding claim 20, Walsh discloses a system comprising a mass spectrometer (MS) instrument configured to generate data indicative of one or more spectra of mass-to-charge ratio (m/z) versus relative abundance of a glycan sample (paragraphs 0049-0051; fig. 4); an output device configured to output a report indicating a predetermined structural characteristic present in the glycan sample; and a processor configured to: based on determining that the ratio is within the range of the predetermined structural characteristic is present in the glycan sample (paragraphs 0013-0015).
While Walsh discloses that the relative abundance is used, Walsh does not explicitly disclose the formula for calculating the relative abundance.
MtoZ Bio labs discloses how to calculate relative abundance as mentioned in response to claim 1. See supra.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to calculate the relative abundance in Walsh, by the method disclosed by MtoZ Biolabs, as this is disclosed as a being a known formula for calculating relative abundance. As set forth in MPEP 2143 I A, “The rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art.”
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brianna K. Slade whose telephone number is (571)272-8514. The examiner can normally be reached Monday - Friday 8:30 AM - 2:00 PM.
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/B.K.S./ Examiner, Art Unit 1796
/ELIZABETH A ROBINSON/ Supervisory Patent Examiner, Art Unit 1796