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 .
DETAILED ACTION
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 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.
Response to Restriction/Election
Applicants’ election of with traverse of Group I, claims 1-2, 4-5, 7-10 and 12, in response to restriction requirement is acknowledged. Applicant’s traversal is on the ground that the WO2019/234544 reference employs fluorescent labeling and does not disclose exciting the native fluorophore, does not anticipate claim 1, and thus Group I and II satisfy the requirement of unity of invention.
The above arguments have fully been considered but are not found persuasive because utilizing native fluorophore in CE system has been found to be obvious over WO2019/234544 in view of Albin (1991) as described in the rejection below.
Therefore, the restriction requirement is still deemed valid and is made FINAL. Therefore, claims 13-14, 16 and 18-25 are withdrawn from further consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03. Applicants preserve their right to file a divisional on the non-elected subject matter.
Status of the claims
Claims 1-2, 4-5, 7-10 and 12are examined on merits in this office action.
Claim Objections
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 1-2, 4-5, 7-10 and 12 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 “exciting at least one native fluorophore. The term “native fluorophore” has not been clearly defined in the specification and thus it is unclear what is intended by “native fluorophore’. Phenylalanine is the least fluorescent aromatic amino acids and since “native fluorophore” has not been defined in the specification, it is unclear as to whether “phenylalanine” is intended to be encompassed by “native fluorophore” in the claims for excitation and utilization in the process as claimed. Moreover, wavelength suitable for exciting phenylalanine if the detection process has not been clearly described and thus it is unclear what “wavelength” is intended for native fluorophore, as for example, phenylalanine for “suitable wavelength” in the process.
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 of this title, 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 1-2, 4-5, 7-10 and 12 are rejected under 35 U.S.C. 103 as obvious over Guttman et al. (WO2019234544A1) in view of Albin et al (Anal Chem. 1991) and Radenovic et al (J. Chromatography 2009).
Guttman discloses a method for protein analysis (claim 1 and para. 5, 6) of a sample in a capillary electrophoresis (CE) system (claim 6), comprising: flowing the sample through a capillary tube of the CE system (fig. 8 and claim 6); utilizing a light source to generate radiation containing at least one wavelength suitable for exciting at least one fluorophore of at least one target protein in the sample; directing an excitation beam containing the at least one excitation wavelength onto a transparent portion of the capillary tube of the CE system so as to excite said at least one fluorophore of the target protein passing through a lumen of the transparent portion in order to cause the at least one fluorophore to generate fluorescent radiation ("illumination source" (810), claim 1 and fig. 8); and detecting at least a portion of fluorescent radiation emitted by the excited target protein (claim 1 ).
Guttman teaches molecules (e.g. protein) labeled with fluorophore for excitation but however, does not teach detection of proteins by exciting aromatic amino acids tryptophan and tyrosine and detection by fluorescence by capillary electrophoresis system.
Albin is directed to fluorescence detection in Capillary Electrophoresis (CE). Albin teaches that since few molecules possess native fluorescence; it is often necessary to prepare derivative that introduce fluorescent moiety (Introduction). Albin teaches protein exhibit native fluorescence (page 419). Albin teaches that compared to 200 nm, exciting at 280nm provides a much larger fluorescence signal corresponding to a tryptophan-containing peptides (page 420).
Radenovic teaches native fluorescence detection of proteins in capillary electrophoresis. Radenovic teaches analysis of proteins (lysozyme, trypsinogen, α-chymotrypsinogen) by detecting native fluorescence (page 4631, 1st para) using most selective absorbance wavelength of 280nm (page 4631, 1st para).
Therefore, given the fact that molecules (as for example, proteins) having native fluorescence by virtue of containing native fluorescence molecule tryptophan can be detected without labeling with a fluorophore (Albin and Radenovic) using selective wavelength at about 280nm (Albin and Radenovic), it would be obvious to one of ordinary skilled in the art to easily envisage detection of proteins without introducing a fluorophore in the capillary electrophoresis method of Guttman with a reasonable expectation of success. One of ordinary skilled in the art would consider not labeling protein with a fluorophore for detection in the CE method of Guttman because Albin teaches introducing fluorescent moiety for molecules that does not have native fluorescence (“since few molecules possess native fluorescence; it is often necessary to prepare derivative that introduce fluorescent moiety”) and proteins possess native fluorescence by virtue of having tryptophan and tyrosine. One of ordinary skilled in the art from the reading of Albin and Radenovic would easily understand the suitable wavelength for excitation when utilizing the CE method of Guttman would be around 280 nm.
In regard to claims 2, Guttman teaches that any type of illumination source device capable of exciting the fluorescently labeled molecules of sample 801, including, but not limited to, a light emitting diode (LED) device or a laser. In various embodiments, illumination source device 810 is preferably a laser in order to allow illumination source device 810 to be positioned at a distance from sample 801 (para [0076]).
In regard to claim 5, Guttman teaches the system of Figure 8 further includes a bandpass filter 880 positioned between second portion 816 and two-dimensional digital image detector 820. Bandpass filter 880 filters the light focused on two- dimensional digital image detector 880 to be within a specific frequency or wavelength range. Thus, filtering radiation to generate excitation beam and utilizing optical bandpass or shortpass filter would be obvious and withing the purview of one of ordinary skilled in the art.
Regarding claim 8, Guttman teaches antibodies (para 5) and Radinovic teaches analysis of various proteins (lysozyme, trypsinogen, α-chymotrypsinogen) by detecting native fluorescence and thus various proteins including analysis of antibody, which is also a protein, would be obvious to one of ordinary skilled in the art.
Regarding claim 10, Guttman teaches image detector for measuring fluorescence (Abstract) and bandpass filters focusing the light to image detector (claim 2). Andras further teaches one or more lenses are positioned between the first portion of the sample and a two-dimensional digital image detector. The one or more lenses focus at least a second portion of the first portion of the sample on the two-dimensional digital image detector (para [0011]).
Regarding claims 4, 7, 9 and 12, both Alvin and Radinovic teach excitation wavelength of about 280nm are suitable for analysis of proteins by virtue of having native fluorescence molecules of tryptophan and tyrosine and thus for analysis of proteins selection of light source and generating radiation with filters and adjusting for exhibiting transmission bandwidth in the range of 280 nm would be obvious to one of ordinary skilled in the art.
Claims 1-2, 4-5, 7-10 and 12 are rejected under 35 U.S.C. 103 as obvious over Landers et al. (WO2005033687) in view of Albin et al (Anal Chem. 1991) and Radenovic et al (J. Chromatography 2009).
Landers discloses a method for protein analysis of a sample in a capillary electrophoresis (CE) system (p. 7, I. 19-20 and claim 1 ), comprising: flowing the sample through a capillary tube of the CE system; utilizing a light source to generate radiation containing at least one wavelength suitable for exciting at least one native fluorophore of at least one target protein in the sample (p. 14, I. 8-13) ; directing an excitation beam containing the at least one excitation wavelength onto a transparent portion of the capillary tube of the CE system (p. 14, I. 7-18) so as to excite said at least one fluorophore of the target protein passing through a lumen of the transparent portion in order to cause the at least one fluorophore to generate fluorescent radiation; and detecting at least a portion of fluorescent radiation emitted by the excited target protein (p. 14, I. 15-18).
Landers teaches molecules (e.g. protein) labeled with fluorophore for excitation but however, does not teach detection of proteins by exciting aromatic amino acids tryptophan and tyrosine of the protein and detection by fluorescence by capillary electrophoresis system.
Albin is directed to fluorescence detection in Capillary Electrophoresis (CE). Albin teaches that since few molecules possess native fluorescence; it is often necessary to prepare derivative that introduce fluorescent moiety (Introduction). Albin teaches protein exhibit native fluorescence (page 419). Albin teaches that compared to 200 nm, exciting at 280nm provides a much larger fluorescence signal corresponding to a tryptophan-containing peptides (page 420).
Radenovic teaches native fluorescence detection of proteins in capillary electrophoresis. Radenovic teaches analysis of proteins (lysozyme, trypsinogen, α-chymotrypsinogen) by detecting native fluorescence (page 4631, 1st para) using most selective absorbance wavelength of 280nm (page 4631, 1st para).
Therefore, given the fact that molecules (as for example, proteins) having native fluorescence by virtue of containing native fluorescence molecule tryptophan can be detected without labeling with a fluorophore (Albin and Radenovic) using selective wavelength at about 280nm (Albin and Radenovic), it would be obvious to one of ordinary skilled in the art to easily envisage detection of proteins without introducing a fluorophore in the capillary electrophoresis method of Landers with a reasonable expectation of success. One of ordinary skilled in the art would consider not labeling protein with a fluorophore for detection in the CE method of Guttman because Albin teaches introducing fluorescent moiety for molecules that does not have native fluorescence (“since few molecules possess native fluorescence; it is often necessary to prepare derivative that introduce fluorescent moiety”) and proteins possess native fluorescence by virtue of having tryptophan and tyrosine. One of ordinary skilled in the art from the reading of Albin and Radenovic would easily understand the suitable wavelength for excitation when utilizing the CE method of Guttman would be around 280 nm.
In regard to claims 2, Landers teaches Laser-induced fluorescence detection (Abstract) and teaches laser driven light source (Example 1).
In regard to claim 5, Landers teaches generating excitation beam and utilizing bandpass filter (Example 1).
Regarding claim 8, Landers teaches detection of proteins (abstract) and Radinovic teaches analysis of various proteins (lysozyme, trypsinogen, α-chymotrypsinogen) by detecting native fluorescence and thus various proteins including analysis of antibody, which is also a protein, would be obvious to one of ordinary skilled in the art.
Regarding claim 10, Landers teaches a light source, such as a laser, which emits light in the wavelengths known to induce fluorescence of the fluorescent dye, is focused onto the optical or visual detection element. Landers teaches that the excitation/emission wavelengths for merocyanine dye are 450-500/520-660 nm, respectively and thus the 488 nm line of an Argon-ion laser can be used for excitation of the fluorophore and emission can be filtered through a 590DF35 band-pass filter for detection of fluorescence. Various lenses and optics can be used to focus and gather excited and emitted lights. The emitted light can be detected and quantify by a photoreceptor, such as a photomultiplier tube, a photodiode, a CCD array, and the like, and can be converted into electrical signals to be sent to a microprocessor for data recording and analysis. From the description in mind of Alvin and Radinovic, which teach excitation wavelength of about 280nm are suitable for analysis of proteins, one of ordinary skilled in the art can easily understand utilizing appropriate radiations and adopting appropriate lens and filters as needed for radiation with suitable wavelength with a reasonable expectation of success.
Regarding claims 4, 7, 9 and 12, both Alvin and Radinovic teach excitation wavelength of about 280nm are suitable for analysis of proteins by virtue of having native fluorescence molecules of tryptophan and tyrosine and thus for analysis of proteins selection of light source and generating radiation with filters and adjusting for exhibiting transmission bandwidth in the range of 280 nm would be obvious to one of ordinary skilled in the art.
Conclusion
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/SHAFIQUL HAQ/Primary Examiner, Art Unit 1678
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