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 Interpretation
The limitation of “corresponding feature” found in line 5 of claim 1 is interpreted as outlined in paragraph 215 of the specification seen below. Additional occurrences of the limitation found claims 18 and 19 are interpreted the same way.
[0215] The degree of coloration—represented by the color value 12 or corresponding property—of a bulk drug substance (product 3) predicted by exciting fluorescent radiation 6 at, e.g., 390 nm of the solution 2 derived from samples of in-process steps (of production or purification of the proteins within the protein-containing solution 2), measuring at least one property, preferably a spectrum 6A or corresponding feature (like an intensity or, e.g., an integral 29/area under the curve thereof) of the—preferably blank subtracted—fluorescent radiation 6, e.g., between 420 nm and 600 nm, which is further divided by a protein concentration of the protein-containing solution 2 sample, resulting in a protein-mass specific/normalized fluorescence intensity.
The limitation “future color value or corresponding future property” found in line 7 of claim 1 is interpreted as outlined in paragraph [0067] as seen below. All other instances of this limitation in claims 4-5, 7-8, 11-16 are interpreted the same way.
[0067] The color or color value preferably corresponds to a property of the solution, the product or the proteins. Thus, a property that corresponds to the color value in particular is a suitability of the solution, the product or the proteins to be used for the intended purpose. The property in particular can be an indicator for pharmaceutical effects or side effects. The property preferably corresponds to the color value when the color value affects the property or the property depends on the color or color value, e.g. due to a regulative requirement, due to the color being an indicator for a suitability for application, or due to the color having a direct or indirect pharmaceutical effect.
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 1-17 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 are generally narrative and indefinite, failing to conform with current U.S. practice. They appear to be a literal translation into English from a foreign document and are replete with grammatical and idiomatic errors.
The final limitation “determining the future color value (12) or corresponding future property of the solution (2) or product (3) based on a correlation between the at least one property of the fluorescent radiation (6) and a present or the future color value (12) or corresponding property of the solution (2) or the product (3).” It is unclear how the future color value or corresponding future property of the solution or product can be determined using itself “the future color value or the corresponding future property of the solution or product.” This reads a circular statement and it not clear how that mathematically would work. Please kindly clarify.
Allowable Subject Matter
Claims 1-17 would be allowable if rewritten or amended to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action.
Regarding claim 1, none of the prior art of record teaches or makes obvious a method of determining a future color value (12) or corresponding future property of a protein-containing solution (2) or of a protein-containing product (3) prepared therefrom, comprising:
exciting fluorescent radiation (6) of the solution (2) or product (3),
measuring at least one property, preferably a spectrum (6A) or corresponding feature, of the fluorescent radiation (6), and
determining the future color value (12) or corresponding future property of the solution (2) or product (3) based on a correlation between the at least one property of the fluorescent radiation (6) and a present or the future color value (12) or corresponding property of the solution (2) or the product (3).
Allowable Subject Matter
Claims 18-19 are allowed.
The following is an examiner’s statement of reasons for allowance:
Regarding claim 18, none of the prior art of record specifies or makes obvious a method for producing a protein-containing solution (2) or a product (3) produced therefrom, comprising the steps of: (i) cultivating a eukaryotic cell expressing a recombinant protein of interest in cell culture; (ii) harvesting the recombinant protein; (iii) purifying the recombinant protein; and (iv) optionally formulating the recombinant protein into a pharmaceutically acceptable formulation suitable for administration; and (v) obtaining at least one sample comprising the recombinant protein in steps (ii), (iii) and/or (iv);
wherein the sample is the solution (2) or product (3), and wherein the method further comprises a method of determining a future color value (12) or corresponding future property of a protein-containing solution (2) or of a protein-containing product (3) prepared therefrom, comprising:
exciting the fluorescent radiation (6) of the solution (2) or product (3), measuring at least one property, preferably a spectrum (6A) or corresponding feature, of the fluorescent radiation (6), and determining the future color value (12) or corresponding future property of the solution (2) or product (3) based on a correlation.
Regarding claim 19, none of the prior art of record specifies or makes obvious an arrangement (1) comprising a light source (4), a spectrometer (7) for measuring a fluorescent radiation (6), and a device (18) adapted to carry out a method of determining a future color value (12) or corresponding future property of a protein-containing solution (2) or of a protein-containing product (3) prepared therefrom, comprising:
exciting the fluorescent radiation (6) of the solution (2) or product (3), measuring at least one property, preferably a spectrum (6A) or corresponding feature, of the fluorescent radiation (6), and
determining the future color value (12) or corresponding future property of the solution (2) or product (3) based on a correlation.
References likes Vijayasankaran (US 2013/0281355 A1; October 24, 2013) [0147] In another example, the polypeptides produced by the methods detailed herein with the media described herein (or present in the compositions provided) may be assessed for color with a quantitative assay. In a variation, the quantitative assay can be done using an automated process. In a variation, the quantitative assay is the normalized fluorescence intensity (NIFTY) assay or the Total Color assay described herein. For example, a solution containing a polypeptide produced by any of the methods described herein may be assessed for color intensity by the NIFTY assay by subjecting a solution comprising a polypeptide to the following steps: 1) applying polypeptide test sample to size exclusion chromatography (SEC) wherein the mobile phase for SEC comprises a buffer at a specific pH with the column maintained at a specific temperature; 2) monitoring the SEC eluent for UV absorption at a specific wavelength (e.g., 280 nm) and for fluorescence with a specific excitation wavelength (e.g., at 350 nm) and emission wavelength (e.g., at 425 nm); 3) integrating the SEC peaks of the polypeptide species using software known in the art (e.g., Agilent Chemstation software) on the UV absorbance and the fluorescence emission chromatograms and normalizing the fluorescence by dividing the fluorescence peak area of the main peak by the UV absorbance peak area of the main peak; and 4) calculating the ratio of the normalized fluorescence of the polypeptide test sample to that of a polypeptide reference sample containing a known COC value based on any of the reference standards disclosed herein such as brown (B), brownish-yellow (BY), yellow (Y), greenish-yellow (GY), or red (R) to obtain a numerical value, wherein a higher numerical value (e.g., a higher NIFTY value) indicates a higher color intensity and a lower numerical value (e.g., a lower NIFTY value) indicates a lower color intensity.
Additionally, references such as Vijayasankaran (Effect of Cell Culture Medium Components on Color of Formulated Monoclonal Antibody Drug Substance; June 11, 2013) teach in order to derive a quantitative value of the relative color of samples we used the CIE System of color measurement.17Briefly, after blanking with water we took the absorption spectrum of a sample in the visible region (380–780 nm) using aHP8453A spectrophotometer (1 cm pathlength cuvette). The absorption spectrum contains information about color perception. In order to quantitatively represent visual perception, the absorption spectrum was then transformed to the CIE L*a*b*color scale (as has been described previously).18L*a*b* is a three dimensional color space with an approximately uniform spacing in visual perception. The L*a*b* color space is able to quantify differences in visual judgment of colors. For example, two solutions that are visually judged to have very different colors will be further apart in the L*a*b*color space when compared with two solutions that have simi-lar color which will be closer together within the L*a*b* color space. Within the three dimensional L*a*b* space the distance between points is calculated as the Euclidian between the points (delta E). This allows for measuring the delta E between points in the L*a*b* color space and correlating this distance to visual perception judgment of color differences. Large delta E represents two solutions of very different colors, small delta E represents two solutions of similar color. The transformation of absorption spectrum to L*a*b*color space requires a defined illuminant. For this work, an artificial flat spectrum in the visible region was used as the illuminant. Although this does not give an exact true perceived color, the relative color computed was sufficient for this study. The “total color” described within this manuscript represents the delta E between the sample and water in the three dimensional CIE L*a*b* color space. It should be noted that “total color” represents the overall color of the sample but does not differentiate between differing hues. Total color measurements were normalized to the value measured for the reference standard. In this work, a reference material lot of monoclonal antibody with a COC reading of B5 was used. Any meaningful measurement of color using the total color method required some level of purification of the cell culture fluid and concentration of the antibody solution to 150g=L. Hence, a sufficiently large cell culture sample was required in order to get the required amount of material for a reasonable absorbance measurement
However, both Vijayasankaran references do not teach the abovementioned limitations.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee. Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.”
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
-US 20160002593 A1 teaches color intensity of a protein determined by NIFTY.
-US 20260008997 A1 teaches color intensity of a protein determined by NIFTY.
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/GISSELLE GUTIERREZ/
Examiner
Art Unit 2884
/UZMA ALAM/Supervisory Patent Examiner, Art Unit 2884
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