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 .
Election/Restrictions
Applicant’s election without traverse of claims 1-10 in the reply filed on 09/03/2025 is acknowledged. Claims 11-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09/03/2025.
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 1-10 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 claim 1, the limitation “by performing one or more operations comprising: comparing (i) a first yield titer of the target molecule in the first elution product to (ii) a concentration threshold of the target molecule, and in response to determining that the first yield titer is less than the concentration threshold, requesting an amount of the harvest product to be inputted into the second chromatography column so that a combination of the first elution product and the amount of the harvest product provides a titer greater than or equal to the concentration threshold.” renders the claim indefinite because it is unclear whether the claim is reciting limitations (i) and (ii) as alternatives. Since comparison of (i) and (ii) is claimed, it does not appear that (i) and (ii) are claimed to be alternative. The phrase “one or more operations” makes the limitations following that phrase ambiguous.
Regarding claim 2, the limitation “to perform a proper chromatography” renders the claim indefinite because it is unclear what differentiates “proper chromatography” from “improper chromatography”. The specification does not provide a standard for ascertaining the requisite degree (differentiating “proper” and “improper”), and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Regarding claim 4, the limitation “a first product” in line 2 renders the claim indefinite because it is unclear whether the limitation is referring to the harvest product or a different product solution.
Regarding claim 6, the limitation “the same type of chromatography procedure” in line 3 renders the claim indefinite because “type” is a relative term.
Regarding claim 7, the limitation “a threshold target yield titer” in line 2 renders the claim indefinite because it is unclear whether the “threshold target yield titer” is same or different from “the concentration threshold” recited in claim 1.
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.
Claim(s) 1, 2, and 5-10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bangtsson et al. (US 2020/0378934A1), in view of Hyckenbeg et al. (US 2019/0336886A1).
Regarding claim 1, Bangtsson teaches a system comprising:
supplying a harvest product that includes a target molecule (via pump 31, refer example in [0047] disclosing capture step for purification of a monoclonal antibody (MAb) from a mixture containing MAb and bovine serum albumin, BSA);
a multi-column chromatography system configured to purify the harvest product with respect to the target molecule (fig. 3 discloses 3 chromatography columns, fig. 4 discloses 4 chromatography columns), the multi-column chromatography system comprising a first chromatography column (39 in fig. 3 or 107 in fig. 5) and a second chromatography column (47 in fig. 3 or 109 in fig. 5)),
wherein the first chromatography column is configured to produce a first elution product, and wherein the chromatography system is configured to input the first elution product into the second chromatography column (first elution product of 39 is connected to feed of second column via 55 and 57; also refer [0029] disclosing “the effluent from the first column 39 can be directed to the inlet of the second column through valves 43, 55, 57 and 49”); and
a computing system comprising one or more processors (refer 71 and 73) configured to control an amount of the harvest product to be inputted into the second chromatography column by performing one or more operations comprising: comparing (i) a first yield titer of the target molecule in the first elution product to (ii) a concentration threshold of the target molecule, and in response to determining that the first yield titer is less than the concentration threshold, requesting an amount of the harvest product to be inputted into the second chromatography column so that a combination of the first elution product and the amount of the harvest product provides a titer greater than or equal to the concentration threshold (refer [0032] disclosing “passing feed comprising at least one target compound across a 1st adsorbent (chromatography media in the first column 39), and directing the outflow from the 1st adsorbent to a 2nd adsorbent (chromatography media in the second column 47) when the Deltasignal (definition as described above in relation to FIG. 2) measured between the feed line and the effluent from the 1st adsorbent reaches a predetermined value x1, and redirecting the feed to the 2nd adsorbent, and passing wash liquid across the 1st adsorbent to which target compound has bound when the Deltasignal measured between the feed line and the effluent from a 1st adsorbent reaches a predetermined value x2”).
Bangtsson does not disclose that the system comprises a bioreactor producing/providing a harvest product. However, such configuration is known in the art.
Hyckenbeg teaches a system comprising:
a bioreactor configured to produce a harvest product that includes a target molecule (refer [0038] and fig. 1 disclosing culturing and holding step 11 and 12 prior to chromatography step 13);
a multi-column chromatography system (refer fig. 1 and 2, the capture step 13 include multi-column chromatography system 20) configured to purify the harvest product with respect to the target molecule (refer [0048]), the multi-column chromatography system comprising a first chromatography column (A) and a second chromatography column (B), wherein the first chromatography column is configured to produce a first elution product, and wherein the chromatography system is configured to input the first elution product into the second chromatography column (refer configuration in fig. 3a); and
a computing system comprising one or more processors for controlling a bioprocess purification system (refer [0082]).
Providing a bioreactor harvesting a target molecule in the system of Bangtsson would have been obvious to one of ordinary skill in the art because Hyckenbeg establishes that such is well known in the art.
Regarding claim 2, modified Bangtsson teaches limitations of claim 1 as set forth above. Bangtsson further teaches (refer [0045]) that the chromatography system comprising more than two chromatography columns can be used for direct capture of a product from a feed stream originated from a perfusion cell culture. For a person skilled in art, it is well known that concentrations of components in such stream will vary with time, and without an automated control algorithm operation of the chromatography system would be impossible without a risk of significant losses of product due to wrongly a priori assigned redirection points. It would have been obvious to one of ordinary skill in the art to input second elution product produced by the 2nd column into a third column. In embodiment of fig. 3, Bangtsson teaches providing a detector (65) at outlet of 3rd column to monitor a target value of the 3rd column (Refer [0029], [0030]).
Regarding claim 5, modified Bangtsson teaches limitations of claim 1 as set forth above. Hyckenberg further teaches that harvest product is filtered through an alternate tangential filtration filter prior to supplying to the chromatography columns.
Regarding claim 6, modified Bangtsson teaches limitations of claim 1 as set forth above. Bangtsson teaches use of four similar column in a system (refer [0047]).
Regarding claims 7-8, modified Bangtsson teaches limitations of claim 1 as set forth above. Hyckenberg further teaches that the product generated from the chromatography column is further polished in step 15 (refer fig. 5), and that the step 15 comprises batch step or contrinuous chromatography (Refer [0044]). Since the product is processed after the multi-column chromatography, the target molecule titer at delivery is obviously greater than the threshold target yield titer of the multi-column chromatography.
Regarding claim 9, modified Bangtsson teaches limitations of claim 1 as set forth above. Bangtsson teaches that the chromatography system is a continuous system (refer [0047]) suggesting that feed from bioreactor is continuously supplied.
Regarding claim 10, modified Bangtsson teaches limitations of claim 1 as set forth above. The limitation “the system is used in producing Cerezyme” is reciting material being worked upon by the apparatus without structurally limiting the apparatus. A claim is only limited by positively recited elements. Thus, "[i]nclusion of the material or article worked upon by a structure being claimed does not impart patentability to the claims." In re Otto, 312 F.2d 937, 136 USPQ 458, 459 (CCPA 1963); see also In re Young, 75 F.2d 996, 25 USPQ 69 (CCPA 1935).
Claim(s) 3-4 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bangtsson et al. (US 2020/0378934A1), in view of Hyckenbeg et al. (US 2019/0336886A1) as applied to claim 1 above, and further in view of Jungbauer et al. (US 2021/0149361A1).
Regarding claims 3-4, modified Bangtsson teaches limitations of claim 1 as set forth above. Modified Bangtsson does not teach that the computing system calculates the first yield titer based on a chromatogram of the first elution product, and the computing system is configured to back calculate a concentration of the target molecule in a first product inputted into the first chromatography column based on a chromatogram of the first elution product.
Jungbauer teaches a method and device which allows in real-time the determination of concentration, purity and potency of a biological product during purification and/or concentration processes in order to intervene into the process, either for process control or real time release (abstract). Jungbauer further discloses that for the establishment of a model based control/release algorithm further information about the process is used and mechanistic models are generated taking into account a priori information such as retention time and the general shape of a chromatogram (refer [0283]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of invention to modify the system of Bangtsson to calculate the first yield titer based on a chromatogram of the first elution product, and to back calculate a concentration of the target molecule in a first product inputted into the first chromatography column based on a chromatogram of the first elution product to allow real-time the determination of concentration, purity and potency of a biological product during purification and/or concentration processes in order to intervene into the process, either for process control or real time release as taught by Jungbauer.
Conclusion
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/PRANAV N PATEL/Primary Examiner, Art Unit 1777