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 .
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.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-2, 4, 6-9, 11-14, and 16-20 in the reply filed on 09 March 2026 is acknowledged.
Claims 21-22, 26, and 29 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 March 2026.
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 2 and 4 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.
Claims 2 and 4 both recite “wherein the long step optionally comprises … “ wherein it is unclear if the limitation following the recited limitation further limits the claim or not and thus ambiguity arises as there is not an alternative. Recommend amend removing “optionally” from the claim language (see MPEP 2173.05(h) II. “OPTIONALLY”).
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.
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 1-2, 4, 6-9, 11-14, and 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over United States Patent Application Publication US 2020/0317726 to Konstantinov et al. (herein Konstantinov) in view of “Non-protein A Purification Platform for Continuous Processing of Monoclonal Antibody Therapeutics” to Kateja et al. (herein Kateja) as cited on the 21 June 2023 IDS.
Regarding claims 1 and 18, Konstantinov discloses continuous processes for manufacturing a therapeutic protein drug substance (see [0004]), wherein “therapeutic protein drug substance” means a recombinant protein that has been sufficiently purified from contaminants (see [0037]), the method comprising:
subjecting the protein to a first periodic counter current chromatography system (PCCS1), wherein one or more columns of the system perform affinity chromatography (see [0007]);
subjecting the eluate from the affinity chromatography to a low pH for viral inactivation (see [0007]) and adjusting the pH using an in-line buffer adjustment reservoir (i.e., neutralization) (see [0008]); and
subjecting the neutralized pool to a second periodic counter current chromatography system (PCCS2), wherein a chromatographic membrane in the PCCS2 performs the unit operation of polishing the recombinant therapeutic protein (see [0008]);
wherein the affinity chromatography unit operation and at least one or more polish chromatography unit operations are operated according to a process configured to control the operation of PCCS1 and PCCS2, wherein the first PCCS1 is disposed on first skid and the second PCSS2 is disposed on a second skid (see [0007, 0022]) through one or more full cycles of the chromatography process (see Tables 1 and 2), each full cycle including a loading step and first elution step of a first column (i.e., long step) lasting longer than a plurality of shorter steps (see Tables 1 and 2), the chromatography process comprising the steps of:
receiving a signal associated with a first one of the plurality of chromatography column skids comprising PCCS1 that the long step is complete at a PCC control system (i.e., control circuit) (see [0133-0134, 0233-0234, 0264-0268]); and
in response to reception of the signal, directing operation with the control circuit of a
second one of the plurality of chromatography column skids comprising PCCS2 to commence operation of the long step (see Tables 1 & 2; [0096-0098]; Example 3).
Konstantinov fails to disclose “wherein at least one of the affinity chromatography unit operation and/or at least one of the one or more polish chromatography unit operations are operated according to a parallel chromatography process” as recited in the instant claim.
Kateja discloses a method for purifying a monoclonal antibody including cation exchange chromatography, multimodal chromatography for capture, and polishing steps (see abstract); and describes that the chromatography is performed by concurrent mode chromatography (CMC) (i.e., parallel chromatography) and compares advantages and disadvantages of PCC (i.e., PCCS), as described in Konstantinov, and CMC for continuous processing (see section 3. Theory; Fig. 2). CMC involves performing unit operations of multiple columns in parallel (see Fig. 2). PCC has the advantage of increased resin utilization but lower selectively while CMC has lower resin utilization but increased selectivity (see section 3. Theory).
Konstantinov and Kateja are analogous in the field of purification of proteins that can be used in pharmaceuticals. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the PCCS1 and PCCS2 systems of Konstantinov to be CMC systems of Kateja for the advantage of increased selectivity (see section 3. Theory of Kateja).
Regarding claim 2, the combination of references above render obvious the invention of claim 1, including the affinity chromatography unit operation operating according to a parallel chromatography process, and Konstantinov discloses, as mentioned above in regards to claim 1, that the long step comprises loading a column of the chromatography column skids (see Tables 1 & 2) and the shorter steps include an elution step, one or more washing steps, an equilibrium step, and a regeneration step (see Tables 1 & 2; [0090]).
Regarding claim 4, the combination of references above render obvious the invention of claim 1, including at least one of the one or more polish chromatography unit operations operating according to a parallel chromatography process. Konstantinov discloses, as mentioned above in regards to claim 1 , that the long step comprises the loading step as well as a first elution step of the first column of PCCS1 (see Tables 1 & 2; [0134]) and the shorter steps include an elution step, one or more washing steps, an equilibrium step, and a regeneration step (see Tables 1 & 2; [0090]).
Regarding claim 6, the combination of references above render obvious the invention of claim 1, including both the affinity chromatography unit operation and at least one of the one or more polish chromatography unit operations operating according to a parallel chromatography process.
Regarding claim 7, the combination of references above render obvious the invention of claim 1, and Konstantinov discloses wherein the chromatography process further comprises the step of directing operation of the plurality of shorter steps on the first one of the plurality of chromatography column skids comprising PCCS1 with the control circuit to complete the full cycle of the chromatography process therefor after reception of the signal (see [0090-0092, 0133-0134, 0233-0234, 0264-0268; Tables 1 & 2).
Regarding claim 8, the combination of references above render obvious the invention of claim 7, and Konstantinov discloses receiving a second signal associated with the second one of the plurality of chromatography column skids at the control circuit that the long step is complete as both skids/systems involve column switching via a control circuit (see [0015]). As Konstantinov discloses the process is continuous including the feeding of the liquid culture medium, the PCCS1 system, in response to the completion of the long step of PCCS2 would commence a second operation of the long step of loading and collecting eluate from a first column of PCCS1.
Regarding claims 9 and 11, the combination of references above render obvious the invention of claim 1, and Konstantinov discloses wherein at least one of the one or more polish chromatography unit operations comprises a first and second polish chromatography as Konstantinov discloses columns present in the PCCS2 system can perform the same operation such as polishing (see [0127]), wherein the polish chromatography can selectively bind (i.e., capture) the target recombinant therapeutic protein (See [0046]) and are arranged in series (see Fig. 9).
Regarding claim 12, the combination of references above render obvious the invention of claim 1, and Konstantinov discloses a buffer system comprising a buffering agent which buffers to a desired pH (see [0144]).
Konstantinov fails to explicitly disclose “wherein the virus inactivated elution pool is neutralized using a neutralizing buffer system capable of minimizing volume expansion of a viral inactivated eluate pool while maintaining conductivity less than or equal to 10 ms/cm”, however, Konstantinov does disclose monitoring conductivity and a specific volume of liquid, such as a buffer, as part of the parameters used by the control circuit to control the overall system (see [0090-0093]. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date to arrive optimize the volume of the viral inactivated eluate pool/buffer solution and conductivity through routine experimentation for the benefit of arriving at neutralizing buffer system with the desired parameters for system control (see MPEP 2144.05 II. Routine Optimization).
Konstantinov fails to disclose “wherein the buffer system comprises a titrant that does not have buffer capacity in the target pH range” as recited in the instant claim.
Kateja discloses a continuous platform for the purification of a protein of interest comprising a buffering system, wherein the buffering system comprises a Tris buffer (see Fig. 1) and a titrant of an acidic solution (see Precipitation).
Konstantinov and Kateja are analogous in the field of purification of proteins that can be used in pharmaceuticals. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the buffer system of Konstantinov to comprise a titrant for the benefit of desired downstream chromatography binding (see Precipitation of Kateja).
Regarding claim 13, the combination of references above render obvious the invention of claim 1 and Konstantinov discloses wherein the viral activation is from 10 min to 1.5 hours which overlaps with the claimed range of “30 minutes or more” ([0007]) (see MPEP 2144.05 I. Overlapping, Approaching, and Similar Ranges, Amounts, and Proportions).
Regarding claim 14, the combination of references above render obvious the invention of claim 1 and Konstantinov discloses a depth filtration and viral filtration as part of the two PCC System (see Table 4).
Regarding claim 16, the combination of references above render obvious the invention of claim 1 and Konstantinov discloses wherein the affinity chromatography is comprises a protein A-binding capture mechanism (see [0007]) and/or protein G-binding capture mechanism (see [0088]).
Regarding claim 17, the combination of references above render obvious the invention of claim 1 and Konstantinov discloses the polishing of the recombinant therapeutic protein can be done through cation or anion exchange chromatography (see [0008]).
Regarding claim 19, the combination of references above render obvious the invention of claim 18 and Konstantinov discloses an isolate, purified, recombinant protein of interest (see [0125]).
Regarding claim 20, the combination of references above render obvious the invention of claim 18 and Konstantinov discloses formulating the therapeutic protein drug substance (i.e., isolated, purified recombinant protein of interest) into a pharmaceutical composition (see [0008]).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHRYN E LIMBAUGH whose telephone number is (571)272-0787. The examiner can normally be reached Monday-Thursday 7:00-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lyle Alexander can be reached at (571) 272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KATHRYN ELIZABETH LIMBAUGH/Primary Examiner, Art Unit 1797
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