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
Claim status
Claims 1-26 are pending
Claims 1-16 are withdrawn
Claims 17-26 are under examination
Election/Restrictions
Applicant’s election of the following invention without traverse in the reply filed on 5/06/2026 is acknowledged.
The requirement is still deemed proper and is therefore made FINAL.
Group II, claims 17-26, drawn to methods of producing a biological molecule comprising a culture bioreactor linked to a production bioreactor.
Claims 1-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable linking claim.
Applicant’s election of the following species is acknowledged.
Claim 21 and 23, drawn to semi-continuous operation.
Rejoinder
The species election requirement as set forth in the Office action mailed 3/11/2026 has been reconsidered in view of the prior art. Continuous operation as recited in Claims 24 and 25 is rejoined.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 5/22/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
However, Applicant is reminded that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Objections to the Specification
The use of the terms CHO-S, Per.C6 and CHO-K1/SF, CHO-K1/GS and CHOZN GS, which are a trade name or a mark used in commerce, has been noted in this application. The term should include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Appropriate correction is required
Claim Objection
Claim 26 is objected to because of the following informalities:
First, there is more than one (1) period: one after “GS” and another after “cells”. The claim should be amended to include only one period. MPEP 608.01(m) states, “Each claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations.”
Second, although Markush claims can vary in scope, there appears to be two Markush claims written into the same claim, wherein the second Markush claim repeats elements of the first Markush claim.
Appropriate corrections are required.
Claim Rejections - 35 USC § 112(b)
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 17-26 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.
Independent Claims 17 and 18 recite the limitations of “the culture bioreactor”, “the production bioreactor”, “the hydrocyclone”. There is insufficient antecedent basis for these limitations in the claim(s) because the method steps (i) and (ii) and wherein clauses of the claims recites “at least one culture bioreactor”, “at least one production bioreactor”, and “at least one hydrocyclone”, and it is unclear which of the “at least one” element is being referred to. Similarly dependent Claims 19-20, 23-25 recite the limitations of “the culture bioreactor”, “the production bioreactor”, and/or “the hydrocyclone”, which makes the claims unclear as to which of the “at least one” element is being referred to. Furthermore, dependent claims 21-22 and 26 are included in the basis of this rejection because they do not clarify the improper antecedence.
Claim 22 recites the limitation "the systems for use in the methods" do not comprise a membrane cell retention device in regard to method of Claim 18. There is insufficient antecedent basis for this limitation in the claim because Claim 18 does not recite “systems”, and it is unclear which “methods” do not comprise the membrane retention device, thereby rendering Claim 22 indefinite. Appropriate correction is required.
Claim 26 contains the trademark/trade names CHO-S and Per.C6 CHO-K1/SF, CHO-K1/GS and CHOZN. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name(s) are used to identify/describe a particular cell line and, accordingly, the identification/description is indefinite.
Because this reagent was developed by the manufacturer Life Technologies Corp. at the time of the applicant’s invention under the trade name CHO-S, by Janssen Vaccine under the trade name Per.C6, by ATCC under the trade name CHO-K1/SF, by Horizon Discovery Group under the tradename CHO-K1/GS, by Merk KGaA under the tradename CHOZN, and as a result is proprietary, which means what constitutes these cell lines can change, and these changes do not need to be disclosed by these companies to the public. Accordingly, the identification of the trade name is indefinite.
Furthermore, Claim 26 is rejected as being indefinite for reciting a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim), since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 26 recites the broad recitation “(BHK-21 derivative)”, and the claim also recites “2254-62.2”, which is the narrower statement of the limitation.
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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 17 is rejected under 35 U.S.C. 103 as being unpatentable over Hiller et al., (US 2019/0031997, filed 1/25/2017, published 1/31/2019, prior art of record), in view of Deckwer et al. (US 6,878,545, filed 3/01/2001, patented 4/12/2005)
[AltContent: textbox ([img-media_image1.png])]Hiller teaches a method for producing a biologic molecule of interest, the method comprising: (i) culturing a plurality of host cells capable of producing a biologic molecule of interest in at least one culture bioreactor; (ii) inoculating at least one production bioreactor with cells obtained from step (i); and (iii) culturing the cells in the production bioreactor under conditions that allow production of the biologic molecule of interest; wherein the culture bioreactor and the production bioreactor are directly linked to each other by a continuous or semi-continuous cell transfer line, and indirectly linked by membrane based cell retention device that recirculates into the culture bioreactor and then into the production bioreactor via the cell transfer line; and wherein the host cells comprise mammalian cells (Summary, [0007-0010], see also excerpt of Fig. 1 of Hiller adjacent).
However, Hiller is silent with respect to the culture bioreactor and the production bioreactor being indirectly linked by a hydrocyclone that serves as a cell retention device for the culture bioreactor. Note that Applicant’s specification defines “linked bioreactor” as having an “indirect connection”, and in instant case the cell retention devices are directly linked to the culture bioreactor and form in an indirect connection to the production bioreactor via the cell transfer line.
Deckwer teaches a bioreactor system and methods of using one or more hydrocyclone based retention devices for a cell culture bioreactor (col 4, 2nd para., Examples 1 & 2, Claims 1-5 of Deckwer, see Figs. 1-3).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to practice the method of producing a biological molecule of interest comprising the linked bioreactors, wherein the culture bioreactor comprises a membrane based retention device as taught by Hiller, and substitute the membrane based retention device for a hydrocyclone based retention device as taught by Deckwer with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so for several reasons. First, Hiller teaches membrane-based cell retention system are prone to plugging or obstruction, which causes and retention of the biological molecules of interest, and are expensive, damaging to cells, and prone to failure [0004-0005, 0047-0048], while the hydrocyclone cell retention system of Decker is not membrane-based and is not prone to plugging or obstruction (see col 1, last para. to col 2, 2nd para. of Deckwer). Furthermore, Deckwer explicitly teaches compared to membrane filter, hydrocyclones are simple, cheap, reliable, and robust devices, and replacing known cell-retention systems with hydrocyclones reduces the use of capital and operating costs (col 7, Example 2, last para.).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 17-26 are rejected under 35 U.S.C. 103 as being unpatentable over Hiller et al., (US 2019/0031997, filed 1/25/2017, published 1/31/2019, prior art of record), in view of Castan et al., (WO2020/193613, filed 3/25/2020, published 10/01/2020)
[AltContent: textbox ([img-media_image2.png])] In regard to claims 17 and 18, Hiller teaches a method for producing a biologic molecule of interest, the method comprising: (i) culturing a plurality of host cells capable of producing a biologic molecule of interest in at least one culture bioreactor; (ii) inoculating at least one production bioreactor with cells obtained from step (i); and (iii) culturing the cells in the production bioreactor under conditions that allow production of the biologic molecule of interest; wherein the culture bioreactor and the production bioreactor are directly linked to each other by a continuous or semi-continuous cell transfer line, and wherein the host cells comprise mammalian cells (Summary, [0007-0010], see also excerpt of Fig. 1 of Hiller adjacent).
However, Hiller is silent with respect to the culture bioreactor and the production bioreactor being linked by a hydrocyclone that serves as a cell retention device for the at least one culture bioreactor, and wherein the hydrocyclone produces an underflow stream containing concentrated mammalian cell culture and a partially cell-free overflow stream, and wherein the underflow stream containing concentrated mammalian cell culture is returned to the culture bioreactor and the partially cell-free overflow stream is directed to the production bioreactor.
[AltContent: textbox ([img-media_image3.png])] Castan teaches a bioreactor system and methods of using a hydrocyclone based retention device for a cell culture bioreactor. Specifically, Castan teaches the hydrocyclone serves as a cell retention device for a culture bioreactor, wherein the hydrocyclone produces an underflow stream via a bottom outlet containing an increased concentration of cells and an overflow stream via a top outlet containing a decreased concentration of cells, and wherein the underflow stream containing the increased concentration of cells is returned to the culture bioreactor and the decreased concentration of cells in the overflow stream is transferred through the top outlet out of the hydrocyclone (Claim 15 of Castan, see Fig. 1, excerpt adjacent).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to practice the method of producing a biological molecule of interest comprising the linked bioreactors, wherein the culture bioreactor comprises a membrane based retention device as taught by Hiller, and substitute the membrane based retention device for a hydrocyclone based retention device as taught by Castan with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so for several reasons. First, Hiller teaches membrane-based cell retention system are prone to plugging or obstruction, which causes and retention of the biological molecules of interest, and are expensive, damaging to cells, and prone to failure [0004-0005, 0047-0048], while the hydrocyclone cell retention system of Castan is not membrane-based and is not prone to plugging or obstruction. Furthermore, Castan teaches the hydrocyclone improves the cell separation especially when the outflow from the bottom outlet freely discharges into the headspace of the culture bioreactor (p. 1, Summary, p. 6, 2nd para.)[AltContent: textbox ([img-media_image4.png])]. Finally, in regard arranging the hydrocyclone such that the overflow from the top outlet is directed to the production bioreactor (as depicted in the combination of Hiller in view of Castan adjacent), Hiller teaches that when the outflow of the cell retention is directed to waste, most of the perfusion media entering the culture bioreactor is lost to the waste as a partially cell-free permeate, which adds additional costs [0111]. However, directing the partially cell-free permeate to the production bioreactor would save these costs and eliminate waste while simultaneously inoculating the production bioreactor through cell transfer. Furthermore, it would have been obvious to one having ordinary skill in the art at the time the invention was filed to arrange the hydrocyclone to have the overflow routed to the production bioreactor, since it has been held that rearranging parts of an invention involves only routine skill in the art. In re Japikse, 86 USPQ 70.
In regard to claims 19-21 and 23-25, as shown supra, Hiller teaches that the transfer of cells from the culture bioreactor to the production bioreactor is by a continuous or semi-continuous transfer. Specifically in regard to claim 23, Hiller teaches the semi-continuous transfer can be from 2 min to 24 hrs or any interval therebetween [0007].
In regard to claim 22, as show supra, the hydrocyclone of Castan would replace the membrane-based cell retention device of Hiller in the methods of using the culture bioreactor system.
In regard to claim 26, Hiller teaches that the mammalian cells used are CHO cells, HEK- 293 cells, VERO cells, NSO cells, PER.C6 cells, Sp2/0 cells, BHK cells, MDCK cells, MDBK cells or COS cells [0007].
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 17-26 are rejected on the grounds of nonstatutory double patenting over claims 1-19 of U.S. Patent No. 11,104,875 (Hiller et al., Patented 8/31/2021), in view of Castan et al., (WO2020/193613, filed 3/25/2020, published 10/01/2020)
The subject matter claimed in the instant application is disclosed in the referenced patent as follows: the method comprising: (i) culturing a plurality of host cells capable of producing a biologic molecule of interest in at least one culture bioreactor; (ii) inoculating at least one production bioreactor with cells obtained from step (i); and (iii) culturing the cells in the production bioreactor under conditions that allow production of the biologic molecule of interest; wherein the culture bioreactor and the production bioreactor are directly linked to each other by a continuous or semi-continuous cell transfer line makes obvious the method of instant application. It is clear that elements of the cited patent claims are to be found in instant claims. The difference between the cited patent claims and the instant claims lies in the fact that the instant claims combine a hydrocyclone linking the culture bioreactor and the production bioreactor.
Castan teaches a bioreactor system and methods of using a hydrocyclone based retention device for a cell culture bioreactor. Specifically, Castan
teaches the hydrocyclone serves as a cell retention device for a culture bioreactor, wherein the hydrocyclone produces an underflow stream via a bottom outlet containing an increased concentration of cells and an overflow stream via a top outlet containing a decreased concentration of cells, and wherein the underflow stream containing the increased concentration of cells is returned to the culture bioreactor and the decreased concentration of cells in the overflow stream is transferred through the top outlet out of the hydrocyclone (Claim 15 of Castan, see Fig. 1).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to practice the method of producing a biological molecule of interest comprising the linked bioreactors as claimed by cited patent, and combine a hydrocyclone based retention device as taught by Castan with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so since Castan teaches the hydrocyclone improves the cell separation efficiency especially when the outflow from the bottom outlet freely discharges into the headspace of the culture bioreactor (p. 1, Summary, p. 6, 2nd para.), and directing the partially cell-free permeate to the production bioreactor would save costs and eliminate waste while simultaneously inoculating the production bioreactor through cell transfer. Furthermore, it would have been obvious to one having ordinary skill in the art at the time the invention was filed to arrange the hydroclone to have the overflow routed to the production bioreactor, since it has been held that rearranging parts of an invention involves only routine skill in the art. In re Japikse, 86 USPQ 70.
Since the instant application claims are obvious over cited patent claims in view of Castan, said claims are not patentably distinct.
Provisional Double Patenting
Claims 17-26 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1-16 of copending Application No. 18/975,157. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented
The subject matter claimed in the instant application is disclosed in the referenced application as follows: the method comprising: (i) culturing a plurality of host cells capable of producing a biologic molecule of interest in at least one culture bioreactor; (ii) inoculating at least one production bioreactor with cells obtained from step (i); and (iii) culturing the cells in the production bioreactor under conditions that allow production of the biologic molecule of interest; wherein the culture bioreactor and the production bioreactor are directly linked to each other by a continuous or semi-continuous cell transfer line makes obvious the method of instant application. It is clear that elements of the cited application claims are to be found in instant claims. The difference between the cited application claims and the instant claims lies in the fact that the instant claims combine a hydrocyclone linking the culture bioreactor and the production bioreactor.
Castan teaches a bioreactor system and methods of using a hydrocyclone based retention device for a cell culture bioreactor. Specifically, Castan teaches the hydrocyclone serves as a cell retention device for a culture bioreactor, wherein the hydrocyclone produces an underflow stream via a bottom outlet containing an increased concentration of cells and an overflow stream via a top outlet containing a decreased concentration of cells, and wherein the underflow stream containing the increased concentration of cells is returned to the culture bioreactor and the decreased concentration of cells in the overflow stream is transferred through the top outlet out of the hydrocyclone (Claim 15 of Castan, see Fig. 1).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to practice the method of producing a biological molecule of interest comprising the linked bioreactors as claimed by cited application, and combine a hydrocyclone based retention device as taught by Castan with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so since Castan teaches the hydrocyclone improves the cell separation efficiency especially when the outflow from the bottom outlet freely discharges into the headspace of the culture bioreactor (p. 1, Summary, p. 6, 2nd para.), and directing the partially cell-free permeate to the production bioreactor would save costs and eliminate waste while simultaneously inoculating the production bioreactor through cell transfer. Furthermore, it would have been obvious to one having ordinary skill in the art at the time the invention was filed to arrange the hydrocyclone to have the overflow routed to the production bioreactor, since it has been held that rearranging parts of an invention involves only routine skill in the art. In re Japikse, 86 USPQ 70.
Since the instant application claims are obvious over cited application claims in view of Castan, said claims are not patentably distinct.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARTHUR S LEONARD whose telephone number is (571)270-3073. The examiner can normally be reached on Mon-Fri 9am-5pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Doug Schultz can be reached on 571-272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ARTHUR S LEONARD/Examiner, Art Unit 1631
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