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
The Examiner for this Application has changed. Please direct all future correspondence to Examiner Juliana Candelaria, AU 1634. Additional contact information can be found at the end of this paper.
This action is in response to the papers filed on 01/16/2026. Claims 1-46 are
currently pending as per claims filed on 01/16/2026.
Claim 24 has been amended and claims 1-23 and 34-46 have been withdrawn by Applicants’ amendment filed on 01/16/2026. No new claims were added or cancelled.
Applicant's election without traverse of Group III, claims 24-33 in the reply filed on 01/16/2026 is acknowledged.
Claim 1-23 and 34-46 are withdrawn from further consideration by Applicants pursuant to 37 CFR 1.142(b), as being drawn to a nonelected subject matter, there being no allowable generic or linking claim.
The requirement is still deemed proper and is therefore made FINAL.
Therefore, claims 24-33 are subject to examination to which the following grounds of rejection are applicable.
Priority
Applicant’s claim for the benefit of prior-filed application 63/315,897 filed 03/02/2022, 63/411,899 filed 09/30/2022, 63/417,873 filed 10/20/2022, 63/436,854 filed 01/03/2023, and 63/448,655 filed 02/27/2023 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Thus, the earliest possible priority for the instant application is 03/02/2022.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 01/05/2026 and
03/18/2024 were filed before the mailing date of the current office action. The submission is in compliance with the provisions of 37 CPR 1.97. Accordingly, the
information disclosure statement is being considered by the examiner.
Claim Objections
Claim 28 is objected to because abbreviations such as rpm should be spelled out at the first encounter in the claims. Appropriate correction is required.
Claim 31 is objected to because abbreviations such as slpm should be spelled out at the first encounter in the claims. Appropriate correction is required.
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.
Claim 32 is 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 applicant regards as the invention
Claim 32 vague and indefinite in the recitation of “…is configured to…”, since this phrase refers to a latent ability, and it is unknown whether the ability is expressed or observed in the invention.
Note, it has been held that the recitation that an element is “capable of” performing a function is not a positive limitation, but only requires the ability to so perform. It does not constitute a limitation in any patentable sense. In re Hutchinson, 69 USPQ 138.
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.
Claim(s) 24-33 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al (WO 2020/096381 A1; as cited in IDS) and further in view of Roca et al (J. Biol. Chem., 2019, pages 18756–18768), Schulz et al (WO 2021/069353 A1; as cited in IDS), Floris et al (Applied Microbiology and Biotechnology, 2018, pages 5495–5504), O’Connor et al (Biotechnology Techniques, 1992, pages 323-328), and Xing et al (Biotechnology and Bioengineering, 2009, pages 733-746).
Regarding claim 24, Kim teaches a method of producing an anti-ILR4α antibody (page 1, abstract) wherein the method includes “(a) culturing the cells; and (b) recovering an antibody or antigen-binding fragment thereof from the cultured cells” (page 14, para 7) and “the cells can be cultured in various media. Any commercially available medium can be used as a culture medium without limitation (page 14, para 8)”, rendering obvious a method of producing an anti-IL-4Rα antibody comprising the steps of: (a) culturing cells expressing an anti-IL-4Rα antibody in a cell culture medium.
However, Kim does not teach wherein a cumulative concentration of one or more polyamines in said cell culture medium is between about 0.03 and about 0.9 mM.
Roca teaches the Chinese hamster ovary cells (CHO cells) “are important for therapeutic protein production” (page 1, left col, para 1), “polyamines have essential roles in cell proliferation, DNA replication, transcription, and translation processes, with intracellular depletion of putrescine, spermidine, and spermine resulting in cellular growth arrest and eventual death” (abstract, page 1) and CHO cells need polyamine supplementation, such as putescine (i.e. a polyamine) (abstract, page 1). Moreover, Roca teaches that cell culture conditions that led to cell growth included 1.08 mg/L of putescine, equivalent to 0.012 mM (results, right col, para 1).
It would have been prima facie obvious to one of ordinary skill, in the art at the time of the effective filing date, to modify the teachings of Kim for producing anti-IL-4Rα antibody comprising steps of culturing cells expressing an anti-IL-4Rα antibody with the teachings of having a polyamine such as putescine at a concentration of 0.012 mM in the culture media from Roca to properly grow cells used for therapeutic protein (i.e. antibody) production such as producing an anti-IL-4Rα antibody. One would be motivated to do so to provide optimal culture conditions to cells that will maximize their yield of the protein/antibody of interest. As generating therapeutic proteins such as antibodies using cells in culture is known technique in the art, one would have reasonable expectation of success.
Applicant is reminded that differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.") See MPEP 2144.05 II. A.
The combined teachings of Kim and Roca do not teach agitating said cell culture and controlling dissolved gas concentrations in said cell culture.
However, Schulz teaches a bioreactor for culturing of cells in suspension in a liquid medium and a stirrer to stir (i.e. agitate) the liquid medium (abstract, page 1). Moreover, Schulz teaches that the bioreactor for cell culturing allows management of the carbon dioxide concentration independently from the oxygen concentration (page 9, line 20-21).
It would have been prima facie obvious to one of ordinary skill, in the art at the time of the effective filing date, to modify the teachings of Kim and Roca for producing anti-IL-4Rα antibody comprising steps of culturing cells expressing an anti-IL-4Rα antibody with the teachings of using a bioreactor that comprises a stirrer to stir/agitate the cell culture medium and that manages concentrations of gases such as oxygen and carbon dioxide from Schulz to develop a cell culture system that provides favorable environmental conditions and a controlled environment for optimal cell growth. One would be motivated to do so to grow cells in optimal conditions for producing the anti-IL-4Rα antibodies at maximum efficiency. As using bioreactors that agitate medium and have abilities to control gas concentrations for cell-based antibody production is known in the art, one would have reasonable expectation of success.
Regarding claim 25, the teachings of Kim, Roca, and Schulz render obvious claim 24.
The combined teachings of Kim, Roca, and Schulz do not teach wherein said cell culture medium is subjected to High Temperature Short Time (HTST) treatment at about 101°C to 106°C for 8 to 15 seconds.
Floris teaches that “high-temperature short-time (HTST) pasteurization is recognized as an effective protective barrier against viral contaminants” and during HTST “culture media are continuously processed and maintained at elevated temperatures of approximately 100 °C for short time intervals (generally 10 s), facilitating the denaturation of viral protein capsids (page 1, right col, para 2).
It would have been prima facie obvious to one of ordinary skill, in the art at the time of the effective filing date, to modify the teachings of Kim for producing anti-IL-4Rα antibody comprising steps of culturing cells expressing an anti-IL-4Rα antibody, the teachings of Roca for having a certain concentration of polyamine in the culture media, and the teachings of Schulz for agitating/stirring the culture and controlling gas concentrations with the teachings of using HTST from Floris to develop a cell culture system for producing anti-IL-4Rα antibodies from cells where the cell culture medium is subjected to HTST. One would be motivated to do so to ensure that the cell culture media is not contaminated with viruses when used for culturing cells that produce antibodies for human therapeutic purposes. As using HTST and cell culture bioreactor systems are known in the art, one would have reasonable expectation of success.
Applicant is reminded that differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.") See MPEP 2144.05 II. A.
Regarding claim 26 and 27, the teachings of Kim, Roca, and Schulz render obvious claim 24. Moreover, Schulz teaches that the bioreactor contains a vessel which contains a liquid medium with a determined filling height and a stirrer provided in the vessel to stir (i.e. agitate) the liquid medium (page 10, line 4-11), “additional stirrers are provided in addition to the stirrer” (page 69, line 30-34, Fig 6A and B shows stirrers with bubbles i.e. below working volume), and that “stirrers which may be used are, for example, impellers” (page 17, line 10), rendering obvious wherein two or more impeller assemblies are positioned below a surface of an initial working volume and wherein agitation of said cell culture is performed using one or more impeller assemblies and an uppermost impeller is positioned below a surface of an initial working volume.
Regarding claim 28, the teachings of Kim, Roca, and Schulz render obvious claim 24. Moreover, Schulz teaches a stirrer frequency of 60 rpm, rendering obvious wherein an initial agitation rate is configured between 20 rpm and 150 rpm.
Regarding claim 29, the teachings of Kim, Roca, and Schulz render obvious claim 24.
The combined teachings of Kim, Roca, and Schulz do not teach wherein said agitation rate is configured to increase by 25%,50%, 75%,100%,125%, 150%,175% or 200% on one or more days selected from the group.
O’Connor teaches culturing of CHO cells in spinner-flask bioreactors and “all cultures were initially grown at 100 rpm. The impeller speed (i.e. agitation rate) in the spinner flasks was increased 20 hr (100 - 340 rpm) or 26 hr (400 rpm) after inoculation” (page 325, para 1) and the increase in impeller speed showed greater number of viable cells (Figure 1, page 325).
It would have been prima facie obvious to one of ordinary skill, in the art at the time of the effective filing date, to modify the teachings of Kim for producing anti-IL-4Rα antibody comprising steps of culturing cells expressing an anti-IL-4Rα antibody, the teachings of Roca for having a certain concentration of polyamine in the culture media, and the teachings of Schulz for agitating/stirring the culture and controlling gas concentrations with the teachings of increasing the agitation rate from O’Connor to develop a cell culture system that can grow cells for producing anti-IL-4Rα antibody and said cells are able to maximally divide and grow. One would be motivated to do so to the grow the maximum number of cells that can subsequently produce the maximal amount of antibody of interest in a cell culture system. As using agitation in cell culture bioreactor systems is known in the art, one would have reasonable expectation of success.
Regarding claim 30, the teachings of Kim, Roca, and Schulz render obvious claim 24. Moreover, Schulz teaches spargers in the bioreactor and the spargers provide oxygen and/or air bubbles into the liquid phase wherein cells or microorganisms are cultivated (page 17, line 13-15). Moreover, Schulz teaches additional spargers “supply additional air bubbles and/or additional oxygen gas bubbles continuously to the liquid medium” and this “has a variety of advantages for the culturing process” (page 17, line 23-25), rendering obvious wherein said dissolved gas concentrations are controlled by one or more spargers.
Regarding claim 31, the teachings of Kim, Roca, and Schulz render obvious claim 24 and 30. Moreover, Schulz teaches sparger gas flow rates from 0, 20, 60, 120 L/min, rendering obvious wherein said one or more spargers are configured at an initial sparging rate of about 25-75 slpm.
Regarding claim 32, the teachings of Kim, Roca, and Schulz render obvious claim 24, 30, and 31.
However, the combined teachings of Kim, Roca, and Schulz do not teach wherein said sparging rate is configured to increase by 25-500% on one or more days selected from the group of days.
Xing teaches that up-scaling cell cultures is important for biopharmaceutical manufacturing and it is important to consider factors such as mixing time, oxygen transfer, and carbon dioxide removal (abstract, page 1). Furthermore, Xing teaches “increasing bottom air sparging rate is more efficient than increasing power input in improving oxygen transfer and carbon dioxide removal”.
It would have been prima facie obvious to one of ordinary skill, in the art at the time of the effective filing date, to modify the teachings of Kim producing anti-IL-4Rα antibody comprising steps of culturing cells expressing an anti-IL-4Rα antibody, the teachings of Roca for having a certain concentration of polyamine in the culture media, and the teachings of Schulz for agitating/stirring the culture and controlling gas concentrations with the teachings of increasing the sparging rate from Xing develop a cell culture system that can grow cells for producing anti-IL-4Rα antibody and said cells are able to maximally divide and grow due to increased sparging rate. One would be motivated to do so the grow the maximum number of cells that can subsequently produce the maximal amount of antibody of interest in a cell culture system. As using a sparger to add dissolved gas into a cell culture bioreactor system is known in the art, configuration of a sparging rate for improving oxygen transfer and carbon dioxide removal would have reasonable expectation of success.
Regarding claim 33, the teachings of Kim, Roca, and Schulz render obvious claim 24 and 30.
However, the combined teachings of Kim, Roca, and Schulz do not teach a sparging rate is automatically configured based on dissolved oxygen levels.
It would have been prima fascie obvious to one of ordinary skill in the art prior to the filing of the instant application to use automation for optimizing a system (e.g. sparging rate that is automatically configured based on dissolved oxygen levels and removal of carbon dioxide). Providing mechanical or automated approaches to replace manual labor would accomplish the same result of culturing cells expressing an anti-IL-4Rα antibody. Motivation to do so would be to increase efficiency and throughput of culturing cells expressing an anti-IL-4Rα antibody and, ultimately, producing a maximal amount of anti-IL-4Rα.
Provisional Rejection, Obviousness Type 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 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 24-33 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claim 19 of co-pending U.S. Patent Application No.18/115,321 as per claims filed on 12/22/2025 in view of Roca et al (J. Biol. Chem., 2019, pages 18756–18768) and Schulz et al (WO 2021069353 A1). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are obvious over the cited claims of Application No 18/115,321.
The claims of co-pending Application No 18/115,321 are drawn to a method of producing an anti-IL-4Rα antibody the method comprising culturing cells capable of expressing an anti-IL-4Rα antibody in a vessel or bioreactor, adjusting cell density, using sensors to measure properties, and transferring cells to another vessel or bioreactor based on the properties (claim 19).
The instant claims are drawn to a method of a method of producing an anti-IL-4Rα antibody comprising the steps of: (a) culturing cells expressing an anti-IL-4Rα antibody in a cell culture medium wherein a cumulative concentration of one or more polyamines in said cell culture medium is between about 0.03 and about 0.9 mM;(b) agitating said cell culture; and (c) controlling dissolved gas concentrations in said cell culture.
The instant claims differ from claim 19 by requiring a concentration of polyamines in the cell culture medium, agitating said cell culture, and controlling dissolved gas concentrations in said cell culture.
However, at the time the invention was made, Roca teaches the Chinese hamster ovary cells (CHO cells) “are important for therapeutic protein production” (page 1, left col, para 1), “polyamines have essential roles in cell proliferation, DNA replication, transcription, and translation processes, with intracellular depletion of putrescine, spermidine, and spermine resulting in cellular growth arrest and eventual death” (abstract, page 1) and CHO cells need polyamine supplementation, such as putescine (i.e. a polyamine) (abstract, page 1). Moreover, Roca teaches that cell culture conditions that led to cell growth included 1.08 mg/L of putescine, equivalent to 0.012 mM (results, right col, para 1).
Additionally, Schulz teaches a bioreactor for culturing of cells in suspension in a liquid medium and a stirrer to stir (i.e. agitate) the liquid medium (abstract, page 1). Moreover, Schulz teaches that the bioreactor for cell culturing allows management of the carbon dioxide concentration independently from the oxygen concentration (page 9, line 20-21).
Therefore, in view of the benefits of having polyamines in the cell culture media at a certain concentration for favorable cell growth and using a bioreactor with stirrers to agitate the cell culture and managing the concentration of gases in the cell culture, It would have been prima facie obvious to one of ordinary skill, in the art at the time of the effective filing date, to modify the instantly claimed method to include the ideal concentration of polyamines from Roca and have stirrers and control gas concentrations from Schulz to have a method of culturing cells that produce an anti-IL-4Rα antibody for therapeutic purposes and the production of said antibody to be maximized by providing favorable culture environment for the cells.
In relation to steps b)-i) of claim 19 of co-pending Application No 18/115,321, these steps are species of claim 24 of the invention and species of a method of producing an anti-IL-4Rα antibody anticipate the genus of producing an anti-IL-4Rα antibody.
This is a provisional obviousness-type double patenting rejection because the
conflicting claims have not in fact been patented.
Conclusion
Claims 24-33 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Juliana Candelaria whose telephone number is (571)272-5488. The examiner can normally be reached Monday - Friday 8am - 5pm.
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/JULIANA IRENE CANDELARIA/ Examiner, Art Unit 1634
/MARIA G LEAVITT/ Supervisory Patent Examiner, Art Unit 1634