DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. The Amendment filed on July 28, 2026, has been received and entered.
Claim Disposition
3. Claims 1-25, 41-44 and 56 have been cancelled. Claims 59-63 have been added. Claims 26-40, 45-55 and 57-63 are pending and are under examination.
Claim objection
4. Claims 26-40, 45-55 and 57-63 are objected to for the following informalities:
For clarity and precision of claim language it is suggested that claims 26-40, 45-55, and 57-63 are amended to delete “including” and “includes” and instead recite for example, ‘comprising/comprises’, a more acceptable language that removes confusion. For example, the art recognizes that comprises means to ‘include all of’ or ‘to be made up of’, whereas ‘includes suggests that the items named are only some of the parts inside the whole, other unmentioned things may also exist.
For clarity and precision of claim language it is suggested that claim 26 is amended to read, “ A method of purifying a target polypeptide from a mixture, [[including the target polypeptide and impurities, the method]] comprising:….”. See also claims 32, 59 and 62 with similar language. The dependent claims hereto are also included.
For clarity it is suggested that claim 57 is amended to delete ‘configured’ and instead recite, for example “……is set to be approximately”....”.
Appropriate correction is required.
Basis For NonStatutory Double Patenting
5. 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. See 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) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent is shown to be commonly owned with this application. See 37 CFR 1.130(b).
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).
6. Claims 26-40, 45-55 and 57-63 are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 2-3, 7-8, 11-17 and 21 of U.S. Application No. 16/459,187. An obvious-type double patenting rejection is appropriate where the conflicting claims are not identical, but an examined application claim is not patentably distinct from the reference claim(s) because the examined claim is either anticipated by, or would have been obvious over, the reference claim(s). See In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); and In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985). Although the conflicting claims are not identical, they are not patentably distinct from each other.
The instant application claims are directed to a method for preparing a target polypeptide from a mixture including the target polypeptide. The copending application claims are drawn to a method for preparing a target polypeptide from a mixture including the target polypeptide. The two sets of claims differ because the instant claims recite ‘a first, second and third zones and the copending application recites first, second and third columns, which are functionally equivalent. In addition, the dependent claims in the instant application and copending applications align with each other since they recite similar embodiments.
Although the scope of the two sets of claims differs, the two sets of claims are an obvious variation of each other, thus prima facie obvious.
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.
7. 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.
8. Claim(s) 26-40, 45-55 and 57-63 is/are rejected under 35 U.S.C. 103 as being unpatentable over Skudas (EP 2 656 892 A1), in view of Gadgil et al. (US 2019/0263855) and Wolk et al. (J Chromatography A, 1227 (2012) .
The claimed invention is directed to a method for preparing a target polypeptide from a mixture including the target polypeptide.
Skudas teaches a method of purifying target molecules from one or more impurities in a sample which includes the steps of providing at least three separation units having the same chromatography matrix which are connected so that liquid can flow from one separation unit to the subsequent one and from the last to the first separation unit. (p. 3, lines 32-34). With respect to the first contacting step of claim 26, Skudas teaches feeding the sample on a first separation unit, (“first zone”) which includes an outlet which is in liquid communication with the inlet of a second separation unit 2 (“second zone”) (p. 13, line 40, p. 13, lines 43-44). The limitation of “contacting the mixture including the target polypeptide to a first zone, …having one or more chromatographic columns and an outlet” is considered met. Regarding the second contacting step of claim 26, Skudas teaches the target molecule not bound to said first separation unit 1 can bind to the next separation unit 2 which includes an outlet (p. 3, lines 38-39; 13, lines 48-49). The limitation “contacting one or more mobile phases to a second zone, .the second zone having one or more chromatography column and an outlet” is accordingly considered met. With respect to antibody (see claim 33), Skudas teaches that the target molecule can be a monoclonal antibody (¶161). Skudas teaches wash and elution buffers for use in the method (see for example ¶163). In addition, Skudas teaches as noted supra that the outlet of separation unit 1, which considered “the first zone”, is in liquid communication with the inlet of separation unit 2, which is considered “the second zone”, so that all parts of the feed that have not bound to separation unit 1 are passed through separation unit 2 (¶112). Further, Skudas teaches that the second column, which is considered equivalent to “the second zone” can during the method be washed, eluted, undergoes cleaning in place and reequilbration (¶114, line 21). Skudas teaches that the cleaning in place (CIOP) typically includes buffers that contain NaOH, which is considered “an alkaline solution”, ethanol, which is considered “an alcohol) (¶147).
Skudas teaches that separation unit 2, which is considered “the second zone” can be connected to a collecting tank where the weakly bound or unbound target molecule removed by said wash is further processed (p. 14, lines 20-23). Skudas further teaches the apparatus includes one or more detectors that can be used for the analysis of sample quality, monitoring, etc. and that these detectors can be located wherever suitably typically prior to the fluid inlet and/or after the fluid outlet or the separation columns. Examples of suitable detectors are pH, UV detectors and detectors for measuring conductivity (¶132). Moreover, Skudas teaches productivity g/L/h) of 271,4 (¶178), 102,34 (¶197), 666 and 720 (¶208) for various embodiments of the continuous chromatography methods; and Skudas teaches steps which are considered to meet all of the elements recited in claims 55 and 57. With respect to “ in a first zone”, Skudas teaches feeding the sample with target protein/antibody on a first separation unit (¶12, line 35; ¶112, lines 45-46; ¶161, lines 18-19) (“loading a quantity of a mixture including the antibody into a first column of the plurality of columns”), passing the target molecules not bound to said first separation unit to the next separation unit (¶12, line 36; ¶112, lines 46-47) (“loading a quantity of the mixture into a second column of the plurality of columns via the first column”) and at the same time at least washing, eluting, cleaning in place (“stripping) and equilibrating a separation unit different from these two separation units (¶12, lines 38-39; ¶112, lines 51-53; ¶161, lines 20-22). (“performing a non-loading step including at least one of washing, stripping, and equilibration processes in a third column of the plurality of columns”).
Regarding the limitation of “ in a second zone”, Skudas teaches feeding the sample on the said next separation unit (“second column”) enabling the target molecules to be bound by said next separation unit which is in fluid communication with the separation unit after the next (“third column”) so that target molecules not bound to said next separation unit can bind to the separation unit after the next (“third column), (¶113, lines 4-5) which is considered equivalent to “loading a quantity of the mixture into the third column via the second column”) and at the same time at least washing, eluting, cleaning in place and/or reequilibrating one separation unit/third column different form the separation unit that is being loaded/Unit 1 and the one that is in fluid communication with the separation unit that is being loaded (¶12, lines 46-47; ¶113, lines 8-9; ¶161, lines 20-22). Moreover, there is also a recited a third zone/ “in a third stage”, Skudas teaches that the feed is switched to the inlet of separation unit 3 (“loading a quantity of the mixture including the antibody into the third column”) (¶114, line 14) and while loading unit 3, separation unit which has been loaded before is washed, eluted, undergoes cleaning place (“stripping”) and re-equilibration (¶114, lines 18-19). (“performing the on-loading step including at least one of washing, stripping and equilibration processes in the second column). Skudas also teaches that the steps can be repeated with the loading and non-loading steps occurring simultaneously(¶7, 12, 96, 110, 207, 164, 171, 177, 183, 189, 196, 203). Skudas teaching differs from the claimed invention in the recitation the apparatus is a “HIC apparatus”. Instead, Skudas clearly exemplifies Protein A resins for the continuous multicolumn chromatography methods (see ¶161, 174, 180, 186, 192). The teachings further differ in the recitation that a residence time for the mixture including the target polypeptide in the first zone is configured to be approximately the same as a residence time of the one or more mobile phases in the second zone; that the duration for the regeneration cycle is configured to be approximately the same as the residence time for the mixture including the target polypeptide in the first zone, and that a duration of one of the loading steps is configured to be approximately the same as a duration of the non-loading step. It is noted that the term “approximately” is defined in the specification as filed at ¶27 to mean equivalent within a variation of +/- 10%.
The prior art teachings further differ in the recitation that the first and second zones include more than one chromatographic column. However, Skudas teaches that examples of ligands attached to the chromatography matrix include hydrophilic interaction groups (¶35). Skudas further teaches experiment conditions using 0,22 minutes residence time for loading and washing, elution, CIP and re-equilibration (¶173). Moreover, Gadgil teaches a continuous process for reducing heterogeneity of a mAb on 4 columns in parallel which includes the steps of in house CPB-CNBR-activated Sepharose 4B column (column 1), followed by Protein A column (column 2), AEX (column 3) and CEX (column 4). Gadgil teaches that other resin chemistry can be incorporated such as hydrophobic interaction chromatography (¶151). For example, the third column and fourth column can be an HIC column (¶35). Gadgil teaches that the two Protein A columns (designed as “column 2) are connected parallelly and that the residence time was about 4.4 min (¶144). As the columns are run in parallel, the residence times is considered to be equivalent on each column. Additionally, Wok teaches three column periodic counter-current chromatography (3C PCC) for the purification of mAbs (section 2.2). Wok teaches that since columns are used in series or parallel depending on processing step, it is critical that the duration of processing steps match, which is accomplished by calculating switch time (2.2.2.1). Motivation exists to use the HIC of Gadgil because the art generally recognizes that HIC separates molecules based on differences in their surface hydrophobicity, is less costly and provides a more stable sample.
Therefore, it would have been obvious to one of ordinary skill before the effective filing date of the claimed invention to substitute a Protein A resin for use in a 3 or 4 continuous chromatography method for purifying a mAB taught by Skudas with a hydrophobic interaction resin. One of ordinary skill in the art at the time the invention was made would have been motivated to do so because Skudas itself as well as Gadgil teach that hydrophobic interaction columns can be used in such multi-column continuous chromatography schemes. Substituting a known element for another , to yield the known result, is obvious. See KSR, 550 U.S. 15 416, 421.
Therefore, it 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 to have included more than one chromatography column within a particular zone/stage in the continuous chromatography purification methods taught by Skudas. Those of skill in the art would have had reason to do so because both Gadgil and Wok teach that it was known in the art to include multiple columns such as the two protein A column 2 taught by Gadgil to carry out specific chromatography purification steps in continuous multi-chromotography schemes for the purification of mAbs. The combination of familiar elements according to known methods is obvious when it does no more than yield predictable results (see KSR Int’l v. Teleflex Inc., 127 S. Ct. 1727, 1739 (2007). While the combined references do not specifically recite that the residence time for the mixture including the target polypeptide in the first zone is configured to be approximately the same as a residence time of the one or more mobile phases in the second zone, it is well settled that “discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art. In re Boesch, 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989) and where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 220 F2d 454, 456, 105 USPQ 233; 235 (CCPA 1955). See MPE §§2144.05 part IIA.
Skudas teaches experiment conditions using 0,22 minutes residence time for loading and washing, elution, CIP and re-equilibration (¶173). Gadgil teaches that the two Protein A columns (designed as “column 2) are connected parallelly and that the residence time was about 4.4 min (¶144). As the columns are run in parallel, the residence times is considered to be equivalent on each column. ). Wok also teaches that since columns are used in series or parallel depending on processing step, it is critical that the duration of processing steps match, which is accomplished by calculating switch time (2.2.2.1). Accordingly, and in absence of evidence to the contrary, those of skill in the art would be motivated to look to keeping residence time similar or the same in the various chromatography process steps. From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Moreover, the Supreme Court pointed out in KSR, “a patent composed of several elements is not proved obvious merely by demonstrating that each of its elements was, independently, known in the prior art.” KSR, 127 S. Ct. at 1741. The Court thus reasoned that the analysis under 35 U.S.C. 103 "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the “inferences and creative steps that a person of ordinary skill in the art would employ.” Id. at 1741. The Court further advised that “[a] person of ordinary skill is…a person of ordinary creativity, not an automation.” Id. at 1742. Therefore, the claimed invention was obvious to make and use at the time the invention was made and was prima facie obvious.
Response to Arguments
9. Applicant’s comments have been considered in full. Withdrawn objections/rejections will not be discussed herein as applicant’s comments are moot. Note that rejections of record remain, however, have been altered to reflect changes made to the claims such as the addition of new claims.
Note also that an objection over the language of ‘includes and including’ remains for the reasons stated above. Applicant traversed this objection, however, the statements made were not deemed persuasive. The examiner has provided additional information to bolster the suggestion for the language modification. Applicant is urged to make the necessary changes.
Applicant opine that the Obvious-type rejection is traversed, however, presented no arguments. It was then stated that applicant would like the rejection to be held in abeyance. Since no terminal disclaimer was furnished or any persuasive arguments the rejection remains.
Applicant traverses the 103 rejection stating that the primary reference teaches Affinity Chromatography and the instant invention is directed to the use of HIC. This argument is not persuasive because the secondary reference provides the missing information and it would be obvious to swap out the affinity chromatography used to purify a protein and use HIC for the protein purification because it know to be a cheaper cost for purification An ordinary skill worker in the field would know to swap out one for the other based on the disclosure in the art of a higher purity with HIC and its more cost effective. Thus the rejection remains. The examiner would welcome an opportunity to discuss the remaining issues with applicant.
Conclusion
10. No claims are presently allowable.
11. Applicant’s amendment necessitated the new/modified ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HOPE A ROBINSON whose telephone number is (571) 272-0957. The examiner can normally be reached 9-5pm on Monday to Friday.
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/HOPE A ROBINSON/Primary Examiner, Art Unit 1652
