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 the species A. redox agent that is metal (claim 2), B. transition metal that is copper (claims 3 and 4), C. affinity column A (claims 6 and 7), D. antigen that is RANKL (claim 38), E. antibody rituximab1 (claim 39), F. BiTE molecule anti-CLDN18.2 and anti-CD3 (claim 40), and H antigen binding region sequence SEQ ID NO. 5 (claim 41), in the reply filed on 03/17/2025 is acknowledged.
The requirement for species election regarding affinity column is withdrawn, as during search/consideration it was determined that there is no additional burden to consider both species without and election (claims 6 and 7 are both examined below).
Claim 42 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species of invention (newly recited claim 42 appears to recite therapeutic antibody against a species of antigen which is not Applicant’s elected species, see the CDRs appear to be CDRs specific to anti-CDD20 antibody, which Applicant’s elected species of antigen is RANKL). Election was made without traverse in the reply filed on 03/17/2025.
Priority
The present application filed on 08/24/2022 is a continuation of application 16/219,871, filed 12/13/2018 (US Pat. No. 11,447,547). Application 16/219,871claims benefit under 35 U.S.C. 119(e) to provisional application No. 62/598,015, filed 12/13/2017.
Information Disclosure Statement
The information disclosure statement (IDS) filed 08/24/2022 has been considered, initialed and is attached hereto.
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 31 and 40 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 31 and 40 contain the trademark/trade names, BiTE®. 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 is used to identify/describe a type of bispecific antibody.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 28 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Specifically, as amended claim 28 fails to depend from any specific prior claim (as amended, the claim no longer depends from 14). For the purpose of consideration under 35 U.S.C. 103 this claim is being interpreted to depend from independent claim 1, however Applicant should clarify in their response. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claim(s) 1-8, 13-15, 29-30, 32, 34-35 and 38 are rejected under 35 U.S.C. 103 as being unpatentable over Zhou et al., WO2006/060083A1 (IDS entered 08/24/2022) in view of Koths et al., GB 2168055A.
Zhou et al. teaches methods involved in preparing and purifying column isolated preparations of proteins (abstract), Zhou teach methods of treating undesirable post-translational modifications to polypeptides (including therapeutic proteins, such as therapeutic antibodies) in order to produce more structurally homogenous, and more therapeutically active polypeptides (page 2, lines 12-26 and page 11, lines 1-19). Zhou teach the redox agent for treating can include copper (page 8, lines 12-13, copper as the redox agent, consistent with Applicant’s elected species of transition metal redox agent). Zhou et al. teach (at page 3, lines 1-16) addition of the redox agent (alone or in combination with mildly denaturing conditions) to a polypeptide that is captured on a column during the purification process to facilitate folding and result in greater structural homogeneity.
Regarding Zhou’s method/technique, Zhou teach refolding on a column of an Fc domain containing polypeptide, columns may be affinity resins, or further affinity columns comprising a polypeptide binding polypeptide (see page 8, line 28 to page 9, line 21, Zhou’s methods comprise subjecting a load composition comprising a therapeutic protein to an affinity chromatography column, washing the column with a solution comprising a redox agent, such as a copper containing agent).
See Zhou’s methods capable of reforming disulfide bonds (page 10, lines 14-16). Zhou teaches the redox reagent can be up to 30 mM (page 3, lines 23-30, a range of 30-1mM, Zhou teaching “or even less depending on the reaction conditions that best suits the Fc domain containing polypeptide”.).
Although Zhou’s method describes reforming disulfide bonds by application of a redox reagent, Zhou teaching the method restores structural integrity while increased homogeneity of the product, Zhou does not explicitly state their method is re-oxidizing, that the result is a decreased level of the partially-reduced therapeutic protein. Zhou et al. also fails to teach the concentration of the copper containing redox reagent ranging from 2 to 50 µM.
Koths et al. teach methods of reoxidizing recombinant proteins having been prepared/purified by HPLC (including therapeutic proteins, see page 2, lines 15-21, page 4, lines 32-43, also see throughout, Koths teaching recombinant IL-2, as well as Examples at pages 5-6) so that the recombinant proteins have essentially the same disulfide bridging and biological activity as their native counterparts (see abstract). Koths methods catalyze disulfide bond formation by using an oxidation promotor containing a Cu+2 cation (page 1, lines 4-7, 40-46, 50-62).
Koths teach (see page 3, lines 35-65), the amount of oxidation promotor employed is at least an effective amount for oxidation, i.e., an amount which at minimum will be necessary to conduct the oxidation reaction effectively within a convenient time period, Koths teach this amount, and an optimum amount for each reaction, may depend specifically on factors such as the type of protein, the type of oxidation promotor, the reaction temperature, the pH of the reaction and the type and concentration of solubilizing agent. Koths recognize that it is likely that independent variables interact in such a way that there may be no unique optimum set of conditions for all proteins. Koths specifically teach in their examples, concentration of CuCl2 from 0.5 to 50µM.
It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Zhou et al. in order to have arrived at a copper redox reagent concentration that is in a range of .2-50 µM, by trying values in the prior art disclosed range of 0.5-50 µM, as an obvious matter of routine optimization of experimental conditions, namely trying different concentrations disclosed by the prior art as appropriate for this purpose, in order to uncover the optimum workable amount necessary to achieve disulfide bound reconstruction. Specifically, the concentration of the copper redox agent is considered to be a result-effective variable, namely a variable that achieves a recognized result, in the present case the result is reforming disulfide bonds and increased product homogeneity with respect to structure, as is supported by Koths et al. See as cited above, Koths teach the amount of oxidation promotor employed as at least an effective amount for oxidation, i.e., an amount which at minimum will be necessary to conduct the oxidation reaction (to form disulfide bonds) effectively within a convenient time period, Koths teach optimum amount for each reaction may depend specifically on various experimental factors such as the type of protein, the type of oxidation promotor, the reaction temperature, the pH of the reaction and the type and concentration of solubilizing agent. Koths recognize that it is likely that independent variables interact in such a way that there may be no unique optimum set of conditions for all proteins. Koths specifically teach in their examples, concentration of CuCl2 from 0.5 to 50µM (a range that overlaps and completely encompasses the claimed range, as a result, it would be obvious try from and select values within this range to arrive at the optimum workable conditions).
As a result of the teaching of Koths, it would have been prima facie obvious to have arrived at the claimed range by specifically selecting form prior art disclosed ranges to uncover the optimum workable concentration to serve as the minimum amount, one would be motivated to have arrived at the concentration because of the direction of Koths, referenced above. Even further, one having ordinary skill in the art would have had a reasonable expectation of success because like Zhou, Koths is teaching the use of a copper redox agent for the purpose of forming disulfide bonds. Considering the redox agent is being used in the same manner (to reform structure), one having ordinary skill in the art would have a reasonable expectation of success applying concentrations as in Koths to the method of Zhou.
Further one having ordinary skill in the art would have a reasonable expectation of success because Zhou teach suitable concentrations may be even lower than 1 mM depending on reaction conditions. Considering that Koths disclose concentrations as low as the range 0.5-50µM, it does not appear that the claimed concentration (which falls within the prior art disclosed range) is a critical concentration or that it achieves an unexpected result (based on Koths, it is expected that such low concentration would achieve re-oxidization, leading to disulfide bonds).
Regarding claims 2-4 and 8, see as cited above, the combination of Zhou and Koths addresses Applicant’s elected species of transition metal, copper.
Regarding claim 5, see as cited above, the combination of Zhou and Koths is teaching a therapeutic protein that is an antigen-binding protein (antibody).
Regarding claims 6 and 7, see as cited above Zhou teach affinity chromatography columns, specifically columns including protein A affinity columns or protein L columns. Specifically see page 4, capturing Fc domain containing polypeptides on any column may be done with conventional methods, Zhou teaching protein A, G or L columns (page 4, lines 20-26; also, page 9, lines 4-5 and 8-10).
Regarding claim 13, see Zhou at page 19 teaches performing their method at temperatures ranging from 4-37° C, typically about 4-25° C (Zhou teaching 25 as ambient temperature), although Zhou teaching this as the typical temperature range for their invention, that it can be performed at lower or higher (suggesting no particular limit). It would have been further prima facie obvious to one having ordinary skill in the art at the time the claimed invention was effectively filed to have arrived a temperature that is room temperature by specifically trying values within the typical range specifically disclosed by Zhou, one having ordinary skill in the art having a reasonable expectation of success because Zhou discloses a range that encompasses that which is considered to be room temperature as suitable.
Regarding claims 14 and 15, Koths further teach storage of recombinantly produced protein at 4°C (see page 7, lines 36-38, stored up to six weeks or see also page 9, lines 20-21, up to 60 days with no change to biological or physical properties). It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have arrived at short term storage (preincubation) prior to methods of reoxidizing, storing at 4°C (a temperature that reads on 2-8°C as claimed) for 1-3 days as an obvious matter of applying a known technique to a known method. See in particular Koths, it was known to short term store recombinant proteins prior to contact with a redox reagent under these conditions, the prior art teaching this temperature as an appropriate temperature for short term storage until use. Koths is teaching storing at this temperature up to 60 days, as such it would have been obvious to have arrived at 1-3 by selecting from within the prior art disclosed range as suitable time for storage under these short-term conditions. One having ordinary skill would have a reasonable expectation of success considering Koths teach at this temperature, recombinant proteins can be stored with no changes to biological or physical properties.
Regarding claim 29, Zhou’s methods further comprise recovering the therapeutic protein (see page 5, lines 1-8, page 9, lines 22-23).
Regarding claims 30 and 32, see Zhou teaches a therapeutic protein that is an antibody (page 9, lines 15-21, page 11, lines 10-19, end of page 11 to page 13).
Regarding claim 34, see Zhou teach for example load composition from harvested cell culture fluid (page 19, lines 1-2, page 22, lines 20-29, see also for example page 25).
Regarding claim 35, see for example, Zhou et al. at page 25, line 3 (IgG2; see also page 27, lines 1-5 including IgG1).
Regarding claim 38, see Zhou teach therapeutic protein binds antigen such as RANKL (page 13, lines 10-13)
Claim(s) 9 and 33 are rejected under 35 U.S.C. 103 as being unpatentable over Zhou et al. and Koths et al. as applied to claim 1 above, and further in view of Chaderjian et al., Effect of Copper Sulfate on Performance of a Serum-Free CHO Cell Culture Process and the Level of Free Thiol in the recombinant Antibody Expressed, Biotechnol. Prog., (2005), 21, p. 550-553 (IDS entered 08/24/2022).
Zhou et al. and the cited art teach a method substantially (Zhou teaching redox agent comprising Copper, Koths specifically teaching redox agent that is copper chloride), however fails to teach the copper in the solution is copper sulfate (claim 9); fails to teach the therapeutic produced in CHO cells (claim 33).
Chaderjian et al. teach the use of CHO cell line to express a humanized antibody (recombinant therapeutic antibody), Chaderjian teach minimization of the level of free thiol by addition of copper sulfate (see abstract). Chaderjian teach the use of copper sulfate as an oxidizing agent, for promoting disulfide bond formation (abstract). See Chaderjian teach addition of concentrations up to 100 µM had no significant interference on cell growth (page 552, col. 1, para 1).
It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the method as taught by Zhou and Koths to rely on copper sulfate as an obvious matter of applying a known redox agent for its art recognized purpose. In particular Zhou and Koths teach copper as an appropriate redox agent for forming disulfide bonds, Chaderjian et al. teach copper sulfate as a known oxidizing agent known for minimizing free thiols (forming disulfide bonds). The prior art contained the base method (of applying copper as an agent for this purpose), and the claimed invention differed from the prior art only in the species of copper agent applied. As cited, copper sulfate was known agent for this intended purpose. As a result, one having ordinary skill in the art would have recognized that applying copper sulfate would have yielded a predictable result and achieved disulfide bond formation. One having ordinary skill in the art would have a reasonable expectation of success because Zhou does not limit to any particular copper containing agent, and further one would expect success using a known agent for its art recognized purpose.
Similarly, regarding claim 33, it would have been further prima facie obvious to have performed the methods as taught by Zhou and Koths on therapeutic proteins produced from a CHO cell line as this was also a known technique, and from the teachings of Chaderjian it is understood that even cells produced in this manner are subject to free thiol formation. As a result, one would expect the benefits as taught by Zhou and Koths to similarly apply to recombinant therapeutic antibodies produced as in Chaderjian (by CHO cell line), and as such one having ordinary skill would be motivated to apply the methods as taught by Zhou and Koths to those antibodies produced by CHO cell line, as in Chaderjian et al. One having ordinary skill in the art would similarly have a reasonable expectation of success because (based on Chaderjian) those therapeutic proteins produced in this way are subject to free thiol formation.
Claim(s) 28 is rejected under 35 U.S.C. 103 as being unpatentable over Zhou et al. and Koths et al. as applied to claim 1 above, and further in view of Thermo Scientific, Tech Tip 43, Protein Stability and storage, (2009), https://assets.thermofisher.com/TFS-Assets/LSG/Application-Notes/TR0043-Protein-storage.pdf. Accessed [08/19/2025] (3 pages).
See as noted above, claim 28 as amended fails to depend from an earlier claim. However, for the purpose of the prior art, the claim is interpreted as depending from independent claim 1. Appropriate correction is required.
Zhou et al. and Koths fails to teach step of freezing and thawing the load prior to incubating (claim 38).
Regarding claim 38, although the combination of Zhou et al. and Koths et al. addresses short term storage of recombinantly produced therapeutics, the prior art recognized alternative ways to store such proteins, for example see Thermo Scientific regarding protein stability and storage, alternative to short term storage, it is known to store such proteins long term (freeze/thaw methods, Table 1 and page 1, last paragraph, frozen samples which are then thawed to be used).
As a result, it would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified Zhou et al. and Koths in order to first perform a step of freezing and thawing the load composition prior to the methods because it was well known to store recombinant proteins in this way (for example alternative to short term storage, it was known to freeze for long term storage and then thaw). It would have been obvious matter of a known storage technique for storing the recombinant antibodies so that they are suitable for subsequent isolation and purification using the methods of the cited combined prior art. One having ordinary skill would have a reasonable expectation of success performing the method on samples first subject to freeze/thawing because it was known at the time that such proteins are able to be stored under either short term or long-term conditions, the long-term requiring freeze/thawing.
Claim(s) 36 and 37 are rejected under 35 U.S.C. 103 as being unpatentable over Zhou et al. and Koths et al. as applied to claim 35 above, and further in view of Janeway CA Jr, Travers P, Walport M, et al. Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science; 2001. The structure of a typical antibody molecule. Available from: https://www.ncbi.nlm.nih.gov/books/NBK27144/ (6 pages).
Zhou and the cited art teach therapeutic proteins comprising antibodies, including antibodies that are IgG1 (see as cited previously above).
However, Zhou and the cited art is silent as to whether the IgG1 antibody is an antibody with a kappa light chain or a lambda light chain (claims 35 and 36).
However, see Janeway et al., IgG antibodies are known in the art to have two light chain sequences, and there are two types of light chain sequences, lambda and kappa, see Janeway et al., a given antibody is known to have either lambda or kappa (see at section 3-1). See regarding IgG antibodies, the two heavy chain sequences of these antibodies linked by disulfide bonds, and each heavy chain linked to each light chain by a disulfide bond (section 3-1).
It would have been further prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention that therapeutic IgG1 antibodies having either lambda or light chain antibodies, both of these being known types of light chains found in IgG type antibodies. One having ordinary skill in the art would have a reasonable expectation of success considering it was known that antibodies of this type as taught by Zhou (IgG) have light chain sequences considered to be lambda or kappa type light chain sequences.
Claim(s) 31 and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Zhou et al. and Koths et al. as applied to claim 35 above, and further in view of Sahin et al., US PB Pub No. 2016/0347815A1.
Regarding claims 31 and 40, Zhou and the combination of the cited art teaches a therapeutic recombinant protein. However, the cited prior art fails to teach a therapeutic protein that is a BiTE molecule (claim 31), which is an anti-CLDN18.2 and anti-CD3 (claim 40).
See specifically Sahin et al., therapeutic BiTE molecules that bind CLDN18.2 and CD3 were known to those of ordinary skill in the art (para [0222]), and further the bispecific molecules were known as able to contain disulfide bonds (para [0217]).
It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the method as taught by Zhou et al. and the cited prior art to apply the method to therapeutic BiTE molecules such as that of Sahin (bispecific for CLDN18.2 and CD3) in order to improve their recovery in terms of structural homogeneity of the produced therapeutic, particularly as these antibody molecules were still known/expected to contain disulfide bonds. One having ordinary skill in the art would have a reasonable expectation of success because the therapeutic of Sahin is a recombinant antibody therapeutic protein molecule, which the method as taught by Zhou et al. and Koths is intended for improving recovered recombinant therapeutic proteins.
Claim(s) 39 and 41 are rejected under 35 U.S.C. 103 as being unpatentable over Zhou et al. and Koths et al. as applied to claims 1 and 30 above, and further in view of Song et al., US PG Pub No. US 2015/0225482 (IDS entered 08/24/2022).
See as noted in detail above (in the Elections/Restrictions section), Applicant’s response indicated an election of “nituximab” however, there is no species listed at the claims or specification which goes by this name. It appears that this was a typographical error and Applicant intended to elect “Rituximab”. For the purposes of prior art, the claims are interpreted this way. However, clarification should be made in Applicant’s next response.
Zhou et al. and the cited art teaching therapeutic antibody, however, fails to teach Applicant’s elected species, rituximab (claim 39).
Song et al. teach the recombinant therapeutic antibody rituximab (antibody comprising antigen-binding region comprising the sequence of SEQ ID NO. 5 as claimed, see Song et al. at SEQ ID NO. 14, para [0124], sequence of rituximab consistent with presently disclosed SEQ ID NO. 5 (Applicant’s elected species, which is a CDR found in the binding region of Rituximab see Song et al.)).
It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the method as taught by Zhou et al. and the cited prior art to apply the method to therapeutic antibodies such as rituximab (as taught by Song) in order to improve the recovery in terms of structural homogeneity of the produced therapeutic. One having ordinary skill in the art would have a reasonable expectation of success because the therapeutic of Song is a recombinant antibody therapeutic protein, which the method as taught by Zhou et al. and Koths is intended for improving recovered recombinant therapeutic proteins such as that of Song.
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.
Claims 1-9, 13-15 and 28-41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-35 of U.S. Patent No. 11,447,547B1.
Although the claims at issue are not identical, they are not patentably distinct from each other because ‘547 similarly recites a method of re-oxidizing a therapeutic protein comprising at least one di-sulfide bridge, the method comprising subjecting a load composition comprising the therapeutic protein to an affinity chromatography column or membrane; and washing with a solution comprising a redox agent (copper) at a concentration of 2-50µM to produce a flow through composition (see ‘547 at claim 1, also claim 11).
Regarding claims 2-4 and 8, ‘547 recites redox agent that is a transition metal, namely copper (see claim 1).
Regarding claim 5, ‘547 recites therapeutic protein that is an antigen-binding protein (see claim 2).
Regarding claims 6 and 7, see ‘547 recites affinity columns comprising a Protein A or L affinity column (see claims 3 and 4).
Regarding claim 9, see ‘547 recites copper sulfate (claim 5).
Regarding claim 13, see ‘547 at claim 8 recites washing at room temperature.
Regarding claim 14, see ‘547 at claim 9 incubating at 2-8°C before step (a).
Regarding claim 15, see ‘547 at claim 10 incubating 1-3 days at 2-8°C wherein the washing part (b) are conditions to achieve at least partial re-oxidization of the therapeutic protein.
Regarding claim 28, see ‘547 at claim 22 (freezing/thawing prior to step (a)).
Regarding claim 29, see ‘547 at claim 23 recites further recovering the therapeutic protein.
Regarding claim 30, see ‘547 at claim 24 (protein that is an antibody).
Regarding claim 31, see ‘547 at claim 25 (protein that is a BiTE molecule).
Regarding claim 32, see ‘547 at claim 26, recombinant produced protein.
Regarding claim 33, see ‘547 at claim 27, recombinant produced in CHO cells.
Regarding claim 34, see ‘547 at claim 28, composition that is harvested cell culture fluid (HCCF).
Regarding claim 35, see ‘547 at claim 29, therapeutic protein that is antibody that is an IgG1 or IgG2.
Regarding claims 36 and 37, see ‘547 at claims 30 and 31 (light chain is kappa or lambda light chain).
Regarding claim 38, ‘547 recites at claim 32 antigen that is Applicant’s elected RANKL antigen.
Regarding claim 39, ‘547 recites at claim 33 antibody that is rituximab (Applicant’s elected species).
Regarding claim 40, ‘547 recites BiTE that is anti-CLDN18.2 and anti-CD3 BiTE molecule.
Regarding claim 41, ‘547 recites antigen binding protein comprising antigen-binding region comprising a sequence selected from SEQ ID Nos. 1-8 (see at claim 35).
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELLEN J MARCSISIN whose telephone number is (571)272-6001. The examiner can normally be reached M-F 8:00am-4:30pm.
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/ELLEN J MARCSISIN/ Primary Examiner, Art Unit 1677
/PATRICIA MALLARI/ Director, Technology Center 1600
1 Applicant’s remarks filed 03/17/2025 indicate Applicant’s election for antibody as “nituximab”; however, this appears to be a typographical error as the closest spelling to the indicated election found in the claims and originally filed specification is “Rituximab”. As such, Applicant’s election is interpreted as “Rituximab”.
Prosecution Insights