DETAILED OFFICE ACTION
Status of the Application
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s preliminary amendment to the claims, filed on November 21, 2023, is
acknowledged. This listing of the claims replaces all prior versions and listings of the
claims.
Claims 1-10 are pending and are being examined on the merits.
Priority
This application is filed as a continuation-in-part of application 17/560,163, filed on December 22, 2021, now U.S. Patent No. 11,884,702, which claims benefit under 35 U.S.C. 119(e) to provisional applications: no. 63/131,097, filed on December 28, 2020, no. 63/208,778 filed on June 9, 2021; and no. 63/272,605 filed on October 27, 2021.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 11/21/2023, 4/23/2024, and 6/26/2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDSs have been considered by the examiner and those references therein have been indicated as such.
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 is objected to for reciting “a second exchange media having a second charge with a second polarity” in lines 12-13. In the interest of improving claim form, the Office suggests clarifying the phrase by amending to “a second ion exchange media having a second charge with a second polarity.”
Claim Rejections - 35 USC § 112(f)
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f):
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f). The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f), is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f). The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f), is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f), except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f), except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f), because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation(s) is/are:
“a fractionation module configured to receive the solution and perform a salt fractionation” in line 3 of claim 1,
“the first separation module is configured to provide a second output comprising a flowthrough fraction” in lines 8-10 of claim 1, and
“the second separation module is configured to retain a third portion of the plurality of contaminants and to provide a third output comprising the target protein” in lines 14-16 of claim 1.
Because these claim limitations are being interpreted under 35 U.S.C. 112(f), they are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
If applicant does not intend to have these limitations interpreted under 35 U.S.C. 112(f), applicant may: (1) amend the claim limitations to avoid them being interpreted under 35 U.S.C. 112(f) (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitations recite sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f).
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.
Claims 1-10 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim limitations “a fractionation module configured to receive the solution and perform a salt fractionation”, “the first separation module is configured to provide a second output comprising a flowthrough fraction”, and “the second separation module is configured to retain a third portion of the plurality of contaminants and to provide a third output comprising the target protein” in claim 1 (claims 2-10 dependent therefrom) invoke 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. However, the written description fails to disclose the corresponding structure, material, or acts for performing the entire claimed function and to clearly link the structure, material, or acts to the function. The instant specification does not provide structures that perform the functions recited in the claim. Therefore, the claim is indefinite and is rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph.
Applicant may:
(a) Amend the claim so that the claim limitation will no longer be interpreted as a limitation under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph;
(b) Amend the written description of the specification such that it expressly recites what structure, material, or acts perform the entire claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(c) Amend the written description of the specification such that it clearly links the structure, material, or acts disclosed therein to the function recited in the claim, without introducing any new matter (35 U.S.C. 132(a)).
If applicant is of the opinion that the written description of the specification already implicitly or inherently discloses the corresponding structure, material, or acts and clearly links them to the function so that one of ordinary skill in the art would recognize what structure, material, or acts perform the claimed function, applicant should clarify the record by either:
(a) Amending the written description of the specification such that it expressly recites the corresponding structure, material, or acts for performing the claimed function and clearly links or associates the structure, material, or acts to the claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(b) Stating on the record what the corresponding structure, material, or acts, which are implicitly or inherently set forth in the written description of the specification, perform the claimed function. For more information, see 37 CFR 1.75(d) and MPEP §§ 608.01(o) and 2181.
Claim 10 is rejected as indefinite for reciting “wherein volume of the solution is at least 500 L.” The system of the recited claim does not require the “solution” but rather is only capable of receiving the solution. Furthermore, it is unclear if the system is required to receive the 500 L at once or if the system can arrive at 500 L in increments. The Office suggests clarifying what is required in the system and how the system is required to receive the recited solution volume. For the purpose of compact prosecution, the recited limitation is interpreted as the fractionation module is capable of receiving and/or holding at least 500 L at once, the entire system is capable of receiving and/or holding at least 500 L at once, or the system is capable of receiving and/or holding a volume which could incrementally process at least 500 L.
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.
Claims 1-6 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Zurlo et al. (US 2019/0055282 A1; cited on the attached Form PTO-892; hereafter “Zurlo”) in view of Kim et al. (US 2020/0347093 A1; cited on the attached Form PTO-892; hereafter “Kim”) and Urmann et al. (mAbs, published 2010, Vol. 2, No. 2, p. 395-404; cited on the attached Form PTO-892; hereafter “Urmann”).
Regarding claim 1 and 5-6, Zurlo teaches a method of producing one or more proteins, from blood-based material, including plasma, comprising a salt fractionation module followed by a first and second chromatography module (para [0012, 0025, 0033, 0074]; Figures 3-5, 8, and 10-11; Claims 2-3, 25-26, and 46-47). Zurlo teaches paste comprises precipitate as well the terms paste and precipitate are used interchangeably (para [0015]). Zurlo teaches salt fractionation of plasma produces a supernatant and a paste, and the paste can comprise the desired protein product as well as other proteins (para [0006, 0010-0011, 0026, 0055]; Figures 4-5). Zurlo teaches a precipitate from a salt fraction can be dissolved and further processed chromatography processes (para [0060]; Figure 4-5). Zurlo teaches a first chromatography step and a second chromatography step can comprise cation exchange or anion exchange chromatography (para [0018; 0027; 0058, 0069]; Figure 5; Claim 14). Zurlo teaches applying a sample from a blood-based material to a first chromatography module which produces at least a flow-through, and wherein the flow-through from the first chromatography module is applied to a second chromatography module which produces at least a flow-through in order to obtain one or more proteins (para [0072-0074]; Figures 3-5 and, 8, 10-11). Zurlo teaches that besides IgGs, plasma can comprise clotting factors as well as other proteins (para [0004, 0040, 0073-74]).
Regarding claim 2, Zurlo teaches a viral inactivation module between a fractionation module a first chromatography module (para [0055, 0070, 0072-0074]; Figure 11; Claims 43 and 53).
Regarding claim 3, Zurlo teaches the first and second chromatography steps can comprise cation exchange or anion exchange chromatography (para [0018; 0027; 0058, 0069]; Claim 14). Zurlo teaches that plasma contains gamma globulins and the protein isolated can be an immunoglobulin such as immunoglobulin G (IgG) (para [0002, 0024, 0033, 0040, 0061, 0073]; Figures 3-5, see Figure 5 below; Claim 19). Zurlo teaches a precipitate formed from the salt fractionation of a blood-based material can yield IgG after further chromatographic processing (Figure 5).
Regarding claim 4, Zurlo teaches that besides IgGs, plasma can comprise clotting factors as well as other proteins (para [0004, 0040]).
Zurlo does not explicitly teach:
regarding claim 1, wherein the first and second chromatography modules comprise opposition ion polarity nor wherein the second chromatography module comprise an amount of the second ion exchange media to provide a capacity of the second ion exchange media such that less than 10% of consent of the target protein in the solution is lost on chromatography over the second ion exchange medium;
regarding claim 3, wherein the first and second chromatography modules comprise anion exchanger medium and cation exchanger medium, respectively;
regarding claim 4, wherein the blood-based material contains contaminants comprising a clotting factor selected from the group consisting of Factor XI, activated Factor XI, Factor XII, and activated Factor XII.
Kim teaches a method of purifying plasma-derived immunoglobulin G (IgG) comprising anion chromatography followed by cation chromatography (Abstract; para [0014, 0044]; Figures 1-2 and 4; Claim 1). Kim teaches plasma contains coagulation factor XI (FXI) and both anion chromatography and cation chromatography columns reduce IgG the FXI content and/or impurities (para [001017, 0020, 0036, 0063-0065, 0068, 0175-0176]; Tables 1-4). Kim teaches cation chromatography resin binds IgG, which can be eluted with by counter ions (i.e., Na+ from NaCl in elution buffer) after washing (para [0063-0064, 159, 0176]). Kim teaches the cation chromatography column binds FXI that is released from the column with higher concentrations of NaCl in the buffer (para [0064, 0175]).
Urmann teaches using a 1 mL Scout Column packed with a cation-exchange resin, EshmunoTM S resin, to isolate antibodies with a yield of 94% when 107 mg protein per mL of resin was applied to the column (p. 399, col 2, para 2; p. 400, col 2, para 2; Figure 8). Urmann teaches EshmunoTM S binds IgG (Table 1).
In view of the combined teachings of Zurlo, Kim, and Urmann, it would have been obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of isolating one or more proteins from blood-based material taught by Zurlo such that the method comprises a system for isolating IgG from plasma comprising:
a salt fractionation module,
that generates and separates a supernatant form a precipitate comprising IgG and other proteins like FXI;
a first chromatography module,
comprising an anion exchange chromatography column that the salt fractionation precipitate is applied to and produces a flow-through that contains IgG and other proteins like FXI,
a second chromatography module,
comprising a cation exchange chromatography column that the anion chromatography column flow-through is applied to and produces an eluate that contains IgG, while other proteins like FXI are bound to the column and removed upon with a buffer with a high salt concentration; and
and wherein the cation chromatography resin is EshmunoTM S and the amount thereof taught by Urmann which has a greater than 90% yield of IgG antibody for the second chromatography module, thereby arriving at the invention of claims 1-6.
An ordinary artisan would have been motivated to and would have had a reasonable expectation of success of modifying the method of isolating proteins and IgG from blood-based material taught by Zurlo and arrived at the modified system for isolating IgG from plasma taught by the combination of Zurlo, Kim, and Urmann recited above. Zurlo already taught that plasma contains gamma globulins, salt fractionation modules, chromatography modules that can comprise anion or cation chromatography, and a method of isolating IgG via:
a salt fractionation that generates a precipitate comprising IgG and other proteins like FXI; and further purification via chromatography to obtain IgG. A simple substitution of the chronographic step capable of isolating IgG taught by Zurlo for the anion chromatography and then cation chromatography steps capable of isolating IgG taught by Kim would have been obvious and expected to yield predicable results because they have the same function. A simple substitution of the cationic resin in the cation chromatography column taught by Kim for the EshmunoTM S cationic resin, and amount thereof, capable of binding antibodies and IgG taught by Urmann would have been expected to yield predicable results because they have the same function.
Regarding claim 10, the combined teachings of Zurlo, Kim, and Urmann as applied to claims 1-6 are discussed above and incorporated herein. An ordinary artisan would have also immediately recognized the system for isolating IgG from plasma taught by the combination of Zurlo, Kim, and Urmann.
Urmann further teaches wherein scaling-up of ion exchange chromatography operations is usually achieved by increasing the column diameter while keeping the resin bed height and linear flow rate constant in order to keep the residence time of the protein the same (p. 400, col 1, para 4).
In view of the combined teachings of Zurlo, Kim, and Urmann, it would have been obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to use the system for isolating proteins and IgG from taught by the combination of Zurlo, Kim, and Urmann to incrementally process any volume of plasma, including 500 L, thereby arriving at the invention of claim 10.
An ordinary artisan would have been motivated to and would have had a reasonable expectation of success of using the system for isolating proteins and IgG from taught by the combination of Zurlo, Kim, and Urmann to incrementally process any volume of plasma, including 500 L, in order to isolate more IgG.
Consequently, the invention of claim 1-6 and 10 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claims 7-9 are rejected under 35 U.S.C. 103 as being unpatentable over Zurlo in view of Kim and Urmann as applied to claims 1-6 and 10 above, and further in view of Liu et al. (mAbs, published 2010, Vol. 2, No. 5, p. 480-499; cited on the attached Form PTO-892; hereafter “Liu”), Nejatishahidein et al. (Biotechnology Progress, published May 23, 2020, Vol. 36, No. e3028; cited on the attached Form PTO-892; hereafter “Nejatishahidein”), and Schultz et al. (US 2014/0051839 A1; cited on the attached Form PTO-892; hereafter “Schultz”).
Regarding claims 7-9, the combined teachings of Zurlo, Kim, and Urmann as applied to claims 1-6 and 10, are discussed above and incorporated herein.
The combined teachings of Zurlo, Kim, and Urmann do not teach a depth filter.
Liu teaches a method for recovery and purification of antibodies wherein cells, debris, and DNA are removed prior to chromatographic purification to protect chromatography columns (Title; Abstract; Figure 1; Table 2). Liu teaches depth filters are typically composed of cellulose, a porous filter aid such as diatomaceous earth, and an ionic charge resin binder (p. 482, col 1, para 4 – p. 482, col 2, para 1). Liu teaches IgG is an antibody (p. 484, col 2, para 3; p. 485, col 2, para 5 – p. 486, col 1, para 1; p. 489, col 1, para 2). Since Liu recites a typical depth filter recites “a filter aid”, an ordinary artisan would immediately recognize Liu indicates a singular filter aid is typically comprised in a depth filter.
Nejatishahidein teaches typical depth filters contain filter aides like diatomaceous earth, perlite, or activated carbon (p. 2, col 2, para 1). Nejatishahidein teaches depth filters comprising diatomaceous earth or perlite (p. 2, col 2, para 1).
Schultz teaches diatomaceous earth adsorbs coagulation factor XI (FXI) and/or activated FXI (FXIa) (para [0030, 0038]; Claim 3). Since diatomaceous earth adsorbs FXI or FXIa, an ordinary artisan would immediately recognize a depth filter comprising diatomaceous earth would inherently adsorb and reduce FXI or FXIa.
In view of the combined teachings of Zurlo, Kim, Urmann, Liu, Nejatishahidein, and Schultz, it would have been obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the system for isolating proteins and IgG from plasma taught by the combination of Zurlo, Kim, and Urmann, such that there is a diatomaceous earth-based depth filter, but not containing perlite, after the fractionation module and before the first chromatography module, thereby arriving at the invention of claims 7-9.
An ordinary artisan would have been motivated and would have had a reasonable expectation of success of modifying the system for isolating proteins and IgG from plasma taught by the combination of Zurlo, Kim, and Urmann, such that there is a diatomaceous earth depth filter, but not containing perlite, after the fractionation module and before the first chromatography module. This is because Liu teaches the use of a depth filter containing diatomaceous earth to remove debris prior to chromatographic purification in order to protect the chromatography columns to improve subsequent chromatography. Therefore, a depth filter containing diatomaceous earth, but not perlite, taught by Nejatishahidein could be used to remove undesirable contaminants from the dissolved plasma precipitate produced from salt fractionation to preserve the subsequent chromatography modules. Since diatomaceous earth inherently adsorbs FXI and/or FXIa, the diatomaceous earth depth filter would inherently adsorb and reduce FXI and/or FXIa.
Consequently, the invention of claim 7-9 would have been obvious to one of ordinary skill in the art before the effective filing date.
Double Patenting Rejections
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 1-6 and 10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-5, 12, and 15 of U.S. Patent No. US 11,884,702 B2 (hereafter “patent‘702”) in view of Zurlo.
Regarding instant claims 1-2 and 6, claim 1 of patent’702 recites a method for isolating a target protein from a solution comprising the target protein and a plurality of contaminants, comprising:
adding a salt to the solution to generate a supernatant and a precipitate;
dissolving the precipitate in an aqueous solution to generate a dissolved precipitate comprising the target protein and a first portion of the plurality of contaminants;
applying the dissolved precipitate to a first ion exchange media having a first charge with a first polarity under first buffer conditions selected to not bind the target protein to generate a first bound fraction comprising a second portion of the plurality of contaminants and a first flow-through, wherein the first flow-through comprises the target protein and a third portion of the plurality of contaminants;
preparing a second ion exchange media selected to bind both the target protein and a fourth portion of the plurality of contaminants under second buffer conditions, wherein the second ion exchange media comprises a second charge with a second polarity that is opposite that of the first polarity;
applying the first flow-through to the second ion exchange media under second buffer conditions to generate a second bound fraction comprising the fourth portion of the plurality of contaminants and a second flow-through comprising the target protein;
wherein preparing comprises selecting a limited capacity of the second exchange media such that greater than 70% of content of the target protein in the solution is recovered in the second flow-through. Claim 12 recites wherein yield of the target protein in the second flow-through is at least 90%.
Regarding instant claim 3, claim 4 of patent’702 recites wherein the first ion exchange media is an anion exchange media, the second ion exchange media is a cation exchange media, and the target protein is immunoglobulin G.
Regarding instant claim 4, claim 5 of patent’702 recites wherein the plurality of contaminants comprises Factor XI or activated Factor XI.
Regarding instant claim 5, claim 2 of patent’702 recites wherein the solution is plasma.
Regarding instant claim 10, claim 15 of patent’702 recites wherein the volume of the solution is at least 500 L.
Regarding instant claim 1, Patent’702 does not explicitly teach wherein the method of isolating IgG from plasma comprises a system that comprises a fractionation module, a first separation module, and a second separation module. Regarding claim 2, Patent’702 does not explicitly teach a viral inactivation module within the fluid path between the fractionation module and the first separation module.
Regarding the limitation of a system for isolating a target protein from a solution comprising the target protein and a plurality of contaminants, comprising: a fractionation module, a first separation module, and a second separation module of instant claim 1; Zurlo teaches a method of producing one or more proteins, from blood-based material, including plasma, comprising a salt fractionation module followed by a first and second chromatography module (para [0012, 0025, 0033, 0074]; Figures 3-5, 8, and 10-11; Claims 2-3, 25-26, and 46-47). Zurlo teaches paste comprises precipitate as well the terms paste and precipitate are used interchangeably (para [0015]). Zurlo teaches salt fractionation of plasma produces a supernatant and a paste, and the paste can comprise the desired protein product as well as other proteins (para [0006, 0010-0011, 0026, 0055]; Figures 4-5). Zurlo teaches a precipitate from a salt fraction can be dissolved and further processed chromatography processes (para [0060]; Figure 4-5). Zurlo teaches a first chromatography step and a second chromatography step can comprise cation exchange or anion exchange chromatography (para [0018; 0027; 0058, 0069]; Figure 5; Claim 14). Zurlo teaches applying a sample from a blood-based material to a first chromatography module which produces at least a flow-through, and wherein the flow-through from the first chromatography module is applied to a second chromatography module which produces at least a flow-through in order to obtain one or more proteins (para [0072-0074]; Figures 3-5 and, 8, 10-11). Zurlo teaches that besides IgGs, plasma can comprise clotting factors as well as other proteins (para [0004, 0040, 0073-74]).
Regarding the limitation of wherein the system comprises a viral inactivation module within the fluid path between the fractionation module and the first separation module of instant claim 2, Zurlo teaches a viral inactivation module between a fractionation module a first chromatography module (para [0055, 0070, 0072-0074]; Figure 11; Claims 43 and 53).
Regarding instant claim 3, Zurlo teaches the first and second chromatography steps can comprise cation exchange or anion exchange chromatography (para [0018; 0027; 0058, 0069]; Claim 14). Zurlo teaches that plasma contains gamma globulins and the protein isolated can be an immunoglobulin such as immunoglobulin G (IgG) (para [0002, 0024, 0033, 0040, 0061, 0073]; Figures 3-5, see Figure 5 below; Claim 19). Zurlo teaches a precipitate formed from the salt fractionation of a blood-based material can yield IgG after further chromatographic processing (Figure 5).
Regarding instant claim 4, Zurlo teaches that besides IgGs, plasma can comprise clotting factors as well as other proteins (para [0004, 0040]).
Also, Kim teaches a method of purifying plasma-derived immunoglobulin G (IgG) comprising anion chromatography followed by cation chromatography (Abstract; para [0014, 0044]; Figures 1-2 and 4; Claim 1). Kim teaches plasma contains coagulation factor XI (FXI) and both anion chromatography and cation chromatography columns reduce IgG the FXI content and/or impurities (para [001017, 0020, 0036, 0063-0065, 0068, 0175-0176]; Tables 1-4). Kim teaches cation chromatography resin binds IgG, which can be eluted with by counter ions (i.e., Na+ from NaCl in elution buffer) after washing (para [0063-0064, 159, 0176]). Kim teaches the cation chromatography column binds FXI that is released from the column with higher concentrations of NaCl in the buffer (para [0064, 0175]).
In view of the teachings of Zurlo and Kim, it would have been obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method for isolating a target protein from plasma, such as IgG, comprising the target protein and a plurality of contaminants of the claims of the patent’702 such that the method comprises a system for isolating IgG from plasma comprising:
a salt fractionation module,
that generates and separates a supernatant form a precipitate comprising IgG and other proteins like FXI;
a first chromatography module,
comprising an anion exchange chromatography column that the salt fractionation precipitate is applied to and produces a flow-through that contains IgG and other proteins like FXI,
a second chromatography module,
comprising a cation exchange chromatography column that the anion chromatography column flow-through is applied to and produces an eluate that contains IgG, while other proteins like FXI are bound to the column and removed upon with a buffer with a high salt concentration; and
and wherein the cation chromatography resin and the amount thereof produces a second flow-through wherein the yield of the IgG in the that is at least 90%, thereby arriving at the invention of claims 1-6 and 10.
An ordinary artisan would have been motivated and would have had a reasonable expectation of success of modifying the method for isolating a target protein from plasma, such as IgG, comprising the target protein and a plurality of contaminants of the claims of patent’702 according to the teachings of Zurlo and Kim because the claims of the patent’702 recite and Zurlo taught methods of isolating IgG from plasma comprising salt fractionation and multiple chromatography steps, and the method of Zurlo comprised salt fractionation modules, and chromatography modules that can comprise anion or cation chromatography.
For the reasons stated herein, claims 1-6 and 10 of this application are unpatentable over claims 1-2, 4-5, 12, and 15 of patent‘702 in view of Zurlo and Kim.
Claims 7-9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-5, 10-12, and 15 of patent‘702 in view of Zurlo and Kim as applied to claims 1-6 and 10 above, and further in view of Liu, Nejatishahidein, and Schultz.
The combination of claims 1-2, 4-5, 12, and 15 of patent‘702, Zurlo, and Kim, as applied to claims 1-6 and 10 above, are discussed above and incorporated herein.
Regarding instant claims 7-8, claim 10 of patent’702 recites removing solids from the treated dissolved precipitate by performing a filtration step that comprises passage through a filter to the treated dissolved precipitate, wherein the filter comprises a material that selectively retains Factor XI or Factor XII.
Regarding instant claim 9, claim 11 of patent’702 recites wherein the filter does not include perlite.
The combination of claims 1-2, 4-5, 10-12, and 15 of patent‘702, Zurlo, and Kim, does not explicitly teach wherein the filter is a depth filter as well as wherein the depth filter interposed between the first output and the first separation module.
Liu teaches a method for recovery and purification of antibodies wherein cells, debris, and DNA are removed prior to chromatographic purification to protect chromatography columns (Title; Abstract; Figure 1; Table 2). Liu teaches depth filters are typically composed of cellulose, a porous filter aid such as diatomaceous earth, and an ionic charge resin binder (p. 482, col 1, para 4 – p. 482, col 2, para 1). Liu teaches IgG is an antibody (p. 484, col 2, para 3; p. 485, col 2, para 5 – p. 486, col 1, para 1; p. 489, col 1, para 2). Since Liu recites a typical depth filter recites “a filter aid”, an ordinary artisan would immediately recognize Liu indicates a singular filter aid is typically comprised in a depth filter.
Nejatishahidein teaches typical depth filters contain filter aides like diatomaceous earth, perlite, or activated carbon (p. 2, col 2, para 1). Nejatishahidein teaches depth filters comprising diatomaceous earth or perlite (p. 2, col 2, para 1).
Schultz teaches diatomaceous earth adsorbs coagulation factor XI (FXI) and/or activated FXI (FXIa) (para [0030, 0038]; Claim 3). Since diatomaceous earth adsorbs FXI or FXIa, an ordinary artisan would immediately recognize a depth filter comprising diatomaceous earth would inherently adsorb and reduce FXI or FXIa.
In view of the combination of the claims of patent’702 and the teachings of Zurlo, Kim, Liu, Nejatishahidein, and Schultz, it would have been obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the system for isolating proteins and IgG from plasma of the claims of patent’702 as modified by Zurlo and Kim, such that there is a diatomaceous earth-based depth filter, but not containing perlite, after the fractionation module and before the first chromatography module, thereby arriving at the invention of claims 7-9.
An ordinary artisan would have been motivated and would have had a reasonable expectation of success of modifying the system for isolating proteins and IgG from plasma of the claims of patent’702 as modified by Zurlo and Kim, such that there is a diatomaceous earth depth filter, but not containing perlite, after the fractionation module and before the first chromatography module. This is because Liu teaches the use of a depth filter containing diatomaceous earth to remove debris prior to chromatographic purification in order to protect the chromatography columns to improve subsequent chromatography. Therefore, a depth filter containing diatomaceous earth, but not perlite, taught by Nejatishahidein could be used to remove undesirable contaminants from the dissolved plasma precipitate produced from salt fractionation to preserve the subsequent chromatography modules. Since diatomaceous earth inherently adsorbs FXI and/or FXIa, the diatomaceous earth depth filter would inherently adsorb and reduce FXI and/or FXIa.
For the reasons stated herein, claims 7-9 of this application are unpatentable over claims 1-2, 4-5, 10-12, and 15 of patent‘702 in view of Zurlo, Kim, Liu, Nejatishahidein, and Schultz.
Conclusion
No claims are currently allowed for the reasons as stated above. Applicants must
respond to the objections/rejections in this Office action to be fully responsive in
prosecution.
The instant Office Action is non-final.
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/SCOTT E. MULDER/Examiner, Art Unit 1656
/David Steadman/Primary Examiner, Art Unit 1656