The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on May 12, 2026 has been entered.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.
Claims 1-48, 54, 59, 61-62, 74 are canceled. Claims 49-53, 55-58, 60, 63, 64-73, 75 are under consideration.
Priority: This application is a CON of U.S. Application 15424072, filed February 3, 2017, abandoned, which is a CON of U.S. Application 14535085, filed November 6, 2014, now U.S. Patent 9598461, which is a CON of PCT/AU2013/001414, filed December 5, 2013.
Objections and Rejections
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.
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.
Claims 49-53, 55-57, 60, 63, 64-71, 73, 75 are rejected under 35 U.S.C. 103 as being unpatentable over EP ‘135 (EP 0555135; IDS 03.01.21) (translation of EP 0555135B1 provided by Google Patents cited herein; previously cited) in view of Lengsfeld et al. (US 20030232969, cited as US 7919592 on IDS 03.01.21; previously cited). EP ‘135 discloses a method for preparing fibrinogen of high purity (at least abstract). EP ‘135 discloses the method for producing fibrinogen having very high purity, comprising passing a solution comprising fibrinogen through an anion exchange column comprising an anion exchange resin under conditions where the fibrinogen is selectively adsorbed or bound to the anion exchange column, eluting the fibrinogen with an elution buffer having the composition 200 mM NaCl, 20 mM Tris, pH 8.8 (at least p. 1 claim 1, p. 2, p. 3 example) to obtain a fibrinogen solution, concentrating the eluted fibrinogen, and then sterilizing the fibrinogen by filtering the fibrinogen solution through a filtration membrane having 0.22 µm pore size (p. 3). Therefore, EP ‘135 reasonably discloses applying the fibrinogen solution obtained from eluting the anion exchange column to a sterilizing filtration. EP ‘135 does not explicitly teach a pore size in the range of from about 15 nm to about 35 nm.
Lengsfeld et al. disclose a method for separating viruses from a protein solution by nanofiltration, comprising adding to the protein solution a chaotropic substance that is alternatively not arginine, in order to decrease or prevent aggregation, and then filtering the protein solution through a filter having a pore size ranging from 15 nm to less than 35 nm (abstract, also p. 2 claim 1). Lengsfeld et al. disclose that the fibrinogen solution is clarified by a 0.22 µm filtration step to remove macrosize particles prior to nanofiltration (paragraph 0018). Lengsfeld et al. disclose the method is suitable for separating off viruses from a fibrinogen solution (at least paragraphs 0013, 0020-0022).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the references and arrive at the claimed method for purifying fibrinogen, comprising: passing a solution comprising fibrinogen through an anion exchange chromatographic resin under conditions that bind fibrinogen monomer; eluting the fibrinogen monomer from the anion exchange chromatographic resin with an elution buffer to obtain a fibrinogen monomer solution; and applying the fibrinogen monomer solution directly onto a filter having a pore size in the range of from about 15 nm to about 35 nm, and wherein the elution buffer comprises about 200 (i.e. about 190) mM NaCl, 20 mM Tris, pH 8.8 and thereby having a conductivity in the recited range 15-21.5 mS/cm and does not contain arginine (instant claim 49). The motivation to do so given by the prior art. It is known that "where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). MPEP 2144.05. In this instance, EP ‘135 discloses a method for purifying fibrinogen comprising subjecting a solution containing fibrinogen to anion exchange chromatography under conditions that bind fibrinogen; eluting the fibrinogen with an elution buffer to obtain a fibrinogen solution; and applying the fibrinogen solution obtained from eluting the anion exchange column to a sterilizing filtration, where the elution buffer comprises the same elements of the recited elution buffer, for the same purpose of eluting fibrinogen from an anion exchange resin, and at similar ionic strength conditions and/or conductivities. Lengsfeld et al. disclose that filtering a fibrinogen protein solution through a filter having a pore size in the range of 15 to 35 nm is suitable for separating viruses from the protein. Therefore, one of ordinary skill would have reasonable motivation to incorporate the nanofilter having a pore size ranging from 15 nm to less than 35 nm disclosed in Lengsfeld et al. for the sterile filter in the method for purifying fibrinogen by anion exchange chromatography of EP ‘135, and further arrive at the elution buffer having a conductivity of from 15-21.5 mS/cm by following the teachings of EP ‘135 because an elution buffer having a conductivity range of from 15-21.5 mS/cm is similar to the elution buffer solution having an ionic strength at 200 mM NaCl disclosed in EP ‘135. One of ordinary skill would have a reasonable expectation of success because methods for purifying fibrinogen by anion exchange chromatography and nanofiltration were known, as disclosed in the cited prior art.
Regarding instant claim 64, Lengsfeld et al. disclose that the fibrinogen solution is clarified with a 0.22 µm to remove macrosize particles before applying the fibrinogen solution to a nanofilter having a pore size ranging from 15 nm to less than 35 nm (paragraph 0018). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to arrive at the claimed method for purifying fibrinogen, comprising: passing a solution comprising fibrinogen through an anion exchange chromatographic resin under conditions that bind fibrinogen monomer; eluting the fibrinogen monomer from the anion exchange chromatographic resin with an elution buffer to obtain a first fibrinogen monomer solution; applying the first fibrinogen monomer solution directly onto a filter having a pore size greater than 35 nm to obtain a second fibrinogen monomer solution; and applying the second fibrinogen monomer solution directly onto a filter having a pore size in the range of from about 15 nm to about 35 nm, and wherein the elution buffer comprises about 200 (i.e. 190) mM NaCl, 20 mM Tris, pH 8.8 and thereby having a conductivity of from 15-24 mS/cm and does not contain arginine (instant claim 64).
Regarding instant claims 50-51, 65-66, EP ‘135 discloses the anion exchange chromatography resin is an anion exchange resin comprising quaternary amine groups (at least abstract, p. 1 claim 1, p. 2, p. 3 example).
Regarding instant claims 52-53, 55, 67-68, 69, EP ‘135 discloses the elution buffer solution comprises the composition 200 mM NaCl, 20 mM Tris, pH 8.8 (at least p. 1 claim 1, p. 2, p. 3 example). As noted above, "where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). MPEP 2144.05. Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. In this instance, EP ‘135 discloses the elution buffer comprises the same elements of the recited elution buffer, for the same purpose of eluting fibrinogen from an anion exchange resin, and at similar concentrations and/or ionic strength conditions; therefore, it would have been obvious to arrive at the recited concentrations and conductivities by routine optimization.
Regarding instant claims 56, 70, Lengsfeld et al. disclose the nanofilters are selected from commercially available Planova 15 N and Pall Ultipor DV20 (at least paragraphs 0009, 0016).
Regarding instant claims 57, 71, Lengsfeld et al. disclose fibrinogen nanofiltration with a chaotropic substance selected from citrulline, and is therefore, not arginine (abstract, also p. 2 claim 1). Therefore, it would be obvious that the fibrinogen can be nanofiltered through a filter having a pore size ranging from 15 nm to less than 35 nm in the presence an amino acid that is not arginine.
Regarding instant claims 60, 73, Lengsfeld disclose concentration of the chaotropic substance at 6% (paragraphs 0020-0022), where the chaotropic substance is selected from citrulline not arginine (abstract, also p. 2 claim 1). Therefore, it would be obvious that the amino acid that is not arginine can be present at a concentration of 6%.
Regarding instant claims 63, 75, as noted above, EP ‘135 discloses an elution buffer having the composition 200 mM NaCl, 20 mM Tris, pH 8.8 (at least p. 1 claim 1, p. 2, p. 3 example). “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). MPEP 2144.05. In this instance, it would have been obvious to arrive at the recited pH of about 7 by routine optimization.
Reply: Applicants’ remarks have been considered but they are not persuasive. The reasons for maintaining the 103 rejection are the same as previously noted and are incorporated herein.
Applicants have amended independent claims 49 and 64 to require elution of the fibrinogen monomer from the AEX (anion exchange) resin with “an aqueous elution buffer having a conductivity above 15 mS/cm and below 21.5 mS/cm.” Applicants assert that the instant specification discloses that plasminogen is an undesired impurity in purified fibrinogen solutions. Applicants assert that instant example 10 compares different methods for purifying fibrinogen and demonstrates that the method exemplified in instant example 6 is more efficient in removing plasminogen compared to two previously described methods. Applicants assert that in these previously described methods, the conductivity of the buffer used for eluting fibrinogen is either very low (13.1-15 mS/cm) or very high (500 mM NaCl, 1.1 mM CaCl2, 10 mM Na-citrate, 10 mM Tris, 45 mM sucrose, pH 7.0) compared to that of the instant exemplified method (200 mM NaCl, 10 mM Tris, 10 mM Tris-sodium citrate, 46 mM sucrose, 1.1 mM CaCl2, pH 7.0). Applicants assert that therefore, in view of instant example 10, one skilled in the art would have understood the advantage of using an elution buffer with a conductivity higher than 15 mS/cm or lower than 500 mS/cm.
Applicants’ remarks are not persuasive. In this instance, the cited 103 reference EP ‘135 discloses an elution buffer having the composition 200 mM NaCl, 20 mM Tris, which is similar in conductivity to the exemplified elution buffer comprising 200 mM NaCl, 10 mM Tris, etc. Therefore, Applicants’ recognized advantage of more efficiently removing plasminogen with an elution buffer comprising 200 mM NaCl, 10 mM Tris, etc., would flow naturally from following the suggestions of the prior art EP ‘135, which discloses an elution buffer having the composition 200 mM NaCl, 20 mM Tris, which reasonably comprises a conductivity similar to the instant exemplified elution buffer having a conductivity higher than 15 mS/cm and lower than 500 mS/cm.
Applicants assert that furthermore, instant example 7 demonstrates that fibrinogen eluted with a buffer having a conductivity of 21.5 mS/cm can successfully pass through a nanofilter having a pore size 15-35 nm without fouling the filter.
Applicants’ remarks are not persuasive. As previously noted, the instant specification discloses that an elution buffer comprising from about 150 mM to about 300 mM NaCl equates to an elution buffer having a conductivity range of about 18 mS/cm (150 mM NaCl) to about 32 mS/cm (300 mM NaCl) (application publication paragraph 0100); and that an elution buffer comprising from about 200 mM to about 220 mM NaCl equates to an elution buffer having a conductivity range of about 22 mS/cm (200 mM NaCl) to about 24 mS/cm (220 mM NaCl) (application publication paragraph 0103).
Therefore, the elution buffer disclosed in EP ‘135 would necessarily have a conductivity in the range of from 15-24 mS/cm (i.e. ~22.5 mS/cm) and also does not contain arginine, as recited in the instant claims.
Instant example 7 demonstrates that fibrinogen eluted with buffers having 190 mM NaCl, 200 mM NaCl, or 210 mM NaCl resulted in similar filtration characteristics.
In this instance, the prior art (EP ‘135) has disclosed an elution buffer comprising the same elements of the recited elution buffer for the same purpose of eluting fibrinogen from an anion exchange resin, and at similar ionic strength conditions and/or conductivities.
Therefore, Applicants’ discovery that elution buffers with the claimed conductivity (15-21.5 mS/cm) and without arginine improved nanofiltration without clogging the filter would flow naturally from following the suggestions of the prior art. See also MPEP 2145.
In this instance, EP ‘135 has already disclosed eluting fibrinogen from an anion exchange column with an elution buffer having a conductivity very similar to the recited range 15-21 mS/cm (i.e. having 200 mM NaCl and a conductivity of ~22.5 mS/cm) (at least p. 1 claim 1, p. 2, p. 3 example) and does not contain arginine. EP ‘135 further disclose that the fibrinogen eluted from the anion exchange column with the elution buffer is sterile filtered (at least p. 1 claim 1, p. 2, p. 3 example).
Lengsfeld et al. disclose fibrinogen nanofiltration with a chaotropic substance selected from alternatives to arginine, such as citrulline (abstract, also p. 2 claim 1). Lengsfeld et al. disclose nanofiltration of fibrinogen with or without arginine and show that the flowthrough increases as the filter increases and that arginine in a fibrinogen solution does not necessarily cause fouling during nanofiltration (paragraphs 0020-0022, Fig. 1).
Therefore, one of ordinary skill would have reasonable motivation to incorporate the nanofilter having a pore size ranging from 15 nm to less than 35 nm disclosed in Lengsfeld et al. for the sterile filter in the method for purifying fibrinogen by anion exchange chromatography of EP ‘135, thereby arriving at the claimed method comprising an elution buffer having a conductivity of from 15-21.5 mS/cm and not containing arginine, because it is similar to the method and elution buffer solution having an ionic strength at 200 mM NaCl disclosed in EP ‘135. One of ordinary skill would have a reasonable expectation of success because methods for purifying fibrinogen by anion exchange chromatography and nanofiltration were known, as disclosed in the cited prior art.
See also the reasons noted on at least p. 7-9 of the December 22, 2025 final office action and p. 6-10 of the May 19, 2025 non-final office action.
Claims 49, 57-58, 64, 71-72 are rejected under 35 U.S.C. 103 as being unpatentable over EP ‘135 (EP 0555135; IDS 03.01.21) (translation of EP 0555135B1 provided by Google Patents cited herein; previously cited) in view of Lengsfeld et al. (US 20030232969, cited as US 7919592 on IDS 03.01.21; previously cited) and Roemisch et al. (US 20010051154; previously cited). The teachings of EP ‘135 and Lengsfeld et al. over at least instant claims 49, 57, 64, 71 are noted above. Lengsfeld et al. do not teach that the amino acid present during nanofiltration of fibrinogen comprises glycine.
Roemisch et al. disclose stabilized protein preparations that are suitable for nanofiltration (at least paragraph 0003), where the protein is fibrinogen (at least paragraph 0008), where the stabilized protein preparation comprises stabilizers selected from amino acids other than arginine, and further comprises glycine (at least paragraph 0010), and where the stabilized protein solution is suitable for nanofiltration (at least paragraph 0013).
Regarding instant claims 58, 72, it would have been obvious that the fibrinogen in the method of EP ‘135 and Lengsfeld et al. noted above can be nanofiltered through a filter having a pore size ranging from 15 nm to less than 35 nm in the presence an amino acid that comprises glycine, as suggested in Roemisch et al. The motivation to do so is given by Roemisch et al. which disclose that stabilized protein preparations, where the protein is fibrinogen, and comprising glycine are suitable for nanofiltration. One of ordinary skill would have a reasonable expectation of success because methods for purifying fibrinogen by anion exchange chromatography and nanofiltration were known, as disclosed in the cited prior art.
Reply: Applicants’ remarks are not persuasive. The reasons for maintaining EP ‘135 and Lengsfeld et al. are the same as noted above. The deficiency of Roemisch et al. to not teach an anion exchange chromatography is remedied by EP ‘135.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Marsha Tsay whose telephone number is (571)272-2938. The examiner can normally be reached M-F.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath N. Rao can be reached on 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Marsha Tsay/Primary Examiner, Art Unit 1656
Prosecution Insights