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 .
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.
Claims 1-20 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.
Regarding Claims 1, 17 and 18:
The claim states “a plurality of separation ligands for formula SL1 or SL2…”. The term “for” renders the claim indefinite because it is not clear it is a typographical error and should be, for example, “of”, or if the claim is intending the plurality of ligands to have a use “for” the formulas SL1 or SL2. It is not clear how a ligand can be “for” a formula. For the purpose of examination, the claim will be interpreted as requiring a plurality of separation ligands “of” formula SL1 or SL2.
The claim states “Rp1, Rp3, and Rp4 each independently comprise the reaction product of any one of…” This limitation renders the claim indefinite because it is not clear two elements are being combined to form the “product”. The instant specification states “ reaction product is the chemical group resulting from the reaction of two cooperative functional handles” (see paragraph [0108]). It is not clear how the reaction product can be “of any one of…”. Also, the claim is not clear whether RpE and RpM are part of the reaction product of any one of RpA through RpK since RpE and RpM appears to be not included.
Regarding Claim 4:
The claim further limits “Sp”, however “Sp” is only required in the alternative if formula SL2 is used. It is therefore not clear whether SL2 is required or Sp is only being limited if SL2 is present.
Regarding Claim 5:
The claim further limits Rp3 and Rp4; however, “Rp3”, and “Rp4” are only required in the alternative if formula SL2 is used. It is therefore not clear whether SL2 is required or if Rp3 and Rp4 are only being limited if SL2 is present.
Regarding Claims 6-7:
The claim states “SL2 comprises…” This limitation renders the claim indefinite because it is not clear if SL2 is required by the claim or only limited if present. This limitation further renders the claim indefinite because it is not clear if the structures provided are intended to represent Rp3-Sp-Rp4-Z or any part of SL2 or in place of Rp3-Sp-Rp4-Z.
The remaining claims are indefinite as they depend from indefinite claims.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 5, 9-11, 14 and 17-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by ARICA et al., "Purification of Lysozyme from Egg White by Reactive Blue 4 and Reactive Red 120 Dye-Ligands Immobilised Composite Membranes", March 2005, Process Biochemistry, Vol. 40 (Issue 3-4), pp. 1433-1442 (hereinafter “Arica”).
Regarding claims 1, 5 and 17, Arica teaches a separation media comprising:
a support substrate of 2-hydroxyethylmethacrylate (HEMA) and chitosan (pHEMA/chitosan) ; and
a plurality of separation ligands of formula SL1 or SL2 wherein:
Z is a separation group comprising a dye including Reactive Blue 4 (Procion Blue MX-R), Reactive Red 120 (Procion Red HE-3B); and
Rp1, Rp3, and Rp4 each independently comprise the reaction product of any one of RpE and RpM as Blue-4 and Red-120 were covalently immobilized onto composite membrane via the nucleophilic reaction between the chloride of its triazine ring and hydroxyl and amino groups of the chitosan and pHEMA, respectively (see 2. Materials and methods on page 1434; particularly sections 2.1-2.3) wherein Arica further discloses a separation device comprising a housing i.e. column and the separation media within the housing (see section 2.4. page 1435).
Regarding claim 9, Arica teaches that the separation media is configured to use with HPLC mobile phase comprising an organic solvent e.g. acetonitrile, an aqueous solvent e.g. trifluoroacetic acid in Milli-Q water or both (see section 2.4. page 1435).
Regarding claims 10-11, 14 and 18-20, Arica teaches the separation of lysozyme i.e. protein from diluted egg white in phosphate buffer i.e. isolation solution using the separation media disclosed above including Blue-4 and Red-120 (triazine dye and azo dye respectively: see Table 3 of the instant specification)(see section 2.5,-2.6. on page 1435) wherein the separation media is washed with a washing solution and the proteins are eluted with elution solution of phosphate buffer containing 0.5 M NaCl (see section 2.5,-2.6. on page 1435).
Claims 1, 5, 8-11, 14 and 17-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by SU et al., "Optimization of adsorption conditions of papain on dye affinity membrane using response surface methodology," April 2009, Bioresource Technology, Vol. 100(Issue 8), Page 2336-2340 (hereinafter “Su”).
Regarding claims 1, 5, 8 and 17, Su teaches a separation media comprising:
a support substrate of nylon membranes, chitosan-coated composite membranes; and
a plurality of separation ligands of formula SL1 or SL2 wherein:
Z is a separation group comprising a dye including Reactive Blue 4; and
Rp1, Rp3, and Rp4 each independently comprise the reaction product of any one of RpE and RpM as Reactive Blue 4 was covalently immobilized onto composite membrane via the nucleophilic addition or substitution reactions with the hydroxyl and amino groups of chitosan and nylon membrane, respectively (see sections 2.1-2.4 on page 2337; section 3.1 on page 2338) wherein Su further discloses a separation device comprising a housing i.e. cartridge and the separation media within the housing (see section 2.7. on page 2338).
Regarding claim 9, Su teaches that the separation media is configured to use with 0.05M Tris-HCl buffer (both an organic solvent and an aqueous solvent (see section 2.7. page 2338).
Regarding claims 10-11, 14 and 18-20, Su teaches the separation of papain i.e. protein from mixture of proteins in 0.05M Tris-HCl buffer i.e. isolation solution using the separation media disclosed above including Reactive Blue 4 (triazine dye: see Table 3 of the instant specification)(see section 2.7, 3.1 on page 2338) wherein the separation media is washed with a washing solution i.e. 0.05M Tris-HCl buffer (pH 7.05) and the proteins are eluted with elution solution of 0.05M Tris-HCl buffer (pH 9.0) containing 1.0 M NaCl (see section 2.7. on page 2338).
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.
Claims 1, 4-11, 14 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over US 2020/0188859 A1 to Zhou et al (hereinafter “Zhou”) in view of US Patent No. 5,270,193 (Eveleigh).
Regarding Claims 1 and 17, Zhou teaches the separation media comprising:
a support structure (cellulose membrane) (see paragraph [0011]); and
a plurality of separation ligands of formula SL1 or SL2 (see Fig. 4, Figure 4 shows a separation ligand equivalent to SL2, wherein Rp3 and Rp4 are each RpE (U5 of RP3 is O and U5 of Rp4 is NH), and Sp is the carbonyl group); wherein Z is a separation group comprising an affinity group, the affinity group comprising a carbohydrate binding domain (Con A) (membranes prepared by method 3, method 3 is represented by figures 4) (see paragraphs [0122], [0090]) a carbohydrate binding ligand, or both. Zho further teaches that membrane is packed in a syringe-filter like membrane holder (see paragraph [0131]).
However, Zhou does not disclose a dye as an affinity group.
Eveleigh teaches a separation media wherein the carbohydrate binding ligand is Reactive Blue 4 (see col. 9, lines 64-65).
Zhou and Eveleigh are analogous inventions in the art of separation media.
It would have been obvious to one skilled in the art before the effective filing date of the invention to replace the binding domain of Zhou with the Reactive Blue 4 of Eveleigh because it is the simple substation of one known affinity group with another know affinity group, obviously resulting in the ability to bind materials, with an expectation of success. The simple substitution of one known element for another is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, B.).
Regarding Claim 4, Zhou teaches the separation media of claim 1, wherein Sp comprises —C(O)— (carbonyl) (see fig. 4).
Regarding Claim 5, Zhou teaches the separation media of claim 1, wherein Rp3 and Rp4 comprises RpE (see Fig. 4, claim mapping of claim 1 above) wherein U5 of RP3 is O and U5 of Rp4 is NH (see Fig. 4).
Regarding Claim 6, Zhou teaches the separation media of claim 1, wherein SL2 comprises
PNG
media_image1.png
95
193
media_image1.png
Greyscale
(see fig. 4, paragraph [0122] which teaches Pro A replaced with Con A).
Regarding claim 7, claimed SL2 is an obvious variation of hydroxyl and amino linkage group.
Regarding Claim 8, Zhou teaches the separation media of claim 1, wherein the support substrate comprises a regenerated cellulose membrane (see paragraph [0011]).
Regarding Claim 9, Zhou teaches the separation media of claim 1, wherein the separation media is configured for use with an organic solvent (see paragraph [0022]).
Regarding Claim 10, Zhou teaches the separation media of claim 1, wherein the biomolecule is a protein e.g. hlgG (see paragraph [0135]).
Regarding Claims 11 and 14, Eveleigh teaches a separation media wherein the carbohydrate binding ligand is Reactive Blue 4 (see col. 9, lines 64-65) which is triazine dye (see Table 3 in paragraph [0086] of the instant specification).
Claims 2-3 are rejected under 35 U.S.C. 103 as being unpatentable over Zhou in view of Eveleigh as applied to claim 1 above and further in view of US Patent No. 5,683,916) to Goffe et al. (hereinafter “Goeffe”).
Zhou in view of Eveleigh teaches the separation media of claim 1.
Zhou teaches the separation media of claim 1, wherein the plurality of separation ligands are of formula SL2 (see Fig. 4, and claim for claim 1 mapping above).
Zhou does not teach Sp is an alkanediyl or alkenediyl comprising one or more catenated functional groups.
Goffe teaches a separation media comprising a linker moiety (spacer Sp), wherein Sp is an alkanediyl or alkenediyl comprising one or more catenated functional groups (ethylene glycol diglycidy ether)(see col. 22, lines 64- col. 23, line 7).
Zhou and Goffe are analogous inventions in the art of separation media.
It would have been obvious to one skilled in the art before the effective filing date of the invention to replace the carbonyl spacer of Zhou with the alkanediyl or alkenediyl comprising one or more catenated functional groups spacer of Goffe because it is the simple substitution of one known spacer group with another known spacer group, obviously resulting in the ability to bind with other ligands (see Goffe: col. 22, lines 54-67) with an expectation of success. The simple substitution of one known element for another is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, B.).
Regarding Claim 3, Zhou, as modified, teaches the separation media of claim 1, wherein the alkanediyl or alkenediyl comprises a backbone chain of length C1 to C18 (C2, ethylene glycol diglycidy ether) (see Goffe: col. 22, lines 64- col. 23, line 7).
Claims 12-13 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Zhou in view of Eveleigh as applied to claim 1 above and further in view of MCGETTRICK et al., "Dye-Ligand Affinity Chromatography", 12 December 2003, In: CUTLER P., (Eds), Protein Purification Protocols: Second Edition, Methods in Molecular Biology, Humana Press, Vol. 244, pp. 151-157 (hereinafter “McGettrick”).
Zhou in view of Eveleigh teaches the separation media of claim 1.
Regarding claim 15, Zhou teaches the separation media of claim 1, wherein the plurality of separation ligands are of formula SL2 (see Fig. 4, and claim for claim 1 mapping above).
Everleigh teaches Reactive Blue 4 (Blue MX-R) (see col. 9, lines 64-65) which is a triazine dye (see Table 3 in paragraph [0086] of the instant specification).
Zhou or Eveleigh does not teach a phenanthridine dye, a polymethine dye, a phenylindole dye or a bisbenzimide dye.
McGettrick teaches a separation media including available dyes including Reactive Blue 4 (Blue MX-R) and Green H-E4BD (GelGreen A) (see Table 1 on page 153) wherein GelGreen A is phenathridine dye for oligonucleotide (see Table 3 in paragraph [0086] of the instant specification).
Zhou, Eveleigh and McGettrick are analogous inventions in the art of separation media.
It would have been obvious to one skilled in the art before the effective filing date of the invention to replace the binding domain of Zhou with the GelGreen A of McGettrick in place of Reactive Blue 4 (Blue MX-R) of Everleigh because it is the simple substation of one known affinity group with another know affinity group, obviously resulting in the ability to bind materials, with an expectation of success. The simple substitution of one known element for another is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, B.).
Regarding claims 12-13, oligonucleotide is either double stranded or single stranded in its inherent form.
Claims 12-16 are rejected under 35 U.S.C. 103 as being unpatentable over Zhou in view of Eveleigh as applied to claim 1 above and further in view of US 2023/0324374 A1 to Bartholomew et al. (hereinafter “Bartholomew”).
Zhou in view of Eveleigh teaches the separation media of claim 1.
Regarding claims 14-16, Zhou teaches the separation media of claim 1, wherein the plurality of separation ligands are of formula SL2 (see Fig. 4, and claim for claim 1 mapping above).
Everleigh teaches Reactive Blue 4 (Blue MX-R) (see col. 9, lines 64-65) which is a triazine dye (see Table 3 in paragraph [0086] of the instant specification).
Zhou or Eveleigh does not teach a triphenylmethane dye, a cyanine dye, an azo dye or a triazine dye (claim 14), a phenanthridine dye, a polymethine dye, a phenylindole dye or a bisbenzimide dye (claim 15), triarylmethane dye or xanthene dye (claim 16).
Bartholomew teaches available dyes which have binding specificity for a target biomolecule used in chromatography (see paragraphs [0003], [0059]) wherein dye molecules are selected from a xanthene, a cyanine, a polymethine, a pyrene, a thiazine, etc. (see paragraph [0080]).
Zhou, Eveleigh and McGettrick are analogous inventions in the art of separation media.
It would have been obvious to one skilled in the art before the effective filing date of the invention to replace the binding domain of Zhou with a xanthene, a cyanine, a polymethine dye of Bartholomew in place of Reactive Blue 4 (Blue MX-R)(triazine dye) of Everleigh because it is the simple substation of one known affinity group with another know affinity group, obviously resulting in the ability to bind materials, with an expectation of success. The simple substitution of one known element for another is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, B.).
Regarding claims 12-13, oligonucleotide is either double stranded or single stranded in its inherent form.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Zhou in view of Everleigh and US 2021/0178290 A1 to Willson et al. (hereinafter “Wilson”).
Zhou teaches the method of isolating a target molecule comprising contacting the isolation solution with the separation media of claim 40 (contacting hIgG with the column containing the membranes) (see paragraph [0117], claim mapping for claim 1 above).
Zhou teaches the separation media comprising:
a support structure (cellulose membrane) (see paragraph [0011]); and
a plurality of separation ligands of formula SL1 or SL2 (see Fig. 4, Figure 4 shows a separation ligand equivalent to SL2, wherein Rp3 and Rp4 are each RpE (U5 of RP3 is O and U5 of Rp4 is NH), and Sp is the carbonyl group); wherein Z is a separation group comprising an affinity group, the affinity group comprising a carbohydrate binding domain (Con A) (membranes prepared by method 3, method 3 is represented by figures 4) (see paragraphs [0122], [0090]) a carbohydrate binding ligand, or both. Zho further teaches that membrane is packed in a syringe-filter like membrane holder (see paragraph [0131]).
However, Zhou does not disclose a dye as an affinity group.
Eveleigh teaches a separation media wherein the carbohydrate binding ligand is Reactive Blue 4 (see col. 9, lines 64-65).
Zhou and Eveleigh are analogous inventions in the art of separation media.
It would have been obvious to one skilled in the art before the effective filing date of the invention to replace the binding domain of Zhou with the Reactive Blue 4 of Eveleigh because it is the simple substation of one known affinity group with another know affinity group, obviously resulting in the ability to bind materials, with an expectation of success. The simple substitution of one known element for another is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, B.).
Zhou also does not teach the isolation solution comprising: an isolation solvent; and the target molecule comprising a lentiviral vector. Zhou further teaches that the target molecules can be viral vectors (see paragraph [0110]).
Willson teaches a method of isolating a target molecule comprising a viral vector from an isolation solution, the isolation solution comprising: an isolation solvent (feed containing LVs, material other than the LV is the solvent); and the target molecule comprising a lentiviral vector (see paragraphs [0130]-[0131]).
Zhou and Willson are analogous inventions in the art of isolating target compounds.
It would have been obvious to one skilled in the art before the effective filing date of the invention to use the method of Zhou to separate lentiviral vectors from an isolation solvent, as disclosed by Willson lentiviral vectors are a desirable product to isolate (see Willson: paragraph [0130]) and Zhou teaches that the separation media of claim 1 can be used to separate viral vectors (see Zhou para. 0110). Further one skilled in the art, through routine experimentation, would have found it obvious to use a known method to separate a known compound. The use of a known technique to improve similar devices (methods or products) in the same way is likely to be obvious. See KSR International Co. v. Teleflex Inc., 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, C.).
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over by Zhou in view of Eveleigh and Wilson as applied to claim 18 above, and further in view WO 2013/190453 A2 to Thompson et al (hereinafter “Thompson”).
Zhou, as modified in view of Eveleigh and Wilson, teaches the method of claim 18.
Zhou does not teach the method further comprises washing the separation media with a washing solution.
Thompson teaches a method of isolating a target molecule (target complexes), wherein the method further comprises washing the separation media with a washing solution (washed) (see para. 00211).
Zhou and Thompson are analogous inventions in the art of isolating target molecules.
It would have been obvious to one skilled in the art before the effective filing date of the invention to add the washing step of Thompson to the method of Zhou (as modified) because it is the simple addition of a known processing step to a known separation method obviously resulting in the removal of un-bound substances from the column (see Thompson para. 00211), with an expectation of success. The combination of familiar elements is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc., 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, A.).
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over by Zhou in view of Eveleigh and Wilson as applied to claim 18 above, and further in view of US 2021/0032297 A1 to Schmidt et al. (hereinafter “Schmidt”).
Zhou, as modified in view of Eveleigh and Wilson, teaches the method of claim 18.
Zhou does not teach wherein the method further comprises eluting the target molecule from the separation media with an elution solution comprising an elution solvent and an affinity group competitive molecule.
Schmidt teaches a method of isolating a target molecule wherein the method further comprises eluting the target molecule (competitive elution) (see paragraph [0106]) from the separation media with an elution solution comprising an elution solvent and an affinity group competitive molecule (adding a competitor) (see paragraph [0106]).
Zhou, as modified in view of Eveleigh and Wilson, and Schmidt are analogous inventions in the art of isolating target molecules.
It would have been obvious to one skilled in the art before the effective filing date of the invention to add the step of eluting with an elution solution comprising an elution solvent and an affinity group competitive molecule, as disclosed by Schmidt, to the method of Zhou, because it is the simple addition of a known method step to a known process, obviously resulting in the removal of the target molecule from the column, with an expectation of success. The combination of familiar elements is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc., 550 U.S. __,__, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, A.).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN KIM whose telephone number is (571)272-1142. The examiner can normally be reached Maxi Flex.
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, INSUK BULLOCK can be reached at 571-272-5954. 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.
/John Kim/Primary Examiner, Art Unit 1772
JK
9/16/26
Prosecution Insights