DETAILED ACTION
The present application is being examined under the pre-AIA first to invent provisions.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 April 8, 2026 has been entered.
Claims 2, 6 and 7 have been canceled. Claims 1, 3-5 and 8-13 are pending and have been considered on the merits. All arguments have been fully considered.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1, 3-5, 8-9, and 11 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Belew et al (US 2005/0267295 A1; 12/1/2005. Cited on IDS) in view of Octylamine (gelifesciences.com. 2008;1-18. Cited on IDS), as evidenced by Mahoney (Newton’s Home Page. 2003;1-2. Cited on IDS).
The instant claims recite a separation medium comprising a porous, hydrophobic core entity; and a porous hydrophilic lid covering the whole outer part of the core entity, wherein the lid only allows molecules under a certain size to penetrate and interact with the internal part of the core entity of the separation medium, wherein the core entity and the lid are based on a hydrophilic matrix internally functionalized with hydrophobic interaction ligands to achieve the hydrophobicity of the core entity, wherein the hydrophilic matrix is made of agarose, and wherein the hydrophobic interaction ligands are octylamine.
Belew teaches a separation medium (para 0025) comprising a porous interior part (a porous hydrophobic core entity) (para 0026, 0031), and a porous outer surface layer (a porous lid covering the whole outer part of the core entity) (para 0029, 0031, 0034), wherein the interior part is in the form of agarose (para 0085), which carries a ligand structure (para 0027) such as hydrocarbon hydrophobic interaction ligands (para 0052, 0053), the outer surface layer is made of agarose (a porous hydrophilic lid, a non-binding lid) and/or dextran (a hydrogel, further decrease and adjust the pore size to prevent high molecular weight molecules from entering the pores) (para 0094, 0096), the interior part has pores with molecular cut-off values that are the same as pores in the outer surface layer, or has pores that are larger or smaller than these pores (the lid only allows molecules under a certain size to penetrate and interact with the internal part of the core entity of the separation medium) (para 0031), and substances to be separated using said separation medium are DNA including fragments (the average molecular weight of a nucleotide pair in DNA is 660 daltons, p.2 of Mahoney, allows adsorption of low molecular weight molecules or small size molecules at low ionic strength 0-1M in the pH interval 2-11) and/or viruses (para 0045).
Belew does not teach the separation medium wherein the hydrophobic interaction ligands are octylamine (claim 1), and a ligand density of the hydrophobic interaction ligands is greater than 90 μmol/mL (claim 3).
However, Belew does teach the separation medium comprises hydrophobic octyl ligands (hydrophobic interaction ligands) (0053, 0081), wherein the outer surface layer only allows molecules under a certain size to penetrate and interact with the interior part of the separation medium (para 0031, 0045). Octylamine teaches that octylamine ligands (a ligand density is greater than 90 μmol/mL) interact strongly with impurities over a wide range of pH and salt concentrations (p.5 col right – para 2).
Thus, at the time of the claimed invention, it would have been obvious to one of ordinary skill in the art to incorporate octylamine ligands as hydrophobic octyl ligands, since Belew discloses a separation medium comprises hydrophobic octyl ligands, and Octylamine discloses that octylamine ligands, hydrophobic octyl ligands, interact strongly with impurities over a wide range of pH and salt concentrations. Moreover, at the time of the claimed invention, one of ordinary skill in the art would have been motivated by the cited reference to incorporate octylamine ligands as hydrophobic octyl ligands with a reasonable expectation for successfully obtaining a separation medium.
Claim 4 is regarded as intended use limitation. The claiming of a new use, function or unknown property does not necessarily make the composition patentable. The intended use of the claimed composition does not patentably distinguish the composition, per se, since such undisclosed use is inherent in the reference composition. In order to be limiting, the intended use must create a structural difference between the claimed composition and the composition of the prior art. In the instant case, the intended use fails to create a structural difference, thus, the intended use is not limiting. Please note that when applicant claims a composition in terms of function, and the composition of the prior art appears to be the same, the Examiner may make rejections under both 35 U.S.C 102 and 103. (MPEP 2112)
References cited above do not teach the separation medium wherein the lid or core entity is functionalized by layer activation (claim 11).
However, Belew does teach that the separation medium comprises an interior part that is made of agarose, which carries a hydrophobic ligand structure, and a porous outer surface layer (the lid or core entity is functionalized by layer activation, as disclosed on page 8 line 21-23 of the instant specification). Furthermore, Belew does teach that two or more different ligands are introduced into the interior part such as anion exchange ligands (para 0052, 0053, 0090), wherein anion exchange ligands exhibit an increased elution ionic strength (para 0075).
Thus, at the time of the claimed invention, it would have been obvious to one of ordinary skill in the art to include anion exchange ligands that exhibit an increased elution ionic strength. Moreover, at the time of the claimed invention, one of ordinary skill in the art would have been motivated by the cited reference to include anion exchange ligands that exhibit an increased elution ionic strength, with a reasonable expectation for successfully obtaining a separation medium.
Claim 10 is are rejected under 35 U.S.C. 103(a) as being unpatentable over Belew et al (US 2005/0267295 A1; 12/1/2005. Cited on IDS) in view of Octylamine (gelifesciences.com. 2008;1-18. Cited on IDS), as evidenced by Mahoney (Newton’s Home Page. 2003;1-2. Cited on IDS) as applied to claims 1, 3-5, 8-9, and 11 above, further in view of Bruker Daltonics (www.care-bdal.com. 2006;1-6. Cited on IDS).
References cited above do not teach the separation medium wherein magnetic particles are incorporated into the core entity (claim 10).
Bruker Daltonics teaches purification kits MB-HIC (Magnetic Beads based Hydrophobic Interaction Chromatography) based on super-paramagnetic microparticles with a highly porous surface functionalized with hydrophobic coatings (p.1 para 2), wherein the MB-HIC kit (C8) is an ideal tool for purification of peptides and protein digests (p.3 para 3).
Thus, at the time of the claimed invention, it would have been obvious to one of ordinary skill in the art to incorporate super-paramagnetic microparticles (magnetic particles) into the interior part (core entity) of Belew, since the separation medium of Belew is used for purifying substances such as polypeptide and protein (Abstract, para 0044), and Bruker Daltonics discloses that the MB-HIC kit (C8) is an ideal tool for purification of peptides and protein digests. Moreover, at the time of the claimed invention, one of ordinary skill in the art would have been motivated by the cited reference to incorporate super-paramagnetic microparticles (magnetic particles) into the interior part (core entity) of the separation medium of Belew with a reasonable expectation for successfully obtaining a separation medium.
Claims 12-13 are rejected under 35 U.S.C. 103(a) as being unpatentable over Belew et al (US 2005/0267295 A1; 12/1/2005. Cited on IDS) in view of Octylamine (gelifesciences.com. 2008;1-18. Cited on IDS), as evidenced by Mahoney (Newton’s Home Page. 2003;1-2. Cited on IDS) as applied to claims 1, 3-5, 8-9, and 11 above, further in view of Maa et al (Journal of Chromatography. 1988;452:331-345. Cited on IDS).
References cited above do not teach the separation medium is mixed with chromatography media such as a cation exchange media as well as the claimed separation medium concentration (claims 12-13).
However, Belew does teach that additional purification steps may involve adsorption/desorption of substances to/from a cation exchanger (para 0105). Maa teaches mixed-bed ion-exchange columns (e.g., cation exchangers) for protein high-performance liquid chromatography (Title), wherein important applications for mixed-sorbent columns are expected to be found in the burgeoning field of preparative chromatography (p.342 para 5). This approach not only permits the manipulation of selectivity for separation of the desired product but also make the use of difficult-to-remove mobile phase additives superfluous (p.342 para 5).
Thus, at the time of the claimed invention, it would have been obvious to one of ordinary skill in the art to mix a separation medium with a cation exchange media as well as to optimize the separation medium concentration, since Maa discloses that mixed-bed ion-exchange columns offer certain advantages in displacement and in other non-linear chromatographic techniques (p.342 para 5). Moreover, at the time of the claimed invention, it would have been within the purview of one of ordinary skill in the art to mix a separation medium with a cation exchange media as well as to optimize the separation medium concentration with a reasonable expectation of success.
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 claims at issue 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); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 3-5 and 8-13 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-6 of U.S. Patent No 11,439,926 B2 (referred to as the ‘926 patent) in view of Maa et al (Journal of Chromatography. 1988;452:331-345. Cited on IDS).
Claims 1-6 of the ‘926 patent recite an agarose-based separation medium, comprising a hydrophobic porous core entity with octylamine ligands having a ligand density of greater than 90 μmole/mL, and a porous hydrophilic lid (a non-binding lid) covering the whole outer part of the core entity, wherein the lid only allows molecules under 60,000D to penetrate and absorb onto the hydrophobic octyl ligands of said core entity of the separation medium, wherein the hydrophobic core entity allows adsorption of molecules under 60,000D at low ionic strength 0-1M in the pH interval 2-11, wherein magnetic particles are incorporated into the core entity, wherein a dextran hydrogel is provided in the lid to fill the pores of the lid and thereby further decrease and adjust the pore size of the lid, and wherein at least one of the lid and core entity are functionalized by layer activation.
Claim 4 is regarded as intended use limitation. The claiming of a new use, function or unknown property does not necessarily make the composition patentable. The intended use of the claimed composition does not patentably distinguish the composition, per se, since such undisclosed use is inherent in the reference composition. In order to be limiting, the intended use must create a structural difference between the claimed composition and the composition of the prior art. In the instant case, the intended use fails to create a structural difference, thus, the intended use is not limiting. Please note that when applicant claims a composition in terms of function, and the composition of the prior art appears to be the same, the Examiner may make rejections under both 35 U.S.C 102 and 103. (MPEP 2112)
The ‘926 patent does not teach the separation medium is mixed with chromatography media such as a cation exchange media as well as the claimed separation medium concentration (claims 12-13).
Maa teaches mixed-bed ion-exchange columns (e.g., cation exchangers) for protein high-performance liquid chromatography (Title), wherein important applications for mixed-sorbent columns are expected to be found in the burgeoning field of preparative chromatography (p.342 para 5). This approach not only permits the manipulation of selectivity for separation of the desired product but also make the use of difficult-to-remove mobile phase additives superfluous (p.342 para 5).
Thus, at the time of the claimed invention, it would have been obvious to one of ordinary skill in the art to mix a separation medium with a cation exchange media as well as to optimize the separation medium concentration, since Maa discloses that mixed-bed ion-exchange columns offer certain advantages in displacement and in other non-linear chromatographic techniques (p.342 para 5). Moreover, at the time of the claimed invention, it would have been within the purview of one of ordinary skill in the art to mix a separation medium with a cation exchange media as well as to optimize the separation medium concentration with a reasonable expectation of success.
Claims 1, 3-5 and 8-13 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-11 of U.S. Patent No 10,493,380 B2 (referred to as the ‘380 patent).
Claims 1-11 of the ‘380 patent recite a method for separating at least one target substance from a sample, the method comprising, applying a sample comprising at least one target substance onto an agarose based separation medium, wherein the at least one target substance is selected from a virus and an antibody, and wherein said separation medium comprises a porous core entity functionalized with hydrophobic octylamine ligands having a ligand density of greater than 90 μmole/mL, and a porous hydrophilic lid (a non-binding lid) covering the core entity (the lid or core entity is functionalized by layer activation), allowing molecules having a size of <60,000 D from the sample to penetrate the hydrophilic lid and absorb onto-the hydrophobic octylamine ligands of said core entity of the separation medium to remove these molecules from the sample, and obtaining said target substance in a flow-through fraction of the sample. The sample comprises at least one of DNA and proteins which absorb onto said hydrophobic octylamine ligands in the core entity of the separation medium and are separated from said target substance in the flow-through fraction of the sample, and the sample comprises host cell proteins (allows adsorption of low molecular weight molecules or small size molecules at low ionic strength 0-1M in the pH interval 2-11). The method further comprises providing a hydrogel to said lid, wherein said hydrogel fills pores within said lid, thereby further decreasing and adjusting the size of said pores to prevent high molecular weight target substance from entering said pores. Magnetic particles are incorporated into said core entity. The separation medium is mixed with a cation exchange chromatography media and said separation medium comprises up to 10% of the total volume of the combined separation medium and the chromatography media.
Response to Arguments
Applicant argues that Claim 1 has been amended to clarify further that the recited separation medium includes a hydrophilic matrix that includes agarose, which is made hydrophobic by the ligands. This configuration is the opposite of Belew’s configuration, as explained in the record, especially at pages 4-5 of the Appeal Brief filed February 21, 2025. Belew does not teach or suggest the “hydrophobic core entity” recited by the Applicant's amended Claim 1.
These arguments are not found persuasive because Belew does teach a separation medium comprising an interior part which carries a ligand structure (para 0025-0027) such as hydrocarbon hydrophobic interaction ligands (para 0052, 0053), wherein the interior part is preferably hydrophilic and in the form of a polymer, suitable polymers include agarose (para 0085), and wherein the ligand structure comprises hydrocarbon groups, e.g., C1-10 (para 0053). Since the cut-off is not clearly defined in the original disclosure, the core entity of Belew read on the claimed core entity. In addition, Belew does teach the separation medium comprises hydrophobic octyl ligands, and Octylamine does teach that octylamine ligands, hydrophobic octyl ligands, interact strongly with impurities over a wide range of pH and salt concentrations. Thus, at the time of the claimed invention, a skill in the art would have been motivated by the cited reference to incorporate octylamine ligands as hydrophobic octyl ligands with a reasonable expectation for successfully obtaining a separation medium. Finally, a patent owner or applicant may be precluded from seeking a claim that is not patentably distinct from a claim that was previously rejected if the rejection was affirmed on appeal and the decision on appeal became final. This rejection is very similar to the one that the board is found valid. (MPEP 2190 II).
Conclusion
No claims are allowed.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN Y FAN whose telephone number is (571)270-3541. The examiner can normally be reached on M-F 7am-4pm.
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, Curtis Mayes can be reached on (571)272-1234. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Lynn Y Fan/
Primary Examiner, Art Unit 1759
Prosecution Insights