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 .
DETAILED ACTION
Election/Restrictions
1. Applicant's election of Group I, claims 1-7, 13, and 15, without traverse, filed June 10, 2026 is acknowledged and has been entered. Claims 8-12 and 14 are withdrawn from further consideration by the examiner, 34 CFR 1.142(b), as being claims drawn to a non-elected invention. Accordingly, claims 1-15 are pending. Claims 1-7, 13, and 15 are under examination.
Priority
2. Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d), which papers have been placed of record in the file.
3. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) and/or foreign priority under 35 U.S.C. 119 (a)-(d) or (f), 365(a) or (b) or 386(a) is acknowledged. This application is a divisional of U.S. Patent Application 17/758,412 filed 07/06/2022, now US Patent 11/965/882, which is a 371 National Stage Application of PCT/EP2021/052331 filed 02/01/2021, which claims the benefit of Foreign Application European Patent Office (EPO) 20154816.1 filed 01/31/2020. Based on the filing receipt, the effective filing date of this this application is January 31, 2020 which is the filing date of EPO 20154816.1 from which the benefit of foreign priority is claimed.
Claim Objections
4. Claim 1 is objected to in reciting “A method of isolating a biological entity from a sample comprising “(i), (ii), (iii), (iv), (vi), (vii), (viii), and (ix).” It appears that (v) is missing. It should recite “(i), (ii), (iii), (iv), (v), (vi), (vii), and (viii)” to be in proper numerical order. Alternatively, if step “(v)” was inadvertently missed; it appears that the missing step should be incorporated into the claim set to recite “(i), (ii), (iii), (iv), (v), (vi), (vii), (viii), and (ix).” Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
5. Claims 1-7, 13, and 15 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1, in steps (i) and (ii), is ambiguous in reciting “the biological entity comprises a surface antigen (2)” in step (i), and “a linking molecule comprising an antigen (2’)” in step (ii) because it is unclear what is encompassed in the surface “antigen (2)” in step (i) relative to the “antigen (2’)” in step (ii). In particular, it is unclear what essential structural or molecular and functional cooperative relationship exists between the “surface antigen (2)” comprised in the biological entity of step (i) and the antigen(2’) comprised in the linking molecule of step (ii).
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance:
claim 1, step (ii) recites the broad recitation “a component for a non-covalent protein-ligand interaction;” and the claim also recites “preferably wherein the component is a ligand” which is the narrower statement of the range/limitation.
claim 1, step (iii) recites the broad recitation “tagging agents each comprising at least one binding domain …,” and the claim also recites “preferably wherein the tagging agents further comprise a component for non-covalent protein-ligand interaction” which is the narrower statement of the range/limitation; and the claim further recites “preferably wherein the component is a ligand” which is a further narrower statement of the range/limitation.
claim 1, step (iv) recites the broad recitation “at least two components for non-covalent protein-ligand interactions” and the claim further recites “preferably wherein the components are ligand binding partners” which is a further narrower statement of the range/limitation.
claim 1, step (vi) recites the broad recitation “a component capable of forming a protein-ligand interaction” and the claim further recites “preferably wherein the component is a ligand binding partner” which is a further narrower statement of the range/limitation.
The claim is considered indefinite because there is a question or doubt as to whether the features introduced by such narrower language in all occurrences of the claim, are (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) required features of the claim.
Claim 1, step (iii) is vague and indefinite in reciting “at least two tagging agents each comprising at least one binding domain capable of specifically binding to the antigen (2) on the biological entity OR the antigen (2’) comprised in the linking molecule” because it is unclear how the biological entity from the sample can be isolated if the binding domain of each of the at least two tagging agents binds only the antigen (2) on the biological entity or the antigen (2’) comprised in the linking molecule, encompassed in the claimed invention. It appears that the binding domain of one of the two tagging agents should bind the antigen (2) on the biological entity and the binding domain of the other of the two tagging agents should bind the antigen (2’) in the linking molecule.
Claim 1, step (vi) is ambiguous in reciting “providing a stationary phase comprising a component” because it is unclear what is encompassed in the recitation of “stationary phase” being that it appears to define a feature of a component rather than a structural component itself. In particular, it is unclear what structural component Applicant intends in the instant recitation of “stationary phase.” Same analogous comments and problems aforementioned apply to all occurrences of “stationary phase” in the claim.
Claim 1, step (vii) lacks antecedent basis in reciting “the beads.”
Claim 1, step (vii) is vague and indefinite in reciting “incubating the sample, linking molecule (10), tagging agents (3), carrier (11) and stationary phase within a container and allowing complex formation between the biological entity (1), the tagging agents (3), the linking molecule (10), the carrier (11) and the beads (6)” and “wherein the biological entity (1) is immobilized on the stationary phase,” because it is unclear how complexes are formed absent recitation of the “beads” which do not appear to have been recited as a provided component of the claimed invention in claim 1. As such, it is therefore unclear how the biological entity can be immobilized, as claimed.
Claim 1, step (viii) is also vague and indefinite in reciting “purifying the biological entity (1) by a chromatographic procedure; and/or (ix) isolating the biological entity (1) by releasing the biological entity (1) from the carrier (11) and the tagging agent (3), respectively“ because it is unclear how the biological entity can be purified by a chromatographic procedure, or otherwise, isolated if complexes have not formed absent recitation of the “beads” supra which are not recited as required components in claim 1.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desir0ed. See MPEP § 2173.05(c). In the present instance,
claim 2 recites the broad recitation “the ligand binding partners comprise streptavidin or a functional analog thereof… and the ligand comprises a streptavidin binding peptide,” and the claim also recites “preferably, wherein the ligand binding partner is StrepTactin and the ligand is Strep-Tag” which is the narrower statement of the range/limitation.
The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. See also claim 15.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance,
claim 6 recites the broad recitation “a body fluid” and the claim also recites “preferably blood or umbilical cord blood” which is the narrower statement of the range/limitation.
claim 6 also recites the broad recitation “a cell, nucleus or a membrane,” and the claim also recites “preferably a cell-derived membrane vesicle” which is the narrower statement of the range/limitation; and the claim further recites “more preferably an exosome” which is an even further narrower statement of the range/limitation.
The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 13 is indefinite in reciting “A kit for use in the method of claim 1, the kit comprising a tagging agent” because it is unclear how the method which requires “at least two tagging agents” can be performed using only one tagging agent in the kit.
Claim 13 is indefinite in lacking clear antecedent basis in reciting “the kit comprising … beads” because claim 1 does not appear to recite providing beads as a structural component of the claimed method.
Claim 13 lacks clear antecedent basis in reciting “further ligand” because claim 1 does not appear to recite “further ligand” in the claimed method.
Claim 13 lacks clear antecedent basis in reciting “further ligand binding partner” because claim 1 does not appear to recite “further ligand binding partner” in the claimed method.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
6. Claims 1-7, 13, and 15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, and 7-19 of U.S. Patent No. 11,965,882. Although the claims at issue are not identical, they are not patentably distinct from each other because both inventions recite a method of isolating a biological entity from a sample comprising: (i) providing a sample comprising the biological entity (1), wherein the biological entity (1) comprises a surface antigen (2); (ii) providing a linking molecule (10) comprising an antigen (2′) and a ligand (5), wherein the antigen (2′) is capable of specifically binding to a binding domain (4) of a second tagging agent (3) via a second antigen recognition interaction (9); (iii) providing at least two tagging agents (3), each comprising at least one binding domain (4) and a ligand (5), wherein a binding domain (4) of a first tagging agent (3) is capable of specifically binding to the surface antigen (2) on the biological entity (1) via a first antigen recognition interaction (9) and a binding domain (4) of the second tagging agent (3) is capable of specifically binding to the antigen (2’) comprised in the linking molecule (10); (iv) providing a carrier (11) comprising at least two components which comprise a first ligand binding partner (7) and a second ligand binding partner (7); wherein the first ligand binding partner (7) is capable of forming a first non-covalent protein-ligand interaction (8) with the ligand (5) of the first tagging agent (3) and the second ligand binding partner (7) is capable of forming a second non-covalent protein-ligand interaction (8) with the ligand (5) of the second tagging agent (3); (v) providing freely movable non-magnetic beads (6) which comprise a third ligand binding partner (7) capable of forming a third non-covalent protein-ligand interaction (8) with the ligand (5) of the linking molecule (10); (vi) incubating the sample, the at least two tagging agents (3), the carrier (11), the linking molecule (10) and the beads (6) within a container and allowing complex formation between corresponding components to occur to form complexes: between the biological entity (1) surface antigen (2) and the binding domain (4) of the first tagging agent (3) in a first antigen recognition interaction (9), the carrier (11) first ligand binding partner (7) and the ligand (5) of the first tagging agent (3) to immobilize the first tagging agent (3) to the carrier (11) in a first non-covalent protein-ligand interaction (8), the carrier (11) second ligand binding partner (7) and the ligand (5) of the second tagging agent (3) to immobilize the second tagging agent (3) to the carrier (11) in a second non-covalent protein-ligand interaction (8), the linking molecule (10) antigen (2’) and the binding domain of the second tagging agent (3) in a second antigen recognition interaction (9), and the beads (6) third ligand binding partner (7) and the ligand (5) of the linking molecule (10) to immobilize the linking molecule (10) in a non-covalent protein-ligand interaction (8);
and, (vii) purifying the biological entity (1) by a chromatographic procedure using chromatographic matrix comprising the beads (6); and/or (viii) isolating the biological entity (1) by releasing the biological entity (1) from the beads (6) and the tagging agent (3), respectively. The ligand binding partners comprise streptavidin or Strep-Tactin and the ligand comprises a streptavidin binding peptide or Strep-Tag. The carrier is a dextran polymer having an average molecular weight of 3,000 kDa. Both inventions recite incorporating the tagging agents, the carrier, the linking molecule, and ligand binding partners, beads, and washing buffers into a kit format.
Prior Art
7. Claims 1-7, 13, and 15 are free of the prior art of record. The prior art of record fails to teach or fairly suggest a method of isolating a biological entity (cell) from a sample comprising:
I. obtaining A) a cell sample comprising cells expressing a specific target surface antigen; B) a linking molecule (10) comprising a ligand (5) and a recombinant antigen (2′) that specifically binds to a binding domain (4) of a second tagging agent (3) via a second antigen recognition interaction (9); C) at least two tagging agents (3) each comprising a binding domain (4) and a ligand (5): Ci) a first tagging agent (3) having a binding domain (4) that specifically binds to the target surface antigen (2) on the cell via a first antigen recognition interaction (9) and Cii) a second tagging agent (3) having a binding domain (4) that specifically binds to the recombinant antigen (2’) comprised in the linking molecule (10); D) a carrier (11) which comprises a first ligand binding partner (7) that binds to a ligand (5) of the first tagging agent (3) in a first non-covalent protein-ligand interaction (8), and a second ligand binding partner (7) that binds to a ligand (5) of the second tagging agent (3) in a second non-covalent protein-ligand interaction (8); and, E) freely movable non-magnetic beads (6) which comprise a third ligand binding partner (7) that binds with the ligand (5) of the linking molecule (10) in a third non-covalent protein-ligand interaction (8);
II. incubating the sample, the two tagging agents (3), the carrier (11), the linking molecule (10) and the beads (6) within a container to allow complex formation between the cell (1) target surface antigen (2) and the binding domain (4) of the first tagging agent (3) in a first antigen recognition interaction (9), complex formation between the ligand (5) of the first tagging agent and the carrier (11)-immobilized first ligand binding partner (7) in a first non-covalent protein-ligand interaction (8), complex formation between the recombinant antigen (2’) in the linking molecule (10) and the binding domain (4) of the second tagging agent (3) in a second antigen recognition interaction (9), complex formation between the ligand (5) of the second tagging agent and the carrier (11)-immobilized second ligand binding partner (7) in a second non-covalent protein-ligand interaction (8)- the linking molecule (10) specifically bound to the second tagging agent (3) via the recombinant antigen (2’) in the linking molecule and the binding domain of the second tagging agent (3), and complex formation between the bead (6)-immobilized third ligand binding partner (7) and the ligand (5) of the linking molecule (10) in a non-covalent protein-ligand interaction (8); and,
III. purifying the cell (1) using a chromatographic matrix comprising the beads (6) by chromatographic procedure; and/or isolating the cells (1) by releasing them from the beads (6) and the tagging agent (3), respectively; wherein the ligand binding partners comprise streptavidin or Strep-Tactin; the ligands comprise streptavidin binding peptides or Strep-Tag; and the carrier is a dextran polymer having an average molecular weight of 3,000 kDa. See Figure 7.
Closest Prior Art
8. Schaeffer et al. (US 2003/0119070) discloses a method of selecting a cell from a sample by contacting the cell with a peptide-ligand conjugate which comprises a first ligand having a binding domain for the cell in the sample that is conjugated to a peptide that displaces a second ligand specific for the peptide to form a cell-conjugate complex; contacting the peptide-ligand conjugate with the second ligand; and isolating the cell-conjugate complex (Abstract; Figure 1A, 1B).
9. No claims are allowed.
Remarks
10. Prior art made of record are not relied upon but considered pertinent to the applicants' disclosure:
Schmidt et al. (The Strep-tag system for one-step purification and high-affinity detection or capturing of proteins. Nature Protocols 2 (6): 1528-1535 (2007)) teach the Strep-tag II consisting of an eight-residue minimal peptide sequence (WRHPQFGG) that exhibits intrinsic affinity toward streptavidin which can be fused to recombinant proteins in various fashions for use in quick and mild purification of Strep-tag II fusion proteins (Abstract).
Korndorfer et al. (Improved affinity of engineered streptavidin for the Strep-tag II peptide is due to a fixed open conformation of the lid-like loop of the binding site. Protein Science 11: 883-893 (2002)) teach the Strep-tag II consisting of an 9 amino acid peptide (AWRHPQFGG) that was developed as an affinity tool for the purification of Strep-tag II fusion proteins on streptavidin columns (Abstract).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GAILENE R. GABEL whose telephone number is (571)272-0820. The examiner can normally be reached Monday, Tuesday, and Thursday 5:30 AM to 4:00 PM.
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/GAILENE GABEL/Primary Examiner, Art Unit 1678
June 23, 2026
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