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 .
Status of the Claims
Claims 1, 4-5, 10-22, and 28-30 are currently pending.
Claims 1 and 10-13 are amended.
Claims 16-22 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.
Claims 2-3, 6-9, and 23-27 are cancelled.
Claims 28-30 are newly added.
Claims 1, 4-5, 10-15, and 28-30 have been considered on the merits.
Withdrawn Rejections
The rejections made onto claims 1-7, 11, and 13-14 under 35 U.S.C. 102 are withdrawn in light of the amendments made on 08/31/2026.
The 35 U.S.C. 103 rejection made employing Zhou et al (US20180078624 A1) has been withdrawn in light of the cancellation of claims 8-9 on 08/31/2026.
New Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 103
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 1, 4-5, 10-11, 13-14, and 28-30 are rejected under 35 U.S.C. 103 as being unpatentable over Thomas et al (US20030092078 A1), in view of Liu et al (Blood 2021, Annual Meeting Abstracts “Single B Cell Immunoglobulin Sequencing Identifies Distinct Features of Monoclonal Antibodies in Patients with Immune Thrombotic Thrombocytoepenic Purpura”).
With regards to claim 1, Thomas teaches a method of isolating and removing a subset of target cells from a whole blood sample ([0017]). Thomas teaches adding a fusion protein comprising a first binding domain, a linker, and a second binding domain ([0017]/[0054]/[0055]/[0099]) wherein the first binding domain is specific for RBCs and the second binding domain is specific for a cell surface antigen expressed on a target blood cell (claim 66 of Thomas and [0044]). Thomas also teaches example 5 which demonstrates centrifuging the blood sample to produce a pellet comprising target cells bound to RBCs ([0102]-[0103]). Thomas teaches that the RBC and target cells have been removed from the blood cells remaining in the supernatant and that the target cells are isolated in the RBC pellet ([0102]-[0103]). Thomas teaches that the target cell is not an RBC and that the target cell is any desired cell type including immune cells such as B cells ([0032]). Thomas teaches that target blood cells are removed from the whole blood ([0017]).
Regarding claims 4 and 5, Thomas teaches that the RBC antigen is glycophorin A (claim 66 of Thomas and [0044]).
Regarding claim 11, Thomas teaches wherein the linker is covalently bound, which is being interpreted to meet the limitation of stable ([0054]).
Regarding claim 13 and 14, Thomas teaches that the target cells are further separated from the RBCs from lysing the RBCs ([0104]).
Thomas does not specifically teach that the method is applied specifically to autoimmune antigen-specific B cells as required by claim 1, however Thomas does teach that their method is applicable to any cell type including B cells ([0032]). Thomas does not specifically teach that the whole blood sample is derived from a patient having a B-cell mediated autoimmune disease as required by claim 1. Thomas does not teach that the second binding domain comprises a B cell autoantigen as required by claim 10. Thomas does not teach that the B cell autoantigen is ADAMTS13 as required by claim 28. Thomas does not teach that the B cell mediated autoimmune disease is immune thrombotic thrombocytopenia purpura (iTTP), systemic lupus erythematosus, myasthenia gravis, or autoimmune hemolytic anemia as required by claim 29. Thomas does not teach that the B cell mediated autoimmune disease is iTTP as required by claim 30.
However, Liu teaches a method of isolating B cells from patient’s blood samples with iTTP using the autoimmune antigen ADAMTS13 (abstract).
Regarding claim 1, Liu teaches the isolation of autoimmune antigen-specific B cells from a peripheral blood mononuclear cells (PBMCs) from a whole blood sample of a patient having a B cell-mediated autoimmune disease (abstract, Results).
Regarding claim 10, Liu teaches that a binding domain to obtain patient B cells is a B cell autoantigen, ADAMTS13 (Results).
Regarding claim 28, Liu teaches that the B cell autoantigen is ADAMTS13 (Results).
Regarding claims 29-30, Liu teaches that the B cell mediated autoimmune disease is immune thrombotic thrombocytopenia purpura (iTTP) (abstract, results).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the method of Thomas including isolating and enriching a desired cell population by effectively capturing the desired cell population using a fusion protein which links the desired cells to RBCs/erythrocytes with the method of isolating autoimmune B cells using the B cell autoantigen ADAMTS13 as taught by Liu to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Thomas teaches the method of isolating cells from a whole blood sample is applicable to any desired cell type, and explicitly teaches the application of the method on B cells ([0004] and [0108]), additionally, Liu teaches an effective B cell autoantigen to isolate autoimmune antigen-specific B cells using blood samples derived from patients having a B cell-mediated autoimmune disease is ADAMTS13 (Abstract, results). Thus, it would be obvious to apply the method of Thomas to a desired cell population using the explicit teachings of Liu that autoimmune antigen-specific B cells are effectively isolated using the B cell autoantigen ADAMTS13. One of ordinary skill in the art would have a reasonable expectation of success when combining Thomas and Liu because Thomas teaches all necessary information to perform the method on a desired immune cell type ([0004] and [[0108]) and Liu provides the necessary information to isolate autoimmune antigen-specific B cells with the ADAMTS13 B cell autoantigen.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 12 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Thomas et al (US20030092078 A1), in view of Liu et al (Blood 2021, Annual Meeting Abstracts “Single B Cell Immunoglobulin Sequencing Identifies Distinct Features of Monoclonal Antibodies in Patients with Immune Thrombotic Thrombocytoepenic Purpura”), as applied to claims 1, 4-5, 10-11, 13-14, and 28-30, and in view of Zhou et al (US20120321626A1).
With regards to claims 12 and 15, the limitations of the independent claim 1 are taught above.
Thomas and Liu do not teach that the linker is cleavable as required by claim 12.
Regarding claim 15, Thomas does teach the steps of resuspending the pellet, and centrifuging the suspension containing RBC and target cells, whereby the RBCs are pelleted as described in the 103 rejection presented above however, the specific step of the linker having been cleaved which is required by claim 15 is not disclosed in Thomas.
However, Zhou teaches about multi-specific fab fusion proteins and methods of use (abstract).
Regarding claim 12, Zhou 2 teaches that the fusion protein contains a cleavable linker and that a well known peptide sequence of PLGLAG in a substrate can be cleaved ([0184]).
Regarding claim 15, as described above, Thomas teaches all the steps of claim 15 besides cleaving the linker. Thomas teaches example 5 which demonstrates centrifuging the blood sample to produce a pellet comprising target cells bound to RBCs ([0102]-[0103]). Thomas teaches that the RBC and target cells have been removed from the blood cells remaining in the supernatant and that the target cells are isolated in the RBC pellet ([0102]-[0103]). Thomas also teaches an embodiment wherein the target cells are left remaining in the supernatant (Example 4, [0089]). Zhou teaches a fusion protein which can be cleaved. Cleaving the fusion protein of Thomas would result in the desired/target cells be left behind in the supernatant during the re-centrifugation step which is a desirable outcome as described by Example 4 of Thomas.
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the method of Thomas with the cleavable linker taught by Zhou to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Thomas teaches the separation of immune cells in general employing the instant method and Zhou teaches that the fusion proteins of the invention allow for selectivity and specificity in a controlled manner (abstract). One of ordinary skill in the art would have a reasonable expectation of success when combining Thomas and Zhou because Thomas teaches all necessary information to perform the method and Zhou provides the necessary information to use a cleavable linker.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant’s arguments, see Remarks, filed 08/31/2026, with respect to the rejection(s) the claims under 35 U.S.C. 103 have been fully considered and are persuasive. Applicant argues that Thomas and Zhou ‘626 do not teach the newly amended limitations of claim 1. Therefore, the rejection has been withdrawn. However, upon further consideration, two new ground(s) of rejections are made relying on Thomas in view of Liu and Thomas in view of Liu and in further view of Zhou.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CONSTANTINA E STAVROU whose telephone number is (571)272-9899. The examiner can normally be reached M-F 8:00-5:00.
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CONSTANTINA E. STAVROU
Examiner
Art Unit 1632
/TITILAYO MOLOYE/Primary Examiner, Art Unit 1632
