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
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Claims 1, 4-9, 11, 13, 15, 17-18, and 20-25 have an effective filing date of 08 NOV 2018.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 9/24/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Election/Restrictions
In the response filed on 5/22/2024, Applicant elected, with traverse:
The treatment combination of clazakizumab, plasmapheresis, IVIG, valganciclovir, fluconazole, alemtuzumab, tacrolimus, mycophenolate mofetil, and prednisone;
The kidney;
Clazakizumab administered subcutaneously at an average dose of about 20-30 mg/month for 1-6 months prior to transplantation and at least 12 times after transplantation (see claim 11);
Combination of the following markers assayed for in blood: anti-HLA donor-specific antibody (DSA), serum creatinine, C-reactive protein (CRP), Treg cells, T-follicular helper (Tfh) cells, Thl7 cells, B-cell, plasmablasts, and IL-6.
Status of Claims
Claim 9 is withdrawn from further examination by Examiner under 37 CFR 1.142(b) as being drawn to a non-elected invention.
Claims 1, 4-8, 11, 13, 15, 17-18, and 20-25 are currently pending and presented for examination on the merits.
Claims 2-3, 10, 12, 14, 16, and 19 are canceled.
Rejections Withdrawn
The rejection filed under 35 U.S.C. 103 is withdrawn in view of Applicant’s amendments to claims.
The Rejections filed under Double Patenting is withdrawn in view of Applicant’s abandonment of co-pending application 15/448,406.
New Rejections
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.
Regarding claim 17, the claim is dependent from a canceled claim, which renders the claim indefinite because the base claim no longer exists, it is unclear what limitations is incorporated into the claim. See MPEP § 608.01(n)(V).
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.
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 factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 4-8, 11, 13, 15, 18, and 20-255 are rejected under 35 U.S.C. 103 as being unpatentable over Jones et al (Interleukin-6 in renal disease and therapy, Nephrol Dial Transplant (2015) 30: 564–574), Latham et al (WO2008144757 A1), Jang et al (Application of Calculated Panel Reactive Antibody Using HLA Frequencies in Koreans, Ann Lab Med 2012;32:66-72), Bedrosian et al (WO2018195034 A1), Uehara et al (Ischemia augments alloimmune injury through IL-6-driven CD4+ alloreactivity, Scientific Reports, 8:2461, 2018), and further in view of Vo et al (A Phase I/II Trial of the Interleukin-6 Receptor Specific Humanized Monoclonal (Tocilizumab) + Intravenous Immunoglobulin in Difficult to Desensitize Patients, Transplantation 2015;99: 2356–2363, IDS 12/13/2021).
Jones et al teaches the impacts of IL-6 on transplant patients [Abstract, pg. 564]. Jones et al further teaches increased IL-6 in patients immediately post transplantation and during acute clinical rejection (AR) [Right column, 2nd Paragraph, pg. 568]. Jones et al further teaches tocilizumab, an IL-6 receptor mAb [Table 1, pg. 566]. Jones et al further teaches the IL-6 therapy clazakizumab [Right Column, 1st Paragraph, pg. 565]. Jones et al further teaches treating elevated IL-6 in a patient and returning levels back to baseline [Right column, 2nd Paragraph, pg. 568].
Jones et al does not specifically teach SEQ ID NOs: 1, 2 or 3, 4 & 5, 6, 7. However this deficiency is made up in the teachings of Latham et al.
Latham et al teaches an antibody that binds IL-6 [0039]. Latham et al further teaches administering the antibody subcutaneously [0286]. Latham et al further teaches administering the antibody in a dosage of 0.05-10.0 mg/kg [00284]. Latham et al further teaches an antibody comprising SEQ ID NO: 424. A comparison of instant SEQ ID NOs: 1, 2, 4 and SEQ ID NO: 424 of Latham et al is shown below.
Instant SEQ ID NOs: 1, 2, 4 and SEQ ID NO: 424 of Latham et al.
ALIGNMENT:
Query Match 86.7%; Score 158.6; Length 125;
Best Local Similarity 42.9%;
Matches 33; Conservative 0; Mismatches 0; Indels 44; Gaps 2;
Qy 1 NYYVT--------------IIYGSDETAYATWAIG------------------------- 21
||||| ||||||||||||||||
Db 49 NYYVTWVRQAPGKGLEWIGIIYGSDETAYATWAIGRFTISKTSTTVDLKMTSLTAADTAT 108
Qy 22 -----DDSSDWDAKFNL 33
||||||||||||
Db 109 YFCARDDSSDWDAKFNL 125
Latham et al further an antibody comprising SEQ ID NO: 440. A comparison of instant SEQ ID NOs: 1, 3, 4 and SEQ ID NO: 440 is shown below.
Instant SEQ ID NOs: 1, 3, 4, and SEQ ID NO: 440 of Latham et al.
ALIGNMENT:
Query Match 86.0%; Score 151.4; Length 109;
Best Local Similarity 41.8%;
Matches 33; Conservative 0; Mismatches 0; Indels 46; Gaps 2;
Qy 1 NYYVT--------------IIYGSDETAYATSAIG------------------------- 21
||||| ||||||||||||||||
Db 31 NYYVTWVRQAPGKGLEWVGIIYGSDETAYATSAIGRFTISRDNSKNTLYLQMNSLRAEDT 90
Qy 22 -------DDSSDWDAKFNL 33
||||||||||||
Db 91 AVYYCARDDSSDWDAKFNL 109
Latham et al further teaches SEQ ID NO: 441. A comparison of instant SEQ ID NOs: 5, 5, 7, and SEQ ID NO: 441 is sown below.
Instant SEQ ID NOs: 5, 6, 7, and SEQ ID NO: 441 of Latham et al.
ALIGNMENT:
Query Match 82.7%; Score 118.3; Length 99;
Best Local Similarity 39.0%;
Matches 30; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 QASQSINNELS---------------RASTLAS--------------------------- 18
||||||||||| |||||||
Db 23 QASQSINNELSWYQQKPGKAPKLLIYRASTLASGVPSRFSGSGSGTDFTLTISSLQPDDF 82
Qy 19 -----QQGYSLRNIDNA 30
||||||||||||
Db 83 ATYYCQQGYSLRNIDNA 99
Jones et al does not specifically teach combination therapies. However, this deficiency is made up in the teachings of Bedrosian et al.
Bedrosian et al teaches methods of reducing antibody mediated rejection in human kidney transplants [Abstract]. Bedrosian et al further teaches methods to sensitize human before the kidney transplant [Line 3, pg. 3]. Bedrosian et al further teaches the desensitization therapy IVIG and plasmapheresis [Line 8, pg. 3]. Bedrosian et al further teaches methods to screen humans for infections [Line 17, pg. 41]. Bedrosian et al further teaches the IVIG and plasmapheresis is administered prior to transplantation [Line 8, pg. 49]. Bedrosian et al further teaches the use of alemtuzumab after transplantation [Line 21, pg. 71]. Bedrosian et al further teaches the use of tacrolimus, mycophenolate mofetil, and prednisone [Line 2, pg. 71]. Bedrosian et al further teaches panel reactive antibodies [Line 27, pg. 1]. Bedrosian et al further teaches using GFR to measure how well the kidneys are working [Line 22, pg. 18].
Jones et al does not specifically teach using the calculated panel reactive antibodies. However, this deficiency is made up in the teachings of Jang et al.
Jang et al teaches the use of a calculated panel of reactive antibodies [Abstract, pg. 66]. Jang et al further teaches sensitized patients with cPRA of > 50% [Left 1st Paragraph, pg. 71]. Jang et al further teaches in sera with 80-100% cPRA, 91.7% and 94.4% of the samples had concordant results (80-100% PRA) in the PRA-screen and PRA-ID assay, respectively [Abstract].
Jones et al does not specifically teach administering clazakizumab before a solid organ transplant. However, this deficiency is made up in the teachings of Uehara et al.
Uehara et al teaches reduced IL-6 in donor transplants had significantly prolonged survival when transplanted [1st paragraph, pg. 10]. Uehara et al further teaches the absence or blockade of IL-6 was associated with a significant reduction in chronic rejections [1st paragraph, pg. 10].
Jones et al does not specifically teach administering an IL-6 inhibitor before transplantation. However, this deficiency is made up in the teachings of Vo et al.
Vo et al teaches the use of anti-IL-6 antibody tocilizumab [Abstract]. Vo et al further teaches attempting to reduce HLA antibody levels (donor specific antibody) in patients awaiting kidney transplant [Right column, pg. 2356]. Vo et al further teaches a major barrier to successful transplantation is performed anti-HLA antibodies [Left column, pg. 2356]. Vo et al further teaches patients were administered tocilizumab at 8mg/kg on day 15, and the monthly for 6 months [Abstract]. Vo et al further teaches if transplanted patients received tocilizumab monthly for 6 months [Abstract]. Vo et al further teaches a significant reduction in donor specific antibodies (DSA) number and strength were seen at transplant [Figure 2B, pg. 2360].
With regard to antibody dosage and frequency, the amount and frequency of the antibody is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient needed to achieve the desired results. Thus, absent some demonstration of unexpected results from the claimed parameters, the optimization of ingredient amounts would have been obvious at the time of applicant's invention.
The principle of law states from MPEP 2144.05: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."(Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382); Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[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).
One of ordinary skill, before the effective filing date, would have been motivated to combine Jones’s method of treating elevated IL-6 in patients after transplantation, with Latham’s method of administering IL-6 antibody comprising SEQ ID NOs: 424, 440, and 441 subcutaneously, with Bedrosian’s method of reducing antibody mediated rejection in kidney transplant patients, with Uehara’s method of eliminating/blocking IL-6 prior to transplantation to reduce transplant rejection, with Vo’s method of administering an anti-IL-6 antibody before transplantation. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to combine the methods of Jones, Latham, Bedrosian, and Vo’s for a method of reducing or eliminating donor-specific antibody in a HLA-sensitized human subject before receiving a kidney transplant, because the prior art teaches clazakizumab as targeting IL-6, tocilizumab for treating IL-6 in disease and Il-6 as blocking therapy in transplantation. It would have been obvious to substitute clazakizumab for tocilizumab to treat transplantation related increases in IL-6. Treatment of subjects who have undergone a solid organ transplant with clazakizumab would be a predictable use of the prior art elements according to their established functions. Furthermore, combining known treatment for reducing antibody mediated rejections in transplant patients to yield predictable results is an exemplary rationale for a prima facie case of obviousness.
Claims 1, 4-8, 11, 13, 15, and 18-25 are rejected under 35 U.S.C. 103 as being unpatentable over Jones et al (Interleukin-6 in renal disease and therapy, Nephrol Dial Transplant (2015) 30: 564–574), Latham et al (WO2008144757 A1), Bedrosian et al (WO2018195034 A1), Jang et al (Application of Calculated Panel Reactive Antibody Using HLA Frequencies in Koreans, Ann Lab Med 2012;32:66-72), Uehara et al (Ischemia augments alloimmune injury through IL-6-driven CD4+ alloreactivity, Scientific Reports, 8:2461, 2018), Vo et al (A Phase I/II Trial of the Interleukin-6 Receptor Specific Humanized Monoclonal (Tocilizumab) + Intravenous Immunoglobulin in Difficult to Desensitize Patients, Transplantation 2015;99: 2356–2363, IDS 12/13/2021) as applied to claims 1, 4-8, 11, 13, 15, and 18-25 above, and further in view of Salvadori et al (Biomarkers in renal transplantation: An updated review, World J Transplant 2017 June 24; 7(3): 161-178), Baan et al (T Follicular Helper Cells in Transplantation: The Target to Attenuate Antibody-Mediated Allogeneic Responses?, Curr Transpl Rep (2014) 1:166–172), Sezer et al (Post-transplant C-reactive protein monitoring can predict chronic allograft nephropathy, Clin Transplant 2004: 18: 722–725), and Chong et al (Memory B cells in Transplantation, Transplantation. 2015 January 15; 99(1): 21–28).
The teachings of Jones et al, Latham et al, Jang et al, Bedrosian et al, Uehara et al, and Vo et al are discussed above.
Salvadori et al teaches biomarkers in renal transplantation to help make diagnosis of rejection [Abstract, pg. 161]. Salvadori et al further teaches monitoring IL-6 [Proteomic Studies, pg. 164]. Salvadori et al further teaches elevated plasma in acute kidney injury (AKI) [Proteomic and genomic studies, pg. 164]. Salvadori et al further teaches the number of circulating Treg in tolerant patients is higher [Right column, pg. 170]. Salvadori et al further teaches monitor B-cells through BCL2 [Table 2].
Salvadori et al does not specifically teach the markers Tfh and Th17. However, this deficiency is made up in the teachings of Baan et al.
Baan et al teaches monitoring Tfh in transplantations [Left column, pg. 170]. Baan et al further teaches monitoring Th17 [Right column, pg. 167].
Salvadori et al does not specifically teach monitoring CRP. However this deficiency is made up in the teachings of Sezer et al.
Sezer et al teaches that C-reactive protein (CRP) is a major problem after renal transplantations [Abstract].
Salvadori et al does not specifically teach the marker plasmablast IgG. However this deficiency is made up in the teachings of Chong et al.
Chong et al teaches a method of monitoring plasmablasts after transplantation for a spike in antigen specific antibodies [ii. Long-lived plasma cells, pg. 3].
One of ordinary skill, before the effective filing date, would have been motivated to combine the methods of Jones, Latham, Jang, Bedrosian, Uehara and Vo, with Salvadori’s method of monitoring IL-6, plasma, Treg, and B-cells in renal transplantations, with Baan’s method of monitoring Tfh and Th17 in renal transplantations, with Sezer’s method of monitoring CRP in renal transplantations, with Chong’s method of monitoring plasmablasts. It would have been prima facie obvious to combine the methods of Jones, Latham, Jang, Bedrosian, Uehara, Vo, Salvadori, Baan and Sezer’s to monitor CRP, Treg, Tfh, B-cell, IL-6, and plasmablasts before a renal transplantation for the safety of the patient and success of the transplanted kidney, because the prior art teaches monitoring these markers in transplantation patients as indicators for transplantation rejections.
Claims 1, 4-8, 11, 13, 15, and 17-25 are rejected under 35 U.S.C. 103 as being unpatentable over Jones et al (Interleukin-6 in renal disease and therapy, Nephrol Dial Transplant (2015) 30: 564–574), Latham et al (WO2008144757 A1), Bedrosian et al (WO2018195034 A1), Jang et al (Application of Calculated Panel Reactive Antibody Using HLA Frequencies in Koreans, Ann Lab Med 2012;32:66-72), Uehara et al (Ischemia augments alloimmune injury through IL-6-driven CD4+ alloreactivity, Scientific Reports, 8:2461, 2018), Vo et al (A Phase I/II Trial of the Interleukin-6 Receptor Specific Humanized Monoclonal (Tocilizumab) + Intravenous Immunoglobulin in Difficult to Desensitize Patients, Transplantation 2015;99: 2356–2363, IDS 12/13/2021) as applied to claims 1, 4-8, 11, 13, 15, and 18-2 above, and further in view of Duncan et al (US 20110111437 A1).
The teachings of Jones et al, Latham et al, Jang et al, Bedrosian et al, Uehara et al, and Vo et al are discussed above.
Duncan et al teaches the use of infectious agents with transplant recipients [0109]. Duncan et al further teaches administering valganciclovir in seronegative recipients and fluconazole to recipients without known fungal colonization to transplant recipients [0109].
One of ordinary skill, before the effective filing date, would have been motivated to combine the methods of Jones, Latham, Jang, Bedrosian, Uehara, and Vo with Duncan’s method of administering infectious agents valganciclovir and fluconazole to transplant recipients. It would have been prima facie obvious to combine Jones, Latham, Jang, Bedrosian, Uehara, Vo, and Duncan’s for a method of administering infectious agents valganciclovir and fluconazole to protect the transplanted kidney and safety of the patient, because the prior art teaches administering these infectious agents to transplant patients. Furthermore, combining known treatments for reducing infections in transplant patients to yield predictable results is an exemplary rationale for a prima facie case of obviousness.
Applicant’s Arguments:
Applicant traverses this rejection.
Overall, the claimed method was highly effective in reducing or eliminating DSA antibodies in HS renal transplantation patients, especially for those with cPRAs >99.5%, as demonstrated in the present application and the above-referenced post-filing data. None of the previously cited references teach or suggest a method for reducing or eliminating DSAs in a HS human subject, wherein the subject has cPRA of 90% or greater, as in claim 1
The claimed method resulted in a significant reduction in DSAs and a 100% transplantation rate.
The present application represent unexpected results that could not have been predicted in view of Vo. Applicant respectfully submits that one of ordinary skill in the art would not have found the disclosure of Vo to teach or suggest a method for reducing or eliminating DSAs in a HS human subject, wherein the subject has cPRA of 90% or greater, much less a method with the unexpected results and advantages as described above.
Jang is silent regarding treatment of a human subject with an anti-IL-6 antibody, let alone a HS human subject having cPRA of 90% or greater. Accordingly, in view of the well-established challenges of treating HS patients, one of ordinary skill in the art would not have found the disclosure in Jang to teach or suggest a method for reducing or eliminating DSAs in a HS human subject, wherein the subject has cPRA of 90% or greater as in claim 1.
Collectively, none of Jones, Latham, Jang, Bedrosian, Uehara, or Vo, alone or in combination, teach or suggest a method for reducing or eliminating DSAs in a HS human subject, wherein the subject has cPRA of 90% or greater.
Examiner’s Response:
Applicant claims unexpected results that could not have been predicted in view of
Applicant states, “the claimed method was highly effective in reducing or eliminating DSA antibodies in HS renal transplantation patients, especially for those with cPRAs >99.5%”.
Vo et al teaches a method of reducing or eliminating donor-specific antibody (DSA) in a HLA-sensitized human subject by administering tocilizumab, a monoclonal antibody directed at IL-6 receptor, to patients waiting for kidney transplant and with a mean cPRA of 93 (+/-5) pretreatment to 89 (+/-9) [Table 2].
Vo et al does not specifically teach the treatment of clazakizumab. However, this deficiency is made up in the teaches of Jones et al.
Jones et al teaches IL-6 in renal transplantation [Right column, 2rnd Paragraph, pg. 568]. Jones et al further teaches therapies that target the cytokine directly, clazakizumab, or the alpha subunit, tocilizumab [Right column, pg. 565].
One of ordinary skill in the art, before the effective filing date, would have been motivated to combine Vo’s method of reducing DSA in renal transplant patients by administering tocilizumab and achieving a mean cPRA of 93 (+/-5) pretreatment to 89 (+/-9), with Jones’s method of targeting IL-6 by targeting the cytokine directly with clazakizumab. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to combine Vo and Jones’s methods for a method of reducing or eliminating DSA in HLA-sensitized human subjects before a solid organ transplant comprising administering clazakizumab and wherein the patient has a cPRA of 90% or greater, because Vo teaches achieving this level or response using another IL-6 axis inhibitor.
An "obvious to try" rationale may support a conclusion that a claim would have been obvious where one skilled in the art is choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success. " [A] person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely that product [was] not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under § 103." KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 421, 82 USPQ2d 1385, 1397 (2007).
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.
Claims 1, 4-8, 11, 13, 15, 17-18, 20, and 22-25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 8, 10-17, and 19-20 of copending Application No. 19/081,867 ('867).
Claims 1, 4-5, and 20 are directed to an invention that is not patentably distinct from claims 1 and 15 of co-pending application ‘867. Specifically, a method of a method of reducing DSA in a human subject comprising administering clazakizumab.
Claims 6-7 is directed to an invention that is not patentably distinct from claims 6 and 16 of co-pending application ‘867. Specifically, further administration further administering IVIG, rituximab, plasmapheresis, or a combination thereof.
Claim 8 is directed to an invention that is not patentably distinct from claim 8 of co-pending application ‘867. Specifically, the organ is a kidney.
Claims 11 and 13 are directed to an invention that is not patentably distinct from claims 10-12 of co-pending application ‘867. Specifically, administering subcutaneously at various dosages and frequencies.
Claims 15 and 17-18 are directed to an invention that is not patentably distinct from claims 13-14 of co-pending application ‘867. Specifically, administering additional anti-infectious agents.
Claims 22 and 23 are directed to an invention that is not patentably distinct from claim 19 of co-pending application ‘867. Specifically, assaying for co-pending markers of CRP, Treg, Tfh, TH17, B-cell, IL-6, plasma cels, plasmablast IgG, or a combination thereof.
Claims 24 and 25 are directed to an invention that is not patentably distinct from claim 20 of co-pending application ‘867. Specifically, the method further comprising glomerular filtration rate, DSA, or both, after the solid organ transplantation.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 4-9, 11, 13, 15, 17-18, and 20-25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 8, 10-17, and 19-20 of copending Application No. 19/081,867 ('867) in view of Bedrosian et al (WO2018195034 A1)
Claims 1, 4-5, and 20 are directed to an invention that is not patentably distinct from claims 1 and 15 of co-pending application ‘867. Specifically, a method of a method of reducing DSA in a human subject comprising administering clazakizumab.
Bedrosian et al teaches methods of reducing antibody mediated rejection in human kidney transplants [Abstract]. Bedrosian et al further teaches methods to sensitize human before the kidney transplant [Line 3, pg. 3]. Bedrosian et al further teaches the desensitization therapy IVIG and plasmapheresis [Line 8, pg. 3]. Bedrosian et al further teaches methods to screen humans for infections [Line 17, pg. 41]. Bedrosian et al further teaches the IVIG and plasmapheresis is administered prior to transplantation [Line 8, pg. 49]. Bedrosian et al further teaches the use of alemtuzumab after transplantation [Line 21, pg. 71]. Bedrosian et al further teaches the use of tacrolimus, mycophenolate mofetil, and prednisone [Line 2, pg. 71].
With respect to claim 21, in view of the teachings of Bedrosian et al, one of ordinary skill in the art would have been motivated to modify the conflicting claims to recite the administration of alemtuzumab or tacrolimus/mycophenolate mofetil/prednisone, because the resultant method would improve immunosuppression (decreased donor-specific antibodies) in transplant patients.
This is a provisional nonstatutory double patenting rejection.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DENNIS JOHN SULLIVAN whose telephone number is (571)272-0509. The examiner can normally be reached Mon - Fri: 7:30AM - 4:30PM.
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/DENNIS J SULLIVAN/Examiner, Art Unit 1642
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642