DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Amendment
2. The amendment filed October 23, 2025 has been entered. Claims 1-25 and 32 are cancelled. Claim 26 was amended. Claim 47 was newly added. Claims 26-31 and 33-47 are under consideration in this Office Action.
New Grounds of Rejection Necessitated By Applicants Amendment
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.
3. Claim 26 is 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 26 now recites ….reducing severity relative to baseline of lupus nephritis, nephrotic syndrome or glomerulonephritis…” However the metes and bounds for determining the reduction of severity are not defined by the instant claims. The claims do not recite what the baseline is or how the baseline is defined. Is the baseline of the reduced severity lupus nephritis, nephrotic syndrome or glomerulonephritis a subject without disease or a subject with only “mild” symptoms or severity. Is the baseline compared to a diagnosed subject who was not administered the Obinutuzumab.
Thus the ability to determine whether or not treatment, inhibition or reduced severity as compared to an undefined baseline is not defined by claim 26. It is suggested that the claim language refer to reducing severity as compared to subjects not administered Obinutuzumab. Therefore clarification is still required to overcome the rejection.
Response to Arguments
4. Applicant's arguments filed October 23, 2025 have been fully considered but they are not persuasive. Applicants have amended claim 26 to overcome the rejection and state the amendment of claim 26 is drawn to reducing the serum creatinine level, and/or urine protein to creatinine ratio as thereby reduce the disease severity based upon Figures 6 and 7. However, the issue is that the claim needs to recite the language as opposed to merely pointing to support within the specification. Therefore applicants amendment does not obviate the rejection.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
5. Claim 47 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
Neither the specification nor originally presented claims provides support for a patient not diagnosed with cancer. Applicant did not point to support for excluding patients diagnosed with cancer. Moreover, applicant failed to specifically point to the identity of such patients. Thus, there appears to be no teaching of excluding patients not diagnosed with a cancer. Contrary to the amendment, the instant specification teaches treatment of leukemias, and a wide variety of specifically named cancers. Applicant has pointed to Example 3 of the instant specification and claims for support of the amendment, however it appears that Example 3 appears to fail to exclude patients with cancer. Instead the instant specification, clearly embraces treating patients with cancers. Therefore, it appears that there is no support in the specification. Moreover, the new claim incorporates new matter and are accordingly rejected.
Maintained Grounds of Rejection
Double Patenting
6. The non-statutory 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 non-statutory 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 non-statutory 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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 e-Terminal Disclaimer may be filled out completely online using web-screens. An e-Terminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about e-Terminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
7. Claims 26-31 and 33-46 are rejected on the ground of non-statutory double patenting as being unpatentable over claims 1-19 and 21-26 of U.S. Patent No. 11,149,091. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the instant application are drawn to:
A method for treating, or inhibiting or reducing severity relative to baseline of, lupus nephritis, nephrotic syndrome, or glomerulonephritis in a subject in need thereof, comprising: administering an effective amount of an anti-CD20 antibody over a period of no more than 21 days to the subject, said anti-CD20 antibody comprising Obinutuzumab, and abstaining from administering the anti-CD20 antibody for at least 12 months from the period of the anti-CD20 antibody administration.
The claims of U.S. Patent No. 11,149,091 recite:
A method of treating, inhibiting or reducing severity of nephrotic syndrome in a subject in need thereof consisting of: administering an effective amount of an anti-CD20 antibody, or a pharmaceutical composition consisting of the anti-CD20 antibody and a pharmaceutically acceptable excipient in two or more doses over a period of no more than 21 days to the subject, so as to treat, inhibit or reduce the severity of nephrotic syndrome in the subject wherein the anti-CD20 antibody comprises obinutuzumab. and the two or more doses have a first dose and a last dose that are 1-20 days apart: or administering an effective amount of the anti-CD20 antibody or the pharmaceutical composition in the two or more doses over a period of no more than 21 days and a standard-of-care treatment to the subject, so as to treat, inhibit or reduce the severity of nephrotic syndrome in the subject.
The claims of both application and patent are drawn to a method of treating, inhibiting or reducing severity of nephrotic syndrome, and glomerulonephritis, in a subject in need thereof. Both the application and patent administer Obinutuzumab in the same recited amounts and dosing schedules; thus they are not patentably distinct from each other. The instant application and patent do not recite patentably distinct subject matter.
Double Patenting
8. Claims 26-31 and 33-46 are rejected on the ground of non-statutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No 11,840,576. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the instant application are drawn to:
A method for treating, or inhibiting or reducing severity relative to baseline of, lupus nephritis, nephrotic syndrome, or glomerulonephritis in a subject in need thereof, comprising: administering an effective amount of an anti-CD20 antibody over a period of no more than 21 days to the subject, said anti-CD20 antibody comprising Obinutuzumab, and abstaining from administering the anti-CD20 antibody for at least 12 months from the period of the anti-CD20 antibody administration.
The claims of U.S. Patent No. 11,840,576 recite:
A method of treating, inhibiting or reducing severity of nephrotic syndrome or glomerulonephritis in a subject in need thereof, wherein the subject is a transplant recipient, the method consisting of: administering an effective amount of an anti-CD20 antibody, or a pharmaceutical composition consisting of the anti-CD20 antibody and a pharmaceutically acceptable excipient, in two or more doses over a period of no more than 21 days to the subject after transplantation, or administering an effective amount of the anti-CD20 antibody or the pharmaceutical composition in the two or more doses over a period of no more than 21 days and a standard-of-care treatment to the subject,
wherein the anti-CD20 antibody comprises Obinutuzumab, so as to treat, inhibit or reduce the severity of nephrotic syndrome or glomerulonephritis in the subject.
The claims of both application and patent are drawn to a method of treating, inhibiting or reducing severity of nephrotic syndrome, glomerulonephritis, and lupus nephritis in a subject in need thereof. Both the instant application and patent claims administer Obinutuzumab in the same recited amounts and the same dosing schedules; thus they are not patentably distinct from each other. The instant application and patent do not recite patentably distinct subject matter.
Response to Arguments
9. Applicant's arguments filed October 23, 2025 have been fully considered but they are not persuasive. Applicants requested the double patenting rejections be held in abeyance. However the rejection of non-statutory double patenting rejection as being unpatentable over claims 1-19 and 21-26 of U.S. Patent No. 11,149,091 is maintained. Additionally, the non-statutory double patenting rejection as being unpatentable over claims 1-20 of U.S. Patent No 11,840,576 is maintained.
It is noted that Applicants requested the rejections be held in abeyance. However, the rejection are maintained until the non-statutory double patenting rejections are addressed.
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.
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.
10. Claims 26-27, 29-31, 33-37, 39, 41, 44-45 and 47 are rejected under 35 U.S.C. 103 as being unpatentable over Gokarn et al., (US 20140314748 published Oct 2023; priority to March 2013); Brown et al., (Blood. Vol. 125 no. 16, pp. 2779-2785, April 2015)
in view of Nozu et al., (Pediatric Nephrology. Vol. 20, pages 1660-1663 (2005) and Mossner et al., (Blood. 2010 Mar 1;115(22):4393–4402).
The claims are drawn to a method for treating, or inhibiting or reducing severity relative to baseline of, lupus nephritis, nephrotic syndrome, or glomerulonephritis in a subject in need thereof, wherein the subject is diagnosed with the lupus nephritis, the nephrotic syndrome, or the glomerulonephritis, the method comprising: administering an effective amount of obinutuzumab in two or more doses over a period of no more than 21 days to the subject, measuring, or obtaining a result of, serum creatinine level, urine protein-to-creatinine ratio, or both of the subject at one or more post-obinutuzumab time points selected from the group consisting of about 1 month, about 2 months, about 3 months, about 4 months, about 6 months, and about 12 months from the period of the obinutuzumab administration, wherein the serum creatinine level, the urine protein-to-creatinine ratio, or both at the one or more post-obinutuzumab time points is lower than before the obinutuzumab administration; and abstaining from administering an anti-CD20 antibody for at least 12 months from the period of the Obinutuzumab administration.
Gokarn et al., teach a method of treating a disease or disorder in a subject comprising administering the formulation to a subject in an amount effective to treat the disease or disorder [para 37]. Examples of disorders include inflammatory renal diseases, such as glomerulonephritis, especially mesangioproliferative glomerulonephritis, nephrotic syndrome, haemolytic uremic syndrome, diabetic nephropathy or hypertensive nephrosclerosis and diseases occurring after transplants including post-transplant lymphoproliferative disorder (PTLD) [para 97-98]. Thus teaching a method for treating, or inhibiting or reducing severity of nephritis, nephrotic syndrome, or glomerulonephritis, post kidney transplant disorders in a subject in need thereof as claimed in claims 26, 29-31 and 45. Additionally, Gokarn et al., teach treatment of chronic lymphocytic leukemia [para 38 and para 106].
The stable aqueous pharmaceutical formulation, the formulation comprising a monoclonal antibody, trehalose and a buffer [para 8]. Gokarn et al., describe the Obinutuzumab, formulations comprising Obinutuzumab, trehalose, sodium phosphate and polysorbate 20 [para 19, 23, and 34]. In one embodiment, the anti-CD20 antibody is obinutuzumab (recommended INN, WHO Drug Information, Vol. 26, No. 4, 2012, p. 453). As used herein, obinutuzumab is synonymous for GA101 or RO5072759 [para 88]. Example 2 teach the development and formulation of Obinutuzumab. The antibody is obinutuzumab. The formulation comprises obinutuzumab in an amount of about 45 mg/mL to about 55 mg/mL [para 15]. Thus teaching claim 37.
The formulation for administration to a subject is for intravenous (IV) administration [para 16], thus teaching claim 41. The antibody is suitably administered to the patient over a series of treatments and may be administered to the patient at any time from diagnosis onwards. The antibody may be administered as the sole treatment or in conjunction with therapies useful in treating the condition in question [para 271]. Dosage regimens include antibody administered at a dose of about 100 or 400 mg every 4 weeks. The dose may be infusions administered as a single dose or as multiple doses (e.g., 2 or 3 doses) [para 272]; thus teaching a single dose for only 1 day as recited by claims 38-39. Thus teaching abstaining from administration for about 1 month as recited by claim 26.
The formulation may also contain more than one protein as necessary for the particular disorder being treated. For example, it may be combined with another agent such as a chemotherapeutic agent, and/or anti-neoplastic agent [para 267]. The “chemotherapeutic agent” is a chemical compound useful in the treatment of cancer. Examples of chemotherapeutic agents include mycophenolic acid [para 110]. Thus teaching claims 35-36. Therefore, Gokarn et al., teach a method for treating, or inhibiting or reducing severity of, lupus nephritis, nephrotic syndrome, glomerulonephritis and/or chronic lymphocytic leukemia in a subject in need thereof, wherein the subject is diagnosed with the lupus nephritis, the nephrotic syndrome, or the glomerulonephritis, the method comprising: administering an effective amount of obinutuzumab in two or more doses over a period of no more than 21 days to the subject. However, Gokarn et al., do not teach the first dose in an amount of 100mg and the second dose at 900mg.
Brown teach human patients received treatment with Obinutuzumab was administered IV (100 mg on day 1, 900 mg on day 2, and 1000 mg on day 8 and day 15 of cycle 1; 1000 mg on day 1 of cycles 2-6) with either fludarabine and cyclophosphamide. Each cycle was 28 days [Treatment]. Thus teaching claim 43.
To enroll, patients had to have adequate renal function (creatinine clearance >60 mL/min for G-FC) [Patient population]. Thus teaching measuring creatinine level at a time point as recited by claim 27. Brown et al., explored the safety and preliminary efficacy of obinutuzumab-bendamustine (G-B) or obinutuzumab fludarabine cyclophosphamide (G-FC) for the therapy [Abstract]. Thus teaching claims 34-35. Obinutuzumab is in combination with chemotherapy has an acceptable safety profile when administered to previously untreated fit patients. After the first infusion of obinutuzumab symptoms were easily handled with corticosteroid premedication and split dosing. Brown et al’s data demonstrate that obinutuzumab in combination with FC or B has promising activity when used in the therapy of patients.
Obinutuzumab (previously known as GA101) is a humanized immunoglobulin G1 antibody targeting CD20, which was developed as a type 2 antibody and glycoengineered for enhanced antibody-dependent cellular cytotoxicity and phagocytosis. Obinutuzumab does induce stronger homotypic aggregation of B cells, resulting in greater direct cell death. In addition, the Fc segment of obinutuzumab is glycoengineered and is more effective at eliciting antibody-dependent cellular cytotoxicity than rituximab.
Gokarn et al., and Brown et al., have been discussed above as teaching a method for treating, or inhibiting or reducing severity of, nephrotic syndrome, in a subject in need thereof, wherein the subject is diagnosed with nephrotic syndrome, the method comprising: administering an effective amount of Obinutuzumab in two or more doses over a period of no more than 21 days to the subject, and abstaining from administering an anti-CD20 antibody for at least 12 months from the period of the Obinutuzumab administration. However, none of the references teach the subject has been administered a standard-of-care treatment prior to the administration of the Obinutuzumab, and the subject does not respond to the standard-of-care treatment prior to the administration of the anti-CD20 antibody or the measurement of urine protein to creatinine ratio at about 3 months, 6 months or 12 months.
Nozu et al., teach a 12-year-old boy who underwent kidney transplantation who developed severe proteinuria immediately after the operation. Because his original disease was nephrotic syndrome (focal segmental glomerulosclerosis, or FSGS), we diagnosed this as a recurrence of nephrotic syndrome to the transplanted kidney [abstract]. Four months after the transplantation, posttransplant lymphoproliferative disorder (PTLD) developed, which was pathologically diagnosed as diffuse large B cell lymphoma. Treatment consisting of a reduction in immunosuppression resulted in improvement in PTLD a month after the start of treatment. However, relapse occurred 2 months after the first onset of PTLD, which was treated with rituximab at 375 mg/m2. The PTLD resolved immediately after the rituximab treatment was started, and, interestingly, urinary protein levels also improved at the same time. Fig. 2 shows the clinical course in terms of peripheral B cell counts, serum IgG levels, and the ratio of urinary protein to urinary creatinine (U-P/U-Cr). Fig 2b shows urinary protein decreased immediately after the rituximab administration. Figure 2 b shows time points at Day 0, day 100, day 200, 300 and 400. Thus teaching measurement of a ratio of urinary protein to urinary creatinine with a before administration comparison and measurement at about 3 months, about 6 month and about 12 months just as instantly recited by claims 26-27. Interestingly, after the rituximab administration, urinary protein as well as peripheral B cells disappeared, suggesting that the activation of B cells may play a pathogenetic role in the recurrence of proteinuria or nephrotic syndrome after renal transplantation in FSGS patients [Discussion]. Three years later, the boy shows no signs of PTLD, and no proteinuria has been detected.
Mossner et al., teach CD20 is an important target for the treatment of B-cell malignancies, lymphoma as well as autoimmune disorders. B-cell depletion therapy using monoclonal antibodies against CD20, such as rituximab, has revolutionized the treatment of these disorders, greatly improving overall survival in patients. Here, Mossner et al., reported the development of GA101 as the first Fc-engineered, type II humanized IgG1 antibody against CD20 [abstract]. It is noted, that GA101 is also known as Obinutuzumab.
Relative to rituximab, GA101 has increased direct and immune effector cell-mediated cytotoxicity and exhibits superior activity in cellular assays and whole blood B-cell depletion assays [Discussion]. In human lymphoma xenograft models, GA101 exhibits superior antitumor activity, resulting in the induction of complete tumor remission and increased overall survival. In nonhuman primates, GA101 demonstrates superior B cell–depleting activity in lymphoid tissue, including in lymph nodes and spleen [Discussion]. Taken together, these results provide compelling evidence for the development of GA101 as a promising new therapy for the treatment of B-cell disorders [abstract]. Because of its superior B cell–depleting activity in lymphoid tissues, GA101 may provide an effective treatment alternative for autoimmune diseases, such as systemic lupus erythematosus where rituximab has shown benefit [Discussion]. Thus, Mossner et al., teach the motivation to exchange rituximab for obinutuzumab.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art to administer Obinutuzumab as taught by Brown et al., using the method of Gokarn et al., already known to administer an Obinutuzumab in conjunction with standard of care agents so patients have enhanced antibody-dependent cellular cytotoxicity and phagocytosis and greater direct cell death for patients with glomerulonephritis (GN). Additionally, it would have been prima facie obvious one of ordinary skill in the art to incorporate the teachings of Nozu et al., into the method of Gokarn et al., in order to treat patients that did not respond to the standard-of-care treatment prior to the administration of the anti-CD20 antibody because Gokarn et al., already taught Obinutuzumab administration for nephrotic syndrome and post-transplant lymphoproliferative disorder; while Mossner et al., teach the motivation to exchange obinutuzumab for rituximab in order to prevent the recurrence of proteinuria or nephrotic syndrome. No more than routine skill is required to treat relapsed kidney transplant patients having post-transplant lymphoproliferative disorder when Gokarn et al., taught treatment. Finally, no more than routine skill, would have been required to incorporate the known Obinutuzumab using the previously taught dosage schedule.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses combining prior art elements according to known methods to yield predictable results, thus the combination is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "The combination of familiar element according to known methods is likely to be obvious when it does no more than yield predictable results". It is well known to combine known methods which function in a predictable manner to yield a reasonable expectation of success along with predictable results to one of ordinary skill in the art at the time of the invention. Thus, it would have been obvious to a person of ordinary skill in the art to combine prior art elements according to known methods that is ready for improvement to yield predictable results. The claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Response to Arguments
11. Applicant’s arguments and amendments filed October 23, 2025, have been considered; however the rejection of record is maintained.
Applicants assert that the claimed methods exhibit significant benefits by lowering the urine protein to creatinine ratio and serum creatinine in patients with nephrotic syndrome, or glomerulonephritis for up to 12 months with just two doses of Obinutuzumab. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies i.e., lowered levels of urine protein to creatinine ratio and/or lowered serum creatinine
are not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). The instant claims merely require measuring the levels urine protein to creatinine ratio or serum creatinine in patients which was taught by the prior art rejections. Furthermore, inherent with the administration of Obinutuzumab is the lowering of urine protein to creatinine ratio or serum creatinine levels within the recipient.
Applicants argue that Gokarn only generically describes the treated diseases. However Gokarn et al., teach a method of treating inflammatory renal diseases, such as glomerulonephritis, especially mesangioproliferative glomerulonephritis, nephrotic syndrome, haemolytic uremic syndrome, diabetic nephropathy or hypertensive nephrosclerosis and diseases occurring after transplants including post-transplant lymphoproliferative disorder (PTLD) just as instantly recited. Gokarn et al., teach abstaining from administering an anti-CD20 antibody for at least 12 months from the period of the Obinutuzumab administration.
Contrary to Applicants assertions, Gokarn et al., teach method for treating, or inhibiting or reducing severity relative to baseline of, lupus nephritis, nephrotic syndrome, or glomerulonephritis in a subject in need thereof, wherein the subject is diagnosed with the lupus nephritis, the nephrotic syndrome, or the glomerulonephritis, the method comprising: administering an effective amount of obinutuzumab in two or more doses over a period of no more than 21 days to the subject. Gokarn et al., specifically teach obinutuzumab. Gokarn et al., clearly and repeated states that as an embodiments, the antibody is obinutuzumab. The MPEP section 2123 teaches that patents are relevant as prior art for all they contain, “The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain.” In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989). See also Celeritas Technologies Ltd. v. Rockwell International Corp., 150 F.3d 1354, 1361, 47 USPQ2d 1516, 1522-23 (Fed. Cir.1998) (The court held that the prior art anticipated the claims even though it taught away from the claimed invention. “The fact that a modem with a single carrier data signal is shown to be less than optimal does not vitiate the fact that it is disclosed.”). Therefore applicant’s argument is not persuasive especially when considering Gokarn et al., definition of antibody clearly and explicitly encompasses Obinutuzumab.
Applicants argue that Brown et al., Nozu et al., and Mossner et al., do not teach each and every aspect of the claimed limitations. In response to applicant's argument regarding the prior art secondary references, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
Brown et al., teach the method comprising: administering an effective amount of Obinutuzumab in two or more doses over a period of no more than 21 days to the subject, and abstaining from administering an anti-CD20 antibody for about 12 months from the period of the Obinutuzumab administration.
Nozu et al., teach measuring urine protein-to-creatinine ratio, or both of the subject at one or more post-obinutuzumab time points selected from the group consisting of about 1 month, about 2 months, about 3 months, about 4 months, about 6 months, and about 12 months from the period of the obinutuzumab administration, wherein the serum creatinine level, the urine protein-to-creatinine ratio, or both at the one or more post-obinutuzumab time points is lower than before the obinutuzumab administration. Nozu et al., specifically shows 100, 200, 300, 400 days and recites day 120 where the urine protein-to-creatinine ratio (U-P/U-Cr) was tested [page 1662, col. 1]. Nozu et al., teach obtaining and measurement of the urine protein-to-creatinine ratio.
Therefore, contrary to Applicants arguments, the prior art references teach measurement to obtain urine protein-to-creatinine ratio result of, serum creatinine level, urine protein-to-creatinine ratio, or both of the subject at one or more post-obinutuzumab time points selected from the group consisting of about 1 month, about 2 months, about 3 months, about 4 months, about 6 months, and about 12 months from the period of the obinutuzumab administration, wherein the serum creatinine level, the urine protein-to-creatinine ratio, or both at the one or more post-obinutuzumab time points is lower than before the obinutuzumab administration.
Mossner et al., teach the motivation to exchange rituximab for obinutuzumab.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Therefore, it would have been prima facie obvious to one of ordinary skill in the art to administer Obinutuzumab as taught by Brown et al., using the method of Gokarn et al., already known to administer an Obinutuzumab in conjunction with standard of care agents so patients have enhanced antibody-dependent cellular cytotoxicity and phagocytosis and greater direct cell death for patients with glomerulonephritis (GN). Additionally, it would have been prima facie obvious one of ordinary skill in the art to incorporate the teachings of Nozu et al., into the method of Gokarn et al., in order to treat patients that did not respond to the standard-of-care treatment prior to the administration of the anti-CD20 antibody because Gokarn et al., already taught Obinutuzumab administration for nephrotic syndrome and post-transplant lymphoproliferative disorder; while Mossner et al., teach the motivation to exchange obinutuzumab for rituximab in order to prevent the recurrence of proteinuria or nephrotic syndrome.
Therefore, Applicants arguments are not found persuasive.
Claim Rejections - 35 USC § 103
12. Claims 26, 28-32, 34-39, 40-42 and 44-47 are rejected under 35 U.S.C. 103 as being unpatentable over Gokarn et al., Brown et al., and Moulin et al., in view of Brunetta et al., (US20090311255 published Dec 2009; priority to Aug 2008) and Mossner et al., (Blood. 2010 Mar 1;115(22):4393–4402).
Gokarn et al., and Brown et al., have been discussed above as teaching a method for treating, or inhibiting or reducing severity of, nephrotic syndrome, or glomerulonephritis in a subject in need thereof, wherein the subject is diagnosed with the lupus nephritis, the nephrotic syndrome, or the glomerulonephritis, the method comprising: administering an effective amount of Obinutuzumab in two or more doses over a period of no more than 21 days to the subject, and abstaining from administering an anti-CD20 antibody during time points of about 1 month, about 2 months, about 3 months, about 4 months, about 6 months and about 12 months from the period of the Obinutuzumab administration.
Moulin et al., analyzed clinical presentation, immunopathological data and renal outcome in 13 patients with glomerulonephritis (GN) and chronic lymphocytic leukemia (CLL) [abstract]. B-cell proliferation and glomerulopathy were simultaneously diagnosed in seven of the 13 patients. Nephrotic syndrome was observed in nine patients. Serum creatinine was elevated (greater than 120 mumol/liter) in 10 patients and exceeded 400 mumol/liter in three patients. A clear cut relationship between GN and hematologic disease could be established in nine cases: five patients had MPGN caused by type I or type II cryoglobulinemia; two had MPGN or mesangial hypertrophy with circulating and deposited noncryoprecipitating monoclonal IgG K and IgM K, respectively; in the two remaining patients, monotypic IgG K glomerular deposits exhibiting fibrillary organization were observed in association with MGN or MPGN, despite the absence of circulating M-component by immunofixation [abstract]. These overall data demonstrate that the occurrence of GN in B-CLL and related lymphoma is not fortuitous, and testify to the paraneoplastic nature of glomerular involvement mediated by deposition [abstract]. However, none of the references teach treating lupus nephritis, comprising administering an effective amount of obinutuzumab.
Brunetta et al., teach administration in an asymptomatic human subject at risk for experiencing one or more symptoms of the autoimmune disease, by administering a CD20 antibody to the subject in an amount to prevent the subject from experiencing one or more symptoms of the autoimmune disease [para 11]. Brunetta et al., teach treating autoimmune diseases including lupus, including lupus nephritis, lupus cerebritis, pediatric lupus, non-renal lupus, extra-renal lupus, discoid lupus and discoid lupus erythematosus, alopecia lupus, systemic lupus erythematosus (SLE) such as cutaneous SLE or subacute cutaneous SLE, neonatal lupus syndrome (NLE), and lupus erythematosus disseminatus, glomerulonephritis (GN) with and without nephrotic syndrome such as chronic or acute glomerulonephritis such as primary GN, immune-mediated GN, membranous GN (membranous nephropathy), idiopathic membranous GN or idiopathic membranous nephropathy, membrano- or membranous proliferative GN (MPGN), including Type I and Type II, and rapidly progressive GN, proliferative nephritis, immune complex nephritis, antibody-mediated nephritis, (IgA nephropathy), idiopathic IgA nephropathy, post-streptococcal nephritis, idiopathic nephritic syndrome, minimal change nephropathy, nephrosis, mixed connective tissue disease, nephrotic syndrome, nephrotic syndrome, focal or segmental or focal segmental glomerulosclerosis (FSGS), glomerulonephritides [para 23]. Thus teaching claims 28-31.
As a general proposition, the effective amount of the antibody administered parenterally per dose will be in the range of about 20 mg/m2 to about 10,000 mg/m2 of subject body, by one or more dosages [para 100]. Thus teaching claims 37. Exemplary IV dosage regimens for intact antibodies include 375 mg/m2 weekly×4; 1000 mg×2 (e.g. on days 1 and 15); or 1 gram×3 [para 100]. Thus teaching claims 38, 40 and 42. Parenteral infusions include intravenous or intraarterial administration [para 102]. Thus teaching claim 41. One may administer other compounds,[103]. The combined administration includes coadministration, using separate formulations or a single pharmaceutical formulation, and consecutive administration in either order, wherein preferably there is a time period while both (or all) active agents simultaneously exert their biological activities [para 103]. For example, glucocorticoid, low-dose prednisone, glucorticoids/prednisone/methylprednisone (glucocorticoids), cyclosporin A. The combined administration includes coadministration, using separate formulations or a single pharmaceutical formulation, and consecutive administration in either order, wherein preferably there is a time period while both (or all) active agents simultaneously exert their biological activities [para 103]. Thus teaching claims 34-36. Aside from the CD20 antibody, the subject may be treated with steroids, one or more immunosuppressants such as cyclosporine [para 235]. Thus teaching claims 34-36.
Mossner et al., teach CD20 is an important target for the treatment of B-cell malignancies, lymphoma as well as autoimmune disorders. B-cell depletion therapy using monoclonal antibodies against CD20, such as rituximab, has revolutionized the treatment of these disorders, greatly improving overall survival in patients. Here, Mossner et al., reported the development of GA101 as the first Fc-engineered, type II humanized IgG1 antibody against CD20 [abstract]. It is noted, that GA101 is also known as Obinutuzumab.
Relative to rituximab, GA101 has increased direct and immune effector cell-mediated cytotoxicity and exhibits superior activity in cellular assays and whole blood B-cell depletion assays [Discussion]. In human lymphoma xenograft models, GA101 exhibits superior antitumor activity, resulting in the induction of complete tumor remission and increased overall survival. In nonhuman primates, GA101 demonstrates superior B cell–depleting activity in lymphoid tissue, including in lymph nodes and spleen [Discussion]. Taken together, these results provide compelling evidence for the development of GA101 as a promising new therapy for the treatment of B-cell disorders [abstract]. Because of its superior B cell–depleting activity in lymphoid tissues, GA101 may provide an effective treatment alternative for autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythomatosus, or immune thrombocytic purpura, where rituximab has shown some benefit [Discussion]. Thus, Mossner et al., teach the motivation to exchange rituximab for obinutuzumab.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art to treat lupus nephritis as taught by Brunetta et al., using the method of Gokarn et al., Brown and Moulin et al., already known to treat inflammatory renal diseases, such as systemic lupus erythematosus, lupus nephritis, and other B-cell diseases by administering obinutuzumab in conjunction with standard of care agents in order to have increased direct and immune effector cell-mediated cytotoxicity and exhibits superior activity. It is prima face obvious to substitute one anti-CD20 antibody rituximab
for another, obinutuzumab when the prior art proves the diseases are all B-cell disorder and the prior art shows that obinutuzumab performs better than rituximab as taught by Mossner et a;.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses combining prior art elements according to known methods to yield predictable results, thus the combination is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "The combination of familiar element according to known methods is likely to be obvious when it does no more than yield predictable results". It is well known to combine known methods which function in a predictable manner to yield a reasonable expectation of success along with predictable results to one of ordinary skill in the art at the time of the invention. Thus, it would have been obvious to a person of ordinary skill in the art to combine prior art elements according to known methods that is ready for improvement to yield predictable results. The claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Response to Arguments
13. Applicant’s arguments and amendments filed October 23, 2025, with respect to the rejections of claims 26, 28-32, 34-39, 40-42 and 44-47 under 35 U.S.C. 103 as being unpatentable over Gokarn et al., Brown et al., Moulin et al., Brunetta et al., and Mossner et al., is maintained.
In response to Applicants arguments, the rejection of record clearly teach how Obinutuzumab will treat patients with subject is diagnosed with the lupus nephritis, the nephrotic syndrome, or the glomerulonephritis. Gokarn et al., clearly teach a method for treating, or inhibiting or reducing severity of, lupus nephritis, nephrotic syndrome, or glomerulonephritis in a subject in need thereof, wherein the subject is diagnosed with the lupus nephritis, the nephrotic syndrome, or the glomerulonephritis, the method comprising: administering an effective amount of Obinutuzumab. Moreover, the prior art teaching of Gokarn et al., and Brown et al., teach the administration of an effective amount of Obinutuzumab. Inherently, serum creatinine and/or urine protein to creatinine ratio is reduced. See also MPEP 2112.01 "Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In this case, Gokarn et al., teach administration of obinutuzumab. Brown teach human patients received treatment with Obinutuzumab and Mossner et al., teach Obinutuzumab demonstrates superior B cell–depleting activity in lymphoid tissue, when compared to rituximab. Therefore one of ordinary skill in the art would clearly be motivated to exchange one antiCD20 antibody for a superior anti-CD20 antibody, obinutuzumab.
Applicants argue that Brown et al., teach treatment for patients with CLL; however Moulin et al., teach a clear cut relationship between CLL and glomerulonephritis (GN), glomerulopathy and nephrotic syndrome. Therefore, there is clear cut evidence for the use of the anti-CD20 monoclonal antibody obinutuzumab with a higher efficacy than rituximab in patients with comorbidities and poor renal functions.
Therefore, Applicants arguments are not found persuasive.
Pertinent Art
14. The prior art made of record and not relied upon is considered pertinent to applicant’s disclosure. See WO2016183104 and WO2015116729.
Conclusion
15. No claims allowed.
16. 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.
17. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JA-NA A HINES whose telephone number is (571)272-0859. The examiner can normally be reached Monday thru Thursday.
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/JANA A HINES/Primary Examiner, Art Unit 1645