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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on January 16, 2026 has been entered.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on January 16, 2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS is being considered by the examiner.
Claim Status
New claims 58-75 are under consideration in this office action.
Claim Objections
Claim 58 is objected to because of the following informalities: in line 5, the phrase “of from” is grammatically incorrect. The claim should recite either “a dosage of 135 to 600 milligrams” or “a dosage from 135-600 milligrams”. Appropriate correction is required.
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.
New claims 58-74 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2012092612 (“Elias”; IDS from 2/9/22) in view of Lokhorst et al, published September 24, 2015 (instant PTO-892).
The claims are directed to a method of treating relapsed/refractory multiple myeloma in a subject comprising administering to the subject an isolated antibody comprising an antibody of heavy chain variable region of SEQ ID NO: 9 and light chain variable region of SEQ ID NO: 10 at a dosage from 135-600 mg
Elias teaches an anti-CD38 antibody comprised of HCVR/LCVR pair of SEQ ID NO: 9/10 and HC/LC pair of SEQ ID NO: 21/22 (pg 58-60); these sequences are identical to the HCVR/LCVR pair of SEQ ID NO: 9/10 of instant claim 58 and HC/LC pair of SEQ ID NO: 11/12 instant claim 59.
Elias teaches anti-CD38 antibody formulations for in vivo administration [00183]; subcutaneous administration is a preferred modality for antibody delivery [00189], as in instant claim 58.
Elias teaches a method for treating multiple myeloma using the claimed anti-CD38 antibody ([00163];[00165];[00173]), as in claim 58.
Elias teaches an antibody flat dose range of 250-2000 mg [00207], and a weight-based antibody dose of 0.1-100 mg/kg [00203]. This weight-based dose can be converted to a flat dose using a conversion factor of 80, as the median body weight for adults is approximately 80 kg, as evidenced by Walpole et al (PTO-892 from 9/7/23); when the weight-based dose is converted, the flat dose is 8-8000 mg. These dose ranges overlap with the dose of 135-600 mg of instant claim 58, 300-600 mg of claim 65, 135 mg of claim 66, 300 mg of claim 67, and 600 mg of claim 68. The dose is administered weekly ([00205], as in instant claim 64.
Elias does not explicitly teach a method for treating relapsed/refractory multiple myeloma.
Lokhorst et al teaches a method for treating patients with relapsed/refractory multiple myeloma with the anti-CD38 antibody daratumumab (abstract). Treatment eligible patients with myeloma had a relapse after, or had disease that was refractory to, two or more different prior therapies, including immunomodulatory agents, proteasome inhibitors, chemotherapy, and autologous stem-cell transplantation (pg 1208). Similarly, according to the specification, patients eligible to receive the claimed anti-CD38 antibody have been previously treated with a proteasome inhibitor, an immunomodulatory drug, an alkylating agent, and a steroid and have refractory disease or are intolerant to proteasome inhibitor therapy or immunomodulatory drug therapy (pg 97-98).
Given that Elias teaches the claimed anti-CD38 antibody and method of treating multiple myeloma, and further given that Lokhorst et al teaches an anti-CD38 antibody for the treatment of relapsed/refractory multiple myeloma, one of ordinary skill in the art would have had a reasonable and predictable expectation of arriving at the claimed method because substituting one equivalent element for another known for the same purpose (i.e. the anti-CD38 antibody of Elias for the anti-CD38 antibody of Lokhorst et al) renders an invention obvious and an “express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious.” In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982).
While Elias in view of Lokhorst et al is silent on (A) the ability of this antibody to bind human red blood cells (instant claim 58), (B) its use results in less than 1% incidence of grade 3 or 4 infusion-related reactions and less than 10% incidence of grade 3 or 4 anemia (claim 58), (C) its ability to not cause hemolytic anemia or thrombocytopenia (instant claim 60), (D) its ability to deplete RBCs less than 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% (instant claim 61), (E) its ability to deplete platelets less than 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% (instant claim 62), (F) its use results in less than 30% incidence of grade 3 or 4 TRAEs or TEAEs (instant claim 63), (G) its use results in less than 10% incidence of grade 3 or grade 4 IRRs (instant claim 58), (H) its use results in a reduction in disease burden of at least 50% (instant claims 69 and 74), (I) it use results in prolonged disease stabilization (instant claims 70 and 74), (J) its use results in a reduction of plasmablasts in blood (instant claim 71), (K) its use results in reduction of plasmablasts in bone marrow (instant claim 72), and (L) its use results in reduction of plasma cells in bone marrow (instant claim 73), it is clear that a subcutaneous unit dosage form comprised of the antibody of Elias when administered to a subject with refractory/relapse multiple myeloma would have the same characteristics as the instantly claimed subcutaneous unit dosage form, since there is no evidence to the contrary. Further, since the subcutaneous unit dosage form of Elias satisfies all the structural limitations set forth in the claims, it necessarily follows that the claimed unit dosage form inherently possesses the functionality and the ability to serve the intended use recited in the claims, e.g., the treatment of relapsed/refractory multiple myeloma.
When the references disclose all the limitations of a claim except a property or function, and the examiner cannot determine whether or not the reference inherently possesses properties which anticipate or render obvious the claimed invention, the burden shifts to the applicant, as in In re Fitzgerald, 619 F.2d 67, 205 USPQ 594 (CCPA 1980), See MPEP 2112-2112.02. In the instant case, Elias in view of Lokhorst et al teaches the antibody, the dose, and the administration step for treating a subject with relapsed/refractory multiple myeloma. In the absence of any unexpected results regarding the method, the instant claims are obvious over the teachings of Elias and Lokhorst et al.
Claims 58-75 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2012092612 (“Elias”) in view of Lokhorst et al, as applied to claims 58-74 above, and further in view of Kang et al, published April 2016 (instant PTO-892).
The teachings of Elias and Lokhorst et al are discussed above; Elias does not teach an antibody dosage formulation at a concentration of 100 mg/ml.
Kang teaches methods for the development of monoclonal antibody formulations (pg 40), including a formulation with an antibody concentration of 100 mg/ml (pg 42).
Given that Elias in view of Lokhorst et al teaches the claimed antibody and method of treating and further given that Kang et al teaches antibody formulation at 100 mg/ml, it would have been obvious to the ordinary artisan to formulate the antibody of Elias at 100 mg/ml. Even though every antibody is unique, because their structures are similar, known successful antibody formulations can guide the development of stable and effective formulations for other monoclonal antibodies (pg 40, column 2). The amount of experimentation necessary to development a formulation for a given antibody at 100 mg/ml is not considered undue, as antibody formulations at this concentration were already known in the art.
Response to Arguments
Applicant's arguments filed January 16, 2026 have been fully considered but they are not persuasive.
Applicant asserts that the claimed method is associated with unexpected and unpredictable results regarding reduction in harmful side effects that are associated with other anti-CD38 antibodies known in the art (remarks, pg 7-10). Further, applicant submits that the claimed method achieves unexpectedly superior efficacy compared to methods using the anti-CD38 daratumumab in patients with relapsed/refractory multiple myeloma (RRMM) (remarks, pg 11-12). When considering a case of nonobviousness regarding unexpected results, the evidence of unexpected results must be commensurate in scope with the claimed invention (see MPEP §716.02(d)). Because Elias in view of Lokhorst teaches the antibody, the dose, and the method, any unexpected results regarding the dose and disease treatment need to be limited to the claimed antibody. To establish unexpected results over a claimed range, applicants should compare a sufficient number of tests both inside and outside the claimed range to show the criticality of the claimed range. In re Hill, 284 F.2d 955, 128 USPQ 197 (CCPA 1960); see MPEP716.02(d).II. Also see MPEP 2144.05.III.A, which states that applicants can rebut a prima facie case of obviousness by showing the criticality of the range. "The law is replete with cases in which the difference between the claimed invention and the prior art is some range or other variable within the claims. . . . In such a situation, the applicant must show that the particular range is critical, generally by showing that the claimed range achieves unexpected results relative to the prior art range." In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Thus, the burden is on the applicant to demonstrate that the concentration of anti-CD38 antibody exhibits unexpected results over the previously taught ranges. Types of unexpected results include greater than expected results, superiority of a property shared with the prior art, presence of an unexpected property, or absence of an expected property (see MPEP 716.02(a)I).
To this point, applicant provides evidence that the claimed dose has unexpectedly superior efficacy compared to a higher dose (1200 mg) (Krishnan et al, remarks, pg 10). These results, however, are not persuasive for nonobviousness. In the three treatment groups receiving 300 mg, 600 mg, and 1200 mg, the overall response rates were 42% (n=12), 47% (n=22), and 33% (n=3), respectively. Given that there were only 3 patients in the group receiving 1200 mg, one of ordinary skill in the art would not be convinced that the decrease in the ORR was due to an unexpected inferior property of the anti-CD38 antibody at the higher dose. The burden is on the applicant to demonstrate the superiority of the claimed doses compared to the higher dose. As is, it remains unclear if the observed higher efficacy at lower doses is an actual increase in efficacy or a sporadic result. Applicant may consider submitting additional evidence to support that this trend can be reliably reproduced to strengthen the support for unexpected results within the prior dose range taught by Elias.
Without evidence of unexpected results or a teaching away in the prior art, the claimed dosages of Elias in the method of treating multiple myeloma would have been obvious to one of ordinary skill in the art. One would modify the teachings of Elias by varying the dosage to arrive at the presently claimed method to treat RRMM, especially since the prior art already recognized that dose modification is part of routine optimization. A person of ordinary skill in the art would have been motivated to apply a dose within the dose range Elias in the method of Elias in view of Lokhorst and have a reasonable expectation of successfully treating RRMM. When provided with all of the starting conditions, including the therapeutic of Elias and the target population of Elias and Lokhorst, discovering the optimum doses in the method of treatment via routine experimentation does not make the instant claims patentable
The double patenting rejection over U.S. patent 12,371,506 has been withdrawn, because the scope of the new claims no longer overlap with the claims of ‘506, which are directed to a method of treating an autoimmune disease.
Conclusion
No claim is allowed.
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Jennifer Benavides
Examiner
Art Unit 1675
/JENNIFER A BENAVIDES/Examiner, Art Unit 1675