RESPONSE TO APPLICANT’S AMENDMENT
1. Applicant's amendment, filed 11/07/2025, is acknowledged.
2. Claims 1-12, 14-19 and 21-24 are pending and under examination.
3. Applicant’s IDS filed 11/07/2025, is acknowledged.
3. The following new grounds of rejection are necessitated by the amendment submitted 11/07/2025.
4. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
5. Claims 1-12, 14 and 21 stand and 18-19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kaufman et al. (JHOP. March 2021, vol. 11, Special Feature, Abstract #CT04).
Kaufman et al evaluate the safety of pre- and post-dose corticosteroid tapering during SC daratumumab (comprising the claimed SEQ ID NOs) administration. Kaufman et al teach that relapsed or refractory multiple myeloma (RRMM) patients with ≥2 previous treatment lines received SC daratumumab (daratumumab 1800 mg plus rHuPH20 30,000 U in 15 mL) by manual SC injection per approved IV monotherapy dosing schedule. Patients received a 3-week tapering schedule (corticosteroid-free by cycle 1, day 22), with methylprednisolone given orally or intravenously predose (cycle 1, day 1, 100 mg; cycle 1, day 8, 60 mg; cycle 1, day 15, 30 mg) and orally postdose (cycle 1, day 1, 20 mg for 2 days; cycle 1, day 8, 20 mg for 1 day; cycle 1, day 15, 20 mg for 1 day), or a 2-week tapering schedule (corticosteroid-free by cycle 1, day 15), with methylprednisolone given orally or intravenously pre-dose (cycle 1, day 1, 100 mg; cycle 1, day 8, 60 mg) and orally post-dose (cycle 1, day 1, 20 mg for 2 days; cycle 1, day 8, 20 mg for 1 day). Kaufman concluded that rapid corticosteroid tapering over 3 or 2 weeks is safe in patients with relapsed or refractory multiple myeloma receiving SC daratumumab. These data help guide future SC daratumumab combinations (ie, T-cell redirectors, CAR T-cell, or checkpoint inhibitors), where limiting concurrent corticosteroids may be preferred (abstract).
Claim 18-19 are included because Nahi et al teaches that patients 30 RRMM patients receiving DARA SC showed that tapering of pre- and post-dose corticosteroids over 3 or 2 weeks was not associated with increased rates of IRRs. The .05 mg/kg/day and 0.01 mg/kg/day is optional “and/or).
The reference teachings anticipate the claimed invention.
Applicant’s arguments, filed 11/07/2025, have been fully considered, but have not been found convincing.
Applicant submits that independent claim 1 is amended to recite “wherein ... the reduction, elimination, or reduction followed by elimination of the pre-dose corticosteroid does not increase immunogenicity to daratumumab post treatment.” Kaufman does not disclose this feature. Applicant concluded that claim 1 is not anticipated by Kaufman. Claims 2-12, 14, and 21 depend, directly or indirectly, from claim 1, and, therefore, are not anticipated by Kaufman for at least the same reason.
This is not found persuasive because the claimed “wherein ... the reduction, elimination, or reduction followed by elimination of the pre-dose corticosteroid does not increase immunogenicity to daratumumab post treatment” is considered inherent properties to the claimed method of SC administer the anti-CD38 and a pre-dose corticosteroid. See MPEP 2111.04, which states that a "whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited" (Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), quoting Minton v. Nat ’I Ass ’n of Securities Dealers, Inc., 336 F.3d 1373, 1381,67 USPQ2d 1614, 1620 (Fed. Cir. 2003)). In the instant case, claim 1 simply expresses the intended result (the reduction, elimination, or reduction followed by elimination of the pre-dose corticosteroid does not increase immunogenicity to daratumumab post treatment) of a positively recited method step (administration of an anti-CD38 antibody and a pre-dose corticosteroid). As such, the teachings of Kaufman et al anticipate each of claims 1-12, 14 and 21.
6. Claims 1-12, 14, and 21 stand and 18-19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nahi et al (Abstract release date 05/14/2020) EHA library, 06/12/2020, 293526, EP1038) for the same reasons set forth in the previous Office Action mailed 05/08/205.
Nahi et al further DARA was given once weekly on days (D) 1, 8, 15, and 22 during Cyles © 1 and 2, every 2 weeks on D1 and D15 during C3, through C6, and every 4 weeks thereafter for C7+. Nahi also teaches patients received a 3-week tapering schedule (Figure 2A); corticosteroid-free by C1D22 or 2-week tapering schedule (Figure 2B; Corticosteroid-free by C1D15). 3-week tapering schedule: methylprednisolone (MP) given orally (PO)/IV pre-dose (C1D1, 100 mg; C1D8, 60 mg; C1D15, 30 mg) and PO post-dose (C1D1, 20 mg for 2days, C1D8, 20 mg for 1 day; C1D15, 20 mg for 1day). For the 2-week tapering schedule: MP given PO/IV pre-dose (C1D1, 100 mg; C1D8, 60 mg) and PO post-dose (C1D1, 20 mg for 2days; C1D8, 20 mg for 1day). The results shows that patients in the 3-week group received a median (range) of 14.0 (2-22) DAR SC doses without corticosteroids. Patients in the 2-week group received a median (range) of 12.0 (3-19) DARA SC doses without corticosteroids. Nahi et al concluded that in 30 RRMM patients receiving DARA SC showed that tapering of pre- and post-dose corticosteroids over 3 or 2 weeks was not associated with increased rates of IRRs. The results suggest that rapid corticosteroid tapering is safe in RRMM patients receiving DARA SC.
Claim 18-19 are included because Nahi et al teaches that patients 30 RRMM patients receiving DARA SC showed that tapering of pre- and post-dose corticosteroids over 3 or 2 weeks was not associated with increased rates of IRRs. The .05 mg/kg/day and 0.01 mg/kg/day is optional “and/or).
Applicant’s arguments, filed 11/07/2025, have been fully considered, but have not been found convincing.
Applicant submits that independent claim 1 is amended to recite “wherein ... the reduction, elimination, or reduction followed by elimination of the pre-dose corticosteroid does not increase immunogenicity to daratumumab post treatment.” Nahi does not disclose this feature. Accordingly, claim 1 is not anticipated by Nahi. Claims 2-12, 14, and 21 depend, directly or indirectly, from claim 1, and, therefore, are not anticipated by Nahi for at least the same reason.
This is not found persuasive because the claimed “wherein ... the reduction, elimination, or reduction followed by elimination of the pre-dose corticosteroid does not increase immunogenicity to daratumumab post treatment” is considered inherent properties to the claimed method of SC administer the anti-CD38 and a pre-dose corticosteroid. See MPEP 2111.04, which states that a "whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited" (Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), quoting Minton v. Nat ’I Ass ’n of Securities Dealers, Inc., 336 F.3d 1373, 1381,67 USPQ2d 1614, 1620 (Fed. Cir. 2003)). In the instant case, claim 1 simply expresses the intended result (the reduction, elimination, or reduction followed by elimination of the pre-dose corticosteroid does not increase immunogenicity to daratumumab post treatment) of a positively recited method step (administration of an anti-CD38 antibody and a pre-dose corticosteroid). As such, the teachings of Kaufman et al anticipate each of claims 1-12, 14 and 21.
7. 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.
8. Claims 1-12, 14-19 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Kaufman et al. (JHOP. March 2021, vol. 11, Special Feature, Abstract #CT04) or Nahi et al (Abstract release date 05/14/2020) EHA library, 06/12/2020, 293526, EP1038.
The teachings of the Kaufman et al and Nahi et al have been discussed, supra.
The reference teachings differ from the claimed invention only in the recitation that the corticosteroid is administered at a dose of < 0.05 mg/kg/day in claim 15,
< 0.01 mg/kg/day in claim 16, maintained at a corticosteroid dose of ≤ 0.05 mg/kg/day in claim 18 or ≤ 0.05 mg/kg/day in claim 19 and about 20 mg pre-dose dexamethasone on day 1 and then eliminated in claim 22.
Given that DARA plus rHuPH20 have been shown by Kaufman et al and Nahi et al to be effective for the treatment of MM. DARA plus rHuPH20 taper and reduce the need fro corticosteroids in the MM treatment with reasonable expectation of success. Those of skilled in the art would have been motivated to use DARA plus rHuPH20 to tapper, reduce or eliminate a need for the corticosteroid in MM in view of the Kaufman and Nahi references to managing corticosteroids side effects while maintaining treatment efficacy of DARA plus rHuPH20. Given that DARA plus rHuPH20 is helpful in reducing the dose of corticosteroids such as MP, needed to achieve an effect which is essential in minimizing the corticosteroid tapering process.
It would have been obvious to one of ordinary skill in the art at the time of the invention to administer the DARA plus rHuPH20 of the Kaufman et al and Nahi et al to taper, reduce and/or eliminate the need for corticosteroid therapy taught by the Kaufman et al and Nahi et al references with reasonably expectation of success reduce or tapered dose of corticosteroids to a patient suffering from relapse or refractory MM who is intolerant or unresponsive to steroids. One of ordinary skill in the art would have been motivated to co-administer DARA plus rHuPH20 with lower doses of corticosteroids such as ≤ 0.05/0.01 mg/kg/day and to reduce or taper the dose of corticosteroids because Kaufman et al and Nahi et al references disclose that the DARA plus rHuPH20 is useful for treating the same disorders RRMM and that steroids produce serious side effects and should therefore be tapered. Would motivate one skill in the art to administer anti- DARA plus rHuPH20 to reduce or eliminate the need for corticosteroids because corticosteroids and DARA plus rHuPH20 are used for treating the same MM and thus can be substituted for each other. One of ordinary skill in the art would have reasonably expected success reducing or tapering the dose of steroids because it is within the ordinary level of skill in the art to substitute one drug for another when both drugs are useful for the same indication.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
9. Claims 22-24 are rejected under 35 U.S.C. 103 as being unpatentable over Kaufman et al. (JHOP. March 2021, vol. 11, Special Feature, Abstract #CT04) or Nahi et al (Abstract release date 05/14/2020) EHA library, 06/12/2020, 293526, EP1038) as applied to claims1-12, 14-19 and 21 and further in view of Faiman et al (Clinical Journal of Oncology Nursing, Suppl 12(3), 53-63, 2008) San-Miguel et al (Haematologica. doi:10.3324/haematol.2019.243790).
The teachings of the Kaufman et al and Nahi et al have been discussed, supra.
The reference teachings differ from the claimed invention only in the recitation of about 20 mg pre-dose dexamethasone on day 1 and then eliminated in claim 22.
Faiman et al provide “Let down” effect: This usually is characterized by fatigue or “weakness” and myalgia following discontinuation of steroids. It may occur when patients are receiving high dose steroids (e.g., dexamethasone) several days each week. Pharmacologic interventions include low-dose steroids for a few days following high-dose steroid administration, tapered doses of steroids, and reduced steroid doses. Figure 2 presents a suggested dexamethasone taper schema. However, dose reductions for dexamethasone should be based on the clinician’s experience and the patient’s symptoms. Reducing the dose of dexamethasone may reduce the risk of thromboembolic events, particularly if administered in combination with other antimyeloma agents (see page 54, under Constitutional Signs and Symptoms). Fig. 2 provide suggestion for dexamethasone taper, wherein dose reductions for dexamethasone should be based on clinician experience and the most current clinical data available, wherein if taking dexamethasone 40 mg PO daily , days 1–4, 9–12, 17–21, consider 50% dose reduction if any grade 2 or grade 3 steroid toxicity occurs. If dose is already reduced, consider reducing dose frequency days 1–4 and 15–18, at a dose of dexamethasone 20 mg PO each day if grade 2 or grade 3 toxicity persists.
San-Miguel et al for the prevention of delayed infusion-related reactions (IRRs), patients also received methylprednisolone 20 mg (or equivalent) on the first two days following all daratumumab infusions. In the absence of infusion-related adverse events (AEs) after the first three infusions, post-infusion corticosteroids were administered per investigator discretion.
Those of skill in the art would have had a reason to use about 20 mg pre-dose dexamethasone on day 1 and in RRMM patients taught by Kaufman and Nahi references based on clinical experience and most current clinical data available as taught by Faiman et al and San-Miguel et al references. A person having ordinary skill in the art would have found it obvious to determine the optimum dexamethasone reductions of pre-dose of dexamethasone based on clinician experience and the most current clinical data available because the dose concentration is effect of result-effective variables known in the art. Recognition that a property (DARA plus rHuPH20 treat RRMM) is affected by the variable (results in reduction of dexamethasone) is sufficient to find the variable result-effective.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
10. No claim is allowed.
11. 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 extension fee 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 date of this final action.
12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAHER M HADDAD whose telephone number is (571)272-0845. The examiner can normally be reached on Monday-Friday from7:00AM to 4:30PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu, can be reached at telephone number 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from Patent Center. Status information for published applications may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center for authorized users only. Should you have questions about access to Patent Center, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) Form at https://www.uspto.gov/patents/uspto-automated- interview-request-air-form.
November 24, 2025
/MAHER M HADDAD/ Primary Examiner, Art Unit 1644