DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant's reply filed on 1/16/2026 is acknowledged. New claim 320 has been added. Claims 203-210, 212-214, 234-236 and 304-320 are pending. Claims 1-202, 211, 215-233 and 237-303 are canceled. Claims 203-210 and 304-309 have been amended.
3. Claims 203-210, 212-214, 234-236 and 304-320 are under examination.
Information Disclosure Statement
4. The information disclosure statement filed on 1/16/2026 has been considered by the examiner.
Objections Withdrawn
5. All objections are withdrawn in view of applicant’s amendments.
Rejection Maintained
Claim Rejections - 35 USC § 112
6. 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.
7. Claims 204 and 304-319 remain 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.
Claim 204 has been amended to recite “the combination dosing regimen is administered for at least 25.3 months”. This limitation is considered new matter since the specification, drawings and claims as filed do not provide support for this limitation. Although the specification discloses “the median duration of treatment was 25.3 months (range: 0.1 to 40.4)” (page 52, lines 1-3), the specification does not disclose “at least 25.3 months” (which has no upper limit).
Claims 304-319 are rejected as being dependent from claim 204 and having the same new matter.
If applicant believes that support for the above-mentioned phrases or terms is present in the specification, claims or drawing as originally filed, applicant must, in responding to this action, point out with particularity, where such support may be found.
Applicant is required to cancel the new matter in the reply to this Office Action.
Claim Rejections - 35 USC § 102
8. 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.
9. Claims 203-210, 213-214, 304-309, 311-312 and new claim 320 remain/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Facon et al. (Blood, 2018, 132(Suppl 1); 8 pages, IDS filed on 12/23/2022).
Regarding claims 203, 209 and new claim 230, Facon et al discloses phase 3 randomized study of daratumumab plus lenalidomide and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) in patients with newly diagnosed multiple myeloma ineligible for transplant (MAIA ) (Title). Facon et al. teaches a method of treating newly diagnosed multiple myeloma patients ineligible for high dose chemotherapy with autologous stem cell transplantation, comprising treating patients with 28-day cycles of Rd±DARA, wherein R (lenalidomide) was administered with a dose of 25 mg (oral) QD on days 1-21, d (dexamethasone) is administered at a dose of 40 mg (oral) on days 1, 8, 15 and 22, DARA was given at 16 mg/kg (intravenously) QW for cycles 1-2, Q2W for cycles 3-6, and Q4W thereafter (page 2). Facon et al. discloses that the subject achieves progression-free survival (PFS) of at least 42 month (see Fig).
The instant specification defines the PFS2 as the time from initiation of therapy to progression on the next line of therapy or death, whichever comes first, and defines PFS as time from initiation of therapy to first evidence of disease progression or death due to any cause, whichever occurs first. (page 12, lines 26-33 of the instant specification). A PFS of 42 month would meet the limitation of a PFS2 of at least 36 month because at 42 month, these patients have not received a next line therapy and are still alive.
Furthermore, the method of Facon would have achieved identical results given that the method steps and patient populations are all identical.
Regarding claim 204, Facon et al. discloses that interim analysis occurred on Sept 24, 2018 with a median follow up of 28 months (Results), indicating these patients have been treated for at least 25.3 months.
Regarding claims 205-208 and 304-307, Facon et al. teaches that the addition of DARA to Rd in patients with transplant-ineligible NDMM significantly reduced the risk of progression or death by 45%, resulted in deeper responses with a complete response (CR) or better rate of 47.6% in the D-Rd arm compared with 24.7% in the Rd arm (odds ratio [OR] 2.75, 95% CI, 2.01 to 3.76; P <0.0001). The very good partial response (VGPR) or better rate was 79.3% in the D-Rd arm compared with 53.1% in the Rd arm (OR3.4, 95% CI, 2.45 to 4.72; P <0.0001) (pages 2-3). Furthermore, Facon and the instant specification both describe the results of the same clinical trial MAIA (See Title of Facon, and page 24, lines 12-14 and Example 3 of the instant specification). The method of Facon would have achieved identical results given that the method steps and patient populations are all identical.
Regarding claims 210 and 309, Facon and the instant specification both describe the results of the same clinical trial MAIA (See Title of Facon, and page 24, lines 12-14 and Example 3 of the instant specification), the patient population of Facon is identical to that of the instant application, as such would necessarily include patients having normal hepatic function.
Regarding claim 308, Facon et al. teaches that the patients are ineligible for high dose chemotherapy with autologous stem cell transplantation (page 2).
Regarding claims 213-214 and 311-312, Facon et al. teaches that lenalidomide is administered orally and dexamethasone is administering orally (page 7, Arms-Experimental), indicating lenalidomide and dexamethasone are self-administered.
Applicant’s Arguments
The response states that independent claim 203 is amended to recite "wherein the method achieves an improved rate of progression-free survival 2 (PFS2) when compared to administration of lenalidomide and dexamethasone alone (Rd)."
Facon does not disclose this feature. Indeed, Facon does not mention PFS2, let alone
providing results demonstrating that daratumumab improves the rate of PFS2 in newly diagnosed multiple myeloma patients. Accordingly, independent claim 203, particularly as amended herein is not anticipated by Facon.
Examiner’s Response
Applicant’s arguments have been carefully considered but are not persuasive. Facon et al. discloses that the subject achieves progression-free survival (PFS) of at least 42 month (see Fig). The instant specification defines the PFS2 as the time from initiation of therapy to progression on the next line of therapy or death, whichever comes first, and defines PFS as time from initiation of therapy to first evidence of disease progression or death due to any cause, whichever occurs first. (page 12, lines 26-33 of the instant specification). A PFS of 42 month would meet the limitation of a PFS2 of at least 36 month because at 42 month, these patients have not received a next line therapy and are still alive. Facon et al. discloses a complete response (CR) or better rate of 47.6% was achieved in the D-Rd arm compared with 24.7% in the Rd arm (odds ratio [OR] 2.75, 95% CI, 2.01 to 3.76; P <0.0001).
Furthermore, because the method of the prior art is identical to the method of instant claims, practicing the method of prior art would inherently or necessarily lead to the same results.
Claim Rejections - 35 USC § 103
10. 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.
11. Claims 203-210, 213-214, 234-236, 304-309, 311-319 and new claim 320 remain/are rejected under 35 U.S.C. 103 as being unpatentable over Facon et al. (Blood, 2018, 132(Suppl 1); 8 pages, IDS filed on 12/23/2022), in view of Prescribing Information of DARZALEX (Daratumumab) (pub. date: 11/2015).
The teachings of Facon et al. have been set forth above as they apply to claims 203-210, 213-214, 304-309, 311-312 and 320.
Regarding claims 234-236 and 317-319, Facon does not disclose that daratumumab is produced in a mammalian cell line, and the mammalian cell line is a Chinese hamster ovary (CHO) cell line, and the molecular weight of daratumumab is about 148 kDa.
Regarding claims 313-316, Facon does not disclose that daratumumab is provided for administration by a manufacturer of daratumumab in a single-dose vial comprising 100 mg daratumumab in 5 mL of solution or in a single-dose vial comprising 400 mg daratumumab in 20 mL of solution, wherein each single-dose vial comprising 100 mg daratumumab in 5 mL of solution contains 0.9 mg glacial acetic acid, 127.5 mg mannitol, 2 mg polysorbate 20, 14.8 mg sodium acetate trihydrate, 17.5 mg sodium chloride and water for injection, and each single-dose vial comprising 400 mg daratumumab in 20 mL of solution contains 400 mg daratumumab, 3.7 mg glacial acetic acid, 510 mg mannitol, 8 mg polysorbate 20, 59.3 mg sodium acetate trihydrate, 70.1 mg sodium chloride and water for injection, wherein daratumumab is diluted into 0.9% sodium chloride prior to administration.
Prescribing Information of Daratumumab teaches that the population PK analysis included 189 patients with normal hepatic function and 34 with mild hepatic impairment patients, no clinical differences in the exposure to daratumumab were observed between patients with mild hepatic impairment and those with normal hepatic function (page 14, para 1). Prescribing Information of Daratumumab teaches that daratumumab has not been studied in patients with moderate or severe hepatic impairment (page 14, para 1). Prescribing information discloses that daratumumab is an IgG1[Symbol font/0x6B] human monoclonal antibody against CD38 antigen, produced in mammalian cell line (Chinese Hamster Ovary (CHO)) using recombinant DNA technology and the molecular weight of daratumumab is about 148 kDa (page 12, para 1).
Prescribing Information of Daratumumab discloses that daratumumab is provided for administration by a manufacturer of daratumumab in a single-dose vial comprising 100 mg daratumumab in 5 mL of solution or in a single-dose vial comprising 400 mg daratumumab in 20 mL of solution, wherein each single-dose vial comprising 100 mg daratumumab in 5 mL of solution contains 0.9 mg glacial acetic acid, 127.5 mg mannitol, 2 mg polysorbate 20, 14.8 mg sodium acetate trihydrate, 17.5 mg sodium chloride and water for injection, and each single-dose vial comprising 400 mg daratumumab in 20 mL of solution contains 400 mg daratumumab, 3.7 mg glacial acetic acid, 510 mg mannitol, 8 mg polysorbate 20, 59.3 mg sodium acetate trihydrate, 70.1 mg sodium chloride and water for injection, wherein daratumumab is diluted into 0.9% sodium chloride prior to administration ((see pages 18 and 19 product label).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used daratumumab described in the Prescribing Information in the method of Facon. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success because the Prescribing Information discloses in detail how to use the commercially available daratumumab to treat patients having myeloma.
Please note that Ahmadi et al. (US2017/0044265A1, pub. date: 2/16/2017) was inadvertently included by the examiner in the title of rejection, as evidenced by the body of the rejection.
12. Claims 203-210, 212-214, 234-236 and 304-319 and new claim 320 remain/are rejected under 35 U.S.C. 103 as being unpatentable over Facon et al. (Blood, 2018, 132(Suppl 1); 8 pages, IDS filed on 12/23/2022), in view of Prescribing Information of DARZALEX (Daratumumab) (pub. date: 11/2015) and Ahmadi et al. (US2017/0044265A1, pub. date: 2/16/2017).
The teachings of Facon et al. and Prescribing Information have been set forth above as they apply to claims 203-210, 213-214, 234-236, 304-309 and 311-320.
Regarding claims 212 and 310, Facon does not teach that dexamethasone is administered as pre-medication on daratumumab administration days.
Prescribing Information of Daratumumab teaches administering pre-infusion medications to reduce the risk of infusion reaction to all patients approximately 1 hour prior to every infusion of daratumumab, wherein the pre-infusion medications include corticosteroid such as methylprednisone or equivalent dose of an intermediate-acting or long acting corticosteroid (page 3, Pre-infusion Medication).
Ahmadi et al. teaches administration of 20 mg dexamethasone at dose of 20 mg before infusion of daratumumab as prophylaxis for infusion-related reactions ([0396]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Facon to administer dexamethasone as premedication for daratumumab in view of Prescribing Information and Ahmadi. One of ordinary skill in the art would have been motivated to do so because Prescribing Information teaches administering pre-infusion medications to reduce the risk of infusion reaction to all patients approximately 1 hour prior to every infusion of daratumumab, wherein the pre-infusion medications include corticosteroid such as methylprednisone or equivalent dose of an intermediate-acting or long acting corticosteroid (page 3, Pre-infusion Medication), and Ahmadi et al. teaches administration of dexamethasone before infusion as prophylaxis for infusion-related reactions ([0396]). One of ordinary skill in the art would have had a reasonable expectation of success because Facon teaches administering 40 mg dexamethasone and Ahmadi et al. teaches administration of 20 mg dexamethasone before infusion as prophylaxis for infusion-related reactions ([0396]).
Applicant’s Arguments
The response states that independent claim 203 is amended to recite "wherein the method achieves an improved rate of progression-free survival 2 (PFS2) when compared to administration of lenalidomide and dexamethasone alone (Rd)." None of Facon, Prescribing Information, and Ahmadi, either alone or in combination, teaches or suggests this feature. In contrast, the Application as filed demonstrates this improvement. The data in the Application as filed suggest that DRd prolongs overall survival compared to Rd. In fact, ASH Clinical News providing commentary on the results in Facon, states that "Dr. Facon noted that the overall survival data from the MAIA trial are not yet mature, which limits comparisons between the daratumumab combination and other regimens for the treatment of myeloma." Therefore, prior to the present invention, the person of ordinary skill in the art would have no expectation that the DRd combination therapy as claimed would achieve prolonged PFS2, and thus overall survival, in newly diagnosed multiple myeloma patients, compared to the control combination therapy.
Examiner’s Response
Applicant’s arguments have been carefully considered but are not persuasive for the same reasons discussed in the 102(a)(1) rejection.
Conclusion
13. No claims are allowed.
THIS ACTION IS MADE FINAL. 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.
14. Any inquiry concerning this communication or earlier communications from the examiner should be directed to HONG SANG whose telephone number is (571)272-8145. The examiner can normally be reached Monday-Friday 8am-5pm.
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/HONG SANG/Primary Examiner, Art Unit 1643