Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 06APR2026 has been entered.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Claims 1-2, 6-19, 21-25, and 31-41 have an effective filing date of 28MAR2019.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 06APR2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Election/Restriction
In the response filed on 7/8/2024 Applicant elected, without traverse:
A distinct pharmaceutical composition with dosage, frequency, route, and duration of administration
pharmaceutical composition with dosage of:
about 1,800 mg of said antibody and about 30,000 U rHuPH20;
about 1.3 mg/m2 of bortezomib;
about 40 mg of dexamethasone
a frequency of:
antibody and rHuPH20: once a week;
bortezomib: twice weekly;
dexamethasone: once a week;
a route of:
antibody and rHuPH20: subcutaneously;
bortezomib: subcutaneously;
dexamethasone: orally or intravenously
a duration of: one or more 3-week cycles
A distinct excipient
10 mM of the excipient histidine
Status of Claims
Claims 1-2, 6-19, 21-23, 25, and 31-41 are currently pending and presented for examination on the merits.
Claims 13, 15-19, 34, and 36 are withdrawn from further consideration by Examiner under 37 CFR 1.142(b) as being drawn to a non-elected invention.
Claim 1 is amended.
Claims 3-5, 20, 24, and 26-30 are canceled.
Rejections Withdrawn
The rejection filed under 35 U.S.C. 112(b) is withdrawn in view of Applicant canceling the claim.
Rejections Maintained
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-2, 6-12, 14, 21, 23, 25, 31-33, 35, and 37-41 are rejected under 35 U.S.C. 103 as being unpatentable over Elias et al (WO 2012092616 A1, IDS 4/22/2024), Sanofi (EP 3421494 A1), and further in view of San-Miguel et al (Subcutaneous Daratumumab in Patients With Relapsed or Refractory Multiple Myeloma: Part 2 Update of the Open-label, Multicenter, Dose Escalation Phase 1b Study (PAVO), PF555, 2018, IDS 4/22/2024).
Elias et al teaches CD38 is upregulated in hematopoietic malignancy multiple myeloma [0010]. Elias et al further teaches a method of treating conditions that express CD38 including multiple myeloma [0155]. Elias et al further teaches response rates can be determined by standardized response criteria to that disease [0251]. Elias et al further teaches the administration of treatments via subcutaneously and orally [0249]. Elias et al further teaches administering the anti-CD38 antibody in combination with additional therapeutics [0272]. Elias et al further teaches the additional chemotherapeutic agent bortezomib [0273]. Elias et al further teaches the antibody comprising the IgG1 isotype [0059]. Elias et al further teaches the anti-CD38 antibody daratumumab [0307]. Elias et al further teaches administering the anti-CD38 antibody once a week, for up to 8 times [0267]. Elias et al further teaches administering an excipient with the formulation [0243]. Elias et al further teaches administering the excipient histidine [0243].
Elias et al teaches an anti-CD-38 antibody comprising SEQ ID NO:24. A comparison of instant SEQ ID NO: 7 and SEQ ID NO: 24 of Elias et al is shown below.
Elias et al SEQ ID NO: 7 and SEQ ID NO: 24 of Elias et al.
Query Match 100.0%; Score 643; Length 122;
Best Local Similarity 100.0%;
Matches 122; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLLESGGGLVQPGGSLRLSCAVSGFTFNSFAMSWVRQAPGKGLEWVSAISGSGGGTYY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLLESGGGLVQPGGSLRLSCAVSGFTFNSFAMSWVRQAPGKGLEWVSAISGSGGGTYY 60
Qy 61 ADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYFCAKDKILWFGEPVFDYWGQGTLVTV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYFCAKDKILWFGEPVFDYWGQGTLVTV 120
Qy 121 SS 122
||
Db 121 SS 122
Elias et al teaches an anti-CD-38 antibody comprising SEQ ID NO:25. A comparison of instant SEQ ID NO: 8 and SEQ ID NO: 25 of Elias et al is shown below.
Elias et al SEQ ID NO: 8 and SEQ ID NO: 25 of Elias et al.
Query Match 100.0%; Score 556; Length 108;
Best Local Similarity 100.0%;
Matches 107; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPA 60
Qy 61 RFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPTFGQGTKVEIK 107
|||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPTFGQGTKVEIK 107
Elias et al does not specifically teach administering overall response rate. However, this deficiency is made up in the teachings of Sanofi.
Sanofi teaches a method of treating multiple myeloma [0002]. Sanofi et al further teaches the initial chemotherapy regimen of bortezomib and dexamethasone [0002]. Sanofi et al further teaches measuring results using Overall Response Rate (ORR) [0032]. Sanofi et al further teaches the ORR is determined by complete response + very good response + partial response [0043]. Sanofi further teach administering bortezomib composition for 6 cycles [0027]. Sanofi further teaches the preferred administration of chemotherapeutic agents is subcutaneously or intravenously [0249]. Sanofi further teaches administering agents orally [0249].
Elias et al does not specifically teach recombinant human hyaluronidase (rHuPH20). However, this deficiency is made up in the teachings of San-Miguel.
San-Miguel et al teaches the use of a CD38-targeted antibody (daratumumab) in combination with 30,000 U of rHuPH20.
One of ordinary skill, before the effective filing date, would have been motivated to combine Elias’s method of treating multiple myeloma comprising anti-CD38 antibodies in combination with bortezomib, with Sanofi’s method of treating multiple myeloma comprising bortezomib and dexamethasone and analyzing the results using ORR, with San-Miguel’s method of treating relapsed multiple myeloma using an anti-CD38 antibody and rHuPH20. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to combine Elias, Sanofi, and San-Miguel’s methods for a method of improving ORR in a subject with multiple myeloma comprising administering an anti-CD38 antibody, rHuPH20, bortezomib and dexamethasone, because all references are teachings methods of treating multiple myeloma. The invention of the conflicting claims, Sanofi, and San-Miguel meets the limitations of claims 1-2, 8, 21, 23, and 40-41.
With respect to claims 6 and 7, given that the instant claims and the invention of the conflicting claims, Sanofi, and San-Miguel are not patentably distinct, one of ordinary skill in the art would expect the instant claims and the invention of the conflicting claims, Sanofi, and San-Miguel to demonstrate similar functional characteristics, such as achieving a non-inferior ORR.
With respect to claims 9 and 10, San-Miguel et al. teaches the administration of 1,800 mg daratumumab and 30,000 U of rHuPH20. Furthermore one of ordinary skill in the art generally recognizes the utility of optimizing the dosage of medicaments in a therapeutic regimen.
With respect to claims 11 and 12, Elias et al teaches administering an excipient with the formulation [0243]. Elias et al further teaches administering the excipient histidine [0243].
With respect to claims 14, 25, 31-33, and 35, one of ordinary skill in the art would appreciate that the administration schedule and dosage of a therapeutic regimen represent optimizable variable that affect the safety and efficacy of a therapeutic regimen, and one of ordinary skill in the art would thus recognize the utility of optimizing the administration schedule and dosage of medicaments in a therapeutic regimen.
With respect to claims 37-39, as indicated above, Elias et al teaches the administration of treatments via subcutaneous and oral routes of administration. Furthermore one of ordinary skill in the art would appreciate that therapeutic agents can generally be either self-administered or administered by others.
Claim(s) 1-2, 6-12, 14, 21-23, 25, 31-33, 35, and 37-41 are rejected under 35 U.S.C. 103 as being unpatentable over Elias et al (WO 2012092616 A1, IDS 4/22/2024), Sanofi (EP 3421494 A1), San-Miguel et al (Subcutaneous Daratumumab in Patients With Relapsed or Refractory Multiple Myeloma: Part 2 Update of the Open-label, Multicenter, Dose Escalation Phase 1b Study (PAVO), PF555, 2018, IDS 4/22/2024) as applied to claims 1-2, 6-12, 14, 21, 23, 25, 31-33, 35, and 37-41 above, and further in view of Jansson et al (US 20170121417 A1, IDS 4/22/2024, IDS 4/22/2024).
The teachings of Elias et al, Sanofi et al, and San-Miguel et al are discussed above.
Elias et al does not specifically teach SEQ ID NOs: 9 &10. However, this deficiency is made up in the teachings of Jansson et al.
With respect to claim 22, Jansson et al teaches an anti-CD38 antibody comprising SEQ ID NO: 12. A comparison of instant SEQ ID NO: 9 and SEQ ID NO: 12 of Jansson et al is shown below.
Instant SEQ ID NO: 9 and SEQ ID NO: 12 of Jansson et al.
Query Match 100.0%; Score 2410; Length 452;
Best Local Similarity 100.0%;
Matches 452; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLLESGGGLVQPGGSLRLSCAVSGFTFNSFAMSWVRQAPGKGLEWVSAISGSGGGTYY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLLESGGGLVQPGGSLRLSCAVSGFTFNSFAMSWVRQAPGKGLEWVSAISGSGGGTYY 60
Qy 61 ADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYFCAKDKILWFGEPVFDYWGQGTLVTV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYFCAKDKILWFGEPVFDYWGQGTLVTV 120
Qy 121 SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ 180
Qy 181 SSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELL 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 SSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELL 240
Qy 241 GGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 GGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ 300
Qy 301 YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR 360
Qy 361 EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS 420
Qy 421 RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 452
||||||||||||||||||||||||||||||||
Db 421 RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 452
Jansson et al teaches an anti-CD38 antibody comprising SEQ ID NO: 13. A comparison of instant SEQ ID NO: 10 and SEQ ID NO: 13 of Jansson et al is shown below.
Instant SEQ ID NO: 10 and SEQ ID NO: 13 of Jansson et al.
Query Match 100.0%; Score 1109; Length 214;
Best Local Similarity 100.0%;
Matches 214; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPA 60
Qy 61 RFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPTFGQGTKVEIKRTVAAPSVFIFPP 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPTFGQGTKVEIKRTVAAPSVFIFPP 120
Qy 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
Qy 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
||||||||||||||||||||||||||||||||||
Db 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
Jansson et al further teaches a method of treating multiple myeloma comprising administer an anti-CD38 antibody and rHuPH20 [0011-0012]. Jansson et al further teaches administering the excipient histidine at 10 mM [0019].
One of ordinary skill, before the effective filing date, would have been to combine the teachings of Elias, Sanofi, and San-Miguel’s methods for a method of improving ORR in a subject with multiple myeloma comprising administering an anti-CD38 antibody, rHuPH20, bortezomib and dexamethasone, with Jansson’s method of treating multiple myeloma comprising SEQ ID NOs: 9 and 10, and the excipient histidine at 10 mM. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to combine Elias, Sanofi, San-Miguel, and Jansson’s for method of improving ORR in a subject with multiple myeloma comprising administering an anti-CD38 antibody SEQ ID NOs: 9 &10, rHuPH20, bortezomib, dexamethasone, and histidine at 10mM, because all references are teachings methods of treating multiple myeloma.
Claim(s) 1-2, 6-12, 14, 21, 23, 25, 31-33, 35, and 37-41 are rejected under 35 U.S.C. 103 as being unpatentable over Elias et al (WO 2012092616 A1, IDS 4/22/2024), Sanofi (EP 3421494 A1), San-Miguel et al (Subcutaneous Daratumumab in Patients With Relapsed or Refractory Multiple Myeloma: Part 2 Update of the Open-label, Multicenter, Dose Escalation Phase 1b Study (PAVO), PF555, 2018, IDS 4/22/2024), and Kapoor et al (Bortezomib Combination Therapy in Multiple Myeloma, Semin. Hematol. 49(3): pgs. 1-22, 2012).
The teachings of Elias et al, Sanofi, and San-Miguel et al are discussed above.
With respect to claims 31-33, and 37-39, and Kapoor et al teaches a method of treating multiple myeloma [Abstract]. Kapoor et al further teaches a method of treating multiple myeloma comprising bortezomib and dexamethasone [Abstract]. Kapoor et al further teaches bortezomib administered at 1.3 mg/m2 twice a week [Table 2, pg. 16]. Kapoor et al further teaches bortezomib and dexamethasone administered in a 3 week cycle [1st Paragraph, pg. 3]. Kapoor et al further teaches dexamethasone administered at 40 mg weekly [B. b. Cyclophosphamide-Bortezomib based combinations, pg. 5]. Kapoor et al further teaches dexamethasone administered orally [Table 2, pg. 16]. Kapoor et al further teaches administering bortezomib intravenously [Table 2, pg. 16]. Kapoor et al further teaches administering bortezomib subcutaneously [B. a. Melphalan-Bortezomib based combinations, pg. 4].
One of ordinary skill, before the effective filing date, would have been to combine the teachings of Elias, Sanofi, and San-Miguel’s methods for a method of improving ORR in a subject with multiple myeloma comprising administering an anti-CD38 antibody, rHuPH20, bortezomib and dexamethasone, with Kapoor’s method of treating multiple myeloma comprising administering bortezomib at 1.3 mg/m2 twice weekly and dexamethasone at 40 mg orally weekly. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to combine Elias, Sanofi, San-Miguel, and Kapoor’s for a method of treating multiple myeloma comprising administering an anti-CD38 antibody, rHuPH20, bortezomib, and dexamethasone, because all reference are methods of treating multiple myeloma. Furthermore, Kapoor teaches methods of administering bortezomib at 1.3 mg/m2 twice weekly and dexamethasone at 40 mg weekly, orally.
Applicant’s Arguments:
The antibody of Sanofi is not interchangeable with the claimed antibody
The Examiner has pointed to no disclosure in Elias that subcutaneous administration of the claimed pharmaceutical composition in combination with bortezomib and dexamethasone achieves an improvement in ORR.
…the Examiner alleges that one of skill in the art would substitute the antibody of Sanofi (isatuximab) with the claimed antibody (daratumumab) in a combination therapy to yield predictable improvements in a clinical endpoint (ORR).
Applicant reiterates there is no evidence of record that those of skill in the art would consider anti-CD38 antibodies to be interchangeable
It is Applicant's position that one of skill in the art would lack motivation to combine the teachings of Elias and Sanofi and that the skilled artisan would further have no reasonable expectation of success in achieving the claimed therapy.
In actuality, isatuximab and daratumumab differ substantially in their functional binding properties and mechanisms of action.
The different binding sites have functional implications.
These mechanistic differences support the conclusion that a person skilled in the art would not have substituted isatuximab with daratumumab because they would not have viewed the two antibodies as being interchangeable.
Sanofi relates to an entirely different combination therapy than claimed
There is no disclosure in the description or examples of a combination of an anti-CD38 antibody with bortezomib and dexamethasone.
Nowhere does Sanofi suggest combination of boretzomib with an anti-CD38 antibody
The Examiner has failed to identify any disclosure of a combination therapy of any anti-CD38 antibody with bortezomib and dexamethasone.
The ORR percentages in Sanofi are aspirational and unsupported by any data in the application
the ORR of "at least 43%" reported in Sanofi at para. [0032] is aspirational and unsupported by any data in the application.
San-Miguel does not cure the deficiencies of Elias and Sanofi
San-Miguel describes a phase lb proof-of-concept study for subcutaneous delivery of daratumumab and rHuPH2O as a monotherapy. The mention of bortezomib and dexamethasone in the introductory section occurs in the context of co-administration with intravenous daratumumab without rHuPH2O.
Examiner’s Response:
Applicant states, “Examiner alleges that one of skill in the art would substitute the antibody of Sanofi (isatuximab) with the claimed antibody (daratumumab) in a combination therapy to yield predictable improvements in a clinical endpoint (ORR)”.
If a proposed modification would render the prior art invention being modified unsatisfactory for its intended purpose, there may be no suggestion or motivation to make the proposed modification. In re Gordon, 733 F.2d 900, 221 USPQ 1125 (Fed. Cir. 1984) (Claimed device was a blood filter assembly for use during medical procedures wherein both the inlet and outlet for the blood were located at the bottom end of the filter assembly, and wherein a gas vent was present at the top of the filter assembly. The prior art reference taught a liquid strainer for removing dirt and water from gasoline and other light oils wherein the inlet and outlet were at the top of the device, and wherein a pet-cock (stopcock) was located at the bottom of the device for periodically removing the collected dirt and water. The reference further taught that the separation is assisted by gravity. The Board concluded the claims were prima facie obvious, reasoning that it would have been obvious to turn the reference device upside down. The court reversed, finding that if the prior art device were turned upside down it would be inoperable for its intended purpose because the gasoline to be filtered would be trapped at the top, the water and heavier oils sought to be separated would flow out of the outlet instead of the purified gasoline, and the screen would become clogged.). But see In re Urbanski, 809 F.3d 1237, 1244, 117 USPQ2d 1499, 1504 (Fed. Cir. 2016) (The patent claims were directed to a method of enzymatic hydrolysis of soy fiber to reduce water holding capacity, requiring reacting the soy fiber and enzyme in water for about 60-120 minutes. The claims were rejected over two prior art references, wherein the primary reference taught using a longer reaction time of 5 to 72 hours and the secondary reference taught using a reaction time of 100 to 240 minutes, preferably 120 minutes. The applicant argued that modifying the primary reference in the manner suggested by the secondary reference would forego the benefits taught by the primary reference, thereby teaching away from the combination. The court held that both prior art references "suggest[ed] that hydrolysis time may be adjusted to achieve different fiber properties. Nothing in the prior art teaches that the proposed modification would have resulted in an ‘inoperable’ process or a dietary fiber product with undesirable properties." (emphasis in original)).
It is further noted that Sanofi teaches a different combination therapy (isatuximab and an anti-PD1 antibody) than presently claimed; however as indicated in the Non-Final Rejection, dated 06/04/2025, Sanofi teaches a method of treating multiple myeloma [0002]. Sanofi et al further teaches the initial chemotherapy regimen of bortezomib and dexamethasone [0002], and Sanofi et al further teaches measuring results using Overall Response Rate (ORR) [0032]. Based upon these teachings, one skilled in the art would have had ample motivation to modify the teachings of Elias et al to include measuring ORR, as this would provide investigators with a means of determining whether a particular therapeutic regimen is effectively treating a disease.
Applicant states, “The ORR percentages in Sanofi are aspirational and unsupported by any data in the application”.
As indicated above Sanofi teaches a chemotherapeutic regimen that comprises the administration of bortezomib and dexamethasone, as instantly claimed, and Sanofi also teaches the measurement of overall response rates (ORR). Based upon these teachings, one skilled in the art would have had ample motivation to modify the teachings of Elias et al to include measuring ORR, as this would provide investigators with a means of determining whether a particular therapeutic regimen is effectively treating a disease. Furthermore the claimed invention would be expected to improve ORR over a method that comprises only the administration of bortezomib and dexamethasone, because the claimed invention comprises the administration of bortezomib and dexamethasone in combination with an additional anti-cancer medicament, specifically, an anti-CD38 antibody, which has been shown by Elias et al to treat multiple myeloma.
Applicant states, “A showing of synergy is not required to demonstrate unexpected results”.
Applicants have not demonstrated that co-treatment with an anti-CD38 antibody, rHuPH20, bortezomib, and dexamethasone had synergistic effects in improving overall response rate (ORR) in a subject or a population of subjects with multiple myeloma.
It is noted that a showing of synergy is not necessarily required to demonstrate unexpected results. For example at MPEP 716.02, it is stated that evidence showing unexpected results may include: 1) greater than expected results, 2) superiority of a property shared with the prior art, 3) presence of an unexpected property, and 4) absence of an expected property. In the instant case, Applicant has not met the burden of demonstrating the instant invention demonstrates results that are unexpected or significant. The claimed invention comprises treating multiple myeloma via the administration of bortezomib and dexamethasone in combination with an additional anti-cancer medicament, specifically, an anti-CD38 antibody. This invention is prima facie obvious over the prior art, as previously indicated, and a sufficient showing of an unexpected result, much less an unexpected result that is commensurate in scope with the claims.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-2, 6-12, 14, 21-23, 25, 31-33, 35, and 37-41 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 203 of copending Application No. 16/797,301 ('301) in view of Elias et al (WO 2012092616 A1, IDS 4/22/2024), Sanofi (EP 3421494 A1), San-Miguel et al (Subcutaneous Daratumumab in Patients With Relapsed or Refractory Multiple Myeloma: Part 2 Update of the Open-label, Multicenter, Dose Escalation Phase 1b Study (PAVO), PF555, 2018, IDS 4/22/2024), and Jansson et al (US 20170121417 A1, IDS 4/22/2024).
The teachings of Elias et al, Sanofi et al, San-Miguel et al and Jansson et al are discussed above.
It is initially noted that the antibody recited in the instant claims 1 and 22 is daratumumab, see p. 8 of the specification. The primary difference between the instant claims and conflicting claims 1 and 2 is that the instant claims recite the administration of a recombinant human hyaluronidase (rHuPH20), bortezomib, and dexamethasone.
The teachings of Elias et al., San-Miguel et al., and Sanofi are discussed above. Based upon the teachings of Elias, one of ordinary skill in the art would have been motivated to modify the conflicting claims to recite the administration of bortezomib, and based upon the teachings of San-Miguel et al, one of ordinary skill in the art would have been motivated to modify the conflicting claims to recite the administration of rHuPH20 and dexamethasone. One of ordinary skill in the art would have been motivated to do so, because Elias et al, San-Miguel et al., and Sanofi teach that these medicaments may be used in the treatment of multiple myeloma. Furthermore Sanofi teaches that ORR may be used as a means to determine the effectiveness of a therapeutic regimen, and Sanofi et al teaches that the ORR is determined by complete response + very good response + partial response. The invention of the conflicting claims, Sanofi, and San-Miguel meets the limitations of claims 1, 2, 8, and 21-23.
With respect to claims 6 and 7, given that the instant claims and the invention of the conflicting claims, Sanofi, and San-Miguel are not patentably distinct, one of ordinary skill in the art would expect the instant claims and the invention of the conflicting claims, Sanofi, and San-Miguel to demonstrate similar functional characteristics, such as achieving a non-inferior ORR.
With respect to claims 9 and 10, San-Miguel et al. teaches the administration of 1,800 mg daratumumab and 30,000 U of rHuPH20. Furthermore one of ordinary skill in the art generally recognizes the utility of optimizing the dosage of medicaments in a therapeutic regimen.
With respect to claims 11 and 12, Elias et al teaches administering an excipient with the formulation [0243]. Elias et al further teaches administering the excipient histidine [0243].
With respect to claims 14, 25, 31-33, and 35, one of ordinary skill in the art would appreciate that the administration schedule and dosage of a therapeutic regimen represent optimizable variable that affect the safety and efficacy of a therapeutic regimen, and one of ordinary skill in the art would thus recognize the utility of optimizing the administration schedule and dosage of medicaments in a therapeutic regimen.
With respect to claims 37-39, as indicated above, Elias et al teaches the administration of treatments via subcutaneous and oral routes of administration. Furthermore one of ordinary skill in the art would appreciate that therapeutic agents can generally be either self-administered or administered by others.
With respect to claims 40 and 41, San-Miguel et al further teaches treating patient relapsed or refractory to treatments [Introduction].
Claims 1-2, 6-12, 14, 21-23, 25, 31-33, 35, and 37-41 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 10, and 19 of copending Application No. 17/343,150 ('150) in view of Elias et al (WO 2012092616 A1, IDS 4/22/2024), Sanofi (EP 3421494 A1), San-Miguel et al (Subcutaneous Daratumumab in Patients With Relapsed or Refractory Multiple Myeloma: Part 2 Update of the Open-label, Multicenter, Dose Escalation Phase 1b Study (PAVO), PF555, 2018, IDS 4/22/2024), and Jansson et al (US 20170121417 A1, IDS 4/22/2024).
The teachings of Elias et al, Sanofi et al, San-Miguel et al and Jansson et al are discussed above.
It is initially noted that the antibody recited in the instant claims 1 and 22 is daratumumab, see p. 8 of the specification. The primary difference between the instant claims and conflicting claims 1 and 2 is that the instant claims recite the administration of a recombinant human hyaluronidase (rHuPH20), bortezomib, and dexamethasone.
The teachings of Elias et al., San-Miguel et al., and Sanofi are discussed above. Based upon the teachings of Elias, one of ordinary skill in the art would have been motivated to modify the conflicting claims to recite the administration of bortezomib, and based upon the teachings of San-Miguel et al, one of ordinary skill in the art would have been motivated to modify the conflicting claims to recite the administration of rHuPH20 and dexamethasone. One of ordinary skill in the art would have been motivated to do so, because Elias et al, San-Miguel et al., and Sanofi teach that these medicaments may be used in the treatment of multiple myeloma. Furthermore Sanofi teaches that ORR may be used as a means to determine the effectiveness of a therapeutic regimen, and Sanofi et al teaches that the ORR is determined by complete response + very good response + partial response. The invention of the conflicting claims, Sanofi, and San-Miguel meets the limitations of claims 1, 2, 8, and 21-23.
With respect to claims 6 and 7, given that the instant claims and the invention of the conflicting claims, Sanofi, and San-Miguel are not patentably distinct, one of ordinary skill in the art would expect the instant claims and the invention of the conflicting claims, Sanofi, and San-Miguel to demonstrate similar functional characteristics, such as achieving a non-inferior ORR.
With respect to claims 9 and 10, San-Miguel et al. teaches the administration of 1,800 mg daratumumab and 30,000 U of rHuPH20. Furthermore one of ordinary skill in the art generally recognizes the utility of optimizing the dosage of medicaments in a therapeutic regimen.
With respect to claims 11 and 12, Elias et al teaches administering an excipient with the formulation [0243]. Elias et al further teaches administering the excipient histidine [0243].
With respect to claims 14, 25, 31-33, and 35, one of ordinary skill in the art would appreciate that the administration schedule and dosage of a therapeutic regimen represent optimizable variable that affect the safety and efficacy of a therapeutic regimen, and one of ordinary skill in the art would thus recognize the utility of optimizing the administration schedule and dosage of medicaments in a therapeutic regimen.
With respect to claims 37-39, as indicated above, Elias et al teaches the administration of treatments via subcutaneous and oral routes of administration. Furthermore one of ordinary skill in the art would appreciate that therapeutic agents can generally be either self-administered or administered by others.
With respect to claims 40 and 41, San-Miguel et al further teaches treating patient relapsed or refractory to treatments [Introduction].
Claims 1-2, 6-12, 14, 21-23, 25, 31-33, 35, and 37-41 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, and 15-21 of copending Application No. 18/ 100,056 ('056) in view of Elias et al (WO 2012092616 A1, IDS 4/22/2024), Sanofi (EP 3421494 A1), San-Miguel et al (Subcutaneous Daratumumab in Patients With Relapsed or Refractory Multiple Myeloma: Part 2 Update of the Open-label, Multicenter, Dose Escalation Phase 1b Study (PAVO), PF555, 2018, IDS 4/22/2024), and Jansson et al (US 20170121417 A1, IDS 4/22/2024).
The teachings of Elias et al, Sanofi et al, San-Miguel et al and Jansson et al are discussed above.
It is initially noted that the antibody recited in the instant claims 1 and 22 is daratumumab, see p. 8 of the specification. The primary difference between the instant claims and conflicting claims 1 and 2 is that the instant claims recite the administration of a recombinant human hyaluronidase (rHuPH20), bortezomib, and dexamethasone.
The teachings of Elias et al., San-Miguel et al., and Sanofi are discussed above. Based upon the teachings of Elias, one of ordinary skill in the art would have been motivated to modify the conflicting claims to recite the administration of bortezomib, and based upon the teachings of San-Miguel et al, one of ordinary skill in the art would have been motivated to modify the conflicting claims to recite the administration of rHuPH20 and dexamethasone. One of ordinary skill in the art would have been motivated to do so, because Elias et al, San-Miguel et al., and Sanofi teach that these medicaments may be used in the treatment of multiple myeloma. Furthermore Sanofi teaches that ORR may be used as a means to determine the effectiveness of a therapeutic regimen, and Sanofi et al teaches that the ORR is determined by complete response + very good response + partial response. The invention of the conflicting claims, Sanofi, and San-Miguel meets the limitations of claims 1, 2, 8, and 21-23.
With respect to claims 6 and 7, given that the instant claims and the invention of the conflicting claims, Sanofi, and San-Miguel are not patentably distinct, one of ordinary skill in the art would expect the instant claims and the invention of the conflicting claims, Sanofi, and San-Miguel to demonstrate similar functional characteristics, such as achieving a non-inferior ORR.
With respect to claims 9 and 10, San-Miguel et al. teaches the administration of 1,800 mg daratumumab and 30,000 U of rHuPH20. Furthermore one of ordinary skill in the art generally recognizes the utility of optimizing the dosage of medicaments in a therapeutic regimen.
With respect to claims 11 and 12, Elias et al teaches administering an excipient with the formulation [0243]. Elias et al further teaches administering the excipient histidine [0243].
With respect to claims 14, 25, 31-33, and 35, one of ordinary skill in the art would appreciate that the administration schedule and dosage of a therapeutic regimen represent optimizable variable that affect the safety and efficacy of a therapeutic regimen, and one of ordinary skill in the art would thus recognize the utility of optimizing the administration schedule and dosage of medicaments in a therapeutic regimen.
With respect to claims 37-39, as indicated above, Elias et al teaches the administration of treatments via subcutaneous and oral routes of administration. Furthermore one of ordinary skill in the art would appreciate that therapeutic agents can generally be either self-administered or administered by others.
With respect to claims 40 and 41, San-Miguel et al further teaches treating patient relapsed or refractory to treatments [Introduction].
Applicant’s Arguments:
..the Examiner has pointed to no claim in the '301 application that discloses an improvement in ORR.
Applicant does not agree with this rejection because the '056 application has a later patent term filing date than the instant application and is therefore an improper ODP reference.
Examiner’s Response:
The double patenting rejection of the claims over the claims of App. No. 16/797,301 and 18/100,056 have been maintained. Although the claims at issue are not identical, the instant claims are prima facie obvious over the conflicting claims in view of the cited references, as detailed in the rejection of the claims under 35 U.S.C. 103. With respect to the nonstatutory double patenting rejection over App. No. 18/100,056, nonstatutory double patenting rejections may be appropriately made over conflicting applications that are filed both before or after an application under examination. The nonstatutory double patenting rejections of record are not the only remaining rejections for the instant application, and as such it would not be appropriate to withdrawn the nonstatutory double patenting rejection over App. No. 18/100,056, even though the instant application may have a filing date that is earlier than the conflicting application.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DENNIS JOHN SULLIVAN whose telephone number is (571)272-0509. The examiner can normally be reached Mon - Fri: 7:30AM - 4:30PM.
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) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at (571) 270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/DENNIS J SULLIVAN/Examiner, Art Unit 1642
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642
Prosecution Insights