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
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 1-12 have an effective filing date of 20MAY2015.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 03/20/2026 & 05/22/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Status of Claims
Claims 1-12 are currently pending and presented for examination on the merits.
Rejections Withdrawn
The rejection filed under Double Patenting is withdrawn in view of Applicant filing a Terminal Disclaimer.
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 1-12 are rejected under 35 U.S.C. 103 as being unpatentable over Lust et al (US 20040141982 A1), Deslandes et al (US 20150118251 A1), and further in view of Venner et al (Cyclophosphamide, bortezomib, and dexamethasone therapy in AL amyloidosis is associated with high clonal response rates and prolonged progression-free survival, Blood, 10 May 2012, Vol 119, Num 19).
In regards to claim 1, Lust et al teaches a method of inhibiting primary amyloidosis comprising administering a therapeutic that specifically binds CD38 [Claims 1 and 15]. Lust et al further teaches the therapeutic is useful in patients with CD38+ plasmaproliferative disorders, such as primary amyloidosis [0012]. Lust et al further teaches the therapeutic may be administered subcutaneously [0096].
Lust et al does not specifically teach daratumumab, bortezomib, cyclophosphamide, and dexamethasone. However, this deficiency is made up in the teachings of Deslandes et al.
Deslandes et al teaches a method of treating a disease with abnormal high expression of CD38 [0093]. Deslandes et al teaches further an antibody that specifically binds CD38 and kills CD38+ cells [0130]. Deslandes et al further teaches the antibody is daratumumab [0128]. Deslandes et al further teaches administering the CD38 antibody with bortezomib, cyclophosphamide, and dexamethasone [0209].
Lust et al does not specifically teach treating light chain amyloidosis. However, this deficiency is made up in the teaches of Venner et al.
Venner et al teaches the therapy for treating light chain amyloidosis comprising administering cyclophosphamide, bortezomib, and dexamethasone (CVD) upfront or relapsed amyloidosis patients[Abstract]. Venner et al further teach the CVD combination is an attractive combination, especially in patients with advanced disease in whom rapid reductions in circulating amyloidogenic light chains are critical to improve outcomes [Left column, 1st Paragraph, pg. 4388].
One of ordinary skill in the art, before the effective filing date, would have been motivated to combine Lust’s method of treating CD38+ disease, such as amyloidosis, with an anti-CD38 therapeutic, with Deslandes’s method of treating disease with abnormally high expression of CD38 comprising administering daratumumab, cyclophosphamide, bortezomib, and dexamethasone, with Venner’s method of treating light chain amyloidosis comprising cyclophosphamide, bortezomib, and dexamethasone. 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 Lust, Deslandes, and Venner’s methods for a method of treating light chain amyloidosis comprising subcutaneously administering daratumumab, cyclophosphamide, bortezomib, and dexamethasone, because Lust and Deslandes both teach the treatment of CD38+ diseases, such as light chain amyloidosis, with anti-CD38 therapies. Furthermore, Deslandes and Venner both teach treating CD38+ diseases with cyclophosphamide, bortezomib, and dexamethasone.
In regards to claims 2-5, and 10-11, Venner et al teaches administering bortezomib at 1.0 mg/m2, and increasing to 1.3 mg/m2 if well tolerated [Right column, 1st Paragraph, pg. 4387]. Venner et al further teaches administering bortezomib on days 1, 4, 8, and 11 [Right column, 1st Paragraph, pg. 4387]. Venner et al further teaches administering cyclophosphamide at 350 mg/m2 on days 1, 8, and 15 [Right column, 1st Paragraph, pg. 4387]. Venner et al further teaches administering dexamethasone at 20 mg on days 1, 4, 8, and 11 [Right column, 1st Paragraph, pg. 4387]. Venner et al further teaches administering therapeutics for 8 cycles [Right column, 1st Paragraph, pg. 4387].
With regard to dosages and frequency of administering daratumumab, cyclophosphamide, bortezomib, and dexamethasone, the amount of the therapies to administer is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient needed to achieve the desired results. Thus, absent some demonstration of unexpected results from the claimed parameters, the optimization of ingredient amounts would have been obvious at the time of applicant's invention.
The principle of law states from MPEP 2144.05: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."(Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382); Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
In regards to claim 6, Venner et al further teaches favorable results for patients, including those on autologous stem cell transplants [Left column, 2nd Paragraph, pg. 4388]. Furthermore, Deslandes et al teaches the patients are undergoing stem cell transplantation [0044].
In regards to claim 7, Deslandes et al further teaches stem cell transplantation includes allogeneic transplantations [0049].
In regards to claim 8, Deslandes et al further teaches stem cell transplantation includes autologous stem cells [0049].
With respect to claim 9, given that Deslandes et al teaches that allogenic transplants are from a matched donor, one of ordinary skill in the art would have been motivated to perform syngeneic transplants, because syngeneic transplants are from genetically identical donors, such as a twin, which would be expected to reduce the potential for transplant rejection compared to an allogenic transplant.
With respect to claim 12, one of ordinary skill in the art would appreciate that the method of Lust et al., Deslandes et al, and Venner et al could be used in healthy individuals, such as individuals who do not have heart failure.
Applicant’s Arguments:
To reject a claim based on this rationale, Office personnel must articulate, among other things, a finding that one of ordinary skill in the art could have combined the elements as claimed by known methods, and that in combination, each element merely performs the same function as it does separately. MPEP 2143(I)(A) (emphasis added).
Daratumumab of Applicant's claim 1 is a therapeutic for treating AL.
The anti-CD38 antibodies of Lust are carriers for introducing therapeutics into CD38+ cells.
MPEP 2143(I)(A) states that:
Each element merely performs the same function as it does separately.
Examiner’s Response:
MPEP 2143.01 (I)states that
The disclosure of desirable alternatives does not necessarily negate a suggestion for modifying the prior art to arrive at the claimed invention. In In re Fulton, 391 F.3d 1195, 73 USPQ2d 1141 (Fed. Cir. 2004), the claims of a utility patent application were directed to a shoe sole with increased traction having hexagonal projections in a "facing orientation." 391 F.3d at 1196-97, 73 USPQ2d at 1142. The Board combined a design patent having hexagonal projections in a facing orientation with a utility patent having other limitations of the independent claim. 391 F.3d at 1199, 73 USPQ2d at 1144. Applicant argued that the combination was improper because (1) the prior art did not suggest having the hexagonal projections in a facing (as opposed to a "pointing") orientation was the "most desirable" configuration for the projections, and (2) the prior art "taught away" by showing desirability of the "pointing orientation." 391 F.3d at 1200-01, 73 USPQ2d at 1145-46. The court stated that "the prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." Id. In affirming the Board’s obviousness rejection, the court held that the prior art as a whole suggested the desirability of the combination of shoe sole limitations claimed, thus providing a motivation to combine, which need not be supported by a finding that the prior art suggested that the combination claimed by the applicant was the preferred, or most desirable combination over the other alternatives. Id. See also In re Urbanski, 809 F.3d 1237, 1244, 117 USPQ2d 1499, 1504 (Fed. Cir. 2016).
Lust et al does not criticize, discredit, or otherwise discourage the use of an anti-CD38 antibody that targets CD38+ the proliferative diseases primary amyloidosis.
Deslandes et al teaches a method of treating a disease with abnormal high expression of CD38 [0093]. Deslandes et al teaches further an antibody that specifically binds CD38 and kills CD38+ cells [0130]. Deslandes et al further teaches the antibody is daratumumab [0128].
One of ordinary skill in the art, before the effective filing date, would have been motivated to combine Lust’s method of treating CD38+ disease, such as amyloidosis, with an anti-CD38 therapeutic, with Deslandes’s method of treating disease with abnormally high expression of CD38 comprising administering daratumumab, cyclophosphamide, bortezomib, and dexamethasone, with Venner’s method of treating light chain amyloidosis comprising cyclophosphamide, bortezomib, and dexamethasone. 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 Lust, Deslandes, and Venner’s methods for a method of treating light chain amyloidosis comprising subcutaneously administering daratumumab, cyclophosphamide, bortezomib, and dexamethasone, because Lust and Deslandes both teach the treatment of CD38+ diseases, such as light chain amyloidosis, with anti-CD38 therapies. Furthermore, Deslandes and Venner both teach treating CD38+ diseases with cyclophosphamide, bortezomib, and dexamethasone.
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 1-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 7-12, 14-15, 24, and 26-27 of U.S. Patent No. 10766965 ('965) in view of Lust et al (US 20040141982 A1), Deslandes et al (US 20150118251 A1), and Venner et al (Cyclophosphamide, bortezomib, and dexamethasone therapy in AL amyloidosis is associated with high clonal response rates and prolonged progression-free survival, Blood, 10 May 2012, Vol 119, Num 19).
The teachings of Lust et al, Deslandes et al, and Venner et al are discussed above.
The primary difference between the instant claim 1 and conflicting claims 1, 5, 7-12, 14-15, and 24 is that the instant claims recite the administration of daratumumab and ‘965 recites an anti-CD38 antibody.
With regards to claim 1, based upon the teachings of Lust et al, one of ordinary skill in the art would have been motivated to treat a CD38+ disease, such as amyloidosis, with an anti-CD38 therapeutic, and based upon the teachings of Deslandes et al, one of ordinary skill in the art would have been motivated to treat a disease with abnormally high expression of CD38 by administering the anti-CD38 antibody daratumumab, cyclophosphamide, bortezomib, and dexamethasone, and based on the teachings of Venner et al, one of ordinary skill in the art would have been motivated to treat light chain amyloidosis by administering cyclophosphamide, bortezomib, and dexamethasone. One of ordinary skill in the art would have been motivated to do so, because Lust, Deslandes, and Venner teach that these medicaments may be used to treat CD38+ diseases, such as amyloidosis. The invention of the conflicting claims, Lust, Delandes, and Venner meet the limitations of claim 1.
With respect to claim 2, the dosage and administration times for daratumumab is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient needed to achieve the desired results. Thus, absent some demonstration of unexpected results from the claimed parameters, the optimization of ingredient amounts would have been obvious at the time of applicant's invention.
With regards to claims 3-5, and 10-11, Venner et al teaches administer bortezomib at 1.0 mg/m2, and increasing to 1.3 mg/m2 if well tolerated [Right column, 1st Paragraph, pg. 4387]. Venner et al further teaches administering bortezomib on days 1, 4, 8, and 11 [Right column, 1st Paragraph, pg. 4387]. Venner et al further teaches administering cyclophosphamide at 350 mg/m2 on days 1, 8, and 15 [Right column, 1st Paragraph, pg. 4387]. Venner et al further teaches administering dexamethasone at 20 mg on days 1, 4, 8, and 11 [Right column, 1st Paragraph, pg. 4387]. Venner et al further teaches administering therapeutics for 8 cycles [Right column, 1st Paragraph, pg. 4387].
With regards to claim 6, claim 26 of US patent ‘965 is not patentably distinct. Specifically, the patient is undergoing hematopoietic stem cell transplantation (HSCT).
With regards to claims 7-9, claim 27 of US patent ‘965 is not patentably distinct. Specifically, the HSCT is allogeneic, autologous, or syngeneic.
With respect to claim 12, one of ordinary skill in the art would appreciate that the method of Lust et al., Deslandes et al, and Venner et al could be used in healthy individuals, such as individuals who do not have heart failure.
Applicant’s Arguments:
Accordingly, instant claim 1 and claim 1 of '965 are directed to treating completely different subpopulations of patients.
The Office Action asserts that "[t]he primary difference between the instant claim 1 and conflicting claims 1, 5, 7-12, 14-15, and 24 is that the instant claims recite the administration of daratumumab and '965 recites an anti-CD38 antibody." Because the Office Action does not recognize a difference in patient subpopulation and does not perform the requisite analysis, the nonstatutory double patenting rejection is not appropriate.
Examiner’s Response:
Venner et al teaches the treatment of in newly diagnosed and relapsed amyloidosis comprising administering cyclophosphamide, bortezomib, and dexamethasone [Abstract].
Lust et al teaches a method of inhibiting primary amyloidosis comprising administering a therapeutic that specifically binds CD38 [Claims 1 and 15]. Lust et al further teaches the therapeutic is useful in patients with CD38+ plasmaproliferative disorders, such as primary amyloidosis [0012].
Deslandes et al teaches a method of treating a disease with abnormal high expression of CD38 [0093]. Deslandes et al teaches further an antibody that specifically binds CD38 and kills CD38+ cells [0130]. Deslandes et al further teaches the antibody is daratumumab [0128].
One of ordinary skill in the art, before the effective filing date, would have been motivated to combine Lust’s method of treating CD38+ disease, such as amyloidosis, with an anti-CD38 therapeutic, with Deslandes’s method of treating disease with abnormally high expression of CD38 comprising administering daratumumab, cyclophosphamide, bortezomib, and dexamethasone, with Venner’s method of treating light chain amyloidosis comprising cyclophosphamide, bortezomib, and dexamethasone. It would have been prima facie obvious to combine adapt ‘965 and ‘480 with Lust, Deslandes, and Venner’s methods for a method of treating light chain amyloidosis comprising subcutaneously administering daratumumab, cyclophosphamide, bortezomib, and dexamethasone, because Lust and Deslandes both teach the treatment of CD38+ diseases, such as light chain amyloidosis, with anti-CD38 therapies. Furthermore, Deslandes and Venner both teach treating CD38+ diseases with cyclophosphamide, bortezomib, and dexamethasone.
Conclusion
No claims 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.
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.
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/DENNIS J SULLIVAN/Examiner, Art Unit 1642
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642
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