DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Continued examination under 37 CFR 1.114 does not apply to an application unless prosecution in the application is closed. As the request filed July 29, 2025 was accompanied by a reply to a non-final office action, the reply will be entered and considered under 37 CFR 1.111. A Notice of Improper Request for RCE was mailed on August 4, 2025.
Claim Status
Claims 1-6, 8-9 and new claims 18-25 are under consideration in this office action.
Modified Rejections Necessitated by Amendment
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.
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 1-6, 8-9, and new claims 18-25 are rejected under 35 U.S.C. 103 as being unpatentable over Comenzo et al, published May 2018 (“Comenzo”; PTO-892 from 5/9/23) in view of US 2017/0008966, published January 12, 2017 (“Chaulagain”; PTO-892 from 5/9/23).
Comenzo teaches a method to treat patients with newly diagnosed light chain amyloidosis, the method comprised of subcutaneously administering daratumumab and hyaluronidase, as in Comenzo’s instant claims 1, 3, 18, and 20. The treated patient population has an age range of 35-77 years, which is an adult, as required by instant claims 1 and 18. As the treatment method of Comenzo is comprised of the same therapeutics, the same dosage, and the same dosing interval as the instant claims, it is predicted both methods would yield the same expected results, i.e. achievement of confirmed hematologic complete response, as in claims 1 and 18.
Comenzo teaches dosages for daratumumab and hyaluronidase of 1800 mg and 30,000 U, respectively (pg 2, ln 5-7), as in instant claim 1 and 18. This co-formulation is given weekly for 8 weeks, followed by every 2 weeks for 16 weeks, and every 4 weeks thereafter (pg 2, ln 7-9), as in claims 1, 8-9, 18, and 24-25. Further, Comenzo teaches combination therapy of daratumumab and hyaluronidase with bortezomib (1.3 mg/m2), cyclophosphamide (300 mg/m2), and dexamethasone (40 mg) administered weekly for less than 24 weeks (pg 2, ln 7-10), as in claims 2, 9, 19, and 25.
Comenzo does not teach a method for treating an adult patient with light chain amyloidosis wherein the patient does not have NYHA Class IIIB or Class IV cardiac disease or wherein the light chain amyloidosis is relapsed or refractory nor does Comenzo teach complete hematologic response in AL patients as a metric for assessing light chain amyloidosis.
Chaulagain teaches a method for treating light chain amyloidosis by administering daratumumab and hyaluronidase; exclusion criteria for this method includes having a NYHA Classification IIIB or IV [0395], as in instant claim 1. The treatment combination of this method is administered to subjects with light chain amyloidosis that is relapsed or refractory [0087] and subjects who have had prior therapy with bortezomib, cyclophosphamide, and/or dexamethasone [0377], as in claims 4-6 and 21-24.
Chaulagain also teaches that the primary objective of the method is the complete hematologic response (HemCR) following combination daratumumab, bortezomib, cyclophosphamide, and dexamethasone administration [0341].
Given that Comenzo teaches a method to treat patients with light chain amyloidosis comprised of administering daratumumab and hyaluronidase at the instantly recited doses and further given that Chaulagain teaches a similar method directed to patients with light chain amyloidosis that do not have NYHA Class IIIB or Class IV cardiac disease and teach a primary end point of hematologic complete response, it would have been obvious to the ordinary artisan to limit the treatment group of Comenzo to those patients without Class IIIB/IV cardiac disease. This is because patients with advanced cardiac disease or severe heart failure have high-risk disease with a poor prognosis; there are no known treatment approaches that can overcome the poor prognosis of these patients (as evidenced by Milani et al, pg 7, column 2, para 2, see PTO-892 from 11/8/23).
Although Comenzo in view of Chaulagain is silent regarding the achievement of HemCR at a rate of about 42%, as set forth in claim 1, and achievement of HemCR at 59 days, as set forth in claim 18, it is clear that the same patient population treated with the same antibody would have the same characteristics and effects as the instantly claimed antibody since there is no evidence to the contrary. Note that rejections are appropriate when the prior art discloses a method (or product) that appears to be identical except that the art is silent as to an inherent property; see MPEP § 2112(III). In such situations, the burden is on applicant to provide evidence that the prior art product (or method) is not obviously the same.
Therefore, claims 1-6, 8-9, and 18-25 are unpatentable over Comenzo in view of Chaulagain.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-6, 8-9, and new claims 18-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 and 30 of U.S. Patent No. 10766965 (‘965) in view of Comenzo and Chaulagain. Although the claims at issue are not identical, they are not patentably distinct from each other because they are directed to overlapping embodiments: a method for treating light chain amyloidosis comprising administration of a formulation comprising daratumumab and hyaluronidase, as in claims 1 and 3-4. The limitation of instant claim 1 of “achieving confirmed hematologic complete response” is drawn to expected results; one of ordinary skill in the art would recognize that using the same anti-CD38 antibody with a hyaluronidase would improve light chain amyloidosis parameter of disease severity.
Claims of ‘965 teach a method to treat patients refractory to at least one prior line of therapy with light chain amyloidosis comprised of administering daratumumab and hyaluronidase in combination with cyclophosphamide, dexamethasone, and bortezomid, as in instant claims 1-2, 4-6, 18-19, and 21-22. ‘965 does not teach a dosage or a dosing schedule for these agents for the treatment light chain amyloidosis nor does it teach the limitation wherein the adult patient does not have NYHA Class IIIB or Class IV cardiac disease.
Comenzo teaches a method to treat patients with newly diagnosed light chain amyloidosis, the method comprised of subcutaneously administering daratumumab and hyaluronidase at a dose of 1800 mg and 30,000 U, respectively (pg 2, ln 5-7), as in instant claims 1 and 18. This co-formulation is given weekly for 8 weeks, followed by every 2 weeks for 16 weeks, and every 4 weeks thereafter (pg 2, ln 7-9), as in instant claims 8 and 24. Further, Comenzo teaches combination therapy of daratumumab and hyaluronidase with bortezomib (1.3 mg/m2), cyclophosphamide (300 mg/m2), and dexamethasone (40 mg) administered weekly for less than 24 weeks (pg 2, ln 7-10), as in claims 9 and 25.
Chaulagain teaches a method for treating light chain amyloidosis by administering daratumumab and hyaluronidase; exclusion criteria for this method includes having a NYHA Classification IIIB or IV [0395], as in instant claim 1.
Given that ‘965 teaches a method to treat patients with light chain amyloidosis and Comenzo teaches administering daratumumab and hyaluronidase at the instantly recited doses and further given that Chaulagain teaches a similar method directed to patients with light chain amyloidosis that do not have NYHA Class IIIB or Class IV cardiac disease, it would have been obvious to the ordinary artisan to limit the treatment group of ‘965 to those patients without Class IIIB/IV cardiac disease. This is because patients with advanced cardiac disease or severe heart failure have high-risk disease, with a poor prognosis; no treatment approach was able to overcome the poor prognosis of these patients (as evidenced by Milani et al, pg 7, column 2, para 2, see PTO-892 from 11/8/2023).
The scope of the ‘965 claims in view of Comenzo and Chaulagain fully overlaps with that of instant claims 1-6, 8-9, and 18-25 and, therefore, the method of the instant claims is not patentable over ‘965.
Claims 1-6, 8-9, and new claims 18-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 19 of U.S. Patent No. 12,091,466 in view of Comenzo and Chaulagain.
Although the claims at issue are not identical, they are not patentably distinct from each other because they are directed to overlapping embodiments: a method for treating light chain amyloidosis comprising administration of a formulation comprising daratumumab and hyaluronidase, as in claims 1, 3-4, 18, and 20-21. The limitation of instant claim 1 of achieving “HemCR at a rate of about 42%” and the limitation of instant claim 18 of achieving “HemCR at 59 days” are drawn to expected results; one of ordinary skill in the art would recognize that using the same anti-CD38 antibody with a hyaluronidase would improve this light chain amyloidosis parameter of disease severity.
Claim 1 of ‘466 is directed to a method of treating a patient with newly diagnosed light chain amyloidosis comprising administration of an anti-CD38 antibody, cyclophosphamide, bortezomib, dexamethasone, and a hyaluronidase, as in instant claims 1-3 and 18-20. ‘466 does not teach a dosage or a dosing schedule for these agents for the treatment light chain amyloidosis nor does it teach the limitation wherein the adult patient does not have NYHA Class IIIB or Class IV cardiac disease.
Comenzo teaches a method to treat patients with newly diagnosed light chain amyloidosis, the method comprised of subcutaneously administering daratumumab and hyaluronidase at a dose of 1800 mg and 30,000 U, respectively (pg 2, ln 5-7), as in instant claims 1 and 18. This co-formulation is given weekly for 8 weeks, followed by every 2 weeks for 16 weeks, and every 4 weeks thereafter (pg 2, ln 7-9), as in instant claims 8 and 24. Further, Comenzo teaches combination therapy of daratumumab and hyaluronidase with bortezomib (1.3 mg/m2), cyclophosphamide (300 mg/m2), and dexamethasone (40 mg) administered weekly for less than 24 weeks (pg 2, ln 7-10), as in claims 9 and 25.
Chaulagain teaches a method for treating light chain amyloidosis by administering daratumumab and hyaluronidase; exclusion criteria for this method includes having a NYHA Classification IIIB or IV [0395], as in instant claim 1.
Given that ‘466 teaches a method to treat patients with light chain amyloidosis and Comenzo teaches administering daratumumab and hyaluronidase at the instantly recited doses and further given that Chaulagain teaches a similar method directed to patients with light chain amyloidosis that do not have NYHA Class IIIB or Class IV cardiac disease, it would have been obvious to the ordinary artisan to limit the treatment group of ‘466 to those patients without Class IIIB/IV cardiac disease. This is because patients with advanced cardiac disease or severe heart failure have high-risk disease, with a poor prognosis; no treatment approach was able to overcome the poor prognosis of these patients (as evidenced by Milani et al, pg 7, column 2, para 2, see PTO-892 from 11/8/2023).
The scope of the ‘466 claims in view of the teachings of Comenzo and Chaulagain fully overlaps with that of instant claims 1-6, 8-9, and 18-25; therefore, the method of the instant claims is not patentable over ‘466.
Claims 1-6, 8-9, and new claims 18-25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/774,480 (‘480) in view of Comenzo and Chaulagain. Although the claims at issue are not identical, they are not patentably distinct from each other because they are directed to overlapping embodiments: a method for treating light chain amyloidosis comprising administration of a formulation comprising daratumumab and hyaluronidase, as in claims 1, 3-4, 18, and 20-21. The limitation of instant claim 1 of achieving “HemCR at a rate of about 42%” and the limitation of instant claim 18 of achieving “HemCR at 59 days” are drawn to expected results; one of ordinary skill in the art would recognize that using the same anti-CD38 antibody with a hyaluronidase would improve light chain amyloidosis parameter of disease severity.
Claim 1 of ‘480 teaches a method to treat patients with light chain amyloidosis comprised of administering daratumumab and hyaluronidase in combination with cyclophosphamide, dexamethasone, and bortezomid, as in instant claims 1-2, 4-6, 18-19, and 21-22. ‘480 does not teach a dosage or a dosing schedule for these agents for the treatment light chain amyloidosis nor does it teach the limitation wherein the adult patient does not have NYHA Class IIIB or Class IV cardiac disease.
Comenzo teaches a method to treat patients with newly diagnosed light chain amyloidosis, the method comprised of subcutaneously administering daratumumab and hyaluronidase at a dose of 1800 mg and 30,000 U, respectively (pg 2, ln 5-7), as in instant claims 1 and 18. This co-formulation is given weekly for 8 weeks, followed by every 2 weeks for 16 weeks, and every 4 weeks thereafter (pg 2, ln 7-9), as in instant claims 8 and 24. Further, Comenzo teaches combination therapy of daratumumab and hyaluronidase with bortezomib (1.3 mg/m2), cyclophosphamide (300 mg/m2), and dexamethasone (40 mg) administered weekly for less than 24 weeks (pg 2, ln 7-10), as in claims 9 and 25.
Chaulagain teaches a method for treating light chain amyloidosis by administering daratumumab and hyaluronidase; exclusion criteria for this method includes having a NYHA Classification IIIB or IV [0395], as in instant claim 1.
Given that ‘480 teaches a method to treat patients with light chain amyloidosis and Comenzo teaches administering daratumumab and hyaluronidase at the instantly recited doses and further given that Chaulagain teaches a similar method directed to patients with light chain amyloidosis that do not have NYHA Class IIIB or Class IV cardiac disease, it would have been obvious to the ordinary artisan to limit the treatment group of ‘480 to those patients without Class IIIB/IV cardiac disease. This is because patients with advanced cardiac disease or severe heart failure have high-risk disease, with a poor prognosis; no treatment approach was able to overcome the poor prognosis of these patients (as evidenced by Milani et al, pg 7, column 2, para 2, see instant PTO-892).
The scope of the ‘480 claim in view of Comenzo and Chaulagain fully overlaps with that of instant claims 1-6, 8-9, and 18-25 and, therefore, the method of the instant claims is not patentable over ‘480.
Response to Arguments
Applicant's arguments filed July 29, 2025 have been fully considered but they are not persuasive.
Regarding the 103 rejection over Comenzo in view of Chaulagain, applicant asserts that the Patent Office has not explained or demonstrated why or how achieving HemCR of about 42% would necessarily flow from the teachings of the applied references (remarks, pg 4). However, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. See MPEP § 2112(I); “Products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Given that a method comprising daratumumab and hyaluronidase had already been described for the treatment of light chain amyloidosis at the dosages recited, the prior art compositions and method of treating would inherently have the same claimed intended results, as a product and its properties are inseparable. The court in Integra Life Sciences | Ltd. v. Merck KGaA, 50 USPQe2d 1846 (DC SCalif, 1999) held that a reference teaching a process may anticipate claims drawn to a method comprising the same process steps, despite the recitation of a different intended use in the preamble or the later discovery of a particular property of one of the starting materials or end products. Because the only active method step recited in claim 1 is administration, and because Comenzo teaches this step, the reference inherently teaches the method of achieving HemCR in patients with light chain amyloidosis and the associated intended results.
Given that Comenzo teaches a method of treating light chain amyloidosis and further given that Chaulagain teaches a method comprised of daratumumab and hyaluronidase that excludes patients with NYHA Class IIIIV or Class IV cardiac disease, it would have been obvious to one of ordinary skill in the art to use the method of Orengo in the patient population taught by Chaulagain, because Chaulagain has already identified this risk factor in patients with light chain amyloidosis. One would treat this patient population with the reasonable expectation that they would benefit from the method of Comenzo. While Comenzo is silent on the intended results of the effect of the daratumumab and hyaluronidase on the achievement of HemCR, it is clear that the same patient population treated with the same antibody would have the same characteristics and effects as the instantly claimed antibody since there is no evidence to the contrary. See MPEP 716.02(c).II, which states: “Where the unexpected properties of a claimed invention are not shown to have a significance equal to or greater than the expected properties, the evidence of unexpected properties may not be sufficient to rebut the evidence of obviousness… In re Eli Lilly, 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (Evidence of improved feed efficiency in steers was not sufficient to rebut prima facie case of obviousness based on prior art which specifically taught the use of compound X537A to enhance weight gain in animals because the evidence did not show that a significant aspect of the claimed invention would have been unexpected.).”
The double patenting rejections over patents ‘965 and ‘466 and patent application ‘480 are maintained because the limitation of achieving a HemCR at a rate of about 42% of the instant claims are still obvious in view of claims 1-15 and 30 of U.S. Patent No. 10766965 (‘965) in view of Comenzo and Chaulagain, the teachings of Comenzo and Chaulagain and claims 1 and 19 of copending patent ‘466 in view of Comenzo and Chaulagain, and the teachings of claim 1 of ‘480 in view of Comenzo and Chaulagain. The intended results of claim 1 when using a method of treating with the combination therapy are expected; using the same antibody with the same method would yield the same expected results. The claims in view of Comenzo teach the composition and the steps of the method; the secondary reference Chaulagain is used to teach the patient population. Taken together, the claimed method is not patentably distinct from the patented or copending claims.
Conclusion
No claim is allowed.
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 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.
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Jennifer Benavides
Examiner
Art Unit 1675
/JENNIFER A BENAVIDES/Examiner, Art Unit 1675
/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675