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 .
Response to Amendment
1. Applicant’s response of 9/15/2025 to the office action of 5/16/2025 is acknowledged and has been entered. Claims 2, 3, 13, and 14 have been cancelled by the Applicant. Claims 1 and 4-12 are currently pending and under examination in this action.
Information Disclosure Statement
2. The information disclosure statement (IDS) submitted on 8/8/2025 was filed after the mailing date of the Non-Final Office Action on 5/16/2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Withdrawn Objections
3. The drawings were objected to due to the poor quality of Figure 1, page 1 of the drawings. In response, Applicant submitted a new Figure 1 that is in higher resolution. The objection to the drawings has been withdrawn.
4. The specification was objected to concerning the proper use of trademarks and tradenames within the specification. Applicant submitted a new specification adequately addressing this issue. The objection to the specification has been withdrawn.
5. The abstract was objected to due to repetitive language and the failure to meet the required word count. Applicant has submitted an amended abstract that is within compliance of the abstract requirements. The objection to the abstract is withdrawn.
6. Claim 11 was objected to due to a minor informality. Applicant has amended claim 11 to properly fix this issue. In response, the objection to claim 11 is withdrawn.
Withdrawn Rejections
7. Claims 2, 3, 7, 8, and 12-14 were rejected under 35 U.S.C. 112(b) as being indefinite for lacking antecedent basis in the recitation of “the subject.” Applicant amended claim 1 to recite “a subject” and cancelled claims 2, 3, and 13-14. Claims 7, 8, and 12 are in proper form and the rejection under 35 U.S.C. 112(b) has been withdrawn.
8. Claims 1, 2, 9-12, and 14 were rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bergen et al. (Bergen et al. Clinical Chemistry, 2016, 62(1):243-251; cited on IDS 1449) as evidenced by Lavatelli et al. (Lavatelli, et al., Biochemica et Biophysica Act (BBA), 2011, 1814(3):411, Table 1; cited on IDS 1449). In light of the new rejections below, the rejection under 35 U.S.C. 102(a)(1) is withdrawn.
9. Claims 3-8 were rejected under 35 U.S.C. 103 as being unpatentable over Bergen et al. (Bergen et al. Clinical Chemistry, 2016, 62(1):243-251; cited on IDS 1449) as evidenced by Lavatelli et al. (Lavatelli, et al., Biochemica et Biophysica Act (BBA), 2011, 1814(3):411, Table 1; cited on IDS 1449) and Barnidge et al. (Barnidge et al., 2014, J. of Proteome Research; pgs. 1419-1427; cited on an IDS 1449). In light of the new rejections below, this rejection is withdrawn.
10. Claim 13 was rejected under 35 U.S.C. 103 as being unpatentable over Bergen et al. (Bergen et al. Clinical Chemistry, 2016, 62(1):243-251; cited on IDS 1449) and Lavatelli et al. (Lavatelli, et al., Biochemica et Biophysica Act (BBA), 2011, 1814(3):411, Table 1; cited on IDS 1449). Applicant has cancelled claim 13 making the rejection moot, therefore the rejection is withdrawn.
Maintained Rejections
(with new arguments)
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.
11. Claims 1 and 4-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6-11, 15, and 18 of copending Application No. 16615814 (Hereinafter App. ‘814) in view of Barnidge (WO2014/150170 A1, pub. 9/25/2014) and Kumar et al. (Lancet Oncol., 2016, 17:e328-46).
App. ‘814 claims a method of identifying and monitoring plasma cell associated disease- including multiple myeloma and AL amyloidosis, comprising purifying free kappa and lambda light chains from a sample- including plasma, serum, urine, blood, or CSF- from a subject, performing mass spectrometry- through MALDI-TOF MS on the sample and then identifying the presence of FLC clones in the sample.
App. ‘814 does not claim a method for identifying minimal residual disease (MRD). App. ‘814 does not claim a method using mass spectrometry over a mass/charge ratio range of 5,000-32,000 m/z. App. ‘814 does not claim a method for detection that includes if the monoclonal FLC clone is detected then the subject is monitored by screening a further sample for monoclonal FLC by MS after a time interval until no monoclonal FLC is detected, or testing bone marrow in the absence of any detection in the other sample. App. ‘814 does not claim a method where the subject is monitored by one or more additional techniques to monitor immunoglobulins in the sample prior to detecting a monoclonal FLC by MS.
Barnidge teaches performing mass spectrometry on light chains at an ideal mass/charge ratio of 21,000-26,000 m/z. (See Barnidge, pg. 12 lines 13-14). Barnidge teaches a method of testing for monoclonal gammopathies using MS that can be performed at diagnoses and during and after treatment to determine whether treatment is effective or not by comparing the detected FLCs with the detection level in the new sample, and if the FLCs have increased or remained the same determining treatment has not been effective. (See Barnidge, pg. 15 lines 8-20). Barnidge discloses the use of other laboratory techniques for diagnosis and monitoring of monoclonal gammopathies including SPEP, IFE, UPEP, and immunonephelometry. (See Barnidge, pg. 5 lines 1-5).
Barnidge does not disclose the use of MS testing for identifying MRD or the testing of bone marrow in the absence of the detection of monoclonal FLCs in other samples.
Kumar teaches that MRD is a condition characterized by the absence of malignant detection in conventional testing strategies but a low level of presence that can be detected in higher sensitivity testing. (See Kumar, pg. e329 “Depth of Response and Long Term Outcome”). Kumar teaches that bone marrow testing for the presence of minimal residual disease has been a cornerstone of disease assessment in the absence of measurable monoclonal protein in serum or urine. (See Kumar, pg. e329 “Detection of Minimal Residual Disease in Bone Marrow”).
It would have been prima facie obvious for a person of ordinary skill in the art prior to the effective filing date to combine the method of App. ‘814 with the teachings of Barnidge for the instant claimed invention. It would have been obvious because App. ‘814 is identifying and monitoring for the similar conditions and Barnidge teaches that further testing helps determine whether treatment is effective or not. Therefore, it would have been obvious to a person of ordinary skill in the art prior to the effective filing date to use the method of App. ‘814 with the teachings of Barnidge with a reasonable expectation of success at monitoring treatment by using the present claimed invention.
It would have been prima facie obvious to a person of ordinary skill in the art prior to the effective filing date to use the method of App. ‘814 and Barnidge with the teachings of Kumar for the present claimed invention. It would have been obvious because Kumar teaches that MRD is a condition of cancer disorders which means monitoring and identifying plasma cell associated disorders like multiple myeloma would include identifying MRD in those subjects, Kumar also teaches that bone marrow examination is a cornerstone of MRD testing following the absence of detection in blood or urine samples. It would have a reasonable expectation of success because it is known in the art to test bone marrow for MRD in the absence of detection in blood or urine samples and because MRD is low levels of expression of cancer disorders like multiple myeloma. Therefore, it would have been obvious to a person of ordinary skill in the art prior to the effective filing date to use the method of App. ‘814 and Barnidge with the teachings of Kumar with a reasonable expectation of success at detecting MRD in a subject with the present claimed invention.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
12. Applicant's arguments filed 9/15/2025 have been fully considered but they are not persuasive.
Applicant argues their amendments to the present claims overcame the provisional NSDP rejection. In response, new arguments are provided above to indicate the present claimed invention is an obvious variant of the co-pending application 16615814. Specifically, App. ‘814 is supplemented with the references of Barnidge (WO WO2014/150170 A1, pub. 9/25/2014) and Kumar et al. (Lancet Oncol., 2016, 17:e328-46). Barnidge discloses methods of testing for monoclonal gammopathies using MS at a mass to charge ratio of 21,000-26,000 m/z and testing at multiple timepoints following the detection of monoclonal FLCs to further monitor treatment and the use of other laboratory techniques other than MS to monitor monoclonal gammopathies. Kumar teaches that MRD is a condition of cancer where low levels of expression are undetected in conventional testing strategies and bone marrow testing in the absence of detection in blood or urine is a cornerstone of MRD testing. In light of the new arguments, the rejection is maintained that the present claimed invention is an obvious variant of co-pending application 16615814.
New Rejections
(Based on New Considerations)
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
13. Claims 1 and 4-12 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature/ a natural phenomenon) without significantly more.
The claims recite a method for identifying minimal residual disease in a subject being treated for or in remission for a monoclonal gammopathy comprising purifying free kappa light chains or free lambda light chains from a sample from the subject, performing mass spectrometry on the purified sample over a mass/charge ratio range of about 5,000 to 32,000 and detecting the presence of monoclonal free light chains in the sample.
Thus, the claims are directed to the judicial exception of a natural phenomenon. This judicial exception is not integrated into a practical application because the claims recite only the detection or observation of a naturally occurring phenomenon, which is data gathering to observe the naturally occurring phenomenon without applying the data to a practical application.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite use of routine laboratory procedures to detect and observe naturally occurring levels of monoclonal free light chains (FLC) to diagnose medical conditions. The claimed steps of detecting the presence of a monoclonal FLC and if detected, then monitoring by screening a further sample or bone marrow sample for a monoclonal FLC by MS after a time interval until there is no detection of monoclonal FLC in a sample or bone marrow sample are considered known, routine steps and are typically taken by those in the field to perform testing for a medical condition and are not elements that are sufficient to amount to significantly more than the judicial exception (see MPEP 2106.05(d)). For example Mills et al. (Clinical Chemistry, 2016, 62(10):1334-1344), Milani et al. (American J. Hematology, 2017, 92(8):772-779), Micallef et al. (J. Hematology & Oncology, 2010, 3:13), Barnidge et al. (J. Proteome Research, 2014, 13(3):1419-1427), and Koomen (WO 2015/131169 A2, pub. 9/3/2015) all teach and demonstrate the use of mass spectrometry for detecting monoclonal FLC for the diagnosis of monoclonal gammopathies.
The claims further recite the judicial exception of abstract ideas- specifically mental processes. As the Federal Circuit explained, "methods which can be performed mentally, or which are the equivalent of human mental work, are unpatentable abstract ideas the ‘basic tools of scientific and technological work’ that are open to all.’" 654 F.3d at 1371, 99 USPQ2d at 1694 (citing Gottschalk v. Benson, 409 U.S. 63, 175 USPQ 673 (1972)). The instant claims recite the decision to perform further testing on future samples or bone marrow samples based on results from the initial detection. These processes are no more than a mental processing step based on using the observations of the detected natural phenomenon to base a judgment or opinion for further monitoring or treatment of a medical condition.
Routine data gathering in order to observe a natural phenomenon/natural principle does not add a meaningful limitation to the method as it would be routinely used by those of ordinary skill in the art in order to observe the natural phenomenon/natural principle, and it fails to narrow the scope of the claims such that others are not foreclosed from using the law of nature/natural phenomenon. Methods of detecting natural phenomenon preempt all practical uses of it as others must use/detect the natural phenomenon to apply it to any other correlations, diagnosis, prognosis, therapeutic response, monitoring, etc.
To obviate the rejection, there must be at least one additional element or physical step that applies, relies on, or uses the natural principle so that the claim amounts to significantly more than the judicial exception itself. The claimed method currently fails to provide a practical application of the judicial exception and fails to add any elements that amount to significantly more than the judicial exception.
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.
14. Claims 1 and 4-12 are rejected under 35 U.S.C. 103 as being unpatentable over Barnidge (WO2014/150170 A1, pub. 9/25/2014) in view of Kumar et al. (Lancet Oncol., 2016, 17:e328-46).
Barnidge discloses methods of detecting the presence of monoclonal immunoglobulins, including free kappa and lambda light chains, for the diagnosis or monitoring of monoclonal gammopathies- including multiple myeloma (Example 5) in a subject using mass spectrometry. (See Barnidge, pg. 2 line21- pg. 3 line 5).
Specifically, Barnidge discloses obtaining a sample for testing that can be a biological fluid including blood, serum, plasma, or urine. (See Barnidge, pg. 9 lines 14-16). Barnidge discloses a process for purifying free kappa and lambda light chains from a broader immunoglobulin light chain. (See Barnidge, pg. 12 line 26- pg. 14 line 13). Barnidge discloses performing MALDI-TOF mass spectrometry on the purified samples of free kappa or lambda light chains at an ideal mass/charge ratio of 21,000-26,000 m/z. (See Barnidge, pg. 12 lines 13-14).
Regarding claims 4-5 and 7, Barnidge teaches that the method can be performed at diagnoses and during and after treatment to determine whether treatment is effective or not by comparing the detected FLCs with the measurement in the new sample, and if the FLCs have increased or remained the same determining treatment has not been effective. (See Barnidge, pg. 15 lines 8-20).
Regarding claim 12, Barnidge discloses the methods as being used along side other antibody interaction techniques including SPEP, IFE, UPEP, and immunonephelometry for diagnoses and monitoring of treatment. (See Barnidge, pg. 5 lines 1-5).
Barnidge does not disclose a method for the identification of MRD or testing bone marrow for the presence of FLC clones in response to no detection in the mass spectrometry assay.
Kumar teaches that MRD is a condition in cancer disorders, including multiple myeloma, characterized by the identification of residual tumor cells in a subject having received a complete response to a therapy possibly leading to relapse of the condition and decreased long-term survival. (See Kumar, pg. e329 “Depth of Response and Long Term Outcome”). Kumar teaches that bone marrow testing for the presence of MRD has been a cornerstone of disease assessment in the absence of measurable monoclonal protein in serum or urine. (See Kumar, pg. e329 “Detection of Minimal Residual Disease in Bone Marrow”).
It would have been prima facie obvious for a person of ordinary skill in the art prior to the effective date to use the method of Barnidge with the teachings of Kumar for the present claimed invention. It would have been obvious because Kumar teaches that MRD is a condition in subjects previously diagnosed with cancer disorders that can indicate relapse and is prevalent in multiple myeloma patients. Kumar also teaches that bone marrow testing has been a cornerstone of MRD testing in response to the absence in detection methods using serum or urine. It would have a reasonable expectation of success because it is known in the art to examine bone marrow in response to undetectable levels in serum or urine for a thorough examination for diagnosis. Therefore, it would have been obvious for a person of ordinary skill in the art prior to the effective date to use the method disclosed in Barnidge with the teachings of Kumar for the process of the present claimed invention with a reasonable expectation of success at diagnosing and monitoring MRD in a subject with a monoclonal gammopathy.
Response to Arguments
15. Applicant's arguments filed 9/15/2025 have been fully considered but they are not persuasive. It should be noted that the Applicant’s former arguments were based on 102/103 rejections based on different references that have been withdrawn. While not addressing Applicant’s arguments directed to the prior references and hereby rendered moot, the following addresses relevant arguments in consideration with the new rejection under 35 U.S.C. 103 discussed above.
Applicant argues that the previous prior art rejections were not applicable to the present claimed invention based on guidance and support from the specification and the acknowledged 132 declaration of Dr. Gregg Wallis filed on 9/15/2025. Specifically, Applicant argues that the particular techniques disclosed in the prior art references differ from the present claimed invention based on their purification techniques, their detection of FLC clones above a polyclonal background, shorter duration for testing, and higher sensitivity.
The present claimed invention is determined using the broadest reasonable interpretation of the claims. According to the MPEP 2111.01(II), “"Though understanding the claim language may be aided by explanations contained in the written description, it is important not to import into a claim limitations that are not part of the claim. For example, a particular embodiment appearing in the written description may not be read into a claim when the claim language is broader than the embodiment." Superguide Corp. v. DirecTV Enterprises, Inc., 358 F.3d 870, 875, 69 USPQ2d 1865, 1868 (Fed. Cir. 2004).
Amended claim 1 recites, “purifying free kappa and lambda light chains from the sample;” the dependent claims provide no further definition of “purification” or any techniques involved that would provide for free kappa and lambda light chains. The specification provides no further definition of purification. Therefore, a reasonable interpretation of claim 1 would include any techniques that purifies kappa and lambda light chains from a sample and allows them to be tested using mass spectrometry.
Further, no limitations in any of the presently claimed invention requires the FLC clone being compared to a polyclonal background, the test being performed in a specific time frame or being limited only to the steps recited in the claims.
Conclusion
16. Claims 1 and 4-12 are rejected.
17. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LINDSAY DUNN whose telephone number is (571)272-5825. The examiner can normally be reached Monday-Friday 8-4:30.
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/LINDSAY DUNN/Examiner, Art Unit 1644
/Laura B Goddard/Primary Examiner, Art Unit 1642
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