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 .
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.
Priority
The present application was filed on 7/25/2025 and is a CON of 17/742,076, filed 05/11/2022. The present application claims benefit under 35 U.S.C. 119(e) to provisional application 63/187,344 filed on 5/11/2021.
Information Disclosure Statement
The five information disclosure statements filed on 5/22/2026 are being considered by the examiner.
Claim Objections
Claims 1 are objected to because of the following informalities:
In claim 1 line 3, Applicant uses the abbreviation "sBCMA", it is recommended that abbreviations be accompanied by their full meaning at least at first instance that the abbreviation is used in order to improve clarity and avoid confusion.
In claim 10 line 2, “administering to the subject about from about” appears to be a typographical error, namely it is suggested that “administering to the subject about from about” read as “administering to the subject .
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 4-5 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 4 recites “A method of treating multiple myeloma or plasmacytoma in a subject in need thereof, comprising: (a) measuring a level of sBCMA in a blood sample obtained from the subject; (b) comparing the level of sBCMA to a reference sBCMA level to measure a tumor burden of the subject; and (c) administering a therapy to the subject based on the tumor burden measured in (b)”.
However, it is not clear what is meant by “(b) comparing the level of sBCMA to a reference sBCMA level to measure a tumor burden of the subject”. More specifically, it is not clear how comparing the level of sBCMA to a reference sBCMA level relates to the measuring a tumor burden of the subject because comparing sBCMA levels fails to address the measuring of the tumor burden of the subject. Note that the specification discloses that “[t]he term "tumor burden" or "tumor load" as used herein refers to the number of tumor cells, the size of a tumor, the total mass of tumor tissue, or the amount of cancer in the body of a subject” (para. 81). Therefore, the specification suggests that measuring a tumor burden requires measuring the number of tumor cells and is not directly associated with a sBCMA level. Furthermore, the specification fails to disclose what sBCMA levels correspond to what level of tumor burden. For these reasons, a person having ordinary skill in the art would not be capable of recognizing the metes and bounds of the claim.
Furthermore, it is not clear what is meant by “(c) administering a therapy to the subject based on the tumor burden measured in (b)” because a step of measuring a tumor burden is not recited in (b). Step (b) fails to recite an active step of measuring the tumor burden of the subject, and instead recites a step of comparing sBCMA levels “to measure a tumor burden of the subject”. In other words, “to measure a tumor burden of the subject” is reasonably interpreted as the intended use of the comparing step, not a measurement step. Because of this, a person having ordinary skill in the art would not be capable of recognizing how the administering step is performed. Thus, the claim is indefinite.
Claim 5 recites “The method of claim 4, further comprising treating the subject with a
therapy against multiple myeloma or plasmacytoma before the blood sample is obtained from the
subject, wherein the reference sBCMA level is measured from a control blood sample obtained
from the subject before the subject is treated with the therapy, and the treatment comprises: (a) continuing treating the subject with the therapy if the level of sBCMA measured in claim 4(a) is lower than the reference sBCMA level, or (b) treating the subject with a second therapy against multiple myeloma or plasmacytoma if the level of sBCMA is the same or higher than the reference sBCMA level”.
However, “a therapy” of claim 5 lines 1-2, “the therapy” of claim 5 line 3 and “the therapy” of claim 5 line 4 (step (a)) are not clear. First, claim 4 already recites “(c) administering a therapy to the subject based on the tumor burden measured in (b)”; therefore, “treating the subject with a therapy against multiple myeloma or plasmacytoma before the blood sample is obtained from the subject” could be referring to the same therapy as the therapy in 4(c) or another therapy. Similarly, “wherein the reference sBCMA level is measured from a control blood sample obtained from the subject before the subject is treated with the therapy” could be referring to the same therapy as in claim 5 lines 1-2, the therapy in 4(c) or another therapy. In the same way, “the therapy” recited in claim 5(a) could be referring to the therapy from before the blood is obtained recited claim 5 line 2, or from after the control blood is obtained in claim 5 line 3 or the therapy of claim 4(c). Given these multiple possible interpretations of the “therapy” of claim 5 line 2, line 4 and line 5, a person having ordinary skill in the art would not recognize the metes and bounds of the claim. Second, “a second therapy” recited in claim 5(b) is not clear. Given that a first therapy is not clear (as discussed above), the “second therapy” of claim 5(b) is indefinite. A person having ordinary skill in the art would not recognize what the metes and bounds of the claim.
Regarding claim 18, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). In this case, it is unclear whether the sample must consist of “serum” or rather if this language is merely exemplary of preferred embodiments.
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.
Claims 1-19 are rejected under 35 U.S.C. 101 because the claimed invention is directed to at least one judicial exception without significantly more.
The U.S. Patent and Trademark Office recently revised the MPEP with regard to § 101 (see the MPEP at 2106). Regarding the MPEP at 2106, in determining what concept the claim is “directed to,” we first look to whether the claim recites:
(1) any judicial exceptions, including certain groupings of abstract ideas (i.e., mathematical concepts, certain methods of organizing human activity such as a fundamental economic practice, or mental processes); and
(2) additional elements that integrate the judicial exception into a practical application (see MPEP § 2106.05(a)-(c), (e)-(h)).
Only if a claim (1) recites a judicial exception and (2) does not integrate that exception into a practical application, do we then look to whether the claim contains an “‘inventive concept’ sufficient to ‘transform’” the claimed judicial exception into a patent-eligible application of the judicial exception. Alice, 573 U.S. at 221 (quoting Mayo, 566 U.S. at 82). In so doing, we thus consider whether the claim:
(3) adds a specific limitation beyond the judicial exception that is not “well-understood, routine, conventional” in the field (see MPEP § 2106.05(d)); or
(4) simply appends well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception.
See MPEP 2106.
ELIGIBILITY STEP 2A: WHETHER A CLAIM IS DIRECTED TO A JUDICIAL EXCEPTION
Step 2A, Prong 1
Prong One asks does the claim recite an abstract idea, law of nature, or natural phenomenon? In Prong One examiners evaluate whether the claim recites a judicial exception, i.e. whether a law of nature, natural phenomenon, or abstract idea is set forth or described in the claim. While the terms "set forth" and "described" are thus both equated with "recite", their different language is intended to indicate that there are two ways in which an exception can be recited in a claim. For instance, the claims in Diehr, 450 U.S. at 178 n. 2, 179 n.5, 191-92, 209 USPQ at 4-5 (1981), clearly stated a mathematical equation in the repetitively calculating step, and the claims in Mayo, 566 U.S. 66, 75-77, 101 USPQ2d 1961, 1967-68 (2012), clearly stated laws of nature in the wherein clause, such that the claims "set forth" an identifiable judicial exception. Alternatively, the claims in Alice Corp., 573 U.S. at 218, 110 USPQ2d at 1982, described the concept of intermediated settlement without ever explicitly using the words "intermediated" or "settlement." See MPEP 2106.04 (II)(A)(1).
Claim 1 recites “A method of monitoring a progression of multiple myeloma in a subject, comprising: (a) measuring a level of sBCMA in a blood sample obtained from the subject; and (b) comparing the level of sBCMA to a reference sBCMA level, wherein the reference sBCMA level is measured from a control blood sample obtained from the subject before the blood sample of (a) is obtained from the subject; wherein an increase in the level of sBCMA compared to the reference sBCMA level indicates one or more of an increased tumor burden or a disease progression, and a decrease in the level of sBCMA compared to the reference sBCMA level indicates one or more of a decreased tumor burden or lack of disease progression”. And claim 2 recites “A method of determining a response to a therapy against multiple myeloma in a subject, comprising: (a) treating the subject with the therapy; (b) measuring a level of sBCMA in a blood sample obtained from the subject after the treating of (a); and (c) comparing the level of sBCMA to a reference sBCMA level, wherein the reference sBCMA level is measured from a control blood sample obtained from the subject before the treating of (a); wherein a decrease in the level of sBCMA compared to the reference sBCMA level indicates the subject is responsive to the therapy, and an increase or no change in the level of sBCMA compared to the reference sBCMA level indicates the subject is not responsive to the therapy”.
The natural relationship to which the claims are directed (i.e., the relation sBCMA and multiple myeloma/responsiveness to therapy) is a law of nature. Similar concepts have been held by the courts to constitute law of nature/ natural phenomena, as in the identification of a correlation between the presence of myeloperoxidase in a bodily sample (such as blood or plasma) and cardiovascular disease risk in Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1361, 123 USPQ2d 1081, 1087 (Fed. Cir. 2017). In Mayo, the Supreme Court found that a claim was directed to a natural law, where the claim required administering a drug and determining the levels of a metabolite following administration, where the level of metabolite was indicative of a need to increase or decrease the dosage of the drug. See Mayo Collaborative Services v. Prometheus Labs., Inc., 566 U.S. 66, 74 (2012).
The instant claims are similar to those in Mayo as they involve a "relation itself [which] exists in principle apart from any human action" (id. at 77), namely the relationship between the naturally occurring blood sBCMA levels and the presence of multiple myeloma or treatment response.
The correlation between sBCMA levels and disease/therapy is a judicial exception as it exists in principle apart from any human action; the correlation itself therefore cannot form the basis for eligibility. Similarly, it is a naturally occurring phenomenon that sBCMA levels are elevated to different extents in different treatments.
Additionally, the claims also recite steps of “comparing …” (see step (b) of claim 1 and step (c) of claim 2)). Furthermore, independent claim 4 recites “A method of treating multiple myeloma or plasmacytoma in a subject in need thereof, comprising: (a) measuring a level of sBCMA in a blood sample obtained from the subject; (b) comparing the level of sBCMA to a reference sBCMA level to measure a tumor burden of the subject”.
The claimed steps of “comparing the level of sBCMA to a reference sBCMA level” may also be categorized as abstract ideas, namely mental processes/concepts performed in the human mind (such as a doctor simply thinking about the measured level of sBCMA in relation to a cutoff value and making an evaluation, judgment, or opinion). The claims, under their broadest reasonable interpretation, cover performance of a comparing step that takes place solely within the human mind, or by a human using pen and paper. Comparing information regarding a sample to a control or reference data represents abstract ideas.
Similar concepts involving comparing information regarding a sample or test subject to a control or target data have been held to be an "abstract mental process", as in University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 113 USPQ2d 1241 (Fed. Cir. 2014) which involved "comparing BRCA sequences and determining the existence of alterations", the collecting and comparing of known information in Classen, the comparing information regarding a sample or test subject to a control or target data in Ambry and Myriad CAFC, as well as Mayo.
Dependent claim 5 recites the limitation “wherein the reference sBCMA level is measured from a control blood sample obtained from the subject before the subject is treated with the therapy”. Therefore, this limitation merely limits when the reference sBCMA level is measured, which is reasonably considered to be directed to the judicial exception, namely the abstract idea of comparing the sBCMA level of the subject and the sBCMA reference level.
Dependent claim 6 recites “The method of claim 2, wherein the therapy is teclistamab or talquetamab”. However, this claim merely limits the therapy to which the natural correlation is directed, i.e. the natural correlation between sBCMA and treatment response. Therefore, this claim is directed to at least one judicial exception.
Dependent claim 8 merely limits when the blood sample is obtained, which is used in the natural correlation between blood sBCMA and response to therapy. Therefore, this claim is directed to at least one judicial exception.
Dependent claims 9-13 further limit the therapy to which the natural correlation is directed, i.e. the natural correlation between sBCMA and treatment response. Therefore, these claims are directed to at least one judicial exception.
Dependent claim 14 limits when the therapy is administered, which is used in the natural correlation between blood sBCMA and response to therapy. Therefore, this claim is directed to at least one judicial exception.
Dependent claims 16-17 merely limit the type of multiple myeloma, directed to the natural correlation between blood sBCMA and response to therapy against multiple myeloma.
Dependent claim 18 merely limits the type of blood sample used in the natural correlation between blood sBCMA and response to therapy. Therefore, this claim is directed to at least one judicial exception.
Step 2A, Prong 2
The above-discussed steps of “measuring a level of sBCMA in a blood sample” and “comparing the level of sBCMA to a reference sBCMA level” are insufficient to integrate the judicial exception(s) into a practical application because steps corresponding to mental activity, which could be performed in a practitioner’s head, are insufficient to constitute a practical application. In this case, measuring sBCMA and comparing numerical values, represent judicial exceptions and not a practical application thereof.
Dependent claim 3 recites “further comprising treating the subject with a second therapy against multiple myeloma if the level of sBCMA indicates the subject is not responsive to the therapy”.
Claim 4 recites “(c) administering a therapy to the subject based on the tumor burden measured in (b)”.
Dependent claim 5 recites “further comprising treating the subject with a therapy against multiple myeloma or plasmacytoma before the blood sample is obtained from the subject… and the treatment comprises: (a) continuing treating the subject with the therapy if the level of sBCMA measured in claim 4(a) is lower than the reference sBCMA level, or (b) treating the subject with a second therapy against multiple myeloma or plasmacytoma if the level of sBCMA is the same or higher than the reference sBCMA level”.
Dependent claim 7 recites “further comprising treating the subject with a second therapy against multiple myeloma or plasmacytoma if the level of sBCMA indicates the subject is not responsive to teclistamab or talquetamab”.
Dependent claim 15 recites “wherein the second therapy comprises one or more of autologous stem cell transplants (ASCT), radiation, surgery, chemotherapeutic agents, CAR-T therapies, cellular therapies, immunomodulatory agents, targeted cancer therapies, or combinations thereof”.
These “treating” steps are insufficient to integrate the judicial exception as (1) they are not limited to a particular treatment, (2) there is not necessarily any relationship between the judicial exception and the treatment step, and (3) the “treating” steps are not clearly required to be performed.
(1) The recited steps of “treating the subject with a second therapy” (claim 3), “administering a therapy to the subject” (claim 4), “treating the subject with a therapy…comprises… continuing treating the subject…or… treating the subject with a second therapy” (claim 5), “treating the subject with a second therapy” (claim 7) or “wherein the second therapy comprises one or more of autologous stem cell transplants (ASCT), radiation, surgery, chemotherapeutic agents, CAR-T therapies, cellular therapies, immunomodulatory agents, targeted cancer therapies, or combinations thereof” (claim 15), are recited at a high level of generality and are not limited to a particular treatment. Such highly generalized treatment limitations – which do not require any specific treatment for multiple myeloma – do not amount to sufficient practical application to provide patentability. Although a claim limitation can integrate a judicial exception by applying or using the judicial exception(s) to effect a particular treatment or prophylaxis for a disease or medical condition, in this case no specific or particular treatment is set forth.
The level of generality in the instant claims stands in contrast to the treatment claims found patent-eligible in Vanda Pharm. Inc. v. West-Ward Pharm. Int’l Ltd., 887 F.3d 1117 (Fed. Cir. 2018) and Natural Alternatives Int’l v. Creative Compounds LLC, 2017 WL 1216226 (Fed. Cir. Mar. 15, 2019). The claims at issue in Vanda recited administering a specific drug (iloperidone) at specific dosage ranges based on a patient’s genotype. Vanda, 887 F.3d at 1135. Accordingly, the court found that although the inventors recognized the relationships between iloperidone, a patient’s genotype, and QTc prolongation, what they claimed is “an application of that relationship,” i.e., “‘a new way of using an existing drug’ that is safer for patients because it reduces the risk of QTc prolongation.” Id. (quoting Mayo, 566 U.S. at 87). The Federal Circuit characterized the Vanda claims as being directed to “a specific method of treatment for specific patients using a specific compound at specific doses to achieve a specific outcome.” Id. at 1136. Similarly, the Federal Circuit found that the claims in Natural Alternatives “contain specific elements that clearly establish they are doing more than simply reciting a natural law,” such as specifying a patient population, particular results to be obtained, specific compounds to be administered to achieve the claimed results, and dosages via an “effective” limitation. Natural Alternatives, 4-5.
In contrast to the claims in Vanda and Natural Alternatives, the present claims do not specify a particular result to be obtained, a compound to be administered to achieve a claimed result, or any specific dosage of a specific compound.
Rather, treating the subject with a “therapy” would be directed to any and all treatments, including no treatment at all. The recited treating steps do not limit the claims to a particular application; instead, the effect of the treatment limitations “is simply to tell doctors to apply the law somehow when treating their patients.” Mayo, 566 U.S. at 81-82.
Here, the claimed treatment step is instead merely an instruction to “apply” the exception in a generic way. Thus, the treatment step does not integrate the abstract idea(s) into a practical application. Although claim 15 recites “autologous stem cell transplants (ASCT), radiation, surgery, chemotherapeutic agents, CAR-T therapies, cellular therapies, immunomodulatory agents, targeted cancer therapies, or combinations thereof”, none of these are considered specific enough. All these treatments are generic. Thus, fail to integrate the judicial exception(s) into a practical application.
(2) Because of the way claim 4 is currently presented, there is not necessarily any relationship between the judicial exception and the treatment step. Specifically, steps c) recites, “administering a therapy to the subject based on the tumor burden measured in (b)”, for which antecedent basis is found in the preamble rather than in step b). The claims do not clearly require that the therapy treated relates to multiple myeloma. Accordingly, under the broadest reasonable interpretation of the claim, steps c) is not clearly a practical applications of the judicial exception(s) and so fail to integrate the judicial exception(s).
(3) Because of the way the claims are currently presented (claims 3, 5 and 7), the “treating” steps are not clearly required to be performed. Because the claims recite “treating” as a conditional statement (see “if”) the claims therefore encompass for example no treatment, i.e., treating is not necessarily performed.
Although the claims recite “one or more of autologous stem cell transplants (ASCT), radiation, surgery, chemotherapeutic agents, CAR-T therapies, cellular therapies, immunomodulatory agents, targeted cancer therapies, or combinations thereof”, as stated above, the claim step of treating is recited as conditional (“if the level of sBCMA indicates”). Therefore, the second therapy limitation fails to integrate the claims into a practical application of the judicial exception.
Dependent claim 19 also recites “wherein the level of sBCMA in the blood sample is measured using an electrochemiluminescence ligand binding assay, an enzyme-linked immunosorbent assay (ELISA), or mass spectrometry”. Such steps are insufficient to integrate the judicial exception(s) because the purpose is merely to obtain data. This does not go beyond insignificant presolution activity, i.e., a mere data gathering step necessary to use the correlation, similar to the fact pattern in In re Grams, 888 F.2d 835 (Fed. Cir. 1989) and Ariosa Diagnostics, Inc. v. Sequenom, Inc. (Fed. Cir. 2015). Furthermore, the assays to measure sBCMA are recited at a high level of generality and are not tied, for example, to any particular machine or apparatus.
ELIGIBILITY STEP 2B: WHETHER THE ADDITIONAL ELEMENTS CONTRIBUTE AN "INVENTIVE CONCEPT"
The additional elements of the claims, including the steps of measuring sBCMA levels using an electrochemiluminescence ligand binding assay, an enzyme-linked immunosorbent assay (ELISA), or mass spectrometry, do not add significantly more to the judicial exception(s). The step of measuring sBCMA is recited at a high level of generality and is not limited, for example, to any specific testing technique.
In this case, it was well-understood, routine and conventional to determine the concentration of sBCMA in samples using an electrochemiluminescence ligand binding assay, an enzyme-linked immunosorbent assay (ELISA), or mass spectrometry. See for example the specification paragraph 138 which discloses that “[t]he disease status can be determined by any suitable method known to those skilled in the art in view of the present disclosure, including, e.g., analysis of serum and urine monoclonal protein concentrations, M-protein levels, sBCMA levels”. See also the specification paragraph 49, which discloses that “[t]he relative level of specific proteins can be determined by methods known in the art. For example, antibody-based methods, such as an immunoblot, enzyme-linked immunosorbent assay (ELISA), or other methods can be used”. Finally, see the specification paragraph 103 discloses that “[i]n certain embodiments, the level (e.g., expression) of the biomarker is measured by electrochemiluminescence ligand binding assay or other similar methods known in the art. In certain embodiments, the level (e.g., expression) of the biomarker is measured by enzyme-linked immunosorbent assay-based methodologies (ELISA) or other similar methods known in the art...In certain embodiments, the level (e.g., expression) of the biomarker is measured by exposing the sample to a mass analysis technique (e.g., mass spectrometry) or other similar methods known in the art”.
When recited at this high level of generality, there is no meaningful limitation, such as a particular or unconventional machine or a transformation of a particular article, in this step that distinguishes it from well-understood, routine, and conventional data gathering activity engaged in by scientists prior to applicant’s invention, and at the time the application was filed, e.g., the routine and conventional techniques of detecting a protein using an antibody to that protein. See also MPEP 2106.05(g).
Furthermore, while the claims recites treating the subject, these steps are not clearly integrated into a practical application of the judicial exception, as discussed above. Furthermore, there is nothing of record to suggest that the claims involve novel treatment steps. Treating is recited at a high level of generality.
Appending a generic, routine, and obvious post-solution treatment step does not provide a sufficient inventive concept to satisfy § 101. As was the case in Mayo and Ariosa, the method claims at issue here amount to "nothing significantly more than an instruction to doctors to apply the applicable laws when treating their patients" using "conventional steps, specified at a high level of generality." Mayo, 132 S. Ct. at 1298, 1300; Ariosa, 788 F.3d at 1377-78.
There is also evidence of record to indicate that the additional elements, alone or in combination, do not go beyond well-understood, routine and conventional activity in that others had previously measured sBCMA in subjects and also treated multiple myeloma in the same subject.
See for example Dettman and Opalinska (WO 2020/089794 A1)-Cite No. 38 of IDS filed on 5/22/2026 containing 15 pages (“Dettman”). Dettman teaches a method of treating multiple myeloma or plasmacytoma in a subject in need thereof (“[a] method for treating cancer in a patient in need thereof” claim 6, “The method of claims 1-3 and 6-10, wherein the cancer is multiple myeloma, lymphoma” claim 13) comprising: measuring a level of sBCMA in a blood sample obtained from the subject; comparing the level of sBCMA to a reference sBCMA level, and treating the subject with a therapy against multiple myeloma (“(a) obtaining a sample from the patient; and (b) testing the sample for expression of soluble BCMA; and (c) if the subject expresses soluble BCMA, administering to the patient an effective amount of a BCMA antigen binding protein” claim 6).
See also Shah et al. Leukemia (Feb. 2020) 34:985–1005 https://doi.org/10.1038/s41375-020-0734-z -Cite No. 3 of IDS 5/22/2026 containing 9 pages (“Shah”). Shah teaches that “[t]he measurements of sBCMA may also be useful for monitoring patient response to ongoing therapy. Patients who have responded to therapy have reduced sBCMA levels compared with patients with progressive disease [7, 27]. Changes in sBCMA levels tend to correlate with the clinical status of patients with MM during anti-MM treatment, as well as tumor mass in preclinical models” (page 988 col. 1 para. 4).
See also Mueller et al. (WO 2017210617 A2) (“Mueller”). Mueller teaches in “Example 5: Soluble BCMA in Peripheral Blood Serum is a Useful Minimal Residual Disease Biomarker for Monitoring Patients with Multiple Myeloma, Chronic Lymphocytic Leukemia and Other B Cell Malignancies Following Treatment with CAR-BCMA or CAR-19” (page 396 lines 20-24).
Sanchez et al. British Journal of Haematology, 2012, 158, 727–738 doi:10.1111/j.1365-2141.2012.09241.x -Cite No. 49 of IDS filed on 5/22/2026 containing 9 pages (“Sanchez”) also teaches that “[c]hanges in serum BCMA levels were found to correlate with changes in an individual patient’s clinical status in response to anti-MM treatment. Except in one case, those patients responding to treatment showed decreases in these levels whereas those with disease progression showed increases in BCMA levels (Fig S3)” (page 730 col. 2 para. 4).
Therefore, the evidence of record indicates that it was known to both measure levels of sBCMA as claimed as well as to also treat the same subjects with treatments against multiple myeloma. The additional steps/elements in the claim, when considered alone or in combination, are insufficient to add significantly more.
The recited multiple myeloma therapies, namely teclistamab or talquetamab, are well-understood, routine and conventional in the art.
See for example, Baldwin et al. (WO 2017/031104 Al)-Cite No. 25 of IDS filed on 10/27/2023 containing 15 pages (“Baldwin”). Baldwin teaches “methods of treating BCMA-expressing cancer in a subject in need thereof include administering to the subject a therapeutically effective amount of a described BCMA x CD3-multispecific antibody or multispecific antigen-binding fragment thereof. In some embodiments, the subject is a mammal, preferably a human” (page 12 lines 3-6). Baldwin teaches that “more preferably a BCMA x CD3-bispecific antibody” (page 53 paragraph 3) is used. Baldwin further teaches that “[i]n some embodiments, the BCMA-expressing cancer is a lymphoma, such as multiple myeloma” (page 12 lines 1-2).
See also, Janssen Research & Development, LLC, ClinicalTrials.gov ID NCT 03145181. Version 22: Posted online on 2019-04-25-Cite No. 3 of IDS filed 5/22/2026 with 9 pages (“Janssen”). Janssen teaches a “dose escalation study of teclistamab, a humanized BCMA*CD3 bispecific antibody, in participants with relapsed or refractory multiple myeloma (MAjesTEC-1). Janssen further teaches “IV and SC administration [of teclistamab]: dose escalation (Part 1) and dose expansion(Part 2)” (Detailed Description page 9).
Also, Verkleij et al. Blood Advances; published online 23 April 2021. Volume 5, number 8- Cite No. 37 of IDS filed on 5/22/2026 containing 9 pages (“Verkleij”) Verkleij teaches “[t]he novel GPRC5D-targeting T-cell redirecting bispecific antibody, talquetamab, effectively kills GPRC5D1 MM cell lines” (Abstract).
In addition, the “second therapy” from claim 15 are insufficient to add significantly more as they are recited at a high level of generality (no specific treatment is set forth). Broadly or generically treating is tantamount to a mere instruction to “apply” the judicial exception using well-understood, routine or conventional techniques in the field. It does not go beyond general instructions to apply or use the judicial exception. A bare statement of a judicial exception, even a newly discovered judicial exception or very narrowly judicial exception, is not sufficient to integrate the judicial exception such that it is practically applied.
Unlike the claims in Vanda Pharm. Inc. v. West-Ward Pharm. Int’l Ltd (Fed. Cir. 2018, which were directed to a specific method of treatment for specific patients using a specific compound at specific doses to achieve a specific outcome (see Vanda decision at page 32, second paragraph), the instant claims, like those in Mayo, while including a treatment step cannot be clearly categorized as being directed to a specific method of treatment; and the treatment steps fail to add significantly more for reasons noted above.
Also, Dettman teaches wherein the second therapy comprises one or more of chemotherapeutic agents, CAR-T therapies, cellular therapies, immunomodulatory agents, targeted cancer therapies, or combinations thereof (“[a] BCMA antigen binding protein for use in the treatment of cancer in a patient, wherein the patient is characterized by a high level of soluble BCMA expression in a sample from the patient” claim 19, “[i]n one aspect of the invention, the BCMA antigen binding protein is a CAR-T ( chimeric antigen receptor T-cell therapeutic)” page 12 lines 18-19, “[t]ypical anti-neoplastic agents useful in the present invention include…immunotherapeutic antibodies…chemotherapeutic agents…immuno-modulatory agents” page 30 line 28 and 30, and page 31 line 8).
For all of these reasons, the claims fail to include additional elements that are sufficient to amount to significantly more than the judicial exception(s).
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2 and 4 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sanchez et al. British Journal of Haematology, 2012, 158, 727–738 doi:10.1111/j.1365-2141.2012.09241.x -Cite No. 49 of IDS filed on 5/22/2026 containing 9 pages (“Sanchez”), as evidenced by Sanchez et al. Supporting Information (British Journal of Haematology, 2012, 158, 727–738 doi:10.1111/j.1365-2141.2012.09241.x).
Regarding claim 1, Sanchez teaches a method of monitoring a progression of multiple myeloma in a subject (“Serum B-cell maturation antigen is elevated in multiple myeloma and correlates with disease status and survival” Title, “serum BCMA levels may be a new biomarker for monitoring disease status and overall survival of MM patients” Abstract), comprising: (a) measuring a level of sBCMA in a blood sample obtained from the subject (“Serum BCMA levels were measured in samples from MM patients (n = 209)” Abstract); and (b) comparing the level of sBCMA to a reference sBCMA level, wherein the reference sBCMA level is measured from a control blood sample obtained from the subject before the blood sample of (a) is obtained from the subject, wherein an increase in the level of sBCMA compared to the reference sBCMA level indicates one or more of an increased tumor burden or a disease progression, and a decrease in the level of sBCMA compared to the reference sBCMA level indicates one or more of a decreased tumor burden or lack of disease progression (“Changes in serum BCMA levels were found to correlate with changes in an individual patient’s clinical status in response to anti-MM treatment. Except in one case, those patients responding to treatment showed decreases in these levels whereas those with disease progression showed increases in BCMA levels (Fig S3)” page 730 col. 2 para. 4). Note that as evidenced by Sanchez’s Supplemental Information, see Figure S3, the reference sBCMA level is measured from a control blood sample obtained from the subject before the blood sample of (a) is obtained from the subject (pages 6-11).
Regarding claim 2, Sanchez teaches a method of determining a response to a therapy against multiple myeloma in a subject (Title, “Serum BCMA levels were higher among patients with progressive disease (n = 80) compared to those with responsive disease (n = 79; P = 0_0038)” Abstract), comprising: (a) treating the subject with the therapy; (b) measuring a level of sBCMA in a blood sample obtained from the subject after the treating of (a); and (c) comparing the level of sBCMA to a reference sBCMA level, wherein the reference sBCMA level is measured from a control blood sample obtained from the subject before the treating of (a); wherein a decrease in the level of sBCMA compared to the reference sBCMA level indicates the subject is responsive to the therapy, and an increase or no change in the level of sBCMA compared to the reference sBCMA level indicates the subject is not responsive to the therapy (“Changes in serum BCMA levels were found to correlate with changes in an individual patient’s clinical status in response to anti-MM treatment. Except in one case, those patients responding to treatment showed decreases in these levels whereas those with disease progression showed increases in BCMA levels (Fig S3)” page 730 col. 2 para. 4). Note that as evidenced by Sanchez’s Supplemental Information, see Figure S3, the reference sBCMA level is measured from a control blood sample obtained from the subject before the treating of (a) (“Pt 1082…Untreated…PR” page 6, “Pt 1634…Untreated…CR IF(-)” page 7, “Pt 1850…Untreated…PR” page 8, pages 10-11).
Regarding claim 4, although the claim is indefinite (see 112b rejection above), in the interest of compact prosecution, the claim is interpreted as reciting “b) comparing the level of sBCMA to a reference sBCMA level administering a therapy to the subject
Sanchez teaches a method of treating multiple myeloma or plasmacytoma in a subject in need thereof (Title, “We also demonstrated that sera from mice with human MM xenografts contained human BCMA, and levels correlated with the change in tumour volume in response to melphalan or cyclophosphamide with bortezomib” Abstract), comprising: (a) measuring a level of sBCMA in a blood sample obtained from the subject; (b) comparing the level of sBCMA to a reference sBCMA level; and (c) administering a therapy to the subject (“Serum human BCMA levels also correlated with tumour growth, IgG levels and response to treatment in mice bearing another human MM xenograft, LAGk-1….Mice receiving melphalan (3 mg/kg, n = 4) twice weekly via i.p. injection showed smaller tumour volumes, IgG and BCMA levels compared to untreated mice (tumour volumes: P < 0.0001; hIgG: P = 0.0033; BCMA: P = 0.0055; Fig 6A–C)” page 734 col. 1 para. 3). See Figure 6C showing sBCMA levels of mice being treated twice weekly with melphalan 3mg/kg over several weeks which anticipates “a) measuring a level of sBCMA in a blood sample obtained from the subject; (b) comparing the level of sBCMA to a reference sBCMA level; and (c) administering a therapy to the subject” as currently interpreted. Although Sanchez fails to use the language “comparing the level of sBCMA to a reference sBCMA level”, the teaching of Figure 6C which shows a line-scatter plot graph of sBCMA levels (“Results presented are group means ± standard error of the mean” page 735 col. 2) over time inherently compares the level of sBCMA to a reference sBCMA level. Here, the reference sBCMA level is interpreted as the sBCMA level measured at day 14 in Fig. 6C; given that the mice are also treated twice weekly, Sanchez anticipates the claim. Also note that as per paragraph 77 of the instant disclosure “[t]he term “subject” as used herein includes any human or nonhuman animal”.
Regarding claim 5, although the claim is indefinite (see 112b rejection above), in the interest of compact prosecution, the therapy recited throughout claim 5 is interpreted to be the same therapy as in claim 4(c). Sanchez teaches further comprising treating the subject with a therapy against multiple myeloma or plasmacytoma before the blood sample is obtained from the subject, wherein the reference sBCMA level is measured from a control blood sample obtained from the subject before the subject is treated with the therapy, and the treatment comprises: (a) continuing treating the subject with the therapy if the level of sBCMA measured in claim 4(a) is lower than the reference sBCMA level (page 734 col. 1 para. 3, Fig. 6C). See Fig. 6C showing that the reference sBCMA level (sBCMA level at day 14 of Fig. 6C) is higher than the level of sBCMA measured in claim 4(a) (sBCMA level at day 7 of Fig. 6C), given that the mice are being treated twice weekly with melphalan 3mg/kg up to day 24, Sanchez anticipates “continuing treating the subject with the therapy if the level of sBCMA measured in claim 4(a) is lower than the reference sBCMA level” and the claim.
Claims 2-3 and 15 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Mueller et al. (WO 2017210617 A2) (“Mueller”).
Regarding claim 2, Mueller teaches a method of determining a response to a therapy against multiple myeloma in a subject (“Example 5: Soluble BCMA in Peripheral Blood Serum is a Useful Minimal Residual Disease Biomarker for Monitoring Patients with Multiple Myeloma, Chronic Lymphocytic Leukemia and Other B Cell Malignancies Following Treatment with CAR-BCMA or CAR-19” page 396 lines 20-24), comprising: (a) treating the subject with the therapy (“Following Treatment with CAR-BCMA or CAR-19” page 396 lines 22-23); (b) measuring a level of sBCMA in a blood sample obtained from the subject after the treating of (a) (“This Example uses ELISA to examine serum samples from MM patients before and after CAR-BCMA therapy on clinical trial UPCC14415” page 396 lines 30-32); and (c) comparing the level of sBCMA to a reference sBCMA level (“and shown that serum sBCMA is greatly reduced in patients experiencing CAR-BCMA expansion and persistence after infusion, and returns if the patients subsequently lose CAR-BCMA cells and undergo clinical relapse” page 396 lines 32-34), wherein the reference sBCMA level is measured from a control blood sample obtained from the subject before the treating of (a) (“serum samples from MM patients before and after CAR-BCMA therapy on clinical trial UPCC14415” page 396 lines 31-32); wherein a decrease in the level of sBCMA compared to the reference sBCMA level indicates the subject is responsive to the therapy, and an increase or no change in the level of sBCMA compared to the reference sBCMA level indicates the subject is not responsive to the therapy (page 396 lines 30-34, “Thus sBCMA is an excellent and convenient minimal residual disease (MRD) biomarker for CAR-BCMA efficacy in MM” page 396 line 34 and page 397 lines 1-2).
Regarding claim 3, Mueller further teaches further comprising treating the subject with a
second therapy against multiple myeloma if the level of sBCMA indicates the subject is not responsive to the therapy (“In one aspect, disclosed herein is a method of treating a subject having hematological cancer, who has received or is receiving a first CAR-expressing cell therapy, comprising: (i) measuring soluble BCMA (sBCMA) level or activity (e.g., level) in the subject (e.g., in the serum of the subject) at at least one time point after the beginning of the first CAR-expressing cell therapy, e.g., using a method described herein, e.g., ELISA, and
(ii) (optionally) comparing the sBCMA level or activity (e.g., level) ("sample value") at
the at least one time point with a reference sBCMA level or activity (e.g., level) ("reference
value"), wherein if the sample value does not decrease from the reference value, administer a
second therapy to the subject” page 18 lines 11-20).
Regarding claim 15, Mueller further teaches wherein the second therapy comprises one or more of CAR-T therapies, immunomodulatory agents, targeted cancer therapies, or combinations thereof (“In one embodiment of the preceding methods, the second therapy comprises a B cell inhibitor. In one embodiment, the B cell inhibitor is a checkpoint inhibitor. In one embodiment, the B cell inhibitor is a second CAR-expressing cell therapy” page 21 lines 34-35 and page 22 line 5).
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.
Claims 6-7, 9-11, 14, 16 and 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Mueller as applied to claim 2 above, and further in view of Baldwin et al. (WO 2017/031104 Al)-Cite No. 25 of IDS filed on 10/27/2023 containing 15 pages (“Baldwin”).
Regarding claims 6 and 9-10, Mueller teaches the method of claim 2 as discussed above.
Mueller further teaches that “Many patients with B cell malignancies are incurable with standard therapy. In addition, traditional treatment options often have serious side effects” (page 1 lines 20-21).
Mueller fails to teach wherein the therapy is teclistamab or talquetamab, wherein the therapy comprises a CD3 bispecific antibody, wherein the therapy comprises intravenously administering to the subject about from about 38 μg/kg to about 720 μg/kg per dose of
teclistamab.
Baldwin teaches “methods of treating BCMA-expressing cancer in a subject in need thereof include administering to the subject a therapeutically effective amount of a described BCMA x CD3-multispecific antibody or multispecific antigen-binding fragment thereof” (page 12 lines 3-6). Baldwin teaches that “more preferably a BCMA x CD3-bispecific antibody” (page 53 paragraph 3) is used. Baldwin further teaches that “[i]n some embodiments, the BCMA-expressing cancer is a lymphoma, such as multiple myeloma” (page 12 lines 1-2). Also note that the BCMA x CD3-bispecific antibody taught by Baldwin is teclistamab as disclosed in the instant specification (“Anti-BCMA/anti-CD3 antibody …described in WO2017031104A1” para. 120). Baldwin further teaches that intravenous injection of 50 µg/kg teclistamab inhibited multiple myeloma tumorigenesis (“intravenous (IV) administration of PBS and BCMB72 …1 μg (0.05 mg/kg) per animal…Interestingly, sc H929 tumors did not grow in the mice treated with 0.5 μg and 1 μg BCMB72 (Figure 21). Thus, BCM72 inhibited the tumorigenesis of H929 human MM xenografts in all animals treated with 0.5 and 1 μg/animal” page 106 paragraph 1). Baldwin further teaches “[s]oluble BCMA quantitation in mouse serum from H929 (human multiple myeloma cells) xenografts in PBMC-Humanized NSG-Mice treated with BCMB72… There was significant reduction of soluble BCMB72 concentration in mouse serum of mice treated with 1 μg and 0. 5 µg of BCMB72 when compared with PBS alone” (Example 22, page 106 paras. 2-4 and page 107 para. 1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Mueller to rely on the treating of the subject with 50 µg/kg teclistamab, i.e. a CD3 bispecific antibody, taught by Baldwin in place of the treatment of Mueller, thereby addressing the instant claims, because Baldwin teaches that this treatment is effective in preventing multiple myeloma tumorigenesis, a current need in the field, and Mueller is interested in therapies against multiple myeloma. One would be motivated to make such a modification in order to receive the expected benefit of effectively treating multiple myeloma, as suggested by Baldwin. A person having ordinary skill in the art would have had a reasonable expectation of success given that both Baldwin and Mueller teach methods for determining the response to therapy for multiple myeloma.
Regarding claim 7, Mueller in view of Baldwin teach the method of claim 6 as discussed above.
Mueller in view of Baldwin further address further comprising treating the subject with a
second therapy against multiple myeloma or plasmacytoma if the level of sBCMA indicates the
subject is not responsive to teclistamab or talquetamab (page 18 lines 11-20 of Mueller and Example 21 of Baldwin page 106 para. 1).
Regarding claim 11, Mueller in view of Baldwin teach the method of claim 6 as discussed above.
Baldwin further teaches that “[t]he preferred mode of administration is parenteral ( e.g. intravenous, intramuscular, intraperitoneal, subcutaneous)” (page 49 paragraph 3). Baldwin further teaches that “[a]n exemplary, non-limiting range for a therapeutically effective amount of a compound of the present invention is about 0.001-10 mg/kg, such as about 0.001-5 mg/kg, for example about 0.001-2 mg/kg, such as about 0.001-1 mg/kg” (page 53 paragraph 2). These ranges are equivalent to 1-10,000µg/kg, 1-5000 µg/kg, 1-2000 µg/kg and 1-1000 µg/kg.
Regarding the specifically claimed administered concentration ranges, the teachings of Baldwin indicate that the amount of teclistamab employed in the treatment of multiple myeloma was recognized in the prior art to be a result-effective variable, i.e., a variable which achieves a recognized result (the concentration results in the effectiveness in treating one’s illness). Furthermore, Baldwin discloses that “[a] physician or veterinarian having ordinary skill in the art may readily determine and prescribe the effective amount of the pharmaceutical composition required” (page 53 paragraph 3).
Applicant is also reminded that 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). See MPEP 2144.05.
Therefore, based on the prior art of record, it would have been further obvious to a person having ordinary skill in the art before the claimed invention was effectively filed to have arrived at the claimed concentration values (namely treating the subjects with teclistamab at a dose ranging from about 80µg/kg to about 3000 µg/kg intravenously, subcutaneously), through routine optimization of experimental conditions because, as discussed above, as an appropriate concentration Baldwin discloses a range of 1-5000 µg/kg; further Baldwin teaches (see as cited above) administration can be achieved either as intravenously or subcutaneously. It would have been obvious, through routine experimentation, to have determined what concentrations close to this amount would have been appropriate for effective treatment (thereby arriving at the claimed ranges including the concentrations claimed). One having ordinary skill would have a reasonable expectation of success considering Baldwin specifically discloses that “[a] physician or veterinarian having ordinary skill in the art may readily determine and prescribe the effective amount of the pharmaceutical composition required” (page 53 paragraph 3).
Regarding claim 14, Mueller in view of Baldwin teach the method of claim 6 as discussed above.
Mueller fails to teach wherein teclistamab or talquetamab is administered bi-weekly or weekly.
Baldwin teaches wherein teclistamab is administered weekly (“In one embodiment, the multispecific antibody or fragment may be administered by infusion in a weekly dosage of calculated by mg/m2. Such dosages can, for example, be based on the mg/kg dosages provided above according to the following: dose (mg/kg)x70: 1.8. Such administration may be repeated, e.g., 1 to 8 times” page 53 paragraph 4).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Mueller in view of Baldwin to rely on wherein teclistamab is administered weekly taught by Baldwin because it would be a simple matter of applying a known technique to a known method. In this case, both Mueller and Baldwin teach administering to the subject a treatment for multiple myeloma, Baldwin simply applies the art-recognized technique of weekly administration of the therapy to the subject. Therefore, it would have been obvious to a person having ordinary skill in the art to simply apply the art-recognized technique taught by Baldwin to the base method of treating multiple myeloma taught by both Mueller and Baldwin. A person having ordinary skill in the art would have had a reasonable expectation of success given that both Baldwin and Mueller teach methods for determining the response to therapy for multiple myeloma.
Regarding claim 16, Mueller in view of Baldwin teach the method of claim 11 as discussed above.
Mueller in view of Baldwin further address wherein the subject has relapsed and/or refractory multiple myeloma (“Pilot Study of Redirected Autologous T Cells Engineered to Contain an Anti-BCMA scFv Coupled to TCRs and 4-IBB Signaling Domains in Patients With Relapsed and/or Refractory Multiple Myeloma” page 400 lines 12-14 of Mueller).
Regarding claim 18, Mueller in view of Baldwin teach the method of claim 6 as discussed above.
Mueller in view of Baldwin further address wherein the blood sample is serum, whole blood, or plasma, preferably serum (“Peripheral Blood Serum” page 396 line 20 of Mueller).
Regarding claim 19, Mueller in view of Baldwin teach the method of claim 6 as discussed above.
Mueller in view of Baldwin further address wherein the level of sBCMA in the blood sample is measured using an electrochemiluminescence ligand binding assay, an enzyme-linked immunosorbent assay (ELISA), or mass spectrometry (“This Example uses ELISA to examine serum samples from MM patients before and after CAR-BCMA therapy on clinical trial UPCC14415” page 396 lines 30-32 of Mueller).
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Mueller in view of Baldwin as applied to claim 6 above, and further in view of Janssen Research & Development, LLC, ClinicalTrials.gov ID NCT 03145181. Version 22: Posted online on 2019-04-25-Cite No. 3 of IDS filed 5/22/2026 with 9 pages (“Janssen”).
Regarding claim 8, Mueller in view of Baldwin teach the method of claim 6 as discussed above.
Mueller in view of Baldwin fail to teach wherein the blood sample is obtained from the
subject from about 4 to about 16 weeks after the subject is treated with the therapy.
Janssen teaches a “dose escalation study of teclistamab, a humanized BCMA*CD3 bispecific antibody, in participants with relapsed or refractory multiple myeloma (MAjesTEC-1). Janssen further teaches “IV and SC administration [of teclistamab]: dose escalation (Part 1) and dose expansion(Part 2)” (Detailed Description page 9). Janssen further teaches that this study “will evaluate safety, tolerability, pharmacokinetics and preliminary antitumor activity of JNJ-64007957 [teclistamab] administered to adult participants with relapsed or refractory multiple myeloma” (Detailed Description page 9). Janssen further teaches obtaining a blood sample from about 4 to about 16 weeks after the subject is treated with teclistamab (“[d]isease evaluations will include peripheral blood and bone marrow assessments at screening (performed within 28 days)” Detailed Description page 9).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Mueller in view of Baldwin to rely on the obtaining the blood sample from about 4 to about 16 weeks after the subject is treated with teclistamab taught by Janssen because it would be a simple matter of applying a known technique to a known method. In this case both Mueller and Janssen teach obtaining a blood sample after treating the subject with a therapy for multiple myeloma. Janssen simply teaches the art-recognized technique of obtaining the blood sample from about 4 to about 16 weeks after the subject is treated with teclistamab. Therefore, it would have been obvious for a person having ordinary skill in the art to simply apply the technique taught by Janssen to the base method taught by both references because the prior art is suggesting this as an appropriate amount of time passed for evaluating effectiveness of the treatment. Furthermore, one would be motivated to make such a modification because Janssen suggests that obtaining the blood sample from about 4 to about 16 weeks after the subject is treated with teclistamab evaluates safety, tolerability, pharmacokinetics and preliminary antitumor activity. A person having ordinary skill in the art would have had a reasonable expectation of success because both references teach method of treating a subject with multiple myeloma.
Claims 12-13 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Mueller in view of Baldwin as applied to claim 6 above, and further in view of Verkleij et al. Blood Advances; published online 23 April 2021. Volume 5, number 8- Cite No. 37 of IDS filed on 5/22/2026 containing 9 pages (“Verkleij”).
Regarding claims 12-13, Mueller in view of Baldwin teach the method of claim 6 as discussed above.
Baldwin further teaches that “[t]he preferred mode of administration is parenteral ( e.g. intravenous, intramuscular, intraperitoneal, subcutaneous)” (page 49 paragraph 3). Baldwin further teaches that “[a]n exemplary, non-limiting range for a therapeutically effective amount of a compound of the present invention is about 0.001-10 mg/kg, such as about 0.001-5 mg/kg, for example about 0.001-2 mg/kg, such as about 0.001-1 mg/kg” (page 53 paragraph 2). These ranges are equivalent to 1-10,000µg/kg, 1-5000 µg/kg, 1-2000 µg/kg and 1-1000 µg/kg.
Mueller in view of Baldwin fail to teach wherein the therapy comprises intravenously administering to the subject from about 0.5 μg/kg to about 180 μg/kg per dose of talquetamab and subcutaneously administering to the subject from about 5 μg/kg to about 800 μg/kg per dose of talquetamab.
Verkleij teaches “[t]he novel GPRC5D-targeting T-cell redirecting bispecific antibody, talquetamab, effectively kills GPRC5D1 MM cell lines” (Abstract). Verkleij further teaches that “[t]here was no difference in talquetamab-mediated killing of MM cells from newly diagnosed, daratumumab-naïve relapsed/refractory (median of 3 prior therapies), and daratumumab-refractory (median of 6 prior therapies) MM patients” (Abstract). Verkleij further teaches “that the GPRC5D-targeting T-cell redirecting bispecific antibody talquetamab is a promising novel antimyeloma agent. These results provide the preclinical rationale for ongoing studies with talquetamab in relapsed/refractory MM” (Abstract). Verkleij further suggests a method of determining a response to talquetamab comprising treating the subject and measuring the level of a biomarker (“Tumor and immune characteristics (eg, GPRC5D expression level, effector:target ratio, Treg count) are determinants of ex vivo response” page 2196 key points). Also note that as per paragraph 77 of the instant disclosure “[t]he term “subject” as used herein includes any human or nonhuman animal”.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Mueller in view of Baldwin to rely on the treating the subjects with talquetamab taught by Verkleij because Verkleij teaches that talquetamab is a promising novel antimyeloma agent that effectively kills multiple myeloma cells in refractory multiple myeloma patients, which is a current need in the field, and Mueller is interested in therapies against multiple myeloma. One would be motivated to make such a modification in order to receive the expected benefit of effectively treating multiple myeloma, as suggested by Verkleij. A person having ordinary skill in the art would have had a reasonable expectation of success because both Mueller, Baldwin and Verkleij teach methods for determining the response to therapy for multiple myeloma.
It would have been further prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Mueller in view of Baldwin and Verkleij to rely on intravenously administering to the subject from about 0.5 µg/kg to about 180 µg/kg, and subcutaneously administering to the subject a treatment dose from about 5 µg/kg to about 800 µg/kg taught by Baldwin because it would be a simple matter of applying a known technique to a known method. In this case, Mueller, and Baldwin teach administering to the subject a treatment for multiple myeloma. Mueller teaches administering to the subjects a CAR-T cell therapy, whereas Baldwin teaches administering to the subject an intravenous dose that is 50µg/kg (thereby addressing a range from about 0.5 µg/kg to about 180 µg/kg, as 50 falls within this range) of teclistamab and administering to the subject a subcutaneous dose ranging from about 80µg/kg to about 3000µg/kg of teclistamab (Baldwin teaches this dose range for the same reasons as discussed in detail previously above, see the rationale applied above, under 35 U.S.C. 103 regarding routine optimization, as the same reasoning would apply presently to arrive at the claimed range). Therefore, it would have been obvious to a person having ordinary skill in the art to simply apply the art-recognized technique taught by Baldwin to the base method of treating multiple myeloma taught by both Mueller and Baldwin. Furthermore, applying this treatment administration technique to talquetamab, taught by Verkleij would have been obvious to a person having ordinary skill in the art because it would be a simple matter of applying a known technique to a known method. In this case, it would have been obvious to rely on talquetamab as a treatment as discussed above, and would have been further obvious to use the administration route and dosages taught by Baldwin because it is an art-recognized technique in the field of multiple myeloma treatments. Both Verkleij and Baldwin teach treating multiple myeloma therefore using the treatment administration technique taught by Baldwin would have been obvious to a person having ordinary skill in the art. A person having ordinary skill in the art would have had a reasonable expectation of success given that Baldwin discloses that a physician or veterinarian having ordinary skill in the art may readily determine and prescribe the effective amount of the pharmaceutical composition required; and, Baldwin, Mueller and Verkleij teach methods for determining the response to therapy for multiple myeloma.
Regarding claim 17, Mueller in view of Baldwin and Verkleij teach the method of claim 13 as discussed above.
Mueller in view of Baldwin and Verkleij further address wherein the subject has relapsed and/or refractory multiple myeloma (page 400 lines 12-14 of Mueller).
Conclusion
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/Fernando Ivich/Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
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