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 .
Claims 1-2, 4-5, 7, 9-11, 14, 16-17, 21-25, 28-30, and 32 are pending and under consideration.
Information Disclosure Statement
Reference C64 (Tonouchi et al.) in the IDS filed 02/25/2025 could not be considered as the reference could not be located in the file.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. See for example, page 2, lines 2 and 16, page 19, lines 11, 24, page 21, lines 14 and 21. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Drawings
Applicants have filed two sets of drawings- both showing identical Figures 1 and 2. The black and white drawing of Figure 2 is not sufficiently distinct. This could result in a printer query should the application pass to the issues branch resulting in delayed prosecution. All drawings must be made by a process which will give them satisfactory reproduction characteristics. Every line, number, and letter must be durable, clean, black (except for color drawings), sufficiently dense and dark, and uniformly thick and well-defined. The weight of all lines and letters must be heavy enough to permit adequate reproduction. This requirement applies to all lines however fine, to shading, and to lines representing cut surfaces in sectional views. See 37 CFR 1.84
The other identical set of drawings has been submitted in color. Applicants are reminded that color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification: Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Claim Objections
Claim 21 is objected to because of the following informalities: Claim 21 recites, the method of claim 11, “wherein the or each treatment dose”. (see lines 1 and 2). It’s not clear what word or phrase should exist between “the” and “or”. 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 2, 5-7, 9, 11, 14, 21, 23-25, and 28-30 are 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.
Regarding claims 2, 5, 6, 7, 9, 11, 14, 17, 25, and 30, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Further, Claims 5, 6, 7, 11, 14, 21, 23, 24, 28, 29, 30 use the word, “optionally”, (often more than once in the same claim and often presented together with the term “such as”) creates ambiguity as to whether or not the alternatives are distinctive limitations. See MPEP 2173.05(h) II.
Regarding items 10-11 above, much of the claims are replete with “such as” and “optionally” type language which can be confusing in context. Thus, the claims were examined to the extent that a proper understanding could be construed.
Claim 30 contains the trademark/trade name Triomab®, and CrossMab®, and BEAT®. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe protein-engineering platforms and technologies associated with bispecific and multispecific antibodies and, accordingly, the identification/description is indefinite.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 4 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 4 is dependent from Claim 1 and states, “wherein the therapeutic intervention comprises administration of one or more doses of an immunotherapy agent”. However, claim 1 already limits the therapeutic intervention to one or more doses of a therapeutic agent. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claim(s) 1-2, 4-5, 7, 9-11, 14, 16, 21-25, and 32 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jensen et al. (US20190112379, published 4-18-2019).
As to claims 1-2, 4, 9-11, 14, and 32, Jensen et al. teach [0080, 0090] a method of prophylactic therapy of a patient who is at risk of the development of cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome (ICANS) [0112] due to a therapeutic intervention comprising administering an antibody or fragment which is capable of inhibiting human IL-6 to the patient in conjunction with the therapeutic intervention; wherein the antibody dosage regimen comprises administering a pre-emptive dose of the antibody before the patient is at risk of the development of CRS. For example, Jensen et al. teach [0007] methods of treatment including administering to a subject having a disease or condition an immunotherapy or a cell therapy (at least one or more doses of an immunotherapy agent; also see [0273-0274]). In some cases the method involves administering to the subject an agent or other treatment capable of treating, preventing, delaying, or attenuating the development of a toxicity. In some cases, the administration of the agent or other treatment is at a time that is less than or no more than ten, seven, six, five, four or three days after initiation of the administration of the therapy. Jensen et al teach [0319] that the agent or other treatment is the antibody siltuximab. As to Claim 10, wherein the antibody or fragment thereof is the only active agent administered pre-emptively as prophylaxis for CRS and or ICANS, Jensen et al. teach [0018] that in some cases, the agent or other treatment is or comprises an agent selected from among tocilizumab, situximab, sarilumab, olokizumab (CDP6038), elsilimomab, ALD518/BMS-945429, sirukumab (CNTO 136), CPSI-2634, ARGX-109, FE301 and FM101. Thus, the only agent is selected from a discrete Markush group that includes an antibody capable of inhibiting human IL-6. Regarding claim 32, Jensen et al. further teach [0080] that the methods permit treatment of a subject with a therapy for treating a disease or disorder, such as an immunotherapy or a cell therapy, that otherwise may result in moderate to severe CRS or neurotoxicity side effects in the subjects. In the provided methods, the early intervention or preemptive treatment with a toxicity-targeting agent(s) prevents or ameliorates the risk of moderate to severe CRS or neurotoxicity while maintaining the efficacy of the therapy, such as, for the case of cell therapy, the persistence of the therapy. In terms of “risk factors” for CRS, Jensen et al. teach [0095] CRS criteria that appear to correlate with the onset of CRS to predict which patients are more likely to be at risk for developing sCRS have been developed and include such factors as fevers, hypoxia, hypotension, neurologic changes, elevated serum levels of inflammatory cytokines, such as a set of seven cytokines (IFNγ, IL-5, IL-6, IL-10, Flt-3L, fractalkine, and GM-CSF) whose treatment-induced elevation can correlate well with both pretreatment disease burden, e.g., tumor burden and sCRS symptoms. Also see Table 1. Thus, the reference anticipates treating a patient that has at least one risk factor for CRS.
Regarding claim 5, Jensen et al. teach [0089] that the pre-emptive dose of the antibody can be administered at a time that is less that three days after initiation of the therapy which encompasses administration up to 1 day after commencement of at least one or more doses of the therapeutic agent.
Regarding claim 7, Jensen et al. teach [0294] that the antibody or fragment (e.g., toxicity targeting agent) is administered intravenously.
Regarding claims 11, 14, and 16, Jensen et al. teach [0321, and Table 3] that in some embodiments, a second administration of tocilizumab (an antibody capable of inhibiting human IL-6) is provided if symptoms recur after 48 hours of the initial dose. This encompasses administering a first treatment dose of the antibody after the pre-emptive dose or within any rolling hour following the diagnosis of CRS. Further, regarding claim 16, the biological effects of administering the first treatment dose of the antibody would naturally reduce the grade and/or duration of CRS and/or ICANS of the patient including treatment-related mortality at 30 days or improving overall survival following diagnosis of CRS.
Regarding Claim 21, Jensen et al. teach [0019] that the antibody dosage can be about 10mg/kg or 8mg/kg which is within the range of 11 +/- 3 mg/kg.
Regarding Claim 22, Jensen et al. teach (see Table 3, and para 0020) that the patient is administered a steroid for the treatment of CRS and/or ICANS.
Regarding Claim 23, Jensen et al. teach [0041] the disease or condition is or comprises a tumor or a cancer. In some cases, the disease or condition is or comprises a leukemia or lymphoma. In some embodiments, the disease or condition is a B cell malignancy or is a hematological disease or condition. In some aspects, the disease or condition is or comprises a non-Hodgkin lymphoma (NHL) or acute lymphoblastic leukemia (ALL).
Regarding Claims 24-25, Jensen et al. teach [0042-0043] that in some embodiments, the therapy is a cell therapy including a dose of cells expressing a recombinant receptor. In some aspects, the recombinant receptor binds to, recognizes or targets an antigen associated with the disease or condition. In some cases, the recombinant receptor is a T cell receptor or a functional non-T cell receptor. In some instances, the recombinant receptor is a chimeric antigen receptor (CAR). In some embodiments, the CAR contains an extracellular antigen-recognition domain that specifically binds to the antigen and an intracellular signaling domain containing an ITAM. In some cases, the antigen is CD19.
(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.
Claim(s) 1-2, 4-5, 7, 9-11, 14, 16-17, 21-23, 28-30, 32 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Khaldoyanidi et al. (US20230146593, effectively filed March 12, 2020)
Regarding Claims 1, 4, 9, 23, and 28, Khaldoyanidi et al. teach [0711-0714] administering pre-emptive dosages of an antibody capable of inhibiting IL-6 in combination with one or more dosages of antibody constructs, including bispecific [0771] immunotherapy for cancer in patients at risk of the development of cytokine release syndrome (also see claim 1 and 3 of Khaldoyanidi et al.).
Regarding claim 2, the reference teaches [0011] that the antibody can be siltuximab.
Regarding claims 5, 7, and 21, Khaldoyanidi et al. teach that the pre-emptive dose of the antibody or fragment is administered within a first period ranging from 5 minutes to 7 days prior to immunotherapy (See claim 1 of Khaldoyanidi et al.) including intravenous administration of tocilizumab at 1mg/kg to 20 mg/kg which is within the range of 11mg/kg [0751-0752].
Regarding claim 10, Khaldoyanidi et al. teach administering an inhibitor/antagonist of TNF/TNFR reducing TNF/TNFR signaling, and/or administering an inhibitor/antagonist of IL6/IL6R that reduces IL6/IL6R signaling. Thus, as the antibodies of the prior art that are capable of inhibiting human IL-6 are claimed in the alternative, they are considered the sole active agent administered pre-emptively as prophylaxis for CRS.
Regarding claims 11 and 17, Khaldoyanidi et al. teach [0716, 0719] administering first and second dosages of the inhibitor/antagonist of IL6 which encompasses administering a first treatment dose after the pre-emptive dose if clinically indicated. A further third dose [0718] is administered within a third period following administration of the antibody construct which encompasses Claim 17- wherein the antibody dosage regimen comprises administering a second treatment dose of the antibody after the first treatment dose.
Regarding claims 14 and 16, Khaldoyanidi et al. teach [0719] at least one further dose of said inhibitor/antagonist of IL6/IL6R that reduces IL6/IL6R signaling according to (b) is/are administered before administration of said antibody construct, and wherein the at least one further dose of said inhibitor/antagonist of IL6/IL6R that reduces IL6/IL6R signaling according to (b) is administered following administration of said antibody construct, wherein the first dose of said inhibitor/antagonist of IL6/IL6R that reduces IL6/IL6R signaling according to (b) is administered within a first period before administration of the antibody construct, said period ranging from 30 minutes to 7 days prior to administration of the antibody construct wherein said administration [0715] comprises the prevention or amelioration or reduction of CRS which encompasses a patient that has been diagnosed with CRS. Further, regarding claim 16, the biological effects of administering the first treatment dose of the antibody would naturally reduce the grade and/or duration of CRS and/or ICANS of the patient including treatment-related mortality at 30 days or improving overall survival following diagnosis of CRS.
Regarding Claim 22, Khaldoyanidi et al. teach [0741] wherein the patient is also given a steroid.
Regarding claims 28-30, and 32, Khaldoyanidi et al. teach [0878] that the bispecific antibody can be Blinatumomab, a bispecific construct that has binding specificity for a T cell antigen (CD3) and a cancer antigen (CD19). Khaldoyanidi et al. further teach [0003] that CRS can present with a variety of symptoms ranging from mild, flu-like symptoms to severe life-threatening manifestations of the excessive inflammatory response. Mild symptoms of CRS include fever, fatigue, headache, rashes, arthralgia, and myalgia. These are considered risk factors and because the reference on the whole teaches treating and preventing CRS, some patients would present at the time of treatment at least one risk factor.
No claim is currently allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GARY B NICKOL, Ph.D. whose telephone number is (571)272-0835. The examiner can normally be reached M-F 9AM-5:30PM.
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/GARY B NICKOL/Primary Examiner, Art Unit 1643
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