Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Election/Restrictions
Applicant's election with traverse of the restriction requirement in the reply filed on 01/28/2026 is acknowledged. The traversal is on the ground(s) that the restriction requirement uses a reference, Novotny et al., which “does not teach or suggest the claimed doses of the anti-LAG-3 antibody, much less in combination with the claimed dose of the anti-PD-1 antibody for treating a HCC in a human subject”. This is not found persuasive because Novotny meets the limitations of the instant invention and the instant invention does not obviate the prior art. As such, the lack of unity of invention is successfully shown in Novotny. The requirement is still deemed proper and is therefore made FINAL.
Applicant’s election of the dose of 480 mg of the anti-LAG-3 antibody in the reply filed 01/28/2026 is acknowledged.
Claims 191-194 and 200-209 are under consideration in the instant Office Action.
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 191-194 and 200-209 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.
Instant claims 191-194 and 201-209 recite the transitional term “having the sequence set forth in” and instant claim 200 recites the transitional term “the sequences set forth in”. This term is problematic because the recitation of these terms in instant claims 191-194 and 200-209 render the claims unclear by what not defining what is encompassed by “having” the sequences. Applicant has not conveyed that they are in possession of all the antibodies that are included in the broad term “having the sequence”. It is not immediately clear whether open or closed claim language is intended, Crystal Semiconductor Corp. v. Trilech Microelectronics Int’l Inc., 246 F.3d 1336, 1348, 57 USPQ2d 1953, 1959 (Fed. Cir. 2001) (term “having” in transitional phrase "does not create a presumption that the body of the claim is open"); Regents of the Univ. of Cal. v. Eli Lilly & Co., 119 F.3d 1559, 1573, 43 USPQ2d 1398, 1410 (Fed. Cir. 1997) (in the context of a cDNA having a sequence coding for human PI, the term “having” still permitted inclusion of other moieties), see MPEP 2111.03. Applicant is encouraged to use transitional phrases “comprising of” or “consisting of” to define the scope of a claim with respect to what unrecited additional components, if any, are excluded from the scope of the claims.
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 191-194 and 200-209 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Novotny et al. (WO 2018/222718 A1, in PTO-892 filed 01/23/2026).
Novotny et al. teaches a method of "treating a tumor in a human patient comprising (i) identifying a patient as having a LAG-3 positive tumor and (ii) administering to the patient a PD-1 pathway inhibitor, a combination of a PD1 pathway inhibitor and an immune checkpoint inhibitor, a combination of a LAG-3 inhibitor and a PD-1 pathway inhibitor. In some embodiments, the method further comprises identifying the patient as having a LAG-3 positive PD-L1 positive tumor. In some embodiments, the LAG-3 inhibitor is an anti-LAG-3 antibody and the PD-1 pathway inhibition is an anti-PD-1 antibody. The methods of the invention can improve response rates to treatment with a PD-1 pathway inhibitor, a combination of a PD1 pathway inhibitor and an immune checkpoint inhibitor, or a combination of a LAG-3 inhibitor and a PD-1 pathway inhibitor", see Abstract. This patient population also includes patients with hepatocellular carcinoma, specifically malignant tumors which are advanced refractory solid tumors, see paragraph 0287. Novotny et al. teaches the identity of the antibody, with the anti-PD-1 antibody as nivolumab. In certain embodiments, the LAG-3 antibody is BMS-986016 [relatlimab], see paragraph 0194. The antibodies taught by Novotny et al. are a match for the instantly claimed antibodies of the same names and their respective sequences SEQ ID NOs: 3-20. This meets the limitations of instant claims 191 and 200 wherein a patient with hepatocellular carcinoma is treated with a combination of an anti-LAG-3 known as relatlimab and an anti-PD-1 antibody known as nivolumab and instant claim 194 wherein the hepatocellular carcinoma is advanced.
Novotny et al. teaches the instant invention can be used for treating a patient afflicted with a malignant tumor, the kit comprising: a dosage ranging from about 0.1 to about 10 mg/kg body weight of an anti-LAG-3 antibody or an antigen-binding fragment thereof; a dosage ranging from about 0.1 to about 10 mg/kg body weight of an anti-PD-1 antibody or an antigen-binding fragment thereof; and instructions for using the anti-LAG-3 antibody and anti- PD-1 antibody or the antigen-binding fragments thereof in any of the methods disclosed herein, see paragraph 0081. Therefore, a subject weighing 48 kg who receives a dosage of either antibody at 10 mg/kg will receive a total dosage of 480 mg of either antibody. This value can be adjusted by patient weight or dosage rate. Novotny et al. also teaches that the anti-PD-1 and anti-LAG-3 antibodies or antigen-binding fragments thereof are formulated for intravenous administration, see paragraph 0069. This meets the limitations of instant claim 191 wherein the subject is administered a dose of about 480 mg of each antibody, and instant claim 201 wherein the antibodies are administered to the subject intravenously.
Novotny et al. teaches the instant invention may be administered in a "fixed dose" with regard to a composition of the invention means that two or more different antibodies in a single composition are present in the composition in particular (fixed) ratios with each other. These fixed doses are “based on the concentration (e.g., mg/ml) of the antibodies. In some embodiments, the ratio is at least about 1:1… For example, the 3:1 ratio of a first antibody and a second antibody can mean that a vial can contain about 240 mg of the first antibody and 80 mg of the second antibody or about 3 mg/ml of the first antibody and 1 mg/ml of the second antibody”, see paragraph 0147. Novotny et al. also teaches that the anti-PD-1 and anti-LAG-3 antibodies or antigen- binding fragments thereof are formulated together. In some embodiments, the anti-PD-1 and anti- LAG-3 antibodies or antigen-binding fragments thereof are formulated separately, see paragraph 0070. This meets the limitation of instant claim 191 wherein the anti-LAG-3 and anti-PD-1 antibodies are administered in equivalent dosages, instant claim 202 wherein the antibodies can be formulated together, instant claim 203 wherein the antibodies are formulated separately, and instant claim 204 wherein the antibodies can be administered concurrently.
Novotny et al. teaches that the anti-PD-1 antibody and anti-LAG-3 antibody are administered as a first line of treatment (e.g., the initial or first treatment). In another embodiment, the anti-PD-1 antibody and anti-LAG-3 antibody are administered as a second line of treatment (e.g., after the initial or first treatment, including after relapse and/or where the first treatment has failed), see paragraph 0331. This meets the limitations of instant claim 192 wherein the treatment is administered as a first line therapy and instant claim 193 wherein the subject has progressed or was intolerant of a prior therapy.
Novotny et al. teaches that “LAG-3 positive or LAG-3 expression positive tumor means that at least about 1%, or in the range of 1- 5% of the total number of tumor-infiltrating inflammatory cells (e.g., T cells, CD8+ T cells, CD4+ T cells, FOXP3+ cells) express LAG-3 on the cell surface”, see paragraph 153. Novotny et al. also teaches that “the term "PD-L1 positive" or "PD-L1 expression positive," relating to cell surface PD-L1 expression, refers to the proportion of cells in a test tissue sample comprising tumor cells and tumor-infiltrating inflammatory cells above which the sample is scored as expressing cell surface PD-L1 . For cell surface expression assayed by immunohistochemistry (IHC), e.g., with the mAb 28- 8, the PD-L1 positive tumor or PD-L1 expression positive tumor means that at least about 0.01%), at least about 0.5%, at least about 1%”, see paragraph 155. This meets the limitations of instant claim 205 wherein 1% of immune cells in tumor tissue express LAG-3, instant claim 206 wherein the immune cells are tumor-infiltrating lymphocytes, instant claim 207 wherein the tumor-infiltrating lymphocytes are CD8+ T cells, and instant claim 208 wherein about 1% of tumor cells express PD-L1.
Novotny et al. also teaches “the invention features any of the aforementioned embodiments, wherein the treatment protocol further comprises the administration of at least one additional therapeutic agent. In some embodiments, the at least one additional therapeutic agent is a chemotherapeutic agent. In some embodiments, the at least one additional therapeutic agent is an immune checkpoint inhibitor”, see paragraph 0337. This meets the limitations of instant claim 209 wherein the subject received an additional therapeutic agent and/or anti-cancer therapy.
Therefore, claims 191-194 and 200-209 are anticipated by Novotny et al.
Conclusion
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/SELAM BERHANE/Examiner, Art Unit 1675 /AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675
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