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 .
Claim Status
Applicant’s amendments and remarks, filed 02/25/2026, are acknowledged.
Claims 1, 15, and 17-19 are canceled.
Claims 2-6, 11-14, and 16 are amended.
Claim 20 is new.
Claims 2-14, 16, and 20 are pending.
Claims 6-12 and 20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 08/13/2025.
As such, claims 2-5, 13, 14, and 16 are pending examination and currently under consideration for patentability under 37 CFR 1.104.
DETAILED ACTION
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02/25/2026 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Withdrawn Objections
The specification objections are withdrawn. Issues regarding minor informalities, trademarks/names, and incorporating the disclosed Sequence Listing by reference have been sufficiently addressed through amendments to the specification on 02/25/2026.
The claim objections are withdrawn. Issues regarding minor informalities have been sufficiently addressed through amendments to the claims filed on 02/25/2026.
Withdrawn Rejections
Applicant’s arguments, see pages 9 and 10, filed 02/25/2026, with respect to claims 1-5 and 13-19 rejected under 35 USC 112(b) as allegedly being indefinite have been fully considered and are persuasive. The issue regarding the claims comprising indefinite language have been sufficiently addressed through amendments to the claims. Further, Examiner acknowledges that claims 1, 15, and 17-19 are canceled thus rendering the rejection moot. As such, the rejection under 35 USC 112(b) is withdrawn.
Applicant’s arguments, see pages 11 and 12, filed 02/25/2026, with respect to claims 14-19 rejected under 35 USC 112(a) as allegedly lacking written description have been fully considered and are persuasive. The issue regarding the specification failing to disclose Applicant’s possession of the claimed method of treating the large genus of tumors, autoimmune diseases, infectious diseases, and/or transplantation rejection reactions with the genus of inadequately described anti-LAG3 antibodies has been sufficiently addressed through amendments to the claims. Further, Examiner acknowledges that claims 15 and 17-19 are canceled thus rendering the rejection moot. As such, the rejection under 35 USC 112(a) is withdrawn.
Maintained Rejections
Claim Rejections - 35 USC § 112(a) Enablement
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 14 and 16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating colon cancer (MC38) and B-cell lymphoma (A20) with the claimed anti-LAG3 antibodies alone or combined with RMP1-14 (anti-mouse PD-1 antibody) or HLX10 (an anti-PD-1 receptor monoclonal antibody), does not reasonably provide enablement for treating all tumors with the claimed anti-LAG3 antibodies alone, or in combination with any anti-PD-1 monoclonal antibody or any small-molecule drug. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
MPEP § 2164.01 states:
The standard for determining whether the specification meets the enablement
requirement was cast in the Supreme Court decision of Minerals Separation Ltd. v. Hyde, 242 U.S.
261, 270 (1916) which postured the question: is the experimentation needed to practice the
invention undue or unreasonable? That standard is still the one to be applied. In re Wands, 858
F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). Accordingly, even though the statute does
not use the term "undue experimentation," it has been interpreted to require that the claimed
invention be enabled so that any person skilled in the art can make and use the invention without
undue experimentation. In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404 (Fed. Cir. 1988).
There are many factors to be considered when determining whether there is sufficient evidence
to support a determination that a disclosure does not satisfy the enablement requirement and whether
any necessary experimentation is "undue." These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content
of the disclosure.
In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). The factors most relevant for this rejection are: (A) the breadth of the claims; (B) the nature of the invention; (E) the level of predictability in the art; (F) the amount of direction provided by the inventor; (G) the existence of working examples; and (H) the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In regard to Wands factors (A) and (B), the breadth of the claims needed to enable the invention
is determined by whether the scope of enablement provided to one skilled in the art by the disclosure is
commensurate with the scope of protection sought in the claims. AK Steel Corp. v. Sollac, 344 F.3d 1234, 1244, 68 USPQ2d 1280, 1287 (Fed. Cir. 2003); In re Moore, 439 F.2d 1232, 1236, 169 USPQ 236, 239 (CCPA 1971). The propriety of a rejection based upon the scope of a claim relative to the scope of the enablement concerns (1) how broad the claim is with respect to the disclosure and (2) whether one
skilled in the art could make and use the entire scope of the claimed invention without undue
experimentation.
The nature of the invention is a method for treating tumors in a patient in need thereof comprising administering the claimed anti-LAG3 monoclonal antibody or a composition comprising the claimed anti-LAG3 monoclonal antibody to the patient, or in combination with any antibody drug or any small molecules. Therefore, the nature of the invention is a biochemical case, where there is natural unpredictability in performance of certain species other than those specifically enumerated; see MPEP § 2163. Accordingly, it is the Office’s position that undue experimentation would be required to practice the functionality of the claimed method, with a reasonable expectation of success, because it would not be predictable from the disclosure of any one particular species may or may not work; see MPEP § 2164.03.
In regard to Wands factors (C), (D), and (E), the state of the prior art is what one skilled in the art would have known, at the time the application was filed, about the subject matter to which the claimed invention pertains and provides evidence for the degree of predictability in the art; see MPEP § 2164.05(a). The claims encompass treating any tumor in a patient in need thereof comprising administering the claimed anti-LAG3 monoclonal antibody or a composition comprising the claimed anti-LAG3 monoclonal antibody to the patient, or in combination with any antibody drug or any small molecules. Cancers are highly heterogeneous at both the molecular and clinical level. Additionally, it is known in the art that cancer cells arising from different tissues differ in etiology and response to treatment. Heppner et al. (Cancer Metastasis Review 2:5-23; 1983; previously submitted with the Office action mailed 09/25/2025) discuss the heterogeneity of tumors from different tissues, as well as the same tissue. A key point made by Heppner et al. is that tumor heterogeneity contributes greatly to the sensitivity of tumors to drugs. Heppner et al. teach that as a tumor progresses to a metastatic phenotype, the susceptibility to a particular treatment can differ, and as such, makes predicting the responsiveness to treatment difficult.
Additionally, Bally et al. (US Patent No. 5,595,756A, publication date: 01/21/1997) stated, "Despite enormous investments of financial and human resources, no cure exists for a variety of diseases. For example, cancer remains one of the major causes of death. A number of bioactive agents have been found, to varying degrees, to be effective against tumor cells. However, the clinical use of such antitumor agents has been highly compromised because of treatment limiting toxicities (See column 1).
Sporn et al. (Chemoprevention of Cancer, Carcinogenesis, Vol. 21 (2000), 525-530; previously submitted with the Office action mailed 09/25/2025) teaches the magnitude of mortality of cancers and that mortalities are in fact still rising and that new approaches to a variety of different cancer are critically needed. Sporn et al. also teach that “given the genotype and phenotype heterogeneity of advanced malignant lesions as they occur in individual patients, one wonders just exactly what are the specific molecular and cellular targets for the putative cure.”
Furthermore, the art indicates the difficulties in going from in vitro to in vivo for drug development for treatment of cancers. Auerbach et al. (Cancer and Metastasis Reviews, 2000, 19: 167-172; previously submitted with the Office action mailed 09/25/2025) indicate that one of the major problems in angiogenesis research has been the difficulty of finding suitable methods for assessing the angiogenic response. For example, the 96 well rapid screening assay for cytokinesis was developed in order to permit screening of hybridoma supernatants…In vitro tests in general have been limited by the availability of suitable sources for endothelial cells, while in vivo assays have proven difficult to quantitate, limited in feasibility, and the test sites are not typical of the in vivo reality (see p. 167, left column, 1st paragraph).
Gura T (Science, 1997, 278(5340): 1041-1042, encloses 1-5; previously submitted with the Office action mailed 09/25/2025) indicates that “the fundamental problem in drug discovery for cancer is that the model systems are not predictive at all” (see p. 1, 2nd paragraph). Furthermore, Gura indicates that the results of xenograft screening turned out to be not much better than those obtained with the original models, mainly because the xenograft rumors don’t behave like naturally occurring tumors in humans—they don’t spread to other tissues, for example (see p. 2, 4th paragraph). Further, when patient’s tumor cells in Petri dishes or culture flasks and monitor the cells’ responses to various anticancer treatments, they don’t work because the cells simply fail to divide in culture, and the results cannot tell a researcher how anticancer drugs will act in the body (see p. 3, 7th paragraph).
Furthermore, Jain RK (Scientific American, July 1994,58-65; previously submitted with the Office action mailed 09/25/2025) indicates that the existing pharmacopoeia has not markedly reduced the number of deaths caused by the most common solid tumors in adults, among them cancers of the lung, breast, colon, rectum, prostate and brain (see p. 58, left most column, 1st paragraph). Further, Jain indicates that to eradicate tumors, the therapeutic agents must then disperse throughout the growths in concentrations high enough to eliminate every deadly cell…solid cancers frequently impose formidable barriers to such dispersion (see p. 58, bottom of the left most column continuing onto the top of the middle column). Jain indicates that there are 3 critical tasks that drugs must do to attack malignant cells in a tumor: 1) it has to make its way into a microscopic blood vessel lying near malignant cells in the tumor, 2) exit from the vessel into the surrounding matrix, and 3) migrate through the matrix to the cells. Unfortunately, tumors often develop in ways that hinder each of these steps (see p. 58, bottom of right most column). Thus, the art recognizes that going from in vitro studies to in vivo studies for cancer drug developments are difficult to achieve.
Hait (Nature Reviews/Drug Discovery, 2010, 9, pages 253-254; previously submitted with the Office action mailed 09/25/2025) states that “The past three decades have seen spectacular advances in our understanding of the molecular and cellular biology of cancer. However, with a few notable exceptions, such as the treatment of chronic myeloid leukemia with imatinib, these advances have so far not been translated into major increases in long-term survival for many cancers. Furthermore, data suggest that the overall success rate for oncology products in clinical development is -10%, and the cost of bringing a new drug to market is over US$1 billion.” (see page 253, left column, the 1st paragraph). Hait further teaches “The anticancer drug discovery process often begins with a promising target; however, there are several reasons why the eventual outcome for a particular cancer target may be disappointing. For example, the role of the target in the pathogenesis of specific human malignancies may be incompletely understood, leading to disappointing results”, “First, many targets lie within signal transduction pathways that are altered in cancer, but, owing to the complex nature of these pathways, upstream or downstream components may make modulating the target of little or no value”; “Second, target overexpression is often overrated. There are some instances in which overexpression predicts response to treatment.”; and “Another confounding factor is that cancer is more than a disease of cancer cells, as alterations in somatic or germline genomes, or both, create susceptibilities to transformational changes in cells and in the microenvironment that ultimately cooperate to form a malignant tissue. The putative role of cancer stem cells in limiting the efficacy of cancer therapeutics is also an area of intense interest. Therefore, effective treatments may require understanding and disrupting the dependencies among the multiple cellular components of malignant tissues. Single nucleotide polymorphisms in genes responsible for drug metabolism can further complicate the picture by affecting drug pharmacokinetics; for example, as with the topoisomerase inhibitor irinotecan.”, for example, page 253, Section “Understanding the target in context”. Hait also teaches “Drug effects in preclinical cancer models often do not predict clinical results, as traditional subcutaneous xenografting of human cancer cell lines onto immunocompromised mice produces ‘tumors’ that fail to recapitulate key aspects of human malignancies such as invasion and metastasis. Several improvements have been made, including orthotopic implantation and use of mice with humanized hematopoietic and immune systems. Newer genetic mouse models can also allow analyses of tumor progression from in situ through locally advanced and, in certain cases, widespread metastatic disease. However, whether or not these models will more accurately predict drug activity against human cancer remains to be determined. Other alternatives, including three-dimensional tissue culture or xenografts of fresh human biopsy specimens onto immunocompromised mice, have the potential advantage of including the human microenvironment. However, these approaches have yet to prove their value relative to their cost.”, for example, page 253, Section “Predictive models”. Furthermore, Hait teaches that “It is now widely thought that biomarkers will drive a personalized approach to cancer drug development. The aim is that they will cut costs, decrease time to approval, and limit the number of patients who are exposed to potential toxicities without a reasonable chance of benefit — as exemplified by the development of imatinib and trastuzumab. However, recent attempts at repeating these successes in other cancer types have been less successful.”, for example, page 254, Section “Stratified/personalized medicine”.
The challenges facing cancer drug development are further confirmed and discussed in Gravanis et al. (Chin Clin Oncol, 2014, 3, pages 1 -5; previously submitted with the Office action mailed 09/25/2025). Gravanis et al. teach “The generic mechanism of action for cytotoxics made the prediction of which tumor types might respond to them very difficult, if not impossible, and necessitated a ‘trial and error’ approach against many different types of tumors.” and “The most prominent change in oncology drug development in the last 20 years has been the shift from classic cytotoxics to drugs that affect signaling pathways implicated in cancer, which belong to the so called ‘targeted therapies’.”, for example, page 1, Section “From cytotoxics to targeted therapies: how far are we from truly personalized medicine?”. Gravanis et al. further teach “Although constantly progressing, an understanding of cancer biology is far from complete. The ability to develop new compounds or generate biological data predictive of the clinical situation relies on good quality basic research data, although the complexity and constantly evolving biology of the tumor may be to blame for the frequent non-reproducibility of research results. Systemic biology approaches of the -omic type still generate largely incomprehensible, mostly due to their volume, analytical data, few pieces of which are currently actionable/drug-g-able. Finally, animal models of cancer are similarly unable to predict the clinical situation (for example, page 3, right column, the 2nd paragraph).
Beans (PNAS 2018; 115(50): 12539-12543; previously submitted with the Office action mailed 09/25/2025) teaches that across cancer types, 90% of cancer deaths are caused not by the primary tumor but by metastasis. Beans teaches that although some drugs may shrink metastases along with primary tumors, no existing drugs treat or prevent metastasis directly (See page 12540). Beans states “Without a targeted approach, metastatic tumors often reemerge. “We shrink them, we send them back to their residual state, and they reenact those survival functions and retention of regenerative powers that made them metastasis-initiating cells in the first place” (See page 12540). Beans teaches that one of the major scientific challenges of studying metastatic disease is that different forms of cancer seem to metastasize through different mechanisms and the same form of cancer may metastasize differently in different subsets of patients (See page 12542). Of note, Beans states “It’s unlikely that one researcher is going to find one pathway that proves to be the key to metastasis” (See page 12542). Beans also teaches that translating many findings into therapies also presents unique hurdles in that it is difficult to measure the effectiveness of the therapy. Secondary tumors are often minuscule, and therefore, measuring success by tumor shrinkage may not work. Measuring the incidence of metastasis after treatment is also more difficult (See page 12542).
Given Bally et al. teaching of treatment-limiting toxicities in clinical use; Sporn's teaching that the cancer progression is heterogeneous as it progresses, both in genotype and phenotype; Auerbach et al. teaching that one of the major problems in angiogenesis research has been the difficulty of finding suitable methods for assessing the angiogenic response; Gura's teaching that the models are unpredictable; Jain's teaching that the existing pharmacopoeia has not markedly reduced the number of deaths caused by the most common solid tumors in adults, among them cancers of the lung, breast, colon, rectum, prostate and brain; both Hait and Gravanis et al teaching various challenges facing cancer drug development, such as an understanding of cancer biology is far from complete, drug effects in preclinical cancer models often do not predict clinical results and many others; and Beans teachings that the field is highly underdeveloped with regards to preventing and treating cancer metastasis; the cited references demonstrate that the treatment of cancer is highly unpredictable, if even possible for many cancers. In conclusion, the art provides evidence that heterogeneity in cancers can display unpredictability in response to the same treatment.
The art teaches the unpredictability of antibody-based cancer immunotherapy. Christiansen et al (Mol Cancer Ther, 2004, 3:1493-1501; previously submitted with the Office action mailed 09/25/2025) teach numerous factors that inhibit successful therapeutic application of antibodies including low or heterogeneous expression of target antigens by tumor cells, high background expression of target antigen on normal cells, host antibody immune responses to the antibodies themselves, insufficient antitumor response after antibody binding, as well as significant physical barriers preventing antibody binding or delivery to a solid tumor mass, including the vascular endothelium, stromal barriers, high interstitial pressure, and epithelial barriers (abstract; p. 1493, col. 2; p. 1496, col. 1, last paragraph through p. 1498, col. 2). Topp et al (Journal of Controlled Release, 1998, 53:15-23; previously submitted with the Office action mailed 09/25/2025) also teach the complications and unpredictability involved with treating tumors using antibody therapy. Topp et al teach that there are several barriers to successful delivery of antibody drugs to extravascular sites of action within target tissues: the antibody drugs must be absorbed into the blood stream, carried by the circulatory system to the capillaries in the target tissue, cross the capillary endothelial cells and the underlying basement membrane that supports the capillary structure and penetrate through the matrix of cells and extracellular components that comprises the tissue itself, bind to the cell surface receptor, initiate endocytosis, encounter possible drug degradation and drug release. Additional connective tissue barriers may also be encountered (p. 15, both columns; Figure 1). While some antibody drugs have been shown to be effective in vitro the results of clinical trials have been disappointing. The inability of the antibodies to penetrate the tumor mass could be a cause of this lack of clinical efficacy. Topp et al cautions against extrapolating in vitro results to in vivo therapy stating that the cell culture system has some limitations including a lack of well-developed extracellular matrix (“stroma”) that is present in many tumors. Normal components of tumor stroma include collagen, fibronectin and glycosaminoglycans (p. 21, col. 2). Given the unpredictable art of treating tumors in vivo using antibody therapy, compounded by the unknown functions and receptors, one of skill in the art could not predictably treat any tumor in vivo comprising administering the claimed antibody that treats tumors as broadly claimed, other than RMP1-14 and HLX10.
In regard to Wands factors (F), (G) and (H), the amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The "amount of guidance or direction" refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling. See, e.g., Chiron Corp. v. Genentech
Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1326 (Fed. Cir. 2004).
The claims are drawn to a method for treating tumors in a patient in need thereof comprising administering the claimed anti-LAG3 monoclonal antibody or a composition comprising the claimed anti-LAG3 monoclonal antibody to the patient, or in combination with any antibody drug or any small molecules.
The working examples provided by Applicant do not demonstrate a method of treating all tumors comprising administering an antibody specifically inhibiting PD-1 and the claimed LAG3 antibodies, with the exception of colon cancer and B-cell lymphoma. The specification discloses of the inhibitory activity of the anti-LAG3 humanized antibody on tumor growth in the hLAG3 KI model (see Example 10). Mouse colon cancer cells are inoculated subcutaneously on the back of the hLAG3 KI mice at 1x106 cells per mouse (see [0122]). When the tumor volume reaches about 80-120 mm3, the intraperitoneal injection of the anti-mouse PD-1 antibody RMPI-14 and the anti-LAG3 humanized antibody h6H11B10#40 (comprising SEQ ID Nos: 10 and 12) is started, and is performed twice a week for approximately 2 to 3 weeks (see [0122]). Compared with the control group injected with PBS, injection of the anti-LAG3 antibody and the anti-mouse PD-1 antibody can significantly inhibit the tumor growth; in the high-dose group, h6H11B10#40 is used in combination with the anti-mouse PD-1 antibody, which has a better efficacy than that of an antibody alone (see [0122]).
The specification also discloses of the efficacy evaluation in the hLAG3/hPD-1 transgenic mice MC38 or A20 subcutaneously transplanted tumor model (see Example 12). In the MC38 and A20 models, the data shows that the combined administration of h6H11B10#40 and HLX10 has better tumor-inhibiting effects than a single agent (see [0127] and Figure 18; see [0128] and Figure 19).
Further, the art shows that treatment of melanoma with anti-LAG3 antibodies is enabled. Bristol-Myers Squibb (doi.org/10.1101/2022.01.24.477551; publication date: 06/03/2017) shows that an anti-LAG3 antibody (BMS-986016) in combination with Opdivo (nivolumab), a PD-1 inhibitor, showed activity in patients with melanoma who were relapsed or refractory to anti-PD-1/PD-L1 therapy (see entire document).
Because the specification only studied mouse models of two types of cancer, one cannot assume that the method of treating a vast variety of cancers will work similarly to the mouse models provided in the specification. In the absence of empirical determination, one skilled in the art would be subjected to undue experimentation to determine if the claimed method of treating any other type of cancer would result in therapeutic response as recited in the claims. Applicant is reminded that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”. See Genentech, 108 F.3d 1361, 1366 (Fed. Cir. 1997).
In view of all of the above, one of skill in the art would be forced into undue experimentation to practice the claimed invention, and thus, the claimed invention does not satisfy the requirements of 35 U.S.C. 112 first paragraph.
Applicant’s Arguments
Applicant respectfully requests reconsideration and withdrawal of the enablement rejection (see pages 12-14 of the Remarks filed on 02/25/2026).
Without conceding the merit of the rejection and solely for the purpose of expediting prosecution, Applicant herewith cancels claims 15 and 17-19, and amends claims 14 and 16 to recite methods for “treating tumors”. As discussed above, the treatment of tumors with embodiments of the claimed anti-LAG3 antibodies is discussed throughout the specification, including, for example, in paragraphs [0051], [0052], and [0056]. Additionally, Examples 10 and 12 demonstrate that an embodiment of the claimed anti-LAG3 antibodies is effective in the treatment of distinct tumor types, i.e., MC38 colon cancer tumors and A20 B-cell lymphoma tumors. In fact, the Office has acknowledged that the specification is enabling for the treatment of MC38 colon cancer tumors and A20 B-cell lymphoma tumors using "the claimed anti- LAG3 antibodies." Office Action at 25.
Applicant also respectfully submits that cancer research publications have shown that the LAG3 protein targeted by embodiments of the claimed antibodies is involved in the tumor microenvironments of many types of tumors. As support, Applicant herewith submits an Information Disclosure Statement citing and providing a copy of Long et al., "The promising immune checkpoint LAG-3: from tumor microenvironment to cancer immunotherapy," Genes & Cancer, Vol. 9, No. 5-6, pp. 176-189 (2018) ("Long"). Long states that "[a]berrant LAG-3 expression has been found in a broad spectrum of human tumors such as melanoma, NSCLC, colorectal cancer, breast cancer, hepatocellular carcinoma, follicular lymphoma, head and neck squamous cell carcinoma, etc., which is significantly associated with aggressive tumor progression and clinicopathological characteristics." See Long at 178, right col., 1st full para. Long summarizes the expression of LAG-3 in 16 different human tumors and its clinicopathological associations. See Long at 178, Table 1. Applicant respectfully submits that, in view of Long's disclosure, a person having ordinary skill in the art would reasonably understand that anti-LAG3 antibodies can be effective in treating a range of tumor types.
Response to Arguments
Applicant's arguments filed 02/25/2026 have been fully considered but they are not persuasive. Examiner acknowledges that claims 15 and 17-19 are canceled thus rendering the rejection moot. Further, Examiner acknowledges the amendment to claims 14 and 16 to now recite “treating tumors”. However, as stated above, the specification only provides support for two types of cancer (i.e., colon cancer and B-cell lymphoma). One cannot assume that the method of treating a vast variety of cancers will work similarly to the mouse models provided in the specification. In the absence of empirical determination, one skilled in the art would be subjected to undue experimentation to determine if the claimed method of treating any other type of cancer would result in therapeutic response as recited in the claims. Applicant is reminded that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”. See Genentech, 108 F.3d 1361, 1366 (Fed. Cir. 1997). Furthermore, simply because Long et al demonstrates that LAG-3 expression has been found in a broad spectrum of human tumors, does not indicate that the claimed antibodies will treat the vast genus of cancers as explained by Christiansen and Topp.
As such, the scope of enablement rejection is maintained.
Allowable Subject Matter
Claims 2-5 and 13 are allowed. The combination of CDR sequences as recited in claim 2, and the corresponding VH/VL sequences as recited in claims 3 and 4, appear to be free of the art. The closest prior art is WO 2019/164219 A1 (publication date: 08/29/2019; previously submitted with the Office action mailed 09/25/2025) which is drawn to mouse antibodies that bind to angiopoietin-2 (Ang2), humanized anti-Ang2 antibodies derived therefrom, and the use thereof (see Abstract). Specifically, the ‘219 document disclose of SEQ ID NO: 29 which shares 54.4% identity with SEQ ID Nos: 18, 19, and 21 (see alignment).
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Conclusion
Claims 14 and 16 are not allowed.
Claims 2-5 and 13 are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANAYA L MIDDLETON whose telephone number is (571)270-5479. The examiner can normally be reached M-F 9:30AM - 6PM with flex.
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/DANAYA L MIDDLETON/Examiner, Art Unit 1674
/VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674