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 05/22/2026, are acknowledged.
Claims 2-3, 5, 9, 15, 18, and 21 are canceled.
Claims 1 and 6 are amended.
Claims 1, 4, 6-8, 10-14, 16, 17, 19, and 20 are pending.
Upon consideration of the remaining rejections, the restriction requirement is hereby withdrawn as to any claim that requires all the limitations of an allowable claim. Specifically, the restriction requirement of Groups I-III is withdrawn. Claims 10-13, 16, and 20, directed to Groups II and III are no longer withdrawn from consideration.
In view of the above noted withdrawal of the restriction requirement, applicant is advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application.
Once a restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
As such, claims 1, 4, 6-8, 10-14, 16, 17, 19, and 20 are pending examination and currently under consideration for patentability under 37 CFR 1.104.
DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 05/22/2026 has been entered.
Withdrawn Rejections
Applicant’s arguments, see page 5, filed 05/22/2026, with respect to claims 1, 4, 6-8, 14, 17, and 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. As such, the rejection under 35 USC 112(b) is withdrawn.
Claim Objections
Claim 10 is objected to because of the following informalities: “associate” should read “associated”. Appropriate correction is required.
Claim Interpretation
Examiner acknowledges that the term “treatment” refers to surgical or therapeutic treatment, the purpose of which is to prevent, alleviate (reduce) the progression of undesirable physiological changes or lesions in the subject of treatment, such as the progression of cell proliferative disorders (see [0069]).
Claim Rejections - 35 USC § 112(b)
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 10-13, 16, and 20 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.
Claim 10 is drawn to an isolated nucleic acid encoding the antibody or antigen-binding fragment thereof according to claim 1, or a combination thereof. It is unclear what “a combination thereof” is referencing as the base claim recites one set of VH CDRs and one set of VL CDRs. As such, claim 10 and its dependent claims are rejected.
The term “abnormal” in claim 16 is a relative term which renders the claim indefinite. The term “abnormal” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. One would not be apprised as to what expression of PD-L1 and/or T cell function is considered “abnormal” as there is no standard provided to compare. As such, claim 16 and dependent claim 20 are rejected.
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 16 and 20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. 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.
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 a disease associated with abnormal expression of PD-L1 and/or abnormal T cell function, comprising administering to a subject in need thereof the antibody or antigen-binding fragment thereof according to claim 1, wherein the disease is a tumor. 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 with the claimed PD-L1 antibody or antigen-binding fragment thereof. These tumors 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) 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) 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) 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) 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) 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) 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). 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) 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.
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 a disease associated with abnormal expression of PD-L1 and/or abnormal T cell function, comprising administering to a subject in need thereof the antibody or antigen-binding fragment thereof according to claim 1, wherein the disease is a tumor.
The working examples provided by Applicant do not demonstrate a method of treating a tumor associated with abnormal expression of PD-L1 and/or abnormal T cell function comprising administering the claimed PD-L1 antibody. Applicant tested the pharmacodynamics of murine PD-L1 antibody PDL1-156 in an animal model of MC38-hPD-L1 colon cancer (see Example 12). On the 21st day of administration, compared with the control group, the positive drug Avelumab group and PDL1-156 murine PD-L1 antibody group had significant and similar inhibitory effects on tumor volume and there was a statistical difference (P < 0.05) (see Example 12; Figs. 8A-C; Table 8). Additionally, Example 13 demonstrates the pharmacodynamics of humanized anti-PD-L1 antibody 156-10H. On the 21st day of administration, compared with the control group, the positive drug Avelumab group and 156-10H murine PD-L1 antibody group had significant and similar inhibitory effects on tumor volume with statistical difference (P < 0.05) (see Example 13; Figs. 9A-C; Table 10). It is noted that the CDR sequences of PDL1-156 and 156-10H are different than the claimed antibody (see Tables 1-4).
Because the specification only studied colon cancer mouse models of two antibodies, one cannot assume that the method of treating a vast variety of cancers with the claimed antibody will work similarly to the mouse models provided in the specification. Further, because the working examples tested structurally different antibodies, one skilled in the art would be subjected to undue experimentation to determine if the claimed method of treating any tumor with the claimed antibody would result in therapeutic response as recited in the claims. The art teaches the unpredictability of antibody-based cancer immunotherapy. Christiansen et al (Mol Cancer Ther, 2004, 3:1493-1501) 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) 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 numerous forms of tumors, one of skill in the art could not predictably treat any tumor in vivo comprising administering the claimed antibody.
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.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
17/925,547
Claims 1, 6-8, 14, 16, 17, 19, and 20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9 and 26 of copending Application No. 17/925,547 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The ‘547 claims are drawn to a protein wherein the protein comprises domains of: (1) the IL-15 mutant polypeptide of claim 1; (2) an immunoglobulin molecule or part thereof fused to the IL-15 mutant polypeptide; and (3) subunits α of interleukin 15 receptor (IL-15Rα) fused to the IL-15 mutant polypeptide (see claim 5).
Particularly, the ‘547 claims are drawn to the protein according to claim 5, wherein the immunoglobulin is an anti-PD-L1 antibody or antigen-binding fragment (see claim 9); wherein the anti-PD-L1 antibody is 794-h1-71; the anti-PD-L1 antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region and the light chain variable region have sequences shown in SEQ ID NO: 99 and SEQ ID NO: 100, respectively; and wherein the IL-15Rα-sushi has an amino acid sequence as shown in SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, or SEQ ID NO:55 (see claim 26). SEQ ID Nos: 99 and 100 of the ‘547 application comprises the CDR sequences of the present invention.
As such, the ‘547 application anticipates the present invention. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
18/711,230
Claims 1, 6-8, 14, 16, 17, 19, and 20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8, 9, 11-13, 15, 17, 19, 20, 23, 26, and 27 of copending Application No. 18/711,230 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The ‘230 application is drawn to a pharmaceutical composition, wherein the pharmaceutical composition comprises an IL-15 variant fusion protein, a buffer, a protein stabilizer, and a surfactant, wherein the IL-15 variant fusion protein comprises the following domains: (1) an IL-15 variant; (2) an immunoglobulin molecule fused to the IL-15 variant; and (3) IL-15Rα; wherein the amino acid sequence of the IL-15 variant is set forth in SEQ ID NO: 5, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 6, or SEQ ID NO: 7; wherein the amino acid sequence of wild-type IL-15 is set forth in SEQ ID NO: 1; wherein the order in which the domains in the IL-15 variant fusion protein are linked from the N-terminus to the C-terminus is: an immunoglobulin molecule, IL-15Rα, and an IL-15 variant; wherein the IL-15Rα or the IL-15 variant is fused to the C-terminus of the immunoglobulin Fc region; and wherein the immunoglobulin molecule is an anti-PD-L1 antibody, the heavy chain of the anti-PD-L1 antibody has the sequence set forth in SEQ ID NO: 19 or SEQ ID NO: 20, and the light chain of the anti-PD-L1 antibody has the sequence set forth in SEQ ID NO: 21 (see claim 1). SEQ ID Nos: 19 and 20 of the ‘230 application comprises the VH CDR sequences of the present invention, and SEQ ID NO: 21 of the ‘230 application comprises the VL CDR sequences of the present invention.
The ‘230 application is also drawn to a method for preventing and/or treating a disease in a patient in need thereof, the method comprising administering to the patient the pharmaceutical composition according to claim 1, wherein the disease is a tumor (see claim 26), wherein the tumor is colorectal cancer (see claim 27).
As such, the ‘230 application anticipates the present invention. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant’s Arguments
Applicant respectfully traverses the provisional double patenting rejection of copending Application No. 17/925,547 (see page 5 of the Remarks filed 05/22/2026). Applicant notes that M.P.E.P. 804(I)(B)(1)(b)(i) provides the following: If a provisional nonstatutory double patenting rejection is the only rejection remaining in an application having the earlier patent term filing date, the examiner should withdraw the rejection in the application having the earlier patent term filing date and permit that application to issue as a patent, thereby converting the provisional nonstatutory double patenting rejection in the other application into a nonstatutory double patenting rejection upon issuance of the patent.
The present application has a patent term filing date as of its PCT filing date on November
5, 2020, while the patent term filing date of U.S. Application No. 17/925,547 is May 17, 2021. Thus, between the two applications, the present application has the earlier patent term filing date. Accordingly, once all other rejections have been resolved, the obviousness-type double patenting rejection in the present application should be withdrawn.
Response to Arguments
Applicant's arguments filed 05/22/2026 have been fully considered but they are not persuasive. Examiner acknowledges the filing dates of the present application and copending Application No. 17/925,547. Examiner further acknowledges that the 112(b) rejection of claim 1 has been sufficiently addressed and has been withdrawn. However, due to rejoining claims 10-13, 16, and 20, there are new 112 rejections introduced therefore the provisional double patenting rejection is not the only rejection remaining and it must be maintained.
Conclusion
No claims are allowed.
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/DANAYA L MIDDLETON/Examiner, Art Unit 1674
/VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674
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