DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims Status
2. Claims 1-12 are pending and under examination.
Information Disclosure Statement
3. The application does not have an information disclosure statement.
4. The incorporation of essential material in the specification by reference to an unpublished U.S. application, foreign application or patent, or to a publication is improper (page 34-37). Applicant is required to amend the disclosure to include the material incorporated by reference, if the material is relied upon to overcome any objection, rejection, or other requirement imposed by the Office. The amendment must be accompanied by a statement executed by the applicant, or a practitioner representing the applicant, stating that the material being inserted is the material previously incorporated by reference and that the amendment contains no new matter. 37 CFR 1.57(g).
Specification
5. The use of the term Invivogen (page 33), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. Please review the specification for other Trademarks and correction is required.
Claim Objections
6. Claim 9 objected to because of the following informalities: The phrase “wherein the subject has a cancer that resistant to” is not grammatically correct. Inserting the word “is” or like between “that” and “resistant” would remedy the objection. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
7. Claims 6 and 9 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 6 and 9 are drawn to a method of inducing the formation of de novo tertiary lymphoid structures in a subject, the method comprising administering to the subject an effective amount of an IL33 protein; the method of claim 1, wherein the subject has cancer; The method of claim 1, wherein the subject has a cancer that resistant to PD-1 and/or PD-L1 inhibitor treatment.
The specification teaches in some such embodiments the subjects have cancer. The specification further teaches in some embodiments the subjects have pancreatic cancer, pancreatic ductal adenocarcinoma (PDAC), breast cancer, and melanoma. The specification further teaches present methods and compositions can be used to treat a PD-1/PD- L1 inhibitor resistant tumor/cancer in a subject in need thereof. The specification further teaches in some embodiments the present methods and compositions can be used to treat PD-1/PD-L1 inhibitor resistant PDAC in a subject in need thereof (i.e., in a subject with PD-1 and/or PD-L1 inhibitor resistant PDAC). The instant specification further teaches that IL-33 was identified as among the genes most highly correlated to TLS transcriptional signatures in human pancreatic ductal adenocarcinoma (PDAC), breast cancer, and melanoma. The instant specification teach orthotopic PDAC mice were treated with 500 ng carrier- free recombinant murine IL33 (R&D Systems) in sterile PBS daily for 10 days. The instant specification teach in the working examples the PDAC mice were used.
The specification teaches administration of IL-33 to mice with PDAC to induce TLSs. The specification further teaches that TLSs can be identified through their unique inducing chemokines (including the canonical CXCL1313), as well as populating cells (activated T cells, B cells, dendritic cells, and myeloid cells (1)), we selected three largely non-overlapping transcriptional signatures that identify TLSs based on such chemokines (9), cells (10), and other immunotherapy-promoting factors (5). Interestingly, we found that interleukin-33 (IL33), which encodes an alarmin rapidly released extracellularly by damaged tissues (2), was among the genes most highly correlated to expression of all three TLS signatures, and to lymphotoxin beta (LTB), which encodes the canonical lymphoid tissue (14) and TLS- inducing cytokine (3) LTb (Fig.1A). The specification further teaches to confirm this, IL33 was tested to see if it is correlated to TLS transcriptional signatures and LTB in a second prospectively collected cohort (Fig. 5A, top), and a third independently published(15) cohort (Fig. 5A, bottom) of PDAC patients. The specification teaches the number of TLSs were determined in at least 3sections using QuPath.
The specification demonstrates induction of de novo tertiary lymphoid structures only in specific and narrow context. The working example administer an IL-33 to mice bearing PDAC and then assay the treated tissue for TLS by detection of chemokines/biomarkers in order to determine whether the induction has occurred. The identification of TLS in the specification is determined made by examining the tissue for relevant markers after administration. The specification does not establish that administration of an IL-33 induces de novo TLS in every subject, in every tissue, or on every occasion. The specifications own method reflect that the outcome is not certain and the specification provides no data or representation that the induction occurs uniformly across the full scope of subjects and conditions embraced by claim 1. The claims do not recite steps by which the induction of de novo TLS is confirmed, measured or detected. The claim requires only administering an effective amount of an IL-33 and states the induction of TLS as a result.
A method of inducing the formation of de novo tertiary lymphoid structures in a subject, the method comprising administering to the subject an effective amount of an IL33 protein; the method of claim 1, wherein the subject has cancer; the method of claim 1, wherein the subject has a cancer that resistant to PD-1 and/or PD-L1 inhibitor treatment, does not meet the written description provision of 35 U.S.C. 112, first paragraph. The claims broadly encompass treating all cancers using the aforementioned method. The specification teaches administering IL-33 can treat pancreatic cancer, breast cancer, PDAC and melanoma; however, this is not deemed to be predicative of treating all cancers using the claimed method. The claims broadly encompass the induction of TLS by administering IL-33 to treat all cancers; however, the specification does not demonstrate that the IL-33 has the function of treating all cancers. Therefore, the method has no correlation with its function. The specification is not deemed sufficient to reasonably convey to one skilled in the art that the inventors, at the time the invention was made, had possession of a method of treating all cancers with the claims method because the genus encompasses conditions which differ from those disclosed in etiologies, molecular mechanisms, diagnostic approaches, treatment modalities, and therapeutic endpoints. Furthermore, the recited genus encompasses conditions yet to be discovered and/or characterized; therefore, the skilled artisan cannot envision preventing all the contemplated diseases encompassed by the instant claims.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
Finally, University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404. 1405 held that:
...To fulfill the written description requirement, a patent specification must describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines Inc. , 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli , 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d 1966.
A "representative number of species" means that the species, which are adequately described, are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]. "See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) "[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated."). "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when ... the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).
The state of the art regarding the use of IL-33 to induce TLS in pancreatic ductal adenocarcinoma is discussed by Ahmed, et al (Ahmed A, Springfeld C, Halama N. De novo induction of tertiary lymphoid structures: an immunotherapeutic strategy in pancreatic cancer. Signal Transduct Target Ther. 2025 May 26;10(1):173. doi: 10.1038/s41392-025-02260-5. PMID: 40414898; PMCID: PMC12104346.). Ahmed, et al. teach potential human drug candidate, H-rIL-33, was developed and showed promising effects in mice with PDAC. Ahmed, et al. further teach the key challenge will be determining whether the same TLS-inducing pathway exists in humans and whether clinical trials can validate the efficacy of an IL-33-based therapy in boosting anti-tumor immunity and improving patient outcomes in PDAC (last paragraph).
The cancer treatment art involves a very high level of unpredictability. 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. 5,595,756) 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) 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 T 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 tumors 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 RK indicates that to eradicate tumors, the therapeutic agents must then disperse throughout the growths in concentrations high enough to eliminate every deadly cells…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 RK 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 ‘tumours’ 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 haematopoietic and immune systems. Newer genetic mouse models can also allow analyses of tumour 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). Bean 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.
Taken together, the prior art recognizes that IL-33 induces TLSs and can treat PDAC. However, the prior art does not teach IL-33 induces TLSs and can treat all cancers, and therefore, it is unclear if the claimed method would have the claimed function. Accordingly, one of skill in the art would conclude that the claimed invention encompasses a broad genus of cancers that may not respond to treatment with the claimed method. It should be noted that the specification has not demonstrated treating all cancers with the claimed method. Based on the teaching of the instant specification and the prior art one of skill in the art would not conclude that Applicant was in possession of the claimed method of treating the genus of cancers.
Consequently, the method for inducing TLS by administering IL-33 to treat all cancers, does not meet the written description provision of 5 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph. The applicant has not disclosed any species representative of the genus, which is highly variant. Applicant is reminded that Vas- Cath makes clear that the written description provision of 5 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is severable from its enablement provision. (See page 1115).
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.
8. Claims 1, 6-9 are rejected under 35 U.S.C. 102(a)(1) as being unpatentable over Moral, et al (Moral, J.A., Leung, J., Rojas, L.A. et al. ILC2s amplify PD-1 blockade by activating tissue-specific cancer immunity. Nature 579, 130–135 (2020). https://doi.org/10.1038/s41586-020-2015-4).
The instant claims are drawn to a method of inducing the formation of de novo tertiary lymphoid structures in a subject, the method comprising administering to the subject an effective amount of an IL33 protein.
Moral teach a method comprising administering an effective amount of an IL33 protein to a subject. Moral treated orthotopic pancreatic ductal adenocarcinoma bearing C57L/6 wild type mice by intraperitoneal injection of 500 ng of recombinant murine IL-33 in sterile phosphate buffered saline, daily for seven days and every two days after (method sections). Moral teach that the treatment prevent tumor establishment in orthotopic PDAC mice and prolonged survival, selectively expanded ILC2s in tumors and draining lymph nodes, double intratumoral CD103+ dendritic cells and enhanced intratumoral CD8+ T cell cytokine capacity with PD-1 upregulated (Fig, 3a-d and Extended data section).
Regarding the limitation “inducing the formation of de novo tertiary lymphoid structure, because Moral teach administering the same antibody, to the same population, the prior method would necessarily have the same inherent properties. It is well settled that “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable (emphasis added); see In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368. Additionally, "Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Because Moral administers an effective amount of an IL33 protein to a subject and because the induction of de novo tertiary lymphoid structures inherently follows from that administration, claim 1 is anticipated.
Moral teach that subjects have pancreatic ductal adenocarcinoma. As such, instant claim 6-8 are anticipated. Moral further teaches administering recombinant IL-22 to subjects having a cancer resistant to PD-1 inhibitor treatment. Moral teaches administering recombinant I33 to mice bearing those anti-PD-1 resistant tumors and reports tumor volume and improved survival (Method section and Figure 4i) Thus, instant claim 9 is anticipated.
9. Claims 1 and 10-12 are rejected under 35 U.S.C. 102(a)(1) as being unpatentable over Pushparaj, et al (Pushparaj PN, Li D, Komai-Koma M, Guabiraba R, Alexander J, McSharry C, Xu D. Interleukin-33 exacerbates acute colitis via interleukin-4 in mice. Immunology. 2013 Sep;140(1):70-7. doi: 10.1111/imm.12111. PMID: 23582173; PMCID: PMC3809707.)
The instant claims are drawn to a method of inducing the formation of de novo tertiary lymphoid structures in a subject, the method comprising administering to the subject an effective amount of an IL33 protein.
Pushparaj teach administering an effective amount of an IL-33 protein to a subject. Pushparaj administered recombinant IL-33 to BALB/c mice at 1 ug per mouse per day by intraperitoneal injection, daily from day 0 for nineteen consecutive days (material and methods section). Pushparaj teach administering IL-33 both to mice receiving dextran sulphate sodium and to mice receiving IL-33 alone without dextran sulphate sodium (Figure 2). The recites amount is an effective amount in either group. In mice given IL-33 alone, Pushparaj reports shortened colon length relative to phosphate buffered saline controls (Figure 2b) and significantly enhanced serum IL-13 and CVCL with reduced IFN and IL-10 (figure 3). In mice given dextran sulphate sodium with IL-33, Pushparaj reports markedly enhanced IL-4, IL-13, IL-6, IL-17, vascular endothelial growth factor, CXCL9 and CXCL10, exacerbated diarrhea, and markedly shorten colon length with colon inflammation persisting at least eight days after dextran sulphate sodium withdrawal (Figure 2a-c, Figure 3).
Regarding the limitation “inducing the formation of de novo tertiary lymphoid structure, because Pushparaj teach administering the same antibody, to the same population, the prior method would necessarily have the same inherent properties. It is well settled that “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable (emphasis added); see In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368. Additionally, "Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Because Pushparaj administers an effective amount of an IL33 protein to a subject and because the induction of de novo tertiary lymphoid structures necessarily follows from that administration, claim 1 is anticipated.
The subject of Pushparaj had dextran sulphate sodium induced colitis. Pushparaj further reports that the colon inflammation persisted for at least eight days after withdrawal of dextran sulphate sodium, that IL-33 induced IL-13 and IL-17 at day 20, and that IL-33 may contribute to chronic stages of ulcerative colitis and Crohn’s disease. The recited chronic inflammatory condition, the chronic inflammatory gastrointestinal condition and colitis is disclosed. Therefore, instant claims 10-12 are anticipated.
10. Claims 1-5 are rejected under 35 U.S.C. 102(a)(1) as being unpatentable over Girard, et al. (US 9611307 B2, issued April 4, 2016).
The instant claims are drawn to a method of inducing the formation of de novo tertiary lymphoid structures in a subject, the method comprising administering to the subject an effective amount of an IL33 protein.
Girard teach administering an effective amount of an IL-33 protein to a subject. Girard teach administering recombinant human IL-33 aa112-270, produced in E. Coli using the pET15b vector in strain BL21 and purified by affinity chromatography, to BALB/c mice by intraperitoneal injection at 4 ug per animal, daily for seven days (Example d; Fig. 5). The recites amount is an effective amount and Girard reports that administration of the aa112-270 form produced measurable in vivo effect on spleen weight and blood granulocyte number relative to the phosphate buffered saline control (FIG. 5A, 5C).
Regarding the limitation “inducing the formation of de novo tertiary lymphoid structure, because Moral teach administering the same antibody, to the same population, the prior method would necessarily have the same inherent properties. Inducing the formation of de novo tertiary lymphoid structure would be inherent properties of administering IL-33. It is well settled that “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus, the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable (emphasis added); see In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368. Additionally, "Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Because Girard administers an effective amount of an IL33 protein to a subject and because the induction of de novo tertiary lymphoid structures necessarily follows from that administration, claim 1 is anticipated.
Girard administered a mature human IL-33 of SEQ ID NO: 5 which is 100% identical to instant SEQ ID NO: 1. As such, instant claims 2-4 are anticipated. Girard further teaches the IL-33 can be administered to humans (paragraph 42). As such, instant claim 5 is anticipated.
RESULT 1
US-14-001-271-5
Query Match 100.0%; Score 839; DB 1; Length 159;
Best Local Similarity 100.0%;
Matches 159; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 SITGISPITEYLASLSTYNDQSITFALEDESYEIYVEDLKKDEKKDKVLLSYYESQHPSN 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 SITGISPITEYLASLSTYNDQSITFALEDESYEIYVEDLKKDEKKDKVLLSYYESQHPSN 60
Qy 61 ESGDGVDGKMLMVTLSPTKDFWLHANNKEHSVELHKCEKPLPDQAFFVLHNMHSNCVSFE 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ESGDGVDGKMLMVTLSPTKDFWLHANNKEHSVELHKCEKPLPDQAFFVLHNMHSNCVSFE 120
Qy 121 CKTDPGVFIGVKDNHLALIKVDSSENLCTENILFKLSET 159
|||||||||||||||||||||||||||||||||||||||
Db 121 CKTDPGVFIGVKDNHLALIKVDSSENLCTENILFKLSET 159
Conclusion
11. No claims are allowed.
12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Syed J Abbas whose telephone number is (571)272-0015. The examiner can normally be reached M-Th, 9:00AM-4:00PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford can be reached at 571-272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SYED J ABBAS/Examiner, Art Unit 1674
/VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674
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