DETAILED ACTION
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 .
This is the first action on the merits.
Claims 1-19 are pending and under examination.
Claim Objections
Claim 15 objected to because of the following informalities: the term chiral is randomly found at the top of page 10 and does not seem associated with anything. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(B) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-6 and 8-19 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 pre-AIA the applicant regards as the invention.
In claim 1, the definition of a “3- to 8-membered spiroheterocycloalkyl” is vague, see the definition of Z, iii). Z is a terminal ring and it’s unclear how a spiro ring may be formed differently than heterocycloalkyl ring at the same position. Thus, claims 1-6, 8-14 and 16-19 are rejected.
With regards to claim 15, the following formula lacks antecedent basis with respect to the carbonyl substituted on the fused 6-membered pyran ring:
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The rejection may be overcome by cancellation of the species or making claim 15 independent.
With regards to claim 15, the following formula lacks antecedent basis with respect to the spiro ring substituted on the fused 6-membered pyran ring:
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The rejection may be overcome by cancellation of the species or making claim 15 independent.
Claim 14 is vague because 35 U.S.C. 112(b) requires that the claim particularly point out the invention. Claims may not refer to the specification. Verily, claims that refer to the specification are improper. See Ex parte Fressola, 27 USPQ.2d 1608 (BPAI 1993). Claim 14 improperly refers to compounds by compound Examples 1-26.
The rejection under 35 U.S.C. § 112(b) may be obviated by the following suggestions: inserting the compounds into the claim.
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 18 and 19 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 a method of treating non-small cell lung cancer (NSCLC), colorectal cancer and pancreatic cancer, does not reasonably provide enablement for a method of treating cancer generally. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The treatment of cancer generally cannot possibly be considered enabled.
As a general rule, enablement must be commensurate with the scope of claim language. MPEP 2164.08 states, “The Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation’.” In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)” (emphasis added). The “make and use the full scope of the invention without undue experimentation” language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: “A lack of enablement for the full scope of a claim, however, is a legitimate rejection.” The principle was explicitly affirmed most recently in Auto. Tech. Int’l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008). See also In re Cortright, 49 USPQ2d 1464, 1466 and Bristol-Myers Squibb Co. v. Rhone-Poulenc Rorer Inc., 49 USPQ2d 1370.
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (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. Some experimentation is not fatal; the issue is whether the amount of experimentation is “undue”; see In re Vaeck, 20 USPQ2d 1438, 1444.
The analysis is as follows:
(A) Breadth of claims.
(a) Scope of the compounds. The instant claims encompass millions of compounds with a tricyclic scaffold with a variety of substituents at four different positions.
(b) Scope of the diseases covered. Cancer is not a single disease, or cluster of closely related disorders. There are hundreds of cancers, which have in common only some loss of controlled cell growth. Cancers are highly heterogeneous at both the molecular and clinical level, something seen especially in, for example, the cancers of the breast, brain and salivary glands. They can occur in pretty much every part of the body. Here are some assorted categories:
A. CNS cancers cover a very diverse range of cancers in many categories and subcategories. There are an immense range of neuroepithelial tumors. Gliomas, the most common subtype of primary brain tumors, most of which are aggressive, highly invasive, and neurologically destructive tumors are considered to be among the deadliest of human cancers. These are any cancers which show evidence (histological, immunohistochemical, ultrastructural) of glial differentiation. These fall mostly into five categories. There are the astrocytic tumors (astrocytomas): pilocytic astrocytoma (including juvenile pilocytic astrocytoma, JPA, and pediatric optic nerve glioma) diffuse astrocytomas (including fibrillary astrocytomas, protoplasmic astrocytomas and gemistocytic astrocytomas), anaplastic astrocytomas (including adult optic nerve glioma), Glioblastoma multiforme (GBM), gliosarcoma and giant cell glioblastoma, and pleomorphic xanthoastrocytoma. GBM exists in two forms, primary and secondary, which have very different clinical histories and different genetics, but GBM is considered to be one clinical entity. second, there are the oligodendroglial tumors (oligodendrogliomas): low grade oligodendroglioma and anaplastic oligodendroglioma. Third, there is oligoastrocytomas (“mixed glioma”), a type of tumor with both astrocytoma & oligodendroglioma features. The fourth type is the ependymomas, which are intracranial gliomas, including papillary ependymoma, myxopapillary ependymoma, tanycytic ependymoma, anaplastic ependymoma and subependymal giant-cell astrocytomas. A fifth type is the gangliogliomas (glioneuronal tumors or glioneurocytic tumors), which have both glial and neuronal components, and are extremely varied, based in part on what types of glial and what types of neuronal components are present. These include Papillary Glioneuronal Tumor (PGNT), a range of supratentorial gangliogliomas, assorted intramedullary spinal cord gangliogliomas, pineal ganglioglioma, hypothalamic ganglioglioma, cerebellar ganglioglioma, ganglioglioma of the right optic tract, rosetted glioneuronal tumor (“glioneurocytic tumor with neuropil rosettes”), composite pleomorphic xanthoastrocytoma (PXA)-ganglioglioma, desmoplastic ganglioglioma (both infantile (DIG) and non- infantile), angioganglioglioma, and others. There are also some glial tumors which do not comfortably fit into these five categories, notably astroblastoma, gliomatosis cerebri, and chordoid glioma, which is found solely in the hypothalamus and anterior third ventricle. Other neuroepithelial tumors include astrocytic tumors (e.g. astrocytomas) oligodendroglial tumors, ependymal cell tumors (e.g. myxopapillary ependymoma), mixed gliomas (e.g. mixed oligoastrocytoma and ependymo-astrocytomas) tumors of the choroid plexus(choroid plexus papilloma, choroid plexus carcinoma), assorted neuronal and neuroblastic tumors (e.g. gangliocytoma, central neurocytoma, dysembryoplastic neuroepithelial tumor, esthesioneuroblastoma, olfactory neuroblastoma, olfactory neuroepithelioma, and neuroblastomas of the adrenal gland), pineal parenchyma tumors (e.g. pineocytoma, pineoblastoma, and pineal parenchymal tumor of intermediate differentiation), embryonal tumors (e.g. medulloepithelioma, neuroblastoma, ependymoblastoma, atypical teratoid/rhabdoid tumor, desmoplastic medulloblastoma, large cell medulloblastoma, medullomyoblastoma, and melanotic medulloblastoma) and others such as polar spongioblastoma and gliomatosis cerebri. A second Division is tumors of the meninges. this includes tumors of the meningothelial cells, including meningiomas (meningothelial, fibrous (fibroblastic), transitional (mixed), psammomatous, angiomatous, microcystic, secretory, lymphoplasmacyte-rich, metaplastic, clear cell, chordoid, atypical, papillary, rhabdoid, anaplastic meningioma) and the non- meningioma tumors of the meningothelial cells (malignant fibrous histiocytoma, leiomyoma, leiomyosarcoma, rhabdomyoma, rhabdomyosarcoma, chondroma, chondrosarcoma, osteoma, osteosarcoma, osteochondroma, haemangioma, epithelioid haemangioendothelioma, haemangiopericytoma, angiosarcoma, kaposi sarcoma). There are also mesenchymal, non-meningothelial tumors (liposarcoma, (intracranial) solitary fibrous tumor, and fibrosarcoma) as well as primary melanocytic lesions (diffuse melanocytosis, melanocytoma, malignant melanoma, and meningeal melanomatosis). A third division are the tumors of cranial and spinal nerves. This includes cellular schwannomas, plexiform schwannomas and the melanotic schwannomas (e.g. psammomatous melanotic schwannoma, neuro-axial melanotic schwannoma, dorsal dumb-bell melanotic schwannoma). There is also Perineurioma (Intraneural and Soft tissue) and malignant peripheral nerve sheath tumor (MPNST), including Epithelioid, MPNST with divergent mesenchymal differentiation, and MPNST with epithelial differentiation. A fourth division are germ cell tumors, including germinoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma (mature teratoma, immature teratoma, and teratoma with malignant transformation). A fifth division are the tumors of the sellar Region, viz. pituitary adenoma, pituitary carcinoma, granular cell myoblastoma and craniopharyngiomas (adamantinomatous and papillary). Yet another division are local extensions from regional tumors, including paraganglioma, chodroma, chordoma, and chondrosarcoma. There are also Primitive Neuroectodermal Tumors (PNETs) including medulloblastomas, medulloepitheliomas, ependymoblastomas and polar spongioblastomas. There are Vascular brain Tumors e.g. the hemangioblastomas, there is CNS Lymphoma (which can be primary or secondary) and Meningeal Carcinomatosis. There are lymphoma and haemopoietic neoplasms including malignant lymphomas (which can be primary or secondary), plasmacytoma, and granulocytic sarcoma. And there are many, many others.
B. Leukemia is any malignant neoplasm of the blood-forming tissues. Leukemia can arise from many different sources. These include viruses such as EBV, which causes Burkitt's lymphoma, and HTLV-1, linked to certain T cell leukemias. Others are linked to genetic disorders, such as Fanconi's anemia, which is a familial disorder, and Down's Syndrome. Other leukemias are caused by exposure to carcinogens such as benzene, and some are actually caused by treatment with other neoplastic agents. Still other leukemias arise from ionizing radiation, and many are idiopathic. Leukemias also differ greatly in the morphology, degree of differentiation, body location (e.g. bone marrow, lymphoid organs, etc.) There are dozens of leukemias. There are B-Cell Neoplasms such as B-cell prolymphocytic leukemia and Hairy cell leukemia (HCL, a chronic Lymphoid leukemia). There are T-Cell Neoplasms such as T-cell prolymphocytic leukemia, aggressive NK cell leukemia, adult T cell leukemia/lymphoma (ATLL), and T-cell granular Lymphocytic leukemia. There are different kinds of acute myeloid leukemias (undifferentiated AML, acute myeloblastic, acute myelomonocytic leukemia, acute monocytic leukemias, acute monoblastic, acute megakaryoblastic (AmegL), acute promyelocytic leukemia (APL), and erythroleukemia). There is also lymphoblastic leukemia, hypocellular acute myeloid leukemia, Ph-/BCR- myeloid leukemia, and acute basophilic leukemia. Chromic leukemias include chronic lymphocytic leukemia (CLL, which exists in a B-cell and a T-cell type), prolymphocytic leukemia (PLL), large granular lymphocytic leukemia (LGLL, which goes under several other names as well), chronic myelogenous leukemia (CML), chronic myelomonocytic leukemia (CMML), chronic neutrophilic leukemia, chronic eosinophilic leukemia (CEL), and many others.
These are just two categories of cancer which were elaborated. Others are:
C. Carcinomas of the Liver,
D. Lung and pleural cancer,
E. Thyroid cancer,
F. Cancer of the skin cells,
G. Colorectal cancers,
H. Renal carcinomas,
I. Prostate Cancer,
J. Penile carcinoma,
K. The carcinomas of the extrahepatic bile ducts,
L. Breast cancers,
M. Ovarian cancers,
N. Testicular cancers,
O. Paratesticular cancers,
P. Cancers of the vulva,
Q. Vaginal cancers,
R. Uterus cancers,
S. Stomach cancers,
T. Cancers of the esophagus,
U. Cancers of the spleen,
V. Salivary gland carcinomas,
W. Cancers of the heart,
X. Odontogenic tumors,
Y. Cancers of the oral cavity and oropharynx,
Z. Cancers of the lymph glands,
AA. Cancers of the adrenal glands,
AB. Cancers of the eye,
AC. Cervical cancers,
AD. Gestational Trophoblastic Neoplasias (cancer of the placenta),
AE. Cancers of the throat,
AF. Cancers of the thymus,
AG. Fallopian Tube Cancer,
AH. Bladder cancers, and
AI. Cancers of the gallbladders.
(B) The nature of the invention and predictability in the art: With specific reference to cancer, Ex parte Kranz, 19 USPQ2d 1216, 1219 notes the “general unpredictability of the field [of] …anti-cancer treatment.” In re Application of Hozumi et al., 226 USPQ 353 notes the “fact that the art of cancer chemotherapy is highly unpredictable”. More generally, the invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
(C) Direction or Guidance: That provided is very limited. The dosage range information, found on page 18 of the specification gives many ranges, which is generic, the same for the many disorders covered by the specification. Thus, there is no specific direction or guidance regarding a regimen or dosage effective specifically for any and all cancers generally.
(D) State of the Prior Art: The claimed compounds are substituted pyrano[2.3-d]pyrimidin-4-yl-diazine ring-C(O)-alkene-amines. So far as the examiner is aware substituted pyrano[2.3-d]pyrimidin-4-yl-diazine ring-C(O)-alkene-amines have not been successfully used as anticancer agents, generally.
(E) Working Examples: The invention is drawn to a method of treating cancer, generally. There are no in vivo working examples in the specification drawn to this utility to support the use of substituted pyrano[2.3-d]pyrimidin-4-yl-diazine ring-C(O)-alkene-amines to treat cancer generally. On pages 86-93 of the specification there are several in vitro assays presented which provides data, 1) Evaluation of inhibitory activity of compounds on KRAS G12C nucleotide (GDP-GTP) exchange reaction in vitro; 2) Evaluation of inhibitory activity of compounds on interaction between KRAS G12C and cRAF (in vitro) ; 3) Assay of growth inhibition activity on KRAS-G12C mutant cell line (MIA PaCa-2) (in vitro); 4) SOS-catalyzed nucleotide exchange assay; and 5) RAS:RAF-RBD binding assay.
(F) Skill of those in the art: Taken as a whole, the skill level in oncology must be considered as low. Many mechanisms have been proposed over the decades as methods of treating the assorted cancers generally. Cytotoxic agents could be applied directly to the tumor cells, directly killing them. Immunotherapy involves stimulating the patient's immune system to attack the cancer cells, either by immunization of the patient, in which case the patient's own immune system is trained to recognize tumor cells as targets, or by the administration of therapeutic antibodies as drugs, so the patient's immune system is recruited to destroy tumor cells by the therapeutic antibodies. Another approach would be to increase the amount or activity of the body’s tumor suppressor genes, e.g. p53, PTEN, APC and CD95, which can for example activate DNA repair proteins, suppress the Akt/PKB signaling pathway, or initiate apoptosis of cancer cells. The angiogenesis inhibitor strategy was based on cutting off the blood supply that growing tumors need by shutting off the growth of new blood vessels by, for example, suppressing proliferation of endothelial cells or inducing apoptosis of endothelial cells. There is also the cancer stem cell paradigm, which hypothesizes that cancer could be treated generally, either by targeting the cancer stem cells themselves, or by targeting the epithelial-to-mesenchymal transition which supposedly generates the cancer stem cells. Many of these approaches --- and there have been others as well --- have produced anti-cancer drugs. However, despite high hopes for success, and a plausible theory why these should work for cancers generally, none of these approaches have ever produced a drug which come anywhere near such a goal.
Specifically, the prior art knows that there never has been a compound capable of treating cancers generally. “The cancer therapy art remains highly unpredictable, and no example exists for efficacy of a single product against tumors generally.” (<http://www.uspto.gov/web/offices/pac/dapp/1pecba.htm#7> ENABLEMENT DECISION TREE, Example F, situation 1). A similar statement appears at In re Application of Hozumi et al., 226 USPQ 353: “In spite of the vast expenditure of human and capital resources in recent years, no one drug has been found which is effective in treating all types of cancer. Cancer is not a simple disease, nor is it even a single disease, but a complex of a multitude of different entities, each behaving in a different way”. There are compounds that treat a modest range of cancers, but no one has ever been able to figure out how to get a compound to be effective against cancer generally, or even a majority of cancers.
The attempts to find compounds to treat the various cancers arguably constitute the single most massive enterprise in all of pharmacology. This has not resulted in finding any treatment for tumors generally. Indeed, the existence of such a "silver bullet" is contrary to our present understanding in oncology. This is because it is now understood that there is no “master switch” for cancers generally; cancers arise from a bewildering variety of differing mechanisms. Even the most broadly effective antitumor agents are only effective against a small fraction of the vast number of different cancers known. This is true in part because cancers arise from a wide variety of sources, primarily a wide variety of failures of the body's cell growth regulatory mechanisms, but also such external factors such as viruses (an estimated at least 20% are of viral origin e.g. Human papillomavirus, EBV, Hepatitis B and C, HHV-8, HTLV-1 and other retroviruses, and quite possibly Merkel cell polyomavirus, and there is some evidence that CMV is a causative agent in glioblastoma), exposure to chemicals such as tobacco tars, excess alcohol consumption (which causes hepatic cirrhosis, an important cause of HCC), ionizing radiation, and unknown environment factors.
Accordingly, there is substantive “reason for one skilled in the art to question the objective truth of the statement of utility or its scope” (In re Langer, 183 USPQ 288, 297). Similarly, In re Novak, 134 USPQ 335, 337-338, says “unless one with ordinary skill in the art would accept those allegations as obviously valid and correct, it is proper for the examiner to ask for evidence which substantiates them.” There is no such evidence in this case. Likewise, In re Cortright, 49 USPQ2d 1464, states: “Moreover, we have not been shown that one of ordinary skill would necessarily conclude from the information expressly disclosed by the written description that the active ingredient” does what the specification surmises that it does. That is exactly the case here. Even if applicants’ assertion that cancer in general could be treated with these compounds were plausible--- which it is not ---, that would not suffice, as was stated in Rasmusson v. SmithKline Beecham Corp., 75 USPQ2d 1297, 1301: “If mere plausibility were the test for enablement under section 112, applicants could obtain patent rights to “inventions” consisting of little more than respectable guesses as to the likelihood of their success.”
Different types of cancers affect different organs and have different methods of growth and harm to the body, and different vulnerabilities. The skill thus depends on the particular cancer involved. There are some cancers where the chemotherapy skill level is high and there are multiple successful chemotherapeutic treatments. The mechanism in these situations, however, is not necessarily the same as is alleged for these compounds.
One skilled in the art knows that chemotherapy of brain tumors is especially difficult. This is because 1) the blood-brain barrier, which is often intact in parts or all of a brain tumor, will block out many drugs, as it is the purpose of the blood-brain barrier to protect the brain from alien chemicals, and 2) CNS tumors are characterized by marked heterogeneity, which greatly decreases vulnerability to chemotherapy. As a result, many categories of CNS tumors simply have no chemotherapy available. These include, generally, hemangioblastomas, meningiomas, craniopharyngiomas, acoustic neuromas, pituitary adenomas, optic nerve gliomas, glomus jugulare tumors and chordomas, to name just some. With regard to gliomas, GBM is considered untreatable; no effective agents have emerged for the treatment of GBM, despite 20 years of enrolling patients in clinical trials. It is radiation and surgery which are used for low grade gliomas (e.g. pilocytic astrocytoma and diffuse astrocytomas), as no drug has been found effective. There is no drug treatment established as effective for optic nerve gliomas or gangliogliomas. Indeed, very few gliomas of any type are treated with pharmaceuticals; it is one of the categories of cancer that is the least responsive to drugs.
Cartilage tumors do not respond to chemotherapy, nor, generally, do cancerous teratomas. Of the thyroid cancers, only one (anaplastic thyroid cancer) can be treated with anticancer agents. The other are treated with radioactivity, surgery, or thyroid suppression hormones. Lymphomas of the stomach are not commonly treated with anti-cancer agents per se, but instead, surgery or radiation and antibiotic therapy (e.g. amoxicillin, metronidazole, bismuth, omeprazole) are the primary treatments. Neuroendocrine tumors of the cervix generally do not respond to chemotherapy. A number of sarcomas, including alveolar soft part sarcoma (ASPS), retroperitoneal sarcoma, most liposarcomas, and the assorted chondrosarcomas, are generally considered not to respond to chemotherapy; no chemotherapeutic agent has been established as effective. Aggressive NK cell leukemia is considered to be untreatable with pharmaceuticals. Myxoma of the heart (atrial myxoma) is the most common primary cardiac tumor and has no chemotherapy; excision is the only treatment. Chemotherapy of spleen tumors is rarely even attempted, and no drug has been established as effective for any primary or secondary splenic tumor types. Many cerebral metastases, such as those from non-small-cell lung cancer and melanoma, are not chemosensitive and will not respond to chemotherapy. Hepatocellular Carcinoma (HCC or hepatoma) is, in humans, possibly the most prevalent solid tumor and in certain parts of the world is the most common cancer; it has long been understood as a chemotherapy-resistant tumor, with only very recently, some success seen with the Tyrosine protein kinase inhibitor Sorafenib. Metastatic esophageal cancer, and malignant melanoma of the esophagus do not respond to chemotherapy.
It is important to note that tumors can need to be treated quite differently even though they are tumors of the same organ. For example, the drugs used most often to treat Wilms tumor, the most common malignant tumor of the kidneys in children, are actinomycin D and vincristine. Such drugs are never used with clear cell renal carcinoma, which is treated, although without much success, with Immunotherapy using the cytokines interleukin-2 and interferon-alpha. However, such immunotherapy has never been established as effective in non-clear cell RCC forms such as papillary renal cell carcinoma. Despite strenuous efforts over a period of decades, no chemotherapeutic agent has ever been found effective against this cancer. Cancers of the stomach can be lymphomas, GISTs, carcinoid tumors, carcinomas, or soft tissue sarcomas, and for a single agent to be effective against all or even most of these categories would be contrary to what is known in oncology.
(G) The quantity of experimentation needed: Given the fact that, historically, the development of new cancers drugs has been difficult and time consuming, and especially in view of factors A and D and F, the quantity of experimentation needed is expected to be great.
MPEP 2164.01(a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim(s) 1-3, 7-9, 12, 14 and 16-18 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Xu et al. (US 20220315598, cited on IDS).
The reference teaches the following species:
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, see pages 12, 13 and 15. The reference further teaches a method of treating a G12C cancer by inhibiting KRAS G12C protein, see page 83, paragraphs 0808, 0810 and 0821 and page 148, Table 1. The compositions are taught on page 190, claim 18.
Thus, said claims are anticipated by Xu et al.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claim(s) 1-3, 7-9, 12, 14 and 16-19 are rejected under AIA 35 U.S.C. 103(a) as being unpatentable over Xu et al. (US 20220315598, cited on IDS).
The 102 rejection above is incorporated here.
Claim 19 is drawn to a composition with an additional active agent. The ‘737 publication teaches compositions on page 158, claim 18 but not in combination with another active ingredient. However, the addition of a second anti-cancer agent would be obvious. It has been held that combinations of two or more compositions each of which is taught by the prior art to be useful for the same purpose in order to form a third composition which is to be used for the very same purpose. In re Susi, 58 CCPA 1074, 1079-80, 440 F.2d 442, 445, 169 USPQ 423, 426 (1971); In re Crockett, 47 CCPA 1018, 1020-21, 279 F.2d 274, 276-77, 126 USPQ 186, 188 (1960).
Thus, said claims are rendered obvious.
Claim(s) 1-3, 7, 8, 11, 12, 14 and 16-19 are rejected under AIA 35 U.S.C. 103(a) as being unpatentable over Hilf et al. (WO 2020236940, cited on the IDS) in view of Xu et al. (US 20220315598, cited on IDS).
The present application claims compounds of formula (I), wherein R1= CH3, R2= CH3, R3 and R4= spiro cyclohexyl fused with a phenyl substituted with a fluoro, R6= CH2CN, n= 1, A= piperidine ring, X1= O, X2= CH2, L= O, Z= methyl-pyrrolidine ring and m= 1, as KRAS inhibitors and a treatment for cancer.
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The ‘940 publication teaches the following species of formula (I), wherein R1= CH3, R2= CH3, R3 and R4= spiro cyclohexyl fused with a phenyl substituted with a fluoro, R6= CH2CN, n= 1, A= piperidine ring, X1= CH2, X2= CH2, L= O, Z= methyl-pyrrolidine ring and m= 1::
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, see page 438, as KRAS inhibitors and a treatment for cancer.
The difference between the claimed compound and the cited compound above is at X1= CH2 versus Applicant’s oxygen.
The ‘598 publication teaches the equivalency of oxygen at this position with the following species of formula (I), wherein R1 = CH3, R2= CH3, R3= naphthyl bicycle, R4= H, R6= CH2CN, n= 1, A= piperidine ring, X1= O, X2= CH2, L= O, Z= methyl-pyrrolidine ring and m= 1:
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159
172
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, see page 12, as KRAS inhibitors and a treatment for cancer.
Therefore, the CH2 and oxygen at X1= are considered alternatively useable. Thus, said claims are rendered obvious.
Conclusion
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/SUSANNA MOORE/Primary Examiner, Art Unit 1624