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 .
Claims 68-87 are currently pending. Claim 68 is independent.
Claim Rejections - 35 USC § 112
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 68-80 and 82-87 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. This is a written description rejection.
Vas-Cath Inc. V. Mahurkar, 19 USPQ2d 1111, states 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 courts have stated:
“To fulfill the written description requirement, a patent specification must describe an invention and do 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 at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The Guidelines for Examination of Patent Applications Under 35 USC 112, ¶1, “Written Description” Requirement (Federal Register, Vol. 66, No. 4, pg. 1105, column 3), in accordance with MPEP § 2163, specifically state that for each claim drawn to a genus the written description requirement may be satisfied through sufficient description of a representative number of species by a) actual reduction to practice; b) reduction to drawings or structural chemical formulas; c) disclosure of relevant, identifying characteristics (ie. structure) by functional characteristics coupled with a known or disclosed correlation between function and structure. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
The rejected claims are drawn to a compound of formula
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and
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wherein
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416
716
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176
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The specification and claim 76 particularly recite that R2-R3 is selected from
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652
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352
640
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268
626
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302
600
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306
614
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306
594
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168
572
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344
576
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300
590
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250
608
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234
610
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314
616
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274
602
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264
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236
566
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.
Further, note the other definitions for R2-R3 at claim 78.
The isoindole moiety of the compounds of formula I, II and III are known. However, the linker R2-R3 between the two isoindole moieties is the inventive subject matter in this application. R2-R3 and R4 encompass an enormous number of disparate groups, as can be seen above.
In contrast, in support of billions of varied compounds, the entirety of the specification only describes compounds wherein R2-R3 are
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, or
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, and R4 is
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, methyl, ethyl, ethenyl, ethynyl, NHCH3, Br or OH. And only one compound of formula III was described in which R2-R3 is
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.
“The examples and description should be of sufficient scope as to justify the scope of the claims”. See MPEP § 608.01(p). If a representative number of adequately described species are not disclosed for a genus, the claim to that genus must be rejected as lacking adequate written description under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, para. 1 (MPEP 2163). In this case, the examples fail to account for the substantial variation found amongst the compounds making up Formula I, II and III.
Chemistry is generally considered to be unpredictable and/or have unpredictable factors. See, e.g.,In re Carleton, 599 F.2d 1021, 202 USPQ 165, 170 (CCPA 1979) ("Although there is a vast amount of knowledge about general relationships in the chemical arts, chemistry is still largely empirical, and there is often great difficulty in predicting precisely how a given compound will behave.”). The pharmaceutical art, that is the use of a chemical compound to affect a desired physiological activity, is generally considered to be unpredictable and/or have unpredictable factors. See, e.g., In re Fisher, 427 F.2d 833, 839 (CCPA 1970); In re Bowden, 183 F.2d 115, 86 USPQ 419, 423 (“chemical reactions frequently are unpredictable”).
For example, the exchange of even one claimed substituent for another is not a trivial manner. Small changes in substituents may bring about unforeseeable changes in reactivity. This result may be observed in the specification at the table on pp. 106. Example 1,
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, demonstrates an IC50 < <0.1 nM. By contrast, adding just one fluoro atom to the 4-position of a methoxyisondole as in Example 2,
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, results in an IC50 of 33.67 nM. Further, changing only the linker R2-R3
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from Example 1 to the linker R2-R3
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as in Example 3,
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results in an IC50 > 150 nM. In addition to unpredictability arising from small changes, synthesizing these changes is not necessarily a predictable proposition.
Synthesizing organic compounds is not necessarily a predictable proposition. The state of the art is that “chemical reactions are known as unpredictable”. In re Marzocchi, et al., 169 USPQ 367, 370 (CCPA 1971); In re Fisher, 166 USPQ 18, 24 (CCPA 1970). Hence, the need for greater disclosure.
At p. 32, the specification discloses a general method of synthesis in Schemes 1,
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, and
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corresponding to formula (I). The specification, however, provides no indication of the starting materials and reaction conditions necessary to synthesize millions of varied compounds that contain all the dissimilar R2-R3 linkages. Instead, the specification presents the general synthetic route (Schemes 1 and 2) and specific synthetic routes of compounds of formula (I) (Examples 1-14) in which linker R2-R3 is
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and
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. Schemes 1 and 2 and the exemplified compounds cannot represent every compound of Formula I, Formula II and Formula III.
MPEP 2163: when a claim presents a genus with substantial variation, the disclosure must adequately reflect such variation with a representative number of species.
Examples 1-128 demonstrate very little variation at R2-R3 and R4, compared to the variables claimed for Formula I, II and III as can be seen in the table of claim 76 (see above). The species prepared cannot adequately describe the variation in the genus. Moreover, Schemes 1, 2 and Examples 1-14 do not account for the synthesis of the Formula II and III. There are no examples of the process in the specification.
The specification describes a genus that provides broad areas of future research and speculation. Note a recent decision, Ariad Pharmaceuticals v. Eli Lilly and Company, 94 USPQ2d 1161 regarding description requirements in the chemical arts, in particular, at p.1171: "But merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species." Later on the same page is stated: "And again in Enzo we held that generic claim language in ipsis verbis in the original specification does not satisfy the written description requirement if it fails to support the scope of the genus claimed. 323 F ,3d at 968".
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.
Claims 85-87 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 instant specification does not provide enablement for “A method of inducing an immune response in a subject, or inducing STING-dependent type I interferon production in a subject; or inducing a STING-dependent cytokine production in a subject; or treating a cell proliferation disorder in a subject. No immune response was tested in this application. Cytokine production and STING-dependent type I interferon production were not tested in this application. Cell proliferation was not tested in this application.
This application states that the compounds do all these things because the compounds are STING agonists. However, the compounds in this application instead appear to be inhibitors. The Biological Assay in page 106 of the specification, with the IC50s, reports that the compounds are STING inhibitors.
In addition, the specification does not reasonably provide enablement for “A method of inducing an immune response”, both an agonist response and antagonist response. Scope of methods: The scope of “A method of inducing an immune response in a subject” is indeterminate. The specification does not reasonably provide enablement for “treating a cell proliferation disorder in a subject” or “wherein the cell proliferation is cancer.” 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” broadly is not 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 Liebel-Flarsheim Co. v. Medrad, Inc. 481 F.3d 1371, 82 USPQ2d 1113; 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).
Enablement is considered in view of the Wands factors (MPEP 2164.01 (A)). These include: nature of the invention, breadth of the claims, guidance of the specification, the existence of working examples, state of the art, predictability of the art and the amount of experimentation necessary. All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Nature of the invention and Breadth of claims:
Scope of compounds: The compounds are of formula
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, wherein the linker R2-R3, and variable R4 are selected from an enormous number of disparate combinations. The claims cover billions of compounds which would not be expected to have similar properties.
Scope of the diseases covered. Cancer is not one disease, or cluster of closely related disorders. It is a group of more than 100 different and distinctive diseases, which have in common only some loss of controlled cell growth (Cancer definition in MedicineNet.com-2005-p.1). 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. Gastric cancer is any cancer of the stomach and can be lymphomas, GISTs, carcinoid tumors, carcinomas, or soft tissue sarcomas. The causes of gastric cancers are unclear. Treatment most often consists on surgical removal and in some instances chemotherapy or radiation (stomach cancer-Mayoclinic.com-April 9, 2011). Stomach MALT lymphoma is a type of Non Hodgkin Lymphoma affecting the stomach and in most cases is associated with infection with H. pylori bacterium. Stomach MALT lymphoma is treated with radiation, chemotherapy, surgery, and, in cases where the patient tests positive for H. pylori, it is treated with antibiotics (GastricMALTLymphoma-LymphomaAssociation-2011).
B. There are over 120 different types of primary brain tumors. The most common primary brain tumors are called gliomas, which originate in the glial tissue. There are a number of different types of gliomas, such as astrocytomas (which come in Grade I, Grade II, Grade III, Grade IV and Brain stem gliomas subtypes), ependymomas, oligodendrogliomas, mixed gliomas, and others. Examples of other brain tumors that are not gliomas are meningiomas, pituitary tumors, craniopharyngiomas, germ cell tumors, and many others. See reference “Adult Brain Tumors Treatment”, National Cancer Institute, pages 1-21 (01/24/2013) and “Types of Brain Cancer” at http://www.cancercenter.com/brain-cancer/types-of-brain-cancer.cfm (03/12/2013).
C. There are many types of colorectal cancers. The carcinomas include adenocarcinoma; mucinous adenocarcinoma; signet-ring cell carcinoma; small cell carcinoma; adenosquamous carcinoma; medullary carcinoma; choriocarcinoma; tumor of familial adenomatous polyposis; and undifferentiated carcinoma. The malignant lymphomas include marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type; mantle cell lymphoma; and many others. There are also some carcinoid tumors, sarcomas (including GISTs, angiosarcoma, and Leiomyosarcoma), primary plasmacytoma of the colon and primary malignant melanoma of the colon. See reference “Colorectal Cancer” at cancer.net (published September 2012), pages 1-2.
The state of the art and predictability in the art: Pharmacological activity in general is a very unpredictable area. Note that in cases involving physiological activity such as the instant case, “the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved.” See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
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”.
Many, many mechanisms have been proposed over the decades as methods of treating the assorted cancers generally. Cytotoxic agents could be applied directly to the tumors cells, directly killing them. Immunotherapy involves stimulating the patient's immune system to attack cancer cells generally; 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. Yet another approach is to inhibit one or more of the assorted HSP90 proteins, which will supposedly disrupt the proper folding of signaling proteins that all cancers rely on. Inhibiting telomerase was said to be able to simply stop cancer cells generally from being able to proliferate. 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 comes remotely 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 cancers 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; 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.
Barber (Nat Rev Immunol. 2015 Nov 25;15(12):760–770) illustrates the unpredictability in the art regarding STING modulation (i.e., activation and inhibition) as follows. Stimulator of interferon genes (STING; also known as MITA and MPYS, and encoded by TMEM173) is a signaling molecule associated with the endoplasmic reticulum (ER) and is essential for controlling the transcription of numerous host defense genes, including type I interferons (IFNs) and pro-inflammatory cytokines, following the recognition of aberrant DNA species or cyclic dinucleotides (CDNs) in the cytosol of the cell. Barber teaches that stimulating STING activity within the tumour microenvironment may comprise a new immunotherapeutic strategy to help treat malignant disease (p768, col 2, para 3). Also, Barber teaches that suppressing STING activity may help to avoid autoinflammatory disease and certain types of cancer, thus, designing drugs that trigger or repress STING activation and/or signaling could be of interest to the anticancer, anti-pathogen, anti-inflammatory and vaccine research fields (p768, col 2, Concluding remarks). Thus, activation of STING is known to elicit inflammatory and autoimmune responses. This reference plainly illustrates the unpredictable nature of targeting STING activity in the treatment of diseases related to autoimmunity, cancer, and viral infection. In addition, there are no known compounds of similar structure or compositions which have been demonstrated to treat all types of diseases encompassed by the claimed methods.
The foregoing state of art plainly demonstrates that there is no established correlation between activators of STING and numerous diseases encompassed by the claims. In addition, that the art of STING- targeting therapy, particularly in humans, is extremely unpredictable, particularly in the case of a single compound or genus of compounds being used for the therapy.
As stated in MPEP §2164.04[R-1], “Doubt may arise about enablement because information is missing about one or more essential parts or relationships between parts which one skilled in the art could not develop without undue experimentation."
Direction or Guidance: Despite claiming billion compounds, the biological data provided covers only a very small portion of the whole genus of compounds. Applicant appears to have only actually tested Compounds #1 through #14, shown in the table, which share the very similar linker R2-R3 and similar R4. The data only shows that some of the compounds may be STING inhibitors, not agonists as claimed. From the specification, a POSA would not be able to determine which compounds would have the use as STING agonists as claimed.
The specification’s data demonstrates that changing even one atom (even internally buried) can significantly change, or even eliminate, STING activity. Small changes in substituents may bring about unforeseeable changes in reactivity. This result may be observed in the specification at the table on pp. 106. Example 1,
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, demonstrates an IC50 < <0.1 nM. By contrast, adding just one fluoro atom to the 4-position of a methoxyisondole as in Example 2,
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, results in an IC50 of 33.67 nM. Further, changing only the linker R2-R3
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from Example 1 to the linker R2-R3
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as in Example 3,
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results in an IC50 > 150 nM. In addition to unpredictability arising from small changes in substituents, synthesizing these changes is not necessarily a predictable proposition.
The skill of those in the art: The artisan would know how to follow and apply standard and known operating procedures.
Based on the state of the art, one of ordinary skill in the art would not use STING activators/agonists to treat inflammation or autoimmune diseases because stimulating STING activity would cause more inflammation and further activate the immune response. Consequently, if the instant compounds are indeed STING agonists, one of ordinary skill in the art would not use STING activators of this application to treat amyotrophic lateral sclerosis (ALS), or a disease in which increased STING signaling contributes to the pathology and/or symptoms and/or progression. Additionally, STING activators cannot be expected to induce an immune response of a STING inhibitor.
Pharmacological art involves screening in vitro and/or in vivo to determine which compounds exhibit the desired pharmacological activities. Here, in vitro screening provided compounds capable of maybe inhibiting STING activity, and there is no reasonable predictability that within the same genus of claimed compounds there would also be compounds capable of activating STING activity.
Further, the state of the art and the lack of certainty in the contemporary knowledge in the art would prevent one of ordinary skill in the art from accepting any widely applicable treatment regimen on its face.
Working Examples: Compounds in this application appear to have the opposite STING activity as that claimed. 14 tested compounds represent only a minute fraction of compounds possible under the claims. They do not provide sufficient guidance or working examples across the full scope of the claims, to allow a POSA to determine which claimed compounds would or would not be effective as STING agonists, without performing extensive testing. The tested compounds lack variation to represent the full claimed scope. While the biological data indicates certain limited groups may inhibit STING, there is a vast majority of the claimed compounds, with different linkers, that are not tested; an some of the tested compounds appear to not be effective. See page 106, at least examples 7, 8 and 10-14.
The quantity of experimentation needed: Given the large breadth of the compounds covered, the lack of examples in the specification to represent the variations within the core, the inactivity of compounds by small changes evidenced by the specification, and given that tested compounds are described here as STING agonists but instead appear to be inhibitors, a POSA would need to engage in undue experimentation just to determine which compounds of the genus would provide a use as STING agonists, and then, which conditions could possibly be treated.
The level of effort required would be aggravated by the fact that it would be time consuming and burdensome for a POSA to create a broad range of compounds for testing using the specification’s synthetic methods, which are represented generically for the billion compounds claimed. The particular preparation examples do not show synthesis of compounds with linkers other than R2-R3
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.
In addition, given that there has never been one single agent capable of treating all cancers, given that the development of new cancer drugs has been difficult and time consuming, and particularly, given that there is no example in the specification that could serve as guidance for the claimed treatment of cancer generally, the quantity of experimentation needed is expected to be great.
At minimum, the ordinary artisan seeking to practice the claimed methods of treatment would be faced with conducting exhaustive research in order to determine whether any of the recited compounds could instead activate STING, then further determining which diseases at which stages in which persons can be treated by which compound(s) of the invention in order to practice the claimed methods. It would take undue experimentation to determine exactly what compounds encompassed by the claims will have efficacy against any given disease in a subject.
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.
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 84-86 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.
Claims 85 and 86 are ambiguous. The term "an effective amount" is unclear when the claim fails to state the function which is to be achieved (MPEP 2173.05(c)).
Claim 84 recites “and other immunomodulatory agents”. There is lack of antecedent basis for this limitation in the claims.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 81 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 81 depends of claim 68, however, includes compounds that are not encompassed by the formulae in claim 68. Compounds 114-128 do not read on the formulae of claim 68. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Conclusion
Claims 68-87 are rejected. No claim is allowable.
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/VALERIE RODRIGUEZ-GARCIA/Primary Examiner, Art Unit 1621
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