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 .
Claim Objections
Claims 22 and 23 are objected to because of the following informalities: the phrase “immunosuppression,comprising” in the 1st line of each claim is missing a space after the comma and should be “immunosuppression, comprising”. Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 11-17 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a naturally occurring product without significantly more. The claim(s) recite(s) naturally occurring cerebrosides from Cordyceps sinensis which are not markedly different than they would occur in nature. This judicial exception is not integrated into a practical application because the combinations of agents (such as in the compositions claimed) would amount to nothing more than a combination of naturally occurring compounds. Naturally occurring saponins would read on the adjuvant in the composition of claims 16 and naturally occurring curcumin is a known anti-inflammatory. Thus, the combination of naturally occurring agents is also not seen to be markedly different than they would occur in nature. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because there are no additional elements when considered separately, or in combination, that would add significantly more to the exception.
Claim Rejections - 35 USC § 112 – 1st paragraph
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 11-14 and 16-23 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.
The claims of the present application are drawn to various compounds of formula I, II, III, or IV, compositions comprising the same, and methods of use of the same. The compounds of formulas I-IV embrace various R-groups and chain lengths for the cerebrosides claimed.
In Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en
banc), the Federal Circuit noted the importance of an application's disclosure and stated, “the hallmark of written description is disclosure.” A disclosure adequately describes an invention when it “reasonably conveys to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date.” Id. at 1351. “A ‘mere wish or plan’ for obtaining the claimed invention is not adequate written description.” Centocor Ortho Biotech, Inc. v. Abbott Labs, 636 F.3d 1341, 1348 (Fed. Cir. 2011).
What is required to meet the written description requirement “varies with the nature and scope of the invention at issue, and with the scientific and technologic knowledge already in existence.” Capon v. Eshhar, 418 F.3d 1349, 1357 (Fed. Cir. 2005). The Federal Circuit explained what is required to meet the written description requirement in Ariad Pharm., Inc. v. Eli Lilly & Co.: This inquiry, as we have long held, is a question of fact. Ralston Purina, 772 F.2d at 575. Thus, we have recognized that determining whether a patent complies with the written description requirement will necessarily vary depending on the context. Capon v. Eshhar, 418 F.3d 1349, 1357-58 (Fed. Cir. 2005). Specifically, the level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology. Id. For generic claims, we have set forth a number of factors for evaluating the adequacy of the disclosure, including “the existing knowledge in the particular field, the extent and content of the prior art, the maturity of the science or technology, [and] the predictability of the aspect at issue.” Id. at 1359.
A written description of a chemical genus “requires a precise definition, such as by structure, formula, [or] chemical name” of the claimed subject matter sufficient to distinguish it from other materials. Regents of the Univ. of Cal. v. Eli Lilly & Co., 199 F.3d 1559, 1568 (Fed. Cir. 1997). The Federal Circuit reflected on Eli Lilly in Ariad while explaining how to sufficiently describe a genus of compounds: We held that a sufficient description of a genus instead requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can “visualize or recognize” the members of the genus. Id. at 1568-69. We explained that an adequate written description requires a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials. Id. at 1568 (quoting Fiers v. Revel, 984 F.2d 1164, 1171 (Fed. Cir. 1993)). We have also held that functional claim language can meet the written description requirement when the art has established a correlation between structure and function. See Enzo, 323 F.3d at 964 (quoting 66 Fed. Reg. 1099 (Jan. 5, 2001)). 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.
A "representative number of species" must typify the entire claimed genus and account for variation between the species of the genus. [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. Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004).
Present independent claim 11 provides for compounds having distinct cores – I, II, III, or IV; combined with having various R-groups attached thereto. Under a broadest reasonable interpretation, the claims embrace numerous different combinations of variables, representing an untenable number of possible combinations.
By contrast, the specification provides a single example of each of formula I, II, III and IV as in claim 15’s compounds 1, 2, 3 and 4. These compounds were not synthetically made, but rather extracted from various Cordyceps. One example for each compound does not serve to typify the entirety of the genus, because one example cannot, by default, account for any variation amongst the claimed genus of combinations of variables.
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 arts, 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 cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved (emphasis added); In re Bowden, 183 F.2d 115, 86 USPQ 419, 423 (“chemical reactions frequently are unpredictable”).
Considering the unpredictability found in chemistry, altering the methods set forth in the present disclosure would not arrive at the scope of compounds claimed. Accordingly, when a claim presents a genus with substantial variation as that currently presented by the present claims, the disclosure must adequately reflect such variation with a representative number of species. The lack of any disclosure of examples may be considered in determining whether a claimed invention was adequately described. Boston Scientific Corp. v. Johnson & Johnson, 647 F.3d 1353 (Fed. Cir. 2011).
One example for each compound does not provide a “representative number of species” for an unpredictable art such as a chemistry. See, e.g., Ariad, 598 F.3d at 1354-55 (claiming that the inventor has an obligation to disclose examples when the art is unpredictable). The specification, then, is considered devoid of sufficiently detailed, relevant, identifying characteristics demonstrating that Applicant was in possession of the entirety of the genus now claimed.
Claims 18-21 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating the immune-related diseases of claims 20-21, does not reasonably provide enablement for prevention of the same. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
Undue experimentation is a conclusion reached by weighing the noted factual considerations set forth below as seen in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). A conclusion of lack of enablement means that, based on the evidence regarding a fair evaluation of an appropriate combination of the factors below, 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.
These factors include:
(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.
The breadth of the claims/Nature of the Invention:
The claims are drawn to methods of treating or preventing all immune-related diseases such as organ transplantation anti-rejection or autoimmune disease. In the absence of an explicit definition in Applicant's specification, "Prevention" as recited in the instant claims, is interpreted to mean the complete and total blocking of all symptoms of a disorder for an indefinite period of time. Any therapy which merely reduces the number or severity of symptoms, or which is effective for a period shorter than the subject's remaining lifespan, is considered to be ineffective at preventing a disorder.
The state of the prior art:
Prevention of any disorder in the sense being used herein is not a recognized clinical outcome in the art.
The level of predictability in the art:
Regarding prevention, prevention of a disease is not the same as treatment of said disease. In order to prevent a disease, as opposed to merely delaying or reducing its symptoms, a dosing must either render the subject completely resistant to said disease after a single treatment or a limited number of treatments, or else, when continued indefinitely, continue to completely suppress the occurrence of said disease. In order to practice a preventative method, one of skill in the art must know the answer to several questions in addition to the effectiveness of the therapy in short-term relief of symptoms, including: 1) What is the duration of a single course of therapy? How often must the therapy be administered to completely suppress the disease? 2) Does the subject develop tolerance to the therapy over time? Does the disease eventually progress to a point where the therapy is unable to completely suppress all symptoms? For example, will a metastatic cancer eventually adapt to overcome treatments directed to preventing it from metastasizing into the bone? Or will a case of osteoporosis or rheumatoid arthritis ultimately progress to a point where symptoms develop regardless of which therapy is administered. 3) What are the long-term effects of the therapy? Does it cause progressive damage to the kidneys, liver, or other organs? Does the active agent accumulate in the subject's tissues? Is the minimum dose necessary to completely prevent the disease safe for long-term administration? Are there any steps that can be taken to reduce side effects? Additionally, because various physiological systems are interdependent and affect one another, any hypothetical preventative treatment would have to be broad-based and treat all of the various causes of a disorder. For example, because osteoporosis is, in the majority of cases, caused at least in part by a reduction in estrogen levels, a true preventative treatment for osteoporosis must be capable of preventing or reversing menopause in a subject. For this reason, many therapies which are suitable for short-term relief of symptoms are not suitable for lifelong prevention of disease. For example, antibiotics, chemotherapeutics, and antiviral drugs are not normally administered to healthy subjects in order to prevent the development of infection or cancer. Furthermore, a tissue can degenerate for a variety of reasons, including but not limited to, exposure to toxins, chronic viral infection, autoimmune attack, and deposition of amyloid protein. To be fully successful, a preventative method would have to guard against all of these possible insults.
The amount of direction provided by the inventor:
Applicant's specification discloses assays by which inhibitory rate% of compounds 1-4 have on the proliferation of spleen lymphocytes induced by Con A. However, no guidance is given in the specification suggesting any reason to believe that administration of the claimed compounds can completely prevent all immune-related diseases.
The existence of working examples:
No working examples are given for the prevention of any disease. Note that lack of working examples is a critical factor to be considered, especially in a case involving an unpredictable and undeveloped art such as the treatment of broad categories of disease with a single agent. See MPEP 2164.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure:
As mentioned above, the short-term usefulness of a therapy for relief of symptoms is no guarantee of its long-term usefulness for prevention of disease. Because no guidance is given for the use of the claimed therapeutic method for the long-term prevention of disease, one skilled in the art wishing to practice the invention would be unable to do so without first gathering information as to the long-term effectiveness of the therapy. In particular, one skilled in the art, in order to practice the invention for prevention of disease, would need to know whether the preventative effect remains potent over the long term. In order to answer these questions in the absence of any existing data, one skilled in the art, in order to practice the invention, would undertake long-term animal tests, preferably over a period of years, preferably involving a relatively long-lived experimental animal such as dogs or monkeys, or a human clinical trial. Animal experiments include, along with induction of the disease state, administration of the potential pharmaceutical compound and collection and analysis of data, additional burdens associated with compliance with animal welfare regulations, care, feeding, and other maintenance of the animals, dissection of dead animals to collect data, and disposal of dead animals after the protocol is finished. Administering the claimed compounds for a period of years to a suitable subject population is an undue amount of experimentation needed in order to practice the full range of the claimed invention. As prevention in the full sense is an extremely high bar for any clinical outcome, there is no reason to believe that the therapy would be successful, and any actual success would be a surprising and unpredictable result.
Claim Rejections - 35 USC § 102
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
Claims 11-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 3,531,374.
‘374 teaches that glucosylceramides are hydrolyzed by an enzyme present in the spleen to produce the ceramide and glucose. See column 1, lines 49-59. It is noted that the present claims are drawn to the compounds set forth in the claims, or metabolites thereof. Thus, the “metabolites thereof” would be seen to embrace glucose and the ceramide portion the compound. The art discloses glucose, and the present claims embrace glucose as they are drawn to “metabolites thereof”, thus the disclosure of glucose anticipates the present claims.
Claim(s) 11-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sun et al. (Fitoterapia, vol. 138, 2019, 104342).
Sun discloses the compound 4 in Figure 1 having the structure:
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which is seen to be the same compound of formula 3 herein:
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Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 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 the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 11-15 are rejected under 35 U.S.C. 103 as being unpatentable over Jenkins et al. (Tetrahedron Letters, vol. 40, 1999, pp 7637-7640 – NPL reference 2 from applicant’s IDS filed 10/13/23).
The claims of the present application are drawn to compounds having formulas I, II, III, or IV with species such as:
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Jenkins discloses compounds having the formula (see top of 7638):
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which is similar to 4 of the present application but has an additional methyl group on the lower hydroxy-containing chain and notes the compounds were shown to have impressive bioactivities (see page 7640, 1st full paragraph).
The homologs of the present application would be prima facia obvious in view of the close structural compounds of Jenkins as the present compounds are only 1 -CH2- different than those in Jenkins. MPEP 2144.09 II states: Compounds which are … homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious); Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293, 84 USPQ2d 1197 (Fed. Cir. 2007) (5(S) stereoisomer of ramipril obvious over prior art mixture of stereoisomers of ramipril.)
Claim(s) 11-23 are rejected under 35 U.S.C. 103 as being unpatentable over Sun et al. as applied to claims 11-15 above.
The claims of the present application are drawn to compounds, compositions comprising the compounds and an adjuvant and additional therapeutic agents; and methods of using the same to treat various diseases such as diabetes.
Sun discloses compounds having the same formula claimed herein as above, but does not incorporate the compounds into pharmaceutical compositions comprising an adjuvant nor use this composition to treat the diseases set forth herein.
It would have been obvious to add an adjuvant to the compositions of Sun as adjuvants are known to be substances which enhance the effect of the primary treatment. It would be obvious to add a substance to enhance the activity of the compounds. Likewise, the compounds of Sun were taught to be used to treat type 2 diabetes (see abstract). Thus, it would have been obvious to administer an adjuvant containing composition comprising the compounds of Sun to treat diabetes as claimed herein as Sun teaches their compounds are effective in doing the same, and it would be obvious to add an adjuvant to the compositions of the art. Regarding the additional agents of present claim 17, such as adding an additional agent for treating diabetes - it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose. The idea of combining them flows logically from their having been individually taught in the prior art. In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious). Thus it would have been obvious to add an additional agent for treating diabetes to the compositions of Sun since they teach their compounds are effective in treating diabetes.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TRAVISS C MCINTOSH III whose telephone number is (571)272-0657. The examiner can normally be reached Monday-Friday 9AM-5:30PM EST.
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TRAVISS C. MCINTOSH III
Primary Examiner
Art Unit 1693
/TRAVISS C MCINTOSH III/ Primary Examiner, Art Unit 1693