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 .
Priority
Receipt is acknowledged of certified copies of foreign priority papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on December 1, 2023, is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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.
Claim 5 is 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.
(a) Claim 5 is dependent upon claim 1 and recites the limitation: “wherein the composition is in the form of a pill or a capsule for an enteral administration, an oral administration,” in lines 2-3 [emphasis added] which is confusing, because as written, it is not clear if Applicant intends to recite “for an enteral administration” or “for an oral administration.” Clarification is requested.
The Specification teaches that the composition is in the form of a pill or a capsule, preferably for oral administration (page 6, lines 15-16). Therefore, in view of a broadest reasonable interpretation of claim 5, the recitation of “wherein the composition is in the form of a pill or a capsule for an enteral administration, an oral administration,” is construed to mean:
“wherein the composition is formulated in a pill or capsule for oral administration.”
6. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
7. Claims 1-6 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 mastocytosis, indolent system mastocytosis, or mast cell activation syndrome, comprising administering a pharmaceutical composition comprising cannabidiol or a pharmaceutically acceptable salt thereof, does not reasonably provide enablement for treating the full scope of diseases embraced by “an IDO1 related disease,” as recited. 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.
8. The standard for determining whether the Specification meets the enablement requirement was cast in the Supreme Court decision of Mineral Separation v. Hyde, 242 U.S. 261 (1916) which postured the question: is the experimentation needed to practice the invention undue or unreasonable? As recognized by the court in In re Wands, 858 F.2d 731 (Fed. Cir. 1988), that is still the standard to be applied, determined by consideration of the Wands factors (MPEP 2164.01(A)); namely, 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 the most relevant factors discussed below.
9. Nature of the Invention: As stated in MPEP 2164.05(a), “[t]he initial inquiry” for determining whether the Specification is enabling “is into the nature of the invention, i.e., the subject matter to which the claimed invention pertains.”
10. In the instant case, the claimed invention pertains to a method for the treatment of pain caused by an IDO1 related disease in a human subject in need thereof, comprising administering to the human subject a composition comprising cannabidiol or a pharmaceutically acceptable salt thereof.
11. The State of the Prior Art and the Relative Skill of those in the Art: As stated in MPEP 2164.05(a), “[t]he state of the prior art is what one skilled in the art would have known, at the time the application was filed, about the subject matter to which the claimed invention pertains” and, as stated in MPEP 2164.05(b), “[t]he relative skill of those in the art refers to the skill of those in the art in relation to the subject matter to which the claimed invention pertains at the time the application was filed.”
12. As discussed above, the instantly claimed invention pertains to a method for the treatment of pain caused by an IDO1 related disease in a human subject in need thereof, comprising administering to the human subject a composition comprising cannabidiol or a pharmaceutically acceptable salt thereof. The Specification discusses that preferably, the IDO1 related disease is a disease chosen from the group comprising: mastocytosis, in particular indolent systemic mastocytosis (ISM), mast cell activation syndrome (MCAS), Crohn's disease, myeloma and rheumatoid arthritis, which embrace a broad scope of complex and unpredictable diseases including autoimmune diseases and cancer (see page 4, lines 9-11).
13. At the time the instant application was filed, the state of the art regarding “IDO1 related diseases” is that “IDO plays a pivotal role in modulating immune responses and influencing a variety of pathophysiological states… The regulation of IDO can be influenced by both genetic and environmental factors, impacting its enzymatic activity. This can lead to either beneficial or detrimental effects on immune responses and treatment outcomes in conditions such as cancer and autoimmune diseases… “Indoleamine 2,3-dioxygenase (IDO) plays a vital role in various diseases, influencing not only biological processes but also therapeutic strategies across a range of medical fields. Understanding IDO's pathophysiological role is crucial for grasping its implications in cancer, autoimmune diseases, and neurodegenerative disorders.” [emphasis added] (Kumar, webpage printout of Indoleamine 2,3-Dioxygenase: Mechanisms and Therapeutic Insights 2026, page 9, paragraph under “Pathophysiological Role of IDO). Kumar goes on to teach the complex role of IDO in cancer: “The relationship between IDO and cancer is complex and multi-faceted. Cancer cells often exploit IDO's activity to escape immune detection,” and teaches autoimmune disorders: “Interestingly, IDO also presents a double-edged sword in autoimmune disorders. On one hand, it plays a protective role by inducing tolerance and preventing excessive immune activation; on the other, its dysregulation can contribute to disease severity. Conditions such as multiple sclerosis and rheumatoid arthritis have demonstrated altered IDO expression and activity levels,” (Kumar, page 10, first and fourth paragraphs).
14. Accordingly, those practitioners who treat cancer, autoimmune diseases, inflammatory diseases and neurodegenerative diseases of any type (medical clinicians, pharmacists and/or pharmaceutical chemists) presumably would be highly skilled in the art.
15. The Level of Predictability in the Art: Regarding drugs for targeting diseases involving/ related to IDO1, Kumar teaches that said drugs can be unpredictable: “The landscape of IDO inhibitors is evolving. Currently, several small molecules are being explored, each aiming to inhibit IDO activity effectively. For example, compounds like 1-Methyltryptophan have shown some promise in preclinical studies, where they block the enzymatic activity of IDO. These inhibitors can renew T cell activity and enhance anti-tumor immunity. However, the path to clinical application is not without hurdles,” (page 11, last paragraph). Kumar goes on to teach that achieving selectivity of IDO inhibitors is crucial as broad-spectrum inhibitors may cause unwanted side effects, and that IDO inhibitors must be investigated for potential toxicities and long-term effects (see page 12).
16. Kumar teaches that this unpredictability is more pronounced when treating cancer, for example: “IDO's duality—it serves vital functions in healthy physiology while becoming a pawn in cancer's hands,” and autoimmune diseases: “IDO's role is equally complex and sometimes paradoxical. While it can foster immune tolerance, its dysregulation may contribute to disease exacerbation. In conditions such as rheumatoid arthritis or multiple sclerosis, IDO has shown both protective and pathogenic effects, depending on the context,” (page 14, second and fifth paragraphs).
17. The Amount of Direction Provided by the Inventor / Existence of Working Examples: The amount of direction provided by the Applicant is considered to be determined by the Specification and the working examples. In the instant case, the Specification discloses one working example wherein 15 patients were administered a capsule comprising cannabidiol at a daily dose of 15 to 400 mg, wherein the patients suffered from either indolent systemic mastocytosis, hypertryptasemia, or mast cell activation syndrome (see Example 1 at pages 11-12).
18. Scope or Breadth of the Claims: The applicable rule is that “Each claim must be separately analyzed and given its broadest reasonable interpretation in light of and consistent with the written description.” MPEP §2163(II)(1), citing In re Morris, 127 F.3d 1048, 1053-1054; 44 USPQ2d 1023, 1027 (Fed. Cir. 1997).
19. Applicants are claiming methods of treating an extremely broad number of diseases or conditions embraced by “pain caused by an IDO1 related disease.” The claims encompass many unrelated disorders including those of inflammatory type, autoimmune, neurodegenerative and/or cancer(s), for many of which there is no known effective treatment or cure (including mastocytosis, particular indolent systemic mastocytosis (ISM), mast cell activation syndrome (MCAS), Crohn's disease, myeloma and rheumatoid arthritis). This unpredictability is more pronounced where the diseases disclosed in the Specification are as complex and diverse in etiology and patient populations as the many different types disclosed in this application. Diseases associated with inflammation (such as mastocytosis or mast cell activation syndrome) comprise an extremely large, officially unrelated group which underlie a broad variety of human diseases. The immune system is often involved with inflammatory disorders, demonstrated in both allergic reactions and some myopathies, with many immune system disorders resulting in abnormal inflammation. Examples of autoimmune disorders include: Hypersensitivities, Inflammatory bowel diseases, Crohn’s, Rheumatoid arthritis, Sarcoidosis, Transplant rejection, Vasculitis, Interstitial cystitis, etc, which covers an extremely broad spectrum of diseases/disorders with varying etiological origins that are difficult to predict and treat. As discussed above, “an IDO1 related disease” also embraces cancer(s) and neurodegenerative diseases, yet the text of claim 1 does not specify or enumerate those many types of cancer or neurodegenerative disorders that could fall within its scope.
20. As noted earlier, the applicable rule is that “Each claim must be separately analyzed and given its broadest reasonable interpretation in light of and consistent with the written description.” In view of this rule, claim 1 encompasses treatment of pain caused by an open-ended set of “IDO1 related disease(s).”
21. It is noted that claim 1 recites the limitation wherein, “said IDO1 related disease being chosen from the group comprising mastocytosis, indolent systemic mastocytosis (ISM), or mast cell activation syndrome (MCAS),” [emphasis added] (lines 2-4). The transitional term “comprising” which is synonymous with “including,” “containing,” or “characterized by,” is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004) (“like the term ‘comprising,’ the terms ‘containing’ and ‘mixture’ are open-ended.”). Invitrogen Corp. v. Biocrest Manufacturing, L.P., 327 F.3d 1364, 1368, 66 USPQ2d 1631, 1634 (Fed. Cir. 2003) (“The transition ‘comprising’ in a method claim indicates that the claim is open-ended and allows for additional steps.”); Genentech, Inc. v. Chiron Corp., 112 F.3d 495, 501, 42 USPQ2d 1608, 1613 (Fed. Cir. 1997) (“Comprising” is a term of art used in claim language which means that the named elements are essential, but other elements may be added and still form a construct within the scope of the claim.); Moleculon Research Corp.v.CBS, Inc., 793 F.2d 1261, 229 USPQ 805 (Fed. Cir. 1986); In re Baxter, 656 F.2d 679, 686, 210 USPQ 795, 803 (CCPA 1981); Ex parte Davis, 80 USPQ 448, 450 (Bd. App. 1948) (“comprising” leaves “the claim open for the inclusion of unspecified ingredients even in major amounts”). In Gillette Co. v. Energizer Holdings Inc., 405 F.3d 1367, 1371-73, 74 USPQ2d 1586, 1589-91 (Fed. Cir. 2005), the court held that a claim to “a safety razor blade unit comprising a guard, a cap, and a group of first, second, and third blades” encompasses razors with more than three blades because the transitional phrase “comprising” in the preamble and the phrase “group of” are presumptively open-ended. “The word ‘comprising’ transitioning from the preamble to the body signals that the entire claim is presumptively open-ended.” Id. In contrast, the court noted the phrase “group consisting of” is a closed term, which is often used in claim drafting to signal a “Markush group” that is by its nature closed. Id. The court also emphasized that reference to “first,” “second,” and “third” blades in the claim was not used to show a serial or numerical limitation but instead was used to distinguish or identify the various members of the group. Id. See MPEP 2111.03 Transitional Phrases.
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22. Therefore claim 1 is not limited to the treatment of just mastocytosis, indolent systemic mastocytosis or mast cell activation syndrome. Considering that “pain caused by an IDO1 related disease” encompasses hundreds of thousands of types of diseases including those of inflammatory type, autoimmune, neurodegenerative and/or cancer, and potentially millions of diseases, it is evident that the claims are broad. Yet, as discussed above, the instant Specification discloses treatment of only three “IDO1 related diseases” as recited by the claims. As such, the claim is extremely broad with respect to the disclosure.
23. Amount of Experimentation Necessary: MPEP §2164.01(a), 4th paragraph, provides that, “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 1157, 1562; 27 USPQ2d 1510, 1513 (Fed. Cir. 1993). Hence, in the absence of a showing of correlation between pain caused by all types and forms of IDO1 related diseases, as currently encompassed by the language of claim 1, as capable of being treated by a pharmaceutical composition comprising cannabidiol, one of skill in the art is unable to fully predict possible results from the administration of the claimed pharmaceutical composition for treating pain caused by the broad scope of diseases embraced by claim 1. There is no question Applicant’s instant composition may play a role in future methods of treating pain caused by some of the aforementioned 1DO1 related diseases. What is disputed is the claim that the recited pharmaceutical composition could be taken by one skilled in the art at the time of filing and used as treatment for pain caused by all of the diseases/disorders encompassed by “IDO1 related disease,” without undue experimentation. That is, the only way one skilled in the art is enabled to use the entire scope of the claim based on the instant disclosure entails undue experimentation.
24. To overcome this rejection, Applicant should narrow the scope of the claims such that they bear a reasonable correlation with the disclosure, i.e., limit the IDO1 related disease to the group “consisting of mastocytosis, indolent systemic mastocytosis, and mast cell activation syndrome.”
Claim Rejections - 35 USC § 103
25. 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.
26. 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.
27. 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.
28. Claims are rejected under 35 U.S.C. 103 as being unpatentable over Walker, Amber, webpage printout of “MCAS and Cannabidiol (CBD)” 2018, in view of Plakogiannis et al., U.S. 20210106541 A1 (cited on Applicant’s IDS of December 1, 2023).
Claim 1 is drawn to a method for the treatment of pain caused by an IDO1 related disease in a human subject in need thereof, said IDO1 related disease being chosen from the group comprising mastocytosis, indolent systemic mastocytosis (ISM), or mast cell activation syndrome (MCAS) comprising administering to the human subject a composition comprising a compound selected from cannabidiol (CBD) and pharmaceutically acceptable salts thereof, as the only active ingredient and at least one pharmaceutically acceptable excipient.
Claim 2 is drawn to claim 1, wherein the compound is administered at a regimen of a dose from 1 to 3000 mg per day, a dose from 50 mg to 2000 mg per day, or a dose from 150 mg to 1500 mg per day.
Claim 4 is drawn to claim 1, wherein the composition is in a form allowing an administration by enteral, parenteral or topical routes.
29. Walker suggests the administration of cannabidiol (CBD) for pain management in the mast cell activation syndrome (MCAS) patient, i.e., “CBD offers a promising future for analgesic therapeutic options for patients with MCAD. While the research is somewhat preliminary, it appears that CBD has tremendous neuroprotective, anti-inflammatory, antimicrobial, and antioxidant effects on the human body and offer a promising potential for patients with mast cell overactivation and allergic disease. CBD oil does not contain THC and it appears that it has been approved in all 50 U.S. states.” (see page ).
30. Walker does not teach the administration of a pharmaceutical composition comprising cannabidiol and a pharmaceutically acceptable excipient.
31. Yet, Plakogiannis et al. teach transdermal and topical drug delivery systems comprising cannabidiol, or a cannabidiol salt thereof for the treatment and/or prevention of pain and/or inflammation in a patient, wherein the patient is preferably a human (see abstract and paragraph [0042]). Plakogiannis et al. specifically teach a cannabidiol topical formulation in the form of an ointment and/or cream base in Example 10 (paragraph [0086]) and alternatively teach that the topical formulation can be formulated as a lotion or gel, wherein the cannabidiol may be dissolved, suspended, dispersed or uniformly mixed in a single carrier, mixture of carriers and combinations of carrier, and do not teach the inclusion of an additional active agent (paragraphs [0071]-[0073]). Plakogiannis et al. teach that the cannabidiol formulation is topically applied to the skin surface for transdermal delivery of cannabidiol (paragraph [0071]) at a dose of greater than, for example, about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 125, 150, 175, 200, 225, 250, or 275 mg/day, which meets the limitation of “from 1 mg to 3000 mg per day” required by claim 2 (paragraph [0039]).
32. As such, one skilled in the art before the effective filing date of the claimed invention would have been motivated to topically administer a formulation comprising CBD and a pharmaceutically acceptable carrier for pain management caused by mast cell activation syndrome (MCAS) in a human patient in need thereof. It would have been obvious to one of skill in the art before the effective filing date of the claimed invention to treat pain caused by the IDO1 related disease MCAS in a human patient in need thereof by administering a formulation comprising CBD by topically applying it to the skin surface for transdermal delivery of cannabidiol to said patient, with a reasonable expectation of success.
Thus, claims 1, 2, 4 and 6 are prima facie obvious.
33. Claims 3 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Walker, Amber, webpage printout of “MCAS and Cannabidiol (CBD)” 2018, in view of Plakogiannis et al., U.S. 20210106541 A1 (cited on Applicant’s IDS of December 1, 2023), as applied to claims 1, 2, 4 and 6 above, and further in view of Larsen et al., J Clin Med Res 2020.
Claim 1 is addressed in detail, above.
Claim 3 is drawn to claim 1, wherein the compound is administered at once at a dose from 150 to 1500 mg per day, by oral administration.
Claim 5 is drawn to claim 1, wherein the composition is in the form of a pill or a capsule for an enteral administration, an oral administration.
In view of a broadest reasonable interpretation of claim 5, the recitation of “wherein the composition is in the form of a pill or a capsule for an enteral administration, an oral administration,” is construed to mean:
“wherein the composition is formulated in a pill or capsule for oral administration.”
34. Walker in view of Plakogiannis et al. teach a method of treating pain caused by the IDO1 related disease MCAS in a human patient in need thereof by administering a formulation comprising CBD by topically applying it to the skin surface for transdermal delivery of cannabidiol to said patient, but do not teach oral administration.
35. However, Larsen et al. teach the pain-relieving and anti-inflammatory effects of cannabidiol (CBD) through its mechanisms of action at the 5HT1A receptor, (page 130, left column, first full paragraph). Larsen et al. summarize available CBD formulations/ routes of administration and dose amounts from published studies and controlled clinical trials in Table 1, (pages 132-135). In particular, Larsen et al. teach CBD compositions in the form of oral capsules and oral solution administered at doses of from 16 mg/day up to 1,000 mg/ day (including dosages of 50 mg, 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 400 mg, 600 mg, and 800 mg) (pages 132-134). While the prior art does not disclose the exact claimed dosage range, but does overlap: in such instances even a slight overlap in range establishes a prima facie case of obviousness. "A prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness." In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003). See also In re Harris, 409 F.3d 1339, 74 USPQ2d 1951 (Fed. Cir. 2005).
36. Thus, one skilled in the art before the effective filing date of the claimed invention would have been motivated to modify Plakogiannis et al. and administer the CBD formulation in the form of an oral capsule at a dose of from 150 to 1500 mg per day to treat pain caused by MCAS in a human patient in need thereof. And, optimization of parameters such as route of administration is a routine practice that would be obvious for a person of ordinary skill in the art to employ.
37. As such, it would have been obvious to one of skill in the art before the effective filing date of the claimed invention to treat pain caused by the IDO1 related disease MCAS in a human patient in need thereof by administering an oral formulation comprising CBD in the form of a capsule or solution to said patient, with a reasonable expectation of success.
Therefore claims 3 and 5 are prima facie obvious.
Conclusion
38. In conclusion, claims 1-6 are pending in the application. Claims 1-6 are rejected. No claim is presently allowed.
39. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JANET L COPPINS whose telephone number is (571)272-0680. The examiner can normally be reached Monday-Friday 8:30AM-5PM EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L Clark can be reached at 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JANET L COPPINS/Examiner, Art Unit 1628
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628