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 .
Claims 1-3, 11-12, 14-28 are pending and considered herein.
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 1-3 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more. The claim(s) recite(s) the deposited organism, but this organism is the same organism, with the same genetics and biochemistry as found in nature. This judicial exception is not integrated into a practical application because Claim 1 is to the organism itself, Claim 2 places it in a pharmaceutically acceptable carrier which may be the naturally occurring substances of their environment, and Claim 3 claims it being at least 90% of a composition which again may include substances found in the environment naturally. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the carrier and purity are well-understood, routine and conventional element in science. For example, the Artisan may use carriers for the growth of the cells, and the purity is affected by the growth of the cells in media.
Claims 23 and 25-26 are rejected under 35 U.S.C. 101 because the claimed invention is directed to natural phenomenon without significantly more. The claim(s) recite(s) a non-human animal comprising the isolated fungus of Claim 1. This judicial exception is not integrated into a practical application because the fungus exists in nature, and is found in the microbiome of animals. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because mice also are exposed to and carry this organism in their body, and as part of the GI tract flora.
Claim 24 is found to be free of a rejection under 101. To wit, while the organism exists in nature, including in the flora of animals, the colonization of the bacteria in a gnotobiotic animal is non-natural, and thus, free of the rejection.
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 11-12, 14-15, 17-18, and 22 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.
The claims are generic for treating or preventing an autoimmune disease (e.g., Claim 11), and specifically multiple sclerosis, psoriasis, and asthma (e.g., Claim 15). Claim 16 is generic for treating or preventing a generic fungal infection in a subject by administering the composition of Claim 1. Claims 17-18 teach Candida clade and Candida albicans infection.
The specification provides antecedent basis for the idea that the autoimmune disease may involve T helper 17 cell-caused immunopathology (paragraph 20), as well as multiple sclerosis, psoriasis, and asthma (paragraph 21). The T helper 17 cell caused disease is also taught to be characterized by induced or increased Th17 activity, and may be a fungal infection (paragraphs 25-27). Further, the treatment may be by reducing the abnundance/activity of the Th17 cells (paragraph 30). In the examples, it is shown that C albicans colonized animals display an increased level of Th17 cells, while K weizmannii did not (Example 4), in what is presumed to Abx-treated mice (the animal is not referred to as a specific species or strain), in the context of K weizmannii outcompeting C albicans in C57Bl/6 mice (example 3), when C albicans WT mice are exposed to C57Bl/6 mice colonized with K weizmannii. Example 6 shows that in these mice, K weizmannii can outcompete C albicans colonized mice, along with mitigating the detrimental effects of C albicans on the mice. Finally, in studies of humans, Applicant used shotgun sequence data of 7,059 human stool samples and 173 vaginal metagenomes (Example 7). In this case it is found that K weizmannii is a regular part of the human microbiome, C albicans were polarized toward IL-17 and IL-22-producing Th17 fates, while weizmannii cells tended toward Th1 cells that react to S. cerevisiae, and in mice, the albicans and weizmannii cell types are anti-correlated, with Kazachstania species being mutually present with Candida species. In this analysis, they state: “Collectively, these data identify Kazachstania spp. as part of the human microbiome and the current data suggest an inverse correlation of these fungi and Candida spp. Warranting further studies on a larger scale” (paragraph 175), and conclude the disclosure with: “This competitive fungal commensal is thus suggested as a potential therapeutic for the management of C. albicans-mediated diseases.” (paragraph 176). This does not appear to evidence description, but simply a wish. From this, it appears that it is proposed that Th17 being lowered, is how the autoimmune disease is treated.
Moreover, strictly speaking of the fungal infections, K weizmannii, as above, is shown to work in mice models, and is shown to be present in humans, but does not evidence a removal of C. albicans, or other yeasts. For example, Wikipedia identifies at least 1,500 yeast species: Authors Unknown, printed 5/18/26, “Yeast”, Wikipedia, San Francisco, CA, 27 pages as printed, downloaded from https://en.wikipedia.org/wiki/Yeast). Just as K weizmannii appears to outcompete C. albicans in mice, other species of yeast may outcompete K. weizmanni, but none are disclosed. Moreover, mouse models do not necessarily translate to humans (or for that matter other large organisms): E. Gudrais (2013) “Mose model doesn’t work for human inflammatory diseases: Mice don’t work as model organisms for human burns, blunt trauma and infection”, Harvard Magazine, Cambridge, MA, 5 pages as printed. Gudrais states that in inflammation, 150 treatments tested positively in mice, yet not one work in humans (e.g., paragraph 3). As for infections, Gudrais states there are differences between how humans and mice respond to infections (p. 3, paragraph 3), pointing to bacterial infections, but it demonstrates how we respond distinctly, and thus, one does not predict the other. Moreover, the mistaken assumption that mouse studies apply to humans (or other large organisms) is due to a system that perpetuates itself (e.g., p. 4, paragraphs 1-2). Thus, the Artisan would not accept a mouse study as predictive of treatment in humans in any instance.
Prior to Applicant’s disclosure, the species K weizmanni was unknown, so there is no prior art concerning the same. However, the Art does recognize the involvement of Th17 in several diseases, including MS, RA, IBD, psoriasis and asthma (e.g., Waite, et al. (2012) “Th17 Response and Inflammatory Autoimmune Disease” International Journal of Inflammation, Article ID 81946, 10 pages, ABSTRACT). In this, it is shown that IL-17 is one of many other factors that affect immune response (e.g., Figure 1), and that although IL-17 may have some involvement, it turns out that other factors may be causative (e.g., p. 2, paragraph bridging columns, stating that GM-CSF not required for differentiation, it is required for autoimmune neuroinflammation). Thus, even if IL-17 production from Th17 cells is reduced, it may not have to do with the autoimmune response of any particular disorder. Moreover, while in some cases inappropriate development of Th17 cells in some infections could lead to increased disease progression and chronic infection, rather than remission and microbe clearance (p. 3, col. 1, last paragraph), such has to do with foreign substances, not autoimmune disorders. In other studies, having to do with IBS and Chrohn’s disease, TH17 is believed to downregulate Th1 and potentially PROTECT against Th1 mediated tissue damage, and other studies conflict with these findings (p. 4, col. 1, last paragraph). This demonstrates that in these diseases (i) it may be desirable to increase IL-17, and (ii) in some diseases, we do not even know for sure what the effects are. In psoriasis, it is shown that IL-17 plays a part in the disease but is not the controlling factor (e.g., p. 4, paragraph bridging pages 4-5). In the conclusion of this review, Waite states (i) there has been substantial progress in understanding IL-17 signal pathways in immune responses, (ii) the ability to target T cell lineage development can greatly ameliorate autoinflammation in preclinical models, however (iii) a better understanding is required re Th17 versus Treg and Th1 development, and (iv) linking disease models with clinical studies could improve our understanding of how these cells contribute to disease pathogenesis (p. 7, col. 2, paragraph 2). Clearly then, the Artisan at the time of invention did not see Th17 as sufficiently known as the causative link between any particular autoimmune disease such that it was understood to treat or prevent any of them.
Further to the point, even in Applicant’s post-filing publications, Applicant has stated that further studies are required before one could say a generic autoimmune disorder, including the specifically disclosed and claimed disorders, could be treated. To wit, in applicant’s disclosure to the Artisan in the non-patent literature: Kralova, et al. (2024) “Competitive fungal commensalism mitigates candidiasis pathology”, Journal of Experimental Medicine, 22(5) e20231686, 21 pages, Applicant states “this competitive fungal commensalism we report for members of the Kazachstania and Candida clades could have potential therapeutic value for the management of C. albicans-mediated diseases” (p. 10, col. 2, paragraph 2). Moreover, the same disclosure does identify the Th17 so it is understood as being there (e.g., p. 10, paragraph bridging). Thus, there is at best, only a disclosure of possible therapy for management of C albicans-mediated disease, but is admittedly requiring more research before one could evidence possession of such therapy. Applicant also characterized their findings in the Article to Kralova, et al. (2024) “Fungus vs. Fungus: Newly Identified Yeast Might Prevent Life-Threatening Fungal Infections”, published by the American Committee for the Weizmann Institute of Science, Published at Fungus vs. Fungus: Newly Identified Yeast Might Prevent Life-Threatening Fungal Infections | Weizmann USA, New York, NY, 17 pages as printed. In the title it is stated it “might” prevent … fungal infections. This is a far cry from actually treating anything, much less autoimmune disorders, much less fugal infections. Also, in May of 2024, Applicant disclosed their findings to the Rockefeller University Press: Kralova, et al. (2024) “Newly identified yeast could prevent fungal infections by outcompeting rivals, study suggests”, The Rockefeller University Press, New York, NY, 18 March 2024, 3 pages as printed. Again, the title here evidences a lack of knowledge yet, stating it “could” prevent fungal infections, but none of the article even addresses an autoimmune disease at all. The last sentence also agrees, stating that it “could have potential therapeutic value for the management of C. albicans-mediated diseases”.
Given the limited showing in mouse models, and the breadth of diseases/disorders/ infections, the breadth of animal subjects and given the lack of understanding in the art of applicability of Th-17 to the generic disorder, and complete understanding that findings in mice do not translate to other large animals, as well as the breadth of fungi species, the Artisan would not have understood Applicant to have been in possession of the generic treatment/preventions and specifically for the distinctly claimed diseases and fungi.
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 11-12, and 14-22 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.
The claims are generic for an “effective amount of a pharmaceutical composition comprising the fungus of Claim 1” to prevent or treat an autoimmune disease in a subject (e.g., Claim 11), and are generic for a “therapeutically effect amount of a pharmaceutical composition comprising the isolated fungus of Claim 1” to prevent or treat a fungal infection in a subject (e.g., Claim 16). Additionally, Claims 19-20 and 21 add additional characteristics to Claim 16 of (i) reducing the amount or abundance of fungus in the GI tract (Claim 19), (ii) by (i) at least 30% compared to a control or (ii) for at least four days, or (iii) both (Claim 20), and, separately, reducing the activity, abundance, or both, of Th17 cells in the subject (Claim 21). Claims 12, 14-15, 17, 18, and 22 further limit Claim 11, indicating the differential effects of the disease being (i) induced T helper 17 cell activity, (ii) characeterized by increased Th17 activity, or both (Claim 12), the subject having a fungal infection (Claim 14), The autoimmune disease being MS, psoriasis, or asthma (Claim 15), the infection being by a candida species (Claim 17), being Candida albicans (Claim 18), and the administration be colonizing the gut of the subject (Claim 22).
The recitation of “a therapeutically effective amount” in the claims denotes that not all amounts of the therapeutic are effective in treating or providing prophylaxis to the disease/infection. What is the objective amount that is not “effective” as opposed to the amount that necessary and predictably “effective”. How does an artisan determine what would be an effective amount to increase coagulation time?
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. The disclosure of a single species is rarely, if ever, sufficient to describe a broad genus, particularly when the specification fails to describe the features of that genus, even in passing. (see In re Shokal 113USPQ283(CCPA1957), Purdue Pharma L.P. vs Faulding Inc. 56 USPQ2nd 1481 (CAFC 2000).
The court explained that "reading a claim in light of the specification, to thereby interpret limitations explicitly recited in the claim, is a quite different thing from "reading limitations of the specification into a claim,' to thereby narrow the scope of the claim by implicitly adding disclosed limitations which have no express basis in the claim." The court found that applicant was advocating the latter, i.e., the impermissible importation of subject matter from the specification into the claim.). See also In re Morris, 127 F.3d 1048, 1054-55, 44 USPQ2d 1023, 1027-28 (Fed. Cir. 1997).
A search of the specification for “effective” provides antecedent basis for “effective amount” administrations of the fungus (paragraphs 14-15, 17, 82, and 109-111), alone or as part of a composition. Further with regard the aspects of the depending claims, there is no specific disclosure as to how much and how to administer the K weizmannii to the individual to effect, alternatively, reduction in the amount of fungus in the gut, reducing the amount in the GI tract, and by 30% or for 4 days, to effect helper T cell activity, which fungal infections require how much and how to administer, how to administer and how much for MS, psoriasis, or athsma, how much and how to administer for a generic candida, and how much or how to administer for C. albicans, and how much and how to administer to colonize the gut with the fungus.
At best there is generic teaching for mice, which do not have disease, water ad libitum (paragraph 132) but this is restricted to the examples to show the colonization, and even the amount in the water and how much water the mice take, was not taught.
Applicant’s disclosure, being the first ever concerning K. weizmannii, demonstrates the Art does not have any disclosure for these administrations.
Thus, the Artisan given the large numbers of organisms, fungal types for infection, Th17 variability, MS, psoriasis and asthma, and varied ways to administer, along with the simple showing of K weizmannii competition experiments with C. albicans, in mouse models, would not have understood Applicant to have possessed effective amounts for the adminitrations for treatment/prophylaxis as presently claimed.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT M KELLY whose telephone number is (571)272-0729. The examiner can normally be reached M-F: 8a-5p.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Tracy Vivlemore can be reached at 571-272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
ROBERT M. KELLY
Examiner
Art Unit 1638
/ROBERT M KELLY/ Primary Examiner, Art Unit 1638
Prosecution Insights