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 .
Election/Restrictions
Applicant’s election without traverse of Group (I), with the addition of immunodeficiency as the elected disease, natural Killer (NK) cells as the elected hematopoietic cell, and Jasplakinolide (JAS) as the elected ARF modulator is maintained. However, the fact that immunodeficiency has been excluded from the claims, the election of species has been expanded to immune-cell mediated disease and inflammatory disease.
Expansion of Election of Species Requirement
A reasonable and comprehensive search conducted by the Examiner determined that the prior art at the time of the present invention was such that it did not anticipate or render obvious the elected species (jasplakinolide). In light of this discovery, the search is expanded to paclitaxel, but not the full scope of the claim.
Lee, Chihyi
Claims Status
Claims 1-19, 21-23, 26, 31-32, 34-35, 37-42, 44-50, 53-54, 57, 59-60 are canceled. Claims 20, 24-25, 27-30, 33, 36, 43, 51-52, 55-56, 58, and 61-65 are pending and are examined in accordance to the elected species and the expanded species.
Action Summary
The objection of claims 55 and 56 are withdrawn in light of the claim amendment.
Claims 20, 24-25, 27-30, 33, 36, 43, 51-52, 55-56 rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kassab et al (US 2013/0085109 A1) as evidenced by Mari et al (Clinic Rev Allerg Immunol 23, 325–340 (2002) and Vredevoe et al (Cardiovascular Research, Volume 104, Issue 2, 1 November 2014, Pages 290–302), are withdrawn in light of the claim amendment.
Claims 20, 24-25, 27-30, 33, 36, 43, 51-52, and 55 rejected under 35 U.S.C. 103 as being unpatentable over Kassab et al (US 2013/0085109 A1) in view of Vredevoe et al (Am J Cardiol 2004;93:1007-1011), Boukouaci et al (Cardiovascular Research, Volume 104, Issue 2, 1 November 2014, Pages 290–302), and Masilamani et al (The Journal of Immunology, 2006, 177: 3590–3596), are withdrawn in light of the claim amendment.
Applicant’s arguments filed 12/20/2025 have been fully considered. Rejections and objections not reiterated form previous Office Action are hereby withdrawn. The following rejections are either reiterated or newly applied. They constitute the complete set of rejections presently being applied to the instant application.
New Rejection necessitated by claim amendment
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 20, 24-25, 27-30, 33, 36, 43, 51-52, 55-56, 58, and 61-65 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.
This rejection encompasses the embodiment of contacting the cell that is defined by the administration of Jasplakinolide (jas) to a subject wherein jas is comprised within liposomes selectively targeted at said NK cells as recited in claim 20 and its dependent claims.
The factors to be considered in determining whether undue experimentation is required are summarized in re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). The court in Wands states: "Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is 'undue,' not 'experimentation.' " (Wands, 8 USPQ2d 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. "Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations." (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (1) the nature of the invention, (2) the relative skill of those in the art, (3) the breadth of the claims, (4) the amount or direction or guidance presented, (5) the presence or absence of working examples, (6) the quantity of experimentation necessary, (7) the state of the prior art, and (8) the predictability or unpredictability of the art.
Although the quantity of experimentation alone is not dispositive in a determination of whether the required experimentation is undue, this factor does play a central role. For example, a very limited quantity of experimentation may be undue in a fledgling art that is unpredictable where no guidance or working examples are provided in the specification and prior art, whereas the same amount of experimentation may not be undue when viewed in light of some guidance or a working example or the experimentation required is in a predictable established art. Conversely, a large quantity of experimentation would require a correspondingly greater quantum of guidance, predictability and skill in the art to overcome classification as undue experimentation. In Wands, the determination that undue experimentation was not required to make the claimed invention was based primarily on the nature of the art, and the probability that the required experimentation would result in successfully obtaining the claimed invention. (Wands, 8 USPQ2d 1406) Thus, a combination of factors which, when viewed together, would provide an artisan of ordinary skill in the art with an expectation of successfully obtaining the claimed invention with additional experimentation would preclude the classification of that experimentation as undue. A combination of Wands factors, which provide a very low likelihood of successfully obtaining the claimed invention with additional experimentation, however, would render the additional experimentation undue.
The nature of the invention
Claim 20 is drawn to the step of administering an effective amount of jasplakinolide that is contained within liposomes selectively targeted at NK cells to a subject wherein said administration step activates NK cell in an inhibitory immunological synapse. Claim 20 encompasses any treatment including cardiovascular disease mediated by immune/inflammatory response.
Claim 30 is drawn to the step of administering an effective amount of jasplakinolide that is contained within liposomes selectively targeted at NK cells to a mammalian subject suffering from an immune-related disorder wherein said administration step activates NK cell in an inhibitory immunological synapse. This claim contemplates any immune-related disorder.
Claim 30 is drawn to the step of administering an effective amount of jasplakinolide that is contained within liposomes selectively targeted at NK cells to a subject for treating, inhibiting, reducing, eliminating or delaying the onset of an immune-related disorder. The invention is in a class of invention which the CAFC has characterized as ''the unpredictable arts such as chemistry and biology.'' Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001). This claim embraces any immune-related disorder.
Level of skill in the art
The level of skill in the art is deemed to be high, generally in the field of cancer immunotherapy.
The breadth of the claims
Applicants broadly claim activating NK cell for any subject (healthy or not) with any route of administration, any effective amount, and any therapeutic use or outcome (claim 20).
Applicants broadly claim any route of administration, any effective amount, and any mammalian subject, and any immune-related disorder (claim 30).
Applicants broadly claim any route of administration, any effective amount, and any subject, and any immune-related disorder (claim 31).
Guidance in the specification and Working Examples
The specification provides numerous working examples of the compound jasplakinolide, demonstrating NK cell activation. Although, the specification contains extensive in vitro assays-demonstrated through various figures-showing NK cell action in vitro by 1 µM jas, there is no clear explanation or data bridging these in vitro findings to the in vivo context. Additionally, the in vivo example 8 appears to be purely prophetic and lacks specific endpoints or data to support the claimed invention. While example 8 of the specification mentions a particular nanoparticle system for ARF modulator in present tense, it does not provide any experimental results or measurable outcome. The prophetic in vivo example does not correlate or show how the in vitro assays translate to an animal model or in vivo efficacy. Thus, the link between the detailed in vivo work and any potential real-world therapeutic or claimed use is not established in the specification. As such, if there is evidence that administration of an effective amount jas to be effective for an animal/human subject as recited in claim 20 or for a mammalian subject suffering from immune-related disorder as recited in claim 30, or treating/inhibiting/reducing/eliminating/delaying the onset of an immune-related disorder in a subject. While it is understood that the absence of working examples should never be the sole reason for rejecting a claim as being broader than an enabling disclosure, the criticality of working examples in an unpredictable art, such as administration of jas in a mammalian subject, is required for practice of the claimed invention.
Quantity of experimentation
The quantity of experimentation in the areas of immunology therapy and jas is extremely large given the unpredictability associated with it in general and the lack of correlation of in vitro findings to in vivo success, and the fact that no known or effective therapeutic application of Jas contained in liposome selectively targeted NK cells in human and animal immune disease and cardiovascular disease mediated by immune/inflammatory response.
The unpredictability of the art and the state of the prior art
Schweikart et al (Toxicol In Vitro. 2012 Dec 20;27(2):745–751) supports the hypothesis that the toxicity observed in rats and dogs is due to toxic effects of jaspamide on cardiomyocytes. (See Abstract.) Schweikart et al teaches based on the narrow therapeutic index observed in these studies, jaspamide was dropped from consideration for further development as an anticancer agent at the National Cancer Institute. (See second paragraph of page 2.)
Cayman Chemical (06/25/2025) teaches jasplakinolide is for research use and not for human or veterinary diagnostic or therapeutic use. (See Section 1.)
Lin et al (Journal of Natural Products 2025 88 (6), 1471-1480) discloses Thus, jaspamide also known as jasplakinolide, has been widely adopted in cell biology studies, resulting in more than 1,000 citations. However, despite considerable attempts, jaspamide was never advanced as a clinical candidate because of a poor therapeutic index
Market Research (Fusion Strategie, innovating through collaboration, Published Nov 6, 2025) highlights that stringent regulatory requirements for marine-derived compounds pose significant hurdles for market growth. Ensuring safety, efficacy, and quality standards through extensive testing prolongs the approval process. Navigating these regulatory pathways demands substantial investment and expertise, which can delay commercialization and impact market penetration.
High Production Costs
Limited Supply Chain Infrastructure
Regulatory Uncertainty
These factors collectively restrict the pace of market expansion and the availability of jasplakinolide-based therapeutics in the United States. Potential safety and toxicity issues associated with jasplakinolide pose significant challenges for clinical development. Its potent biological activity necessitates thorough evaluation to prevent adverse effects. Addressing these concerns requires extensive preclinical and clinical testing, which can delay product development and increase costs. (See Regulatory Challenges on page 3 bridging first paragraph of page 4.)
Gaspar et al (Blood (2013) 122 (23): 3749–3758) outlines that he severity of the clinical and immunologic phenotype of severe combined immunodeficiency (SCID) requires prompt intervention, and for most patients, the only curative treatment is allogeneic hematopoietic stem cell transplantation (HSCT). Gene therapy offers a cure for two specific forms of SCID and, although other SCID forms may become amenable to this form of treatment in the future, it is likely that HSCT will continue to be the mainstay of treatment of the majority of SCID patients. (See first paragraph of the Introduction Section.)
Christina Palmer (GoodRx inc, March 10, 2021) notes that autoimmune conditions such as rheumatoid arthritis, lupus, multiple sclerosis, and psoriasis can be hard to diagnose and even harder to treat. While they all share the common underlying issue of your body attacking its own cells, there are over 100 autoimmune conditions and they can vary greatly in their symptoms and severity. (See Introduction Section.)
In conclusion, the unpredictability stems from a combination of factors: the documented toxicity of jaspamide in cardiomyocytes, the absence of clinical development due to its poor therapeutic index, and the extensive testing hurdles for marine-derived compounds. Despite in vitro promise, prior art shows inconsistent translation to safe human and animal use. Thus, one skilled in the art would face undue experimentation to achieved the claimed in vivo efficacy with the application of jas contained in liposome selectively targeted NK cells. Furthermore, incorporating a compound like jas into a liposome may help with delivery and reduce off-target toxicity. But to move from theory to a practical, therapeutically effective doe, a skilled artisan would need extensive experimentation. The challenge is that the skilled artisan known how the liposome delivery would affect its distribution, its stability, or its ability to target actin safely in a living system. Lastly, the references underscore those autoimmune conditions, like SCID require stem cell transplantation or complex autoimmune diseases like rheumatoid arthritis, are extremely difficult to treat. The Christiana Palmer reference highlights the complexity and variability of autoimmune disease, making them hard to diagnose and even harder to treat. Meanwhile, Gaspar shows that for severe cases, like SCID, only advance interventions, such as stem cell transplantation or gene therapy, are effective. Given that Jaspamid has never demonstrated safe or effective use in humans and animals, and considering the stringent and highly specialized approaches needed for autoimmune conditions, it would be speculative and unsupported to extrapolate that jaspamide could be effective in treating such conditions. In short, the complexity and established difficulty of treating autoimmune diseases and the lack of efficacy and safety for jaspamide reinforce that administering jaspamide contained in liposome selectively targeted NK cells would require substantial, unpredictable experimentation and is not reasonably enabled.
With regards to the unpredictability in the art, those of skill in the art can reasonably conclude that the claimed method cannot be expected to active NK cell in a subject with cardiological condition and a mammalian subject suffering from immune-related disease, and treat immune-related disease, in a mammalian/human subject. Absent such guidance, the experimentation required, without needing to resort to random speculation, what therapeutic amounts, testing each compounds claimed, each route of administration and each subject would be available to even start testing for a therapeutic effect, would clearly be undue. Further, it is noted that, while the lack of a working embodiment cannot be the sole factor in determining enablement, the absence of substantial evidence commensurate in scope with the breadth of the presently claimed subject matter, in light of the unpredictable nature of the chemical and pharmaceutical arts and the limited direction that Applicant has presented, provides additional weight to the present conclusion of insufficient enablement in consideration of the Wands factors as a whole.
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. In the absence of this information, the specification fails to provide adequate guidance and/or direction to one of skill in the art at the time of the invention that would have enabled such a person to practice the instantly claimed invention without having to resort to undue experimentation to determine how, in fact, one would achieve the instantly disclosed therapeutic objective(s).
`The basis for the present rejection is not simply that experimentation would be required, since it is clear from the state of the prior art and Applicant's disclosure and remarks that experimentation in this particular art is not at all uncommon, but that the experimentation required in order to practice the full scope of the invention would be undue. Please reference in re Angstadt, 537 F.2d 498, 504, 190 USPQ 214, 219 (CCPA 1976), which states, "The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue.” (emphasis added) Accordingly, in the absence of any adequate disclosure, direction or guidance as to how one would go about using the instantly claimed compound with a reasonable expectation of successfully treating the disclosed disorder(s), it remains that the pharmaceutical, chemical and medical arts are notoriously complex such that methods of use would have been sufficiently unpredictable to warrant the need for undue experimentation to actually practice the full scope of the invention as instantly claimed.
As the cited art and discussion of the above factors establish, practicing the claimed method in the manner disclosed by Applicant would not imbue the skilled artisan with a reasonable expectation or ability to make and use the full scope of the invention as instantly claimed, given the disclosure and supporting examples provided in the present specification and the state of the art at the time of the invention. In order to actually achieve the claimed invention, it is clear from the discussion above that the skilled artisan could not rely upon Applicant's disclosure as required by 35 U.S.C. 112, first paragraph, and would have no alternative recourse but the impermissible burden of undue experimentation in order to practice the full scope of the embodiments presently claimed.
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 20, 24-25, 27-29, 61, 62, and 64 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. The claim recites “… contacting a cell….” and “contacting is by administration to a subject.” The claim is unclear because the proviso conditions “contacting a cell” on “administration to a subject.” While the claim suggests contacting a cell might occur directly (e.g., in vitro), the condition that “contacting” is by “administration” introduces ambiguity. “Administration” typically implies system processing in a subject, whereas “contacting” a cell directly might not. This inconsistency makes it clear whether the claim covers only systemic administration or only direct contact method, or both.
New Rejection necessitated by claim amendment
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 20, 24-25, 27-30, 33, 36, 43, 51-52, 55-56, 58, and 61-65 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hong et al (WO97/41852 A1).
This rejection is based on the interpretation of claim 20 is in vivo method and the interpretation that if another agent other than jasplakinolide like paclitaxel is used, then, the containment of jas within liposome is immaterial to the claims.
Hong teaches a method of treating systemic lupus erythematosus comprising administering an effective amount of paclitaxel to a subject. (See lines 23-36 of page 5 bridging lines 1-10 along with lines 15-35 of page 7.)
With the limitation of the proviso (containment of jas within liposome selectively targeted at NK cell) that is further limited by claims 61-66. Since the prior art deal with paclitaxel, which is not subject to the proviso, the extra liposome requirement does not apply. Thus, the prior anticipates the claim because the claim covers agents beyond the proviso. In other words, the claim is broad-encompassing actin inhibitors-generally-and paclitaxel, as disclosed in the specification, falls with that broader scope, meeting the limitations.
Moreover, since the prior art discloses the same agent-paclitaxel-and the specification identifies is an inhibitor of the same mechanism (like ARF or actin retrograde flow), the independent claims 20, 30, and 33) and all the dependent claims 24-25, 27-29, 36, 43, 51-52, 55-56, and 58) limitations tied to that mechanism necessarily apply. In other words, because it is the same known agent acting the same way, the functional characteristics follow. Thus, the prior necessarily anticipates the dependent claims as well.
Furthermore, with respect to the limitation of activating NK cell in an inhibitory immunological synapse as recited in independent claims 20 and its dependent claims and independent claim 30 and its dependent claims. The prior art discloses the same compound administered to the same patient population (a subject suffering from systemic lupus erythematosus as an immune-related disorder). The claimed “activating Nk cells” is merely a natural result or intended outcome of administering this known agent to this known group. Thus, the prior art anticipates the claimed methods because the intended outcome naturally flows, from what is taught.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/JEAN P CORNET/Primary Examiner, Art Unit 1628