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
This application is a Continuation (CON) of International Application PCT/US25/40083, filed 7/31/2025, which claims benefit to U.S. Provisional Patent Application Numbers 63/761,698, filed 2/21/2025 and 63/678,697, filed 8/2/2024. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. The earliest effective priority date is 8/2/2024.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 2/6/2026 (2); 4/14/2026; 4/20/2026; and 5/22/2026 are acknowledged. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Response to Amendment
Applicant’s amendment to the claims filed 5/22/2026 is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Election/Restrictions
Applicant’s election without traverse of the species of the invention wherein the brain cancer against which treatment is sought is a glioblastoma (also known as a grade 4 astrocytoma, see [0083] of the specification), in the reply filed on 5/22/2026 is acknowledged.
Upon further consideration, because the generic claim 1 has been found to recite subject matter not taught in the prior art, the requirement for election of species has also been withdrawn, and the species of the inventions recited in claims 9-15 which are embraced by the generic claim 1 have been fully considered (see 37 C.F.R. § 1.141).
Claims 1-25 and 27-30 are pending and have been examined on the merits.
Claim Interpretation
The term "about" in reference to a number or range of numbers is being interpreted in light of the specification at [0040] to mean the stated number and numbers +/-10% thereof.
The terms "treat," "treating," and "treatment" is defined in the specification ([0042]) to include alleviating or abrogating a disorder, disease, or condition; or one or more of the symptoms associated with the disorder, disease, or condition; or alleviating or eradicating the cause(s) of the disorder, disease, or condition itself.
The term "therapeutically effective amount" is defined in the specification ([0043]) as meaning an amount of a compound that, when administered, is sufficient to prevent development of, or alleviate to some extent, one or more of the symptoms of the disorder, disease, or condition being treated.
Claim Objections
Claim 25 is objected to because of the following informalities:
In line 2, the terms “Intensity-modulated” and “Image-guided” should not be capitalized. These should instead say “intensity-modulated” and “image-guided”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 2 and 7 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.
Claim 2 recites: “wherein the at least two species of sea cucumber are Holothuria scabra or Holothuria nobilis”. However, the amended claim 1 already recites that “the at least two species of sea cucumber comprise Holothuria scabra and Holothuria nobilis”, in lines 12-13. Thus, it is unclear how the at least two species of sea cucumber can be either Holothuria scabra or Holothuria nobilis when both are already required of claim 2. One of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The intended scope of claim 2 is thus unascertainable and the claim is rejected as being indefinite.
Claim 7 recites: “wherein the biomass material extract is derived from Holothuria scabra, Holothuria nobilis, Heliocidaris erythrogramma, Styela clava, and Sargassum pallidum to the subject”. There is no way to determine the metes and bounds of this claim. The inclusion of “to the subject” here is unclear and has no proper meaning in this claim. Claim 1 already requires that a composition comprising biomass material extracts from these five species is administered to a subject in need thereof. What is the intended limitation of this dependent claim? The meaning of the claim is indiscernible, the limits of the claimed subject matter cannot be determined, and the claim is rejected as being indefinite.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 2-7 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
In the instant case, the claims fail to further limit the subject matter of the claim upon which it depends. Claim 1 has been amended to recite that “the at least two species of sea cucumber comprise Holothuria scabra and Holothuria nobilis”; “the species of seagrass comprises Sargassum pallidum”; “the species of sea squirt comprises Styela clava”; and “the species of sea urchin comprises Heliocidaris erythrogramma”.
Therefore, none of the additional recitations in claims 2-7 further limit the identity of the species from which the bio mass material extract is derived from.
It is noted that claim 1 recites that the species comprise the recited species and thus is an open-type language. The language of the dependent claims recite “are” and “is”. However, this is not the standard means to recite closed claim language. Under the B.R.I, these claims are not effectively limited compared to the independent claim 1.
If the intent of the dependent claims 2-7 was to make these species extracts closed and not open to any additional species, then it is suggested that the terms “are” (in claims 2 and 3) and “is” (in claims 4-7) should be amended to “consists of”, which is the proper transitional phrase for closed claim terms.
Applicant may cancel the claims, amend the claims to place the claims in proper dependent form, rewrite the claims in independent form, or present a sufficient showing that the dependent claims complies with the statutory requirements.
Claim Rejections - 35 USC § 112(a) - Scope of Enablement
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 1-8, 15-25, and 27-30 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 glioblastomas, astrocytomas, and diffuse intrinsic pontine gliomas, as recited in claims 9-14, does not reasonably provide enablement for any and all brain cancers and any gliomas. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to perform the invention commensurate in scope with these claims.
“The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue.” In re Angstadt, 537 F.2d 498, 504, 190 USPQ 214, 219 (CCPA 1976). Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). The factors include, but are not limited to: (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. See MPEP § 2164.01(a). The factors considered to be most relevant to the instant invention are addressed in detail below.
(A) The breadth of the claims
The claims are drawn to methods of treating brain cancer by the administration of a particular composition having extracts of five marine organisms (see e.g. claim 1).
Claim 1 recites “brain cancer” and does not further limit the species.
Claim 8 recite “gliomas”, which as evidenced from the specification includes all tumors formed from a glial cell origin ([0002]; [0082]-[0086]).
Claims 9-14 further limit the cancer to an astrocytoma (e.g. originating from astrocytes), including glioblastoma and diffuse intrinsic pontine glioma.
Claim 15 recites “the brain cancer is an oligodendroglioma, an ependymoma, a medulloblastoma, a choroid plexus carcinoma, a pineoblastoma, a meningioma, an acoustic neuroma, or a craniopharyngioma.”, including gliomas and distinct types of cancers ([0082]).
(B) The nature of the invention:
The invention, as best understood from the embodiments and the working examples, comprises administering to patients a mixture of biomass materials from two species of sea cucumbers, a species of sea grass, a species of sea squirt, and a species of sea urchin was utilized. The embodiment described in the disclosure of Formulation A comprises 45% H. nobilis, 40% H. scabra, 5% S. pallidum, 5% S. clava and 5% H. erythrogramma (pg. 43: Table 2; [00141]). The specification also describes that the composition affects the tumor immune microenvironment, which may aid in the treatment effectiveness against GBM ([0081]; [0165]).
However, the broad nature of the claims is not commensurate with the enablement provided by the disclosure with regard to the tumors against which the treatment is efficacious.
(C) The state of the prior art
The art generally recognizes the numerous types and vast numbers of subtypes of brain cancer and the complexity and difficulty in treating these cancers. Some representative studies are cited below, as evidence regarding the inability to predict the effectiveness of the claims composition between distinct patient populations.
Louis et al. (“The 2021 WHO Classification of Tumors of the Central Nervous System: a summary.” Neuro Oncol. 2021;23(8):1231-1251) is an article describing the classification of brain and CNS tumors (Title Abstract) and teaches that tumor types and subtypes are introduced, some based on novel diagnostic technologies (Abstract). Louis et al. describes the vast diversity and number of types of CNS tumors in Table 1, and that each of these have numerous subtypes (pg. 1232 right col.: “subtypes listed in the Subtype(s) subsections and described under Histopathology and/or Diagnostic Molecular Pathology of individual sections... Meningioma is a single type with only one entry in the classification, but with many histological subtypes and grades further described in the text.”). Table 1 of Louis is evidence of the vast amount of tumors encompassed by the claims at issue here. Further, Table 2 of Louis et al. demonstrates the some of the diversity in genetic profiles among cancer subtypes. Louis describes that “Because of the growing importance of molecular information in CNS tumor classification, diagnoses and diagnostic reports need to combine different data types into a single, “integrated” diagnosis.” (See pg. 1240, left column). Thus, one having ordinary skill would be aware of the diversity and large breadth of the claims involving all brain cancers.
Schaff et al. (“Glioblastoma and Other Primary Brain Malignancies in Adults: A Review”. JAMA. 2023;329(7):574-587. doi:10.1001/jama.2023.0023) reviews the state of knowledge about glioblastomas and other brain cancers around 2023, prior to the instant filing date. Schaff discusses that approximately 49% of malignant brain tumors are glioblastomas, and 30% are diffusely infiltrating lower-grade gliomas, while other malignant brain tumors include primary central nervous system (CNS) lymphoma (7%) and malignant forms of ependymomas (3%) and meningiomas (2%) (see Abstract, Figures 1 and 2). Schaff discusses that treatment varies by tumor type and often includes combination of surgery, chemotherapy, and radiation (Abstract, Tables 1 and 2). Schaff further teaches that many new drugs have not proven effective in late-stage clinical trials, highlighting gaps in early clinical drug development (see page 580, right col). Schaff concludes that the 5-year survival following diagnosis of a malignant brain tumor is approximately 36% at that time (see “Prognosis” on pg. 584). Overall, Schaff provides evidence in the variability and difference in treatment modalities for different tumor types.
“Grant” (US PGPub No. 20140161897, from the same inventor as the instant application) describes a composition “TBL-12” for treatment of cancers including multiple myeloma, breast, prostate, and cervical cancer (Abstract, claim 1). TBL-12 is a natural product, extracted from sea cucumber and other natural, marine ingredients ([0009]). However, Grant only demonstrates the use of this composition, which appears to be distinct from that recited in the instant claims, for the treatment of human myeloma cell lines (U266, MM1, KMS1, and APR1, see [0015]-[0026]).
Adrian et al. (US PGPUB No. 20200054657) discloses methods of treating cancer using combinations of one or more sea cucumber glycosides, such as Frondoside A or other sea cucumber glycosides, and andrographolide or an andrographolide analog (Abstract, Claims 1-3). The composition described in Adrian involves anti-cancer triterpenoid glycosides from the Atlantic sea cucumber (Cucumaria frondosa) and is distinct from the instantly described composition ([0001]). Further, Adrian does not provide any evidence regarding the use of the claimed invention against brain cancers, just prophetic examples.
Karbhari et al. (Onco. 04 November 2024, cited on IDS filed 2/6/2026) describes two clinical cases in which marine-derived compositions (SeaCare®, which appears to be the same extract as instantly disclosed, see Table 2 therein) were used in the management of glioblastoma and led to an increased survival benefit (Abstract, Summary). The publication date is after that of the instant effective filing date, yet is cited herein as evidence concerning the specificity of the claimed treatment. From the case descriptions in Karbhari, it is evident that this method has predictable benefits for the treatment of glioblastomas (see e.g. Conclusions on page 377). However, there is no evidence that the results can be interpolated to any brain cancer.
“Pacific Marine Biotech Australia Inc.” (“Phase 2 Trial on IMMUNE-12 for high grade gliomas - Glioblastoma Multiforme (GBM)” ANZCTR, Retrieved on 10/13/2025, cited on the IDS filed 2/6/2026) describes a Phase 2 clinical trial for using a composition according to the instant claims on subjects with high grade gliomas, particularly Glioblastoma Multiforme (GBM). This appears to be the same as the instantly describe marine organism extract (see pg. 2, under “Description of intervention(s) /exposure”). The participants in the study will have either completed radiotherapy but not yet started chemotherapy with temozolomide (Group 1), or had been treated with temozolomide (Group 2). However, as of the publication date of the study that was provided (10/14/25), the clinical trial had yet to commence, as the study was still in the recruitment stages).
Since the means for treatment of brain cancers, even among just gliomas remains largely unsolved, the results of using the instantly described composition for the treatment of any brain cancer is highly unpredictable.
(D) The relative skill of those in the art:
In the instant case, the artisans researching and testing treatments for brain cancer are typically doctors, particularly oncologists, and scientists in either academia or industry. Accordingly, the levels of education, training, and experience of the ordinary artisans are high. The level of skill in the art would be high, as suggested from the art cited above.
However, MPEP§ 2141.03 states “A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton.” KSR International Co. v. Teleflex Inc., 127 S.Ct. 1727, 167 LEd2d 705, 82 USPQ2d 1385, 1397 (2007). “[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle.” Id. Office personnel may also take into account “the inferences and creative steps that a person of ordinary skill in the art would employ.” Id. At 1396, 82 USPQ2d at 1396. The “hypothetical person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988).”
In such a case, those having an ordinary level of skill in the art would recognize the complexity and difficultness of treating any and all brain cancers with a single extract. It would be highly unpredictable and unexpected to achieve efficacious results in all the types of cancer recognized by the art. Thus, one would turn to the specification for additional guidance.
(E) The predictability or unpredictability of the art:
It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved”. MPEP§ 2164.03 states that “[i]n cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) (contrasting mechanical and electrical elements with chemical reactions and physiological activity). See also In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); In re Vaeck, 947 F.2d 488, 496, 20 USPQ2d 1438, 1445 (Fed. Cir. 1991). This is because in art areas having a high degree of uncertainty (i.e. the unpredictable arts) it is not reasonably predictable from the disclosure of one species, what other species will work”.
The biological arts are often unpredictable, and such brain cancer treatments as claimed herein would require each embodiment of the disease against which treatment is sought to be adequately optimized and tested. It is unclear from the disclosure what patient populations would be necessary to test for the effectiveness of the instantly described extracts without further optimization. There is no description of particular genetic factors (other than IDH1, of which the claimed method is inclusive of both wild-type and mutant forms) that might be advantageous or discouraged when deciding the patients for treatment with the instant method.
In vivo animal models may be useful, but these are merely prophetic in the instant disclosure regarding all brain cancers, other than the studies for glioblastomas described in the next section. There is no adequate disclosure in the instant application that would enable one to treat any brain cancer, as defined in the full breadth of claim 1.
(F) The amount of direction or guidance presented and (G) the existence of working examples:
The specification has provided a number of embodiments, including both prophetic embodiments and working examples of the method. However, when reducing the invention to practice, only treatments for glioblastoma (GBM) and 1 case of diffuse intrinsic pontine glioma (DIPG) have been described in the disclosure (see the Examples). Generally, the specification describes a number of brain tumors against which treatment may be sought. However, as discussed above, there is a large number of types of brain cancer, even among only gliomas, and each have numerous subtypes. The specification does not provide adequate guidance for using the claimed marine organism-derived composition against any brain cancer, as fully embraced in the broadest claims here.
The disclosure includes three clinical studies of the instant Formulation A including two subjects having glioblastoma multiforme (GBM) with wild-type IDH1 (Examples 3-4) and one pediatric subject having a diffuse intrinsic pontine glioma (DIPG) (Example 5). The data presented herein demonstrates benefits and efficacy of Formulation A having extracts of the five specific marine species recited in the amended claim 1.
The working examples herein also include several studies of the effect of the composition (namely of Formulation A as described in Table 2) for in vitro assays on glioblastoma cell lines (Examples 1, 6, 8-12, 14, 16). However, the described in vitro cell studies only demonstrate the effects against glioblastoma cell lines. Additionally, efficacy was demonstrated in an animal model of glioblastoma (Example 15). However, in vitro studies with additional tumor cell lines or animal cancer models other than the above described glioblastoma cells are not disclosed.
Therefore, there is no reduction to practice for any brain cancer against which treatment is sought, other than glioblastoma (e.g. GBM) and the singular patient study with DIPG. This is not considered adequate guidance or evidence for performing the claimed method on subjects having any brain cancer, as in the broadest claims.
(H) The quantity of experimentation necessary:
Considering the state of the art as discussed above and the high unpredictability and the lack of guidance provided in the specification, one of ordinary skill in the art would be burdened with a great amount of undue experimentation to test and treat any form of brain cancer with the instantly described method, requiring pre-clinical studies, optimization of treatment modalities, patient recruitment, and performing the clinical trials, over a significant length of time.
When weighing all of the factors described above, it is herein determined that the results of the method as claimed would have been highly unpredictable to one skilled in the art at the time of the invention and it would require undue experimentation to determine the effectiveness and best treatment regimen for each of the distinct cancers encompassed by the claims. When considering just gliomas, as in claim 8, or the cancer types of claim 15, one would be presented with an undue amount of experimentation to treat these cancers, which are not adequately enabled by reduction to practice or the evidence of working examples in the specification.
Thus, it is concluded that claims 1-8, 15-25, and 27-30 are drawn to subject matter which is not described in the specification in such a way to enable any person skilled in the art to make and use the entire scope of the claimed invention without undue experimentation.
Allowable Subject Matter
Claims 9-14 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter: Claims 9-14 are allowable over the prior art, and limit the cancer for which treatment is sought to a glioblastoma, astrocytoma, or a diffuse intrinsic pontine glioma, which are demonstrated to be effective targets of the instantly described marine sea organisms extract composition
Conclusion
Claims 1-8, 15-25, and 27-30 are herein rejected.
Claims 9-14 are objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREW TERRY MOEHLMAN whose telephone number is (571)270-0990. The examiner can normally be reached M-F 9am-5pm EST.
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/A.T.M./Examiner, Art Unit 1655
/ANAND U DESAI/Supervisory Patent Examiner, Art Unit 1655
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