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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 05/18/2026 has been entered.
Response to Amendment
The Amendment filed 05/18/2026 has been entered. Applicant’s amendments are in response to in the Final Office Action mailed 03/17/2026 (note the new Examiner for this Application, where continuity of rationale will continue as much as possible, but style may slightly differ due to process specific practices). Furthermore, with regard to the approach to the Application within this Office Action, “there is nothing unusual, certainly, about an examiner changing his viewpoint as to the patentability of claims as the prosecution of a case progresses, and so long as the rules of Patent Office practice are duly complied with an applicant has no legal ground for complaint because of such change in view. The life of a patent solicitor has always been a hard one. In re Ruschig, 154 USPQ 118, 120-21 (CCPA 1967).” In this case, the difference in search and interpretation of the Prior Art has led to a modified approach to the instant claim set, while attempting to be consistent with the previous round of prosecution.
Applicant’s claims have been amended in the following manner: independent claim 15 has been broadened by removal of diethylcarbamazine (DEC) (which has been moved to dependent claim 76) and modified by introduction of “physically” isolated and “or physical barrier” (in conjunction with the filed Affidavit). Applicant amendments find support at [0179-0181] in the Specification, that describe an illustration of an embodiment (Figures 1A) compared to an unacceptable variant (Figure 1B). The Examiner has tailored the Office Action to address Applicant’s remarks, while including Art of the previous Office Action. Furthermore, new claims 57-76 have been entered to draw a new ground of rejection. The “barrier” concept introduced into the claims finds support in Applicant’s Specification at [0228-0232].
The following objections/rejections are withdrawn: none.
The Examiner further acknowledges the following:
Claims 15-17, 20, 22-23, 26-28, 32-36, 40-49, 53, and 56-76 are pending.
No claims are withdrawn, although a restriction requirement (filed 10/31/2024) remains in place.
Claims 15-17, 20, 22-23, 26-28, 32-36, 40-49, 53, and 56-76 are presented for examination and rejected as set forth below.
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.
Claims 22, 33, and 41 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.
Claims 22, 33, and 41 recites the limitation "the DEC". There is insufficient antecedent basis for this limitation in the claim (because “a DEC” is not established in claim 75 nor independent claim 65).
Claim Rejections - 35 USC § 112
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 22, 33, and 41 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.
Claims 22, 33, and 41 are each improperly dependent on claim 75 (i.e., claim 75 nor independent claim 65 refer to “a DEC” that is found in claims 22, 33, and 41, and thus, “the DEC” does not provide a meaningful limitation of the claims). Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 15-17, 23, 27-28, 36, 40, 46, 56-71, and 73-75 are rejected under 35 U.S.C. 103 as being unpatentable over Cheng (US20210128479A1, published 5/6/2021 vs. the provisional filing date of 11/10/2021), and in further view of Brewer (US20040009237A1), as evidenced by Kathpalia (J. Adv. Pharm. Edu. & Res. 2014).
Applicant’s claims are directed to a pharmaceutical composition comprising: a therapeutically effective amount of ammonium tetrathiomolybdate (ATTM), and a pharmaceutically acceptable carrier, wherein the ATTM is encapsulated inside a first capsule, and the first capsule is encapsulated inside a larger second capsule, wherein the larger second capsule contains a filler, and the first capsule inside the second capsule is physically isolated from the larger second capsule by the filler or physical barrier such that the first capsule is not in contact with the second capsule, and wherein the composition is in a delayed release oral dosage form that releases the ATTM in the gastrointestinal tract after the oral form passes the stomach.
Note that, in terms of obviousness, for intended uses of a composition (e.g., the elements “cooperate” to reduce exposure of ATTM to moisture and oxygen and therefore, reduces degradation of ATTM by an H2S releasing mechanism in instant claims 57-59, 61-62, 65, 68-69, and 73-74), this does not provide significant patentable weight, because composition patentability depends on structural features, and it’s unclear what specifically enables elements to “cooperate” in the manner claimed.
The Examiner considers the BRI of barrier agent as any ingredient that is able to form the instant “filler” or “physical barrier” of instant claim 1 such as common excipients found in oral pharmaceutical dosage forms, that can remain intact to prevent oxygen and/or moisture ingress into a dosage form. In Applicant’s Specification at [0229], Applicant defines the “barrier agent layer is such that it either absorbs water, or slowly dissolves (e.g., a functional controlled-release polymer), or is a lipophilic (hydrophobic) coating substance, e.g., lipids and other hydrophobic excipients.” Thus, the Examiner considers ingredients disclosed in the Specification that are taught to have these functions (e.g., extended release prevents oxidation [0113], enteric coating to protect from stomach acid [0044], adsorbent minimizes water/stomach acid exposure [0099]) as additional demonstrations of “barrier agents.” As a non-limiting example of common excipient function within a formulation, Kathpalia (J. Adv. Pharm. Edu. & Res. 2014) teaches common excipients that are known to protect against moisture and/or oxidation: excipients such as HPMC create an effective barrier to moisture, which helps the probiotic remain inactive until it is consumed (page 170, first paragraph); excipients such as pullulan and PVA provide an oxygen barrier for oxidation sensitive APIs (pg 167-168).
Cheng teaches a dosage form of controlled release at specific gastrointestinal sites, such as the stomach, small intestine, and large intestine (Cheng – claim 6), that comprises multiple compartments (abstract), whereby one compartment is within a larger compartment (Cheng – claim 47, for embodiments, see Figures).
Regarding claim 15-16, 27-28, 57-62, 65, and 67: Cheng teaches a drug dosage form that has a first particle comprising a first active pharmaceutical ingredient (API) wrapped by a first coat (reads on “encapsulated inside a first capsule”, where capsule nomenclature is made obvious by [0003] and representative Figures of Cheng) and is encapsulated inside a shell (reads on “a second larger capsule”, as explicitly stated in [0123]) (Cheng – claim 47).
Because APIs are described to have biological activity [0068-0069], removal of the second and/or third API/particle from the dosage form of Cheng – claim 47 is obvious, if an additional biological activity is not required and/or desired (i.e., a “compartment” is defined by Cheng “to contain API or a material different from that from the compartment” [0089], to read on the instant “filler or physical barrier”, whereby different materials are extensively discussed [0012-0016, etc.] in many exemplary configurations [0017-0022, etc.]). Furthermore, Cheng teaches the obviousness of a soluble material 111 or 112 (reads on “filler or physical barrier” in terms of the referenced figure 1) that releases API at certain locations in the GI tract [0012-0016, 0112-0113, etc.]. Thus, the specific configuration of the dosage form of instant claim 15 is obvious to a PHOSITA based on the concepts disclosed by Cheng. Further note, in terms of obviousness of shell/filler/coating space/thickness (and also the wide variability of shell/filler thickness), Cheng teaches exemplary values for the multi-layer formulations [0082-0100] (i.e., demonstrating the instant “physical barrier” of claim 15).
Regarding the instant active agent, Cheng teaches tetrathiomolybdate as an API [0069], whereby APIs are ingredients that are biologically active (whereby salt forms of APIs are biologically active) [0068], and include examples of salt forms or free base forms (e.g., finafloxacin, finafloxacin hydrochloride, alendronate sodium, etc.) [0069]. Thus, the fact that Cheng teaches TM [0069] to reach its target in the GI would mean that Cheng’s TM multi-compartment drug formulations survive the moisture and oxygen (i.e., both on storage and also encountered in transit to the GI target).
Regarding barrier agents and/or moisture/oxygen ingress (see instant claims 57-59, 61-62, 65, 68-69, and 73-74, and also discussion above regarding the limited patentable weight given to an “intended use” of a composition), when Cheng teaches a dosage form of controlled release at specific gastrointestinal sites such as the stomach, small intestine, and large intestine (Cheng – claim 6), then, the coating layers of Cheng (Cheng - claim 47) are considered to survive the oxygen and moisture filled environments of the GI in order to prevent degradation of APIs, while transiting the GI, in order to improve bioavailability [0005]. Furthermore, Cheng teaches an oral dosage form [0051] and can be delayed release or sustained release (i.e., extended release) [0076-0077] with an enteric coating [0057], whereby ingredients with extended release and/or enteric coating function are considered “barrier agents” by Applicant’s Specification (e.g., extended release prevents oxidation [0113], enteric coating to protect from stomach acid [0044], adsorbent minimizes water/stomach acid exposure [0099]).
Cheng teaches hydroxypropylmethylcellulose (or hypromellose) as a material for a compartment and/or shell [0012-0016], which is a suitable “barrier agent” (where Applicant discusses in the Specification extended release systems prevent oxidation [0113]).
Regarding claim 17 and 46: Cheng teaches pharmaceutical compositions that are extended-release oral dosage forms [0076-0077].
Regarding claims 23 and 28: Cheng teaches an additional API can include sulforaphane [0069], whereby Cheng’s use of “comprises” includes consideration of “one or more” components [0041], including an ingredient such as the API [0069].
Regarding claim 36 and 56: Cheng also teaches gelatin as an ingredient for capsule formation [0057] , in addition to enteric coating [0057].
Regarding claim 40: Cheng teaches a dosage range of 1-60 mg for the APIs [0071].
Regarding claim 63-64 and 75: Cheng teaches tablets [0003], powders [0105, 0107], and matrix [0108], whereby furthermore, the inner first particle of Cheng-claim 47 is framed by the definition of a compartment [0089] that would be interpreted to encompass tablet and matrix forms.
Regarding claim 66: Cheng teaches solid and semi-solid dosage forms [0003-0004], which would be obvious forms to implement in the compartments (Cheng – claim 47; [0089]).
Regarding claim 68-69 and 73-74: When Cheng teaches the obviousness of the instant composition (see above for mapping of independent claims 15 and 65), the result of reducing moisture ingress and oxygen diffusion and improving chemical stability is expected. Furthermore, Cheng’s compositions are able to protect APIs until controlled release at specific locations of the GI, such as the stomach, small intestine, and large intestine (Chen – claim 6).
Regarding claim 70-71: Cheng teaches lipophilic and/or hydrophobic excipients such as cocoa butter [0065], hydrogenated castor oil [0064], etc.
In summary, Cheng teaches a dosage form of controlled release at specific gastrointestinal sites, such as the stomach, small intestine, and large intestine, that comprises multiple compartments, whereby one compartment is housed within a larger compartment, and includes the API tetrathiomolybdate (TM) and active amount, including obvious selection of salt or free base forms. However, Cheng does not teach the specific species of ammonium tetrathiomolybdate (ATTM) (all instant claims).
Brewer teaches a method of treating inflammatory or fibrotic disease in a patient (abstract), using a therapeutic amount of tetrathiomolybdate (TM) or any thiomolybdate may be utilized as one or several of different salts ([0102]), such as ammonium (i.e., ammonium tetrathiomolybdate (ATTM)) [0103]. Brewer teaches ATTM, as one of several known TM salts, that is certified for human use, commercially-available, and has mild air instability [0103-0105].
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the tetrathiomolybdate taught by Cheng for the ATTM taught by Brewer, because Brewer teaches ATTM is a merely one of many salt forms of TM in general, and is useful for the treatment of disease (abstract, [0103]), and Cheng is interested in the controlled release of TM [0069] to specific locations of the GI to improve bioavailability [0005-0006]. Additionally, ATTM is certified for human use, and is commercially-available [0103-0105].
Claims 15-17, 20, 22-23, 26-28, 32-36, 40-49, 53, and 56-76 are rejected under 35 U.S.C. 103 as being unpatentable over Cheng (US20210128479A1) and Brewer (US20040009237A1), as evidenced by Kathpalia (J. Adv. Pharm. Edu. & Res. 2014), as applied to 15-17, 23, 27-28, 36, 40, 46, 56-71, and 73-75, and in further view of Kim (Journal of Nutritional Biochemistry, 2017), Drugs.com (Diethylcarbamazine (Oral), 2016), Wang (J. Excipients and Food Chem., 2014), and Kanzer (US20070207191A1), and Schor (US4389393A).
As discussed above, the combined Prior Art teaches a dosage form of controlled release at specific gastrointestinal sites, such as the stomach, small intestine, and large intestine, to improve bioavailability, that comprises multiple-layered structures (i.e., made from compartments, coats, shells, that include enteric coatings and/or extended release layers), whereby one compartment is housed within a larger compartment, and includes one or more APIs (whereby the API is housed in a material) and in a general dosage amount (i.e., 1-60 mg), and more specifically the API ATTM.
However, the combined Prior Art does not teach the API astaxanthin (ATX) (instant claims 20, 32, 34-35, 42, 47, 49, and 72), the API diethylcarbamazine (DEC) and amount (instant claims 22, 33-35, 41, 48-49, and 76), or that the filler comprises mesoporous dicalcium phosphate, colloidal silicon dioxide, or a combination thereof (instant claims 26), or ATTM particle size (instant claims 43-45), or water content of 2-3.5 wt% (instant claim 53).
Kim teaches that astaxanthin (ATX) (instant claims 20 and 42) is a xanthophyll carotenoid that inhibits inflammation and fibrosis in the liver and adipose tissue (Abstract). Note that Cheng teaches a general dosage of 1-60 mg as obvious [0071].
Drugs.com teaches diethylcarbamazine (DEC) (instant claims 21, 41, and 76) reduces inflammation (pg 5) and has a typical dose of 2-3 mg/kg (i.e., at 60 kg body weight, this would mean 120-180 mg dose) (pg 1).
Wang discloses a filler comprising colloidal silicon dioxide (instant claim 26) with a surface area of 200 m2/g called Aerosil 200®, used in the construction of bilayer tablets, whereby colloidal silicon dioxide is a moisture scavenger that helps avoid moisture driven process degradation via delamination in multi-compartment tablet manufacture (abstract, Table 1).
Kanzer teaches the size of the tetrathiomolybdate (including ATTM) crystal size (reads on “particle size” because Applicant Specification discusses ATTM within the framework of crystal size at [0165]) are controlled to provide selected, sustained or delayed release in the stomach and the intestines [0174-0175]. For example, smaller ATTM crystals (<50 um) rapidly dissolve in acidic buffer, while larger ATTM crystals (>1700 um) dissolve more slowly [0175]. Thus, the variability of dissolution rate renders the entire range as obvious for an oral ATTM formulation (instant claims 43-45), because with regard to the numerical range, note that "[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 2144.05(I)). Additionally, Kanzer discusses the stability issues inherent to tetrathiomolybdate, and that desiccation (protection from water) and sacrificial oxidation (protection from oxidation) are known techniques to improve stability [0173].
Schor teaches a solid unit dosage form having a carrier base material being hydroxypropyl methylcellulose (Abstract). The moisture content (i.e., water content) of the carrier used in the preparation of the sustained release tablets may be in the 0.1-10% range, the lower end of the range being preferable when moisture sensitive medicaments are used (col 5, lines 51-54).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the ATTM composition of Cheng and Brewer by adding DEC and ATX in obvious amounts, as taught by Drugs.com and Kim, because DEC and ATX have anti-inflammatory biological activity, and Cheng is directed to improving the bioavailability [0005-0006] of combination formulations (abstract) that comprise the anti-inflammatory tetrathiomolybdate (TM) [0069]. Furthermore, all of the configurations of ATTM, DEC, and ATX in various locations of the multi-layered formulation are made obvious by Zheng’s teaching of the general multi-layered formulation structures (i.e., discussed as obvious throughout the publication and exemplified by select embodiments).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the ATTM composition of Cheng and Brewer by adding colloidal silicon dioxide, as taught by Wang, because colloidal silicon dioxide is a moisture scavenger that helps avoid moisture driven process degradation via delamination in multi-compartment tablet manufacture (abstract, Table 1), whereby Brewer and Kanzer teach ATTM as sensitive to oxidative and moisture-based degradation. Furthermore, Cheng teaches “materials” generally (reads on filler) to be used in “compartments” [0089], whereby colloidal silicon dioxide is a common filler/excipient in tablet formulations.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the ATTM composition of Cheng and Brewer by specifying an ATTM small and/or large particle size, as taught by Kanzer, because small particle size allows for rapid dissolution while a larger particle size slows dissolution (i.e., a delayed action). Thus, Kanzer teaches the size of the tetrathiomolybdate crystals is controlled to provide selected, sustained or delayed release in the stomach and the intestines [0174], whereby, in complementary fashion, Cheng teaches a dosage form of controlled release at specific gastrointestinal sites, such as the stomach, small intestine, and large intestine (Cheng – claim 6), that comprises multiple compartments (abstract), that incorporates tetrathiomolybdate [0069].
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the ATTM composition of Cheng and Brewer by specifying a water content of 0.1-10%, because that is suitable sustained release tablet forms, with the lower end of the range being preferable when moisture sensitive medicaments are used (col 5, lines 51-54), whereby Brewer and Kanzer teach ATTM as sensitive to oxidative and moisture-based degradation. This coincides with Cheng’s ultimate goal of improving API bioavailability [0005], because lower moisture levels, ensure better stability of the API.
Response to Arguments
Applicants arguments, see pg 11-28, filed 05/18/2026, with respect to the 103 rejection of claims 15-17, 20, 22-23, 26-36, 38, 40-49, 53, and 56 under rejection have been fully considered but they are not persuasive. However, a new ground of rejection is established in this Office Action on the basis of incorporating Drugs.com as a more precise reference (i.e., Drugs.com explicitly teaches human diethylcarbamazine (DEC) dosage amounts), in comparison to Santos da Silva of the prior Office Action. Additionally, Kanzer explicitly teaches ATTM particle size and a motivation to optimize particle size (i.e., compared to the Office’s previous reliance on Cheng). Furthermore, the 103 rejection has been modified with respect to amendments made to the claim set (including movement of DEC out of independent claim 15), and new added claims.
On page 11-12, Applicant summarizes the instant composition by point to inventive example of Figure 1A (compared to comparative example of Figure 1B). Note that Cheng provides similar depictions of multi-compartmental formulations with spacer regions (i.e., inclusive of a “filler or physical barrier”):
Instant Drawings (Fig.1):
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Cheng [0112]:
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On page 12-16, Applicant argues a proposed “unexpected effect” (i.e., unexpected result) related to improved formulation stability (i.e., an unexpected ATTM stability), while Cheng is directed to release timing in the GI tract. While the Examiner understands the argument, a demonstration of unexpected results that are commensurate in scope with the claim set has not been made in comparison to Cheng (deemed the closet Prior Art). Thus, the current position with regard to Applicant’s proposed “unexpected effect” is that Cheng’s multi-compartment formulations (Cheng – claim 47) of tetrathiomolybdate (TM) [0069] that makes obvious different dimensions [0084-0100] would provide a similar protective effect toward TM (and/or the functionally equivalent ATTM, as taught by Kanzer) (i.e., the evidenced of this being Cheng’s formulations are taught to survive the moisture and oxygen filled GI tract environment).
Furthermore, the Art recognizes (especially, Kanzer) the stability issues inherent to tetrathiomolybdate (including salt forms of TM such as ATTM), and that desiccation (protection from water) and sacrificial oxidation (protection from oxidation) are known techniques to improve stability [0173-0175]. Additionally, the mechanism of sulfur-based degradation described on pg 12, is inherent to ATTM (as taught by the Prior Art). Therefore, stability issues of TM are known, and Cheng describes multi-compartment formulations that allow TM to successfully traverse the oxygen and moisture rich GI tract. Furthermore, Cheng does not describe any stability challenges related to the multi-compartment formulations of the disclosure.
Furthermore, the use of excipients to protect sensitive API to water and oxidation is known, and would be an expected benefit of multilayer formulations described by Cheng. As evidenced by Kathpalia (J. Adv. Pharm. Edu. & Res. 2014) Duo Cap Technology is a single, oral-dosage unit that comprises a capsule-in-capsule and offers broad therapeutic applications wherein the capsules may contain different actives for use with combination therapies or actives that are incompatible in a single capsule and the inner capsule may contain liquid, semi-solid, powder or pellet formulations and the outer capsule contains liquid or semi-solid formulations (page 169, D. Capsule). Additionally, Micro-FloraGuard™ is presented in a unique DuoCap - capsule in a capsule. The design enhances product stability by protecting the probiotic inner capsule in an HPMC capsule. This creates an effective barrier to moisture, which helps the probiotic remain inactive until it is consumed (page 170, first paragraph). Thus, a pill within a pill capsule design was known in the art previous to the filing date of the instant invention and further, such a design was known to protect the inner active ingredient within a capsule to provide enhanced stability. Furthermore, excipients such as pullulan and PVA provide an oxygen barrier for oxidation sensitive APIs (pg 167-168). With regard to Kathpalia’s ingredients, Cheng teaches Hypromellose (aka HPMC), PVA (polyvinylacetate), etc. [0012-0016] of the many compartments and layers (Cheng – claim 47) for TM [0069] to transit the GI tract (abstract).
Thus, the protection (from moisture and oxygen, which ATTM is known to be sensitive to) and the resulting improved stability afforded by the multi-compartment tetrathiomolybdate formulation of Cheng is expected by the combined Prior Art (i.e., similar capsule-in-capsule formulations, including certain excipients, are known to increase stability of APIs by preventing moisture and oxygen ingress, as discussed above by Kathpalia), whereby Applicant has not demonstrated criticality of range and/or ingredient combination (that is commensurate with the claim scope) to demonstrate the non-obviousness of the instant configuration, in comparison to the embodiments made obvious by Cheng. To establish unexpected results over a claimed range, applicants should compare a sufficient number of tests both inside and outside the claimed range to show the criticality of the claimed range. In re Hill, 284 F.2d 955, 128 USPQ 197 (CCPA 1960). Any range demonstrated as critical should be commensurate in scope with the claim set. The burden of explaining an unexpected result, based on objective data, is the responsibility of the Applicant.
Furthermore, the fact that Cheng teaches TM [0069] (including the obviousness of salt forms) to reach its target in the GI would mean that Cheng’s ATTM multi-compartment drug formulations survive the moisture and oxygen encountered (both in storage, and also while in transit to the GI target). Thus, the TM formulations of Cheng exhibit a stability against moisture and oxygen (even though Cheng does discuss stability in depth). Applicant has provided no objective evidence that the disclosure of Cheng in this configuration is inoperable, nor objective data that represents an unexpected result that contrasts with Cheng’s compositions.
Thus, the proper comparison to demonstrate unexpected results is not against “conventional dosage forms of ATTM” (as discussed on pg 17 of the remarks, paragraph 2) or “industry standard capsules having an enteric coating” but instead against the obvious TM (in which ATTM is an obvious salt form of TM) multi-compartment embodiments of Cheng.
Furthermore, simply providing the functional outcome (e.g., “barrier architecture designed to prevent oxygen permeation and moisture ingress into ATTM”) as a limitation of the claim set is not enough to demonstrate a claim scope that is commensurate with the proposed unexpected result, but it is unclear what specific limitation(s) allow for the functional outcome to occur (i.e., it is not readily apparent in the claim scope what would provide a measurable and significant unexpected result). By not claiming specific ranges in the instant claim scope, then there is no differentiation of the teachings of the instant claim scope and the obviousness demonstrated by the Prior Art, and the proposed unexpected result then becomes a result that is expected by the Prior Art. As discussed previously in the 103 rejection, the function outcomes of the compositions are intended uses that do not provide patentable weight in an obviousness analysis.
On page 16-18, Applicant recites case law to support the scientific argument which is noted. However, the Examiner is still not persuaded by the framework of the instant claims in spite of the recitation of case law, and the lack of objective data, which is required to support an unexpected result.
Specifically, Applicant has not demonstrated criticality of range and/or ingredient combination to obtain the unexpected result (which should also be commensurate with claim scope), to distinguish the instant invention from Cheng’s disclosure. The broader way the claim language is currently written, there is no way to distinguish the instant invention from an obvious embodiment of Cheng.
Where Applicant singles out Brewer and da Silva (note, swapped for Drugs.com, to teach DEC dosage of claim 41) for failing to recognizes Applicant’s specific problem to solve, note that in terms of obviousness, the motivation for obviousness can be different from Applicant: In an obviousness analysis, it is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006) (motivation question arises in the context of the general problem confronting the inventor rather than the specific problem solved by the invention); Cross Med. Prods., Inc. v. Medtronic Sofamor Danek, Inc., 424 F.3d 1293, 1323, 76 USPQ2d 1662, 1685 (Fed. Cir. 2005) (“One of ordinary skill in the art need not see the identical problem addressed in a prior art reference to be motivated to apply its teachings.”); In re Lintner, 458 F.2d 1013, 173 USPQ 560 (CCPA 1972) (discussed below); In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990), cert. denied, 500 U.S. 904 (1991). The rationale to combine references are provided in the 103 rejection above.
Furthermore, attacking references individually is per se unpersuasive, when it is the combined teachings that represent the Art. Thus, Brewer and da Silva teachings are combined with the other Art on record, and they are not required to teach all elements of the claim scope.
On page 19-20, Applicant refers to the April 10, 2025 Declaration (filed 04/16/2026); however, the data provided of the Declaration does not compare the instant composition against the teachings of Cheng (i.e., closest Prior Art). Note that any differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Consequently, we must determine whether the results obtained in the closest prior art and those set forth by Applicants are sufficiently different in kind, and not merely in degree, so as to be unexpected by a person of ordinary skill in the art at the time of invention. See Iron Grip Barbell Co. v. USA Sports, Inc., 392 F.3d 1317, 1322 (Fed. Cir. 2004) (Unexpected results that are probative of nonobviousness are those that are "different in kind and not merely in degree from the results of the prior art") (citation omitted). In this case, it is unclear what specific limitations of the instant claim scope (i.e., criticality of range and/or ingredient combination, as compared to the broader disclosure of Cheng) would lead to an unexpected improved stability over Cheng, whereby a protection of TM by Cheng’s multi-compartment formulations would already be expected, based on teachings of the Prior Art.
Furthermore, as stated before, the fact that Cheng teaches TM [0069] (which is noted by Kanzer, as functionally equivalent to ATTM) to reach its target in the GI would mean that Cheng’s TM multi-compartment drug formulations survive the moisture and oxygen encountered in transit to the GI target and on storage. Applicant has provided no objective evidence that the disclosure of Cheng in this configuration is inoperable, nor objective data that represents an unexpected result that contrasts with Cheng’s compositions.
On page 20- 21, Applicant attacks Cheng for only teaching selective release within the GI tract, and remaining silent on chemical and/or storage stability.
First the motivation for obviousness can be different from Applicant: In an obviousness analysis, it is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006) (motivation question arises in the context of the general problem confronting the inventor rather than the specific problem solved by the invention); Cross Med. Prods., Inc. v. Medtronic Sofamor Danek, Inc., 424 F.3d 1293, 1323, 76 USPQ2d 1662, 1685 (Fed. Cir. 2005) (“One of ordinary skill in the art need not see the identical problem addressed in a prior art reference to be motivated to apply its teachings.”); In re Lintner, 458 F.2d 1013, 173 USPQ 560 (CCPA 1972) (discussed below); In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990), cert. denied, 500 U.S. 904 (1991). Thus, for obviousness, the selective release in the GI is sufficient rationale to select Cheng’s teachings compared to the instant composition.
Second, in terms of unexpected results: In this case, the beneficial results are expected based on the teachings of the prior art: “Expected beneficial results are evidence of obviousness of a claimed invention, just as unexpected results are evidence of unobviousness thereof.” In re Gershon, 372 F.2d 535, 538, 152 USPQ 602, 604 (CCPA 1967), see also In re Skoner, 517 F.2d 947, 950 (CCPA 1975). As discussed above, Kanzer teaches sensitivity of ATTM, and Kathpalia demonstrates the success of capsule in capsule formulations providing added protection to APIs, including common excipients that protect against oxidation and/or moisture. Thus, a PHOSITA would reasonably expect that the TM loaded multi-compartmental configurations of Cheng would afford improved stability of TM, which is demonstrated by the fact that Cheng’s TM multi-layered capsules survive the moisture and oxygen of GI transit (abstract).
On page 21, Applicant argues that Brewer teaches away from using the ATTM species due to its instability. However, in contrast to this position, Brewer teaches methods of treating patients using tetrathiomolybdate (Brewer – claim 4), including the ammonium ATTM variant [0104-0106]. So, this point is not persuasive. Furthermore, Cheng teaches general use of tetrathiomolybdate (TM) molecules, whereby a salt form is obvious [0069], where Brewer names ATTM as a species of this general class of compounds [0104-0106]. Also, Brewer teaches ATTM, as one of several known TM salts, that is certified for human use and is commercially-available, providing additional motivation to use ATTM for therapeutic use.
On pg 21-22, Applicant argues there is no reasonable expectation of success for the combined elements. For reasonable expectation of success note: With regard to reasonable expectation of success: “Applicants are reminded that obviousness does not require absolute predictability. See In re Rinehart, 531 F.2d 1048, 189 USPQ 143 (CCPA 1976) (indicating that evidence showing there was no reasonable expectation of success may support a conclusion of nonobviousness).” Sufficient rationale was provided in the 103 rejection to combine the Art elements. Furthermore, Applicant has not provided evidence that unpredictability of the art to challenge the obviousness of the modification, in the face of Cheng teaching TM multi-compartmental drug formulations that successfully transit the moisture and oxygen filled GI tract.
On pg 22, Applicant argues that a PHOSITA would not consider the combination of two active ingredients (e.g., ATTM + DEC). However, Cheng teaches many embodiments that comprise one or more APIs (an ingredient with biological activity), whereby Drugs.com teaches DEC as an API with biological activity. Thus, the combination of ATTM and DEC is obvious. Furthermore, DEC and ATTM have anti-inflammatory biological activity, and thus the combination of these APIs for the benefit of additive anti-inflammatory activity is also obvious.
On page 22-24, Applicant discusses the Declaration. For conciseness, this section of remarks will be addressed in the ‘response to amendment’ section below, in combination with the Declaration remarks.
On page 24, Applicant argues that a PHOSITA would not consider the combination of two active ingredients (e.g., ATTM + ATX). However, Cheng teaches many embodiments that comprise one or more APIs (an ingredient with biological activity), whereby Kim teaches ATX as an API with biological activity. Thus, the combination of ATTM and ATX is obvious. Furthermore, ATX and ATTM have anti-inflammatory biological activity, and thus the combination of these APIs for the benefit of additive anti-inflammatory activity is also obvious.
Regarding the additional role of ATX (i.e., the stabilization of ATTM), note that for obviousness, the rationale for combination need not be the same as Applicant: In an obviousness analysis, it is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006) (motivation question arises in the context of the general problem confronting the inventor rather than the specific problem solved by the invention); Cross Med. Prods., Inc. v. Medtronic Sofamor Danek, Inc., 424 F.3d 1293, 1323, 76 USPQ2d 1662, 1685 (Fed. Cir. 2005) (“One of ordinary skill in the art need not see the identical problem addressed in a prior art reference to be motivated to apply its teachings.”); In re Lintner, 458 F.2d 1013, 173 USPQ 560 (CCPA 1972) (discussed below); In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990), cert. denied, 500 U.S. 904 (1991). Thus, the biological activity of ATX (and also DEC) is suitable rationale to modify Cheng, when Cheng teaches incorporation of APIs (compounds with biological activity) including TM [0067-0069].
Furthermore, Applicant has not attempted to demonstrate ATX’s stabilization of ATTM through objective data, in the form of an unexpected result (i.e., improved barrier properties of the system) that stems from ATX incorporation into the ATTM formulation.
On page 25, Applicant argues against Wang and Schor; however, attack of individual references is per se unpersuasive, because these references teach limitations specific to the claim set, where proper rationale for combination has been provided in the 103 above.
On page 26, Applicant argues against the evidentiary use of Kathpalia. Note that the broader teaching of Kathpalia (i.e., capsule-in-capsule units are used to enhance stability) does not depend on teaching every single limitation of the claim set, because it is reasonably relevant to the Application’s subject matter of multi-compartmental formulations. Instead, it is the teachings of Kathpalia as a whole that apply in an evidentiary teaching. Thus, Kathpalia describes capsule-in-capsule formulations and certain excipient ingredients (i.e., that protect against moisture and oxygen) proving stability enhancements as expected benefits (i.e., as in the multi-layered compositions of Cheng, even if Cheng is silent on the stability aspect/advantage of the disclosure). With regard to Kathpalia’s ingredients, Cheng teaches Hypromellose (aka HPMC), PVA (polyvinylacetate), etc. [0012-0016] of the many compartments and layers (Cheng – claim 47) for TM [0069] to transit the GI tract (abstract).
On page 26-27, Applicant discusses support from the Specification, for newly added claims, which is acceptable.
On page 28, Applicant concludes. The Examiner reiterates that the proposed unexpected result would be expected within the embodiments of Cheng, based on the Art, and the objective data provided is generally not sufficient to distinguish a proposed unexpected result of the instant disclosure from the disclosure of Zheng. Thus, the claims remain under 103 rejection as obvious.
Response to Amendment
The affidavit under 37 CFR 1.132 filed 05/18/2026 is insufficient to overcome the rejection of claims 15-17, 20, 22-23, 26-36, 38, 40-49, 53, and 56 based upon the 103 rejection as set forth in the last Office action because of the reasons below, in response to specific points made within the affidavit:
Parts I and II (pg 1-2) sets up the more detailed points (discussed below).
In response to III (pg 2): The Prior Art (especially, Kanzer) discusses the stability issues inherent to tetrathiomolybdate, and that desiccation (protection from water) and sacrificial oxidation (protection from oxidation) are known techniques to improve stability [0173]. Additionally, the mechanism of sulfur-based degradation described on pg 12, is inherent to ATTM.
Furthermore, the use of excipients to protect sensitive API to water and oxidation is known, and would be an expected benefit of multilayer formulations described by Cheng. As evidenced by Kathpalia (J. Adv. Pharm. Edu. & Res. 2014) Duo Cap Technology is a single, oral-dosage unit that comprises a capsule-in-capsule and offers broad therapeutic applications wherein the capsules may contain different actives for use with combination therapies or actives that are incompatible in a single capsule and the inner capsule may contain liquid, semi-solid, powder or pellet formulations and the outer capsule contains liquid or semi-solid formulations (page 169, D. Capsule). Additionally, Micro-FloraGuard™ is presented in a unique DuoCap - capsule in a capsule. The design enhances product stability by protecting the probiotic inner capsule in an HPMC capsule. This creates an effective barrier to moisture, which helps the probiotic remain inactive until it is consumed (page 170, first paragraph). Thus, a pill within a pill capsule design was known in the art previous to the filing date of the instant invention and further, such a design was known to protect the inner active ingredient within a capsule to provide enhanced stability. Furthermore, excipients such as pullulan and PVA provide an oxygen barrier for oxidation sensitive APIs (pg 167-168). With regard to Kathpalia’s ingredients, Cheng teaches Hypromellose (aka HPMC), PVA (polyvinyl acetate), etc. [0012-0016] of the many compartments and layers (Cheng – claim 47) for TM [0069] to transit the GI tract (abstract).
Thus, the protection (from moisture and oxygen, which ATTM is known to be sensitive to) and the resulting added stability afforded by the multi-compartment tetrathiomolybdate (TM) formulation of Cheng is expected by the Art (whereby , and Applicant has not demonstrated criticality of range and/or ingredient combination (that is commensurate with the claim scope) to demonstrate the non-obviousness of this configuration.
In response to obviousness of the “barrier architecture” of IV (pg 2-3): Note that Zheng teaches the obviousness of a solution that goes beyond an enteric coat, as discussed above and recited here: “Cheng teaches a dosage form of controlled release at specific gastrointestinal sites, such as the stomach, small intestine, and large intestine (Cheng – claim 6), that comprises multiple compartments (abstract), whereby one compartment is within a larger compartment (Cheng – claim 47, for embodiments, see Figures)….(i.e., a “compartment” is defined to contain API or a material different from that from the compartment (reads on “filler or physical barrier”) [0089], whereby materials are extensively discussed [0012, 0016, etc.] in many exemplary configurations [0017-0022, etc.]).” Thus, Cheng teaches the obviousness of a “first capsule within a second capsule.”
In response to V (pg 3): The conventional ATTM capsules of the comparative data are not representative of the closest Prior Art being Zheng. Furthermore, all the benefits attributed to the instant invention and generally found within the Prior Art as expected benefits. Thus, when the invention is taught as obvious, and there is no objective data to demonstrate non-obviousness in relation to the combined Prior Art (including the benefits that are expected by the Prior Art), then the claim set remains rejected under obviousness.
In response to the “unexpected activity” of VI and VII (pg 3-5 of Affidavit): While the conventional approach of applying an enteric coat is claimed to fail, note that Zheng teaches the obviousness of a solution that goes beyond an enteric coat, as discussed above and recited here: “Cheng teaches a dosage form of controlled release at specific gastrointestinal sites, such as the stomach, small intestine, and large intestine (Cheng – claim 6), that comprises multiple compartments (abstract), whereby one compartment is within a larger compartment (Cheng – claim 47, for embodiments, see Figures)….(i.e., a “compartment” is defined to contain API or a material different from that from the compartment (reads on “filler or physical barrier”) [0089], whereby materials are extensively discussed [0012, 0016, etc.] in many exemplary configurations [0017-0022, etc.]).” Thus, Cheng teaches the obviousness of a “first capsule within a second capsule.”
With respect to conventional barrier thickness or layering, there is no claim limitation that demonstrates how the compositions of instant claims 15 and/or 65, differ from “conventional” thickness. Note that claiming functionality alone (e.g., “reduces exposure of the ATTM to moisture and oxygen” in claim 65, etc.) is not sufficient to capture the claim scope, because the claim scope does detail how a PHOSITA would achieve this goal, when Applicant has already stated that conventional barrier thickness or layering is insufficient. In order to claim criticality of range (and/or ingredient combination) for an unexpected resulted, some objective evidence must be provided in support of the numerical range (i.e., the unexpected result is consistently obtained), whereby the range is also a claimed limitation that consistently produces the unexpected result.
Further note, in terms of obviousness of shell/filler/coating space/thickness (and also the wide variability of shell/filler thickness), Cheng teaches exemplary values for the multi-layer formulations [0082-0100] (i.e., demonstrating the instant “physical barrier” of claim 15). For example, Cheng teaches: “In some embodiment, each layer of the multi-layered structure has a thickness of about any of 0.05 mm, 0.1 mm, 0.15 mm, 0.2 mm, 0.25 mm, 0.3 mm, 0.35 mm, 0.4 mm, 0.45 mm, 0.5 mm, 0.55 mm, 0.6 mm, 0.65 mm, 0.7 mm, 0.75 mm, 0.8 mm, 0.85 mm, 0.9 mm, 0.95 mm, or 1 mm” [0100].
In this regard, compare Applicant’s inventive (Figure 1A) and comparative (Figure 1B) embodiments to Cheng’s inventive embodiment, where Cheng places the protected API 112 away from the outer shell, providing the same “physical” separation/barrier. Thus, Applicant has not provided a limitation or value (e.g., by objecting demonstrating criticality of compartment size or wall size) in the instant claim scope that differs the instant invention from an obvious embodiment of Cheng.
Instant Drawings (Fig.1):
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Cheng [0112]:
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Furthermore, the anecdotal data point (pg 4, point VII), regarding a TTM capsule being stored for 1 year with a biological response is not meaningful with regard to controls (and/or comparators), examining stability result(s) in terms of the unexpected result being commensurate with claim scope, and additional contextual information. To counteract an obviousness rejection: “[A]ppellants have the burden of explaining the data…they proffer as evidence of non-obviousness.” Ex parte Ishizaka, 24 USPQ2d 1621, 1624 (Bd. Pat. App. & Inter. 1992). The evidence relied upon should establish “that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance.” Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992).
Thus, the proper comparison to demonstrate unexpected results is not against “conventional dosage forms of ATTM” or “industry standard capsules having an enteric coating” but instead against the obvious TM (whereby ATTM is an obvious salt form of the larger TM genus) multi-compartment embodiments of Cheng, whereby a demonstration of criticality of a claimed range may be necessary to provide distinction from Cheng.
Furthermore, Applicant does not point to objective data, representing specific claimed configurations (e.g., instant claim 32-34, etc.), that would form the basis for secondary considerations, such as unexpected results.
Note, the Examiner also addresses the data of the previous Affidavit (filed 4/16/25) in the ‘Response to Arguments’ section above.
Correspondence
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/R.P./Examiner, Art Unit 1614 6/29/2026
/ALI SOROUSH/Supervisory Patent Examiner, Art Unit 1614
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