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, filed 9 December, 2023, is a CON of Application 18/088,692 filed 26 December, 2022, a CON of Application 16/966,892, filed 1 August, 2022, which is a national stage application of PCT/EP2019/052492, filed 1 February, 2019, which claims benefit of the prior filed application PRO 62/625,354, filed 2 February, 2018.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 19 January, 2026 has been entered.
Status of the Application
Receipt is acknowledged of Applicant's claimed invention, filed 19 January, 2026, in the matter of Application N° 18/534,576. Said documents have been entered on the record.
Claim 23 has been amended. No new matter was introduced.
Thus, Claims 23-33 represent all claims currently under consideration.
Specification
Examiner notes: Applicant’s remarks refer to paragraph numbering in the published application (Remarks, Pg. 5, Linking Table). For consistency and clarity, the present action cites to the paragraph numbering of the instant specification, which corresponds to the same disclosure (including Example 3, tables and figures) in a more complete form.
The disclosure is objected to because of the following informalities: instant Specification, Example 3, Para 0174 refers to “FIG. 5A.”; however, the drawings and the description of the drawings only include “FIG. 5.” Accordingly, the specification and drawings are inconsistent. Applicant is required to correct this inconsistency by either: (i) amending the specification to refer to “FIG. 5,” or (ii) providing corrected drawings including “FIG. 5A,” as appropriate.
Response to Amendment/Arguments
Applicant’s amendment is sufficient to overcome the previous rejections of Claims under 35 U.S.C. 102(a)(1) and 103.
Regarding claim interpretation, Applicant's arguments (Remarks, Pg. 5-7) filed 19 January, 2026 have been fully considered but they are not persuasive.
Applicant’s interpretation of the “formulation means” limitation as requiring “a uniform formulation comprising throughout a release-retarding agent” is not supported by the specification. The specification does not describe a “uniform formulation” as a structural requirement. Rather, references to “uniform” in the specification relate to the release profile (i.e., uniform release), which is a functional result, not a structural feature of the formulation.
As construed under 35 U.S.C. 112(f), the limitation “a formulation means for providing sustained release of colchicine resulting in less than approximately 70% of the drug being released in vitro within about 2 hours at 37 °C” encompasses the corresponding structures disclosed in the specification including hydrophilic matrix formulations comprising a release-retarding agent (e.g., RETALAC®,) such as those described in Example 3, and equivalents thereof.
Accordingly, Applicant’s proposed construction improperly imports a limitation that is not supported by the specification and is not adopted.
Below can be found new grounds of rejection necessitated by amendments.
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 23-33 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 certain embodiments, does not reasonably enable the full scope of the claimed invention without undue experimentation.
As construed under 35 U.S.C. 112(f), the limitation “a formulation means for providing sustained release of colchicine resulting in less than approximately 70% of the drug being released in vitro within about 2 hours at 37 °C” encompasses the corresponding structures disclosed in the specification including hydrophilic matrix formulations comprising a release-retarding agent (e.g., RETALAC®,) such as those described in Example 3, and equivalents thereof.
The claim requires achieving a specific dissolution profile under defined conditions (in water with stirring at 37 °C). However, the specification provides only limited and non-generalizable guidance for achieving this performance. In particular, Example 3 (instant Specification, Para 0167) evaluates multiple formulations varying in RETALAC® concentration and tablet compression strength, and demonstrates substantial variability in dissolution behavior across tested batches.
Notably, the specification presents multiple sets of dissolution data (e.g., Fig. 3 and Fig. 6) that use differing vertical axis descriptors, such as “drug release (%)” and “drug dissolved in %,” without clearly defining or distinguishing these terms or explaining their relationship. While both figures are described as “dissolution profiles” (instant Specification, Para 0171 – “FIG. 3 shows the dissolution profiles for Batches 1-4” and Para 0175 – “The dissolution profiles of the four compositions [of Batch 4] are shown in FIG. 6”), the specification does not adequately clarify whether the measurements are equivalent or how the data should be interpreted relative to one another. As a result, it is unclear how one of ordinary skill in the art would use the disclosed data to predicably achieve the claimed dissolution profile.
Additionally, the specification acknowledges that the balance between erosion and diffusion “is very sensitive and has to be fine-tuned to reach a very specific dissolution profile” (instant Specification, Para 0176), indicating that achieving the claimed dissolution characteristics depends on precise adjustment of formulation parameters and is not readily predictable based on the disclosure.
The specification also discloses dosage amounts of colchicine, including a range of about 0.25-0.75 mg and a specific value of about 0.5 mg (instant Specification, Para 0099). While the claimed dosage of about 0.6 mg falls within the disclosed range, the specification does not demonstrate that the specific formulations disclosed, such as the hydrophilic matrix systems described in Example 3, when comprising the claimed dosage amount, achieve the claimed dissolution profile. Nor does the specification provide sufficient guidance linking dosage, formulation parameters, and release behavior in a predictive manner.
Accordingly, one of ordinary skill in the art would be required to engage in undue experimentation, involving iterative trial-and-error across multiple formulation parameters, to identify formulations that satisfy the claimed dissolution limitation. Therefore, the specification does not enable the full scope of the claimed invention.
Claims 24-33 are dependent from Claim 23, and fail to cure the deficiencies as
stated above.
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 29-33 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 29 recites “at least one other immune modulating therapy,” which lacks proper antecedent basis and renders the scope of the claim unclear.
Additionally, the term “immune modulating therapy,” as recited in Claim 29, lacks clarity due to inconsistent usage in the dependent claims. Specifically, Claim 30 defines the immune modulating therapy as one or more of interleukins, cytokines, chemokines, and antagonists of immune checkpoint blockades, which are classes of molecular agents that directly modulate immune function. In contrast, Claim 31 defines the immune modulating therapy as a “cancer therapy,” and Claim 32 further defines the cancer therapy as including surgery, radiation therapy, and chemotherapy, which are treatment modalities and are not necessarily immune-modulating.
Accordingly, it is unclear whether the term “immune modulating therapy” is limited to therapies that directly modulate immune function or instead broadly encompasses any cancer treatment modality. This inconsistent characterization renders the scope of the claims unclear.
Additionally, Claim 33 recites that the colchicine and the immune modulating therapy are administered “separately or concurrently,” which is inconsistent with Claim 29 requiring concurrent administration, thereby further obscuring the scope of the claims.
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.
Claim 33 is 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.
Claim 33 depends from Claim 29, which requires that the colchicine and the immune modulating therapy are administered concurrently. However, Claim 33 recites that the combination is administered “separately or concurrently,” which broadens the scope of the method beyond that of Claim 29.
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
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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 23-28 are rejected under 35 U.S.C. 103 as being unpatentable over He et al. (CN 101485637 B, of previous record), hereinafter He, and Riel, S. (US 2016/0081936 A1), hereinafter Riel.
‘936 shares Assignee with instant Application.
Regarding Claims 23-24, 26 and 28, He teaches a sustained release tablet (‘637, Para 0002) comprising 0.5 mg of colchicine (‘637, Para 0061). The formulation is used for its anti-inflammatory properties for treating gout and for treating cancer, such as leukemia and breast carcinoma, by suppressing cell mitosis (‘637, Para 0004). Further, He discloses a dissolution profile under defined conditions – in purified water, 100 rev/min, at 37 °C (‘637, Para 0055), with a release profile at 2 hours below 70% (‘637, Fig. 2.)
He fails to teach a dosage of 0.6 mg of colchicine, nor explicitly disclose inhibition of IL-1B mediated responses (as in instant Claim 25) or release of TNF-a and IL-10 (as in instant Claim 27.)
However, Riel teaches a sustained-release colchicine formulation for the treatment of an inflammatory disorder (‘936, Para 0044), which is administered at a daily dose of colchicine of between about 0.25 mg to about 0.75 mg (‘936, Para 0124), and further, that “in all known indications, [colchicine] is generally administered orally as solid tablets in strengths of 0.5-0.6 mg/tablet” (‘936, Para 0042). The formulations and dissolution data presented in Riel (e.g., Example 3 - Para 0142-0148, Tables 2-7, and Figures 2-3,) correspond to the same or substantially the same subject matter as that relied upon in the instant specification, demonstrating sustained-release colchicine formulations with comparable composition and dissolution behavior.
Claims 25 and 27, recite that the formulation inhibits IL-1B mediated signaling and inhibits release of TNF-a and IL-10. However, such effects are known to be associated with the pharmacological activity of colchicine as an anti-inflammatory agent, as evidenced by Riel (‘936, Para 0041-0042) and the general knowledge in the art.
The instant specification does not demonstrate that these effects are dependent upon or uniquely attributable to the claimed sustained-release formulation. Rather, such effects would have been reasonably expected to occur upon administration of colchicine, regardless of whether the drug is delivered in an immediate-release or sustained-release form.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to modify the method of He by administering colchicine in a sustained-release formulation as taught by Riel. He teaches the use of a sustained-release colchicine for treating cancer, including by suppression of cell mitosis which would have been understood to inhibit or reduce tumor growth, while Riel teaches sustained-release colchicine formulations, including hydrophilic matrix systems, that provide controlled drug release and improved dosing characteristics.
One of ordinary skill in the art would have been motivated to employ such sustained-release formulations in the method of He in order to achieve known advantages of sustained drug delivery, including patient compliance, reduced dosing frequency, and more consistent plasma drug levels. Furthermore, the therapeutic effects of colchicine are attributable to the pharmacological activity of the drug itself, which is known to exhibit anti-inflammatory and anti-mitotic properties across multiple disease indications. Accordingly, one of ordinary skill in the art would have reasonably expected that administering colchicine in a sustained-release formulation would maintain these known therapeutic effects while benefitting from the improved delivery characteristics taught by Riel.
Claims 29-33 are rejected under 35 U.S.C. 103 as being unpatentable over He and Riel as applied to Claims 23-28 above, and further in view of Bosch et al. (WO 2015/069770 A1, of previous record), hereinafter Bosch.
The teachings of He and Riel are set forth in the above 35 U.S.C. 103 Rejections and are incorporated herein. He and Riel together teach a method of inhibiting or reducing tumor growth in a subject diagnosed or suffering from cancer, by administration of a daily, oral composition comprising 0.5-0.6 mg of colchicine in a sustained-released formulation resulting in less than 70% of the drug being released in vitro within 2 hours at 37 °C.
He and Riel fail to teach the subject is concurrently administered an effective amount of at least one immune modulating therapy.
However, Bosch teaches a pharmaceutical composition comprising a checkpoint inhibitor and a therapeutic for treating cancer to enhance or prolong the anti-tumor response (‘770, Para 0012 and 0021. Additionally, the combination can delay tumor recurrence, tumor growth or tumor spread (‘770, Para 0029).
It would have been prima facie obvious to further modify the method of He and Riel by administering a sustained release colchicine formulation in combination with an immune modulating therapy as taught by Bosch, as it is well established in the art that cancer therapies are frequently combined to enhance therapeutic efficacy through complementary mechanism of action. One of ordinary skill in the art would have had a reasonable expectation of success in combining these known therapies for treating cancer.
"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) See MPEP
§
2144.06(I).
Communication
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/D.M.N./ Examiner, Art Unit 1627
/SARAH PIHONAK/ Primary Examiner, Art Unit 1627