Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
In view of Applicant's amendments, the groups of inventions which are not so linked as to form a single general inventive concept under PCT Rule 13.1 have been updated and set forth below:
Group I, claims 1-4, 6, 8, 10-16 drawn to an alginate gel particle and kit.
Group II, claims 7 & 17, drawn to a method for preparing an alginate gel particle.
However, the restriction requirement remains proper for the reasons provided below and in the CTRS of 7/7/2026.
Applicant's election with traverse of Group I in the reply filed on 9/8/2026 is acknowledged. The traversal is on the grounds that:
(1) Group I and Group II are drawn to a product, a process specially adapted for the manufacture of the said product, and a use of the said product; and therefore, the claims are so linked as to form a single general inventive concept, and all indeed possess unity of invention, since each of Group I and II claims possess the same corresponding technical features and are so linked to form a single general inventive concept, and hence, comply with at least 37 CFR § 1.475(b)(3); and
(2) Jolk's describes a "formulation comprising nano-sized solid particles and a gel forming system. Hence, the invention provides a special technical feature making a contribution over the prior art.
This is not found persuasive because 37 CFR 1.475(b) does not override the requirement of a technical relationship among those inventions outlined in 37 CFR 1.475(a). The present application recites 3 different inventions (a product, a process specially adapted for the manufacture of the product, and the use of the product). A process is "specially adapted" for the manufacture of a product if the claimed process inherently produces the claimed product with the technical relationship being present between the claimed process and the claimed product. MPEP 1893.03(d). A "technical relationship" is a relationship involving one or more of the same or corresponding special technical features. 37 CFR 1.475(a). When no such technical relationship exists, the claims cannot be considered to fall within the combinations outlined in 37 CFR 1.475(b). Therefore, the group of inventions must have a technical relationship among them to satisfy the requirement of unity of invention. In the present case, Group I and Group II lack a technical relationship for the reasons provided in the CTRS of 7/7/2026 and therefore do not comply with 37 CFR § 1.475(b)(3).
Moreover, Applicant's arguments are not persuasive because the phrase "the gel composition" refers to the composition of matter recited in claim 1. A composition of matter is a combination of two or more substances and includes all composite articles, no matter the form (i.e., whether they be gases, fluids, powders or solids). Thus, in identifying a composition of matter, there is no meaningful distinction between an "alginate gel," an "alginate gel particle," or the "gel [alginate] composition" because they are all compositions of matter regardless of their form. To that end, the technical features outlined in the CTRS of 7/7/2026 are identical to the technical features purported by the Applicant above. Furthermore, Applicant's assertions regarding Jolk's disclosure rely on teachings that are neither cited nor necessary to establish that the claimed technical feature is not a special technical feature. The expression "special technical features" is defined as technical features that define the contribution which each claimed invention, considered as a whole, makes over the prior art. MPEP 1893.03(d). Notably, a special technical feature does not require that the prior art recite the same purpose as the claimed technical feature or disclose a specific embodiment of the claimed technical feature. Accordingly, the Office maintains that the claimed technical feature is not a special technical feature because it does not make a contribution over the prior art for the reasons provided in the CTRS dated 7/7/2026.
The requirement is still deemed proper and is therefore made FINAL.
Applicant's election of radium-223, radium-224, and actinium-225 in the reply filed on 9/8/2026 is acknowledged. Applicant's election is directed to more than one species (radium-223, radium-224, and actinium-225) and is therefore nonresponsive to the requirement to elect a single species. Applicant must make their own election; the examiner will not make the election for the applicant. MPEP 818. To the extent that Applicant contends that radium-223, radium-224, and actinium-225 are patentably indistinct from one another, Applicant should explicitly state so. Otherwise, radium-223, radium-224, and actinium-225 are treated as distinct species that require a single election.
Status of Claims
Cancelled: 5, 9
Withdrawn: 7, 17
Examined Herein: 1-4, 6, 8, 10-16
Priority
Acknowledgment is made of applicant's claim for priority under based upon an application filed in NO20211268 on 10/21/2021 and PCT/EP2022/079090 on 10/19/2022. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 7/22/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings received on 4/19/2024 are accepted.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 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.
Claim 15 rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 15 recites the limitation “The alginate gel particle according to claim 1 or the composition according to claim 8…wherein the gel or composition is administered.” This limitation renders the claim indefinite because it claims both a product and method steps of using the product. As a result, it is unclear when direct infringement occurs. MPEP 2173.05(p).
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:
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 1-4, 6, 8, and 11-16 are rejected under 35 U.S.C. 103 as being unpatentable over Ramdahl (US 2015/0306257 A1, Published 10/29/2015), in view of Melvik (US 2011/0053886 A1, Published 3/3/2011).
With respect to claim 1, Ramdahl discloses an alginate gel particle comprising:
an alginate gel bead
a divalent cation, sr2+ or ca2+
a radionuclide, bismuth-211, lead-211, radium-223, and/or thorium-227
wherein the alginate chelates (bind/capture) the divalent cations and the radionuclides. [Ramdahl, 0055, 0066, 0070, 0071, 0073, 0076, 0079, 0086, 0087, 0092]
With respect to claim 8, Ramdahl discloses a composition comprising the alginate gel particle and a pharmaceutically acceptable carrier, diluent, and excipient, including saline or PBS. [Ramdahl, 0066, 0070, 0073, 0076, 0079, 0087, 0092]
With respect to claims 11-14, the limitations "for use as a medicament" and "for use in the treatment of a proliferative disease (cancer, hyperplastic, neoplastic)" recite an intended use. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. Ramdahl discloses that the alginate gel particle is suitable for use as a medicament or for treating a proliferative disease. [Ramdahl, 0001-0003, 0014, 0027, 0057-0059] Therefore, this limitation does not patentably distinguish the claimed invention from the prior art.
With respect to claim 15, the limitation "wherein the gel or composition is administered" does not limit the scope of claim 1 or 8. Claim scope is not limited by claim language that does not limit a claim to a particular structure. Administering the gel or composition does not limit the structure of the gel or composition. Therefore, this limitation does not patentably distinguish the claimed invention from the prior art.
Ramdahl does not disclose that the alginate gel particle comprises at least one peptide having a peptide sequence for interacting with a receptor of a cell affected by a proliferative disease (claim 1), that the radionuclide cation is located less than 100 μm below the surface of the alginate gel particle (claim 6), or that the particle is a nanoparticle or a microparticle with a diameter of 1 nm to 1000 μm (claim 16).
However, with respect to claims 1-4, Melvik discloses an alginate gel particle comprising:
an alginate gel particle
a divalent cation, Ca2+
[Melvik, 0045, 0096-0108]
Melvik further discloses that the composition may further comprise a peptide coupled to the alginate gel, including RGD, YIGSR, IKVAV, REDV, DGEA, GRGDS, LDV, RGDV, RGDS, RGDF, HHLGGALQAGDV, GREDVY, GRGDY, GRDSP, GGGGRGDSP, GGGGRGDY. [Melvik, 0059-0062] All of these peptides comprise integrin-binding sequences. Melvik discloses that techniques for coupling peptides to alginate are known in the art. [Melvik, 0063] Moreover, peptide-coupled alginates like NOVATACH RGD, which comprises RGD peptide-coupled alginate, are commercially available. [Melvik, 0063] Melvik discloses that peptide-coupled alginates may be used, for example, in immobilizing cells to promote cell proliferation and cell differentiation. [Melvik, 0061]
With respect to claims 6 and 16, Melvik discloses that the alginate gel particle has a particle size of 25-175 um. [Melvik, 0071, Claim 1 & 26] Melvik discloses that the particle size of the gel may be controlled by milling and sifting the alginate. [Melvik, 0057-0058, 0071] Melvik further discloses that the smaller the particle size, the more rapidly gel formation completes, and that larger particle sizes produce stronger gels. [Melvik, 0071]
Modifying the alginate gel particle disclosed by Ramdahl by coupling a peptide selected from RGD, YIGSR, IKVAV, REDV, DGEA, GRGDS, LDV, RGDV, RGDS, RGDF, HHLGGALQAGDV, GREDVY, GRGDY, GRDSP, GGGGRGDSP, GGGGRGDY to the particle results in the alginate gel particle of claims 1, 2, 3 and/or 4.
Modifying the particle size of the alginate gel particles disclosed by Ramdahl to 25-175 µm results in the alginate gel particle of claims 6 and 16.
Specifically, with respect to claim 6, Ramdahl discloses that the alginate gel particle captures the radionuclide. If the particle size of the alginate gel disclosed by Ramdahl is 25-175 µm, then nothing inside the bead can be located more than 87.5 µm from the surface of the bead because the distance from any interior point in the bead to the surface of the bead is limited by the radius of the bead. Therefore, the radionuclide captured within the alginate gel particle disclosed by Ramdahl and Melvik is necessarily less than 100 µm.
It would be obvious to one of ordinary skill in the art to modify the alginate gel particle disclosed by Ramdahl by coupling a peptide selected from RGD, YIGSR, IKVAV, REDV, DGEA, GRGDS, LDV, RGDV, RGDS, RGDF, HHLGGALQAGDV, GREDVY, GRGDY, GRDSP, GGGGRGDSP, GGGGRGDY to the particle and have a reasonable expectation of success. Ramdahl discloses an alginate gel particle comprising a divalent cation and a radionuclide. Melvik discloses an alginate gel particle comprising a divalent cation. Melvik further discloses that a peptide selected from RGD, YIGSR, IKVAV, REDV, DGEA, GRGDS, LDV, RGDV, RGDS, RGDF, HHLGGALQAGDV, GREDVY, GRGDY, GRDSP, and GGGGRGDSP, or GGGGRGDY may be coupled to the alginate gel particle, thereby forming a peptide-coupled alginate. Melvik further discloses that said coupling may be accomplished through techniques known in the art and that RGD peptide-coupled alginate is commercially available. Accordingly, the combined teachings of Ramdahl and Melvik reasonably suggest that the aforementioned peptides may be coupled to the alginate gel particle disclosed by Ramdahl. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II). In the present case, Melvik discloses that peptide-coupled alginates may be used, for example, to immobilize cells to promote cell proliferation and cell differentiation. [Melvik, 0062] Therefore, one would have been motivated by the expectation that coupling a cell-adhesion peptide selected from RGD, YIGSR, IKVAV, REDV, DGEA, GRGDS, LDV, RGDV, RGDS, RGDF, HHLGGALQAGDV, GREDVY, GRGDY, GRDSP, GGGGRGDSP, GGGGRGDY to the alginate gel particle disclosed by Ramdahl would enable the particle to be used in immobilizing cells to promote cell proliferation and cell differentiation.
It would be obvious to one of ordinary skill in the art to modify the particle size of the alginate gel particles disclosed by Ramdahl to 25-175 µm and have a reasonable expectation of success. Ramdahl discloses an alginate gel nanoparticle with bismuth-211, radium-223, and/or thorium-227 captured within. Melvik discloses alginate gel particles with a particle size of 25-175 µm. Melvik further discloses that the particle size is achieved by milling and sifting the alginate to the desired size. Accordingly, the combined teachings of Ramdahl and Melvik reasonably suggest that the alginate gel particles disclosed by Ramdahl may be controlled to achieve a particle size of 25-175 µm through known techniques, for example, milling and sifting. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II). In the present case, Melvik discloses that the smaller the particle size, the more rapidly gel formation completes, and that larger particle sizes produce stronger gels. [Melvik, 0071] Ramdahl discloses that the radiation range of typical alpha-emitters in physiological surroundings is generally less than 100 um, which makes them well-suited for treatment of tumors including micrometastases, because when they are targeted and controlled effectively, relatively little of the radiated energy will pass beyond the target cells, thus minimizing damage to the surrounding healthy tissue. [Ramdahl, 0003] Therefore, one would have been motivated to modify the particle size of the alginate gel particle disclosed by Ramdahl to 25-175 µm to obtain desirable gel properties, including rapid formation or a stronger gel, and to ensure that the captured alpha-emitting radionuclide remains within effective range.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Melvik, in view of Ramdahl.
With respect to claim 10, Melvik discloses a kit for making an alginate gel particle comprising:
In a first container:
a water-soluble alginate
a solvent
optionally a drug, a peptide, a protein, a cell, a detectable label or a contrast reagent
Melvik discloses that the peptides suitable for coupling to alginate include RGD, YIGSR, IKVAV, REDV, DGEA, GRDS, LDV, RGDV, RGDS, RGDF, HHLGGALQAGDV, GREDVY, GRGDY, GRGDSP, GGGGRGDSP, GGGGRGDY. [Melvik, 0059-0062] All of these peptides comprise integrin-binding sequences.
In a second container:
Insoluble alginate and gelling ion particles (Ca2+, Sr2+, Ba2+, Zn2+, Cu2+)
A solvent
In a third container:
Optionally, a drug, a peptide, a protein, a cell, a detectable label, or a contrast reagent
[Melvik, 0066, 0088-0092]
Melvik discloses that suitable solvents for making an alginate gel particle include water, saline, sugar solution, cell culture solution, a solution such as a drug solution, protein, or nucleic acid solution, a suspension such as a cell suspension, liposomes, or a contrast reagent suspension. [Melvik, 0072] In exemplified embodiments, Melvik discloses that the solvent used to prepare alginate gel particles is purified water. [Melvik, 0100-0103]
Melvik does not disclose that the third container comprises at least one radionuclide cation and a suitable solvent.
However, with respect to claim 10, Ramdahl discloses an alginate gel particle comprising:
an alginate gel beads
a divalent cation, Sr2+ or Ca2+
a radionuclide, bismuth-211 (in PBS), lead-211 (in PBS), radium-223 (in PBS), and/or thorium-227 (in PBS)
[Ramdahl, 0066, 0070, 0071, 0073, 0076, 0079, 0086, 0087, 0092]
Ramdahl further discloses that bismuth-211, lead-211, radium-223, and thorium-227 bind with or are captured by the alginate beads and are detectable by HPGe. [Ramdahl, 0067, 0073, 0076, 0079, 0087]
Modifying the kit disclosed by Melvik by selecting RGD, YIGSR, IKVAV, REDV, DGEA GRDS LDV, RGDV, RGDS, RGDF, HHLGGALQAGDV, GREDVY, GRGDY, GRGDSP, GGGGRGDSP, or GGGGRGDY as the peptide, water as the solvent, and bismuth-211, lead-211, radium-223 and/or thorium-227 as the detectable label results in the kit of claim 10.
It would be obvious to one of ordinary skill in the art to modify the kit disclosed by Melvik by selecting RGD, YIGSR, IKVAV, REDV, DGEA GRDS LDV, RGDV, RGDS, RGDF, HHLGGALQAGDV, GREDVY, GRGDY, GRGDSP, GGGGRGDSP, or GGGGRGDY as the peptide and have a reasonable expectation of success. Melvik discloses a kit comprising a first container comprising soluble alginate and a peptide. Melvik further discloses that peptides suitable for coupling to alginate include RGD, YIGSR, IKVAV, REDV, DGEA, GRDS, LDV, RGDV, RGDS, RGDF, HHLGGALQAGDV, GREDVY, GRGDY, GRGDSP, GGGGRGDSP, and GGGGRGDY. Melvik further discloses that said coupling may be accomplished through techniques known in the art and that RGD peptide-coupled alginates are commercially available. In view of this express disclosure, it is reasonable to expect that RGD, YIGSR, IKVAV, REDV, DGEA GRDS LDV, RGDV, RGDS, RGDF, HHLGGALQAGDV, GREDVY, GRGDY, GRGDSP, GGGGRGDSP, or GGGGRGDY may be selected as the peptide in the first container of the kit. One would have been motivated to do so because the selection of a known material based on its suitability for its intended use is prima facie obvious. MPEP 2144.07. Accordingly, the selection of the aforementioned peptides based on their suitability for coupling to the alginate in the first container of the kit is prima facie obvious. Moreover, it is prima facie obvious to modify a reference when the rationale for doing so may be reasoned from the disclosure. MPEP 2144(I). In the present case, Melvik discloses that peptide-coupled alginates may be used, for example, in immobilizing cells to promote cell proliferation and cell differentiation. [Melvik, 0061-0062] Therefore, one would have been motivated by the expectation that selecting the aforementioned cell adhesion peptides as the peptide in the first container would result in a kit capable of preparing alginate gel particles useful for immobilizing cells to promote cell proliferation and cell differentiation.
It would be obvious to one of ordinary skill in the art to modify the kit disclosed by Melvik by selecting water as the solvent and have a reasonable expectation of success. Melvik discloses a kit for preparing alginate gel particles comprising a first container comprising soluble alginate and a solvent and a second container comprising insoluble alginate/gelling ion particles and a solvent. Melvik further identifies water as a solvent that is used to prepare the insoluble alginate and/or soluble alginate components. In view of this express teaching, it is reasonable to expect that water may be selected as the solvent in the kit disclosed by Melvik. One would have been motivated to do so because the selection of a known material based on its suitability for its intended use is prima facie obvious. MPEP 2144.07. Accordingly, selecting water as the solvent in the kit used for preparing alginate gel particles based on its known suitability for the same purpose is prima facie obvious.
It would be obvious to one of ordinary skill in the art to modify the kit disclosed by Melvik by selecting bismuth-211, radium-223 and/or thorium-227 (in aqueous solution) as the detectable label and have a reasonable expectation of success. Melvik discloses a kit comprising a third container comprising a detectable label. Ramdahl discloses that bismuth-211, radium-223, and thorium-227 (in aqueous solution) bind with alginate particles with high efficiency. Ramdahl further discloses that, when captured by or bound to alginate, bismuth-211, radium-223, and/or thorium-227 is detectable using a high-performance germanium detector. Accordingly, the combined teachings of Melvik and Ramdahl suggest that bismuth-211, radium-223 and/or thorium-227 may function as the detectable label in the third container of the kit disclosed by Melvik. Moreover, because bismuth-211, radium-223 and/or thorium-227 are in aqueous solution, the third container would necessarily comprise a water solvent. One would have been motivated to do so because it is prima facie obvious to combine references when some advantage or expected beneficial result would have been produced by their combination. MPEP 2144(II). In the present case, Melvik discloses that the kit is used to prepare alginate gel particles useful in biomedical applications such as embolization in the treatment of benign or malignant tumors. [Melvik, 0078] Ramdahl discloses that the radiation range of typical alpha-emitters in physiological surroundings makes them especially well-suited for treating tumors, including micrometastases. When targeted and controlled effectively, relatively little radiated energy passes beyond the target cells, minimizing damage to surrounding healthy tissue. [Ramdahl, 0003] Therefore, one would have been motivated by the expectation that selecting bismuth-211, radium-223, and/or thorium-227 as the detectable label would result in a kit capable of preparing gel particles that treat tumors while minimizing damage to surrounding healthy tissue.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAILA A CRAIG whose telephone number is (703)756-4540. The examiner can normally be reached Monday-Friday 0800-1600.
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/K.A.C./ Examiner, Art Unit 1618
/Michael G. Hartley/ Supervisory Patent Examiner, Art Unit 1618
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