DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This Office Action is in response to the paper filed 5 July 2026. Claims 1 and 8 have been amended. Claims 2, 3, and 15-20 have been cancelled. Claims 22-28 are newly added. Claims 5, 13, and 14, remain withdrawn. Claims 1, 4, 6-11, 15, 17, 18, and 20-28 are currently pending and under examination.
This Application is a national phase application under 35 U.S.C. §371 of International Application No. PCT/EP2020/087811, filed 23 December 2020, which claims priority to European Application No. EP19219707.7, filed 24 December 2019.
Withdrawal of Objections:
The objection to claim 8, is withdrawn.
Maintenance/Modification of Rejections Necessitated by Amendment:
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.
Claims 1, 8-11, 21-24, and 28, are rejected under 35 U.S.C. 103 as being unpatentable over Marmo et al. (IDS; US 2005/0080484, Published 2005).
With regard to claim 1, Marmo et al. teach an ophthalmological device (Abs.), the ophthalmological device comprising a lens, which is a cell carrier substrate (Abs.). The cells on the carrier substrate can include stem cells, a mixture of stem cells and differentiated epithelial cells, or differentiated epithelial cells (Para. 17). The stem cells are limbal stem cells, from which epithelial cells are derived (Abs.), thus the stem cells are limbal epithelial stem cells. As Marmo et al. expressly teach that the cells on the carrier substrate may be, or include, stem cells, and where the stem cells include limbal epithelial stem cells, it would have been obvious to one of ordinary skill in the art to provide a culture of limbal epithelial stem cells on the cell carrier substrate.
The stem cell carrier substrate comprises a hydrogel containing collagen or collagen-mimicking peptides (Para. 16, 87). The device, including the stem cell carrier substrate, is a circular lens (see Fig. 3A), which is a ring. The device may also include cellular attachment elements, such as indentations over all or a fraction of the lens, where the indentations may be provided in a plurality of concentric rings, where each ring is “ring-shaped,” emanating from the center of the lens and expanding radially outward (Para. 86). The indentations that are a plurality of concentric rings are an area on the surface of the stem cell carrier substrate that is a pattern of niches, which are in a position to coincide with a limbus after transplantation.
Marmo et al. render obvious the device as claimed, utilizing the components as claimed. As the device cannot be separated from its properties, the device as rendered obvious would necessarily be capable of being used for treatment of Limbal Stem Cell Deficiency.
With regard to claim 8, Marmo et al. teach that the stem cell carrier substrate hydrogel may comprise Type I collagen, include recombinant collagen (Para. 16, 70).
With regard to claims 9, 10, and 21, Marmo et al. teach that the device may include cellular attachment elements, where the indentations may be provided in a plurality of concentric rings emanating from the center of the lens and expanding radially outward (Para. 86), wherein the concentric rings are deemed to be regularly spaced groves. It is further taught that the lens of the device has a diameter between about 6 mm and about 12 mm, the thickness of the lens near the center is about 30 and 200 µm thick, and the thickness of the peripheral edge of the lens is less than about 30 µm (Para. 66-68). While the distance between the concentric rings is not specifically taught, it would have been routine for an ordinary artisan to determine the most appropriate width between grooves that fit on the diameter and thickness of the lens as taught, depending on the type and concentration of all the cells and components desired to be loaded onto the lens for implantation.
Additionally, please also note that "the discovery of an optimum value of a variable in a known process is usually obvious." Pfizer v. Apotex, 480 F.3d at 1368. The rationale for determining the optimal parameters for prior art result effective variables "flows from the 'normal desire of scientists or artisans to improve upon what is already generally known.'" Id. (quoting In re Peterson, 315 F.3d 1325, 1330 (Fed. Cir. 2003)). Accordingly, it would have been obvious to optimize the width of grooves, including from 15-150 µm, or 50-90 µm, to result in grooves of an appropriate width depending on the type and concentration of all the cells and components desired to be loaded onto the lens for implantation.
With regard to claim 11, Marmo et al. teach that the carrier substrate can include a mixture of stem cells and differentiated epithelial cells (Para. 17), wherein the differentiated epithelial cells are a pharmaceutical component that is loaded onto the stem cell carrier substrate.
With regard to claims 22-24 and 28, Marmo et al. teach that the device can include cellular attachment elements including indentations, on the lens, where the indentations can be on an anterior surface, can extend between the anterior surface and the posterior surface, can be provided over the entire lens, over a faction of the lens, and in patterns (Para. 86). As Marmo et al. essentially teach that the indentations, which are niches, may be positioned anywhere on the lens, and in any configuration, it would have been obvious to one of ordinary skill in the art from the teachings of Marmo et al. that the pattern of niches may be positioned only on one side of the lens, including the posterior side.
Claims 1, 4, 6, 7, and 25-27, are rejected under 35 U.S.C. 103 as being unpatentable over Marmo et al., as applied to claim 1 above, and further in view of Griffith et al. (WO 2018/069873; Published 2018 – Previously presented).
The teachings of Marmo et al. as applied to claim 1 have been set forth above.
With regard to claims 4, 6, and 7, while Marmo et al. teach that the stem cell carrier substrate comprises collagen (Para. 70), it is not taught that stem cell carrier substate comprises a 12% or 18% Collagen-Like Peptide (CLP) hydrogel, or that the CLP hydrogel is crosslinked with DMTMM.
Griffith et al. teach collagen and collagen-like peptide-based hydrogels for use as corneal implants, where the collagen and collagen-like peptides are crosslinked with DMTMM, and their use in the preparation of a hydrogel and corneal implant is highly efficacious and robust compared to existing corneal implants (Abs.). The CLP is present in amounts between 10% to 18% (claim 16), wherein it would have been obvious to one of ordinary skill in the art to utilize an amount within the expressly taught range, which includes 12% and 18% CLP.
It would have been obvious to one of ordinary skill in the art to combine the teachings of Marmo et al. with Griffith et al., because both teach a collagen-containing ophthalmological device for implantation. CLP-based hydrogels for use as corneal implants, where the CLP is present in amounts including 12% and 18%, and is crosslinked with DMTMM, is known in the art as taught by Griffith et al. The use of DMTMM crosslinked 12% and 18% CLP hydrogels as taught by Griffith et al., as the stem cell carrier substrate in the ophthalmological device of Marmo et al., amounts to the simple substitution of one know collagen-based hydrogel material for another, and would have been expected to predictably and successfully provide an alternative material for the hydrogel of Marmo et al.
With regard to claims 25-27, Marmo et al. teach that the device can include cellular attachment elements including indentations, on the lens, where the indentations can be on an anterior surface, can extend between the anterior surface and the posterior surface, can be provided over the entire lens, over a faction of the lens, and in patterns (Para. 86). As Marmo et al. essentially teach that the indentations, which are niches, may be positioned anywhere on the lens, and in any configuration, it would have been obvious to one of ordinary skill in the art from the teachings of Marmo et al. that the pattern of niches may be positioned only on one side of the lens, including the posterior side.
Response to Arguments
With regard to Marmo, Applicant urges that this reference does not disclose or suggest treatment of Limbal Stem Cell Deficiency (LSCD), and does not disclose any structural configuration directed to limbal niche reconstruction, limbal alignment, or restoration of limbal stem cell function. Marmo’s objective of covering the corneal surface with a refractive device is structurally and functionally distinct from limbal reconstruction. Marmo does not describe a ring-shaped area specifically engineered as a limbal niche region, or a pattern of niches configured to replicate limbal stem cell microenvironments. Additionally, Applicant urges that “a ‘ring’ is structurally defined by an inner boundary and an outer boundary with material absent from the central region.” Wherein Marmo’s device includes a central optical zone that is essential to its stated purpose of vision correction, and Marmo contains no teaching or suggestion of removing the central portion of the lens to create a stem cell carrier substrate having the shape of a ring for treatment of LSCD. Griffith does not cure the deficiencies of Marmo.
Applicant’s arguments have been fully considered, but have not been found persuasive.
With regard to Applicant’s argument that Marmo does not teach or render obvious the structure of the device as claimed, because Marmo’s device does not include a ring-shaped substrate, and includes a central optical zone that is essential; in response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., that a ‘ring’ is structurally defined by an inner boundary and an outer boundary with material absent from the central region) is not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Applicant does not narrowly define “ring” as suggested in their arguments. Giving the term “ring” and “ring-shaped” their broadest reasonable interpretation in light of the specification, the circular lens substrate, and each of the concentric rings of Marmo, are a “ring” and are “ring-shaped.” There is no requirement in the claims as currently written, or a definition in the specification, that requires material to be absent from a central region of the substrate. The indentations that are a plurality of concentric rings as taught by Marmo, are a ring-shaped area on the surface of the stem cell carrier substrate that is a pattern of niches, which are in a position to coincide with a limbus after transplantation.
It is further noted that the transitional phrase "comprising" is inclusive or open-ended and does not exclude additional, unrecited elements or method steps (see MPEP 2111.03, I.). Applicant’s use of the transition phrase “comprising” does not preclude additional unrecited features. Thus, as currently claimed, more than one ring (e.g. the concentric rings of Marmo) is permissibly present, as is a central region in the substrate.
With regard to Applicant’s argument that Marmo does not disclose or suggest treatment of LSCD, or any structural configuration directed to limbal niche reconstruction, limbal alignment, or restoration of limbal stem cell function; it is noted that the claims are directed to a device, and not to a method of using that device. Further, "apparatus claims cover what a device is, not what a device does." Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990) (emphasis in original). Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established (see MPEP 2112.01). In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Marmo et al. render obvious the device as claimed, including the components as currently claimed. As the device cannot be separated from its properties, the device as rendered obvious would necessarily be capable of being used for treatment of LSCD.
With regard to Griffith, the alleged deficiencies of Marmo have been addressed previously.
Conclusion
No claims are allowable.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNIFER M.H. TICHY whose telephone number is (571)272-3274. The examiner can normally be reached Monday-Thursday, 9:00am-7:00pm ET.
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/JENNIFER M.H. TICHY/Primary Examiner, Art Unit 1653
