Notice of Pre-AIA or AIA Status
The present application, filed on or after 16 Mar 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Amendments to the claims filed 03 Jul 2026 are acknowledged. Claims 1-2, 4, 8-9, and 11 are amended. Claims 5-7, 10, and 15-16 are canceled. Claims 13-14 are withdrawn. Claims 17-21 are added.
Claims 1-4, 8-9, 11, 13-14, and 17-21 are pending. Claims 1-4, 8-9, 11, 13-14, and 17-21 are considered on the merits.
Election/Restrictions
Applicant requests rejoinder of non-elected inventions drawn to claims 13-14 as Applicant believes claim 1 to be allowable (Remarks filed 03 Jul 2026 p. 18).
In response, claim 1 is not allowed for reasons set forth in the rejections below. Therefore, the requirement for restriction is maintained.
Claim Objections
Objection to claim 5 is moot due to cancellation of the claim.
Objections to claims 8-9 are withdrawn due to amendments to, or cancellation of, the claims.
Claims 1 and 17 are newly objected to because of the following informalities:
Regarding claim 1, the first instance of any abbreviation recited in the claims should be accompanied by the full, written out term, then the abbreviation may be used alone thereafter.
Regarding claim 17, the term "and' is missing in the phrase, "human albumin, albumin, recombinant human albumin, insulin, transferrin, and recombinant transferrin".
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. § 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Rejection of claims 1-12 under 35 U.S.C. § 112(b) are moot due to cancellation of claims 5-7 and 10 or withdrawn due to amendments to claims 1-2, 4, 8-9, and 11.
§ 112(b) - Response to Arguments
While the rejection of claim 9 under 35 U.S.C. § 112(b) with respect to inclusion of trademark/trade names is withdrawn due to amendment to the claim to no longer recite the media MEM, M-199, DMEM, IMDM, and RPMI 1640, arguments by Applicant are considered as the media are now recited in amended claim 1. In response, Applicant's arguments are found persuasive and new ground of rejection is not included.
As noted by Applicant in remarks filed 03 Jul 2026, MEM, M-199, DMEM, IMDM, and RPMI 1640 are not registered trademarks and each is based on a specific published formulation (Remarks p. 12-13). Based on arguments by Applicant, the claims are interpreted to mean that MEM (minimal essential medium) is the culture medium as described in Eagle (H. Eagle, Science, 1959), M-199 is the culture medium as described in Morgan (J.F. Morgan, et al., Proc Soc Exp Biol Med, 1950), DMEM (Dulbecco's Modified Eagle's Medium) is the culture medium as described in Dulbecco (R. Dulbecco and G. Freeman, Virology, 1959), IMDM (Iscove' Modified DMEM) is the culture medium described in Iscove (N.N. Iscove and F. Melchers, J Exp Med, 1978), and RPMI 1640 is the culture medium described in Moore (G.E. Moore, et al., JAMA, 1967).
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. § 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Rejection of claim 6 under 35 U.S.C. § 112(d) is moot due to cancellation of the claim.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. § 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Rejection of claims 1-4 under 35 U.S.C. § 102(a)(1) as being anticipated by Xiaoyunkang (W. Xiaoyunkang, et al., CN102827807B, 2012, machine translation) as evidenced by He (X.M. He and D.C. Carter, Nature, 1992) is withdrawn due to amendments to the claims.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. § 103:
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.
Rejection of claims 1-2, 5, 7, and 9-10 under 35 U.S.C. § 103 as being unpatentable over Soll (D.B. Soll, et al., US 7,601,487 B2, 2009) are withdrawn due to amendments to the claims.
Rejection of claims 1 and 11-12 under 35 U.S.C. § 103 as being unpatentable over Soll (D.B. Soll, et al., US 7,601,487 B2, 2009) in view of Thareja (T. Thareja, et al., Br J Ophthalmol, 2020) and Wesselingh (J.A. Wesselingh and H.W. Frijlink, CRC Press, 2008) are withdrawn due to amendments to the claims.
Rejection of claims 5-7 under 35 U.S.C. § 103 as being unpatentable over Böhnke (M. Böhnke, et al., Fortschr Ophthalmol, 1991, cited in IDS) in view of Steen (S. Steen, US 7,255,983 B2, 2007), Sleep (D. Sleep, Expert Opin Drug Deliv, 2015), and Ponzin (D. Ponzin, US 6,838,338 B2, 2005), and as evidenced by Price (P.J. Price and E.A. Gregory, In Vitro, 1982) are moot due to cancellation of the claims.
Claims 1-3 and 8 remain rejected and claim 19 is newly rejected under 35 U.S.C. § 103 as being unpatentable over Böhnke (M. Böhnke, et al., Fortschr Ophthalmol, 1991, cited in IDS, translation by Google translated 21 Sep 2026 provided) in view of Steen (S. Steen, US 7,255,983 B2, 2007), Sleep (D. Sleep, Expert Opin Drug Deliv, 2015), and Ponzin (D. Ponzin, US 6,838,338 B2, 2005), and as evidenced by Eagle (H. Eagle, Science, 1959), He (X.M. He and D.C. Carter, Nature, 1992), and Price (P.J. Price and E.A. Gregory, In Vitro, 1982). The rejection is amended as necessitated by amendments to the claims and addition of new claims.
Böhnke discloses a corneal preservation solution comprising minimal essential medium with Earle’s salts (MEM-Earle, culture medium for biological tissues, claim 1), 1% weight/volume (% w/v) hyaluronic acid with molecular weight 250 kDa (a glycosaminoglycan polymeric compound having oncotic properties, claims 1 and 8), and 2% w/v fetal calf serum (FCS) (Abstract). MEM comprises about 11 g amino acids, vitamins, and salts per liter of aqueous component and Böhnke teaches using the medium in a sterile environment; therefore, Böhnke inherently discloses about 11% MEM by weight dissolved in sterile deionized water in sufficient quantity to reach 100% of preservation solution (Böhnke Materials and Methods and Discussion last par. and Eagle Table 1). Albumin (a nutrient protein, claims 1-3) in fetal bovine serum (FBS, another term for FCS) has a mean concentration of 2.3% w/v (Price Table 1 p.577). Therefore, a solution with 2% FCS would comprise about 0.046% w/v albumin. Human albumin has a molecular weight of 65 kDa (within the claimed range of 4 to 75 kDa, claim 3) (He, Introduction, p. 209).
Note that the recitation, "for preserving human corneal tissues in vitro" in claim 1 lines 1-2 is a statement of intended use. Statements reciting purpose or intended use may impose structural limitations. However, in the instant case there appear to be no structural limitations imparted by the recitation on the solution claimed, and therefore, the intended use is not given patentable weight. See MPEP § 2111.02.
Böhnke does not teach 0.05% to 5% w/v nutrient protein free of animal-derived substances and/or which has not been obtained from animal sources or hyaluronic acid with molecular weight of 30 to 200 kDa as required by claim 1, that the nutrient protein is human albumin, albumin, recombinant human albumin, insulin, transferrin, or recombinant transferrin as required by claim 2, or that the nutrient protein is recombinant human albumin and that the hyaluronic acid has molecular weight of 50 to 150 kDa as required by claim 8.
However, regarding the source of nutrient protein, Steen teaches that for tissue preservation solutions, a primary function of albumin is to maintain correct oncotic pressure and that recombinant human albumin has the same physical action as albumin derived from animal serum (recombinant human albumin, claims 2-3, recombinant human albumin of synthetic origin, claim 8, human protein of synthetic origin, claim 19) (col. 4 lines 12-18 and 26-56). Furthermore, Sleep teaches that recombinant albumin has reduced immunogenicity compared to wild-type human albumin and bovine albumin, allow for animal-free production, have improved consistency and purity, and that use of recombinant albumins allows for the introduction of new functionalities not found in wild-type albumins (p. 798).
Furthermore, regarding the concentration of albumin in the medium taught by Böhnke, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985) (Court held as proper a rejection of a claim directed to an alloy "having 0.8% nickel, 0.3% molybdenum, up to 0.1% iron, balance titanium "as obvious over a reference disclosing alloys of 0.75% nickel, 0.25% molybdenum, balance titanium and 0.94% nickel, 0.31% molybdenum, balance titanium. "The proportions are so close that prima facie one skilled in the art would have expected them to have the same properties."). Where the proportions of components in a composition can be varied and result in the same properties, the claimed ranges are patentably indistinct from the prior art. Furthermore, it is routine procedure to optimize component amounts to arrive at an optimal product that is superior for its intended use, since it has been held where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. See MPEP § 2144.05. In the present case, Böhnke teaches a medium suitable for storage of corneal tissue and therefore, the concentration of albumin in the medium taught by Böhnke is not patentably distinct from the claimed range of 0.05% to 5% w/v.
Regarding the molecular weight of hyaluronic acid, Ponzin teaches that solutions comprising high molecular weight hyaluronic acid, greater than 800 kDa, are too viscous to be suitable for corneal preservation solutions (col. 3 lines 22-26). Ponzin teaches, instead, that hyaluronic acid in corneal preservation solutions should preferably have a molecular weight of 50 to 150 kDa (within the claimed range of 30 to 200 kDa, claim 1 and the same as the claimed range of 50 to 150 kDa, claim 8), which is sufficient to preserve endothelial cells at low temperatures, avoid corneal swelling, and form a hyaluronic acid meshwork (col 4 lines 47-58).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the corneal storage medium taught by Böhnke by substituting albumin derived from calf serum for recombinant albumin as taught by Steen and Sleep and substituting a lower molecular weight hyaluronic acid as taught by Ponzin to arrive at the claimed invention. One would be motivated to substitute fetal calf serum taught by Böhnke for recombinant human albumin as natural and recombinant albumins perform the same function in tissue preservation solutions as taught by Steen and because recombinant human albumin has reduced immunogenicity compared to wild-type human and bovine albumins as taught by Sleep. One would be motivated to substitute a lower molecular weight hyaluronic acid as Ponzin teaches that high molecular weight hyaluronic acid is too viscous to be a suitable storage medium. One would have a reasonable expectation of success in substituting serum-derived albumin for recombinant albumin as Steen and Sleep teach recombinant human albumin as a known substitute in the art for bovine albumin that performs the same function and with improved immunogenicity, consistency, purity, and functionality. One would have a reasonable expectation of success in substituting a lower concentration hyaluronic acid as Ponzin teaches that hyaluronic acid with molecular weight in the claimed range is sufficient to preserve endothelial cells at low temperatures, avoid corneal swelling and form a hyaluronic acid meshwork.
Claims 4, 9, and 17-18 are newly rejected under 35 U.S.C. § 103 as being unpatentable over Böhnke (M. Böhnke, et al., Fortschr Ophthalmol, 1991, cited in IDS, translation by Google translated 21 Sep 2026 provided) in view of Steen (S. Steen, US 7,255,983 B2, 2007), Sleep (D. Sleep, Expert Opin Drug Deliv, 2015), and Ponzin (D. Ponzin, US 6,838,338 B2, 2005) as applied to claims 1-3 and 8 above and in further view of Soll (D.B. Soll, et al., US 7,601,487 B2, 2009). The rejection is added as necessitated by amendments to the claims and addition of new claims.
Böhnke, Steen, Sleep, and Ponzin teach a corneal preservation solution comprising MEM, hyaluronic acid, and recombinant human albumin as discussed in the rejection of claims 1-3 and 8 under 35 U.S.C. § 103 above.
Böhnke, Steen, Sleep, and Ponzin do not teach a preservation solution comprising two different nutrient proteins of synthetic origin as required by claim 4 and 17, that the two different nutrient proteins are synthetic albumin and synthetic insulin as require by claim 18, or an additive selected from an antibiotic, an antimycotic, an antioxidant, sodium bicarbonate, sodium pyruvate, or one of calciferol, i-inositol, inosine, or L-alanyl-L-glutamine as required by claim 9.
However, Soll teaches a corneal preservation solution as a similar base product ready for improvement. Soll teaches that insulin (a nutrient protein) is an important component for a corneal storage solution that is essential for tissue development and growth and glucose homeostasis and is found naturally in the tear film and in corneal epithelium (col. 6 lines 32-36). Soll further teaches that the insulin is preferably recombinant human insulin as it is less likely to be immunogenic (synthetic origin, claim 4, insulin, claim 17, insulin of synthetic origin, claim 18) (col. 6 lines 43-46). Soll additionally teaches adding at least one antibiotic for killing gram-positive and gram-negative bacteria to the solution, which may include about 200 μg/mL streptomycin, 100 μg/mL gentamycin (also spelled gentamicin), or about 1 to about 15 mg/mL of the fluoroquinolone antibiotics moxifloxacin or gatifloxacin (at least one antibiotic at a quantity of 0.5 to 1000 μg/mL, claim 9 lines 8-13) (col. 6 lines 48-61). Soll additionally teaches adding at least one antioxidant to slow and reverse senescence and preserve cell integrity, which may be selenium, lutein, alpha-tocopherol, Trolox, vitamin E, carnosine, or ascorbic acid at a concentration of about 100 μM to about 1 mM and preferably ascorbic acid at a concentration of about 0.018 to about 0.176 g/L (at least one antioxidant at a quantity of 1 μg/L to 500 g/L, claim 9 lines 19-23) (col. 7 lines 1-20). Soll additionally teaches addition of about 0.1 to about 0.2 mg/L calciferol, about 0.5 mg/L i-inositol, about 5 mg/L inosine, or about 3.6 to about 4.4 mM L-alanyl-L-glutamine (about 782 to about 956 mg/L) (at least one of calciferol, i-inositol, inosine, or L-alanyl-L-glutamine at a quantity of 5 μg/L to 30 g/L, claim 9 lines 24-26) (col. 7 lines 34-44). Soll further teaches that calciferol is desirable to dissolve fats and is important in cell health, that i-inositol is important in signal transduction, and that L-alanyl-L-glutamine comprises essential amino acids critical to cell growth, metabolism, and endurance (col. 7 lines 16-63). Soll additionally teaches addition of about 1.3 to about 2.5 g/L sodium bicarbonate as a buffer (about 0.13% to about 0.25% w/v, within the claimed range of 0.1 to 5% w/v, claim 9 lines 27-28). Soll additionally teaches addition of about 1 mM sodium pyruvate as a citric acid cycle component to support ATP production (about 0.011% w/v, within the claimed range of 0.01% to 2% w/v, claim 9 lines 27-28). Soll further teaches that addition of such components results in better preservation of the corneal epithelium compared to Optisol™, a commonly used, commercially available corneal preservation solution (col. 10 lines 38-61 and Table 2).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to combine the base corneal preservation taught by Böhnke, Steen, Sleep, and Ponzin with recombinant human insulin, an antibiotic, an antioxidant, sodium bicarbonate, sodium pyruvate, calciferol, i-inositol, inosine, and L-alanyl-L-glutamine as taught by Soll to arrive at the claimed invention. One would be motivated to make such a combination as Soll teaches that insulin is important for corneal tissue glucose homeostasis and as recombinant human insulin is less immunogenic than other sources, that an antibiotic is important for killing gram-positive and gram-negative bacteria, that carnosine can act as an antioxidant and can prevent or reverse cellular senescence, as calciferol is important in cell health, that i-inositol is important in signal transduction, that L-alanyl-L-glutamine comprises essential amino acids critical to cell growth, metabolism, and endurance, that sodium bicarbonate acts as a buffer, and that sodium pyruvate is a critical metabolite in ATP production. One would have a reasonable expectation of success in making the combination as Soll demonstrates that addition of such components improves preservation of corneal epithelium compared to a commercially available preservation medium without the components.
Claims 11 and 20-21 are newly rejected under 35 U.S.C. § 103 as being unpatentable over Böhnke (M. Böhnke, et al., Fortschr Ophthalmol, 1991, cited in IDS, translation by Google translated 21 Sep 2026 provided) in view of Steen (S. Steen, US 7,255,983 B2, 2007), Sleep (D. Sleep, Expert Opin Drug Deliv, 2015), Ponzin (D. Ponzin, US 6,838,338 B2, 2005), and as applied to claims 1-3 and 8 above and in further view of Soll (D.B. Soll, et al., US 7,601,487 B2, 2009), Thareja (T. Thareja, et al., Br J Ophthalmol, 2020) and Wesselingh (J.A. Wesselingh and H.W. Frijlink, CRC Press, 2008). The rejection is added as necessitated by amendments to the claims and addition of new claims.
Böhnke, Steen, Sleep, and Ponzin teach a corneal preservation solution comprising MEM, hyaluronic acid, and recombinant human albumin as discussed in the rejection of claims 1-3 and 8 under 35 U.S.C. § 103 above.
Böhnke, Steen, Sleep, and Ponzin do not teach a preservation system comprising a bottle and a tablet comprising a lubricating substance, an aggregating substance, a disaggregating substance, and an additive selected from an antibiotic, an antimycotic, and an antioxidant as required by claims 11 and 20-21.
However, Soll teaches a preservation system comprising a vial (or bottle) and sterile corneal preservation solution packaged in the vial for storing human corneal tissue (col. 2 lines 41-49 and Fig. 4). Soll teaches that the vial is sized to accommodate a corneal sclera and allows for easy placement and removal of the tissue by a transplant surgeon (and col. 8 lines 44-61). Soll further teaches that the bottom of the vial is optically clear to allow visualization of the tissue during storage without needing to remove the tissue from the vial, thereby lowering risk of contamination (col. 9 lines 6-9). Soll further teaches that compared to other vials in the prior art, the preferred vial has a larger volume, which allows for extended storage time by allowing for use of a larger volume of storage solution, allows for storage of larger corneal tissue, and facilitates easier handling of the tissue (col. 9 lines 10-17).
Furthermore, Thareja teaches that a kit has been developed called Kerasave, which comprises a corneal preservation solution and a dissolvable tablet comprising the antimycotic amphotericin B (a tablet comprising at least one antimycotic substance, claims 11 and 20-21) (p. 1038). Thareja further teaches that increasing rates of fungal infection after corneal transplantation from 2005 to 2010 prompted the industry to address fungal contamination in donor tissues (Introduction) and that “most European eye banks use amphotericin B as the fungicide of choice” (p. 1038). Thareja further teaches that use of a dissolvable tablet circumvents the instability of amphotericin B in solution, which degrades quickly enough to fall below the minimal inhibitory concentration required to control contamination from clinically relevant fungal species within the time course that many corneas are stored prior to transplant (p. 1038). Kerasave significantly prolonged shelf life of corneal tissue for transplant (Thareja p. 1038). The other components of the Kerasave tablet were not disclosed in Thareja.
Furthermore, Wesselingh teaches that the common classes of materials for creating a pharmaceutical tablet, in addition to the active pharmaceutical ingredient, include binders (compounds with aggregating properties), disintegrants (compounds with disaggregating properties), and lubricants (compounds with lubricating properties) (claims 11 and 20) (p. 4). Wesselingh further teaches that lubricants are added to aid in manufacturing so the tablet can be easily removed from the tableting machine (p. 5). Wesselingh further teaches that disintegrants are added to improve rate of tablet dissolution (p. 5). Wesselingh further teaches that binders are added to render the formulation compactible so as to form a stable tablet (p. 5). Wesselingh further teaches that tablet dissolution rate is dependent on tablet size and that tablets can comprise granules that dissolve independently to increase the overall release rate (p. 48 and Fig. 35). Therefore, a skilled artisan would be able to create a preservation system in which the components are split between multiple tablets (a plurality of tablets, claim 20) to increase the rate that the components dissolve in solution.
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to combine the corneal preservation solution and bottle taught by Böhnke, Steen, Sleep, and Ponzin with the preservation system and vial taught by Soll, the tablet comprising amphotericin B taught by Thareja, and the tablet formulation taught by Wesselingh to arrive at the claimed invention. One would be motivated to make the combination as Soll teaches that their vial allows longer storage times and facilitates easier handling and as Soll teaches that visualization during storage without needing to open the vial lowers risk of contamination. One would be motivated to make the combination as Thareja teaches use amphotericin B in corneal preservation solutions is standard in most European eye banks and that addition of a tablet comprising amphotericin B is a known technique to improving similar corneal preservation solutions for the purpose of reducing fungal contamination. One would be motivated to combine amphotericin B with a lubricating substance, and an aggregating substance, and a disaggregating substance Wesselingh teaches that lubricating substances and aggregating substances to enable and improve manufacture of tablets and that disaggregating substances aid dissolution of tablets that would otherwise dissolve very slowly. One would have a reasonable expectation of success as Soll teaches that the vial accommodates larger tissue and a larger volume of solution, which extends storage times and the optically clear bottom allows visualization during storage. One would have a reasonable expectation of success in making the combination as Thareja teaches that addition of a tablet comprising amphotericin to a corneal preservation solution improves the shelf life of corneal tissues for transplant and overcomes the instability of amphotericin B in solution. One would further have a reasonable expectation of success in making the combination as Wesselingh teaches that lubricating substances, aggregating substances, and disaggregating substances are generic, standard ingredients in manufacture of pharmaceutical tablets and that control over tablet size and dissolution rate is standard practice in the art.
§ 103 – Response to Arguments
Applicant traverses the rejection of claims 1-2, 5, 7, and 9-10 under 35 U.S.C. § 103 as unpatentable over Soll, claims 1 and 11-12 under 35 U.S.C. § 103 as unpatentable over Soll in view of Thareja and Wesselingh, and claims 1-3 and 5-8 under 35 U.S.C. § 103 as unpatentable over Böhnke in view of Steen, Sleep, and Ponzin (Remarks filed 03 Jul 2026 pp. 14-16). Applicant argues that the cited art of record does not show or suggest the composition of the amended claims (Remarks p. 16 lines 12-15).
In response, arguments by Applicant have been fully considered and are not persuasive.
A prima facie case of obviousness for combining the teachings of the cited art was set forth in the previous Office Action, and a mere statement that the references fail to teach or suggest the combination does not overcome the rejection. Once a prima facie case of obviousness is made by the USPTO through citation of references, burden is on the applicant to produce contrary evidence. See In re Hoeksema, 399 F.2d at 274, 158 USPQ at 601 In Hoeksema, the contrary evidence was that the applied reference did not disclose or render obvious a process for producing the claimed compounds. Id. at 274-75, 158 USPQ at 601. See MPEP § 2145. The cited art teaches the composition encompassed by the amended claims as set forth in the rejections above.
Applicant further traverses the rejection on the grounds that the combination of features cannot be considered an optimization of ranges based on experimental findings that the composition can preserve corneal tissue at a temperature of about 2 to about 37 °C for up to 4 wk and that a physical interaction occurs between hyaluronic acid, or a salt thereof, and the nutrient protein of synthetic origin (Remarks filed 03 Jul 2026 p. 16 lines 16-27 – p. 17 lines 1-4). Applicant argues that the compositions of the cited art are not capable of achieving such a result (Remarks filed 03 Jul 2026 p. 17 lines 5-6).
In response, arguments by Applicant have been fully considered and are not persuasive.
Preservation of corneal tissue at a temperature of about 2 to about 37 °C for up to 4 wk and a physical interaction between hyaluronic acid, or a salt thereof, and the nutrient protein of synthetic origin are not required elements of the claims. The prior art need not disclose limitations not present in the claims.
Furthermore, there is no evidence of record supporting the assertion that the compositions are not capable of achieving such a result. As previously stated in the Office Action, statements of intended use can impose structural limitations, but where those limitations are unclear, the intended use holds no patentable weight. See MPEP § 2111.02.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Provisional rejection of claims 5-7, 10 and 12 on the ground of nonstatutory double patenting as being unpatentable over claim 1-2, 4, 7-8, and 10 of copending Application No. 18/506,225 (reference application, hereafter ‘225) in view of Parekh (M. Parekh, et al., Acta Ophthalmol, 2018, cited in IDS filed 11 Nov 2024) and as evidenced by Sleep (D. Sleep, Expert Opin Drug Deliv, 2015) is moot due to cancellation of the claims.
Claims 1-3, 8-9, 11, and 19-21 of this application are patentably indistinct from claims 1, 5, 7, 9, and 15-16 of Application No. 18/506,225. Pursuant to 37 CFR 1.78(f), when two or more applications filed by the same applicant or assignee contain patentably indistinct claims, elimination of such claims from all but one application may be required in the absence of good and sufficient reason for their retention during pendency in more than one application. Applicant is required to either cancel the patentably indistinct claims from all but one application or maintain a clear line of demarcation between the applications. See MPEP § 822.
Claims 1-3, 9, and 11 remain provisionally rejected and claims 19-21 are newly provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 5, 7, 9, and 15-16 of copending Application No. 18/506,225 (reference application, hereafter ‘225) in view of Parekh (M. Parekh, et al., Acta Ophthalmol, 2018, cited in IDS filed 11 Nov 2024) and as evidenced by Sleep (D. Sleep, Expert Opin Drug Deliv, 2015). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. The rejection is amended as necessitated by amendments to the claims and addition of new claims.
Claim 1 of ‘225 is drawn to a preservation solution comprising 0.05% to 15% weight/volume (% w/v) culture medium, 1% to 10% w/v hyaluronic acid or a salt thereof with mean molecular weight of 30 to 200 kDa, 1 to 10% w/v of fetal animal serum, fetal bovine serum (FBS), newborn calf serum, human serum, or any of the previous sera inactivated by heat or irradiation, and quantity sufficient sterile deionized water.
Each element of claim 1 of ‘225 is recited in claims 1-3 and 19 of the immediate application except that claims 1-3 and 19 of the immediate application requires that the nutrient protein to be between 0.05% and 5% w/v and be animal-free and/or not obtained from animal sources. In some embodiments of claims 1-3 and 19 that nutrient protein is recombinant human albumin.
Each element of claim 5 of ‘225 is recited in claim 8 of the immediate application except that claim 8 requires that the nutrient protein be recombinant human albumin and that hyaluronic acid have molecular weight between 50 and 150 kDa.
Claim 7 of ‘225 further recites additives selected from 0.5 to 1000 μg/mL of at least one antibiotic, 0.05 to 15 μg/mL of at least one antimycotic, 1 μg/L to 500 g/L of at least one antioxidant, 5 μg/L to 30 g/L of calciferol, i-inositol, inosine, or L-alanyl-L-glutamine, 0.1% to 5% w/v sodium bicarbonate, and 0.01% to 2% w/v sodium pyruvate. Each element of claim 7 of ‘225 is recited in claim 9 of the immediate application except that claim 9 requires that the nutrient protein be of synthetic origin.
Claim 15 of ‘225 is drawn to a preservation system for human corneal tissue of claim 9 of '225 comprising the preservation solution as discussed in claim 1 of ‘225 above, a bottle containing the preservation solution, and a tablet. Claim 15 of '225 further comprises a plurality of said tablets. Each element of claim 15 of ‘225 is recited in claims 11 and 20 of the immediate application except that claims 11 and 20 requires that the nutrient protein be of synthetic origin.
Claim 16 of '225 is drawn to a preservation system or human corneal tissue comprising a bottle containing a sterile solution and a tablet comprising one of a culture medium, a polymer compound with oncotic properties, hyaluronic acid or a salt thereof, and a nutrient of fetal or embryonic origin. Each element of claim 16 of '225 is recited in claim 21 of the immediate application except that claim 21 requires that the nutrient be of synthetic origin.
Parekh, however, teaches comparison between corneal preservation solutions supplemented with serum-based media or recombinant human albumin (Abstract). Parekh teaches that animal serum is undesirable in corneal preservation solutions due to contamination risk, batch variability, and ethical concerns in sourcing from animals (pp. 80 and 84). Further, Parekh demonstrates improvements in corneal health when using solution supplemented with rHSA compared to serum, particularly with regard to health of the endothelium (Discussion p. 85).
Human albumin has a molecular weight of 66 kDa (claims 2-3) and recombinant human albumin is structurally identical to serum-derived albumin (Sleep pp. 794 and 798).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to substitute animal serum of ‘225 with recombinant human albumin as taught by Parekh to arrive at the claimed invention. One would be motivated to make the substitution to minimize contamination risk, batch variability, and ethical concerns when using animal serum as taught by Parekh. One would have a reasonable expectation of success in making the combination as Parekh teaches improved corneal tissue health when using a preservation with recombinant human albumin compared to a storage solution with serum.
Double Patenting – Response to Arguments
Applicant traverses the rejection and states the amended claims are patentably indistinct from the claims presented in copending application 18/506,225 (Remarks p. 17-18). Applicant does not provide support or argument as to how the claims are distinct.
In response, arguments by Applicant have been fully considered and are not persuasive.
Arguments of counsel alone cannot take place of evidence in the record once a prima facie case of obviousness has been established. Once a prima facie case of obviousness is made by the USPTO through citation of references, burden is on the applicant to produce contrary evidence. See In re Hoeksema, 399 F.2d at 274, 158 USPQ at 601 In Hoeksema, the contrary evidence was that the applied reference did not disclose or render obvious a process for producing the claimed compounds. Id. at 274-75, 158 USPQ at 601. See MPEP § 2145.
Conclusion
No claim is allowed.
References cited but not relied upon by the examiner:
Giurgola, L., Gatto, C., Parel, J.-M., Miller, D. & D’Amato Tóthová, J. Antimycotic Efficacy and Safety of a New Cold Corneal Storage Medium by Time–Kill and Toxicity Studies. Cornea 38, 1314–1321 (Year: 2019)
Tran, K. D. et al. Efficacy and Safety of Various Amphotericin B Concentrations on Candida albicans in Cold Storage Conditions. Cornea 39, 110–117 (Year: 2020)
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 Eric B Wright whose telephone number is (571) 272-2607. The examiner can normally be reached Mo - Fr, 09:00 a.m. - 05:00 p.m. Eastern. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached at (571) 272-4517.
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Eric B Wright, PhD
Examiner
Art Unit 1632
/Eric B Wright/Examiner, Art Unit 1632
/VALARIE E BERTOGLIO/Primary Examiner, Art Unit 1632
