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
Applicant’s election without traverse to Group I, encompassed in claims 1-12, in the reply filed 04 Mar 2026 is acknowledged.
Claims 13-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed 04 Mar 2026.
Claims 1-12 are pending and under consideration.
Claim Objections
Claims 5 and 8-9 are objected to because of the following informalities:
Regarding claims 5 and 9, 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 8, “rSHA” should be corrected to rHSA.
Regarding claim 9 fourth par., a comma is missing between lutein and alpha-tocopherol.
Appropriate correction is required.
Claim Interpretation
For the purposes of examination, the recitation “nutrient protein being of a uniquely synthetic origin” of claim 1 is interpreted as “nutrient protein or amino acid being of a uniquely synthetic origin” in light of the Markush group recited in claim 2, which includes the amino acid glutamine.
The recitations “for preserving corneal tissues in vitro” and “said preservation solution being suitable ... and approximately +37°C” in claim 1 are statements of intended use. Statements reciting purpose or intended use may impose structural limitations. However, in the instant case it is unclear what, if any, structural limitations the recitations are intended to impart on the preservation solution claimed. For the purposes of examination, the recitations are interpreted to not impose any structural limitations and are not given patentable weight. See MPEP § 2111.02.
For the purposes of examination, “recombinant human serum albumin” recited in claim 8, is interpreted as recombinant human albumin in light of the definition provided in the specification for a “protein of uniquely synthetic origin”, which is a “protein that has been obtained biochemically and/or through genetic engineering processes and that is free of animal derivatives and/or that has not been obtained from animal sources” (par. 43). Therefore, inclusion of the word “serum” in “recombinant human serum albumin” is not given patentable weight.
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.
Claims 1-12 are 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 inventors regard as the invention.
Claims 1-12 are rejected under 35 U.S.C. § 112(b) as being incomplete for omitting essential elements, such omission amounting to a gap between the elements. See MPEP § 2172.01. Claim 1 recites elements of the preservation solution as approximately 0.05 to approximately 15 percent weight/volume of culture medium, approximately 0.05 to approximately 20 percent weight/volume of at least one polymeric compound, and approximately 0.05 to approximately 5 percent weight/volume of at least one synthetic nutrient protein. Solutions for preservation of cells typically have a density about that of water, 1 g/mL. The elements of claim 1 amount to between 0.15 and 40 g of components per 100 mL of total solution. This leaves 60 to 99.85 percent of the elements of the preservation solution unclaimed. Based on comparative examples, Example 1 and Example 2, in the specification it appears the omitted element is sterile deionized water (pp. 43-48).
Claims 1-12 are rejected under 35 U.S.C. § 112(b) because the recitations “for preserving corneal tissues in vitro” and “said preservation solution being capable ... and approximately +37°C” in claim 1 render the claim indefinite. Statements reciting purpose or intended use may impose structural limitations; however, in the instant case it is unclear what, if any, structural limitations the recitations are intended to impart on the preservation solution claimed. See MPEP § 2111.02.
Claim 2 is rejected under 35 U.S.C. § 112(b) on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of “glutamine of synthetic origin” in the group of nutrient proteins is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: Glutamine is an amino acid, not a protein. As noted in the specification, a protein is a “compound comprising a chain of plurality of amino acids linked to each other through peptide bonds by condensation of an amino group of an amino acid with the carboxyl group of the subsequent one, and having a molecular weight greater than 4000-10000 Daltons” (par. 42). This definition is consistent with the art, and it excludes individual amino acids.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claims 2 and 9 are rejected under 35 U.S.C. § 112(b) on the basis that the claims contain improper Markush groupings of alternatives. The recitations “wherein said at least one nutrient protein of a uniquely synthetic origin is selected from the group comprising of:” in claim 2, “wherein said culture medium is selected from a group comprising” in claim 9, and “preferably comprising between approximately 0.001 mg/L and approximately 500000 mg/L of one or more selected additives” in claim 9 are indefinite because the use of comprising language is open-ended and does not exclude additional, unrecited elements. It is thus unclear whether the intended scopes of the claims are limited only to the recited alternative members. A proper Markush group is a closed group of alternatives, i.e. the selection is made from a group “consisting of” the alternative members rather than “comprising” or “including”. Abbott Labs., 334 F.3d at 1280, 67 USPQ2d at 1196. See MPEP 2173.05(h).
Claims 5, 8, and 9 are rejected under 35 U.S.C. § 112(b) on the basis that the use of parentheticals renders the claims indefinite. It is unclear whether the limitations within the parentheticals are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 5, it is unclear how the parentheticals relate to the preceding terms. Presumably, the parentheticals are molecular weights, but even under that assumption is unclear whether the recited values are limitations on the weights of the recited polymers.
Regarding claim 9, the fourth paragraph of claim 9 recites “alpha-tocopherol (vitamin E)”. However, alpha-tocopherol is just one species of the genus of chemicals referred to in the art as vitamin E, which includes multiple tocopherols and tocotrienols. Therefore, it is unclear whether the scope of the claim is limited to alpha-tocopherol or the entire genus of vitamin E analogues.
Regarding claim 9, the fourth paragraph of claim 9 recites “Trolox (analogue of water-soluble vitamin E)”. It is unclear whether the breadth of the claim is limited only to Trolox or encompasses other water-soluble analogues of vitamin E.
Claims 5 and 9 are rejected under 35 U.S.C. § 112(b) on the basis that the use of the term "preferably" renders the claim indefinite. It is unclear whether the limitation(s) following the phrase are required parts of the claimed invention. A broad claim limitation followed by a narrower limitation or preferred embodiment within a single claim leads to confusion over the intended scope of the claim. See MPEP § 2173.05 subsections (c), (d), and (h).
Regarding claim 5, it is unclear whether the polymer compound must be selected from polysucrose 400, Ficoll PM400, Ficoll PM70, polyvinyl pyrrolidone PVP360, and polyvinyl pyrrolidone PVP40.
Regarding claim 9, it is unclear whether the culture medium must be MEM or may be selected from MEM, M-199, DMEM, IMDM, or RPMI 1640. It is also unclear whether the preservation solution must include one of the additives recited in the claim.
Claim 5 contains the trademark/trade names polysucrose 400, Ficoll PM400, Ficoll PM70, polyvinyl pyrrolidone PVP360, and polyvinyl pyrrolidone PVP40. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. § 112(b). See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, not the goods themselves. Thus, a trademark or trade name does not identify or describe the associated goods. In the present case, the trademark/trade name is used to identify/describe a polysucrose with mean molecular weight of 400 kDa, a copolymer of sucrose and epichlorohydrin with mean molecular weight of 400 kDa, a copolymer of sucrose and epichlorohydrin with mean molecular weight of 70 kDa, polyvinyl pyrrolidone with mean molecular weight of 360 kDa, and polyvinyl pyrrolidone with mean molecular weight of 40 kDa, respectively. Accordingly, the identification/description is indefinite.
Claim 6 is rejected under 35 U.S.C. § 112(b) on the basis that the intended scope of the claim is unclear. Claim 1 requires that the “at least one polymer compound having oncotic properties” have a “mean molecular weight between 5000 and 550000 Dalton”. However, claim 6 requires that the polymer compound be hyaluronic acid and have “a molecular weight between approximately 5000 Dalton and approximately 550000 [Dalton]”, which is a broader scope than the claim 1, from which claim 6 depends. Therefore, it is unclear whether the intended scope of claim 6 encompasses hyaluronic acid with molecular weight less than 5000 Dalton or greater than 550000 Dalton. See MPEP 2173.05(f).
Claim 9 contains the trademarks/trade names MEM, M-199, DMEM, IMDM, and RPMI 1640. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. § 112(b). See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, not the goods themselves. Thus, a trademark or trade name does not identify or describe the associated goods. In the present case, the trademark/trade name is used to identify/describe basal media for cell culture and, accordingly, the identification/description is indefinite.
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.
Claim 6 is rejected under 35 U.S.C. § 112(d) or 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 1 requires that the “at least one polymer compound having oncotic properties” have a “mean molecular weight between 5000 and 550000 Dalton”. However, claim 6 requires that the polymer compound have “a molecular weight between approximately 5000 Dalton and approximately 550000 Dalton”, which is a broader scope than the claim 1, from which claim 6 depends. Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
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.
Claims 1-4 are rejected 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).
Xiaoyunkang discloses a solution comprising 17.7 g/L Iscove’s Modified Eagle’s Medium (IMDM, 1.77 percent weight/volume (%w/v), cell culture medium for biological tissues, claim 1), 4 g/L recombinant human albumin (0.4% w/v, nutrient protein of uniquely synthetic origin and polymeric compound having oncotic properties and mean molecular weight between 5 and 550 kDa, claims 1-4), and recombinant human insulin (claim 4) (par. 15 and Table 3).
Human albumin has a molecular weight of 65 kDa, contributes to the colloid osmotic pressure (also known as oncotic pressure in the art) in blood, and, being a protein, is a polymer of amino acids (He, Introduction, p. 209).
The concentrations and molecular weights of components taught by Xiaoyunkang each fall within, and thus anticipate, the claimed ranges.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. § 103 are summarized as follows:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in the pertinent art.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-12 are rejected under 35 U.S.C. § 103.
Claims 1-2, 5, 7, and 9-10 are rejected under 35 U.S.C. § 103 as being unpatentable over Soll (D.B. Soll, et al., US 7,601,487 B2, 2009).
Soll teaches a preferred embodiment for a corneal storage solution (preservation solution, claim 1) for preserving human corneal tissue (claim 10) (col. 2 lines 28-49). The solution comprises M199 culture medium (claims 1 and 9), 10 g/L high molecular weight dextran (1 percent weight/volume (% w/v), a polysaccharide polymer with oncotic properties, claims 1, 5, and 7), 30 g/L chondroitin sulfate C (3% w/v, a glycosaminoglycan polymer with oncotic properties, claims 1, 5, and 7), 4 mM L-glutamine (0.058% w/v, nutrient protein, claims 1 and 2), 200 μg/mL streptomycin (antibiotic, claim 9), 100 μg/mL gentamycin (also spelled gentamicin, antibiotic, claim 9), 250 μM ascorbic acid (44 mg/L, antioxidant, claim 9), 0.005 g/L inosine (5 mg/L, claim 9 fifth par.), 1.7 g/L sodium bicarbonate (0.17% w/v, claim 9 sixth par.), and 1 mM sodium pyruvate (0.011% w/v, claim 9 seventh par.) (col. 8, Table 1).
Soll teaches that “the term ‘high molecular weight dextran’ encompasses dextran having a molecular weight of at least about 500,000 Daltons”, which overlaps with the range of mean molecular weights for the oncotic polymer of claim 1 (col. 4, lines 22-25). Soll further teaches that the molecular weight of chondroitin sulfate can range between 20 and 100 kDa, which is within the range of mean molecular weights for the oncotic polymer of claim 1 (col. 4, lines 43-47).
Soll does not teach approximately 0.05 to approximately 15% w/v of a culture medium for biological tissues as required by claim 1 or an anti-mycotic in its preferred embodiment as required by claim 9.
However, 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.").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.
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to optimize the concentration of base culture media in the corneal storage solution taught by Soll to arrive at the claimed invention. One would be motivated to vary the concentration of cell culture medium as optimization of component concentrations is routine in the development of corneal preservation solutions. One would have a reasonable expectation of success in making the combination as optimization of component concentrations is routine.
Claims 1 and 11-12 are rejected 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).
Soll teaches a corneal preservation solution for human corneal tissue comprising culture medium dextran, chondroitin sulfate, and L-glutamine as discussed in the rejection of claim 1 under 35 U.S.C. § 103 above. Soll further teaches a preservation system comprising a vial (or bottle) and corneal preservation solution (claim 11) for storing human corneal tissue (claim 12) (col. 2 lines 41-49). The preservation system taught by Soll does not include 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 claim 11.
However, 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 (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.
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 (a compounds with lubricating properties) (claim 11) (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).
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 Soll with the amphotericin B tablet 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 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 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.
Claims 1-3 and 5-8 are rejected under 35 U.S.C. § 103 as being unpatentable over Böhnke (M. Böhnke, et al., Fortschr Opthalmol, 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).
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 5 to 550 kDa, claims 1, 5-6, and 8), and 2% w/v fetal calf serum (FCS, nutrient protein, claim 1) (Abstract).
Price provides that albumin in fetal bovine serum (FBS, another term for FCS) has a mean concentration of 2.3% w/v (Table 1 p.577). Thus, a solution with 2% FCS would comprise about 0.046% w/v albumin. Because the specification does not provide a definition by which the inventor considers values to be approximate, it is considered that 0.046% w/v albumin as taught by Böhnke is within the range of approximately 0.05% to approximately 5% w/v of a nutrient protein as required by claim 1.
Böhnke does not teach approximately 0.05 to 15% w/v of a culture medium for biological tissues as required by claim 1, recombinant human albumin as required by claim 1, or hyaluronic acid with molecular weight approximately 50 to approximately 150 kDa as required by claim 8.
However, 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.").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.
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 (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).
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, 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 optimize the concentration of culture medium taught by Böhnke, substitute the albumin in the animal serum for recombinant albumin as taught by Steen and to use a lower molecular weight hyaluronic acid as taught by Ponzin to arrive at the claimed invention. One would be motivated to vary the concentration of cell culture medium as optimization of component concentrations is routine in the development of corneal preservation solutions. One would be motivated to try a lower molecular weight hyaluronic acid as Ponzin establishes molecular weight as a results effective variable in corneal preservation solutions. 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 have a reasonable expectation of success in making the combination because optimization of component concentrations is routine, because Ponzin teaches that hyaluronic acid with molecular weight in the claimed range are sufficient to preserve endothelial cells at low temperatures, avoid corneal swelling, and because Steen and Sleep teach recombinant human albumin as an established substitute for bovine albumin that performs the same function and with improved immunogenicity, consistency, purity, and functionality.
Double Patenting
Claim 1-3, 5-7, and 9-12 of this application is patentably indistinct from claims 1-2, 4, 7-8, and 10 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.
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.
Claims 1-3, 5-7, and 9-12 are provisionally rejected 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 Opthalmol, 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.
Claim 1 of ‘225 is drawn to a preservation solution comprising approximately 0.05 to approximately 15% weight/volume (% w/v) culture medium, approximately 0.05 to approximately 20% w/v of at least one oncotic polymer with mean molecular weight of approximately 20 to approximately 550 kDa, and approximately 0.05 to approximately 5% w/v of at least one nutrient protein of fetal or embryonic origin. Claim 2 of ‘225 further comprises the preservation solution of claim 1 of ‘225, wherein the nutrient protein is selected from fetal animal serum, fetal bovine serum (FBS), newborn calf serum, human serum, or any of the previous sera inactivated by heat or irradiation.
Each element of claim 2 of ‘225 is recited in claim 1 of the immediate application with two exceptions. The mean molecular weight range of the oncotic polymer of claim 1 of ‘225 is narrower than, and thus falls within the scope of, the mean molecular weight range of the oncotic polymer recited in claim 1. Claim 1 of the immediate application requires that the nutrient protein be of “uniquely synthetic origin”, which requires that the nutrient protein not be sourced from animals or have derivatives of animal products (Specification par. 43). Claim 2 requires that the nutrient protein be selected from albumin, glutamine, insulin, or transferrin. Claim 3 requires that the nutrient protein have a mean molecular weight of 4 to 75 kDa.
Claim 4 of ‘225 further comprises the preservation solution as discussed in claim 1 of ‘225 above, wherein the oncotic polymer compound(s) is selected from the group consisting of “polysucrose 400 (PM 400000 g/mol), Ficoll PM400 (PM 400,000), Ficoll PM70 (PM 70,000), polyvinyl pyrrolidone PVP360 (PM360000), and polyvinyl pyrrolidone PVP40 (PM 40,000)”.
Each element of claim 4 of ‘225 is recited in claim 5 of the immediate application except that claim 5 requires that the nutrient protein be of “uniquely synthetic origin”.
Claim 5 of ‘225 further comprises the preservation solution as discussed in claim 1 of ‘225 above, wherein the oncotic polymer compound(s) is a hyaluronic acid with molecular weight between approximately 5 and approximately 550 kDa.
Each element of claim 5 of ‘225 is recited in claim 6 of the immediate application except that claim 6 requires that the nutrient protein be of “uniquely synthetic origin”.
Claim 6 of ‘225 further comprises the preservation solution as discussed in claim 1 of ‘225 above, wherein the oncotic polymer compound(s) are preferably selected from a polysaccharide or a glycosaminoglycan.
Each element of claim 6 of ‘225 is recited in claim 7 of the immediate application except that claim 7 requires that the nutrient protein be of “uniquely synthetic origin”.
Claim 7 of ‘225 further comprises the preservation solution as discussed in claim 1 of ‘225 above, wherein the media is selected from MEM, M-199, DMEM, IMDM, and RPMI 1640. Claim 7 of ‘225 further recites approximately 1 to approximately 1000 pg/mL of at least one antibiotic, approximately 0.05 to approximately 15 pg/mL of at least one antimycotic, approximately 1 μg/L to approximately 500 g/L of at least one antioxidant, approximately 5 μg/L to approximately 30 g/L of calciferol, i-inositol, inosine, or L-alanyl-L-glutamine, approximately 0.1 to approximately 5% w/v sodium bicarbonate, and approximately 0.01 to approximately 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 “uniquely synthetic origin”.
Claim 8 of ‘225 further comprises the preservation solution as discussed in claim 1 of ‘225 above, wherein the preservation solution is suitable for storage of human corneal tissue.
Each element of claim 8 is recited in claim 10 of the immediate application except that claim 10 requires that the nutrient protein be of “uniquely synthetic origin”.
Claim 10 of ‘225 is drawn to a preservation system for human corneal tissue comprising the preservation solution as discussed in claim 1 of ‘225 above, a bottle containing the preservation solution, and a tablet.
Each element of claim 10 of ‘225 is recited in claims 11-12 of the immediate application except that claims 11-12 require that the nutrient protein be of “uniquely synthetic origin”.
Parekh, however, teaches comparison between corneal preservation solutions supplemented with serum-based media or recombinant human serum albumin (rHSA) (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 rHSA 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 rHSA compared to a storage solution with serum.
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)
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/Eric B Wright/ Examiner, Art Unit 1632
/VALARIE E BERTOGLIO/Primary Examiner, Art Unit 1632
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