DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
Applicant elected Group I, claims 1-9 with traverse in an amendment and response filed May 11, 2026. Applicant elects NGF isoform of SEQ ID NO:1, which consists of 118 amino acids. Claims 1-9 have been amended. Claims 4, 5 and 10-15 have been withdrawn because they are drawn to a nonelected invention or nonelected species. Claims 1-3 and 6-9 are under examination.
Restriction Requirements
Applicant urges that the reference that support a lack of unity of invention of Group I and Group II does not teach NGF molecules that are 118 amino acids which are reflected in the amendment. Based on the amended claims, Imbimbo et al (WO2021/052926 A1 published March 25, 2021 and has a priority date of September 17, 2019). Imbimbo et al teach the 118 amino acid sequence of SEQ ID NO. 1 (see Imbimbo et al, SEQ ID NO:2) or over Lambiase et al (WO 0044396 published August 3, 2000) which teach NGF of 118 amino acids (see page 3 of the disclosure).
Therefore, the special technical feature does not make a contribution over the prior art. Thus, the restriction is made FINAL.
Specification Objections
The use of the term for example, Thermo Scientific which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. Applicant is asked to review the specification for other trademarks. Clarification/correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Written Description
Claims 1-3 and 6-9 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention.”
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the Applicants were in possession of the claimed genus.
The instant claims are directed to a method for treating an ocular pathology selected from retinopathies, corneal pathologies, optic neuropathies, conjunctival pathologies, and limbal stem cell deficiency in a subject, or for the prevention of allograft rejection in corneal transplantation in a subject, the method comprising administering nerve growth factor (NGF) to the subject, wherein said NGF comprises more than 50% by weight of the NGF isoform consisting of the sequence of SEQ ID NO: 1.
The specification discloses a NGF for use in the prevention and/or treatment of an ocular pathology selected from retinopathies, preferably selected from diabetic retinopathy, retinopathy of prematurity, retinal vascular occlusions, phototoxic retinopathy, retinal detachment, age-related macular degeneration, macular degeneration, macular atrophy, macular hole, macular edema and epiretinal membrane; limbal stem cell deficiency; corneal pathologies, preferably selected from keratoconus, phototoxic keratopathy, persistent epithelial defects, corneal ulcers, corneal dystrophies and degeneration and keratoconjunctivitis sicca; conjunctival pathologies; optic neuropathies, preferably selected from glaucoma, ischemic, degenerative, traumatic, inherited and congenital optic neuropathies; and in the prevention of allograft rejection in corneal transplantation, wherein said NGF comprises more than 50% by weight of the NGF isoform of SEQ ID NO: 1 relative to the total weight of all NGF isoforms comprised in said NGF.
The claims encompasses a method for treating an ocular pathology selected from retinopathies, corneal pathologies, optic neuropathies, conjunctival pathologies, and limbal stem cell deficiency in a subject, or for the prevention of allograft rejection in corneal transplantation in a subject, the method comprising administering NGF. The claims encompass a plurality of ocular diseases. The state of the art makes it clear that there are a number of challenges that make it difficult to treat ocular disease. A brief summary is provided herein. Whalen et al (Bioengineering (Basel), 2024 Feb 12; 11(2):179) teach ocular diseases present a unique challenge and opportunity for therapeutic development. The eye has distinct advantages as a therapy target given its accessibility, compartmentalization, immune privilege, and size. Various methodologies for therapeutic delivery in ocular diseases are under investigation that impact long-term efficacy, toxicity, invasiveness, and delivery range (see the Abstract). Whalen et al teach an important factor to consider for the safety and efficacy of ocular therapeutics is the route for delivering each of these treatment types into ocular tissues. Certain routes of delivery will elicit different responses and potential risks. Each of these therapeutic modalities vary in immune and inflammatory responses, as well as the duration of delivery. Implants, nanoparticles, and viral therapeutic delivery systems each offer distinct advantages and challenges (see Background section).
Regarding the role of nerve growth factor on the ocular surface, Kahuman-Lopez et al (International Journal of Molecular Sciences, 2025, 26, 6012) teach the ocular surface is susceptible to a wide spectrum of inflammatory, degenerative, and neurotrophic diseases that can impair vision. The complex pathophysiology and limited therapeutic options associated with these conditions continue to pose significant clinical challenges (see the Abstract). Kahuman-Lopez et al teach although NGF is recognized for its neuroprotective properties and its ability to support epithelial healing, its role in ocular surface disease appears to be context dependent. Elevated concentrations of NGF have been reported in the tear film of patients with contact-lens-associated dry eye, Sjögren’s syndrome, ocular cicatricial pemphigoid, keratoconjunctivitis sicca, and dry eye following refractive surgery suggesting that NGF is not consistently deficient across disease states. In such chronic inflammatory conditions, increased NGF levels may contribute to disease persistence by sustaining immune cell activation and inflammation. The occurrence of corneal neovascularization during rhNGF therapy also raises concerns about a potential proangiogenic effect in susceptible patients. Finally, while activation of the high-affinity TrkANGFR receptor is generally associated with beneficial outcomes such as nerve regeneration and epithelial repair through PI3K/Akt and MEK/ERK signaling, unopposed or excessive engagement of the low-affinity p75NTR receptor may initiate proapoptotic and pro-inflammatory cascades via the JNK and NF-κB pathways. Thus, although NGF upregulation may initially aid tissue repair, prolonged or dysregulated signaling may drive nerve dysfunction, chronic inflammation, and tissue remodeling (see section 6).
Regarding limbal stem cell deficiency, Kittipibul et al (Cornea 2025, April 01:44(4):405-411) teach limbal stem cell deficiency (LSCD) is an ocular surface disease caused by a decrease in the population of corneal epithelial stem/ progenitor cells, known as limbal stem cells (LSCs). Kittipibul et al teach LSCD has a wide spectrum of clinical presentations, including stippling and late fluorescein staining in a vortex pattern, persistent or recurrent epithelial defects, epithelial thinning leading to vision loss, and eventually blindness. Due to the subtle nature of its clinical presentation in the mild stage and the presence of comorbidities, LSCD might be misdiagnosed or over diagnosed, resulting in inappropriate treatment. Because challenges remain in establishing the diagnosis and staging, the actual incidence of LSCD has not yet been determined. Kittipibul et al teach ocular surface inflammation (e.g., conjunctival injection, dilation of conjunctival vessels) and corneal fibrovascular pannus can be confused with LSCD for some physicians. This finding emphasizes the challenges of LSCD diagnosis, and the necessity for ophthalmologists and corneal specialists to incorporate additional diagnostic modalities as recommended by the global consensus on the diagnosis and classification of LSCD (see section III). Kittipibul et al teach significant advances have been made in the diagnosis and management of LSCD in recent years. A precise diagnosis and stagging of LSCD using standardized criteria remains a bottleneck in the development of customized treatment, without which efficacy of different treatments can’t be compared (see the Conclusion section).
Regarding the prevention of allograft rejection in corneal transplantation, Mandal et al (Indian J Ophthalmologyl 2023, Aug 21;71(9):3149-3159) teach prevention of an episode of graft rejection is of utmost importance as it can reduce the need for donor cornea significantly (see the Abstract). Corneal graft rejection (CGR) is the most common cause accounting for the majority of graft failure cases. The management of an episode of CGR is primarily by steroids. The quest to find a suitable steroid-sparing agent has provided some alternatives but not as efficacious as steroids. Management of high-risk grafts offers significant challenges. The advent of new oral immunosuppressive agents like MMF has improved the outcome of corneal grafts in such cases. The clinical spectrum of corneal graft rejection following EK offers a challenge in early diagnosis (see the Conclusion).
The instant specification only shows in vitro data as it relates to the claimed invention.
Therefore, the specification provides insufficient written description to support the genus encompassed by the claim. Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that
"applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
The skilled artisan cannot envision the detailed chemical structure of the encompassed polypeptides, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. In Fiddes v. Baird, 30 USPQ2d 1481, 1483, claims directed to mammalian FGF's were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence.
University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404. 1405 held that:
...To fulfill the written description requirement, a patent specification must describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines Inc. , 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli , 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2datl966.
Given the teachings of these references that point out the limitations and challenges with regard to treating ocular diseases and the lack of a representative number of species across the breadth of the genus, one of skill in the art would not reasonably conclude that the full breadth of the claims meet the written description provision of 35 USC 112(a).
Applicant is reminded that generally, in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus (Enzo Biochem, Inc. v. Gen- Probe Inc., 323 F.3d 956 (Fed. Cir. 2002); Noelle v. Lederman, 355 F.3d 1343 (Fed. Cir. 2004); Regents of the University of California v. Eli Lilly Co., 119 F.3d 1559 (Fed. Cir. 1997)). A patentee must disclose “a representative number of species within the scope of the genus of structural features common to the members of the genus so that one of skill in the art can visualize or recognize the member of the genus” (see Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017) at page 1358). An adequate written description must contain enough information about the actual makeup of the claimed products — “a precise definition, such as structure, formula, chemic name, physical properties of other properties, of species falling with the genus sufficient to distinguish the gene from other materials”, which may be present in “functional terminology when the art has established a correlation between structure and function” (Amgen page 1361).
Adequate written description requires more than a mere statement that is part of the invention. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. v. Chungai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. In Fiddes v. Baird, 30 USPQ2d 1481, 1483, claims directed to mammalian FGF's were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence.
The University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404, 1405 held that: …To fulfill the written description requirement, a patent specification must describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines Inc. 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus an Applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2dat1966.
MPEP § 2163.02 states, “[a]n objective standard for determining compliance with the written description requirement is, 'does the description clearly allow person of ordinary skill in the art to recognize that he or she invented what is claimed’”. The courts have decided: the purpose of the "written description" requirement is broader than to merely explain how to "make and use"; the Applicant must convey with reasonable clarity to those skilled in the art, that as of the filing date sought, he or she was in possession of the invention. The invention is for purposes of the “written description” inquiry, whatever is now claimed. See Vas-Cath, Inc v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991).
Furthermore, the written description provision of 35 USC §112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993). And Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. Moreover, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was “ready for patenting” by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has the Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed.
Therefore for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that Applicant had possession of the claimed invention at the time the instant application was filed.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claim(s) 1-3 and 6 is/are rejected under 35 U.S.C. 102(a)(1) as being unpatentable over Lambiase et al (referred to as Lambiase I) (Pharmacokinetics of Conjunctively Applied Nerve Growth Factor in Retina and Optic Nerve of Adult Rats, Physiology and Pharmacology October 2005, Vol. 46, 3800-3806).
Claim 1 is drawn to a method for treating an ocular pathology selected from retinopathies, corneal pathologies, optic neuropathies, conjunctival pathologies, and limbal stem cell deficiency in a subject, or for the prevention of allograft rejection in corneal transplantation in a subject, the method comprising administering nerve growth factor (NGF) to the subject, wherein said NGF comprises more than 50% by weight of the NGF isoform consisting of the sequence of SEQ ID NO: 1, relative to the total weight of all NGF isoforms comprised in said NGF.
Claim 2 is drawn to a The method according to claim 1, wherein said NGF comprises at least 60% by weight of the NGF isoform consisting of the sequence of SEQ ID NO: 1
Claim 3 is drawn to the method according to claim 1, wherein said NGF isoforms comprised in said NGF comprise or are selected from NGF isoforms consisting of the sequence of SEQ ID NO: 1, 2, 3 or 4 or admixtures thereof, relative to the total weight of all NGF isoforms comprised in said NGF.
Claim 6 is drawn to the method according to claim 1, wherein said NGF isoform consisting of the sequence of SEQ ID NO: 1 does not contain any post-translational modification.
Lambiase I teach after topical conjunctival administration of NGF, high levels were detected in ocular tissues, including the retina and optic nerve, showing a peak increase 6 hours after administration at a concentration of 200 μg/mL. NGF treatment was associated with an increase in BDNF protein and mRNA levels in rat retina. Lambiase I teach that these data demonstrate the bioavailability of NGF to the retina and optic nerve in rats when administered topically. Lambiase I teach that these findings justify investigating the clinical effects of topical NGF therapy for treatment of posterior segment diseases. See the Abstract. Claim limitations such as “the method comprising administering nerve growth factor (NGF) to the subject, wherein said NGF comprises more than 50% by weight of the NGF isoform consisting of the sequence of SEQ ID NO: 1, relative to the total weight of all NGF isoforms comprised in said NGF”, “wherein said NGF comprises at least 60% by weight of the NGF isoform consisting of the sequence of SEQ ID NO: 1, relative to the total weight of all NGF isoforms comprised in said NGF”, “wherein said NGF isoforms comprised in said NGF comprise or are selected from NGF isoforms consisting of the sequence of SEQ ID NO: 1, 2, 3 or 4 or admixtures thereof” and “wherein said NGF isoform consisting of the sequence of SEQ ID NO: 1 does not contain any post-translational modification and SEQ ID NO:1 is inherent in the teachings of the prior art. Lambiase I anticipate the claimed invention.
Claim(s) 1-3 and 6-9 is/are rejected under 35 U.S.C. 102(a)(2) as being unpatentable over Lambiase et al (referred to as Lambiase II) (WO 00/44396 published August 3, 2000).
Claim 1 is drawn to a method for treating an ocular pathology selected from retinopathies, corneal pathologies, optic neuropathies, conjunctival pathologies, and limbal stem cell deficiency in a subject, or for the prevention of allograft rejection in corneal transplantation in a subject, the method comprising administering nerve growth factor (NGF) to the subject, wherein said NGF comprises more than 50% by weight of the NGF isoform consisting of the sequence of SEQ ID NO: 1, relative to the total weight of all NGF isoforms comprised in said NGF.
Claim 2 is drawn to the method according to claim 1, wherein said NGF comprises at least 60% by weight of the NGF isoform of SEQ ID NO: 1, relative to the total weight of all NGF isoforms comprised in said NGF.
Claim 3 is drawn to the method according to claim 1, wherein said NGF isoforms comprised in said NGF comprise or are selected from NGF isoforms consisting of the sequence of SEQ ID NO: 1, 2, 3 or 4 or admixtures thereof.
Claim 6 is drawn to the method according to claim 1, wherein said NGF isoform consisting of the sequence of SEQ ID NO: 1 does not contain any post-translational modification.
Claim 7 is drawn to method according to claim 1, wherein said retinopathies are selected from diabetic retinopathy, retinopathy of prematurity, retinal vascular occlusions, phototoxic retinopathy, retinal detachment, age-related macular degeneration, macular degeneration, macular atrophy, macular hole, macular edema and epiretinal membrane.
Claim 8 is drawn to the method according to claim 1, wherein said corneal pathologies are selected from keratoconus, phototoxic keratopathy, persistent epithelial defects, corneal ulcers, corneal dystrophies and degeneration and keratoconjunctivitis sicca.
Claim 9 is drawn to the method according claim 1, wherein said optic neuropathies are selected from glaucoma and ischemic, degenerative, traumatic, inherited and congenital neuropathies.
Lambiase II teach a nerve growth factor (NGF) in the form of a preparation to be administered over ocular surface, is suggested as being suitable for therapy and or prophylaxis of intraocular tissue pathologies, with particular reference to sclera, ciliary body, crystalline lens, retina, optic nerve, vitreous body and choroidea affections. Lambiase II teach when administered in the form of external ophthalmic preparation, for example as collyrium or ointment, NGF is capable to go through ocular tissues and it has been found out that it shows a therapeutic activity not only against retina and optic nerve pathologies but also against affections involving the above reported internal structures of eye (See the Abstract). Lambiase II teach NGF of 118 amino acids (page 3). Lambiase II teach to evaluate the efficacy of the NGF administration on ocular surface for retina pathologies in a first step experiments disclosed in literature carried out on animal models were repeated using, in addition to intravitreous or retrobulbar administrations, the administration of NGF in the form of collyrium, every two hours, at a concentration of 250 μg/ml in saline balanced solution. In all the experiments both in retinal ischemic and ocular hypertonia damage NGF administered in the form of collyrium exhibited the same activity as when administered by other administration routes. Lambiase II teach on the basis of the results obtained from animals a total of 7 patients were treated, three of which suffering from pigmentary retinopathy, two for senile atrophic maculopathy and one for myopic retinopathy. Therapeutic protocol included the instillation of one or two drops of NGF in the form of collyrium at a concentration of 250 μg/ml in balanced saline solution every two hours for 4 weeks. Treatment results were evaluated by objective exam, electroretinogram (ERG) r blood flow from central retina artery (evaluated by OBF) , contrast sensitivity, thickness of the layer of nervous fibers (evaluated by OCT), microperimetry and visus (page 22-23). Lambiase II disclose that NGF is suitable for a successful treatment of ocular surface pathologies (cornea and conjunctiva) both of acquired and congenital type and, particularly, of various dystrophic or neurodystrophic pathologies for which therapeutic treatments did not exist previously. The discovery of the presence of NGF and of its high affinity receptor (TrkA, tyrosinkinase A), by immunohystochemical techniques, was the condition for such innovative result. Evidently the expression of the NGF high affinity receptor is an essential prerequisite for NGF to exert its therapeutic activity (page 6). Claim limitations “ wherein said NGF comprises more than 50% by weight of the NGF isoform consisting of the sequence of SEQ ID NO: 1, relative to the total weight of all NGF isoforms comprised in said NGF, wherein said NGF comprises at least 60% by weight of the NGF isoform of SEQ ID NO: 1, relative to the total weight of all NGF isoforms comprised in said NGF, and SEQ ID NO:1 is inherent in the teachings of the prior art. Lambiase II anticipate the claimed invention.
Claim(s) 1-3 and 6-9 is/are rejected under 35 U.S.C. 102(a)(2) as being unpatentable over Lambiase et al (referred to as Lambiase III) (WO 0044396 published August 3, 2000).
Claim 1 is drawn to a method for treating an ocular pathology selected from retinopathies, corneal pathologies, optic neuropathies, conjunctival pathologies, and limbal stem cell deficiency in a subject, or for the prevention of allograft rejection in corneal transplantation in a subject, the method comprising administering nerve growth factor (NGF) to the subject, wherein said NGF comprises more than 50% by weight of the NGF isoform consisting of the sequence of SEQ ID NO: 1, relative to the total weight of all NGF isoforms comprised in said NGF.
Claim 2 is drawn to the method according to claim 1, wherein said NGF comprises at least 60% by weight of the NGF isoform of SEQ ID NO: 1, relative to the total weight of all NGF isoforms comprised in said NGF.
Claim 3 is drawn to the method according to claim 1, wherein said NGF isoforms comprised in said NGF comprise or are selected from NGF isoforms consisting of the sequence of SEQ ID NO: 1, 2, 3 or 4 or admixtures thereof.
Claim 6 is drawn to the method according to claim 1, wherein said NGF isoform consisting of the sequence of SEQ ID NO: 1 does not contain any post-translational modification.
Claim 7 is drawn to method according to claim 1, wherein said retinopathies are selected from diabetic retinopathy, retinopathy of prematurity, retinal vascular occlusions, phototoxic retinopathy, retinal detachment, age-related macular degeneration, macular degeneration, macular atrophy, macular hole, macular edema and epiretinal membrane.
Claim 8 is drawn to the method according to claim 1, wherein said corneal pathologies are selected from keratoconus, phototoxic keratopathy, persistent epithelial defects, corneal ulcers, corneal dystrophies and degeneration and keratoconjunctivitis sicca.
Claim 9 is drawn to the method according claim 1, wherein said optic neuropathies are selected from glaucoma and ischemic, degenerative, traumatic, inherited and congenital neuropathies.
Lambiase III teach nerve Growth Factor (NGF), in the form of a preparation to be administered over ocular surface, is suggested as being suitable for therapy and/or prophylaxis of intraocular tissue pathologies, with particular reference to sclera, ciliary body, crystalline lens, retina, optic nerve, vitreous body and choroidea affections. When administered in the form of external ophthalmic preparation, for example as collyrium or ointment, NGF is capable to go through ocular tissues and it has been found out that it shows a therapeutic activity not only against retina and optic nerve pathologies but also against affections involving the above reported internal structures of the eye (see the Abstract). Lambiase III teach a 118 amino acid NGF. Lambiase III teach the NGF administration by intra-vitreous or also retro-bulbar injections proved to be effective for the mouse retinal degeneration model, which is similar to human pigmentary retinopathy. Lambiase III teach that NGF is suitable for a successful treatment of ocular surface pathologies (cornea and conjunctiva) both of acquired and congenital type and, particularly, of various dystrophic or neurodystrophic pathologies for which therapeutic treatments did not exist previously. The discovery of the presence of NGF and of its high affinity receptor (TrkA, tyrosinkinase A), by immunohystochemical techniques, was the condition for such innovative result. Evidently the expression of the NGF high affinity receptor is an essential prerequisite for NGF to exert its therapeutic activity. Lambiase III teach studies on the effect of NGF administration in the form of collyrium for sclera pathologies, studies on the effect of NGF administration in the form of collyrium for the production of aqueous humour and studies on the effect of NGF treatment in the form of collyrium for the cataract prevention. These studies include evaluation of retina pathologies and optic nerve pathologies (see Tables 4 and 5). Claim limitations “ wherein said NGF comprises more than 50% by weight of the NGF isoform consisting of the sequence of SEQ ID NO: 1, relative to the total weight of all NGF isoforms comprised in said NGF, wherein said NGF comprises at least 60% by weight of the NGF isoform of SEQ ID NO: 1, relative to the total weight of all NGF isoforms comprised in said NGF, and SEQ ID NO:1 is inherent in the teachings of the prior art. Lambiase III anticipate the claimed invention.
No claims allowed.
Conclusion
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/VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674
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