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 .
Application Status
This action is written in response to applicant’s correspondence received on 12/22/2025. Claims 1-15, 20, 23, 25 are currently pending.
Election/Restrictions
Applicant's election with traverse of Group III, claims 1-3 (in part), 4-15, 20, 23 (in part), and 25 (in part), drawn to a method of ameliorating or treating a retinal or choroidal disease by administration of a nucleotide sequence encoding PLVAP, and the species of age-related macular degeneration (AMD) in the reply filed on 12/22/2025 is acknowledged. Upon reconsideration, the restriction and election of species requirement is withdrawn. Preliminary amendments to claims 1 & 25, filed on 12/22/2025, are acknowledged and Claims 1-15, 20, 23, 25 are examined on the merit.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. KR10-2020-0131953, filed on 10/13/2020.
Specification
The disclosure is objected to because of the following informalities:
Page 47, lines 21-22 recite “(a red dotted line area)” while referencing FIG. 16, whereas FIG. 16 is black and white with a faint white dotted line visible in the referenced control fundus photography.
The use of the terms, Lucentis®, Eylea®, Beovu®, and Avastin® (Page 3, lines 15-18) which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms 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.
Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 23 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., law of nature, natural phenomenon, or product of nature) without significantly more. The inventor discloses and claims naturally occurring proteins and nucleic acid constructs. The judicial exception is not integrated into a practical application and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Regarding claim 23, see the subject matter eligibility test below:
Step 1: Is the claim directed to a process, machine, manufacture, or composition of matter? Yes.
Claim 23 recites “A PLVAP protein” and “an isolated nucleotide sequence encoding the PLVAP protein”. Thus, the claimed inventions are directed to a process, machine, manufacturer or composition of matter.
Step 2A,
Prong 1: Does the claim recite an abstract idea, law of nature, or natural phenomenon? Yes.
Claim 23 recites “A PLVAP protein” and “an isolated nucleotide sequence encoding the PLVAP protein”. The specification teaches “… PLVAP … refers to a naturally occurring … PLVAP … protein, … an amino acid sequence that is the same or substantially the same as that of a naturally occurring … protein … comprises a polymorphic or allelic variant … produced by, for example, alternative splicing or other cellular processes, which occurs naturally …may comprise or consist of an amino acid sequence of NCBI Reference Sequence: NP_112600.1, …, a nucleotide sequence encoding the PLVAP protein may comprise a base sequence represented by SEQ ID NO: 1, ....”(Page 15, Lines 1-14).
Thus, claim 23 refers to a judicial exception because the recited limitations encompass naturally occurring PLVAP protein and PLVAP gene or mRNA that comprises a naturally occurring a nucleic acid sequence encoding a PLVAP protein (See NCBI Protein RefSeq NP_112600.1, NCBI mRNA RefSeq NM_031310.3, NCBI Gene ID: 83483, and sequence search summaries for SEQ ID NO: 1 and 25, attached and listed in PTO-892).
Markedly different characteristic analysis, see MPEP § 2106.04(c)(II): No.
There are no markedly different characteristics in terms of structure between the claimed inventions and the closest natural counterparts, See MPEP § 2106.04(c)(II)(C)(2). The recited “…is effective to improve an ultra-microstructure of choroidal vessels” is a common characteristic associated with the claimed inventions. However, it lacks markedly different characteristics from nature because it is merely a limitation of intended use or intended outcome.
The claimed inventions are thus products of nature exceptions.
Step 2A,
Prong 2: Does the claim recite additional elements that integrate the judicial exception into a practical application? No.
Claim 23 recites “…is effective to improve an ultra-microstructure of choroidal vessels” when reciting the judicial exception, however, this element merely recites an intended use or intended outcome and fails to amount to a “particular treatment and prophylaxis”. See MPEP § 2106.04(d)(2). Therefore, they do not include or recite additional elements that integrate the judicial exception into a practical application.
Step 2B: Does the claim recite additional elements that amount to significantly more? No.
Claim 23 does NOT recite any additional elements, and therefore, they do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Claim Rejections - 35 USC § 112
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 3, 5, 6, 13, 15, 20, 23, 25 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 3, the claim recites the term “variant”. This language is considered to be indefinite despite the recitation “the term PLVAP, which is used interchangeably herein, comprises a polymorphic or allelic variant and other isoforms of a PLVAP protein produced by, for example, alternative splicing or other cellular processes” (Page 15, lines 6-8). Neither the claims nor the specification defines what else is a “variant”. The recited “polymorphic or allelic variant and other isoforms…” are not limitations for “variant” because of the recitation of “comprises”. PHOSITAs will not be appraised of the metes and bounds of this limitation.
Regarding claim 5, the recitation “an exogenous gene sequence” creates indefiniteness because it is unclear how the recited “exogenous gene sequence” relates to the nucleic acid sequence encoding the PLVAP protein of claim 1.
Regarding claim 6, the recitation “an operably linked gene sequence” creates indefiniteness because it is unclear how the recited “operably linked gene sequence” relates to the nucleic acid sequence encoding the PLVAP protein of claim 1.
Regarding claim 13, the recitation “restore fenestrations of endothelial cells” creates indefiniteness because since the claimed inventions encompass systemic delivery routes in the claimed method, the delivery of the therapeutics will reach every accessible tissue and organ. Uhlén et al. (Tissue-based map of the human proteome. Science. 2015 Jan 23;347(6220):1260419; Hereinafter, Uhlén) teaches that PLVAP has diverse and heterogeneous expression profiles (See attached Human Protein Atlas profile attached and listed in PTO-892). Systemic delivery of PLVAP and nucleic acids that encode PLVAP expression would have diverse and heterogeneous impact on the presence of endothelial fenestration in various organs where the levels of endogenous PLVAP expression and the numbers of endothelial fenestrations are diverse and the impact of said treatments unpredictable. Since retinal or choroidal disease are not systemic diseases, not all systemic endothelial fenestrations suffer from the same pathophysiology seen in retinal or choroidal tissues, hence the recitation “restore” creates indefiniteness, and a PHOSITA would not be appraised of the metes and bounds of what constitutes “restore”, as the levels of fenestration in the endothelial cells of multiple organs are unknown.
Regarding claim 15, the recitation of “quasi drug composition” creates indefiniteness because there is no “quasi drug composition” status in the USA. A “quasi drug composition” is a foreign regulatory concept and it does not inform a PHOSITA about the scope of the invention with reasonable certainty under 35 U.S.C.
Regarding claims 23 & 25, the recitation of “improve” or “improving an ultra-microstructure of choroidal vessels” creates indefiniteness.
In the specification (Page 22, lines 13-25, page 23, line 1), it was taught:
“In the present invention, "the ultra-microstructure of the choroidal vessels" may refer to one or more comprising the subretinal space, Bruch's membrane, the retinal pigment epithelium, the choroidal vessels, the endothelial cells of the choroidal vessels, the fenestrations of the endothelial cells, and the overall structure of the above components, but is not limited thereto. The ultra-microstructure may be confirmed by fundus photography, choroidal angiography, electroretinograms, and the like, but is not limited thereto.”
“In the present invention, "the improvement of ultra-microstructure of choroidal vessels" refers to all actions which reduce the severity of symptoms including parameters related to deformation of the choroidal vascular ultra microstructure, for example, a decrease in the number of fenestrations, a change in the polarity of fenestrations, a change in the thickness of endothelial cells, an accumulation of retinal waste in endothelial cells, and a loss of fenestration diaphragms.”
The recitation of “but is not limited thereto” renders “the ultra-microstructure of the choroidal vessels” indefinite. Neither the claims nor the specification defines the full scope of what the recited “parameters” are. The recitation “for example” does not limit the examples that follow, and PHOSITAs would not be appraised of the metes and bounds of these limitations.
Those claims identified in the statement of rejection but not explicitly referenced in the rejection are also rejected for depending from a rejected claim but failing to remedy the indefiniteness therein.
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.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], 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 3 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, 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.
The recitation of “variant”, which does not have a definition in either the claims or the specification, broadens the scope of the claim to encompass undefined structures beyond the scope of “a PLVAP” protein of claim 1 upon which It 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(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112 Written Description
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.
Claims 1-15, 20, 23, 25 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), the first paragraph, for failing to comply with the written description requirement. The claims contain 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP 2163.II.A.3.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the 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”.
For claims drawn to a genus, MPEP § 2163 states 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, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., 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 applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USP USPQ2d at 1406.
Claims 1, 23, & 25 direct to a broad term “an expression or activity activator of the PLVAP protein” that has no definition, description, or work example in the specification, despite being recited for 18 times. There is no reduction to practice for such an extremely broad genus, and no disclosure of the structure associated with the desired function. Under the broadest reasonable interpretation (BRI), there is a high degree of variation in the art for “an expression or activity activator” of a protein, e.g. Wolan et al. (Small-molecule activators of a proenzyme. Science. 2009 Nov 6;326(5954):853-8; Title), Mapp et al. (Activation of gene expression by small molecule transcription factors. Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):3930-5; Title), Macias et al. (Ion Activation Methods for Peptides and Proteins. Anal Chem. 2020 Jan 7;92(1):227-251; Title), and Chen et al. (Nucleic Acid Modifications in Regulation of Gene Expression. Cell Chem Biol. 2016 Jan 21;23(1):74-85; Title) teach that a broad spectrum of molecular structures spanning from small synthetic molecules, ions, to complex biological macromolecules could serve as “an expression or activity activator” of a protein.
The disclosure of insufficient species of a broad genus, the high degree of variation in the art, and the failure to disclose correlation between structure in the specification and the claimed function led to the determination that claims 1, 23, & 25 are overly broad with insufficient evidence of possession at the time of filing to one with ordinary skill in the art. Therefore, claims 1, 23, & 25 do not meet the written description requirement.
Claim Rejections - 35 USC § 112 Enablement
Claims 1-15, 20, 25 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the inventions.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the specification coupled with information known in the art without undue experimentation (United States v. Telectronics., 8 USPQ2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is needed is not based upon a single factor but rather is a conclusion reached by weighing many factors. These factors were outlined in Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and again in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988), and the most relevant factors are indicated below:
Nature of the Invention
Claim 1 directs to a method of ameliorating or treating a retinal or choroidal disease using PLVAP protein or an isolated nucleotide sequence encoding the PLVAP protein. Thus, the method requires a reliable implementation of: 1) delivering the composition comprising a PLVAP protein or a nucleotide sequence encoding the PLVAP protein to a subject in need thereof; 2) ameliorating or treating a retinal or choroidal disease.
Claim 25 directs to a method of improving an ultra-microstructure of choroidal vessels. Thus, the method requires a reliable implementation of: 1) administering a pharmaceutically effective amount of a composition comprising a PLVAP protein or an isolated nucleotide sequence encoding a PLVAP protein as an active ingredient; 2) improving an ultra-microstructure of choroidal vessels in a subject in need thereof.
Breadth of the Claims
Claim 1 broadly directs to ameliorating or treating any retinal or choroidal diseases, these terms are broad because, despite the further limitations in dependent claim 8, there are still a wide spectrum of retinal or choroid diseases with distinct etiology and clinical indications included therein”:
“…retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), Stargardt disease, Usher's syndrome, choroideremia, rod-cone or cone-rod dystrophy, ciliopathy, a mitochondrial disorder, progressive retinal atrophy, a degenerative retinal disease, age-related macular degeneration (AMD),wet AMD, dry AMD, central serous chorioretinopathy, the pachychoroid disease spectrum, degenerative myopia, nodular choroidopathy, chorioretinitis, choroidal tumors, choroidal neovascularization, hereditary choroidal disease, geographic atrophy, familial or acquired maculopathy, a retinal photoreceptor disease, a retinal pigment epithelial-based disease, diabetic retinopathy, diabetic chorioretinopathy, cystoid macular edema, uveitis, retinal detachment, traumatic retinal injury, iatrogenic retinal injury, macular holes, macular telangiectasia, a ganglion cell disease, an optic nerve cell disease. glaucoma, optic neuropathy, an ischemic retinal disease, retinopathy of prematurity, retinal vascular occlusion, a familial retinal arterial macroaneurysm, a retinal vascular disease. an ocular vascular disease, retinal nerve cell degeneration retinal nerve cell degeneration due to glaucoma, ischemic optic neuropathy, or a combination thereof.”
Regarding claim 25, the recitation “improving an ultra-microstructure of choroidal vessels” broadly directs to a method of administering a pharmaceutically effective amount of a composition comprising a PLVAP protein, or an isolated nucleotide sequence encoding the PLVAP protein, as an active ingredient, to a subject in need thereof.
Guidance of the Specification
However, the instant specification focuses on animal models of age-related macular degeneration (AMD) and diabetic retinopathy (DR) as examples (Page 43-48, Examples 2-5), and is silent on the relevance or contribution of a reduced PLVAP expression in any of the remaining retinal or choroid diseases listed above.
The instant specification teaches in example 7 that “Only the eyeballs from donors having no ophthalmic and metabolic underlying diseases were used, and the patients were divided into Young … and Old …” (page 50, lines 7-8), which indicates that a reduction in PLVAP expression in the choroidal vasculature does not necessarily lead to retinal or choroidal diseases, nor does having various recited ultra-microstructure pathology, such as:
“the absolute number of fenestrations decreased as the PLVAP expression was reduced in choriocapillary endothelial cells in the elderly people…” (page 50, lines 19-21);
“a change in polarity of fenestrations in the capillary vessel … as the fenestrations were directed toward the sclera rather than the retina, which is the opposite direction…” (page 50, lines 21-23);
“…waste was not excreted from the retina but was accumulated in the retina to cause inflammation…” (page 50, lines 24-25);
Without any limitations for what a “subject in need thereof” is in the claim, and without any relevant teaching in the specification, claim 25 could encompass methods of administering a treatment using a composition comprising a PLVAP protein or a nucleotide sequence encoding the PLVAP protein, as an active ingredient to human patients without any ophthalmic or metabolic underlying disease under the broadest reasonable interpretation (BRI), based on the teachings of example 7 (page 50, lines 7-25).
The specification is silent regarding the breadth of diseases claimed for the PLVAP-based methods. There is no guidance on the therapeutic strategies or therapy efficacy evaluation methods for retinal or choroidal diseases other than experimental guidance for AMD and DR using animal models of these two diseases. For instance, there is no guidance regarding how to use PLVAP to treat traumatic retinal injury, iatrogenic retinal injury, or macular holes, since there is no known causal link between these mechanical damages and the levels of PLVAP. And a reduction in PLVAP expression in the choriocapillaris is not recognized symptom in mechanical damages in the retina. Search terms for these retinal trauma and various synonyms for PLVAP (FELS, PV-1, MECA-32, DIAR10) on Pubmed, STNext, or PE2E generated no relevant results (see attached search history or query summary for each search platform).
State of the Art
The role of PLVAP on retinal or choroid diseases is still not well understood in the art, based on a comprehensive review on the roles of PLVAP in a variety of human diseases, published by Denzer et al. (The role of PLVAP in endothelial cells. Cell Tissue Res. 2023 May;392(2):393-412; Hereinafter, Denzer), 3 years after the priority date of the instant application. Denzer (2023) does not mention the vast majority of the retinal diseases listed above while discussing the role of PLVAP. The only retina-related diseases mentioned by Denzer are “wet age-related macular degeneration, retinopathy of prematurity (ROP), retinal vein occlusion, and proliferative diabetic retinopathy” (Page 407, first 3 lines).
Based on the review by Guo et al. (Plasmalemma vesicle-associated protein: A crucial component of vascular homeostasis. Exp Ther Med. 2016 Sep;12(3):1639-1644; Hereinafter, Guo) and Bosma et al. (The role of plasmalemma vesicle-associated protein in pathological breakdown of blood-brain and blood-retinal barriers: potential novel therapeutic target for cerebral edema and diabetic macular edema. Fluids Barriers CNS. 2018 Sep 20;15(1):24; Hereinafter, Bosma), published before the priority date of the instant application, the current state of the art overwhelmingly points to elevated PLVAP levels in retinal and choroid diseases is correlated with edema development, angiogenesis, increased vascular permeability or leakiness in retinal diseases (See Table 1 taught by Guo below, red box shows the effects of PLVAP expression increase observed during retinal diseases progression).
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Guo (2016) teaches “Loss of blood‑retinal barrier (BRB) integrity is an important feature underlying the pathogenesis of diabetic macular edema (DME) …… displayed retinal neovascularization and hyperglycemia, which are characteristics of advanced clinical DR… BRB loss, which was characterized by fluorescein leakage, … was associated with focal angiogenesis and PLVAP gene expression, suggesting a vital role for PLVAP in regulating the permeability of the BRB…” (Page 1643, left column, last 2 ¶).
Bosma (2018) teaches “Although the sieving function of PLVAP during macromolecular
transport in fenestrated endothelium is well established, PLVAP regulates vascular permeability in multiple and complex additional ways that remain incompletely understood” (Page 13/17, left column, 2nd ¶, lines 4-8).
Denzer (2023) further teaches that “upregulation of PLVAP was documented to be involved in cancer, traumatic spinal cord injury, acute ischemic brain disease, transplant glomerulopathy, Norrie disease and diabetic retinopathy” (Page 407, left column, 2nd ¶, lines 5-10), suggesting that PLVAP upregulation in diabetic retinopathy was still a prevailing notion in the art 3 years after the priority date of the instant application.
The state of the prior art indicates that the invention of the instant application is highly unpredictable for retinal and choroid diseases because it is still a developing research topic not well understood in the art.
The Level of Predictability in the Art
The unpredictability of the claimed methods in claims 1 and 8 is high because the prevailing understanding in the art is that PLVAP expression is elevated in various retinal diseases associated with vascular permeability pathophysiology, e.g. in certain types of AMD and diabetic retinopathy (see cited references above, such as Guo (2016) and Bosma (2018), and Denzer (2023).
The unpredictability of the claimed method in claim 25 is also high, because example 7 in the instant specification demonstrates that people with normal eyes, “without underlying ophthalmic or metabolic diseases” (Page 50, lines 7-8), can also have reduced PLVAP expression in the choroid vascular tissue and a wide range of ultra-microstructure changes different from normal control eye tissue samples (page 50, lines 7-25).
This disclosure further confirms the unpredictability of the art because the only definitive evidence of PLVAP expression levels or ultra-microstructure patterns can only be obtained in patient tissue samples from donated eyeballs. One skilled in the art would not be able to ascertain whether a living patient have these tissue-based indications or not without tissue biopsy, an invasive procedure unlikely available from living patients, with or without retinal or choroid diseases, as Do et al. (Chapter 124 - Vitreous, Retinal, and Choroidal Biopsy, Editors: Stephen J. Ryan, et al. Retina (Fifth Edition), W.B. Saunders,2013,Pages 2047-2057,ISBN 9781455707379; Hereinafter, Do) teaches only limited clinical indications warrants the use of retinal or choroidal biopsies (Page 3, Table 124.1, Common indications for biopsy).
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Lim et al. (The role of choroidal and retinal biopsies in the diagnosis and management of atypical presentations of uveitis. Trans Am Ophthalmol Soc. 2005;103:84-91; discussion 91-2; Hereinafter, Lim) teaches that “Choroidal and retinal biopsies are often the investigation of last resort …, because of the possible morbidity of such procedures…” (Page 1, under Introduction, lines 1-2).
Therefore, boosting PLVAP levels is highly unpredictable as a treatment without knowing whether a subject has reduced PLVAP levels in the choroidal tissue and altered ultra-microstructures.
Experimentation Required
In light of the high level of unpredictability in the art, and the limited amount of direction provided by the inventor, and the noticeable contradictory working examples with regard to the prevailing views in the prior art cited above, the quantity of experimentation necessarily needed to make or use the invention would be high. For example, it would be necessary for one skilled in the art to determine whether the levels of PLVAP expression in patients with retinal or choroidal diseases in patients’ eye tissue are actually lower than patients with no underlying ophthalmic diseases.
Taking into consideration the factors outlined above, including the nature of the invention, the breadth of the claims, the state of the art, the guidance provided by the applicant and the specific examples that contradict with prevailing views in the art, it is the conclusion that an unreasonable amount experimentation would be required to make and use the invention as claimed.
Those claims identified in the statement of rejection but not explicitly referenced in the rejection are also rejected for depending from a rejected claim but failing to remedy the lack of enablement in scope with the claimed inventions therein.
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Delphinus D. Yu whose telephone number (571) 272-1576. The examiner can normally be reached Mon-Thr 7:30am to 4:30pm Fri 10am to 2pm ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil P Hammell can be reached on (571) 270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DELPHINUS DOU YI YU/Examiner, Art Unit 1636
/NEIL P HAMMELL/ Supervisory Patent Examiner, Art Unit 1636