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 .
Detailed Action
This action is in response to the papers filed January 29, 2026.
Amendments
Applicant's amendment(s), filed January 29, 2026, is acknowledged. Applicant has cancelled Claims 2-68 and 71, and amended Claims 70 and 72.
Claims 1, 69-70, and 72-78 are pending.
Priority
Applicant’s claim for the benefit of a prior-filed application provisional application 62/776,839 filed on December 7, 2018 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Election/Restrictions
Applicant has elected without traverse the following species, wherein:
i) the alternative viral vector is an adenoviral vector; and
ii) the alternative structural element is a CMV promoter sequence controllable via a Tetracycline Response Element (TRE), as recited in Claim 72.
Information Disclosure Statement
Applicant has filed an Information Disclosure Statement on July 8, 2025 that has been considered.
The information disclosure statement filed July 8, 2025 fails to comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because 37 CFR 1.98(b) requires that each item of information in an IDS be identified properly. Each publication must be identified by publisher, author (if any), title, relevant pages of the publication, and date and place of publication. The date of publication supplied must include at least the month and year of publication, except that the year of publication (without the month) will be accepted if the applicant points out in the information disclosure statement that the year of publication is sufficiently earlier than the effective U.S. filing date and any foreign priority date so that the particular month of publication is not in issue.
See also MPEP 707.05(e) for electronic documents, including, but not limited to:
(D) reference to the unique Digital Object Identifier (DOI) number, or other unique identification number, if known.
NPL citation 3 has been lined through for being defective of one or more requirements.
The signed and initialed PTO Forms 1449 are mailed with this action.
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.
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.
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.
1. Claim 73 is 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, Claim 73 recites the broad recitation “suspension”, and the claim also recites “liquid, solution” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. The claim appears to be internally redundant because those of ordinary skill in the art that solutions are liquid, and that the pharmaceutical agent is suspended in said solution/liquid.
2. Claim 74 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.
Claim 1 recites a method of treating corneal injury, the method comprising the step(s) of topically administering to the injured cornea a viral vector expressing MG53.
Claim 74 recites administering to the eye, topically, which is the same scope as the topical administration step of the independent claim.
Claim 74 recites administering to the eye, the orbit of the eye, tissue adjacent the eye, intramuscularly, intravenously, subcutaneously, subconjunctivally, and/or systemically, which are broader in scope than the topical administration step of the independent claim.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
3. Claim 74 is 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, Claim 74 recites the broad recitation “systemically”, and the claim also recites “intravenously”, which is the narrower statement of the range/limitation.
The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Those of ordinary skill in the art have long recognized intravenous administration to be systemic.
4. Claims 74 and 77-78 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.
The terms “acutely” and “chronically” in Claim 75 are relative terms which renders the claims indefinite. The terms “acutely” and “chronically” are not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
A claim may be rendered indefinite by reference to an object that is variable. (MPEP §2173.05(b)).
The claim denotes that there is a variable administration regimen that is “acutely”, as opposed to some other variable administration regimen that is not “acutely”. The claims fail to recite, and the specification fails to disclose, an objective administration regimen that falls within “acutely”, as opposed to an objective administration regimen that does not fall within “acutely”. That which is, or is not, “acutely” is considered an arbitrary and subjective determination.
The claim denotes that there is a variable administration regimen that is “chronically”, as opposed to some other variable administration regimen that is not “chronically”. The claims fail to recite, and the specification fails to disclose, an objective administration regimen that falls within “chronically”, as opposed to an objective administration regimen that does not fall within “chronically”. That which is, or is not, “chronically” is considered an arbitrary and subjective determination.
If there are multiple ways to measure “acutely” and/or “chronically”, yet each yields a different result, then the claim may be indefinite because it is unclear which method is to be performed to determine infringement.
Claim 77 recites the limitation “even longer as needed”.
Claim 78 recites the limitation “as frequently or infrequently as needed”.
A claim may be rendered indefinite by reference to an object that is variable. (MPEP §2173.05(b)).
That which is, or is not, “as needed” is considered an arbitrary and subjective determination.
The instant claims as a whole do not apprise one of ordinary skill in the art of its scope and, therefore, does not serve the notice function required by 35 U.S.C. 112, second paragraph, by providing clear warning to others as to what constitutes infringement of the patent.
5. Applicant is advised that should Claim 78 be found allowable, Claims 75-77 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). The claims recite overlapping temporal administration regimens, each of which fall within the genera and/or subgenera recited in the other claims.
6. Claims 1, 70, and 73-78 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. While it is clear in Claim 1 that a viral vector is to be administered topically to the injured cornea, and that the viral vector is to cause the cells of the cornea to express recombinant MG53, the claim suffers from a gap in the method steps and/or structures in that the positively recited viral vector is not recited to encode and express MG53.
Rather, see instead, Claim 69.
Thus, the method of Claim 1 fails to recite a step of administering a first nucleic acid vector encoding MG53 upon which the thus-administered viral vector is expresses the recombinant MG53 from said first nucleic acid.
Claim 1 fails to recite that which is encoded and expressed [structure(s)] by the viral vector that causes expression of the recombinant MG53 from some other, separate, nucleic acid molecule [function].
The instant claims as a whole do not apprise one of ordinary skill in the art of its scope and, therefore, does not serve the notice function required by 35 U.S.C. 112, second paragraph, by providing clear warning to others as to what constitutes infringement of the patent.
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim(s).
7. Claims 1, 70, and 73-78 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 Examiner incorporates herein the above 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, rejection.
Claim 1 fails to recite that which is encoded and expressed [structure(s)] by the viral vector that causes expression of the recombinant MG53 from some other, separate, nucleic acid molecule [function].
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. The disclosure of a single species is rarely, if ever, sufficient to describe a broad genus, particularly when the specification fails to describe the features of that genus, even in passing. (see In re Shokal 113USPQ283(CCPA1957); Purdue Pharma L.P. vs Faulding Inc. 56 USPQ2nd 1481 (CAFC 2000).
The court explained that “reading a claim in light of the specification, to thereby interpret limitations explicitly recited in the claim, is a quite different thing from ‘reading limitations of the specification into a claim,’ to thereby narrow the scope of the claim by implicitly adding disclosed limitations which have no express basis in the claim.” The court found that applicant was advocating the latter, i.e., the impermissible importation of subject matter from the specification into the claim.). See also In re Morris, 127 F.3d 1048, 1054-55, 44 USPQ2d 1023, 1027-28 (Fed. Cir. 1997).
The specification fails to disclose a step of administering a first nucleic acid vector encoding MG53 upon which the thus-administered viral vector is to cause expression of the recombinant MG53 from said first nucleic acid.
The specification fails to disclose that which is encoded and expressed [structure(s)] by the viral vector that causes expression of the recombinant MG53 from some other, separate, nucleic acid molecule [function].
Rather, the specification discloses administering an adenovirus whose genome encodes rMG53 to ocular cells (e.g. Example 14, [0178], “infected with tet-on tPA-MG53 adenovirus”).
The Federal Circuit has explained that a specification cannot always support expansive claim language and satisfy the requirements of 35 U.S.C. 112 “merely by clearly describing one embodiment of the thing claimed.” LizardTech v. Earth Resource Mapping, Inc., 424 F.3d 1336, 1346, 76 USPQ2d 1731, 1733 (Fed. Cir. 2005).
For inventions 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. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are “representative of the full variety or scope of the genus,” or by the establishment of “a reasonable structure-function correlation.” Such correlations may be established “by the inventor as described in the specification,” or they may be “known in the art at the time of the filing date.” See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014)
Without a correlation between structure and function, the claim does little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (“definition by function ... does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is’).
Applicant is essentially requiring the ordinary artisans to discover for themselves that which Applicant fails to disclose.
Thus, for the reasons outlined above, it is concluded that the claims do not meet the requirements for written description under 35 U.S.C. 112, first paragraph.
MPEP 2163 - 35 U.S.C. 112(a) and the first paragraph of pre-AIA 35 U.S.C. 112 require that the “specification shall contain a written description of the invention ....” This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en banc)
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claims.
8. Claims 1, 69-70, and 72-78 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.
Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). The term “viral vector” in Claim 1 is indefinite because dependent Claim 69 recites wherein the viral vector comprises a plasmid.
However, those of ordinary skill in the art have long-recognized that the term “viral vector” refers to a virus, not a plasmid vector, as shown below:
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Similarly, the specification disclose “viral vector” in the context of a virus (e.g. [029], “infecting….with a viral vector-MG53”).
While it is understood in the art that plasmids are used to clone the artisan’s gene(s) of interest into the genome of a recombinant viral vector (e.g. instant Figure 12), the whole plasmid is not encapsidated into the virus particle. The entire plasmid is not the virus genome, and the viral genome is not a plasmid.
The term “viral vector” in Claim 1 is indefinite because the specification does not clearly redefine the term.
The specification fails to disclose a virus particle whose genome is and/or comprises a plasmid.
The instant claims as a whole do not apprise one of ordinary skill in the art of its scope and, therefore, does not serve the notice function required by 35 U.S.C. 112, second paragraph, by providing clear warning to others as to what constitutes infringement of the patent.
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim(s).
The Examiner suggests cancelling recitation of the phrase “a plasmid comprising”.
9. Claims 1, 69-70, and 72-78 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 Examiner incorporates herein the above 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, rejection.
The term “viral vector” in Claim 1 lacks adequate written description because dependent Claim 69 recites wherein the viral vector comprises a plasmid.
As discussed above, those of ordinary skill in the art have long-recognized that the term “viral vector” refers to a virus, not a plasmid vector.
Similarly, the specification disclose “viral vector” in the context of a virus (e.g. [029], “infecting….with a viral vector-MG53”).
While it is understood in the art that plasmids are used to clone the artisan’s gene(s) of interest into the genome of a recombinant viral vector (e.g. instant Figure 12), the whole plasmid is not encapsidated into the virus particle. The entire plasmid is not the virus genome, and the viral genome is not a plasmid.
The specification fails to disclose a virus particle whose genome is and/or comprises a plasmid.
Thus, for the reasons outlined above, it is concluded that the claims do not meet the requirements for written description under 35 U.S.C. 112, first paragraph.
MPEP 2163 - 35 U.S.C. 112(a) and the first paragraph of pre-AIA 35 U.S.C. 112 require that the “specification shall contain a written description of the invention ....” This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) (en banc)
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claims.
The Examiner suggests cancelling recitation of the phrase “a plasmid comprising”.
Claim Rejections - 35 USC § 103
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 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.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
10. Claims 1 and 73-78 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Ma et al (U.S. 2009/031348; hereafter Ma-1) in view of Chandler et al (ABSTRACT NO: 055, Targeting plasma membrane repair in corneal wound healing, Veterinary Ophthalmology (2015) 18(6): E17, E25 (2 pages), Abstracts: 46th Annual Meeting of the American College of Veterinary Ophthalmologists, Coeur l'Alene, ID October 7-10, 2015 DOI:10.1111/vop.12319;. Applicant's own work not cited in an IDS; hereafter Ma-2; of record), Weisleder et al (U.S. 2009/0208473; of record; hereafter Ma-3), Jessup et al (In vitro adenovirus mediated gene transfer to the human cornea, Br J Ophthalmol 89:658–661; doi: 10.1136/bjo.2004.061754, 2005), Yang et al (Adenovirus-mediated delivery of p27KIP1 to prevent wound healing after experimental glaucoma filtration surgery, Acta Pharmacol. Sin. 30(4): 413-423, 2009), and Mohan et al (Gene therapy in the Cornea: 2005-present, Progress in Retinal and Eye Research 31: 43-64, 2012).
Determining the scope and contents of the prior art, and Ascertaining the differences between the prior art and the claims at issue.
While it is clear that the viral vector is to be administered topically to an injured cornea, the claim does not recite wherein the cornea is in an animal subject or human patient. Thus, the breadth of the claim reasonably encompasses:
i) ex vivo contexts, such as corneal explants in tissue culture, as well as
ii) in vivo contexts, such as the treatment of an ocular disease/disorder/condition in an animal subject or human patient.
Ma-1 is considered relevant prior art for having disclosed nucleic acids encoding recombinant MG-53 (rMG53) (e.g. [0040, 170]) for use in a method of treating injured membranes and facilitating membrane repair (e.g. [0031, 34], “vesicular fusion during acute membrane repair is driven by MG53”) present in a disease/disorder/condition comprising wounds, lesions, cuts, abrasions, or age-related tissue degeneration (e.g. [0047]).
Ma-1 disclosed the nucleic acid may be in a viral vector (e.g. [0173, 221]) and is administered locally to the site of interest to be treated (e.g. [0221]), including being compatible with its intended route of administration, e.g. topically (e.g. [0211]).
Ma-1 do not disclose the disease/disorder/condition to be treated is an ocular disease/disorder/condition.
However, prior to the effective filing date of the instantly claimed invention, and with respect to Claim(s) 1, Ma-2 is considered relevant prior art for having taught a method of treating corneal injury, the method comprising the step(s) of administering to the injured cornea of a subject a pharmaceutical composition comprising MG53 in a dosage form ("treatment with recombinant human MG53 (rhMG53)", "application of rhMG53 significantly protected corneal epithelial cells against mechanical injury").
Ma-2 taught said dosage form releases or provides MG53 into or onto the eye ("application of rhMG53 significantly protected corneal epithelial cells against mechanical injury"), and wherein the dosage form releases or provides MG53 to the surface of the eye or corneal surface of the eye, wherein the dosage form is administered to the eye ("application of rhMG53 significantly protected corneal epithelial cells against mechanical injury").
Neither Ma-1 nor Ma-2 taught/disclose the step of administering a viral vector to corneal tissue.
However, prior to the effective filing date of the instantly claimed invention, and with respect to Claim(s) 1, Ma-3 is considered relevant prior art for having disclosed that genetic overexpression of MG53 prevents membrane damage (e.g. [0049]).
Ma-3 disclosed an adenovirus whose genome encodes and expresses recombinant MG-53 (rMG53) to infect target cells (e.g. [0288]).
Jessup et al is considered relevant prior art for having taught a method of administering an adenovirus to corneal explants cultured ex vivo (e.g. pg 658, col. 2, Transduction; pg 659, col. 2, “corneas from donors”), whereby said corneas “were efficiently transduced” with the adenovirus (e.g. Table 1) and express the artisan’s transgene of interest encoded by the adenoviral genome (e.g. Figure 2).
Yang et al is considered relevant prior art for having taught that those of ordinary skill in the art previously recognized and successfully reduced to practice topically administering the artisan’s adenovirus of interest to injured corneal tissue in vivo (e.g. pg 421, col. 1, “topical treatment can deliver recombinant adenovirus”).
Mohan et al is considered relevant prior art for having taught that those of ordinary skill in the art previously recognized adenoviruses have long-been recognized by the ordinary artisan for its ability to efficiently transport genes into corneal tissue in both ex vivo and in vivo contexts (e.g. pg 44, col. 1; pg 45, col. 1, “multiple studies have examined the efficiency of adenovirus vectors for corneal gene therapy… was found to be most efficient in transducing”).
Mohan et al taught that topical application is the most acceptable approach to deliver therapeutics to the eye due to its non-invasive nature, preservation of corneal integrity, and minimal systemic side effects (e.g. pg 53, col. 2), whereby topical administration of the artisan’s viral vector has been successfully reduced to practice (e.g. pg 45, col. 2).
Resolving the level of ordinary skill in the pertinent art.
People of the ordinary skill in the art will be highly educated individuals such as medical doctors, scientists, or engineers possessing advanced degrees, including M.D.'s and Ph.D.'s. Thus, these people most likely will be knowledgeable and well-read in the relevant literature and have the practical experience in molecular biology and the creation of pharmaceutical compositions comprising viral vectors for gene therapy. Therefore, the level of ordinary skill in this art is high.
"A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1397 (2007). "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle." Id. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at ___, 82 USPQ2d at 1396.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The focus when making a determination of obviousness should be on what a person of ordinary skill in the pertinent art would have known at the time of the invention, and on what such a person would have reasonably expected to have been able to do in view of that knowledge. This is so regardless of whether the source of that knowledge and ability was documentary prior art, general knowledge in the art, or common sense. M.P.E.P. §2141.
The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning). See MPEP §2144.
Prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to arrive at a method of treating corneal injury comprising the step of topically administering to the cornea a recombinant adenovirus whose genome encodes and expresses recombinant MG53 with a reasonable expectation of success because those of ordinary skill in the art previously recognized the scientific and technical concepts that:
i) viral vectors encoding and expressing MG53 are useful in a method of treating injured membranes and facilitating membrane repair, whereby viral vector is administered locally to the site of interest to be treated, being compatible with its intended route of administration, e.g. topically (Ma-1);
ii) viral vectors encoding and expressing MG53 include adenoviruses (Ma-3);
iii) Ma-2 successfully demonstrated a method of treating corneal injury, the method comprising the step(s) of topically administering to the injured cornea of a subject a pharmaceutical composition comprising MG53 in a dosage form, whereby “application of rhMG53 significantly protected corneal epithelial cells against mechanical injury"; and
iv) topical administration of adenoviruses whose genomes encode and express the artisan’s gene of interest to corneal tissue has long-been successfully reduced by those of ordinary skill in the art, as topical application is the most acceptable approach to deliver therapeutics to the eye due to its non-invasive nature, preservation of corneal integrity, and minimal systemic side effects (Jessup et al, Yang et al, Mohan et al).
It is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741,82 USPQ2d 1385, 1396 (2007). See also Id. At 1742, 82 USPQ2d 1397 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton.").
It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, —USPQ2d—, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
With respect to Claim 73, Jessup et al taught wherein the adenovirus dosage form is a liquid, solution, or suspension (e.g. pg 658, col. 2, Adenoviral vectors, Transduction, pfu/ml).
Yang et al taught wherein the adenovirus dosage form is a liquid, solution, or suspension (e.g. pg 414, col. 2, Adenoviral vectors, pfu/ml).
With respect to Claim 74, the claim fails to further limit the independent claim. See 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, rejection above.
With respect to Claims 75-78, wherein the dosage form is administered:
acutely or chronically;
one, two, three or more times per day;
daily, weekly, monthly, bimonthly, quarterly, semiannually, annually or even longer as needed; and/or
every other day, five times per week, four times per week, three times per week, two times per week, once daily, twice daily, one to four times daily, continuously, or as frequently or infrequently as needed,
Ma-1 disclosed the MG53 pharmaceutical may be administered as a single daily dose (e.g. [0054]).
Those of ordinary skill in the art immediately recognize that Ma-2 must have administered the MG53 to the cornea at least once for at least one day (syn. once daily, one time per day).
Ma-3 disclosed the MG53 pharmaceutical may be administered as a single daily dose (e.g. [0116]).
Those of ordinary skill in the art immediately recognize that Jessup et al and Yang et al must have administered the adenovirus to the cornea at least once for at least one day (syn. once daily, one time per day).
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). 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. Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are close enough that one skilled in the art would have expected them to have the same properties. See M.P.E.P. §2144.05(I).
The cited prior art meets the criteria set forth in both Graham and KSR, and the teachings of the cited prior art provide the requisite teachings and motivations with a clear, reasonable expectation of success. Thus, the invention as a whole is prima facie obvious.
11. Claims 70 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Ma et al (U.S. 2009/031348; hereafter Ma-1) in view of Chandler et al (Ahereafter Ma-2; of record), Weisleder et al (U.S. 2009/0208473; of record; hereafter Ma-3), Jessup et al (2009; of record), Yang et al (2009; of record), and Mohan et al (2012; of record), as applied to Claims 1 and 73-78 above, and in further view of Chen et al (A novel adenoviral vector carrying an all-in-one Tet-On system with an autoregulatory loop for tight, inducible transgene expression, MBC Biotechnol. 15(4): 8 pages, DOI 10.1186/s12896-015-0121-4, 2015).
Determining the scope and contents of the prior art, and Ascertaining the differences between the prior art and the claims at issue.
Jessup et al taught wherein the adenovirus genome comprises a CMV promoter operably linked to the artisan’s gene of interest (e.g. pg 658, col. 2, “CMV promoter”).
Yang et al taught wherein the adenovirus genome comprises a CMV promoter operably linked to the artisan’s gene of interest (e.g. pg 414, col. 2).
Mohan et al wherein the adenovirus genome comprises a CMV promoter operably linked to the artisan’s gene of interest (e.g. pg 45, col. 1, “CMV promoter”).
Neither Ma-1, Ma-2, Ma-3, Jessup et al, Yang et al, nor Mohan et al teach/disclose wherein the viral vector genome comprises a tetracycline-response element (TRE).
However, prior to the effective filing date of the instantly claimed invention, and with respect to Claim(s) 70, Chen et al is considered relevant prior art for having taught a recombinant adenovirus whose genome comprises a tetracycline-response element (TRE) operably linked to a CMV promoter and the artisan’s transgene of interest (e.g. Figure 1; Tet-ON). Chen et al taught that the tetracycline-regulated system, especially the Tet-ON system, for gene expression has long-been recognized to be one of the most valuable tools for controlling gene expression (e.g. Abstract), and that Chen et al’s modified Tet-ON system has improved dox-inducible gene expression, including high induced expression and high responsiveness to doxycycline, and thus has great potential for gene therapy applications (e.g. Abstract).
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The focus when making a determination of obviousness should be on what a person of ordinary skill in the pertinent art would have known at the time of the invention, and on what such a person would have reasonably expected to have been able to do in view of that knowledge. This is so regardless of whether the source of that knowledge and ability was documentary prior art, general knowledge in the art, or common sense. M.P.E.P. §2141.
The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning). See MPEP §2144.
Prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to modify an adenovirus genome that encodes a CMV promoter operably linked to the artisan’s transgene of interest, including MG53, to further comprise a tetracycline-response element (TRE) operably linked to a CMV promoter and the artisan’s transgene of interest with a reasonable expectation of success and motivation because Chen et al successfully reduced to practice the construction of an adenovirus genome comprises a tetracycline-response element (TRE) operably linked to a CMV promoter and the artisan’s transgene of interest, whereby those of ordinary skill in the art had long-recognized that the tetracycline-regulated system, especially the Tet-ON system, for gene expression has long-been recognized to be one of the most valuable tools for controlling gene expression, and Chen et al’s modified Tet-ON system has improved dox-inducible gene expression, including high induced expression and high responsiveness to doxycycline, and thus has great potential for gene therapy applications.
It is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741,82 USPQ2d 1385, 1396 (2007). See also Id. At 1742, 82 USPQ2d 1397 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton.").
It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, —USPQ2d—, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
The cited prior art meets the criteria set forth in both Graham and KSR, and the teachings of the cited prior art provide the requisite teachings and motivations with a clear, reasonable expectation of success. Thus, the invention as a whole is prima facie obvious.
12. Claims 69 and 72-73 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Ma et al (U.S. 2009/031348; hereafter Ma-1) in view of Chandler et al (Ahereafter Ma-2; of record), Weisleder et al (U.S. 2009/0208473; of record; hereafter Ma-3), Jessup et al (2009; of record), Yang et al (2009; of record), Mohan et al (2012; of record), and Chen et al (2015; of record), as applied to Claims 1, 70, and 73-78 above, and in further view of Wang et al (Improved expression of secretory and trimeric proteins in mammalian cells via the introduction of a new trimer motif and a mutant of the tPA signal sequence, Appl. Microbiol. Biotechnol. 91: 731-740, 2011), Kopfler et al (Adenovirus-Mediated Transfer of a Gene Encoding Human Apolipoprotein A-I Into Normal Mice Increases Circulating High-Density Lipoprotein Cholesterol, Circulation 90: 1319-1327, 1994), and Sumariwalla et al (Antagonism of the Human Epidermal Growth Factor Receptor Family Controls Disease Severity in Murine Collagen-Induced Arthritis, Arthritis & Rheumatism 58(10)L 3071-3080, 2008).
Determining the scope and contents of the prior art, and Ascertaining the differences between the prior art and the claims at issue.
Ma-1 disclosed wherein the nucleic acid encodes a human MG53 cDNA (e.g. SEQ ID NO: 2, “human MG53 cDNA”).
Ma-2 taught the MG53 is human MG53.
Ma-3 disclosed wherein the nucleic acid encodes a human MG53 cDNA (e.g. [0036], “MG53….human cDNA”; SEQ ID NO: 2, “human MG53 cDNA”).
Neither Ma-1, Ma-2, Ma-3, Jessup et al, Yang et al, Mohan et al, nor Chen et al teach/disclose wherein the viral vector genome comprises a tPA leader sequence operatively linked to a human MG53 cDNA.
However, prior to the effective filing date of the instantly claimed invention, and with respect to Claim(s) 69 and 72, Wang et al is considered relevant prior art for having taught that those of ordinary skill in the art had long-recognized and successfully reduced to practice the use of the tPA secretory signal (syn. leader) sequence to drive expression of the artisan’s protein of interest into the cellular secretory pathway (e.g. pg 732, col. 1).
Kopfler et al is considered relevant prior art for having taught an adenovirus whose genome comprises a CMV promoter operably linked to a tPA secretory signal (syn. leader) sequence operably linked to a heterologous cDNA encoding the artisan’s protein of interest (e.g. Figure 1). Kopfler et al taught that their protein of interest was successfully expressed and secreted from cells transduced with the adenovirus when administered in vivo to a mouse subject (e.g. pg 1322, col. 2; pg 1324, Table).
Similarly, Sumariwalla et al is considered relevant prior art for having taught an adenovirus whose genome comprises a CMV promoter operably linked to tPA secretory signal (syn. leader) sequence operably linked to a heterologous cDNA encoding the artisan’s protein of interest (e.g. pg 3072, col. 2, Generation of tPG-herstatin-expressing recombinant adenovirus). Sumariwalla et al taught that the tPA secretory signal (syn. leader) sequence yielded abundant secretion of the artisan’s protein of interest (e.g. pg 3071, Results, “detected in abundance”), including from cells transduced with the adenovirus when administered in vivo to a mouse subject (e.g. Figure 3; Table 1).
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The focus when making a determination of obviousness should be on what a person of ordinary skill in the pertinent art would have known at the time of the invention, and on what such a person would have reasonably expected to have been able to do in view of that knowledge. This is so regardless of whether the source of that knowledge and ability was documentary prior art, general knowledge in the art, or common sense. M.P.E.P. §2141.
The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning). See MPEP §2144.
Prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to modify an adenovirus genome that encodes a CMV promoter, including a tetracycline-response element (TRE) operably linked to a CMV promoter, operably linked to the artisan’s transgene of interest, including MG53, to further comprise tPA secretory signal (syn. leader) operatively linked to the artisan’s transgene of interest, including MG53, with a reasonable expectation of success and motivation because those of ordinary skill in the art previously recognized the scientific and technical concepts that:
i) the tPA secretory signal (syn. leader) sequence had long-recognized and successfully reduced to practice to drive expression of the artisan’s protein of interest into the cellular secretory pathway (Wang et al);
ii) adenoviral vectors encoding a CMV promoter operably linked to a tPA secretory signal (syn. leader) sequence operatively linked to the artisan’s protein of interest was successfully reduced to practice to drive expression and secretion of the artisan’s protein of interest, including in vivo gene delivery (Kopfler et al, Sumariwalla et al); and
iii) secretion of MG53 from the thus-transduced virus expressing recombinant MG53 would recapitulate the reductions to practice of Ma-1, Ma-2, and Ma-3 using purified recombinant MG53 protein, administered topically, to demonstrate the ability of recombinant MG53 protein to treat injured membranes and facilitate membrane repair present in a disease/disorder/condition comprising wounds, lesions, cuts, abrasions, or age-related tissue degeneration (Ma-1), including injured cornea of an ocular disease/disorder/condition (Ma-2; "treatment with recombinant human MG53 (rhMG53)", "application of rhMG53 significantly protected corneal epithelial cells against mechanical injury").
It is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741,82 USPQ2d 1385, 1396 (2007). See also Id. At 1742, 82 USPQ2d 1397 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton.").
It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, —USPQ2d—, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
With respect to Claim 73, Jessup et al taught wherein the adenovirus dosage form is a liquid, solution, or suspension (e.g. pg 658, col. 2, Adenoviral vectors, Transduction, pfu/ml).
Yang et al taught wherein the adenovirus dosage form is a liquid, solution, or suspension (e.g. pg 414, col. 2, Adenoviral vectors, pfu/ml).
Kopfler et al taught wherein the adenovirus dosage form is a liquid, solution, or suspension (e.g. pg 1321, col. 1, Preparation of purified viral stocks).
Sumariwalla et al taught wherein the adenovirus dosage form is a liquid, solution, or suspension (e.g. pg 3073, col. 2, Pharmacokinetics of Ad-tPA-Her expression in vivo).
The cited prior art meets the criteria set forth in both Graham and KSR, and the teachings of the cited prior art provide the requisite teachings and motivations with a clear, reasonable expectation of success. Thus, the invention as a whole is prima facie obvious.
Conclusion
13. No claims are allowed.
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KEVIN K. HILL
Examiner
Art Unit 1638
/KEVIN K HILL/Primary Examiner, Art Unit 1638
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