DETAILED ACTION
Applicant’s amendment and response received on 11/10/25 has been entered. Claims 16, 21-22, and 46 have been canceled, and new claim 49 has been added. Claims 1-2, 6-7, 9-10, 13-15, 17-18, 28, 37, 43-45, and 49 are now pending and under examination in the instant application. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . An action on the merits follows.
Those sections of Title 35, US code, not included in this action can be found in a previous office action.
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 17-18, 28, 37, 42-45, and 49 are newly 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.
Independent claim 28 has been amended to recite a method of treating glaucoma in a mammal comprising in part the steps of injecting a therapeutic composition comprising a rAAV vector comprising a polynucleotide sequence encoding human matrix metalloproteinase 3 (MMP-3) operably linked to a constitutive promoter into the anterior chamber of said mammal's eye, transducing cells in the anterior chamber; wherein the transduced cells secrete human MMP-3; modifying the extracellular matrix of the trabecular meshwork of said mammal's eye; and increasing permeability of the extracellular matrix of the trabecular meshwork of said eye. As amended, the step of “transducing cells in the anterior chamber”, the step of “modifying the extracellular matrix of the trabecular meshwork of said mammal’s eye”, and the step of “increasing permeability of the extracellular matrix of the trabecular meshwork of said eye” are confusing. The claims previously clearly identified that the recited rAAV which has been administered to the anterior chamber of the eye transduced the cells in the anterior chamber of the eye, and that the human MMP-3 secreted by the transduced cells modified the extracellular matrix of the trabecular meshwork of said eye. As currently written, the transducing, modifying, and increasing permeability are recited as independent steps that are not clearly limited to the effects of the injection of the rAAV vector encoding human MMP-3. As such these steps are confusing as it is unclear whether they are intended to recite active independent steps of transducing, modifying, and increasing permeability which encompass the administration of vectors, compounds, drugs etc. which can achieve these active steps and functional effects other than the rAAV vector encoding human MMP-3. Thus, the metes and bounds of claim 28 cannot be determined. Claims 17-18, 37, 42-45 depend on claim 28 and thus are included in this rejection. If applicant intends these steps to relate to the administration of the rAAV encoding human MMP-3 then it is suggested that applicant amended these step to tie these steps to the administered rAAV or to human MMP-3 expressed by the rAAV.
New Independent claim 49, similar to claim 28, includes a step of “transducing cells in the anterior chamber”. This step, as written, does not identify what is transducing the cells. While the preceding step involves the administration of an rAAV vector encoding human MMP-3 into the anterior chamber of the eye, it is not clear whether the subsequent step of transducing cells in the anterior chamber is limited to transduction with the recited rAAV vector or whether this step is intended to encompass any means of transduction such as the use of other viral vectors. As such, the metes and bounds of the claim cannot be determined.
Claim Rejections - 35 USC § 103
The rejection of claims 1-2, 6-7, 9-10, 13-18, 21-22, 28, 37, and 42-48 under 35 U.S.C. 103 as being unpatentable over O’Callaghan et al. (September, 2016) Invest. Opthamol. Vis. Science, Vol. 57, 793, abstract, pages 1-2, hereafter referred to as O’Callaghan 2016, in view of Mamiya et al. (2004) Exp. Eye Research, Vol. 79, 405-410, and GenBank Accession Number BC074815 (2005) Homo sapiens matrix metallopeptidase 3 (stromelysin 1), is withdrawn over canceled claims 16, 21-22, and 46, further withdrawn over amended method claims 17-18, 28, 37, and 42-45 in view of applicant’s amendments to the claims and arguments, and maintained over amended product claims 1-2, 6-7, 9-10, and 13-15. Applicant’s amendments to the claims and arguments have been fully considered but have not been found persuasive in overcoming the rejection of product claims 1-2, 6-7, 9-10, and 13-15.
The applicant has amended product claims 1-2, 6-7, 9-10, and 13-15 to recite a number of functional properties which occur when the product is administered to the anterior chamber of the eye such as transduction of cells, secretion of human MMP-3 in the transduced cells, modification of the extracellular matrix of the trabecular meshwork of the eye, increased permeability of the extracellular matrix of the trabecular meshwork of said eye, increased outflow of said eye, and decreased intraocular pressure of said eye without surgical intervention.
The applicant reiterates their prior arguments that O’Callaghan 2016 only teaches an AAV vector encoding mouse MMP-3. According to applicant, O’Callaghan does not teach to use human MMP-3 and does not disclose or suggest that human MMP-3 modifies the extracellular matrix of the trabecular meshwork of the eye, or that glaucoma can be treated without surgical intervention by administering human MMP-3 to increase outflow and decrease IOP through modification of the extracellular matrix of the trabecular meshwork. The applicant also argues that Mamiya et al. does not teach an AAV vector as claimed and only teaches a pTracer-CMV-vector containing human MMP-3, and that Mamiya et al. does not teach injection of any vector into the anterior chamber of the eye. The applicant also argues that the claims as amended recite functional features which are specific characteristics of the claims and not “intended” (intended use?). According to applicant these recited “characteristics” are not inherent in the murine MMP-3 taught by O’Callaghan. In addition, the applicant argues that O’Callaghan et al. does not provide evidence that the skilled artisan at the time of filing would have expected success in cloning a sequence other than murine MMP-3 into the AAV2/9 vector. Finally, the applicant argues that the teaching of Mamiya that human MMP-3 can be expressed under the control of the CMV promoter in the eye does not “require” that human MMP-3 expressed from an AAV would have the functional characteristics now recited in claim 1.
As noted, claims 1-2, 6-7, 9-10, and 13-15 are product claims, not method claims. The claims as amended now, as described above, list a number of functional effects stemming from an intended use of administering the claimed rAAV vector to the anterior chamber of the eye. The applicant has argued the nonobviousness of the product in two ways. The applicant argues that neither O’Callaghan et al. nor Mamiya et al. independently teach an rAAV encoding human MMP-3 under operative control of a constitutive promoter and that neither reference provide evidence that the skilled artisan at the time of filing would have expected success in cloning a sequence other than murine MMP-3 into the AAV2/9 vector. The applicant also argues that claimed functional properties are not inherent and that neither reference teaches these specific functional characteristics.
In response to applicant’s argument that there is no evidence that the skilled artisan would have expected success in cloning human MMP-3 into an AAV2/9 vector, it is noted that O’Callaghan 2016 was cited for teaching a pseudotyped AAV 2/9 vector comprising a CMV promoter operatively linked to a murine MMP3 coding sequence (O’Callaghan 2016, abstract, page 1). O’Callaghan et al. reported no issues with the well-known technique utilized to make recombinant AAV2/9 encoding murine MMP-3. The applicant has also previously acknowledged that the vector taught by O’Callaghan et al. is the same as that claimed with the difference being that O’Callaghan used a mouse rather than a human MMP3 coding sequence in the AAV vector. Mamiya et al. was cited to supplement O’Callaghan et al. by teaching a plasmid encoding human MMP3 under transcriptional control of the CMV promoter which can be used to express human MMP3, including in the eye of patients with glaucoma (Mamiya et al., pages, 405-406). Thus, Mamiya et al. teaches vectors encoding human MMP3 useful for expressing human MMP3 in the eye of patients with glaucoma. Both O’Callaghan et al. and Mamiya were therefore equally successful in inserting MMP3 sequences into vectors, including an AAV vector, using well known methods of genetic engineering, where the resulting vectors where capable of expressing the MMP3 protein, either the murine or human MMP3 protein, in the eye. Based on the success generation of vectors encoding MM3, including human MMP3 using well known techniques of genetic engineering, the skilled artisan would have had more than a reasonable expectation of making an AAV vector encoding the human MMP3 protein instead of the mouse MMP3 protein. Further, the applicant has not actually provided any evidence that the skilled artisan would not have predicted that well known techniques in genetic engineering would have failed to insert a human MMP3 coding sequence into an AAV such as the AAV2/9 vector taught by O’Callaghan. As such, this argument is not found persuasive.
Turning to the newly recited functional characteristics, it is noted that these functional characteristics are clearly related to an intended use of the AAV vector for administration into the anterior chamber of the eye. The functional effects recited stem from the activity of the AAV vector when present in the anterior chamber of the eye, or from the human MMP3 protein expressed from the vector in cells of the eye. Such effects, including transduction of eyes in the eye, and the effects of human MMP3 on elements within the eye, such as the extracellular matrix of the trabecular meshwork of the eye, outflow, or intraocular pressure, are considered inherent functional affects of the AAV vector and encoded MMP3 in the anterior chamber of the eye. Note that the express, implicit, and inherent disclosures of a prior art reference may be relied upon in the rejection of claims under 35 U.S.C. 103. "The inherent teaching of a prior art reference, a question of fact, arises both in the context of anticipation and obviousness." In re Napier, 55 F.3d 610, 613, 34 USPQ2d 1782, 1784 (Fed. Cir. 1995), See also In re Grasselli, 713 F.2d 731, 739, 218 USPQ 769, 775 (Fed. Cir. 1983). Furthermore, in terms of whether mouse MMP-3 and human MMP-3 are inherently capable of affecting the trabecular network, the applicant is further reminded that there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003). See also the Federal Circuit decision in Santarus, Inc. v. Par Pharms., Inc., 694 F.3d 1344 (Fed. Cir. 2012), affirming the district court’s holding that claims directed to certain pharmaceutical compositions would have been obvious. The patent claims at issue recited specific blood serum concentrations following administration, and the prior art did not disclose these concentrations. The court nevertheless found that the prior art rendered the formulation obvious, because “an obvious formulation cannot become nonobvious simply by administering it to a patient and claiming the resulting serum concentrations.” Id. at 1354. The court further stated that ”[t]o hold otherwise would allow any formulation—no matter how obvious—to become patentable merely by testing and claiming an inherent property.” The instant claims, like those in Santarus, Inc. v. Par Pharms., Inc, are now claiming inherent functional effect stemming from the administration of either an AAV vector, or human MMP-3 in the anterior chamber of the eye.
O’Callaghan et al. clearly teaches that AAV2/9 vector, when administered to the anterior chamber of the eye, transduced cells in the eye, resulting in secretion of encoded protein, specifically murine MMP3. O’Callaghan et al., further teaches that secreted MMP in the aqueous humor will be directed by the flow of the aqueous humor to the trabecular meshwork (O’Callaghan et al., abstract page 2). O’Callaghan et al. also demonstrated increased outflow facility, where increased outflow is associated with lower intraocular pressure, and suggests use of their method for therapy of glaucoma. While applicant is correct that O’Callaghan et al. expressed murine not human MMP3, there is no evidence of record that the function of human MMP3 differs from that of murine MMP3. Further, Mamiya et al. was cited to supplement O’Callaghan et al. by teaching the delivery of a plasmid encoding human MMP3 under transcriptional control of the CMV promoter to the eye in rabbits and the effects of expression of human MMP3 on intraocular pressure following trabeculectomy surgery, a widely used surgical means for treating glaucoma (Mamiya et al., pages 405-406). Mamiya et al. teaches that expression of human MMP3 significantly decreased intraocular pressure following trabeculectomy and that the expression of human MMP-3 may be used for glaucoma patients (Mamiya et al., abstract, and pages 405-408). Thus, Mamiya et al. provides evidence that the human MMP3 protein can be expressed by a vector in the eye and that the human MMP3 protein, like the murine MMP3 protein tested by O’Callaghan et al., is functional in the eye of a mammal, can decrease intraocular pressure in the eye, and be therapeutic for glaucoma. As such, the evidence provided by O’Callighan et al. and Mamiya et al. supports the similarity in the effects of murine and human MMP3 in the eye of a mammal, supports the ability to transduce cells the anterior chamber of the eye with an AAV vector, supports the secretion of an MMP3 protein from a transduced cell in the anterior chamber of the eye, and supports the role of secreted MMP3 in increasing outflow and deceasing intraocular pressure. O’Callaghan et al. further supports that secretion of MMP3 the anterior chamber of the eye reaches the trabecular meshwork via the flow of aqueous humor. Thus, the evidence provided by O’Callaghan and Mamiya support the inherency of any effect of human MMP3 on trabecular meshwork stemming from administration of an AAV vector encoding MMP3 under operative control of a constitutive promoter. Thus, applicant’s arguments that the newly recited functional characteristics overcome the rejection is not found persuasive.
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication from the examiner should be directed to Anne Marie S. Wehbé, Ph.D., whose telephone number is (571) 272-0737. If the examiner is not available, the examiner’s supervisor, Maria Leavitt, can be reached at (571) 272-1085. For all official communications, the technology center fax number is (571) 273-8300. Please note that all official communications and responses sent by fax must be directed to the technology center fax number. For informal, non-official communications only, the examiner’s direct fax number is (571) 273-0737. For any inquiry of a general nature, please call (571) 272-0547.
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Dr. A.M.S. Wehbé
/ANNE MARIE S WEHBE/Primary Examiner, Art Unit 1634