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 .
Applicant’s response filed 02/27/2026 has been received and entered into the case record.
No new claims are added, no claims are amended and no claims are canceled.
Therefore, claims 2, 4-9, 11-13, 22, 24, 28, 42, 45, 49-50, 55, 62 and 67 are pending in the application and examined on the merits.
Maintained objections/ Rejections in response to Applicants’ arguments or amendments
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 (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
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.
Claim 2, 22, 24, 28, 55 and 67 remain rejected under 35 U.S.C. 103 as being unpatentable over Dodge et al. (US 2010/0267812; IDS Reference Citation No. 1 filed on 08/30/2018) in view of Kay (US2010/0324127; previously cited in PTO-892) and Cenik (THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 286, NO. 18, pp. 16101–16108; previously cited in PTO-892)
Regarding Claims 2 and 67, Dodge et al. teaches a method of treating a disease effecting a subject’s motor function via a vector or recombinant AAV particles (para. 0001, 0009, 0034, 0073, 0084, 0092). Dodge teaches that progranulin mutations cause frontotemporal lobar degeneration (para. 0067). The treatment solution was administered to a mammal’s brain ventricle, such as a lateral ventricle, so that it contacts the CSF (para. 0081, 0090, Example 1-3). This treatment involves the therapeutic product being delivered to target cells of the CNS which can be neurons or glial cells (para. 0049).
However Dodge et al. does not specifically disclose that the progranulin encoding vector has a 95% or more identity to that of SEQ ID: 1 of the instant application, nor does it disclose that the method is specifically for the treatment of Frontal Temporal Dementia (FTD).
Kay teaches methods and compositions for treating neurodegenerative diseases such as Alzheimer’s, Parkinson’s and ALS (Abstract, 0100). In said method a nucleic acid encoding a progranulin polypeptide is administered to a patient via a vector and said peptide has at least a 95% homology to SEQ ID NO: 2 and modifies the expression of progranulin in order to modify the expression and reduce symptoms of the neurological disease (para. 0007-0009, 0013-0014, 0081, 0082, 0085-0086). These polypeptides can be administered via vector and nucleic acid constructs intraventricularly, intracerebrally and through other routes (para. 0009, 0085-0086). A sequence search was performed, and showed that SEQ ID NO: 2 of Kay and SEQ ID NO: 1 of the instant application are the same sequence (i.e. 100% sequence identity).
Cenik et al. teaches that FTD is caused by a loss-of-function mutation (p. 16101, bridging paragraph). Thus, enhancing the expression of PGRN (i.e. increased amount of PGRN) is a method which could potentially prevent the progression or slow down FTD (i.e. treat FTD) as haploinsufficiency of progranulin is a frequent cause of the syndrome (Abstract, p. 16101, 2nd column).
It would have been obvious to one of ordinary skill in the art to substitute the progranulin nucleotide in the progranulin encoding vector as taught by Dodge et al. with the nucleic acid encoding the progranulin polypeptide corresponding to SEQ ID NO: 2 (i.e. SEQ ID NO: 1 of the instant application) contained in a vector as taught by Kay to treat FTD with a reasonable expectation of success. An artisan would be substituting known sequences for encoding the progranulin protein in vectors for the same purpose of treating neurodegenerative disease. As each and every method step is taught by the references of Kay and Dodge, it would be obvious to one of ordinary skill in the art that the same result of an increase of progranulin would additionally be the same. As Cenik et al. teaches that a lack of progranulin causes FTD and that enhancing the expression of PGRN in a subject lacking PGRN is a method which could potentially prevent the progression or slow down the disease (p. 16101, 2nd column), an artisan would be motivated to utilize the method steps of the combined references of Dodge and Kay for the purpose of treating FTD by increasing progranulin.
Regarding the limitation that the progranulin would be found in the lateral ventricle, frontal cortex, striatum and brain stem, as each and every method step is taught by the combination of references above in administering progranulin, the same method steps would yield the same predictable results of progranulin being expressed within the CSF and brain.
Regarding claim 22, Dodge et al. teaches that the therapeutic product is delivered to target cells of the CNS which can be neurons or glial cells (para. 0049).
Regarding claim 24, Dodge et al. teaches that the cell can secrete the therapeutic gene product (i.e. progranulin) in the CSF (para. 0006, 0009).
Regarding claim 28, Dodge et al. teaches that the vector can be injected into one or more of the ventricular spaces of the brain (i.e. more than one location in the brain) (para. 0091).
Regarding claim 55, Dodge et al. teaches that the subject is a mammal and said mammal is a human (para. 0040).
Therefore, the invention as a whole would be obvious to one of ordinary skill at the time of the effective filing date.
Claim 2, 4-9, 11-13, 42, 45, 49, 50 and 67 are rejected under 35 U.S.C. 103 as being unpatentable over Passini et al. (US 2013/0287736; IDS Reference Citation No. 2 filed on 08/30/2018) in view of Kay (US2010/0324127; previously cited in PTO-892) and Cenik (THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 286, NO. 18, pp. 16101–16108; previously cited in PTO-892)
Regarding claims 2, 4, 49, 50, and 67, Passini et al. teaches a method of treating neurodegenerative disorders via a rAAV vector. The vector can be administered via intrathecal injection, intraparenchymal injections, and ventricular region wherein it contacts cells in the CSF and expresses progranulin (Abstract, para. 0061, 0073, 0148, 0155). Passini et al. also teaches that a sequence coding for a transgene, such as progranulin, is inserted between a pair of inverted terminal repeats (ITRs) in the AAV vector (para. 0073, 0090, 0176, 0158).
However, Passini et al. does not specifically disclose that the progranulin encoding vector has a 95% or more identity to that of SEQ ID: 1 of the instant application, nor does it disclose that the method is specifically for the treatment of FTD.
Kay teaches methods and compositions for treating neurodegenerative diseases such as Alzheimer’s, Parkinson’s and ALS (Abstract, 0100). In said method a nucleic acid encoding a progranulin polypeptide is administered to a patient via a vector and said peptide has at least a 95% homology to SEQ ID NO: 2 and modifies the expression of progranulin in order to modify the expression and reduce symptoms of the neurological disease (para. 0007-0009, 0013-0014, 0081, 0082, 0085-0086). These polypeptides can be administered via vector and nucleic acid constructs intraventricularly, intracerebrally and through other routes (para. 0009, 0085-0086). A sequence search was performed, and showed that SEQ ID NO: 2 of Kay and SEQ ID NO: 1 of the instant application are the same sequence (i.e. 100% sequence identity).
Cenik et al. teaches that FTD is caused by a loss-of-function mutation (p. 16101, bridging paragraph). Thus, enhancing the expression of PGRN (i.e. increased amount of PGRN) is a method which could potentially prevent the progression or slow down FTD (i.e. treat FTD) as haploinsufficiency of progranulin is a frequent cause of the syndrome (Abstract, p. 16101, 2nd column).
It would have been obvious to one of ordinary skill in the art to substitute the progranulin nucleotide in the progranulin encoding vector as taught by Passini et al. in the method of treating neurodegenerative disorders with the progranulin polypeptide corresponding to SEQ ID NO: 2 (i.e. SEQ ID NO: 1 of the instant application) contained in a vector as taught by Kay in a method of treating FTD via as taught by Cenik et al. with a reasonable expectation of success. An artisan would be substituting known sequences encoding the progranulin protein in vectors for the same purpose of treating neurodegenerative disease when utilizing the progranulin polypeptide of Kay in place of the progranulin polypeptide of Passini et al.
As each and every method step is taught by the references of Kay and Dodge, it would be obvious to one of ordinary skill in the art that the same result of an increase of progranulin would additionally be the same. An artisan would be motivated to increase progranulin in a patient with FTD as Cenik et al. teaches that a lack of progranulin causes FTD and that enhancing the expression of PGRN is a method which could potentially prevent the progression or slow down the disease (p. 16101, 2nd column). Furthermore, the limitations of preventing worsening or improving symptoms of FTD are inherent to the treatment of FTD. If FTD is treated, symptoms would be improved.
Regarding the limitation that the progranulin would be found in the lateral ventricle, frontal cortex, striatum and brain stem, as each and every method step is taught by the combination of references above. the same method steps would yield the same predictable results of the location at which the progranulin is expressed within the CSF and brain would be obtained with a reasonable expectation of success.
Regarding claim 5, Passini et al. teaches rAAV virons can encode a gene of interest (i.e. nucleic acid sequence) between its two AAV ITRs. (para. 0097-0098, 0100-0101)
Regarding claim 6, Passini et al. teaches the AAV capsid protein of the rAAV virons can be selected from AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, and AAV9 (para 0147).
Regarding claim 7, Passini et al. teaches the ITRs of the rAAV virons can be derived from AAV-1, AAV-2, AAV-3, AAV-4, AAV-5, AAV-6, AAV-7, AAV-8, and AAV-9 (para. 0107)
Regarding claims 8, 9, and 11, Passini et al. teaches that AAV vectors are known to have expression control elements such as promoters or enhancers like the CMV enhancer and chicken beta actin promoter (para. 0108).
Regarding claims 12 and 13, Passini et al. teaches that a dose of about 106 to about 1015 genome particles are administered to a subject (para. 0160).
Regarding 42 and 45, Passani et al. does not explicitly teach that method of treatment inhibits, decreases, or prevents neuron degeneration nor that said neurons are cortical neurons, however, as the combined references of Passani, Kay and Cenik et al. teach each and every method step in the claimed invention, the results would be the same in that the treatment would inhibit, decrease or prevent cortical neuron degeneration.
Therefore, the invention as a whole would be obvious to one of ordinary skill in the art.
Claim 62 is rejected under 35 U.S.C. 103 as being unpatentable over Passini et al. (supra) in view of Kay (supra) and Cenik et al. (supra) as applied to claims 2, 4-9, 11-13, 42, 49, and 50 above, and in further view of Pasqualetti et al. (Curr Neurol Neurosci Rep (2015) 15: 17)
As discussed in the above 103 rejection, Passini et al., Kay and Cenik et al. make obvious a method of treating FTD by administering a vector comprising a progranulin encoding polynucleotide sequence with a 95% identity to the polynucleotide sequence of the instant claims SEQ ID NO: 1. Furthermore, regarding the limitation that the progranulin would be found in the lateral ventricle, frontal cortex, striatum and brain stem, as each and every method step is taught by the combination of references in administering progranulin, the same method steps would yield the same predictable results of the location at which the progranulin is expressed within the CSF and brain would be obtained with a reasonable expectation of success. These references however do not teach administering one or more immunosuppressive agents during the treatment involving administering progranulin polypeptides.
The instant specification discloses that the immunosuppressive agents are anti-inflammatory agents (para. 0056).
Pasqualetti et al. teaches that neuroinflammation is a common feature of dementia (Abstract). The reference further teaches that the inflammatory signals induce microglia to an activated state leading to morphological changes and secretion of pro-inflammatory which in turn maintain the inflammatory status and favor the production of reactive oxygen species (ROS) which can cause neuronal death (Figure 1 + description).
It would be obvious to one of ordinary skill in the art to utilize the method of treating neurodegenerative disease such as FTD and its symptoms via administering a vector comprising a polypeptide encoding progranulin as taught by Passini et al. additionally with an anti-inflammatory agent. An artisan would be motivated to administer an anti-inflammatory agent in a method of treating FTD as Pasqualetti et al. teaches that inflammatory signals cause a series of events which can lead to neuronal death in FTD (Figure 1 + description). Thus administering an anti-inflammatory agent would be beneficial in preventing neuronal death.
Therefore, the invention would have been obvious to one of ordinary skill in the art at the time of the effective filing date.
Response to arguments
Applicant’s arguments filed 02/27/2026 with respect to the 103 rejections set forth in the previous Office Action have been considered, however they are not persuasive.
First, Applicant addresses the 103 rejection over Dodge, Kay and Cenik. Applicant argues that the references fail to support that the wherein limitations are inherent or predictable as there is no evidentiary basis provided for the conclusion being made. Specifically, Applicant states that the references do not mention the presence of progranulin in each of the recited regions.
In response to applicant's argument that there is no evidentiary reference stating the presence of progranulin in the regions of the brain, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). Obviousness does not need evidentiary references, as each and every method step is the same, the predictability that the same outcome would also occur is present as it would naturally flow from the process claimed and what the references teach. Applicant has not pointed out any specific detail such as dosage or critical element nor made an amendment that separates the present invention and its method from the prior art references combined teachings. If there is an element which provides for the progranulin reaching brain regions which is not contemplated by the combined references and without which the administration of vectors as taught by Dodge, Kay and Cenik will not reach the regions, it must be indicated and claimed.
Applicant additionally argues that claim 2 is not limited to patients having a progranulin mutation or a need for restoration of progranulin.
Examiner agrees that it is not. As stated in the rejection, Cenik et al. teaches that FTD is caused by a loss-of-function mutation (p. 16101, bridging paragraph). The claims are directed towards individuals with FTD therefore the claims encompass a mutation which causes a loss of function of progranulin and is rescued in order to treat the symptoms. If the invention is not directed towards those with a mutation, Applicant is advised to amend the claims as such to better indicate the population treated by the method.
Applicant reiterates arguments of Gonzalez previously discussed in multiple office actions and also states that many of the references state that progranulin is pleiotropic which can be implicated in tumorigenesis.
Examiner reiterates that while Gonzalez states that tumor cells can form in the SVZ, it does not specifically teach away from administering therapeutics such as PGRN to the CSF would result in said tumor cells. Gonzalez-Perez merely states general risk factors of SVZ cells in general therapies and is not a deterrent which would directly teach away from the practice and the references utilized to support obviousness. Therefore, the reasonable expectation of success is still founded based on the references.
Second, Applicant addresses the 103 rejection over Passini, Kay and Cenik. Applicant argues that progranulin is one choice among a numerous list. Additionally, Applicant argues that one cannot assert the same results because method steps are taught in references. Lastly, Applicant argues that the Office has improperly associated intended purpose with guaranteed result in claims such as claim 49 and 50.
Examiner states that while progranulin is in a list in Passini, the secondary references are utilized in order to support the obviousness of choosing progranulin from the list. Examiner reiterates that as each and every method step is the same, the predictability that the same outcome would also occur is present as it would naturally flow from the process claimed and what the references teach. Applicant has not pointed out any specific detail such as dosage, method step or critical element nor made an amendment that separates the present invention and its method from the prior art references combined teachings. If there is an element which provides for the claimed method results which is not contemplated by the combined references and without which the administration of vectors as taught by Passini, Kay and Cenik will not have the same results, Applicant is advised to indicate and include the limitation within the claims. Regarding the arguments of claims 49 and 50, it is not stated in the rejection that the intended purpose teaches the guaranteed outcome. It is known in the art that if an artisan is to treat FTD, treatment indicates an improvement in a symptom or a lessening of an adverse effect by definition. Therefore, it would be inherent to the concept of treatment itself.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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.
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/ALEXANDRA F CONNORS/Examiner, Art Unit 1634
/JAMES D SCHULTZ/Supervisory Patent Examiner, Art Unit 1631
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