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 .
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.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission of RCE on 5/13/26 and the amendment of claims has been entered.
Status of the Claims
Applicant’s election without traverse of Group II, drawn to a method of treating obesity or obesity related disorder comprising administering an FKBP-L polypeptide, a biologically active fragment of an FKBP-L polypeptide, a derivative of an FKBP-L polypeptide, or a derivative of a biologically active fragment of an FKBP-L polypeptide, or a nucleic acid sequence capable of being expressed in a subject to provide FKBP-L or a biologically active fragment or derivative thereof, claimed in claims 8-11 and 14-16 was previously acknowledged.
Election was made without traverse of the nucleic acid, SEQ ID NO: 30 (nucleic acid sequence) and diabetes (disorder).
A search of the prior art uncovered the elected and unelected species. Therefore, the species election was withdrawn.
In the reply filed 2/12/24, Applicants amended claims 8 and 14. Claims 9-11 and 15-16 were canceled. Claims 17-22 are newly added.
In the reply filed 9/30/24, Applicants amended claim 8.
In the reply filed 8/12/25, Applicants amended claim 8.
In the RCE filed 5/13/26, Applicants did not amend or cancel any claims.
Claims 1-8, 12-14 and 17-22 are pending.
Claims 1-7 and 12-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group, there being no allowable generic or linking claim.
Claims 8, 14 and 17-22 read on the elected Group II and are under consideration.
Claim Rejections - 35 USC § 103-Maintained and Modified
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.
The rejection of claims 8, 14 and 17-20 are rejected under 35 U.S.C. 103 as being unpatentable over Robson et al. (US 2009/0192085) as evidenced by NIH National Eye Institute (https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/diabetic-retinopathy accessed 2/8/25) is maintained.
Robson et al. teach FKBP-L polypeptides and nucleic acids for treatment of a disorder mediated by angiogenesis with a polynucleotide encoding an FKBP-L polypeptide [0010]. Robson et al. claims a method of inhibiting angiogenesis in a subject in need thereof, comprising a polynucleotide encoding an FKBP-L peptide (claim 34). In particular, Robson et al. teach treatment of diabetic retinopathy [0094, 0222,0226]. Robson et al. teach angiogenic damage is associated with diabetic retinopathy [0226] and claims treatment of a subject with an ocular disorder mediated by angiogenesis (claim 37) Robson et al. teach FKBP-L polynucleotides that encode FKBP-L peptides are shown in nucleotide sequences of SEQ ID NO: 30-39. Figure 2 ,discloses polypeptide sequences of full length FKBP-L and some of its deletion mutants and variant [0015]. Instant SEQ ID NO: 30 is identical to SEQ ID NO: 30 of Robson et al. Robson et al. teach the invention comprises vectors containing the isolated nucleic acid molecules of the invention, and comprise cells transfected with such vectors, such that an FKBP-L polypeptide is expressed [0107]. Therefore, Robson et al. teach the FKBP-L polypeptide encoded by the nucleic acid sequence of SEQ ID NO: 30, meeting the limitations of claims 8 (in part a).
Robson et al. does not teach an example of treatment of diabetic retinopathy or diabetes. However, the teachings of Robson et al. are suggestive of the limitation.
In addition to the teachings above, Robson et al. teach treatment of wound healing including diabetic chronic ulcers [0220]. Robson et al. teach that methods of the invention can be used to treat diabetic retinopathy and diabetic neovascularization [0094, 0222, 0226].
Diabetic retinopathy is an eye condition that can cause vision loss and blindness in people who have diabetes. Please note that MPEP 2131.01 states: that an extra reference or evidence can be used to show an inherent characteristic of the thing taught by the primary reference. In the instant case, The NIH National Eye Institute is relied upon only to establish that diabetic retinopathy is an eye condition is people who are diabetic.
A person of ordinary skill in the art would have been motivated to administer the nucleic acid and FKBP-L peptides of Robson et al. (SEQ ID NO: 2, 10, 30) to diabetic subjects because the Robson et al. teaches its use for diabetes associated conditions including diabetic retinopathy, and diabetic chronic ulcers. Given that the reference teaches methods of making and administering the polypeptides and identifies diabetes associated disorders as therapeutic targets, a person of ordinary skill in the art would have had a reasonable expectation of success in using the FKBP-L peptide in diabetic subjects. Furthermore, because the prior art method makes obvious administering the same polypeptide to the same patient population, the anti-diabetic activity would have inherently been present even though the reference does not expressly disclose the property. In other words, Robson et al. teach administering the same composition (FKBP-L nucleic acid or polypeptide ) to the same patient population (a subject that has diabetes and is suffering from diabetic retinopathy), therefore the same results would necessarily occur. Moreover, MPEP 2112.01 states: “Products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.
With respect to claim 14, Robson et al. teach nucleic acids, including RNA [0060,0175].
With respect to claims 17-20, Robson et al. teach nucleic acids, including DNA and RNA [0060,0175]. Robson et al. teach a wide variety of host cells may be used for expression of the nucleic acids [0177]. Robson et al. teach FKBP-L fragments of SEQ ID NO: 10 (which identical to instantly claimed SEQ ID NO: 10), SEQ ID NO: 14 (which is identical to instantly claimed SEQ ID NO: 40), meeting the limitations of claims 17-20.
Response to Arguments
Applicant's arguments filed 5/13/26 have been fully considered but they are not persuasive. Applicants argue that the Examiner’s rejection is predicated on a fundamental mischaracterization of the claimed invention. Applicants argue that the claims are expressly directed to the treatment of the systemic metabolic disorder-diabetis0 and the ameliorating the effects of that disease, not diabetic retinopathy. Applicants argue that Robson is drawn to treatment of disorders mediated by angiogenesis and does not suggest the peptides/nucleic acids could be used for treatment of diabetes. Applicants argue that diabetes is systemic disorder of glucose and metabolic regulation while diabetic retinopathy is a retinal specific microvascular and neuroinflammatory pathology. Applicants argue that the retinal abnormalities, once established may continue to progress despite improvements in systemic glycemic parameters. Applicants argue that large clinical trials demonstrate that improved glycemic control can reduce the risk of retinopathy onset and slow progression at a population level but retinopathy may continue to progress in individual patients despite achievement in guideline recommended glycemic targets. Applicants further argue that the management of established diabetic retinopathy relies on eye specific interventions, including intravitreal pharmacotherapies targeting angiogenic and inflammatory pathways. Applicants argue these ocular therapies address local retinal disease mechanisms that are not adequately managed by systemic antidiabetic therapy alone. Applicants argue that any therapeutic effect of FKBP-L based agents in diabetic retinopathy would arise from their direct biological activity on retinal pathogenic pathways, such as modulation of angiogenesis and vascular stability, rather than representing a consequence of improved systemic glycemic control. Applicants argue that the reliance on inherency is wrong because it equates treating an ocular condition with treating an underlying systemic metabolic disease. Applicants argue that Robson teaches treatment of diabetic retinopathy as an angiogenesis mediated ocular disorder and anti-angiogenic activity directed at retinal vasculature does not inherently ameliorate the systemic effect of diabetes. Applicants argue there is no basis to conclude that administration of an anti-angiogenic agent to a patients eye would necessarily treat the patients underlying disease. Applicants state that they agree that a subject with diabetic retinopathy is necessarily a subject that is diabetic, however it does not establish that treating one condition necessarily treats the other. Applicants argue that not all diabetic patients have diabetic retinopathy. Applicants argue that Robsons entire disclosure is focused on modulating angiogenesis and tumor metastasis.
These arguments were considered but are not persuasive because administering the same nucleic acid or polypeptide of Robson et al. would necessarily have all of the activities and properties of the composition of claim 8. Please see MPEP § 2112. Robson et al. teach administering the same composition (FKBP-L nucleic acid or polypeptide ) to the same patient population (a subject that has diabetes and is suffering from diabetic retinopathy), therefore the same results would necessarily occur. Moreover, MPEP 2112.01 states: “Products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. The rejection does not rely upon a finding that treating diabetic retinopathy necessarily constitutes treatment of diabetes. Rather, Robson teaches administering the same peptide to diabetic patients suffering from diabetic retinopathy or diabetic ulcers. Thus, the reference teaches administration of the claimed compound to the same patient population. Importantly, applicants specification discloses administration of the peptide improves glucose tolerance. Therefore, administration of the identical compound would inherently possess the same biological properties regardless of whether the reference expressly recognized or describes such properties. The arguments regarding the pathophysiology of diabetes and diabetic retinopathy do not rebut the finding that the prior art teach administration of the identical compound to diabetic subject. The argument that the patient population is distinct because not all diabetic patients have diabetic retinopathy is not persuasive because diabetic retinopathy is a complication of diabetes and occurs in subjects that have diabetes. Therefore, a subject that has diabetic retinopathy is necessarily a subject that is diabetic.
For the reasons presented above, the rejection is maintained.
The rejection of claims 8, 14 and 17-22 under 35 U.S.C. 103 as being unpatentable over Robson et al. (US 2009/0192085, cited on IDS) as evidenced by NIH National Eye Institute in view of McCarthy et al. (WO2014/087023, cited on IDS) is maintained.
The teachings of Robson et al. are presented above in detail. The reference does not teach the composition further comprises the delivery peptide, RALA. However, the teachings of McCarthy et al. cure this deficiency.
McCarthy et al. teach amphipathic peptides for delivery of small molecules, in particular therapeutic agents that include nucleic acids or other small molecules (Abstract; Introduction p. 1, 1st para.). McCarthy et al. teach the amphipathic peptide of RALA (Table 1, p. 3). McCarthy et al. teach that it is understood that the amphipathic cell penetrating peptide complexes to nucleic acids or other agents to form a nanoparticle which penetrates a cell (p. 4, lines 18-23). McCarthy et al. provides examples of RALA peptide for complexed with nucleic acids for delivery to a cell (Fig. 2-9).
With respect to claims 21 and 22, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the invention to complex the FKBP-L nucleic acid to the RALA peptide of McCarthy et al. for delivery to a cell. A person of ordinary skill in the art would be motivated to include the RALA peptide because McCarthy et al. teach that RALA complexes to nucleic acids and forms a nanoparticle which penetrates a cell. Therefore, a skilled artisan would be motivated to include RADA with the nucleic acid of Robson et al. to deliver the nucleic acid for treatment diabetic retinopathy. There is a reasonable expectation of success given that McCarthy et al. teaches RALA nucleic acid complexes are delivered to cells.
Response to Arguments
Applicant's arguments filed 5/13/26 have been fully considered but they are not persuasive. Applicants argue McCarthy does not cure the deficiencies of Robson.
This argument is not persuasive for the reasons presented above.
Response to Amendment
The Affidavit under 37 CFR 1.132 filed 5/13/26 is insufficient to overcome the rejection of claims. The Declaration states the diabetes is the primary systemic risk factor for diabetic retinopathy and development of retinopathy is related to the duration and quality of metabolic control in diabetes mellitus. The Declaration states that large clinical trials have demonstrated that improved glycemic control and optimization of systemic factors such as blood pressure are essential components of diabetic retinopathy management and can reduce the risk of retinopathy onset and slow progression at a population level. The Declaration states that evidence indicates that retinopathy may continue to progress despite achievements in guideline recommended glycemic targets. The Declaration states that management of diabetic retinopathy relies on eye specific interventions including intravitreal pharmacotherapies alongside systemic optimization of glycemic control and blood pressure. The Declaration states that on this basis, any therapeutic effect of FKBP-L based agents in diabetic retinopathy would arise from their direct biological activity on retinal pathogenic pathways such as modulation of angiogenesis and vascular stability, rather that representing a consequence of improved glycemic control.
The Declaration and references cited were considered but are not persuasive. First, diabetic retinopathy is by definition a diabetic disease manifestation. A diagnosis of diabetic retinopathy occurs from diabetes and the fact that a patients glucose is controlled does not mean the patient no longer has diabetes. .Importantly, applicants specification discloses administration of the peptide improves glucose tolerance. Therefore, administration of the identical compound would inherently possess the same biological properties regardless of whether the reference expressly recognized or describes such properties. The arguments regarding the pathophysiology of diabetes and diabetic retinopathy do not rebut the finding that the prior art teach administration of the identical compound to diabetic subject. The argument that the patient population is distinct because not all diabetic patients have diabetic retinopathy is not persuasive because diabetic retinopathy is a complication of diabetes and occurs in subjects that have diabetes. Therefore, a subject that has diabetic retinopathy is necessarily a subject that is diabetic.
Conclusion
No claims are allowed.
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/TARA L MARTINEZ/ Examiner, Art Unit 1654
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