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
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 filed on 10/8/2025 has been entered.
Claim Status
Claims 1, 19-20, 49 and 51-56 are pending. Claims 52-56 have been added. Claims 23, 25, 27, 29, 31, 41-46 and 50 have been canceled. Claims 1, 49 and 51 have been amended. Claims 1, 19-20, 49 and 51-56 are being examined in this application. In the response to the restriction requirement, Applicants elected Group I, SEQ ID NO: 2, SEQ ID NO: 13 (cell penetrating agent), diabetic nephropathy, and metformin.
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.
This rejection has been modified.
Claims 1, 19-20, 49 and 51-56 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the treatment of diabetic nephropathy with SEQ ID NO: 33, does not reasonably provide enablement for curing or preventing diabetic nephropathy with SEQ ID NO: 33. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The MPEP states:
“There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.” These factors include, but are not limited to: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.”
(A) The breadth of the claims; and (B) The nature of the invention;
The claims are drawn to a method for treating a renal disorder in a subject in need thereof, the method comprising administering to a subject having diabetic nephropathy an effective amount of a peptide comprising the amino acid sequence set forth in SEQ ID NO: 33, wherein, following the administering step, the level of renal fibrosis and/or the level of renal inflammation are reduced, thereby slowing the progression of the diabetic nephropathy.
The specification teaches that the term “treat” includes preventing and curing (paras [0041]-[0042]).
(C) The state of the prior art;
Gao et al. (J Diabetes Res. 2014 Jan 5;2014:918396) teach that diabetic nephropathy cannot be prevented (para bridging left and right column on page 6).
Nuovo (Am Fam Physician. 1998;57(11):2826) teaches that diabetic nephropathy cannot be cured (page 1, 1st para).
(D) The level of one of ordinary skill;
The skill of those skilled in the art is high.
(E) The level of predictability in the art;
Considering that diabetic nephropathy cannot be prevented or cured, the unpredictability of the prevention or cure of diabetic nephropathy is very high.
Furthermore, considering that the specification only demonstrates the treatment of diabetic nephropathy with SEQ ID NO: 33, the unpredictability of preventing or curing diabetic nephropathy with SEQ ID NO: 33 is very high.
(F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The specification provides only one example showing that SEQ ID NO: 33 could be used to treat diabetic nephropathy.
The MPEP (2164.02) states that " The specification need not contain an example if the invention is otherwise disclosed in such manner that one skilled in the art will be able to practice it without an undue amount of experimentation. In re Borkowski, 422 F.2d 904, 908, 164 USPQ 642, 645 (CCPA 1970).” The MPEP further states that
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“Lack of a working example, however, is a factor to be considered, especially in a case involving an unpredictable and undeveloped art.”
In the instant application, the specification does not provide any guidance to allow for the cure or prevention of diabetic nephropathy with SEQ ID NO: 33.
Considering the state of the art as discussed above and the high unpredictability and the lack of guidance provided in the specification, one of ordinary skill in the art would be burdened with undue experimentation to use the invention as claimed.
Response to Arguments
Applicant’s arguments filed on 10/8/2025 have been fully considered but they are not persuasive.
Applicant argues that the Specification enables the skilled person to use the full scope of currently amended independent Claim 1 and the claims that depend therefrom without undue experimentation.
Applicant’s arguments are not persuasive because, as discussed above, the specification teaches that the term “treat” includes preventing and curing (paras [0041]-[0042]). Therefore, one of ordinary skill in the art would be burdened with undue experimentation to use the invention as claimed.
For the reasons stated above the rejection is maintained.
To overcome this rejection, Applicant’s should amend the specification.
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.
This rejection has been modified.
Claims 49 and 51-56 are 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. Claims 49 and 51 are drawn to inherent properties of SEQ ID NO: 33. Once administered to a patient with diabetic nephropathy, SEQ ID NO: 33, would inherently eliminate fluid accumulation, slow and/or ameliorate increased matrix production, etc. Therefore, claims 49-51 fail to further limit the subject matter of claim 1. With respect to claims 52-56, it has been held that the recitation that an element is “capable of” performing a function is not a positive limitation but only requires the ability to so perform. It does not constitute a limitation in any patentable sense. In re Hutchinson, 69 USPQ 138. Furthermore, the phrase “the subject can have at least….” implies that the subject can also NOT have at least….. Thus, claims 52-56 fail to further limit the subject matter of claim 1. 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.
Response to Arguments
Applicant’s arguments filed on 10/8/2025 have been fully considered but they are not persuasive.
Applicant argues that the claim amendments overcome this rejection.
Applicant’s arguments are not persuasive because, as discussed above, instant claims 49 and 51 are drawn to inherent properties of SEQ ID NO: 33. Therefore, the claims fail to further limit the subject matter of claim 1.
For the reasons stated above the rejection is maintained.
Claim Rejections - 35 USC § 103
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.
This rejection has been modified.
Claims 1, 49, and 51-56 are rejected under 35 U.S.C. 103 as being unpatentable over Offen et al. (WO 2011/033511) in view of Hosseini et al. (Oxid Med Cell Longev. 2013 Apr 24;2013:168039) and Eltoweissy et al. (Mol. BioSyst., 2016, 12, 1842-1859).
With respect to claim 1, Offen et al. teach a method of treating an oxidative stress-related disorder in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an isolated peptide, or peptide mimetic thereof, no longer than 25 amino acids comprising at least 2 consecutive amino acids from the amino acid sequence as set forth in SEQ ID NO: 1, and a pharmaceutically acceptable carrier, wherein the isolated peptide increases viability of a cell under oxidative stress conditions, thereby treating the oxidative stress-related disorder (claim 2), wherein the isolated peptide is SEQ ID NO: 24 (claim 34), which corresponds to instantly claimed SEQ ID NO: 33.
Offen et al. do not teach that the oxidative stress-related disorder is diabetic nephropathy.
Hosseini et al. teach that diabetic nephropathy is an oxidative stress-related disorder (title; abstract; passim).
Eltoweissy et al. teach that protein DJ-1, by incorporating as an endogenous antioxidant defense protein, had an added benefit in ameliorating the progression of fibrosis in renal cells exposed to higher oxidative stress (OS) levels (page 1843, left column, 2nd para).
It would have been obvious to use the method of Offen et al. for the treatment of diabetic nephropathy because Offen et al. teach a method of treating an oxidative stress-related disorder comprising administering the claimed peptide, and Hosseini et al. teach that diabetic nephropathy is an oxidative stress-related disorder.
The skilled artisan would have had a reasonable expectation of success, because the peptide of Offen et al. is a DJ-1 related peptide (see Offen et al. at page 9, lines 25-30), and Eltoweissy et al. teach that protein DJ-1 is effective as an antioxidant defense protein in renal cells exposed to higher oxidative stress (OS) levels.
With respect to the limitation “wherein following the administering step, the level of renal fibrosis and/or the level of renal inflammation are reduced thereby slowing the progression of the diabetic nephropathy”, it is noted that such limitation is inherent to the administering of SEQ ID NO: 33. Once administered, SEQ ID NO: 33 would inherently reduce the level of renal fibrosis and/or the level of renal inflammation.
With respect to the claimed “effective amount”, Offen et al. teach that “[P]harmaceutical compositions suitable for use in context of the present invention include compositions wherein the active ingredients are contained in an amount effective to achieve the intended purpose. More specifically, a therapeutically effective amount means an amount of active ingredients (DJ-1 related peptides) effective to prevent, alleviate or ameliorate symptoms of a disorder (e.g., Parkinson's Disease) or 15 prolong the survival of the subject being treated. Determination of a therapeutically effective amount is well within the capability of those skilled in the art, especially in light of the detailed disclosure provided herein” (page 26, lines 10-17).
Furthermore, the MPEP 2144.05 A states that “[G]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997)”.
Since Applicant has not disclosed that the specific limitations recited in the instant claims are for any particular purpose or solve any stated problem, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum amount to be administered by normal optimization procedures known in the pharmaceutical art.
With respect to claims 49 and 51-56, as discussed above, these claims fail to further limit the subject matter of claim 1, thus, they are obvious over the references.
Response to Arguments
Applicant’s arguments filed on 10/8/2025 have been fully considered but they are not persuasive.
Applicant argues that “[T]he combination of these 3 references does not render as obvious currently amended independent Claim 1. Offen focuses on Parkinson's Disease (PD) and notes that the pathogenesis of PD centers on the formation of reactive oxygen species and the onset of oxidative stress leading to the oxidative damage to substantive nigra pars compacta. (page 1, 11. 26-28). Although Offen lists a number of "oxidative stress related diseases" (page 2, 11. 6-12), Offen fails to identify diabetic nephropathy (as currently claimed) as one of those oxidative stress related diseases (which the Office Action acknowledged). But, Hosseini cannot cure this deficiency. Contrary to the Office Action's assertion, Hosseini does not teach "that diabetic nephropathy is an oxidative stress-related disorder". (See Office Action, p. 7). Rather, Hosseini teaches that diabetic neuropathy is "a microvascular complication of diabetes, comprises disorders of peripheral nerve in people with diabetes when other causes are ruled out." (Hosseini, page 1, col. 1, para. 2). As known to the skilled person, diabetic neuropathy is not a teaching of diabetic nephropathy.
Applicant also argues that Althought Hosseini characterizes diabetic neuropathy as a "widespread disabling disorder comprising peripheral nerves' damage" (see Abstract), and "focused on the links between DN and oxidative stress", Hosseini fails to teach that "diabetic nephropathy is an oxidative stress-related disorder" as stated by the Office Action (see p. 7, final sentence). In fact, Hosseini fails to provide any teaching or suggestion of diabetic nephropathy, the kidney, or renal function. Hosseini cannot cure the deficiencies of Offen and cannot be used to extend Offen's teaching of an "oxidative stress-related disorder" to diabetic nephropathy. For at least these reasons, the obviousness rejection is untenable. Finally, the Office Action's relied on Eltoweissy for teaching "that protein DJ-1, by incorporating as an endogenous antioxidant defense protein, had an added benefit in ameliorating the progression of fibrosis in renal cells exposed to higher oxidative stress (OS) levels". (Office Action, p. 8, citing top. 1843, col. 1, para. 2). This statement cannot cure the deficiencies of Offen and Hosseini”.
Applicant further argues that “[I]n the absence of any teaching or suggestion in Eltoweissy of the use of small peptides of DJ-1 in the treatment of diabetic nephropathy, the skilled person would not be motivated to carve DJ-1 into random pieces, attach those random pieces to a cell-penetrating peptide (to yield, for example, the currently claimed peptide of SEQ ID NO:33), and then exogenously administer that peptide to a subject having diabetic nephropathy. Even if Eltoweissy teaches that exogenous DJ-1 provides a benefit to the kidney (which Applicant does not concede), any asserted teaching by Eltoweissy would only concern only full- length DJ-1. Moreover, Eltoweissy fails to provide any suggestion to the skilled person to abandon the full-length DJ-1 protein (189 amino acids) in favor of a small 13 amino acid fragment”.
Applicant’s arguments are not persuasive.
From the teachings of Eltoweissy et al., it is clear that that protein DJ-1 is effective as an antioxidant defense protein in renal cells exposed to higher oxidative stress (OS) levels.
Furthermore, the Examiner submit the evidentiary reference of Jha et al. (Antioxid Redox Signal. 2016 Oct 20;25(12):657-684), which also teaches that diabetic nephropathy is an oxidative stress-related disorder (title; abstract; passim).
Therefore, in contrary to Applicant’s arguments, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to treat diabetic nephropathy with the instantly claimed peptide.
Moreover, in contrary to Applicant’s arguments, the instantly claimed method does NOT relate to a 13 amino acid fragment of the full-length DJ-1 protein. In fact, instant claim 1 recites “….a peptide comprising the amino acid sequence set forth in SEQ ID NO: 33”. The open language “comprising” encompasses peptides of all lengths as long as they comprise instant SEQ ID NO: 33.
For the reasons stated above the rejection is maintained.
This rejection is maintained.
Claims 1, 19-20, 49 and 51-56 are rejected under 35 U.S.C. 103 as being unpatentable over Offen et al. (WO 2011/033511) in view of Hosseini et al. (Oxid Med Cell Longev. 2013 Apr 24;2013:168039) and Eltoweissy et al. (Mol. BioSyst., 2016, 12, 1842-1859) as applied to claims 1, 49, and 51-56 above, and further in view of Zhang et al. (Exp Ther Med. 2017 May 18;14(1):383–390).
The teachings of Offen et al., Hosseini et al. and Eltoweissy et al. with respect to claims 1, 49, and 51-56 have been discussed above.
Offen et al., Hosseini et al. and Eltoweissy et al. do not teach further administering metformin.
Zhang et al. teach that Metformin ameliorates diabetic nephropathy (title).
Zhang et al. also teach that “[M]etformin treatment significantly attenuated the pathological characteristics of type 2 diabetic nephropathy (T2DN), by reducing blood glucose, protecting renal functions and retaining normal morphology (page 389, left column, last para).
The MPEP 2144.06 states that "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from them having been individually taught in the prior art." In re Susi, 58 CCPA 1074, 1079-80, 440 F.2d 442, 445, 169 USPQ 423, 426 (1971); In re Crockett, 47 CCPA 1018, 1020-21, 279 F.2d 274, 276-77, 126 USPQ 186, 188 (1960). As the court explained in Crockett, the idea of combining them flows logically from them having been individually taught in prior art.
Therefore, since the references teach that the instantly claimed peptide and metformin are effective in treating type 2 diabetic nephropathy, it would have been obvious to combine the two compounds with the expectation that such a combination would be effective in treating type 2 diabetic nephropathy. Thus, combining them flows logically from them having been individually taught in prior art.
Response to Arguments
Applicant’s arguments filed on 10/8/2025 have been fully considered but they are not persuasive.
Applicant arguments have been addressed above under “Response to Arguments” on pages 11-13.
For the reasons stated above the rejection is maintained.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SERGIO COFFA whose telephone number is (571)270-3022. The examiner can normally be reached M-F: 6AM-4PM.
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/SERGIO COFFA Ph.D./
Primary Examiner
Art Unit 1658
/SERGIO COFFA/Primary Examiner, Art Unit 1658