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 .
Claim 48 has been cancelled.
New claim 63 has been added.
Claims 43-47 and 49-63 are pending in this application.
Applicant elected without traverse of SEQ ID NO: 3 (completely inverso) as the species of a synthetic peptide, Type 1 diabetes as the species of diabetes, FPG level greater than about 130 mg/dl as the species of symptom of the patient, preserving pancreatic islets as the species of end-results, an adolescent as the species of a patient, intravenous administration as the route of administration, SEQ ID NO: 8 as the species of a cell recognition moiety, and SEQ ID NO: 12 and SEQ ID NO: 13 as the species of modification to the synthetic peptide in the reply filed on October 7, 2025. Restriction was deemed to be proper and was made FINAL in the previous office action. Claims 53, 57 and 60 remain withdrawn from consideration as being drawn to nonelected species. Claims 43-47, 49-56, 58-59 and 61-63 are examined on the merits in this office action.
Withdrawn Objections and Rejections
Objection to claim 43 is hereby withdrawn in view of Applicant’s amendment to the claim.
Objection to claim 46 is hereby withdrawn in view of Applicant’s amendment to the claim.
Objection to claim 49 is hereby withdrawn in view of Applicant’s amendment to the claim.
Objection to claims 59 and 61-62 is hereby withdrawn in view of Applicant’s amendment to the claims.
Objection to claim 61 is hereby withdrawn in view of Applicant’s amendment to the claim.
Rejection of claim 50 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is hereby withdrawn in view of Applicant’s amendment to the claim.
Rejection of claim 56 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is hereby withdrawn in view of Applicant’s amendment to the claim.
Rejection of claim 58 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is hereby withdrawn in view of Applicant’s amendment to the claim.
Rejection of claim 51 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is hereby withdrawn in view of Applicant’s amendment to the claim.
Rejection of claim 54 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is hereby withdrawn in view of Applicant’s amendment to the claim.
Rejection of claim 51 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, is hereby withdrawn in view of Applicant’s amendment to the claim.
Maintained Objection
Please note, the specification has not been checked to the extent necessary to determine the presence of all possible error. Applicant's cooperation is required in correcting any errors of which applicant may become aware in the specification. MPEP § 608.01.
Maintained and Revised Rejections
35 U.S.C. 112(a)
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.
Claims 43-47, 49-56, 58-59 and 61-63 remain/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 treating the progress of diabetes type 1, does not reasonably provide enablement for preventing the progress of diabetes type 1. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims. This rejection is maintained but revised due to Applicant’s amendment to the claims.
The factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Among these factors are: (1) the nature or the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. When the above factors are weighed, it is the examiner’s position that one skilled in the art could not practice the invention without undue experimentation.
(1) The nature of the invention and (5) The breadth of the claims:
The invention is drawn to a method for treating diabetes and/or preventing the progress of diabetes, comprising administering to a subject in affected with prediabetes or with diabetes a therapeutically effective amount of a pharmaceutical composition comprising at least one synthetic peptide selected from the group consisting of SEQ ID NO: 1 and SEQ ID NO: 2.
The term “diabetes” includes both types, 1 and 2, of diabetes and gestational diabetes (see e.g., claim 45 and paragraph [0057] of instant specification US 2023/0066049). The claims therefore, encompass the embodiment of preventing type 1 diabetes in a prediabetic patient or a patient with type 2 diabetes.
Please note: Claim 43 currently recites, “A method for at least one (i) preserving pancreatic islets number and/or size and/or function and (ii) restoring the number of functional pancreatic islets to a normal level in a subject affected with prediabetes or diabetes thereby treating and/or preventing the progress of diabetes…” Claim 63 currently recites, “A method for treating and/or preventing the progress of diabetes type 1 or prediabetes in a subject in need thereof…“ “Preventing the progression of diabetes” implies that the patient already has diabetes. Whereas, the phrase “preventing the progression to diabetes” implies that the patient does not have diabetes.
(2) The state of the prior art:
In regards to “preventing the progress of diabetes type 1”, it is well known in the art that type 1 diabetes cannot be prevented. CDC.gov (https://www.cdc.gov/diabetes/about/about-type-1-diabetes.html, Type 1 Diabetes) indicates that type 1 diabetes is less common than type 2—about 5-10% of people with diabetes have type 1. Currently, no one knows how to prevent type 1 diabetes, but it can be managed successfully (see p. 1, “Overview”). CDC.gov also indicates that “It can take months or years before symptoms of type 1 diabetes are noticed. Type 1 diabetes symptoms can develop in just a few weeks or months. Once symptoms appear, they can be severe” (see p.1 “Signs and Symptoms”). CDC.gov indicates that “a simple blood test is used to screen for diabetes” (see p. 2, “Testing and screening”). Additionally, CDC.gov indicates
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(see p. 2, “Causes”).
The art indicates that “no one knows how to prevent type 1 diabetes” and provide guidance to how to test and screen for diabetes, and treatment methods (see pp. 1-3).
(3) The relative skill of those in the art:
The relative skill of those in the art is high.
(4) The predictability or unpredictability of the art:
Applicant’s activity is based on the determination of predicting those who are susceptible to type 1 diabetes. Since the activity is based on determining the patient population that is susceptible to type 1 diabetes, the predictability in the art is low. This is due to the fact that the art has recognized that it can take months or years for symptoms of type 1 diabetes are noticed. Additionally, the art has recognized that type 1 diabetes is thought to be caused by an autoimmune reaction, and the process can go on for months or years before any symptoms appear.
Since the art has indicated that “no one knows how to prevent type 1 diabetes” and that it can take months or years before symptoms of type 1 diabetes appear, there are too many variables between the experimentation, thus, it clearly shows the unpredictability of the art.
(6) The amount of direction or guidance presented and (7) The presence or absence of working examples:
The specification has not provided guidance in the way of a disclosure as how to determine individuals that need protection against type 1 diabetes. There is no clear guidance as how to determine the patient population that needs preventions from progression to type 1 diabetes, from type 2 to type1 and gestational to type 1 progression. The working examples utilized STZ/GHD-32 model and this is a model for type 2 diabetes and NAFLD. The specification discloses that “…mice induced to have steatosis NASH and Type 2 diabetes phenotypes (designated herein STZ/HFD-32 mice or STZ/HFD-32-fed mice…” (see paragraph 90055] of instant specification). Furthermore, Applicant has not demonstrated that the instantly claimed method can prevent at least type 1 diabetes. Since the prior art is still unclear as to who are susceptible to type 1 diabetes, more guidance is necessary. Thus, coupled with the knowledge in the prior and post filing art, there would be undue experimentation to make and/or use the claimed invention.
(8) The quantity of experimentation necessary:
Since it is uncertain to predict the patient population who are susceptible for type 1 diabetes, and the Applicant has not provided the appropriate time frame at which the compound should be administered, one of ordinary skill in the art would be burdened with undue “painstaking experimentation study” make and/or use the claimed invention.
Response to Applicant’s Arguments
19. Applicant argues:
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20. Applicant’s arguments have been fully considered but are not found persuasive. As indicated in the office action above, “preventing the progression of diabetes” implies that the patient already has diabetes. In regards to “preventing the progress of diabetes type 1”, it is well known in the art that type 1 diabetes cannot be prevented. CDC.gov (https://www.cdc.gov/diabetes/about/about-type-1-diabetes.html, Type 1 Diabetes) indicates that type 1 diabetes is less common than type 2—about 5-10% of people with diabetes have type 1. Currently, no one knows how to prevent type 1 diabetes, but it can be managed successfully. CDC.gov also indicates that “It can take months or years before symptoms of type 1 diabetes are noticed. Type 1 diabetes symptoms can develop in just a few weeks or months. Once symptoms appear, they can be severe”. CDC.gov indicates that “a simple blood test is used to screen for diabetes”. Additionally, CDC.gov indicates
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The art indicates that “no one knows how to prevent type 1 diabetes” and provide guidance to how to test and screen for diabetes, and treatment methods. Thus, prevention of progression of type 1 diabetes implies that type 1 diabetes can be prevented. Since there is no prevention of type 1 diabetes, no one knows how to prevent the progression of type 1 diabetes. Methods of treatment of type 1 diabetes are known; no methods of prevention of type 1 diabetes progression is known. In regards to Applicant’s arguments that “subjects that already have diabetes, either type 1 or type 2 or having prediabetes” since the art teaches that no one knows how to prevent type 1 diabetes, it can be implied that the prevention of progression of type 1 diabetes also is unknown. Additionally, the new claim 63 explicitly recites a method for treating and/or preventing the progress of diabetes type 1 or prediabetes in a subject in need thereof, Applicant is not enabled for any prevention and/or prevention of progression of type 1 diabetes.
35 U.S.C. 103
21. 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.
22. 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.
23. 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.
24. Claims 43, 45, 49-52, 54-56, 58-59 and 61-62 remain/are rejected under 35 U.S.C. 103 as being obvious over Shoshan-Barmatz (US 2018/0134760 and issued as US Patent No. 10,385,104) in view of Dharmalingam et al (Indian Journal of Endocrinology and Metabolism, 2018, 22: 421-428). Please note: the Shoshan-Barmatz reference will be cited from US 2018/0134760.
The applied reference has a common Applicant and Assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
25. Shoshan-Barmatz reference teaches analogs of VDAC 1-derived peptides (see for example, abstract). Shoshan-Barmatz reference teaches reducing symptoms associated with fat accumulation in liver cells particularly with nonalcoholic fatty liver disease (NAFLD) and symptoms associated thereto (see abstract). Shoshan-Barmatz reference teaches the exact same peptide sequence as instant SEQ ID NO: 3 (see SEQ ID NO: 2), instant SEQ ID NO: 8 (see SEQ ID NO: 8), instant SEQ ID NOs: 12 and 13 (see SEQ ID NOs: 12-13), and instant SEQ ID NO: 14 (see SEQ ID NO: 14). Shoshan-Barmatz reference teaches that the VDAC1-derived peptide capable of inducing apoptosis in cancerous cell is designated as LP4 and consists of the amino acid sequence set forth in SEQ ID NO: 1 (KKLETAVNLAWTAGNSN) and the amino acids sequence of the retro analogue is as set forth in SEQ ID NO: 2 (NSNGATWALNVATELKK) (see paragraph [0023]). Shoshan-Barmatz reference teaches a method of treating and/or preventing non-alcoholic fatty liver disease (NAFLD) and/or a symptom associated with NAFLD comprising administering to a subject in need thereof a therapeutically effective amount of the pharmaceutical composition comprising at least one synthetic peptide (see claims 14 and 20) and the synthetic peptide comprising an analogue of VDAC1-derived peptide, the VDAC1-derived peptide is selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, and SEQ ID NO: 6 (see claims 1-3), meeting the limitation of instant claims 43, 45, 52, 54-56, 58-59 and 61-62, in part. Shoshan-Barmatz reference teaches the blood glucose levels in mice that received chew diet (ND), mice that received HFP-32 diet and mice that received HFD-32 and treated with the Retro-Tf-D-LP4 peptide (see FIG. 14, and description on paragraph [0073]). Shoshan-Barmatz reference teaches that blood glucose levels were highly increased in mice receiving the HFD-32 diet, from about 150 mg/dL in mice fed with regular (chow) food up to 450 mg/dL in mice fed with HFD-32. This increase was suppressed in mice treated with Retro-Tf-D-LP4, showing blood glucose levels comparable to those of mice fed with regular food (see paragraph [0181]). Shoshan-Barmatz reference teaches that the pharmaceutical composition may be administered by any suitable means, such as topically or parenterally, including intranasal, subcutaneous, intramuscular, intravenous, intraarterial, intraarticular, or intralesional administration (see paragraph [0113]), meeting the limitation of instant claim 50, in part. Shoshan-Barmatz reference teaches that treatment group-1 (n=10) received retro-Tf-D-LP4 (SEQ ID NO: 14) 10/mg/kg, and treatment group-2 (n=10) received retro-Tf-D-LP4 (SEQ ID NO: 14) 18 mg/kg, all by intravenous injection (see paragraph [0138]), meeting the limitation of instant claim 51, in part. With respect to the limitation in the preamble of claim 43, “A method for at least one of (i) preserving pancreatic islets number and/or size and/or function and (ii) restoring the number of functional pancreatic islets to a normal level in a subject affected with prediabetes or diabetes...”, please note that MPEP 2111.02 II states "a preamble generally is not limiting when the claim body describes a structurally complete invention such that deletion of the preamble phrase does not affect the structure or steps of the claimed invention." In the instant case, the preamble does not affect the method steps. The preamble in this case recites a statement of purpose or use, and therefore was not treated as a claim limitation.
The difference between the reference and instant claims is that the reference does not explicitly teach a method of treating diabetes and/or preventing the progress of diabetes.
26. However, Dharmalingam et al teach that Type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) commonly exist together. It has been regarded as a manifestation of the metabolic syndrome…NAFLD has a prevalence of 70% among T2DM patients. Overweight/obesity and insulin resistance (IR) have been strongly linked with NAFLD…The principle behind the management of NAFLD with T2DM involves an indirect effect through improvement in IR and glycemia and thus is used for the treatment of T2DM as well (see abstract). Dharmalingam et al further teach the following:
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(see p. 422, right column). In regards to claim 49, Dharmalingam et al teach the procedures of diagnosis (see pp. 423-424, for example) and indicates that the patient population is human adults (e.g., p. 424, left column, “Lifestyle Modification”).
Furthermore, with respect to “wherein the treating and/or preventing the progress of diabetes comprises at least one of…(claim 48)” according to MPEP 2111.04: "Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure. However, examples of claim language, although not exhaustive, that may raise a question as to the limiting effect of the language in a claim are:
(A) “adapted to” or “adapted for” clauses;
(B) “wherein” clauses; and
(C) “whereby” clauses.
The determination of whether each of these clauses is a limitation in a claim depends on the specific facts of the case. In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), the court held that when a “whereby’ clause states a condition that is material to patentability, it cannot be ignored in order to change the substance of the invention.” Id. However, the court noted (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” Id. <”. In the instant case, the wherein clause recited in claim 48 recites end results of the treatment. Therefore, it is not deemed that the “wherein” clause limits the claim to particular structural features.
27. Therefore, it would have been obvious to one of ordinary skill in the art to combine the teachings of Shoshan-Barmatz reference and Dharmalingam et al to, since both references teach treatment of NAFLD. One of ordinary skill in the art would be motivated to try treating diabetes or preventing the progression of diabetes by administering a therapeutically effective amount of a pharmaceutical composition comprising an analogue of VDAC1-derived peptide is SEQ ID NO: 3, further comprising a cell recognition or localization moiety (e.g., SEQ ID NO: 8, transferring-receptor binding domain) and further comprising SEQ ID NO: 12 and SEQ ID NO: 13 located at the C- or N-terminus of VDAC1- derived peptide analog (e.g., the SEQ ID NO: 14) with a reasonable expectation of success since Dharmalingam et al provide the nexus between NAFLD and type 2 diabetes mellitus (T2DM).
It has been held that under KSR that “obvious to try” may be an appropriate test under 103. The Supreme Court stated in KSR, When there is motivation “to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to anticipated success, it is likely the product not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under § 103.” KSR Int’l Co. v. Teleflex Inc., 127 S. Ct. 1727,_,82 USPQ2d 1385, 1397 (2007).
The “problem” facing those in the art was developing new therapeutic methods to treat diabetes and/or delay or prevent the progression of diabetes, and there were a limited number of methodologies available to do so, for example (insulin derivatives, GLP-1 and GLP-2 analogs, etc.,). The skilled artisan would have had reason to try these methodologies with the reasonable expectation that at least one would be successful. In the instant case, Shoshan-Barmatz reference teaches that when retro-Tf-D-LP4 peptide was administered after mice were fed with HFD-32, the blood glucose levels were comparable with mice fed with regular (chow) food. Shoshan-Barmatz reference teaches the method of treating NAFLD by administering, for example, retro-Tf-D-LP4 peptide. Shoshan-Barmatz established that NAFLD is treated by administering the retro-Tf-D-LP4 peptide, that is the same as instant SEQ ID NO: 14 (SEQ ID NO: 3, SEQ ID NO: 8, SEQ ID NO: 12 and SEQ ID NO: 13). Dharmalingam et al teach that type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) commonly exist together, and that NAFLD has a prevalence of 70% among T2DM patients. Thus, treating diabetes or preventing the progression of diabetes by administering a therapeutically effective amount of a pharmaceutical composition comprising an analogue of VDAC1-derived peptide is SEQ ID NO: 3, further comprising a cell recognition or localization moiety (e.g., SEQ ID NO: 8, transferring-receptor binding domain) and further comprising SEQ ID NO: 12 and SEQ ID NO: 13 located at the C- or N-terminus of VDAC1- derived peptide analog (e.g., the SEQ ID NO: 14) is a “the product not of innovation but of ordinary skill and common sense,” leading to the conclusion that invention is not patentable as it would have been obvious.
Therefore, it is deemed that the combined arts is prima facie obvious over instant claims 43, 45, 49-52, 54-56, 58-59 and 61-63.
Response to Applicant’s Arguments
28. Applicant argues that “Claim 43 was amended to recite that the method comprises “at least one of (i) preserving pancreatic islets number and/or size and/or function and (ii) restoring the number of functional pancreatic islets to a normal level in a subject affected with prediabetes or diabetes by administering a VDAC1-derived peptide.” Applicant argues that “the present invention shows that the peptides of the invention increased the number and average size of pancreatic islets…the current claims recite that the VDAC1-derived peptides have diabetic-specific effects via preservation and even restoration of functional pancreatic islet, which is distinct from an effect on insulin resistance.” Applicant further argues:
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. Applicant argues that “New claim 63 is directed to a method of treating and/or preventing the progress of diabetes type 1 or prediabetes using the VDAC1-derived peptide recited therein. It is well known that the pathogenesis of diabetes type 1 and type 2 are completely different and that diabetes type 1 is not related to NAFLD.”
29. Applicant’s arguments have been fully considered but are not found persuasive. Shoshan-Barmatz reference teaches analogs of VDAC 1-derived peptides. Shoshan-Barmatz reference teaches reducing symptoms associated with fat accumulation in liver cells particularly with nonalcoholic fatty liver disease (NAFLD) and symptoms associated thereto. Shoshan-Barmatz reference teaches the exact same peptide sequence as instant SEQ ID NO: 3, instant SEQ ID NO: 8, instant SEQ ID NOs: 12 and 13, and instant SEQ ID NO: 14. Shoshan-Barmatz reference teaches that the VDAC1-derived peptide designated as LP4 and consists of the amino acid sequence set forth in SEQ ID NO: 1 (KKLETAVNLAWTAGNSN) and the amino acids sequence of the retro analogue is as set forth in SEQ ID NO: 2 (NSNGATWALNVATELKK). Shoshan-Barmatz reference teaches a method of treating and/or preventing non-alcoholic fatty liver disease (NAFLD) and/or a symptom associated with NAFLD comprising administering to a subject in need thereof a therapeutically effective amount of the pharmaceutical composition comprising at least one synthetic peptide. Dharmalingam et al teach that type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) commonly exist together, and that NAFLD has a prevalence of 70% among T2DM patients. Thus, treating diabetes or preventing the progression of diabetes by administering a therapeutically effective amount of a pharmaceutical composition comprising an analogue of VDAC1-derived peptide is SEQ ID NO: 3, further comprising a cell recognition or localization moiety (e.g., SEQ ID NO: 8, transferring-receptor binding domain) and further comprising SEQ ID NO: 12 and SEQ ID NO: 13 located at the C- or N-terminus of VDAC1- derived peptide analog (e.g., the SEQ ID NO: 14) is a “the product not of innovation but of ordinary skill and common sense,” leading to the conclusion that invention is not patentable as it would have been obvious. Because the combined arts teach the active method steps, i.e., SEQ ID NO: 1 and SEQ ID NO: 2, and treating diabetes and/or prediabetes, the administering SEQ ID NO: 1 and SEQ ID NO: 2 would necessarily lead to the end results, i.e., preserve pancreatic islets numbers and/or size and/or function or restore the number of functional pancreatic islets to a normal level of the claims. Therefore, the rejection is deemed to be proper and is maintained herein.
DOUBLE PATENTING
30. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
31. Claims 43-47, 49-52, 54-56, 58-59 and 61-63 remain/are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 10,385,104 in view of Dharmalingam et al (Indian Journal of Endocrinology and Metabolism, 2018, 22: 421-428). Although the claims at issue are not identical, they are not patentably distinct from each other because if one of ordinary skill in the art practiced the claimed invention of instant claims, one would necessarily achieve the claimed invention of US Patent claims, and vice versa.
32. Instant claims are drawn to:
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33. US Patent claims are drawn to:
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. The specification of US Patent discloses that “type II diabetes mellitus and NAFLD have a particularly close relationship. A study of patients with type II diabetes mellitus reported a 69% prevalence of ultrasonographic NAFLD (see US Patent column 2, lines 55-67).
34. Dharmalingam et al teach that Type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) commonly exist together. It has been regarded as a manifestation of the metabolic syndrome…NAFLD has a prevalence of 70% among T2DM patients. Overweight/obesity and insulin resistance (IR) have been strongly linked with NAFLD…The principle behind the management of NAFLD with T2DM involves an indirect effect through improvement in IR and glycemia and thus is used for the treatment of T2DM as well (see abstract).
35. Instant SEQ ID NO: 3 is the same as US Patent SEQ ID NO: 2; instant SEQ ID NO: 8 is the same as US Patent SEQ ID NO: 8; instant SEQ ID NO: 14 is the same as US Patent SEQ ID NO: 14. Additionally, instant claims are drawn to a method of treating diabetes and/or preventing the progress of diabetes, comprising administering to a subject affected with prediabetes or with diabetes a therapeutically effective amount of a pharmaceutical composition comprising at least one synthetic peptide comprising a retro modified and partially or completely inverso modified analogue of a VDAC I-derived peptide, wherein the VDAC I-derived peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 1 and SEQ ID NO: 2. US Patent claims are drawn to a synthetic peptide comprising the peptides claimed in the instant claims and additionally drawn to a pharmaceutical composition comprising the synthetic peptide. Therefore, if one of ordinary skill in the art practiced the claimed invention of instant claims, one would necessarily achieve the claimed invention of US Patent claims, and vice versa.
Please note: instant claims are drawn to a method of using the pharmaceutical composition comprising the synthetic peptides of US Patent claims. Therefore, the double patenting rejection is proper.
Response to Applicant’s Arguments
36. Applicant argues that “Applicant respectfully requests that this rejection be held in abeyance until such time that the Examiner finds allowable subject matter in the current claims. Until such time, a complete determination regarding the merits of the double patenting rejections cannot be made.”
37. Applicant’s arguments have been fully considered but are not found persuasive. While a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP 714.02). Until a proper Terminal Disclaimer is filed and approved by the Office, the rejection is maintained.
IMPROPER MARKUSH
38. Claims 43 and 52 are rejected on the judicially created basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F. 2d 716, 721-22 (CCPA 1980) and Ex parte Hazumi, 3 USPQ 2d 1059, 1060 (BPAI 1984). The improper Markush grouping includes species of the claimed invention that do not share both a substantial structural feature and a common use that flows from the substantial structural feature. The members of the improper Markush grouping do not share a substantial feature and/or a common use that flows from the substantial structural feature for the following reasons: The compounds claimed do not share a common structural feature and a common use. For example, instant SEQ ID NO: 1 has the sequence KKLETAVNLAWTAGNSN; instant SEQ ID NO: 2 has the sequence MAVPPTYADLGKSARDVFTKGYGFGL; instant SEQ ID NO: 3 has the sequence NSNGATWALNVATELKK; and instant SEQ ID NO: 5 has the sequence LGFGYGKTFVDRASKGLDAYTPPVAM. These sequences do not share a common core sequence. Instant SEQ ID NO: 3 is an inverso sequence of instant SEQ ID NO: 1; instant SEQ ID NO: 5 is an inverso sequence of instant SEQ ID NO: 2.
In response to this rejection, Applicant should either amend the claim(s) to recite only individual species or grouping of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claims(s) share a substantial structural feature as well as a common use that flows from the substantial structural feature. This is a rejection on the merits and may be appealed to the Board of Patent Appeals and Interferences in accordance with 35 U.S.C. § 134 and 37 CFR 41.31 (a)(1) (emphasis provided).
Response to Applicant’s Arguments
39. Applicant argues that “a peptide comprising amino acid sequences SEQ ID NO: 1 and 2 are both derived from VDAC1 and they both show the same biological activity, subsequently they have the same function…It is a well-known fact that peptides may have a completely different sequence but still have the same structure and the same function…Therefore, they are valid structural and functional alternatives. The same is true for SEQ ID NOs: 3 and 5 which are inverso sequences of SEQ ID NO: 1 and 2.”
40. Applicant’s arguments have been fully considered but are not found persuasive. The peptide sequences do not share a common core sequence. For example, instant SEQ ID NO: 1 has the sequence KKLETAVNLAWTAGNSN; instant SEQ ID NO: 2 has the sequence MAVPPTYADLGKSARDVFTKGYGFGL; instant SEQ ID NO: 3 has the sequence NSNGATWALNVATELKK; and instant SEQ ID NO: 5 has the sequence LGFGYGKTFVDRASKGLDAYTPPVAM. These sequences do not share a common core sequence. Instant SEQ ID NO: 3 is an inverso sequence of instant SEQ ID NO: 1; instant SEQ ID NO: 5 is an inverso sequence of instant SEQ ID NO: 2. Just from the sequences alone, one of ordinary skill in the art cannot determine the function of each peptide sequence, and that the sequences are derived from VDAC1 peptide. Therefore, the rejection is deemed to be proper and is maintained herein.
New Rejection
U.S.C. 112(b)
41. 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.
42. Claim 63 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.
43. Claim 63 recites, “A method for treating and/or preventing the progress of diabetes type 1 or prediabetes in a subject in need thereof…” The metes and bounds of the claim is unclear. The phrase “preventing the progress of diabetes” in the preamble of claim 63 implies that the patient has diabetes whereas “progression to diabetes” implies that the patient does not have it. It is suggested that the Applicant amend the preamble to clarify the metes and bounds of the claim.
Art of Interest
These references were cited in the previous office action
44. Pittala et al (Cells, 2020, 9(2): 1-23, filed with IDS) teach VDAC1-based peptide, R-Tf-D-LP4 peptide decreased the elevated glucose levels in a mouse displaying obese, diabetic, and metabolic symptoms due to a mutation in the obese (ob) gene (see abstract, lines 13-15). Pittala et al teach that the VDAC1-based R-Tf-D-LP4 peptide has potential as a treatment for diabetes (see abstract, last two lines). Pittala et al teach the following: The R-Tf-D-LP4 peptide comprises a VDAC1-derived sequence defined as LP4, fused to a cell-penetrating peptide-the human transferrin receptor (hTfR)-recognition sequence HAIYPRH (Tf). The amino acids of the VDAC1-derived sequence are in the D-configuration, promoting higher oral bioavailability, and are less immunogenic than the corresponding L-peptides. In the retro-inverso R-Tf-D-LP4 peptide, the direction of the R-Tf-D-LP4 peptide bond is reversed, producing a side chain topology similar to that of the original L-amino acid R-Tf-D-LP4 peptide (see p. 2, lines .21-26). Pittala et al teach that the R-Tf-D-LP4 has the sequence: (KWTWK-216-NSNGATWALNVATELKK-199-EWTWSHRPYIAH) (see p. 3, Section 2.1, “Materials”). This sequence is the same as instant SEQ ID NO: 14.
45. Pittala et al (Neoplasia, 2018, 20(6): 594-609, filed with IDS) teach the same peptide as instant SEQ ID NO: 14 (R-Tf-D-LP4, KWTWK-216-NSNGATWALNVATELKK-199-EWTWSHRPYIAH) (see p. 595, right column, “Materials”). Pittala et al teach that VDAC1 peptide, R-Tf-D-LP4 was highly effective in liver cancer treatment (see abstract and throughout the reference). Pittala et al do not teach the effect of R-Tf-D-LP4 on treating diabetes.
CONCLUSION
No claim is 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.
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/JULIE HA/Primary Examiner, Art Unit 1654
4/22/2026
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