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 .
Priority
This application was filed on and is a U.S. national Stage application under 35 U.S.C. 371 of International Patent Application No. PCT/US2021/053537 filed 10/05/2021, which claims the benefit of the priority of US Provisional application 63/089,122 filed 10/08/2020.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements submitted on 03/27/2023, 01/09/2024, 03/20/2024, 12/31/2024, 04/14/2025, and 07/17/2025 have been considered by the examiner.
Claim Status
Claims 1, 8-15, 17-27 are being examined on the merits in this office action.
Claim Objections
Claim 11 and 25 are objected to because of the following informalities:
Claim 11 recites “…comprises an insulin…”. Claim 11 should be amended to recite “…comprises insulin…”.
Regarding claim 25, the claim should be amended to recite “The method of claim 24, wherein the preservative is meta-cresol and the zinc source is zinc oxide”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 20 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.
Regarding claim 20, the claim contains a parenthesis in line 2. It is unclear whether the limitations in the parenthesis are a required part of the claimed invention.
Further, the phrase "for example" renders the claim 20 indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
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.
Claim 9 is 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.
Claim 9 depends on claim 8 and recites “…peptide is administered at least once daily for at least 7 weeks”.
Examiner notes that claim 9 does not further limit because the peptide is administered at the same frequency and duration recited in claim 8 since the peptide is administered at least once every day (i.e. the seven days in the week), for 7 weeks and the peptide in claim 8 is administered at least one a day for at least five days (which also includes the seven days in the week) for 7 weeks.
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.
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.
Claims 1, 8-9, 11-15, 17-20 are rejected under 35 U.S.C. 103 as being unpatentable over Harrison et al. (Diabetes Care 27:2348–2355, 2004), in view of Al-Waili et al. (J Pak Med Assoc. 1999 Jul; 49(7): 167-9).
Harrison teaches administration of insulin peptide Humulin, and that Humulin was administered to human subjects with Type 1 diabetes (Title; Abstract; Page 2349, right col., paragraph 1-3), that the Humulin was administered orally to the human subjects (Page 2348, right col., 1st paragraph; page 2353, right col., last paragraph). Harrison further teaches that the method did not accelerate loss of pancreatic β -cell function (Title; Abstract; Page 2350, left col., last paragraph).
Harrison does not teach that the insulin was sublingually administered.
However, administration of insulin sublingually to subjects with Type 1 diabetes is known in the art as taught by Al-Waili et al. Al-Waili teaches sublingual administration of insulin to Type 1 diabetes subjects and that the insulin dose has a hypoglycemic effect and could be used to control hyperglycemia in type I diabetes (Abstract). Al-Waili teaches that administration of insulin sublingually exposed insulin for a longer period and may allow a larger amount of insulin to be absorbed (Page 3, line 10).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by Harrison and administer insulin sublingually as taught by Al-Waili so as to increase the exposure of insulin (Page 3, line 10). One of ordinary skill in the art would be motivated and would have had a reasonable expectation of success in administering insulin sublingually as taught by Al-Waili to allow a larger amount of insulin to be absorbed (Page 32nd paragraph). The disclosure render obvious claim 1.
Regarding claims 8-9, Harrison teaches that the insulin was administered daily for 10 consecutive days or 2 days a week for 6 months (Page 2348, left col., 2nd paragraph; Page 2349, right col., last paragraph). Harrison teaches that the insulin can be administered on more occasions over a 6-month period based on monthly interview and monitoring (Page 2350, whole of left col.). In addition, the concentration of the active agent is a result effective variable and the determination of the optimum or workable ranges of said variable may be characterized by routine experimentation (See MPEP 2144 II). It would be obvious and routine experimentation to a person of ordinary skill in the art with a reasonable expectation of success to optimize the dosages and duration to arrive at the dosages and duration of administration of the instant claims 8-9.
Regarding claims 11-13, Harrison teaches that Humulin was administered to the subjects and that Humulin contains pure recombinant human insulin at 4 mg/ml in a carrier of water (Page 2349, right col., 3rd paragraph, line 1-9).
Regarding claims 14, 15, and 17, Harrison teaches that the method of administering insulin was on human subjects at risk of developing Type 1 diabetes (Title; Abstract; (Page 2349, right col., 2nd paragraph, line 1-9). Examiner notes that the disclosure reads on “predisposed to the development of Type 1 diabetes”.
Regarding claim 18, Harrison teaches that the subjects were first-degree relatives of someone with type 1 diabetes (Page 2349, right col., 2nd paragraph, line 1-9).
Regarding claims 19-20, Harrison teaches that the method of administering insulin was on human subjects at risk of developing Type 1 diabetes (Title; Abstract; (Page 2349, right col., 2nd paragraph, line 1-9). Further, Harrison teaches that the subjects were first-degree relatives of someone with type 1 diabetes (Page 2349, right col., 2nd paragraph, line 1-9). Further, Harrison teaches the subjects has the HLA-DR genotype (Table 1 and Table 1 description). Examiner notes that such a subject is genetically predisposed to developing type 1 diabetes rendering obvious claim 19.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Harrison et al. (Diabetes Care 27:2348–2355, 2004), in view of Al-Waili et al. (J Pak Med Assoc. 1999 Jul; 49(7): 167-9) as applied to claim 1 above, and further in view UniProt (https://www.uniprot.org/uniprotkb/P01308/entry).
The teachings of Harrison and Al-Waili are disclosed above and incorporated herein by reference.
Harrison does not teach the sequence of the insulin peptide as recited in claim 10.
Examiner notes that Harrison teaches that Humulin was administered to the subjects and that Humulin contains pure recombinant human insulin at 4 mg/ml in a carrier of water (Page 2349, right col., 3rd paragraph, line 1-9). Examiner notes that human insulin comprises the A and B chains and as taught by UniProt, and the A and B chains of insulin comprise the instant SEQ ID NO: 9 and 4 (See page 8 of UniProt).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by Harrison and Al-Waili and use the insulin peptide with A and B chains as taught by Uniprot so as to arrive to the instant petides. One of ordinary skill in the art would be motivated and would have had a reasonable expectation of success in administering the human insulin peptide taught by Uniprot sublingually so as to allow a larger amount of insulin to be absorbed for conserving pancreatic beta cell function. The disclosures render obvious claim 10.
Claims 21-27 are rejected under 35 U.S.C. 103 as being unpatentable over Harrison et al. (Diabetes Care 27:2348–2355, 2004), in view of Al-Waili et al. (J Pak Med Assoc. 1999 Jul; 49(7): 167-9) as applied to claim 1 above, and further in view of Nguyen et al. (American Journal of Rhinology & Allergy. 2011; 25(5): 342-345), FDA label (https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/018781s181lbl.pdf) and Becker et al. (US20110301081A1 – hereinafter “Becker”).
The teachings of Harrison and Al-Waili are disclosed above and incorporated herein by reference.
Harrison does not teach the addition of at least 30% glycerin as recited in claim 21, and does not teach the addition of zinc oxide as recited in claim 25.
Regarding the addition of glycerin at the recited amounts, Nguyen teaches compositions for sublingual administration (Title; Abstract) and that the composition comprises 50% glycerin and the 50% glycerin helps with protein stability preservation and has been shown to provide the most complete protection against loss of antigen potency (Page 344, left col., last paragraph). Nguyen teaches that unpleasant oral sensation or nausea that could be characterized as potential adverse events were less commonly reported with 50% glycerin (Page 344, right col., last paragraph) and that the use of 50% glycerin is recommended for compositions administered sublingually (Page 345, left col. Last paragraph). Examiner notes that one of ordinary skill in the art would be motivated to modify the composition of Harrison to include 50% glycerin.
Further, with regards to zinc oxide, FDA label teaches Humulin compositions that comprises human insulin and that the amino acid sequence of HUMULIN is identical to human insulin (page 5 section 11), and that the composition comprises 100 units of insulin human, 0.35 mg of protamine sulfate, 16 mg of glycerin, 3.78 mg of dibasic sodium phosphate, 1.6 mg of metacresol, 0.65 mg of phenol, zinc oxide content adjusted to provide 0.025 mg zinc ion (Page 5 section 11). In addition, Becker teaches insulin formulations that comprise human insulin and that the formulation comprises 90 μg zinc, 2.7 mg m-cresol, 20 mg glycerol 85%, HCl and NaOH, and phosphate buffer(Abstract; [0039, 0048, 0829, 0836]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the composition of Harrison to include at least 30% glycerin since Nguyen teaches that compositions for sublingual administration with 50% glycerin helps with protein stability preservation and has been shown to provide the most complete protection against loss of antigen potency (Page 344, left col., last paragraph). It would have been obvious to include zinc oxide in the insulin composition as taught by FDA label and Becker since both references teach insulin composition comprising zinc so as to use the composition to treat diabetes. One of ordinary skill in the art would be motivated and would have had a reasonable expectation of success in including glycerin in the composition since Nguyen teaches that the unpleasant oral sensation or nausea that could be characterized as potential adverse events were less commonly reported with 50% glycerin (Page 344, right col., last paragraph).
Regarding claims 21, and 23, Harrison teaches that the Humulin administered to the subjects contains pure recombinant human insulin at 4 mg/ml in a carrier of water with 1.6 mg/ml glycerol and 0.25/ml m-cresol preservative (Page 2349, right col., 3rd paragraph, line 1-11). With regards to the amount of glycerin recited, Nguyen teaches compositions for sublingual administration (Title; Abstract) and that the composition comprises 50% glycerin and the 50% glycerin helps with protein stability preservation and has been shown to provide the most complete protection against loss of antigen potency (Page 344, left col., last paragraph). Nguyen teaches that unpleasant oral sensation or nausea that could be characterized as potential adverse events were less commonly reported with 50% glycerin (Page 344, right col., last paragraph) and that the use of 50% glycerin is recommended for compositions administered sublingually (Page 345, left col. Last paragraph). Examiner notes that one of ordinary skill in the art would be motivated to modify the composition of Harrison to include 50% glycerin.
Regarding claims 22 and 27, Harrison teaches that the Humulin administered to the subjects contains pure recombinant human insulin at 4 mg/ml in a carrier of water with 1.6 mg/ml glycerol and 0.25/ml m-cresol preservative (Page 2349, right col., 3rd paragraph, line 1-11). Further, Becker teaches insulin formulation and that the formulation comprises 90 μg zinc, 2.7 mg m-cresol, 20 mg glycerol 85%, HCl and NaOH, and phosphate buffer(Abstract; [0039, 0048, 0829, 0836]). In addition, Nguyen teaches compositions for sublingual administration (Title; Abstract) and that the composition comprises 50% glycerin (Page 344, left col., last paragraph). Examiner notes that one of ordinary skill in the art would be motivated to modify the composition of Harrison to include 50% glycerin. The disclosures render obvious claim 22 and 27.
Regarding claim 24, Harrison teaches that the Humulin administered to the subjects contains pure recombinant human insulin at 4 mg/ml in a carrier of water with 1.6 mg/ml glycerol and 0.25/ml m-cresol preservative (Page 2349, right col., 3rd paragraph, line 1-11).
Regarding claim 25, Becker teaches insulin formulation and that the formulation comprises 90 μg zinc, 2.7 mg m-cresol, 20 mg glycerol 85%, HCl and NaOH, and phosphate buffer(Abstract; [0039, 0048, 0829, 0836]). Further, with regards to zinc oxide, FDA label teaches Humulin compositions that comprises human insulin and that the amino acid sequence of HUMULIN N is identical to human insulin (page 5 section 11), and that the composition comprises 100 units of insulin human, 0.35 mg of protamine sulfate, 16 mg of glycerin, 3.78 mg of dibasic sodium phosphate, 1.6 mg of metacresol, 0.65 mg of phenol, zinc oxide content adjusted to provide 0.025 mg zinc ion (Page 5 section 11). It would have been obvious to modify the composition of Harrison and add zinc oxide as a preservative.
Regarding claim 26, Harrison teaches that the Humulin administered to the subjects contains pure recombinant human insulin at 4 mg/ml (Page 2349, right col., 3rd paragraph, line 1-11).
Double Patenting
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.
Claims 1, 8-15, 17-23, and 27, provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 9-11, 13, 34-36, 39-41, 64, 69, 72-75 of copending Application No. 17/778,624. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the copending application recite a method of delaying the onset of Type 1 diabetes or decreasing the likelihood of Type 1 diabetes in a subject in need thereof comprising: sublingually administering a therapeutically effective amount of an insulin-related peptide to the subject (claim 1).
The instant claims recite a method for delaying the onset of reduced serum C-peptide levels in a mammal, conserving pancreatic beta cell function in a mammal, or delaying the onset of decreased pancreatic beta cell function in a mammal, comprising: sublingually administering an effective amount of an insulin-related peptide to the mammal (claim 1).
The claims of the copending application anticipate the instant claims because the claims recite the same method step and same patient population, but different intended use. However, a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. In the instant case, the claims of the copending application recite the same active ingredient, administered in the same way to the same patient population, and as a result, is capable of performing the claimed intended use (see MPEP § 2112.01).
Regarding claims 8-9, the claims of the copending application recite wherein the insulin-related peptide is administered once a day, at least five days a week, for at least 7 weeks (claim 9) and wherein the insulin-related peptide is administered at least once daily for at least 7 weeks (claim 10).
Regarding claims 10, the claims of the copending application recite wherein the insulin-related peptide comprises a first amino acid sequence comprising an insulin beta chain 7-26 peptide sequence (SEQ ID NO: 9) or a variant thereof having one or more amino acid substitutions; and a second amino acid sequence comprising an insulin alpha chain 6-20 peptide sequence (SEQ ID NO: 4) or a variant thereof having one or more amino acid substitutions (claim 11, 36, 64).
Regarding claims 11-13, the claims of the copending application recite wherein:(a) the insulin-related peptide comprises one or more of insulin, proinsulin and preproinsulin; or (b) the insulin-related peptide comprises human insulin; or (c) the insulin-related peptide comprises human proinsulin and/or human preproinsulin (claim 13, 41), wherein the insulin-related peptide is a recombinant human insulin-related peptide (claim 34).
Regarding claims 14-15, 17-19, the claims of the copending application recite the method of decreasing the likelihood of Type 1 diabetes in a subject in need thereof comprising (claim 1), attenuating an antigenic response in a mammalian subject (claim 5).
Regarding claims 21-23, 27, the claims of the copending application recite wherein the composition comprises an effective amount of an insulin-related peptide; and an aqueous pharmaceutically acceptable carrier, which comprises at least about 30 vol.% glycerin; or (b) a composition comprising: an insulin-related peptide; and an aqueous pharmaceutically acceptable carrier, which comprises at least about 30 vol.% glycerin (claim 35, 72), wherein the aqueous pharmaceutically acceptable carrier further comprises a buffer (claim 39, 73-75).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mercy H. Sabila whose telephone number is (571)272-2562. The examiner can normally be reached Monday - Friday 5:00 am - 3:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko G. Garyu can be reached at (571)270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MERCY H SABILA/Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654