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.
Information Disclosure Statement
The information disclosure statement filed 18 July, 2025 fails to comply with 37 CFR 1.98(a)(3)(i) because it does not include a concise explanation of the relevance, as it is presently understood by the individual designated in 37 CFR 1.56(c) most knowledgeable about the content of the information, of each reference listed that is not in the English language. One document in this IDS was not in English, with no explanation of the relevance of the document, and so was not considered.
Claims Status
Claims 13-15, 17, 21-23, 25, and 27-29 are pending.
Claims 13-15 and 23 have been amended.
Claims 27-29 are new.
Withdrawn Rejections
The rejection of claims 13-15, 17, 21, and 22 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph due to the introduction of new matter is hereby withdrawn due to amendment.
The rejection of claims 13-15, 17, 21 and 22 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite due to the phrase “inherent to the microneedle array” is hereby withdrawn due to amendment.
Maintained/Modified Rejections
Claim Rejections - 35 USC § 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 13-15, 17, 21-23, 25, and 27-29 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
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: 1) the breadth of the claims; 2) the nature of the invention; 3) the state of the prior art; 4) the level of one of ordinary skill; 5) the level of predictability in the art; 6) the amount of direction provided by the inventor; 7) the existence of working examples; and 8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure” (MPEP 2164.01(a).
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1 and 2) the breadth of the claims and the nature of the invention: Applicants are claiming a sustained release formulation of GLP analogs using a polyvinylpyrrolidone microneedle system. Sustained release is defined as release or continual dispensing over at least 2 hours (p4, 3d paragraph).
3) the state of the prior art: Jin (US 9,320,878, cited by applicants) discusses a controlled release microneedle formulation (abstract). The reference describes a drug reservoir connected to a microneedle array, where the microneedles absorb water to form a hydrogel through which the drug diffuses (column 2, line 59-column 3, line 7). It explicitly states that polyvinyl pyrrollidone microneedles are incapable of offering a sustained release (column 2, line 15-21). An approach where the microneedle dissolves leaving a hole in the stratum conium which allows topically applied materials to enter the skin is problematic due to closure of the holes (column 2, line 21-26).
Sun et al (Acta Biomater. (2013) 9(8) p7767-7774, cited by applicants) discusses polyvinyl pyrrolidone microneedles for delivery of proteins (title). In a test using ex-vivo skin samples, the needles were significantly dissolved after 2.5 min and completely dissolved after 5 min (7th page, 2nd paragraph). This fast delivery is touted as a benefit for certain applications, in contrast to continuous delivery of therapeutics over a long period of time (8th page, 2nd paragraph). Note that this test appears to have been conducted at room temperature (5th page, 2nd paragraph); it is reasonably expected that at the higher temperatures in vivo, dissolution will be even faster.
4) the level of one of ordinary skill: The level of skill in the art is high.
5) the level of predictability in the art: This is a field that has been studied extensively; the level of predictability is relatively high.
6 and 7) the amount of direction provided by the inventor and the existence of working examples: Applicants discuss extended release multiple times through their disclosure, but provide no information on how the system can be tweaked to get the extended release required by the claims. There is an “in vitro” results of dissolution of various formulations (p7, 4th paragraph, continues to p8), but the test is not described at all, and the formulation descriptions are incomplete (some of the terms describing components are not defined, and the ratios are not given at all). It is not clear if this is dissolution of microneedles or dissolution of bulk material. Given the description of how the material is made (example 1, p8, 2nd paragraph to the end of the specification), and the similarities of these formulations to those of Sun et al, it is not clear that this test is representative of the dissolution time of the microneedles in vitro.
8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure: The prior art clearly states that polyvinyl pyrrolidone microneedles rapidly dissolve in vivo, and are unsuitable for extended release formulations. The various ways described in the prior art to use microneedle technology for extended release – slow dissolution, hollow needles attached to a reservoir, holes in skin allowing a topically applied drug to permeate – are described as ineffective (holes in skin), or will not work once the microneedle rapidly dissolves (slow dissolution, reservoir supply). There is no discussion of how to render polyvinyl pyrrolidone less soluble or to extend the rapid release of this polymer – from a reading of the specification, the polyvinyl pyrrolidone itself is responsible for extended release, in contradiction with the prior art. While applicants have data showing a 24 hour release time, this is for poorly defined formulations in a completely undefined test; it is not clear that this test is relevant to what occurs when the material is used as intended in a subject. Given that formulations that meet the claim limitations save for a different polypeptide were demonstrated by Sun et al to dissolve orders of magnitude faster than required by the claims, it will take undue experimentation to make and use the invention as claimed.
response to applicant’s arguments
Applicants argue that the drug is not released when the microneedle has dissolved, that the compounds of Sun et al are different than those of applicants, so the diffusion of those materials does not show that applicant’s drugs will diffuse similarly, that the MW of the PVP is higher, which will slow dissolution, and that the additional components will slow dissolution. This is supported by a declaration by Dr. Danny Brodkorb, employee of the assignee.
Applicant's arguments filed 2 Oct, 2025 have been fully considered but they are not persuasive.
Applicants argue that, after dissolution, the polymer still binds the materials, and so it is not released. While Sun et al shows that this effect does not occur, applicants argue that the differences between the materials of Sun et al and the GLP-1 analogs of applicants are different enough so the reference cannot be extrapolated. However, applicants have provided no evidence besides speculation that this effect occurs. There is no experimental data, save a very poorly described in vitro dissolution test, and no references demonstrating this effect. Nor have applicants suggested what physical features the GLP-1 analogs have that the materials of Sun et al do not that cause them to be bound after dissolution. In other words, this is merely speculation, and the data of Sun et al is more persuasive than speculation by applicants of a new and undemonstrated effect.
Applicants argue that the higher molecular weight of their material compared to that of Sun et al will slow dissolution. Lee et al (cited by applicants in IDS of 16 April, 2025) made PVP microneedles of both 10K (the MW used by Sun et al) and 360K (abstract). Both dissolved immediately in an ex vivo assay (p5071, 2nd column, 1st paragraph). So while MW may affect dissolution time, it clearly is not sufficient to make a significant difference.
Finally, applicants argue that the other excipients in the claims will increase the dissolution time. Once again, there is no evidence presented. Nor is the extent of the effect even suggested; applicant’s declaration is consistent with extending the time of dissolution by a few percent compared to that of Sun et al or Lee et al, which is not sufficient to meet the claim limitations. Nor is it clear how the concentration of these excipients plays a role. In other words, applicants have provided no evidence that the claimed arrays will meet the extended release limitation.
Claim Rejections - 35 USC § 112(b)
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 13-15, 17, 21-23, 25, and 27-29 are 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.
The claims require that the PVP have a molecular weight of greater than 10 kDa. However, applicants have not stated how the MW is calculated. Gaube et al (J. Chem. Eng. Data (1993) 38 p207-210) shows that, even for relatively monodisperse materials, a number weighted MW will be lower than a mass based molecular weight (table 1, p207, 2nd column, top of page). This means that there are embodiments that will read on this molecular weight limitation if the MW is measured one way, but not another.
response to applicant’s arguments
Applicants argue that they have limited the MW to that corresponding to PVP K29/32 and K90.
Applicant's arguments filed 2 Oct, 2025 have been fully considered but they are not persuasive.
Applicants have claimed the molecular weight in Daltons, not as viscosity grade. While the claimed MWs may correspond to a viscosity grade, it is not defined that way in the claim. In essence, applicants are trying to read a limitation into the claim from the specification, which is not permitted.
New Rejections
Claim Rejections - 35 USC § 112(a)
The legal basis for rejections under this statue was given above, and will not be repeated here.
Claims 13-15, 17, 21-23, 25, and 27-29 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claims 13 and 23 have been amended to include a MW of greater than 1000kDa to about 1.3 MDa. Support is from K90. There are two issues with this amendment. First, applicants state that K90 has a MW of ~1.3MDa. The definition of a term in the specification governs, so this is interpreted as ~1.3Mda, not greater than 1000 kDa to about 1.3 MDa. Second, if we ignore the first point and rely upon the MW of standard K90, it is 1-1.3 MDa, not greater than 1 MDa to about 1.3 MDa. In other words, the boundaries of what applicants are claiming are slightly different than the MW in the prior art of what they are pointing to for support. Under either interpretation, this is new matter.
Claim Rejections - 35 USC § 112(b)
The legal basis for rejections under this statute was given above, and will not be repeated here.
Claims 27-29 are 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.
Applicants have defined K29/32 as a medium molecular weight PVP, ~58 KDa (footnote of table 1, bottom of p7, continues to top of p8). It is unclear what the molecular weight range of ~58 KDa encompasses, and what the basis of the measurement is (note the previous rejection under this statue).
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FRED REYNOLDS whose telephone number is (571)270-7214. The examiner can normally be reached M-Th 9-3:30.
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/FRED H REYNOLDS/Primary Examiner, Art Unit 1658