DETAILED ACTION
The receipt is acknowledged of applicant’s amendment filed 04/20/2026; IDS filed 09/11/2026; and IDS filed 03/09/2026.
Claims 20-38 previously presented. Claims 39-42 are currently added. Claims 20-42 are pending and subject of this office 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 .
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 39-42 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 depend on canceled claim 1. In order to advance the prosecution the claims will be treated as depending on generic claim 20.
Claim 42 recites the acronyms “1-NOX-B11-2”. The term should be fully recited when it first appears in the claim followed by bracketed abbreviation, and abbreviation can be used later in the claim and in the dependent claims.
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 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 20-33 and 39-42 are rejected under 35 U.S.C. 103 as being unpatentable over Bryant et al. (US 2003/0211967, currently cited in PTO 892), combined with the article by Monkare et al.(“IgG-loaded hyaluronan-based dissolving microneedles intradermal protein delivery”, previously provided) evidenced by Nakazato et al. (“A Role for Ghrelin in the central Regulation of Feeding”, IDS filed 08/29/2023), and further combined with either Park et al. (US 2002/0082543, of record in the parent application), or Liu et al. (US 20018/0236215, of record in the parent application).
Applicant Claims
Claim 20 is directed to a method of modulating a subject’s appetite, comprising:
applying a dermal patch having a plurality of projections to a subject’s skin such that the projections penetrate into the skin, wherein said dermal patch includes a ghrelin blocker incorporated in the plurality of projections at a concentration configured to modulate the subject’s appetite,
wherein the projections include a biodegradable matrix material that is degradable in the skin so as to release a sufficient amount of the ghrelin blocker into the skin such that the ghrelin blocker is introduced into the subject’s circulatory system so as to bind to circulating ghrelin to modulate its biological activity, thereby modulating the subject’s appetite.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Bryant teaches method for inhibiting ghrelin activity to treat obesity by administering agents that neutralize ghrelin or ghrelin receptors antagonist, e.g. growth hormone secretagogue receptor antagonist (GHS-RA) and ghrelin neutralizing agent (GNA) to treat obesity by inhibition of food intake (abstract; ¶¶ 0004, 0012). Elevated ghrelin increases appetite and fat deposition, and antagonizing ghrelin action induces energy consumption from fat stores (¶¶ 0010, 0050). The preferred routes of administering ghrelin receptors antagonists is that introduce the antagonists to the systemic circulation by transdermal or topical delivery, or by using hypodermic needle (¶¶ 0014, 0015, 0036). The reference teaches anti-ghrelin antibodies and anti-ghrelin antibodies fragments (¶¶ 0019-0021, 0032-0034). A GHS-RA is any compound that partially or fully antagonizes, blocks, or otherwise inhibits the biological action of ghrelin by binding to the GHS-R without stimulating the release of growth hormone. GHS-RA are compounds useful in the methods and include natural products, synthetic organic compounds, peptides, proteins, antibodies, antibody fragments, single chain antibodies, and antibody based constructs (¶¶ 0028-0029; claims).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.012)
While Bryant teaches transdermal and hypodermic delivery of ghrelin antagonists, i.e. ghrelin blockers, to systemic circulation, the reference does not explicitly teach dermal patch comprising projections as claimed by claim 1.
Monkare teaches dissolvable microneedles for dermal efficient noninvasive delivery of IgG (immunoglobulin-G). The microneedles penetrate the epidermis and dissolve to deliver the IgG (see the entire document, and in particular abstract and conclusion). Immunoglobulin-G (IgG) is an anti-ghrelin as evidenced by Nakazato. Nakazato further teaches anti-ghrelin i.e. ghrelin blocker, is an acylated peptide that suppresses feeding i.e. reduced appetite (see abstract).
Park teaches microneedle device comprising substrate and plurality of microneedles extending from the substrate. The microneedles comprising drug in longitudinal channels. The microneedle device used to deliver drugs into the skin or for systemic delivery (abstract; ¶¶ 0015, 0035, 0036, 0038, 0119, 0123, 0125, 0134). The microneedles are formed of biodegradable biocompatible polymers (¶ 0016). The microneedle comprises a shaft that includes a channel and two layers around the shaft. the channel can be filled with a matrix material containing a drug. The drug would then be released at a controlled rate following microneedle insertion, by degradation of the matrix material (¶¶ 0046, 0049). The microneedles may comprise chambers comprising the drug (¶ 0065), that read on encapsulation of the drug. The microneedles provides controlled drug delivery by selecting the rate of biodegradation or dissolution of the microneedles or of a biodegradable matrix having drug dispersed within the matrix, for example by selection of the appropriate polymeric matrix material. The matrix comprises synthetic or natural polymer, ceramic material, etc. (¶¶ 0064, 0068). The active agent can be particles encapsulated in the polymer forming the microneedles, and can be stored in chambers in the microneedles (¶¶ 0045, 0065). Microneedles device is relatively painless, and provides controlled and safe delivery of drugs across the skin for local or systemic delivery (¶¶ 0012, 0119, 0123, 0125, 0134).
Liu teaches device comprising microneedle array projecting from a substrate to deliver active agent that are loaded into the microneedles to a patient through the skin (abstract; ¶¶ 0006-0008). The microneedles are made of dissolvable polymer that dissolve when inserted into skin and release the active agent (¶¶ 0009). The microneedle dissolve after separation from the substrate (¶¶ 0086, 0087). Each microneedle comprises two layers of different dissolvable polymer and having different degradation and dissolution (¶¶ 0014, 0015, 0052, 0053). The dissolvable polymer includes collagen and carboxymethyl cellulose (¶¶ 0017, 0058). The active agent is incorporated in the microneedles within a matrix defined by a dissolvable polymer (¶ 0011), i.e. encapsulated. The active agents include antibodies, and is present in amount of 0.001-15% (¶ 0065, 0067). Advantages of the microneedle arrays include increasing skin permeability for a variety of biological entities or active ingredients, permitting slow therapeutic release while reducing complications from localized or systemic diffusion, providing a large treatment area relative to a single-site injection, and creating less pain for a subject compared to hypodermic administration of an active material (¶ 0072).
Finding of Prima Facie Obviousness Rational and Motivation
(MPEP §2142-2143)
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the present invention to reduce food intake by administration of ghrelin antagonist to reduce appetite because ghrelin increases appetite, and administer ghrelin transdermally or using hypodermic needles as taught by Bryant, and use microneedles taught by Monkare as evidenced by Nakazato, Park or Lui. One would have been motivated to do so because Monkare, as evidenced by Nakazato, teaches microneedles are efficient noninvasive method for delivering IgG that is a known ghrelin blocker through the skin. Further, one having ordinary skill in the art would have used transdermal microneedle devices taught by any of Park or Lui to deliver ghrelin antagonist because Park teaches microneedles device is relatively painless, and provides controlled and safe delivery of drugs across the skin to systemic circulation, and because Liu teaches microneedles device has the advantages of increasing skin permeability for the active ingredients, permitting slow therapeutic release while reducing complications from localized or systemic diffusion, providing a large treatment area relative to a single-site injection, and creating less pain for a subject compared to hypodermic injection. One would reasonably expect reduce food intake, suppress appetite and treat obesity by delivering ghrelin antagonist using microneedles in a subject in need thereof wherein the delivery method is painless and advantageous over hypodermic injection.
Regarding the claimed method of suppressing appetite as claimed by claim 20, Bryant teaches elevated ghrelin increases appetite and fat deposition, and antagonizing ghrelin action induces energy consumption from fat stores, and this teaching implies that blocking ghrelin will suppress appetite.
Regarding plurality of projections as claimed by claim 20, this is taught by Monkare, Park and Lui.
Regarding ghrelin blocker incorporated in the plurality of projections as claimed by claim 20, this is taught by combination of the cited references.
Regarding the concentration of ghrelin antagonist is configured to modulate the subject’s appetite as claimed by claim 20, this is implied by the teachings of the references in combination, appetite and food intake being suppressed and obesity being treated.
Regarding claim 20 that the projections include a biodegradable matrix material is degradable in the skin so as to release a sufficient amount of the ghrelin blocker into the skin such that the ghrelin blocker is introduced into the subject’s circulatory system so as to modulate the subject’s appetite, Monkare, Park and Lui teach biodegradable projections that deliver ghrelin to the circulatory system.
Regarding the functional limitation of claim 20 that “ghrelin blocker is introduced into the subject’s circulatory system so as to bind to circulating ghrelin to modulate its biological activity, thereby modulating the subject’s appetite”, combination of the cited references teaches the instantly claimed method and device used to practice the method as claimed by claim 20 that delivers ghrelin into the circulatory system, and any property or function applicant achieved would be intrinsic inevitable function inseparable from the method and device taught by combination of the cited references. Note that both Park and Liu teach systemic administration of active agents using microneedles, and Lui teaches microneedles are advantageous over hypodermic injection taught by Bryant.
Regarding the ghrelin blocker comprises an anti-ghrelin antibody, antibody fragment, aptamer, catalyzer as claimed by claims 21, 22, 23-24, and 39-42, Bryant teaches antibodies, antibodies fragments, and Monkare evidenced by Nakazato teach IgG that is a known ghrelin antagonist. Further, applicants failed to claim specific aptamer or catalyzer and failed to show any unexpected results of any of the claimed ghrelin blockers.
Regarding claim 25 that the ghrelin blocker exhibits specific binding to ghrelin, acylated ghrelin or a ghrelin precursor, and claim 26 that the ghrelin precursor is prepro-ghrelin, these are properties inseparable from ghrelin blocker, specially applicants used immunoglobulin-G taught by Monkare, evidenced by Nakazato, that teaches IgG suppresses appetite by blocking acylated ghrelin.
Regarding the concentration of the ghrelin blocker in the plurality of the projections is in a range of about 1% to about 80%, about 10% to about 70%, about 20% to about 60% and about 30% to about 50% as claimed by claims 27, 28, 29 and 30, respectively, one having ordinary skill in the art would have determined the effective amount based on the desired degree of appetite suppression, and specific patient condition, e.g. age, weight, health condition, etc.
Regarding claim 31 that the ghrelin blocker is configured to interact with any of circulating ghrelin and at least one of its precursors for modulating the subject’s appetite, this is property of the ghrelin blocker once it reaches the circulation after administration by the microneedles.
Regarding the anti-ghrelin comprises immunoglobulin-G claimed by claim 32, this is taught by Monkare evidenced by Nakazato.
Regarding the material of the biodegradable matrix as claimed by claim 33, Liu teaches collagen and carboxymethyl cellulose.
Absent any evidence to the contrary, and based upon the teachings of the prior art, there would have been a reasonable expectation of success in practicing the instantly claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present invention.
Claims 34-37 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of Bryant, Monkare evidenced by Nakazato, and Park or Liu as applied to claims 20-33, and 39-42 above, and further in view of Francis et al. (US 2018/0161252, of record).
Applicant Claims
Claims 34-35 recite that the ghrelin blocker is encapsulated in polymer particles. Claim 36 recites particles have different sizes and claims 37 recites particle have different materials.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
The combined teachings of Bryant, Monkare evidenced by Nakazato, and Park or Liu, are previously discussed in this office action.
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.012)
While Park teaches encapsulation of the active agent in polymeric matrix in channels in the microneedles, the reference however does not teach encapsulating the active agent in polymeric particles as claimed by claims 34-35. The cited references do not teach different sizes or different materials of the particles as claimed by claims 36 and 37 respectively.
Francis teaches microneedle device to deliver active agent to the skin, the device comprises dissolvable microneedles and active agent encapsulated in biocompatible or biodegradable polymer microparticles, e.g. PVP, PEG (abstract; ¶¶ 0029, 0057, 0058).
Finding of Prima Facie Obviousness Rational and Motivation
(MPEP §2142-2143)
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the present invention to suppress appetite using ghrelin blocker administered from microneedle device and included in a polymer matrix within a channel in the microneedles as taught by the combination of Bryant, Monkare evidenced by Nakazato, and Park or Liu, and encapsulate the ghrelin blocker in polymeric microparticles and incorporate them in the matrix in the channels of the microneedles as taught by Francis. One would have been motivated to do so because Francis teaches suitability of polymeric microparticles to deliver active agent to the skin from microneedle device. One would reasonably expect formulating microneedle device comprising microparticles encapsulating ghrelin blocker in channels of the microneedles that successfully deliver the active agent to the skin.
Regarding claim 34 that microneedles comprises a plurality of polymeric particles encapsulating ghrelin blocker material, Francis teaches polymeric microparticles encapsulating active agent, and combination of all the cited references teaches polymeric microparticles encapsulating ghrelin blocker.
Regarding claim 35 that the particles are disposed in channel in the microneedles, combination of the cited references teaches drug is present in channel, and therefore, the polymeric particles encapsulated the drug will be present in the channel.
Regarding claim 36 that the polymeric particles exhibit different sizes, one having ordinary skill in the art would have formulated the particles of different sizes to provide different release profile, based on the amount of the drug and its desired period of release.
Regarding claims 37 that the polymeric particles are formed of a plurality of different polymeric materials, one having ordinary skill in the art would have formulated the particles of different polymeric material based on desired period and mode of drug release, and site of application.
Absent any evidence to the contrary, and based upon the teachings of the prior art, there would have been a reasonable expectation of success in practicing the instantly claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present invention.
Claim 38 is rejected under 35 U.S.C. 103 as being unpatentable over the combination of Bryant, Monkare evidenced by Nakazato, Park or Liu, and Francis as applied to claims 20-37 and 39-42 above, and further in view of Chen et al. (US 2016/0058992, of record).
Applicant Claims
Claim 38 recites different polymeric materials and exhibit different dissolution rates in the skin.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
The combined teachings of Bryant, Monkare evidenced by Nakazato, Park or Liu and Francis are previously discussed in this office action.
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.012)
The combination of the references does not explicitly teaches different polymeric materials as claimed by claims 38.
Chen teaches device for delivering active agent to the skin without discomfort,
inconvenience and instability associated with regular needle. The device comprises
backing layer and microneedles projections attached to the backing by adhesive. The
microneedles comprises biodegradable bioerodible polymers, e.g. chitosan, gelatin,
carboxymethyl cellulose. The microneedles comprises different portions made of
different polymers of different solubilities, e.g. different layers. The microneedles
comprises shaft (abstract; ¶¶ 0008, 0009, 0044, 0045, 0060, 0071, 0079, 0087, 0088,
0089, 0098).
Finding of Prima Facie Obviousness Rational and Motivation
(MPEP §2142-2143)
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the present invention to suppress appetite using ghrelin blocker administered from microneedle device and included in a polymer matrix within a channel in the microneedles as taught by the combination of Bryant, Monkare evidenced by Nakazato, Park or Liu, and Francis, and use different polymers of different solubilities and different materials in different portions or layers of the microneedles as taught by Chen. One would have been motivated to do so because Chen teaches Chen teaches suitability of using different polymers of different solubilities and different materials. One would reasonably expect suppressing appetite using ghrelin blocker administered from microneedle device and included in a polymer matrix within a channel in the microneedles, wherein the polymers have different materials and consequently different solubility.
Absent any evidence to the contrary, and based upon the teachings of the prior art, there would have been a reasonable expectation of success in practicing the instantly claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present invention.
Response to Arguments
Applicant's arguments filed 04/20/2026 have been fully considered but they are not persuasive.
Rejections Under 35 U.S.C. §103
Regarding Claims 20-33
Applicants argue that the combination of Bryant with the microneedle references (Monkare, Park, or Liu) relies on impermissible hindsight and fails to appreciate the significant technical hurdles a POSA would have faced at the time of the invention. The Office Action argues it would have been obvious to turn to microneedle technology to implement transdermal administration of a ghrelin blocker in Bryant. This is, however, an oversimplification that ignores the profound leap in complexity and the lack of a reasonable expectation of success.
In response to the argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In the instant case, the examiner relied on what was known in the art before the effective time of the present invention to construe the rejection, and not on applicant’s own disclosure. Motivation to combine the references exists, as well as reasonable expectation to achieve the present invention, as set forth in this office action. It should be noted that the motivation to combine references can be different from the ones set forth by Applicant. That is, as long as motivation exists to combine the elements, the problem to be solved does not have to involve the same reason. As such, the examiner respectfully submits that there is motivation to combine the cited references as well as reasonable expectation to achieve the present invention. Obviousness does not require absolute predictability of success all that is required is a reasonable expectation of success. See In re Kubin, 561 F.3d at 1360. The Court has held that "the test of obviousness is not express suggestion of the claimed invention in any or all of the references but rather what the references taken collectively would suggest to those of ordinary skill in the art presumed to be familiar with them." See In re Rosselet, 146 USPQ 183, 186 (CCPA 1965). "There is no requirement (under 35 USC 103(a)) that the prior art contain an express suggestion to combine known elements to achieve the claimed invention. Rather, the suggestion to combine may come from the prior art, as filtered through the knowledge of one skilled in the art." Motorola, Inc. V. Interdigital Tech. Corp., 43 USPQ2d 1481, 1489 (Fed. Cir. 1997). An obviousness determination is not the result of a rigid formula disassociated from the consideration of the facts of a case. Indeed, the common sense of those skilled in the art demonstrates why some combinations would have been obvious where others would not. See KSR Int'l Co. V. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007) ("The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.").
Significant Formulation and Stability Challenges: Applicants argue that a ghrelin blocker, e.g., an antibody, is a complex molecule and a POSA would be acutely aware that formulating such a molecule (e.g., a large protein) into a solid, dissolvable polymer matrix without destroying its biological activity is a major, non-trivial undertaking. The Monkare notes the "critical importance of the protein stability in microneedles," highlighting the numerous stresses proteins face during fabrication, including "heating, drying, complex formation with excipients and interfacial effects" (Monkare, p. 54). Successfully co- formulating an anti-ghrelin antibody into a polymer matrix while ensuring it remains stable, avoids aggregation, and retains its ability to bind ghrelin upon dissolution would not have been predictable.
In response to this argument, Bryant teaches transdermal, topical and hypodermic delivery of ghrelin antagonists, i.e. ghrelin blockers, to systemic circulation, and Monkare teaches dissolvable microneedles for dermal efficient noninvasive delivery of protein IgG, and anti-ghrelin is IgG. Bothe Park and Lui teaches advantages of microneedles for delivering drugs to the circulation. The prior art dealt with the same problem and material applicants used to achieve delivery of such material from dissolvable microneedle device. Obtaining the claimed method from the teachings of the prior art is reasonable and its success is evident by combination of the cited references. Conclusion of obviousness does not require absolute predictability, only reasonable expectation of success, and references are evaluated to what they suggest to one having ordinary skill in the art, rather by their own disclosure.
Improper "Obvious to Try" Rationale: applicants argue that the Office Action's rationale amounts to an improper "obvious to try" argument. Without a reasonable expectation of success, attempting to combine these technologies is merely speculative research, not obviousness.
In response to this argument, it is argued as cited in the "Examination Guidelines Update: Developments in the Obviousness Inquiry After KSR v. Teleflex" from the Federal Register (9/1/2010 - vol. 75, no. 169), "an obvious to try rational may be proper when the possible options for solving a problem were known and finite. However, if the possible options were not either known or finite, then an obvious to try rationale cannot be used to support a conclusion of obviousness." Rolls-Royce PLC v. United Technologies Corp., 603 F.3d 1325 (Fed. Cir. 2010). However, the number of possible of solutions from the many references relied upon represents an infinite number of solutions and actually establishes that the applicants' claimed invention is prima facie unobvious, especially in light of the claims as amended. In the instant case, as set forth in this office action, the rejections of the claims are not based on obvious to try. Rather, the rejections are based on reasonable combination of what was known in the art before the effective filing date of the present invention. The rejections provide motivation to combine the cited references, as well as reasonable expectation of success to arrive to the present invention as a whole. 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. This is the case here in the rejections standing in this office action.
Uncertain Introduction Into the Circulatory System: applicants argue that, even assuming arguendo that the ghrelin blocker could be successfully incorporated into and released from a dissolvable microneedle without losing its functionality, the Examiner's conclusion that it would be "inevitable" for the antibody to reach the circulatory system (Office Action, p. 16) is speculative and unsupported. A person of ordinary skill in the art would recognize that introducing a large biomolecule like an antibody into the dermis does not guarantee systemic uptake. On the contrary, a POSA would anticipate significant and well-known biological hurdles that would prevent or severely limit entry into the bloodstream. These hurdles include the slow diffusion of large molecules through the dense dermal extracellular matrix, rapid clearance and sequestration into the lymphatic system and local enzymatic degradation by proteases present in the skin. Hence, The cited prior art provides no data or teaching to overcome these barriers, and thus a POSA would lack any reasonable expectation that a therapeutically effective amount of the ghrelin blocker would ever reach the systemic circulation to modulate appetite as claimed.
In response to this argument, it is argued that Bryant teaches method for inhibiting ghrelin activity to treat obesity by administering agents that neutralize ghrelin or ghrelin receptors antagonist, that are large biomolecules currently claimed, and further teaches the preferred routes of administering ghrelin receptors antagonists is that introduce the antagonists to the systemic circulation by transdermal or topical delivery, or by using hypodermic needle. Therefore, delivery of ghrelin blockers to the systemic circulation following transdermal administration was known before the effective filing date of the present invention, and not a speculative and unsupported as applicants assert. No teachings of the cited references that biological hurdles would prevent or severely limit entry of ghrelin blockers into the bloodstream. The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain. In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir 1983). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989). See also Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005).
Applicants argue that the Examiner's reliance on Nakazato is misplaced. Nakazato exclusively investigates the central effects of ghrelin by administering an anti-ghrelin antibody directly into the brain via intracerebroventricular (ICV) injection (Nakazato, Abstract; Methods). This invasive laboratory technique bypasses the blood-brain barrier. Crucially, Nakazato provides no teaching or suggestion regarding the efficacy of systemic administration of an anti-ghrelin antibody for appetite modulation. A POSA would understand that an effect observed with direct-to-brain injection provides no reasonable expectation of success for a systemic delivery method, which must overcome the formidable blood-brain barrier.
In response to this argument, it is noted that Nakazato is an evidentiary reference relied upon for solely teaching the immunoglobulin-G (IgG) taught by Monkare is an anti-ghrelin. Nakazato further teaches anti-ghrelin i.e. ghrelin blocker, is an acylated peptide that suppresses feeding i.e. reduced appetite. Nakazato does not need to provide any teaching or suggestion regarding the efficacy of systemic administration of an anti-ghrelin antibody for appetite modulation. The reference satisfies the purpose for which it was applied. A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments.
Regarding Claims 34-37
Applicants argue that the primary combination of references fails to render claim 20 obvious. Because claims 34-37 depend from claim 20, they are likewise not obvious for at least the same reasons. Moreover, the addition of Francis to teach encapsulating the active agent in polymeric microparticles to be incorporated into the microneedle matrix further exemplifies the hindsight-driven nature of the rejection, proposing a complex "matrix-within-a-matrix" system with no motivation or suggestion in the art.
In response to this argument, it is argued that claim 20 in unpatentable as discussed in this office action. Francis is relied upon for teaching encapsulation of the ghrelin blocker taught by the combination of, Bryant, Monkare evidenced by Nakazato, Park, or Liu in polymeric microparticles and incorporate them in the matrix in the channels of the microneedles. Francis does not need to reteach elements taught by other references. Francis satisfied the purpose for which it was applied.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In the instant case the examiner relied on what was known before the effective filing date to construe the rejection, as set forth in this office action.
Regarding Claim 38
Applicants argue that the underlying rejections of claims 20 and 34-37 are improper. Because claim 38 depends from this subject matter, it is likewise not obvious. The Examiner has now combined five or six separate references to arrive at the specific features of claim 38. This "obviousness" argument is constructed with the blueprint of Applicant's claims in hand and does not reflect what a POSA would have actually found obvious.
In response to this argument, it is argued that claim 20 in unpatentable as discussed in this office action. Chen is relied upon for teaching the of use different polymers of different solubilities and different materials in different portions or layers of the microneedles as claimed by claim 38. Chen satisfied the purpose for which it was applied. The arguments regarding blueprint is hereby repeated as set forth in this office action.
New Claims
Applicants argue that support for new dependent claims 39 - 42 can be found, e.g., at paragraphs 15 and 18 of Applicant's Published Application. These claims are patentable at least based on their dependence on claim 1. Moreover, they recite features not disclosed or suggested by any of the cited references.
The examiner disagrees because the claims are taught either expressly or implicitly by the cited references as set forth in this office action.
Finally, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). Further, reasonable expectation to achieve the resent invention was presented as set forth in this office action. The obviousness does not require absolute predictability of success all that is required is a reasonable expectation of success. See In re Kubin, 561 F.3d at 1360. The Court has held that "the test of obviousness is not express suggestion of the claimed invention in any or all of the references but rather what the references taken collectively would suggest to those of ordinary skill in the art presumed to be familiar with them." See In re Rosselet, 146 USPQ 183, 186 (CCPA 1965). "There is no requirement (under 35 USC 103(a)) that the prior art contain an express suggestion to combine known elements to achieve the claimed invention. Rather, the suggestion to combine may come from the prior art, as filtered through the knowledge of one skilled in the art." Motorola, Inc. v. Interdigital Tech. Corp., 43 USPQ2d 1481, 1489 (Fed. Cir.1997). An obviousness determination is not the result of a rigid formula disassociated from the consideration of the facts of a case. Indeed, the common sense of those skilled in the art demonstrates why some combinations would have been obvious where others would not. See KSR Int'l Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007) ("The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.").
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 Isis A D Ghali whose telephone number is (571)272-0595. The examiner can normally be reached Monday through Friday, 8:30 AM to 5:00 PM EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bethany Barham can be reached on 571-272-6175. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ISIS A GHALI/Primary Examiner, Art Unit 1611
