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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 03 December 2025 has been entered.
Formal Matters
Applicant’s amendments and arguments along with the declaration Carl Eric Elmquist in the reply filed on 03 December 2025 are acknowledged and have been fully considered. Claims 1-8, 10-11, 41-43, 45-46, 49, 59, and 82 are pending. Claims 1-8, 10-11, 41-43, 45-46, 49, 59, and 82 are under consideration in the instant office action. Claims 9, 12-40, 44, 47-48, 50-58, 60-81, and 83 are canceled. Applicant’s claim amendments, arguments, and comparison data provided in the declaration did not overcome the rejections under 35 USC 103 for reasons set forth in the previous office action and herein below.
Withdrawn Objections/Rejections
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn as are those rejections and/or objections expressly stated to be withdrawn.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03 December 2025 is noted and the submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the examiner has considered the references. A signed copy is attached herein.
New Rejections
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 1 and 3 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 term “substantially” in claims 1 and 3 is a relative term which renders the claim indefinite. The term “substantially” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear to what extent the compound is free of valerolactone residues or if present what amount of valerolactone residue is permissible. The metes and bounds of “substantially free of” is unclear. Appropriate clarification is requested.
Rejections Maintained
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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, 10-11, 41-43, 45-46, 49, 59, and 82 remain rejected under 35 U.S.C. 103 as being unpatentable over Le Dévédec et al. (US 2017/0100343, IDS reference).
Applicant Claims
Applicant claims a compound or a pharmaceutically acceptable salt thereof comprising the structure as depicted in claims 3 and 4. Applicant amended instant claim 1 by adjusting the amount of allyl lactide residues in the copolymer.
Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
Le Dévédec et al. teach crosslinked particles (e.g., microparticles) that are capable of storing and releasing drugs. The particles can be macroparticles, microparticles, or nanoparticles and can be composed of polyester backbones. The particles can be loaded with a drug. The particles can degrade in vivo to release the drug. The particles can be prepared by crosslinking functionalized polyester backbones and loaded with a given drug. The particles of the present disclosure can be injected with a syringe. In some embodiments, the particles of the present disclosure are administered in connection with a surgery and release the drug after the site of the surgery for a period of 1-6 months (see abstract). In another aspect, the present disclosure provides a method of preparing a crosslinked degradable particle, comprising: [0019] dissolving a polyester containing a plurality of allyl groups, a dithiol, and a photoinitiator in at least one solvent to form a solution; [0020] emulsifying the solution in an aqueous phase to form an emulsion; [0021] irradiating the emulsion with UV light to react the dithiol with two of the allyl groups to form a crosslink; and [0022] evaporating at least a portion of the solvent from the emulsion. [0205] The microparticles of the present disclosure can have a diameter between about 1 μm and about 999 μm, including all ranges and subranges therebetween, and more preferably, the microparticles can have a diameter between about 1 μm and about 100 μm, including all ranges and subranges therebetween. In some embodiments, the microparticles of the present disclosure can have a diameter between about 5 μm and about 30 μm, including all ranges and subranges therebetween (e.g., between about 7 μm and about 15 μm or about 10 μm). [0209] In one or more embodiments, any of the valerolactone, caprolactone, lactic acid, lactide, or glycolic acid is functionalized with a functional group. In some embodiments, the functional group can be selected from an allyl group, a propargyl group, or a carboxylic acid group (e.g., the functional groups can be allyl lactide, allyl valerolactone and the like). Alternatively, the functional group can be a trans-cyclooctene, norbornene, or a carbonyl group (e.g., an aldehyde or ketone). Alternatively, the functional group can be a thiol group, an amine, or a tetrazine. [0247] The polyesters of the present disclosure can be prepared using a variety of different suitable monomers. In some embodiments, lactic acid, glycolic acid, allyl lactide, and combinations thereof can be used as monomers to prepare the polyesters disclosed herein. One of skill in the art will readily understand how to select an appropriate monomer to arrive at a desired polyester backbone. [0212] In some embodiments, the crosslinker comprises a dithiol group. In some embodiments, the dithiol group forms a thioether with an olefin functional group on the polyester backbone.[0229] The definition of the crosslinking density of the particle is based on the percentage of the pendant functionality (e.g., allyl, propargyl, or epoxy) of the linear polymer precursor (e.g., polyester) (van der Ende, A.E., et al.. (2008) J. Am Chem. Soc. 130, p. 8706). As used herein, the term “cross-linking density” refers to the proportion of functionalized monomer (e.g., allyl valerolactone) used in preparing a polymer such as a copolymer, expressed as a weight percentage of monomers used. For example, if 4% allylvalerolactone and 96% valerolactone are used (by weight) to prepare a polymer backbone, then the crosslinking density of the resulting particle is understood to be 4%. Actual crosslinking density can be determined by analytical techniques including, but not limited to, infrared spectroscopy, pyrolysis gas chromatography, and nuclear magnetic resonance. [0230] The crosslinking densities of the particles of the present disclosure can be between 1% and 100%, inclusive. In some embodiments, the crosslinking density is about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10%.[0236] According to embodiments of the present disclosure, the microparticles are crosslinked. Schemes 1 through 3 below show general routes to the crosslinked particles of the present disclosure (the examiner notes that it is an example).
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Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP §2141.012)
Le Dévédec et al. do not exemplify the elected species wherein m=1, n=1, q=1, and p=1 in anticipating manner and also the properties of the compound as recited in claim 59. These are clearly addressed by the prima facie arguments as set forth below.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the instant invention to produce the instant invention by following the teachings of Le Dévédec et al. because Le Dévédec et al. teach the instantly claimed compound in its general teachings. Le Dévédec et al. teach crosslinked particles (e.g., microparticles) that are capable of storing and releasing drugs. The particles can be macroparticles, microparticles, or nanoparticles and can be composed of polyester backbones. The particles can be loaded with a drug. The particles can degrade in vivo to release the drug. The particles can be prepared by crosslinking functionalized polyester backbones and loaded with a given drug. The particles of the present disclosure can be injected with a syringe. In some embodiments, the particles of the present disclosure are administered in connection with a surgery and release the drug after the site of the surgery for a period of 1-6 months (see abstract). In another aspect, the present disclosure provides a method of preparing a crosslinked degradable particle, comprising: [0019] dissolving a polyester containing a plurality of allyl groups, a dithiol, and a photoinitiator in at least one solvent to form a solution; [0020] emulsifying the solution in an aqueous phase to form an emulsion; [0021] irradiating the emulsion with UV light to react the dithiol with two of the allyl groups to form a crosslink; and [0022] evaporating at least a portion of the solvent from the emulsion. [0205] The microparticles of the present disclosure can have a diameter between about 1 μm and about 999 μm, including all ranges and subranges therebetween, and more preferably, the microparticles can have a diameter between about 1 μm and about 100 μm, including all ranges and subranges therebetween. In some embodiments, the microparticles of the present disclosure can have a diameter between about 5 μm and about 30 μm, including all ranges and subranges therebetween (e.g., between about 7 μm and about 15 μm or about 10 μm). [0209] In one or more embodiments, any of the valerolactone, caprolactone, lactic acid, lactide, or glycolic acid is functionalized with a functional group. In some embodiments, the functional group can be selected from an allyl group, a propargyl group, or a carboxylic acid group (e.g., the functional groups can be allyl lactide, allyl valerolactone and the like). Alternatively, the functional group can be a trans-cyclooctene, norbornene, or a carbonyl group (e.g., an aldehyde or ketone). Alternatively, the functional group can be a thiol group, an amine, or a tetrazine. [0247] The polyesters of the present disclosure can be prepared using a variety of different suitable monomers. In some embodiments, lactic acid, glycolic acid, allyl lactide, and combinations thereof can be used as monomers to prepare the polyesters disclosed herein. One of skill in the art will readily understand how to select an appropriate monomer to arrive at a desired polyester backbone. It must be very clear that the above teachings of Le Dévédec et al. clearly contemplates a copolymer compound comprising allyl lactide residues, lactide residues, and glycolide residues as claimed. [0212] In some embodiments, the crosslinker comprises a dithiol group. In some embodiments, the dithiol group forms a thioether with an olefin functional group on the polyester backbone. [0230] The crosslinking densities of the particles of the present disclosure can be between 1% and 100%, inclusive. In some embodiments, the crosslinking density is about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10%.[0236] According to embodiments of the present disclosure, the microparticles are crosslinked. Schemes 1 through 3 below show general routes to the crosslinked particles of the present disclosure (the examiner notes that it is an example).
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With regard to the features wherein m=1, n=1, q=1, and p=1 in the compound and all the ratio recitations in claims 10-11, Le Dévédec et al. teach that [0247] The polyesters of the present disclosure can be prepared using a variety of different suitable monomers. In some embodiments, lactic acid, glycolic acid, allyl lactide, and combinations thereof can be used as monomers to prepare the polyesters disclosed herein. One of skill in the art will readily understand how to select an appropriate monomer to arrive at a desired polyester backbone. It is within the purview of one of ordinary skill in the art to select an appropriate amount and monomer type to produce the claimed compound absent evidence to the contrary by following the teachings of Le Dévédec et al. Applicants have not shown any criticality about the amounts or number of monomers in the compound or on the ratios. In the case where the claimed ranges for amounts of ingredients, ratios, and level of crosslinking "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Furthermore, a prima facie case of obviousness exists because differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. It is not inventive to discover the optimum or workable ranges by routine experimentation" (see MPEP 2144.05 and In re Aller, 220 F. 2d 454, 456, 105 USPQ 233,235 (CCPA 1955)). One of ordinary skill in the art would have had a reasonable chance of success in producing the instant invention by following the teachings of Le Dévédec et al. because Le Dévédec et al. teach the claimed compound as described above in obvious manner.
The examiner also brings applicant’s attention to the whole concept of picking and choosing of the allyl lactide residues, lactide residues and perhaps the glycolide residues from the broader teachings of Le Dévédec et al. The specific combination of features claimed are disclosed within the broad generic ranges taught by the reference but such “picking and choosing” within several variables does not necessarily give rise to anticipation. Corning Glass Works v. Sumitomo Elec., 868 F.2d 1251, 1262 (Fed. Circ. 1989). If applicants resort to argue the reference does not provide any motivation to select this specific combination of ingredients and their amounts, it must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious.” KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious,” the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR at 1741. The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742. Consistent with this reasoning, it would have been obvious to have selected various combinations of various disclosed ingredients and their workable amounts and ratios from within a prior art disclosures, to arrive compositions or compounds “yielding no more than one would expect from such an arrangement.” One of ordinary skill in the art would have had a reasonable chance of success in producing the instant invention by following the teachings of Le Dévédec et al. because Le Dévédec et al. teach a substantially similar or identical compounds in microparticles form as claimed.
With regard to the property of the compound recitation in claim 59, the examiner takes the position that "[I]nherency may supply a missing claim limitation in an obviousness analysis." PAR, 773 F.3d at 1194-1195 ; see also Endo Pharms. Sols., Inc. v. Custopharm Inc., 894 F.3d 1374 , 1381 , 127 U.S.P.Q.2D (BNA) 1409 (Fed. Cir. 2018). However, the examiner does recognize the fact that the initial burden to allege inherency by the examiner is high. In recognition of this burden the examiner carefully reviewed Applicant’s disclosure for a specific features or ingredients that will uniquely result in the recited properties and also any critical ingredients that are responsible for the recited properties. The examiner carefully looked Applicant’s specification and failed to identify an objective experimental data showing the criticality of ingredient(s) and a specific amount or range of amounts that are responsible for the claimed properties. The properties are mainly the result of the fact that the compound contains the recited monomeric units which Le Dévédec et al. clearly teach as described above.
Therefore, based on the above identified fact patterns, one of ordinary skill in the art would reasonably expect that the compound of Le Dévédec et al. would necessarily result in a substantially identical or similar properties absent evidence to the contrary.
"[I]nherency may supply a missing claim limitation in an obviousness analysis." PAR, 773 F.3d at 1194-1195 ; see also Endo Pharms. Sols., Inc. v. Custopharm Inc., 894 F.3d 1374 , 1381 , 127 U.S.P.Q.2D (BNA) 1409 (Fed. Cir. 2018) ("An inherent characteristic of a formulation can be part of the prior art in an obviousness analysis even if the inherent characteristic was unrecognized or unappreciated by a skilled artisan."). It is long settled that in the context of obviousness, the "mere recitation of a newly discovered function or property, inherently possessed by things in the prior art, does not distinguish a claim drawn to those things from the prior art." In re Oelrich, 666 F.2d 578 , 581 (C.C.P.A. 1981). The Supreme Court explained long ago that "[i]t is not invention to perceive that the product which others had discovered had qualities they failed to detect." Gen. Elec. Co. v. Jewel Incandescent Lamp Co., 326 U.S. 242 , 249 , 66 S. Ct. 81 , 90 L. Ed. 43 , 1946 Dec. Comm'r Pat. 611 (1945). We too have previously explained that "an obvious formulation cannot become nonobvious simply by administering it to a patient and claiming the resulting serum concentrations," because "[t]o hold otherwise would allow any formulation—no matter how obvious—to become patentable merely by testing and claiming an inherent property." Santarus, Inc. v. Par Pharm., Inc., 694 F.3d 1344 , 1354 (Fed. Cir. 2012). In In re Kao, we found that the claimed controlled-release oxymorphone formulation was obvious because an inherent pharmacokinetic property of oxymorphone that was present in controlled-release oxymorphone "add[ed] nothing of patentable consequence." In re Huai-Hung Kao, 639 F.3d 1057 , 1070 , 98 U.S.P.Q.2D (BNA) 1799 (Fed. Cir. 2011). In In re Kubin, we found an inherent property obvious, explaining that "[e]ven if no prior art of record explicitly discusses the [limitation], the . . . application itself instructs that [the limitation] is not an additional requirement imposed by the claims on the [claimed protein], but rather a property necessarily present in [the claimed protein]." In re Kubin, 561 F.3d 1351 , 1357 , 90 U.S.P.Q.2D (BNA) 1417 (Fed. Cir. 2009). Our predecessor court similarly concluded that it "is not the law" that "a structure suggested by the prior art, and, hence, potentially in the possession of the public, is patentable . . . because it also possesses an [i]nherent, but hitherto unknown, function which [the patentees] claim to have discovered." In re [*1191] Wiseman, 596 F.2d 1019 , 1023 (C.C.P.A. 1979).
Inherency, however, is a "high standard," that is "carefully circumscribed in the context of obviousness." PAR, 773 F.3d at 1195 . Inherency "may not be established by probabilities or possibilities," and "[t]he mere fact that a certain thing may result from a given set of circumstances is not sufficient." Oelrich, 666 F.2d at 581 (emphasis added) (quoting Hansgirg v. Kemmer, 102 F.2d 212 , 214 , 26 C.C.P.A. 937 , 1939 Dec. Comm'r Pat. 327 (C.C.P.A. 1939); see also In re Rijckaert, 9 F.3d 1531 , 1533-1534 (Fed. Cir. 1993). Rather, inherency renders a claimed limitation obvious only if the limitation is "necessarily present," or is "the natural result of the combination of elements explicitly disclosed by the prior art." PAR, 773 F.3d at 119511 -96; see also Alcon Research, Ltd. v. Apotex Inc., 687 F.3d 1362 , 1369 (Fed. Cir. 2012) (relying on inherency where the claims recited "a property that is necessarily present" in the prior art). "If . . . the disclosure is sufficient to show that the natural result flowing from the operation as taught would result in the performance of the questioned function, it seems to be well settled that the disclosure should be regarded as sufficient" to render the function inherent. Oelrich, 666 F.2d at 581 (quoting Hansgirg v. Kemmer, 102 F.2d 212 , 214 , 26 C.C.P.A. 937 , 1939 Dec. Comm'r Pat. 327 (C.C.P.A. 1939)). On appeal, Persion contends that the district court erred in applying the inherency doctrine in its obviousness analysis because Devane does not teach administering its hydrocodone-only formulation to patients with mild or moderate hepatic impairment. Thus, Persion asserts, "'the natural result flowing from the operation as taught' in Devane cannot be the claimed [pharmacokinetic] values for [hepatically impaired] patients." Appellant's Br. 37 (quoting Oelrich, 666 F.2d at 581 ); Reply Br. 19. To the extent Persion contends that inherency can only satisfy a claim limitation when all other limitations are taught in a single reference, that position is contrary to our prior recognition that "inherency may supply a missing claim limitation in an obviousness analysis" where the limitation at issue is "the natural result of the combination of prior art elements." PAR, 773 F.3d at 1194-1195 (emphasis added, internal quotations omitted). Here, the district court specifically found that Devane, together with Jain, the state of the prior art at the time of invention, and the Vicodin and Lortab labels, taught the combination of elements that inherently result in the claimed pharmacokinetic parameters. The district court found that a person of ordinary skill in the art would have been motivated, with reasonable expectation of success, to administer an unadjusted dose of the Devane formulation to hepatically impaired patients. There was also no dispute that the Devane formulation, which was identical to the Zohydro ER formulation described in the patents in suit, necessarily exhibited the claimed parameters under these conditions. Pernix, 323 F. Supp. 3d at 607 , 610 . In this context, the district court did not err by finding that the pharmacokinetic limitations of the asserted claims were inherent and added no patentable weight to the pharmacokinetic claims.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 1-8, 10-11, 41-43, 45-46, 49, 59, and 82 remain rejected under 35 U.S.C. 103 as being unpatentable over Stevens et al. (WO 2018/106938, provided to Applicant before as pertinent prior art).
Applicant Claims
Applicant claims a compound or a pharmaceutically acceptable salt thereof.
Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
Stevens et al. teach for example, in some embodiments, the polymer backbone comprises a copolymer (e.g., a block copolymer or random copolymer) of a functionalized monomer and a substantially inert monomer. For example, the polymer backbone can comprise both PLGA (i.e., a substantially inert monomer) and allyl lactide (i.e., a functionalized monomer). The resulting polymer backbone can be, e.g., a poly(lactic-co-glycolic acid)-co-poly(allyl lactide) copolymer. In some embodiments, co-polymerizing PLGA and allyl lactide can result in a functionalized (i.e., an allyl-functionalized) polymer backbone e.g., wherein some repeating units such as the lactic and/or glycolic acid units are substantially inert (see paragraph 0055). The examiner noted that these copolymers are free of valerolactone residues. The coatings can include a substrate-coordinating functionality as well as additional functionality for interacting with the surrounding environment. For example, the coatings can be functionalized for a variety of applications such as imparting antimicrobial properties on a substrate such as an implant; drug delivery; or as an adhesive layer between a substrate and an additional coating (see abstract). Set forth below is a first exemplary experimental process for preparing coatings of the disclosure. First, in some embodiments, a polymer backbone (e.g., a p(avl-vl) polymer backbone can be prepared. Next, the polymer backbone can be modified. For example, the polymer backbone can be modified to include a substrate-coordinating group such has a thiolate of a bisphosphonate (e.g., alendronate). For example, the thiol-alendronate can be conjugated to the polymer backbone (e.g., the p(avl-vl) backbone using a percentage of the allyl groups on the backbone as the reactive functionality for attachment. In some embodiments, substantially all of the functional groups (e.g., the allyl groups) can be used to attach the substrate-coordinating group such as the thiol-alendronate. In some embodiments, less than all of the functional groups are used to attach the substrate-coordinating groups. In such cases, the remaining (i.e., unreacted) functional groups such as the allyl groups are left available as reactive functional groups for further elaboration of the polymer backbone. In some embodiments, about 90%, about 80%, about 70%, about 60%, about 50%, about 40%, about 30%, about 20%, or about 10% of the functional groups are reacted with a substrate- coordinating group. The examiner interprets these amounts to be equivalent to the amount of ally lactides. In some cases, between about 20% and about 80% of functional groups (e.g., allyl groups) are converted to substrate coordinating groups. In some embodiments, between about 30% and about 70%, or between about 40% and about 60% of functional groups (e.g., allyl groups) are converted to substrate coordinating groups (see paragraph 00187). In some embodiments, an additional component can be incorporated into a solution comprising a polymer coating of the present disclosure. For instance, a drug or other therapeutic agent can be incorporated into the solution, and thus can be incorporated onto the substrate coating after application of the solution. In some embodiments, the drug and/or agent is soluble in the solvent (e.g., ethyl acetate) and the coating solution is a uniform solution consisting of the polymer and the drug and/or other agent (paragraphs 00145-00146). In some embodiments, the coatings of the present disclosure can be used to prepare polymersomes and stable nanoparticles. In some embodiments, the polymersomes and stable nanoparticles can comprise crosslinkable and/or amphiphilic polymers (e.g., poly(avl-vl)-PEG; PEG-poly(avl-vl)-PEG; poly(avl-vl)-PEG-poly(avl-vl)) (paragraph 00179). In some embodiments, the polymeric coatings of the present disclosure can be crosslinked. For example, the polymeric backbones of the present disclosure can be crosslinked using PEG. In other words, PEG can be incorporated into the polymeric backbone of the polymeric coatings. Additionally or alternatively, PEG can also be incorporated into the polymeric coatings as a crosslinking agent (paragraph 0098). In some embodiments, a functionalized polyglycidol polymer backbone of the present disclosure can be prepared by crosslinking monomers that are pre-functionalized. For example, an allyl-functionalized polyglycidol backbone can be prepared by co-polymerizing glycidol with allyl glycidyl ether. Similarly, a functionalized polyglycidol backbone can be prepared by co-polymerizing glycidol with glycidyl acrylate. In some embodiments, the percentage of free hydroxyl groups that are converted to alkene groups (e.g., as shown above) can be between about 1% and 100% (paragraphs 0091-0092). The examiner noted that the conversion entails crosslinking.
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP §2141.012)
Stevens et al. do not exemplify the elected species wherein m=1, n=1, q=1, and p=1 in anticipating manner and also the properties of the compound as recited in claim 59. These deficiencies are cured by the prima facie arguments as set forth below.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious to a person of ordinary skill in the artbefore the effective filing date of the instant invention to produce the instant invention by following the teachings of Stevens et al. Stevens et al. teach for example, in some embodiments, the polymer backbone comprises a copolymer (e.g., a block copolymer or random copolymer) of a functionalized monomer and a substantially inert monomer. For example, the polymer backbone can comprise both PLGA (i.e., a substantially inert monomer) and allyl lactide (i.e., a functionalized monomer). The resulting polymer backbone can be, e.g., a poly(lactic-co-glycolic acid)-co-poly(allyl lactide) copolymer. In some embodiments, co-polymerizing PLGA and allyl lactide can result in a functionalized (i.e., an allyl-functionalized) polymer backbone e.g., wherein some repeating units such as the lactic and/or glycolic acid units are substantially inert (see paragraph 0055). The examiner noted that these copolymers are free of valerolactone residues. The coatings can include a substrate-coordinating functionality as well as additional functionality for interacting with the surrounding environment. For example, the coatings can be functionalized for a variety of applications such as imparting antimicrobial properties on a substrate such as an implant; drug delivery; or as an adhesive layer between a substrate and an additional coating (see abstract). Set forth below is a first exemplary experimental process for preparing coatings of the disclosure. First, in some embodiments, a polymer backbone (e.g., a p(avl-vl) polymer backbone can be prepared. Next, the polymer backbone can be modified. For example, the polymer backbone can be modified to include a substrate-coordinating group such has a thiolate of a bisphosphonate (e.g., alendronate). For example, the thiol-alendronate can be conjugated to the polymer backbone (e.g., the p(avl-vl) backbone using a percentage of the allyl groups on the backbone as the reactive functionality for attachment. In some embodiments, substantially all of the functional groups (e.g., the allyl groups) can be used to attach the substrate-coordinating group such as the thiol-alendronate. In some embodiments, less than all of the functional groups are used to attach the substrate-coordinating groups. In such cases, the remaining (i.e., unreacted) functional groups such as the allyl groups are left available as reactive functional groups for further elaboration of the polymer backbone. In some embodiments, about 90%, about 80%, about 70%, about 60%, about 50%, about 40%, about 30%, about 20%, or about 10% of the functional groups are reacted with a substrate- coordinating group. The examiner interprets these amounts to be equivalent to the amount of ally lactides. In some cases, between about 20% and about 80% of functional groups (e.g., allyl groups) are converted to substrate coordinating groups. In some embodiments, between about 30% and about 70%, or between about 40% and about 60% of functional groups (e.g., allyl groups) are converted to substrate coordinating groups (see paragraph 00187). In some embodiments, an additional component can be incorporated into a solution comprising a polymer coating of the present disclosure. For instance, a drug or other therapeutic agent can be incorporated into the solution, and thus can be incorporated onto the substrate coating after application of the solution. In some embodiments, the drug and/or agent is soluble in the solvent (e.g., ethyl acetate) and the coating solution is a uniform solution consisting of the polymer and the drug and/or other agent (paragraphs 00145-00146). In some embodiments, the coatings of the present disclosure can be used to prepare polymersomes and stable nanoparticles. In some embodiments, the polymersomes and stable nanoparticles can comprise crosslinkable and/or amphiphilic polymers (e.g., poly(avl-vl)-PEG; PEG-poly(avl-vl)-PEG; poly(avl-vl)-PEG-poly(avl-vl)) (paragraph 00179). In some embodiments, the polymeric coatings of the present disclosure can be crosslinked. For example, the polymeric backbones of the present disclosure can be crosslinked using PEG. In other words, PEG can be incorporated into the polymeric backbone of the polymeric coatings. Additionally or alternatively, PEG can also be incorporated into the polymeric coatings as a crosslinking agent (paragraph 0098). In some embodiments, a functionalized polyglycidol polymer backbone of the present disclosure can be prepared by crosslinking monomers that are pre-functionalized. For example, an allyl-functionalized polyglycidol backbone can be prepared by co-polymerizing glycidol with allyl glycidyl ether. Similarly, a functionalized polyglycidol backbone can be prepared by co-polymerizing glycidol with glycidyl acrylate. In some embodiments, the percentage of free hydroxyl groups that are converted to alkene groups (e.g., as shown above) can be between about 1% and 100% (paragraphs 0091-0092). The examiner noted that the conversion entails crosslinking. With regard to the features wherein m=1, n=1, q=1, and p=1 in the compound and all the ratio recitations in claims 10-11, Stevens et al. teach that Stevens et al. teach for example, in some embodiments, the polymer backbone comprises a copolymer (e.g., a block copolymer or random copolymer) of a functionalized monomer and a substantially inert monomer. For example, the polymer backbone can comprise both PLGA (i.e., a substantially inert monomer) and allyl lactide (i.e., a functionalized monomer). The resulting polymer backbone can be, e.g., a poly(lactic-co-glycolic acid)-co-poly(allyl lactide) copolymer. In some embodiments, co-polymerizing PLGA and allyl lactide can result in a functionalized (i.e., an allyl-functionalized) polymer backbone e.g., wherein some repeating units such as the lactic and/or glycolic acid units are substantially inert (see paragraph 0055). It is within the purview of one of ordinary skill in the art to select an appropriate amount and monomer type to produce the claimed compound absent evidence to the contrary by following the teachings of Stevens et al. Applicants have not shown any criticality about the amounts or number of monomers in the compound or on the ratios. In the case where the claimed ranges for amounts of ingredients, ratios, and level of crosslinking "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Furthermore, a prima facie case of obviousness exists because differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. It is not inventive to discover the optimum or workable ranges by routine experimentation" (see MPEP 2144.05 and In re Aller, 220 F. 2d 454, 456, 105 USPQ 233,235 (CCPA 1955)). One of ordinary skill in the art would have had a reasonable chance of success in producing the instant invention by following the teachings of Stevens et al. because Stevens et al. teach the claimed compound as described above in obvious manner.
With regard to the property of the compound recitation in claim 59, the examiner takes the position that "[I]nherency may supply a missing claim limitation in an obviousness analysis." PAR, 773 F.3d at 1194-1195 ; see also Endo Pharms. Sols., Inc. v. Custopharm Inc., 894 F.3d 1374 , 1381 , 127 U.S.P.Q.2D (BNA) 1409 (Fed. Cir. 2018). However, the examiner does recognize the fact that the initial burden to allege inherency by the examiner is high. In recognition of this burden the examiner carefully reviewed Applicant’s disclosure for a specific features or ingredients that will uniquely result in the recited properties and also any critical ingredients that are responsible for the recited properties. The examiner carefully looked Applicant’s specification and failed to identify an objective experimental data showing the criticality of ingredient(s) and a specific amount or range of amounts that are responsible for the claimed properties. The properties are mainly the result of the fact that the compound contains the recited monomeric units which Stevens et al. clearly teach as described above.
Therefore, based on the above identified fact patterns, one of ordinary skill in the art would reasonably expect that the compound of Stevens et al. would necessarily result in a substantially identical or similar properties absent evidence to the contrary.
"[I]nherency may supply a missing claim limitation in an obviousness analysis." PAR, 773 F.3d at 1194-1195 ; see also Endo Pharms. Sols., Inc. v. Custopharm Inc., 894 F.3d 1374 , 1381 , 127 U.S.P.Q.2D (BNA) 1409 (Fed. Cir. 2018) ("An inherent characteristic of a formulation can be part of the prior art in an obviousness analysis even if the inherent characteristic was unrecognized or unappreciated by a skilled artisan."). It is long settled that in the context of obviousness, the "mere recitation of a newly discovered function or property, inherently possessed by things in the prior art, does not distinguish a claim drawn to those things from the prior art." In re Oelrich, 666 F.2d 578 , 581 (C.C.P.A. 1981). The Supreme Court explained long ago that "[i]t is not invention to perceive that the product which others had discovered had qualities they failed to detect." Gen. Elec. Co. v. Jewel Incandescent Lamp Co., 326 U.S. 242 , 249 , 66 S. Ct. 81 , 90 L. Ed. 43 , 1946 Dec. Comm'r Pat. 611 (1945). We too have previously explained that "an obvious formulation cannot become nonobvious simply by administering it to a patient and claiming the resulting serum concentrations," because "[t]o hold otherwise would allow any formulation—no matter how obvious—to become patentable merely by testing and claiming an inherent property." Santarus, Inc. v. Par Pharm., Inc., 694 F.3d 1344 , 1354 (Fed. Cir. 2012). In In re Kao, we found that the claimed controlled-release oxymorphone formulation was obvious because an inherent pharmacokinetic property of oxymorphone that was present in controlled-release oxymorphone "add[ed] nothing of patentable consequence." In re Huai-Hung Kao, 639 F.3d 1057 , 1070 , 98 U.S.P.Q.2D (BNA) 1799 (Fed. Cir. 2011). In In re Kubin, we found an inherent property obvious, explaining that "[e]ven if no prior art of record explicitly discusses the [limitation], the . . . application itself instructs that [the limitation] is not an additional requirement imposed by the claims on the [claimed protein], but rather a property necessarily present in [the claimed protein]." In re Kubin, 561 F.3d 1351 , 1357 , 90 U.S.P.Q.2D (BNA) 1417 (Fed. Cir. 2009). Our predecessor court similarly concluded that it "is not the law" that "a structure suggested by the prior art, and, hence, potentially in the possession of the public, is patentable . . . because it also possesses an [i]nherent, but hitherto unknown, function which [the patentees] claim to have discovered." In re [*1191] Wiseman, 596 F.2d 1019 , 1023 (C.C.P.A. 1979).
Inherency, however, is a "high standard," that is "carefully circumscribed in the context of obviousness." PAR, 773 F.3d at 1195 . Inherency "may not be established by probabilities or possibilities," and "[t]he mere fact that a certain thing may result from a given set of circumstances is not sufficient." Oelrich, 666 F.2d at 581 (emphasis added) (quoting Hansgirg v. Kemmer, 102 F.2d 212 , 214 , 26 C.C.P.A. 937 , 1939 Dec. Comm'r Pat. 327 (C.C.P.A. 1939); see also In re Rijckaert, 9 F.3d 1531 , 1533-1534 (Fed. Cir. 1993). Rather, inherency renders a claimed limitation obvious only if the limitation is "necessarily present," or is "the natural result of the combination of elements explicitly disclosed by the prior art." PAR, 773 F.3d at 119511 -96; see also Alcon Research, Ltd. v. Apotex Inc., 687 F.3d 1362 , 1369 (Fed. Cir. 2012) (relying on inherency where the claims recited "a property that is necessarily present" in the prior art). "If . . . the disclosure is sufficient to show that the natural result flowing from the operation as taught would result in the performance of the questioned function, it seems to be well settled that the disclosure should be regarded as sufficient" to render the function inherent. Oelrich, 666 F.2d at 581 (quoting Hansgirg v. Kemmer, 102 F.2d 212 , 214 , 26 C.C.P.A. 937 , 1939 Dec. Comm'r Pat. 327 (C.C.P.A. 1939)). On appeal, Persion contends that the district court erred in applying the inherency doctrine in its obviousness analysis because Devane does not teach administering its hydrocodone-only formulation to patients with mild or moderate hepatic impairment. Thus, Persion asserts, "'the natural result flowing from the operation as taught' in Devane cannot be the claimed [pharmacokinetic] values for [hepatically impaired] patients." Appellant's Br. 37 (quoting Oelrich, 666 F.2d at 581 ); Reply Br. 19. To the extent Persion contends that inherency can only satisfy a claim limitation when all other limitations are taught in a single reference, that position is contrary to our prior recognition that "inherency may supply a missing claim limitation in an obviousness analysis" where the limitation at issue is "the natural result of the combination of prior art elements." PAR, 773 F.3d at 1194-1195 (emphasis added, internal quotations omitted). Here, the district court specifically found that Devane, together with Jain, the state of the prior art at the time of invention, and the Vicodin and Lortab labels, taught the combination of elements that inherently result in the claimed pharmacokinetic parameters. The district court found that a person of ordinary skill in the art would have been motivated, with reasonable expectation of success, to administer an unadjusted dose of the Devane formulation to hepatically impaired patients. There was also no dispute that the Devane formulation, which was identical to the Zohydro ER formulation described in the patents in suit, necessarily exhibited the claimed parameters under these conditions. Pernix, 323 F. Supp. 3d at 607 , 610 . In this context, the district court did not err by finding that the pharmacokinetic limitations of the asserted claims were inherent and added no patentable weight to the pharmacokinetic claims.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 03 December 2025 have been fully considered but they are not persuasive.
Applicant argues without acquiescing to the rejection of claim 1, Applicant has amended claim 1 to advance prosecution of this application. Specifically, Applicant has amended claim 1 to recite, in part, "from 6 wt% to 50 wt% allyl lactide residues; and lactide residues, wherein the compound or pharmaceutically acceptable salt thereof is substantially free of valerolactone residues," As discussed in an interview with the Examiner on September 9, 2024, Applicant provides herewith data outlining performance characteristics of polymers within the scope of the claims with allyl lactide percentages ranging from 6 wt% to 50 wt%. Such polymers are tested alongside analogous polymers that include valerolactone residues. The polymers without the valerolactone residues demonstrate slower release profiles of tenofovir alafenamide (TAF) over a 17-day period. Such results are unexpected and render the claimed subject matter non-obvious over the cited references.
The above assertions are not found persuasive because first the examiner would like to discuss Applicant’s comparison data with respect to what the claim 1 and dependent claims thereof are drawn to. Instant claim 1 recites “A compound or a pharmaceutically acceptable salt thereof, comprising: between about from 6 wt% and about to 50 wt% allyl lactide residues; and lactide residues, wherein the compound or pharmaceutically acceptable salt thereof is substantially free of valerolactone residues wherein the compound or pharmaceutically acceptable salt thereof exhibits a slower drug release profile compared to an analogous compound containing valerolactone residues.” The examiner would like to bring to Applicant’s attention first the experiment was not performed to the closest example as a control. The closest example which will be used as a control must be a compound containing allyl lactide, lactide, and valerolactone residues which is missing from the list of compounds tested. As applicant alleges the absence of the valerolactone residue is the main reason why the release profile shows a slow or delayed release pattern, a compound that contains the claimed residues with the presence of the valerolactone residue would the control compound to establish surprising or unexpected results. Applicants may compare the claimed invention with prior art that is more closely related to the invention than the prior art relied upon by the examiner. In re Holladay, 584 F.2d 384, 199 USPQ 516 (CCPA 1978); Ex parte Humber, 217 USPQ 265 (Bd. App. 1961). Additionally, the examiner would like to bring to applicant’s attention that whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980) (Claims were directed to a process for removing corrosion at "elevated temperatures" using a certain ion exchange resin (with the exception of claim 8 which recited a temperature in excess of 100C). Appellant demonstrated unexpected results via comparative tests with the prior art ion exchange resin at 110C and 130C. The court affirmed the rejection of claims 1-7 and 9-10 because the term "elevated temperatures" encompassed temperatures as low as 60C where the prior art ion exchange resin was known to perform well. The rejection of claim 8, directed to a temperature in excess of 100C, was reversed.). See also In re Peterson, 315 F.3d 1325, 1329-31, 65 USPQ2d 1379, 1382-85 (Fed. Cir. 2003) (data showing improved alloy strength with the addition of 2% rhenium did not evidence unexpected results for the entire claimed range of about 1-3% rhenium); In re Grasselli, 713 F.2d 731, 741, 218 USPQ 769, 777 (Fed. Cir. 1983) (Claims were directed to certain catalysts containing an alkali metal. Evidence presented to rebut an obviousness rejection compared catalysts containing sodium with the prior art. The court held this evidence insufficient to rebut the prima facie case because experiments limited to sodium were not commensurate in scope with the claims.). Claim 1 is drawn to the combination of lactide and allyl lactide residues with broader concentration. Specifically, Applicant’s five compounds in the declaration do not specify the amount of the lactide residue or the glycolide residue if present. In the experimental data the copolymers are made using specific ratios and or amounts of each of the residues. The examiner maintains that Applicant should make the claims commensurate in scope with the data. Therefore, the examiner maintains the rejections set forth above under 35 USC 103.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
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/TIGABU KASSA/
Primary Examiner, Art Unit 1619