DETAILED ACTION
Status of the Claims
Claims 1, 6, 26-27, 36, 60-61, 82, 86-87, 89, 155-160, 162-163 and 169 are pending in the instant application and are being examined on the merits in the instant application.
2nd Non-Final Office Action
The examiner confirms the call with Robert Cerpa, and based on a review of the Non-Final noted that, while the Applicant claims section did include language that was previously presented, the body of the obviousness rejection had addressed all the instantly claimed limitations. However, in deference to Mr. Cerpa, the examiner has further delineated the limitations of the instant claims in the body of the obviousness rejection and has made the instant Office Action Non-Final.
Advisory Notice
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
All rejections and/or objections not explicitly maintained in the instant office action have been withdrawn per Applicants’ claim amendments and/or persuasive arguments.
Priority
The instant case is a U.S. national stage Application (371) of PCT/US2020/059537 filed 11/06/2020 and claims priority to U.S. Provisional Application No. 62/933226 filed 11/08/2019.
The U.S. effective filing date has been determined to be 11/08/2019, the filing date of U.S. Provisional Application No. 62/933226.
Information Disclosure Statement
The information disclosure statement submitted on 12/30/2025 was filed after the mailing date of the first office action on the merits subsequent to the RCE filed 09/05/2025, however Applicant has indicated the fee set forth in 37 CFR 1.97(e) has been submitted. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the Examiner.
Objections
Claim 82 is objected to because the claim recites “thepolyethylene” in line 2, which should be two words “the polyethylene”. Appropriate correction is required.
Claim 160 is objected to because the claim recites “configured to degrade with the stomach” in line 2. The claim should read “configured to degrade within the stomach”. Appropriate correction is required.
The amendment to the Specification has been review and the examiner finds no new matter. The amendment resolves the objections raised.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 6, 26-27, 36, 60-61, 82, 86-87, 89, 155-160, 162-163 and 169 remain rejected under 35 U.S.C. 103 as being unpatentable over BELLINGER (US 2019/0262265, published August, 2019; or WO 2017/100367 A1, published June, 2017; the former cited herein) in view of KANASTY (US 2019/0254966, published August, 2019; or WO 2017/205844 A2, published November, 2017; the former cited herein); RICHEY (US 2016/0317453; published November, 2016); and Martin et al. (“Hydrophilic Matrix Tablets for Oral Controlled Release,” 2015; SPRINGER; Chapter 5 – “Applications of Polyethylene Oxide (POLYOX) in Hydrophilic Matrices,” pp. 123-141).
Applicants Claims
Applicant claims gastric residence system, comprising: one or more first structural members comprising a carrier polymer and an agent, the one or more first structural members attached to a second structural member through a polymeric linker wherein the polymeric linker comprises: i) poly(lactic-co-glycolide) (PLGA); ii) polycaprolactone (PCL); and iii) optionally, a plasticizer in an amount from 0.5% to 20%; wherein the polymeric linker loses 20% or more of its flexural modulus or breaks after incubation in an aqueous solution at pH 1.6 for 30 days at 37 °C; and wherein the gastric residence system is retained in the stomach for a period of at least 24 hours (instant claim 1). Applicant claims the polymeric linker further comprises polyethylene glycol as a plasticizer (instant claim 6), wherein the polyethylene glycol is polyethylene oxide 100K (instant claim 60).
Applicant claims the linker comprises about 48% to about 58% PLGA, about 40% to 50% PCL, and about 1% to 3% polyethylene glycol (instant claim 26).
Applicant claims the polymeric linker comprises about 44.95% PCL, about 53% acid-terminated PLGA, about 2% polyethylene oxide 100K, and about 0.05% iron oxide (instant claim 27).
Applicant claims a method of delivering an agent to an individual, comprising deploying the gastric residence system of claim 1, within the stomach of the individual, wherein the individual is a human (instant claim 169).
Determination of the scope
and content of the prior art (MPEP 2141.01)
BELLINGER teaches a “gastric residence systems with configurations and geometrical dimensions that allow for improved shelf life during prolonged storage, and optimal residence properties when the systems are deployed in the stomach of a patient.” (abstract).
BELLINGER teaches the system geometry including “An example of a stellate system 200 is shown schematically in FIG. 2. Multiple "arms" (only one such arm, 208, is labeled for clarity) are affixed to asterisk-shaped (disk-shaped) central elastomer 206. The arms depicted in FIG. 2 are comprised of segments 202 and 203, joined by a coupling polymer 204. This configuration permits the system to be folded or compacted in the manner shown for the system 290 in FIG. 2C. Only two arms are shown in FIG. 2C for clarity, and only one arm (298) is labeled for clarity. The central elastomer 296 is folded, such that the overall length of the system is reduced by approximately a factor of two, and the system can be conveniently placed in a container such as a capsule or other container suitable for oral administration.” ([0169])(instant claims 160, “wherein the gastric residence system is contained within a capsule configured to degrade with[in] the stomach”; instant claims 162-163, “the second structural member is an elastomer” and “a central elastomer”; instant claim 169, “deploying the gastric residence system of claim 1 within the stomach”).
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The examiner is interpreting segments 202 and 203, the coupling polymer 204 as “structural members” (instant claim 1, line 2), wherein each of inner segments 203, the coupling polymers 204, and the outer segments 202 can constitute “one or more first structural members” (instant claim 1, line 2). The examiner is interpreting coupling polymers 204 as “a polymeric linker” or “linker polymer” (instant claim 1, lines 3-4). Instant claim 159, “comprising a plurality of first structural members […] each first structural member is attached to the second structural member through a separate polymeric linker”.
BELLINGER teaches that: “The coupling polymer components are chosen such that they gradually weaken and/or degrade over the residence period in the stomach. When the coupling polymer components are sufficiently weakened or degraded, the gastric residence system breaks apart into smaller pieces, which are able to pass through the pyloric sphincter. The system then passes through the intestines and is eliminated from the patient.” ([0165])(instant claim 1, “wherein the polymeric linker loses 20% or more of its flexural modulus or breaks after incubation in an aqueous solution at a pH 1.6 for 30 days at 37°C”; instant claims 61 & 89).
RICHEY teaches that: “The PLGA polymers can either be non-end capped having a free carboxylic acid terminal group, or end-capped, by esterification. For similar polymer molecular weights, carboxylic acid non-end capped polymers are more hydrophilic and thus allow water penetration and eventual hydrolysis and degradation to occur faster compared to the more hydrophobic polymers.” [emphasis added]([0062])(instant claims 27, 36, 86, acid-terminated or ester-terminated). Which is also reflected in the product literature for RESOMER biodegradable polyesters (Evonik Industries, RESOMER Product Range, 2015, pp. 1-4) disclosing that: “End group Control various polymer properties (degradation and water uptake) by modifying end-groups: Acid (A) or Ester (E)” (p. 3, right side bottom, RESOMER Select naming - caption for “E”). Therefore, it would have been prima facie obvious to select the appropriate end-group “acid-terminated PLGA, or ester-terminated PLGA” based on the desired degradation rate (instant claims 27, 36, 86 – acid-terminated or ester-terminated PLGA).
BELLINGER teaches carrier polymers for carrier polymer-agent component including that “The carrier polymer-agent component contains the therapeutic agent substance to be eluted from the gastric residence system in the gastric environment. Therapeutic agent is blended into the carrier polymer to form a carrier polymer-agent mixture. This mixture can be formed into the desired shape or shapes for use as carrier polymer-agent components in the systems, such as rods for the systems depicted in FIG. 2 and FIG. 2A. […] polyurethane […] Polycaprolactone (PCL) is a preferred carrier polymer, particularly PCL with a number-average molecular weight (Mn) of 80,000.” ([0127])(instant claims 1 & 169, “carrier polymer and an agent”). BELLINGER further teaches the therapeutic agent encompasses drugs ([0141])(instant claim 160, “the agent is a drug”).
BELLINGER teaches that: “In any of the embodiments of the gastric residence systems described herein, the linkers can comprise hydroxypropyl methyl cellulose acetate succinate (HPMCAS) and polycaprolactone (PCL); […].” [emphasis added]([0009] & [306]). And that: “Exemplary coupling polymers include, but are not limited to, […] poly(lactic-co-glycolic acid) (PLGA), and copolymers, mixtures, blends and combinations thereof.” [emphasis added] ([0241]). BELLINGER does not expressly describe a PLGA/PCL blend, as now claimed, however, it would have been immediately conceivable to combine/substitute species within the context of the subgenus biodegradable polyesters including PLGA such as “poly(lactic acid), poly(glycolic acid), poly(lactic-co-glycolic acid) (PLGA)” and “poly(caprolactone)” (PLC). Where one of ordinary skill in the art clearly recognizes that PLGA is a copolymer of poly(lactic acid) and poly(glycol acid) in various ratios (such as 50:50; 5% PLA1 and 95% PGA2; 95% PLA and 5% PGA) each of which would result in different degradation rates as poly(glycolic acid) is generally known to degrade faster than poly(lactic acid). And that poly(caprolactone) is a similar biodegradable polyester polymer (MPEP §2144.06)(instant claim 1, “the polymeric linker comprises: (i) poly(lactic-co-glycolide)(PLGA); (ii) polycaprolactone (PCL)”). One of ordinary skill in the art would have appreciated the polycaprolactone (PCL) and poly(lactic-co-glycol acid)(PLGA) are both in the same class of biodegradable polyesters with different degradation rates. And that PLGA and PCL could have been blended with the predictable result of varying the time-dependent degradation and therefore the degradation of the connections between segments during gastric residence and eventual passage of the device after the desired residence period, per the disclosure BELLINGER, could have been varied. MPEP §2144.05 – “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation."” In the instant case BELLINGER clearly teaches the function of the linker, and varying the composition thereof for the desired residence time in the patient’s stomach (instant claims 26-27, amount of PLGA and PCL).
Regarding the claim limitation “wherein the polymeric linker loses 20% or more of its flexural modulus or breaks after incubation in an aqueous solution at pH 1.6 for 30 days at 37° C.” (instant claim 1), and the additional limitations regarding the flexural modulus of the linker (instant claims 61 and 89), the examiners position is that it would have been well within the ordinary level of skill in the art, particularly in view of the teaching of BELLINGER, to modify the polymeric linker(s) to weaken or break in a desired period of time to achieve the desired therapeutic effect (MPEP §2144.05). The gastric residence system of BELLINGER and the instant claims is structurally identical including the same component, for the same intended use, therefore one it would have been prima facie to optimize the residence time of the “an agent” or multiples thereof (the same or different drug(s)) in order to better treat patient needs (instant claims 1, 61 & 89, linker degradation rate).
Particularly, BELLINGER teaches that: “In further embodiments, the invention provides methods of administering a therapeutic agent to a patient, comprising administering a gastric residence system according to any of the embodiments disclosed herein. In some embodiments, the gastric residence system has a gastric retention period of about D days, and a new gastric residence system is administered to the patient every D days over a total desired treatment period. The gastric retention period can be about three days, about five days, about seven days, about fourteen days, or about thirty days.” ([0067]). BELLINGER teaches that: “The system is designed to eventually break apart in the stomach at the end of the desired residence time. Once the coupling polymers break, the remaining components of the system are of dimensions that permit passage of the system through the pyloric sphincter, small intestine, and large intestine. Finally, the system is eliminated from the body by defecation, or by eventual complete dissolution of the system in the small and large intestines.” ([0211]). AND that: “The residence time of the systems in the stomach is adjusted by the choice of coupling polymers. The systems will eventually break down in the stomach, despite the use of enteric coupling polymers, as the mechanical action of the stomach and fluctuating pH will eventually weaken the enteric coupling polymers. Coupling polymers which degrade in a time-dependent manner in the stomach can also be used to adjust the time until the system breaks apart, and hence adjust the residence time. Once the system breaks apart, it passes into the intestines and is then eliminated.” ([0214]). BELLINGER teaches that: “It should be noted that a "time-dependent linker" is made of a material which degrades over time, but does not exclude some weakening under conditions where an enteric polymer would no longer function to link components. By "time-dependent polymer which are pH-resistant" (or equivalently, "pH-resistant time-dependent polymers") is meant that, under conditions where an enteric polymer would degrade to the point that it would no longer link the components together, the time-dependent polymer will still have sufficient mechanical strength to link the components together. In some embodiments, the time-dependent polymer retains about the same linking capacity, that is, about 100% of its linkage strength, after exposure to a solution between about pH 7 to about pH 8 as it has after exposure to a solution between about pH 2 to about pH 3, where the exposure is for about an hour, about a day, about three days, or about a week; […] In some embodiments, the time-dependent polymer retains at least about 25% of its linkage strength, after exposure to a solution between about pH 7 to about pH 8 as it has after exposure to a solution between about pH 2 to about pH 3, where the exposure is for about an hour, about a day, about three days, or about a week; […] Linkage strength can be measured by any relevant test that serves to test coupling ability, such as the four-point bending flexural test (ASTM D790) described in Example 3.” ([0239]). BELLINGER teaches that: “Polymers that degrade or otherwise weaken in a time-dependent manner in the gastric environment can be prepared from a variety of materials, or blends of materials. For example, the liquid plasticizer triacetin releases from a polymer formulation in a time-dependent manner over seven days in simulated gastric fluid, while Plastoid B retains its strength over a seven-day period in simulated gastric fluid. Thus, a polymer that degrades or weakens in a time dependent manner can be readily prepared by mixing Plastoid B and triacetin; the degradation time of the Plastoid B-triacetin mixture can be extended by increasing the amount of Plastoid B used in the mixture (that is, by using less triacetin in the mixture), while the degradation time can be decreased by decreasing the amount of Plastoid Bused in the mixture (that is, by using more triacetin in the mixture). As the triacetin releases over time, the Plastoid B-triacetin mixture weakens over time.” ([0240]). BELLINGER further teaches that: “Since enteric linkers are chosen to weaken at higher pH, the enteric linkers used in the gastric residence system weaken to a greater extent when incubated in simulated intestinal fluid (SIF, preferably fasted-state SIF) than in simulated gastric fluid (SGF; preferably fasted-state SGF). The relative percentage of weakening after incubation in SIF versus SGF is calculated by dividing the force at which the linker breaks or yields after incubation in SIF by the force at which the linker breaks or yields after incubation in SGF; subtracting that quotient from 1; and then multiplying by 100 to obtain a relative percentage weakening in SIF versus SGF. Thus, if a linker breaks under a force of 50 Newtons after incubation in SGF, and breaks under a force of 10 Newtons after incubation in SIF, the relative weakening is {[1-(5/50)]x100}=90%, or 90% relative weakening in SIF versus SGF. The force at which a linker breaks can be measured by the test as described in Example 13 below. In one embodiment, the relative weakening of the enteric linkers after incubation in SIF versus incubation in SGF is at least about 10%. In one embodiment, the relative weakening of the enteric linkers after incubation in SIF versus incubation in SGF is at least about 20%.” ([0242]). And BELLINGER teaches that: “Arms with linkers were incubated in fasted state simulated gastric fluid (FaSSGF) and fasted state intestinal fluid (FaSSIF). FaSSGF was prepared by dissolving 2 g of NaCl in 0.9 L of purified water. The pH was adjusted to 1.6 using HCI.” ([0521]). And further that: “Both the adhesion and flexural force of linkers remained stable in FaSSGF, but quickly reduced in FaSSIF (FIG. 25A: adhesion, left, FaSSGF; right, adhesion, FaSSIFB) (FIG. 25B: bending, left, FaSSGF; right, bending, FaSSIF-B).” ([0526] and Fig. 25).
Regarding the limitation, “wherein the gastric residence system is retained in the stomach for a period of at least 24 hours” (instant claims 1), BELLINGER teaches that Embodiment 1 includes a gastric residence system for administration to the stomach of a patient, and “wherein the gastric residence system is retained in the stomach for a period of at least about 24 hours” ([0390]).
BELLINGER teaches that: “Plasticizers can also be added to either enteric (pH-dependent) linkers or time-dependent linkers to adjust their properties as desired. Examples of plasticizers that can be added to the linkers are triacetin, triethyl citrate, tributyl citrate, poloxamers. Additional plasticizers that can be added to the linkers include polyethylene glycol, polypropylene glycol, diethyl phthalate, dibutyl sebacate, glycerin, castor oil, acetyl triethyl citrate, acetyl tributyl citrate, polyethylene glycol monomethyl ether, sorbitol, sorbitan, a sorbitol-sorbitan mixture, or diacetylated monoglycerides.” [emphasis added]([0009] & [0253])(instant claim 1, optionally a plasticizer in an amount of from 0.5% to 20%”; instant claim 6, “the polymeric linker further comprises polyethylene glycol”).
BELLINGER does not teach the amount of the plasticizer in the range of about 0.5 wt% to about 20 wt% (claim 86) or about 0.5 wt% to 12 wt.% (instant claims 86-87). However, the examiners position is that it would have been well within the ordinary level of skill in the art, particularly in view of the teaching of BELLINGER, to modify the polymeric linker(s) to weaken or break in a desired period of time, by inclusion of a plasticizer, to achieve the desired therapeutic effect (MPEP 2144.05). The gastric residence system of BELLINGER and the instant claims is structurally identical including the same component, for the same intended use, therefore one it would have been prima facie to optimize the residence time of the “an agent” or multiples thereof (the same or different drug(s)) in order to better treat patient needs.
Regarding the limitation, “wherein materials in the polymeric linker are homogenously blended” (instant claim 155), BELLINGER teaches that “Linker components were blended by twin screw extrusion using a Haake MiniCTW micro-compounder. Polymer powders or pellets were weighed and blended into a physical mixture before loading onto the extruder.” ([0530]), which the examiner is reading as resulting in homogenously blended “materials in the polymeric linker”.
BELLINGER teaches that: “The gastric residence system is contained in a capsule or other container which can be swallowed by the patient, or which is otherwise able to be administered to the stomach for patients unable to swallow (e.g., via gastrostomy tube, feeding tube, gastric tube, or other route of administration to the stomach).” ([0160]), and includes therapeutic agent such as a drug ([0141])(instant claim 160). BELLINGER teaches the term “patient” includes a human ([0149])(instant claim 169).
Regarding the limitation “wherein the polymeric linker is substantially free of agent” instant claim 156, the instant Specification discloses that: “"Substantially free" of the agent refers to the absence of the agent or the presence of agent in trace amounts that may be present due to diffusion from or bonding to an adjacent member, or normal handling, packaging, or storage of the gastric residence system, and without including the agent with the polymer or other material used to form the inactive segment.” (p. 71-72, [0231]). BELLINGER teaches the Drug-loaded formulation is linked to the elastomeric hub through a “Linker” which is not taught to include a drug (Figure 33, Entry A). BELLINGER teaches that: “The coupling polymer is used to link one or more carrier polymer-agent components to one or more carrier polymer-agent components, to link one or more carrier polymer-agent components to one or more elastomer components, or to link one or more elastomer components to one or more elastomer components, to link one or more inter facing polymers to one or more elastomer components, or to link one or more carrier polymer-agent components to one or more interfacing polymers. The coupling polymer component of the gastric residence systems that is used to link carrier polymer-agent components, elastomer components, or interfacing polymers to other polymer-agent components, elastomer components, or interfacing polymers can be referred to simply as a linker.” ([0238]).
Ascertainment of the difference between
the prior art and the claims (MPEP 2141.02)
The difference between the rejected claims and the teachings of BELLINGER is that BELLINGER does not expressly teach: (1) the plasticizer is polyethylene oxide 100K (instant claims 27, 60, 82, 87); (2) a color-absorbing dye (colorant, pigment) such as iron oxide (instant claims 27, 157 & 158).
KANASTY teaches a substantially identical gastric residence system as BELLINGER, and further teaches that: “To create the reinforcement layer, PCL doped with black iron oxide pigment was extruded as a ribbon approximately 500 micrometers thick and cut into small pieces of 20 mm length. The thin 100% black PCL layer was placed compression molded on one-side of a 38% drug loaded arm by keeping the two layers in close contact with each other and incubating in an oven for 10 minutes at 75° C. and then compressing together.” ([0285], see whole document). KANASTY does not teach the amount of iron oxide is 0.05% (instant claim 27), however, MPEP §2144.05-II(A) makes clear that: “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical.”
Regarding the species polyethylene oxide 100 K, BELLINGER teaches “Hot Melt Extrusion for Production of Drug Arms and Linkers” ([0528] – Example 10), and KANASTY teaches similarly hot melt extrusion ([0154]). Martin et al. teaches that: “While it is structurally similar to polyethylene glycol (PEG), PEG has a significantly shorter chain length and, depending on its molecular weight (from 200 to 35,000 Da), is a liquid or waxy solid. PEO polymers have significantly higher molecular weights than PEG (100,000–7,000,000 Da) and are free-flowing white crystalline powders.” [emphasis added](p. 123, §5.2, 1st paragraph). And that: “Pharmaceutical grades of PEO are manufactured by the Dow Chemical Company and are distributed globally by Colorcon Inc. under the trade name of POLYOX™ water-soluble resins (WSR).” (p. 124, 2nd paragraph). And further that: “These properties, coupled with the wide range of molecular weights available, make them suited to application in several controlled- release technologies, particularly in osmotic and hydrophilic matrix tablets. Despite its high molecular weight, POLYOX is highly crystalline and has a melting point temperature around 65 °C, above which, the polymer becomes thermoplastic. At temperatures far above the crystalline melting point, high molecular weight polymers of POLYOX still retain a very high degree of crystalline character. For this reason, when formulating extended-release oral solid dosage forms, the low molecular weight PEO grades are more suitable for hot-melt extrusion applications, whereas the high molecular weight grades will provide better sustained release dissolution profiles.” [emphasis added](p. 125, 1st paragraph). Therefore, it would have been prima facie obvious to select a solid polyethylene oxide of low molecular weight such as WSR N-10 (polyethylene oxide 100K) for hot melt extrusion in the invention of BELLINGER/KNASTY as suggested by Martin et al. as suitable for the same.
Finding of prima facie obviousness
Rationale and Motivation (MPEP 2142-2143)
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to produce a gastric residence system for administration to a human patient for a desired therapeutic effect over a desired gastric retention time, as suggested by BELLINGER and KANASTY, and produce the claimed invention for the best possible patient therapy; and particularly the selection of an acid-terminated or ester-terminated PLGA based on the function of the same, as suggested by RICHEY, and to select polyethylene oxide 100K based on suitability for intended purpose in holt melt extrusion as suggested by Martin et al., BELLINGER and KANASTY teaching hot melt extrusion of their dosage forms.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention because BELLINGER teaches the structure, materials, and modifications for achieving the desired therapeutic gastric retention period. 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 claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
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(a).
Response to Arguments:
Applicant's arguments filed 09/05/2025 have been fully considered but they are not persuasive.
Applicant argues that: “However, the Examiner is combining polymers recited for different purposes in the gastric residence system. Paragraph [0241] of Bellinger recites exemplary coupling polymers-that is, polymers useful in the linkers of the gastric residence system. Paragraph [0217] of Bellinger recites exemplary carrier polymers-that is, polymers useful in the arms of the gastric residence system, not in the linkers of the gastric residence system. Over 70 polymers and polymer classes are listed in that paragraph as carrier polymers. PCL is listed as a preferred polymer-but as a preferred carrier polymer, not as a preferred linker polymer. Thus, the motivation to select a combination of PLGA and PCL for a polymeric linker is lacking.” (p. 13, 1st paragraph).
In response the examiner argues that BELLINGER clearly teaches the linker can comprise polycaprolactone (PCL) ([0009]) and the linker can include “poly(lactic-co-glycolic acid) (PLGA), and copolymers, mixtures, blends and combinations thereof.” ([0241]). And it would have been understood by one of ordinary skill in the art the these species PCL and PLGA are time-dependent linkers in the context of the BELLINGER disclosure (see, e.g., [0239] & [0306]). It would have been immediately conceivable to combine species within the context of the subgenus biodegradable polyesters including PLGA such as “poly(lactic acid), poly(glycolic acid), poly(lactic-co-glycolic acid) (PLGA)” and “poly(caprolactone)” (PLC). Where one of ordinary skill in the art clearly recognizes that PLGA is a copolymer of poly(lactic acid) and poly(glycol acid) in various ratios (such as 50:50; 5% PLA3 and 95% PGA4; 95% PLA and 5% PGA) each of which would result in different degradation rates as poly(glycolic acid) is generally known to degrade faster than poly(lactic acid). And that poly(caprolactone) is a similar biodegradable polyester polymer (MPEP §2144.06)(instant claim 1, “the polymeric linker comprises: (i) poly(lactic-co-glycolide)(PLGA); (ii) polycaprolactone (PCL)”).
One of ordinary skill in the art would have appreciated the polycaprolactone (PCL) and poly(lactic-co-glycol acid)(PLGA) are both in the same class of biodegradable polyesters with different degradation rates. And that PLGA and PCL could have been blended with the predictable result of varying the time-dependent degradation and therefore the degradation of the connections between segments during gastric residence and eventual passage of the device after the desired residence period in the patient’s stomach, per the disclosure BELLINGER, could have been varied. MPEP §2144.05 – “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation."” In the instant case BELLINGER clearly teaches the function of the linker, and varying the composition thereof for the desired residence time in the patient’s stomach (instant claims 26-27, amount of PLGA and PCL).
Applicant further argues that: “However, HPMCAS and PLGA have very different properties, and are not directly substitutable for each other. HPMCAS is an enteric polymer, which weakens at high pH, as disclosed in Table 2 at page 20 of Kanasty. PLGA is not an enteric polymer. The skilled artisan would not use PLGA in place of HPMCAS in the linkers disclosed in Kanasty, as that would render the HPMCAS/PCL linkers of Kanasty unsuitable for their intended purpose as enteric linkers (MPEP 2143.01 V., "The proposed modification cannot render the prior art unsatisfactory for its intended purpose"). Thus, the cited publications do not provide motivation to combine PLGA and PCL.” (p. 13, 2nd paragraph).
In response the examiner argues that BELLINGER clearly teaches that linker can be an enteric linker or a time-dependent linker (see, e.g., [0007]-[0008], [0038]), and particularly that: “The residence time of the systems in the stomach is adjusted by the choice of coupling polymers. The systems will eventually break down in the stomach, despite the use of enteric coupling polymers, as the mechanical action of the stomach and fluctuating pH will eventually weaken the enteric coupling polymers. Coupling polymers which degrade in a time-dependent manner in the stomach can also be used to adjust the time until the system breaks apart, and hence adjust the residence time. Once the system breaks apart, it passes into the intestines and is then eliminated.” ([0214]). KANASTY similarly discloses the linkers can be enteric or time-dependent polymeric linkers (see, e.g., [0013], [0014]), and particularly that: “In additional embodiments, a time-dependent coupling polymer or linker can be used. Such a time-dependent coupling polymer or linker degrades in a predictable, time dependent manner. In some embodiments, the degradation of the time-dependent coupling polymer or linker may not be affected by the varying pH of the gastrointestinal system.” ([0088]). And that: “In one embodiment, time-dependent polymers can be used as the first linker material. In one embodiment, low molecular weight polycaprolactone is used.” ([0108]). The examiner notes that while both BELLINGER and KANASTY teach combinations of enteric and time-dependent polymeric linkers such as PCL and HPMCAS (BELLINGER: [0009]; KANASTY: [0184]), MPEP 2123(II) makes clear that: “Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments.”
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP §§ 706.02(l)(1) - 706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 6, 26-27, 36, 60-61, 82, 86-87, 89, 155-160, 162-163 and 169 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,992,552 (hereafter ‘552) in view of KANASTY (US 2019/0254966; published August, 2019; or WO 2017/205844 A2; the former cited herein); RICHEY (US 2016/0317453; published November, 2016); and Martin et al. (“Hydrophilic Matrix Tablets for Oral Controlled Release,” 2015; SPRINGER; Chapter 5 – “Applications of Polyethylene Oxide (POLYOX) in Hydrophilic Matrices,” pp. 123-141).
Instant claims a are discussed above.
‘552 claim 1 recites a gastric residence system for administration to a stomach of a patient, comprising: a central elastomer component, wherein the central elastomer component is mono-concave, bi-concave, concavo-convex, or toroidal; a plurality of at least three carrier polymer-agent components comprising a carrier polymer and a therapeutic agent or a salt thereof, wherein each of the plurality of carrier polymer-agent components comprises an elongate member comprising a proximal end, a distal end, and an outer surface there between; wherein the proximal end of each elongate member is attached to the central elastomer component and projects radially from the central elastomer component, each elongate member having the distal end not attached to the elastomer component and located at a larger radial distance from the central elastomer component than the proximal end; wherein the central elastomer component is attached directly or indirectly to each elongate member by an intercomponent anchor, wherein the intercomponent anchor is a separate component from the central elastomer component and each of the elongate members; wherein a first portion of each intercomponent anchor is located within the central elastomer component, and a second portion of each intercomponent anchor is located within: a) a corresponding first segment of interfacing polymer, wherein each corresponding first segment of interfacing polymer is also attached directly or indirectly to a corresponding one of the elongate members; b) a corresponding segment of linker, wherein each corresponding segment of linker is also attached directly or indirectly to a corresponding one of the elongate members; or c) a corresponding one of the elongate members; wherein i) the central elastomer component is overmolded over the first portions of the intercomponent anchors, or ii) the first segment of each interfacing polymer, a first segment of the corresponding segment of each linker, or a first segment of each elongate member is overmolded over the corresponding second portion of the intercomponent anchors; wherein the gastric residence system has a compacted form when within a container that provides a constraining force, and is suitable for administration orally or through a feeding tube in the compacted form; and has an uncompacted form resulting from elastic recoil of the gastric residence system when released from the constraining force provided by the container in the stomach of the patient; wherein the gastric residence system is configured to be retained in the stomach for a period of at least about 24 hours; and wherein the gastric residence system is configured to release a therapeutically effective amount of the therapeutic agent or the salt thereof over at least a portion of the period in which the gastric residence system is retained in the stomach. ‘552 claim 2 recites the gastric residence system of claim 1, wherein the linker comprises hydroxypropyl methyl cellulose acetate succinate (HPMCAS) and polycaprolactone (PCL); or wherein the linker comprises poly(lactic-co-glycolic acid) (PLGA).
The difference between the instantly rejected claims and the claims of ‘552 is that the claim of ‘552 do not expressly claim the flexural modulus and/or breaking over D days, or the inclusion of a pigment.
Regarding the flexural modulus and/or breaking over D days, the examiners position is that it would have been well within the ordinary level of skill in the art, particularly in view of the teaching of KANASTY (see whole document), to modify the polymeric linker(s) to weaken or break in a desired period of time to achieve the desired therapeutic effect (MPEP 2144.05). The gastric residence system of the claims of ‘552 (and KANASTY) and the instant claims are structurally identical including the same component, for the same intended use, therefore one it would have been prima facie to optimize the residence time of the “an agent” or multiples thereof (the same or different drug(s)) in order to better treat patient needs.
KANASTY teaches a substantially identical gastric residence system as BELLINGER, and further teaches that: “To create the reinforcement layer, PCL doped with black iron oxide pigment was extruded as a ribbon approximately 500 micrometers thick and cut into small pieces of 20 mm length. The thin 100% black PCL layer was placed compression molded on one-side of a 38% drug loaded arm by keeping the two layers in close contact with each other and incubating in an oven for 10 minutes at 75° C. and then compressing together.” ([0285]).
RICHEY teaches the function of acid-terminated and ester-terminated PLGA polymers as discussed above.
Martin et al. teaches polyethylene oxide species suitable for hot melt extrusion, as discussed above.
It would have been prima facie obvious before the effective filing date of the claimed invention that the instantly rejected claims are an obvious variant of the claims of ‘552 because both sets of claims are directed to identical or substantially identical gastric residence system of delivery of drug(s) to a patient via gastric retention over a period of time. The skilled artisan would have been motivated to modify the claims of ‘552 and produce the instantly rejected claim because optimization of the gastric retention time would have resulted in improved efficacy. Furthermore, the skilled artisan would have had a reasonable expectation of success in producing the invention of the instantly rejected claims because KANASTY and the claims of ‘552 teach the structure, materials, and modifications for achieving the desired therapeutic gastric retention period.
Response to Arguments:
Applicant's arguments filed 02/21/2025 have been fully considered but they are not persuasive.
Applicant argues that: “
This rejection is respectfully traversed. The Examiner cites claim 2 of U.S. 11,992,552, which recites that "the linker comprises hydroxypropyl methyl cellulose acetate succinate (HPMCAS) and polycaprolactone (PCL); or wherein the linker comprises poly(lactic-co-glycolic acid) (PLGA)." However, as discussed above, HPMCAS and PLGA have very different properties, and a linker comprising PCL and HPMCAS has very different properties from a linker comprising PLGA. The skilled artisan would not be motivated to replace the HPMCAS in a PCL/HPMCAS linker (which is an enteric linker, designed to weaken at high pH) with PLGA, a non-enteric polymer. The Richey and Martin references do not supply the missing motivation for the combination.” (p. 10).
In response the examiner argues that claim 2 of US 11,992,552 in reciting that: “or wherein the linker comprises poly(lactic-co-glycolic acid) (PLGA).” encompasses PCL/PLGA blends because the transitional phrase “comprising” is open-ended “The transitional term "comprising", which is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps.” (MPEP §2111.03). Therefore, it would have been prima facie obvious to provide a time-dependent linker that is independent of pH composed of PLGA and PCL both of which are descried as such.
Conclusion
Claims 1, 6, 26-27, 36, 60-61, 82, 86-87, 89, 155-160, 162-163 and 169 are pending and have been examined on the merits. Claims 82 and 160 are objected to. Claims 1, 6, 26-27, 36, 60-61, 82, 86-87, 89, 155-160, 162-163 and 169 are rejected under 35 U.S.C. 103; and claims are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. 11,992,552. No claims allowed at this time.
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/IVAN A GREENE/Examiner, Art Unit 1619
/TIGABU KASSA/Primary Examiner, Art Unit 1619
1 Poly(Lactic Acid).
2 Poly(Glycolic Acid).
3 Poly(Lactic Acid).
4 Poly(Glycolic Acid).
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