The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Formal Matters
Claims 3, 5-8, 11-22, 32, 35-36, and 38-51 are cancelled. Claims 54-68 are new. Claims 1, 2, 4, 9-10, 23-31, 33-34, 37 and 52-68 are pending. Claims 58-59 are withdrawn. Claims 1, 2, 4, 9-10, 23-31, 33-34, 37, 52-57 and 60-68 are under examination.
Priority
The instant application claims priority from US provisional application 62/893,529 filed on 8/29/2019.
Rejections Withdrawn
The objection over claim 24 is withdrawn per applicant’s amendment to the claim.
The rejection under USC 112(b) over claims 27 and 39 per applicant’s amendment and claim cancellation.
The rejection under USC 112(b) over claims 46 and 47 and claims 48-51 are withdrawn per applicant’s cancellation of the claims.
The rejection under USC 112(d) over claim 2 is withdrawn per applicant’s amendment to claim 2.
As the above rejections have been withdrawn, applicant’s arguments toward these rejections are now moot.
Claim Objection – New Claims
Claims 55, 64 and 65 are objected to for the parentheticals which only recite synonymous terms for what is outside of the parenthetical. Applicant only needs to choose one option of the synonymous word, and thus, may consider deleting the parentheticals. Appropriate correction is required.
Claims 57 and 63 are objected to for being dependent on a claim that is rejected over the prior art. If either of these limitations is imported into claim 54 properly, applicant may have an allowable claim.
New Rejection – As Necessitated by New Claims 54-68 and Amendment to Claim 37
New claim 54 removes the presence of polyethylene glycol, which provides for a different claim scope requiring further search and consideration.
Amended claim 37 was amended to be an independent claim and the final “wherein” clause specifies that the hydrolysis of the hydrolytically degradable groups releases the multi-component backbone polymer chains and poly(ethylene glycol) groups covalently bound thereto. This provides a functional requirement that the released component after hydrolytic degradation has the polyethylene glycol groups covalently bound to the multi-component backbone polymer chains with the methacrylate and alkyl methacrylate monomers. It was not previously indicated what each released component had to be made up of besides any possible chains of the multi-component backbone polymer chains or that they were amphiphilic (some combination of a hydrophilic portion and hydrophobic portion).
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 37, 54-56, 60, 62, 64, 66, and 68 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kim et al (Polymer Degradation and Stability, 2015, volume 121, pages 303-310).
Kim teaches “Dimethacrylate or divinyl-functionalized acetal-based crosslinkers were synthesized as building elements of acid-sensitive crosslinked hydrogels” (abstract). Kim teaches “The hydrophilicity of the crosslinkers was tuned to control acidic-hydrolysis rate. We report the synthesis of hydroxyethyl dimethacrylate-functionalized dimethyl ketal (CL1), meta- or para-methoxybenzaldehyde based acetals (CL2m and CL2p), poly(ethylene glycol) dimethacrylate-functionalized dimethyl ketal-based crosslinker (CL3), and divinyl-functionalized meta-methoxybenzaldehyde-based acetal crosslinker (V-CL2m)” (abstract). Kim teaches Network films containing CL2m were prepared by thermally initiated polymerization with either hydroxyethylmethacrylate (HEMA) or methylmethacrylate (MMA) (abstract). Kim teaches the crosslinked films composed of the hydrophilic monomer, HEMA, show faster hydrolysis than those containing more hydrophobic monomers (e.g. MMA) (abstract). Kim teaches acid degradable film with MMA monomer (table 1). Figure 1 teaches synthesis of acid sensitive crosslinker monomers (figure 1). Kim teaches “CL3 is so sensitive to hydrolysis and hydrophilic due to the PEG content that no purification was attempted after quenching the reaction with TEA and the only post-reaction processes were removal of salts and molecular sieves by filtration” (section 3.1). Kim teaches CL3 is PEG-MA and its used in the place of HEMA that is used to make CL1 (section 2.2). PEG-MA is shown to be 360 g/mol (section 3.2). Kim teaches different molar concentrations of crosslinker (including 3.2, 9 and 50 mol% of crosslinker) (figure 7, Figure 7b extrapolates a line that would intersect through 10 to 40 mol%). Kim teaches “In the case of 2,2′-DMP-based acetal groups, CL3 revealed the highest acid-sensitivity (t1/2 < 14 min at pH 5 and t1/2 < 2 min at pH 4). Acetal functional groups based on meta or para methoxybenzaldehydes (CL2m or CL2p) gave crosslinkers with a reduced hydrolysis” (conclusions). Kim teaches “This is because MMA imparts a much more hydrophobic nature to the network slowing diffusion of aqueous buffer and hence lowering the observed rate of hydrolysis. Control of rate of hydrolysis should be selectable by controlling the relative amounts of hydrophilic or hydrophobic comonomers in the network” (section 3.4).
In regards to multi-component backbone polymer chains being released upon degradation of the hydrolytically degradable functional group, Kim provides for the use of hydrolytically degradable linkers with methacrylate functional groups and a hydrolytically degradable functional group (acetal) and methyl methacrylate polymerization incorporating the linkers. Thus, the degradation of these linkers will lead to release of the of the multi-component backbone.
In regards to multi-component backbone polymer chains being released upon degradation of the hydrolytically degradable functional group where multi-component backbone polymer chains and poly(ethylene glycol) groups covalently bound thereto, Kim provides for the use of hydrolytically degradable linkers with methacrylate functional groups and a hydrolytically degradable functional group (acetal), polyethylene glycol, and methyl methacrylate polymerization incorporating the linkers. Thus, the degradation of these linkers will lead to release of the of the multi-component backbone with polyethylene glycol covalently bound.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
New Rejection – As Necessitated by Amendment/New Claims
Claim 61 in addition to Claims 37, 54-56, 60, 62, 64, 66, and 68 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al (Polymer Degradation and Stability, 2015, volume 121, pages 303-310).
Kim teaches “Dimethacrylate or divinyl-functionalized acetal-based crosslinkers were synthesized as building elements of acid-sensitive crosslinked hydrogels” (abstract). Kim teaches “The hydrophilicity of the crosslinkers was tuned to control acidic-hydrolysis rate. We report the synthesis of hydroxyethyl dimethacrylate-functionalized dimethyl ketal (CL1), meta- or para-methoxybenzaldehyde based acetals (CL2m and CL2p), poly(ethylene glycol) dimethacrylate-functionalized dimethyl ketal-based crosslinker (CL3), and divinyl-functionalized meta-methoxybenzaldehyde-based acetal crosslinker (V-CL2m)” (abstract). Kim teaches Network films containing CL2m were prepared by thermally initiated polymerization with either hydroxyethylmethacrylate (HEMA) or methylmethacrylate (MMA) (abstract). Kim teaches the crosslinked films composed of the hydrophilic monomer, HEMA, show faster hydrolysis than those containing more hydrophobic monomers (e.g. MMA) (abstract). Kim teaches acid degradable film with MMA monomer (table 1). Figure 1 teaches synthesis of acid sensitive crosslinker monomers (figure 1). Kim teaches “CL3 is so sensitive to hydrolysis and hydrophilic due to the PEG content that no purification was attempted after quenching the reaction with TEA and the only post-reaction processes were removal of salts and molecular sieves by filtration” (section 3.1). Kim teaches CL3 is PEG-MA and its used in the place of HEMA that is used to make CL1 (section 2.2). PEG-MA is shown to be 360 g/mol (section 3.2). Kim teaches different molar concentrations of crosslinker (including 3.2, 9 and 50 mol% of crosslinker) (figure 7, Figure 7b extrapolates a line that would intersect through 10 to 40 mol%). Kim teaches “In the case of 2,2′-DMP-based acetal groups, CL3 revealed the highest acid-sensitivity (t1/2 < 14 min at pH 5 and t1/2 < 2 min at pH 4). Acetal functional groups based on meta or para methoxybenzaldehydes (CL2m or CL2p) gave crosslinkers with a reduced hydrolysis” (conclusions). Kim teaches “This is because MMA imparts a much more hydrophobic nature to the network slowing diffusion of aqueous buffer and hence lowering the observed rate of hydrolysis. Control of rate of hydrolysis should be selectable by controlling the relative amounts of hydrophilic or hydrophobic comonomers in the network” (section 3.4).
In regards to multi-component backbone polymer chains being released upon degradation of the hydrolytically degradable functional group, Kim provides for the use of hydrolytically degradable linkers with methacrylate functional groups and a hydrolytically degradable functional group (acetal) and methyl methacrylate polymerization incorporating the linkers. Thus, the degradation of these linkers will lead to release of the of the multi-component backbone.
In regards to multi-component backbone polymer chains being released upon degradation of the hydrolytically degradable functional group where multi-component backbone polymer chains and poly(ethylene glycol) groups covalently bound thereto, Kim provides for the use of hydrolytically degradable linkers with methacrylate functional groups and a hydrolytically degradable functional group (acetal), polyethylene glycol, and methyl methacrylate polymerization incorporating the linkers. Thus, the degradation of these linkers will lead to release of the of the multi-component backbone with polyethylene glycol covalently bound.
One of ordinary skill in the art before the time of filing would have adjusted amounts of the linker to within the range of 10 to 30 mol% as Kim provides for uses of 9 mol% and 50 mol% of linker which both provides an overlapping range and presents the value of 9 mol% which is very near to 10 mol% that there would be a reasonable expectation of success in making a similarly formed hydrogel (see MPEP 2144.05).
Maintained Rejection – Modified As Necessitated by Amendments/New Claims
Claims 1-2, 4, 23, 25, 26, 27, 30-31, 34, 52-55, 60-62, 64, and 66 are rejected under 35 U.S.C. 103 as being unpatentable over Louguet et al (Acta Biomaterialia, 2014, volume 10, pages 1194-1205) and Cai US 20080305007 as evidenced by Gillies et al (Journal of the American Chemical Society, 2004, volume 126, pages 11936-11943) and as evidenced by Runarsdottir thesis (Use of modified PEG as a solubility enhancer for poorly soluble drugs: possible dosage forms and taste masking evaluation, Faculty of Pharmaceutical Sciences, School of Health Sciences, University of Iceland, May 2017).
The claim provides that “multi-component backbone polymer chains comprising…”. Thus, other items are allowed in the multi-component backbone polymer of the hydrogel in claim 1.
Claim 1 indicates that the crosslinkers are covalently bound to and connecting two or more of said backbone polymer chains, but it is not provided that they are necessarily connected through methacrylate and/or methyl methacrylate monomers.
Louguet teaches poly(ethylene) methacrylate hydrolysable microspheres for transient vascular embolization (title and abstract). Louguet teaches “poly(ethylene glycol) methacrylate (PEGMA) hydrolyzable microspheres intended for biomedical applications were readily prepared from poly(lactide-co-glycolide) (PLGA)–poly(ethylene glycol) (PEG)–PLGA crosslinker and PEGMA as a monomer using a suspension polymerization process. Additional co-monomers, methacrylic acid and 2-methylene-1,3-dioxepane (MDO), were incorporated into the initial formulation to improve the properties of the microspheres.” (abstract). The introduction provides that additional ester linkages from a cyclic ketene acetal monomer, 2-methylene-1,3-dioxepane, were incorporated into the hydrogel backbone to shorten the size of the polymer degradation products below (50kgmol-1) to facilitate renal elimination. Section 2.3 provides for a PLGA-PEG-PLGA hydrolysable crosslinker. Louguet provides for linear polymers and gels synthesis (section 2.4) as well as microsphere preparation with the polymers and crosslinkers (section 2.5). Note that the polymer backbone only has to comprise methacrylate monomer and alkyl methacrylate monomer. Thus, PEGMA is a polymer with a methacrylate unit. Louguet teaches loading doxorubicin (a pharmaceutical agent, has a lipophilic partition coefficient of 0.49-1.3, a molecular weight of 543/5 g/mol and melting temperature of 216 degrees C) on microspheres (section 2.9 and section 4.3). Louguet teaches in vitro degradation of the microspheres (section 2.10) and hydrolytic degradation totally within 2 days (section 3.5). Tables 3 and 4 teach PEG-PLGA, PEG-PLGA, PEG-PLGA-MDO and PEG-PLGA-MA-MDO. Louguet teaches the hydrolysable MS behave similarly to the non-degradable MS that are used (Conclusion). Louguet teaches “The presence of MA in the polymer matrices accelerates the degradation (+16.5%). As seen above, the infiltration of water molecules into the hydrogel is promoted by the presence of anionic groups, especially in PBS at pH 7.4, and, as a consequence, there is greater water uptake and quicker hydrolysis of the ester bonds take place. The presence of MDO associated with MA had no impact on the degradation profile despite its relative hydrophobicity. Thus, by adjusting the ability of the network to attract more water, the degradation times were speeded up even after a short period of time” (section 4.4). Louguet teaches “incorporation of 10 mol.% MA into the polymer matrices increased the swelling ratio of microspheres in PBS” (section 4.1). Louguet teaches “PEGMA was selected as the monomer because of its amphiphilic nature, which results from its water-soluble PEG side chain and its hydrophobic methacrylate group. The amphiphilic nature of PEGMA makes possible mixing it directly with the hydrolyzable crosslinker in hydrocarbon phase to perform the polymerization by direct oil in water suspension process for making microspheres. The hydrolyzable crosslinker was designed to achieve rapid degradation time. An anionic co-monomer, methacrylic acid (MA) was combined to the PEGMA monomer and the crosslinker to adjust the water uptake and to allow the ionic loading of drugs. A large part of the strategy was devoted to the biocompatibility of the material. First, the initial components were chosen to generate water-soluble macromolecules after hydrolysis in order to avoid any accumulation in the organism, which might lead to inflammatory reactions [18]. Second, additional ester linkages from a cyclic ketene acetal monomer, 2-methylene-1,3-dioxepane (MDO), were incorporated into the hydrogel backbone to shorten the size of the polymer degradation products (below 50 kg mol-1 ), facilitating their renal elimination” (section 1). Louguet teaches a crosslinker with PEG having a molecular weight of at least 3000 g/mol and notes PEGMA and cyclic ketene acetal (section 4.4). Louguet teaches 10 mol% MDO (the acetal) in monomer mixture (section 3.1, also tables 1 and 2 about mol% and ratios). Figure 4 teaches loading of Dox by % for each of the hydrogels. Gillies evidences that lowering pH leads to increased hydrolysis of hydrolysable polymers (abstract and figure 3). Thus, Louguet’s formulation is expected to have a very fast degradation rate when the pH is lower, especially down to pH 1 as in the claims. Runarsdottir evidences that PEG is a soluble enhancer for lipophilic compounds (title and abstract and figure 1.2 and section 1.3). Thus, since PEG is significant part of the hydrolysable hydrogel polymer of Louguet, it and portions with PEG will be available to solubilize the drug/active after hydrolysis has taken place.
Louguet does not teach alkyl methacrylates, but it does note that MDO associated with MA had no impact despite its relative hydrophobicity. Thus, monomers with hydrophobic nature can be compatible with the system. Louguet notes that by adjusting the ability of the network to attract more water, the degradation times were speeded up even after a short period of time” (section 4.4).
Cai teaches a hydrogel matrix with PEGDMA, methacrylic acid and methyl methacrylate (abstract and paragraph 27). Cai teaches polyethylene glycol (paragraph 18). Cai teaches crosslinking (paragraph 18). Cai teaches crosslinking reagents of various types (paragraphs 24-26) and that other general methods for crosslinking are known in the art. Paragraph 20 notes that monomers used to create copolymers include methacrylate, methyl methacrylate, alkylacrylates and others (paragraph 20). Cai teaches preparing the matrix with PEGDMA and acrylate with acrylates being MAA, MMA or combinations thereof (paragraph 27). Cai teaches entrapping or encapsulating the protein of the matrix (paragraphs 32 and 36). In this way the added component would be enveloped/within a space in the hydrogel matrix and there is a basis in Cai to entrap/encapsulate useful additives in the hydrogel matrix that can extend to other hydrogels containing various actives to be carried in the prior art. Additionally, general mention of proteins as a genus contains those with therapeutic or nutritional value even though Cai sees the option of sensing/analyzing. Proteins can be considered cell-based since proteins are made in cells. Paragraph 36 also provides for the forms of microspheres.
One of ordinary skill in the art before the time of filing would have observed methyl methacrylate as an acceptable polymer for making hydrogel along with methacrylate as they are both acrylates for this purpose by the teachings of Cai. Thus, one would incorporate methyl methacrylate into hydrogel polymers of Louguet and reasonably expect similarly functioning hydrogels particularly as Louguet’s crosslinkers give the hydrogel the ability to hydrolyze and cause the hydrogel to degrade. The prior art sees these combinations of monomers and crosslinkers as being able to form functioning hydrogels. Since PEGMA (an amphiphilic molecule) is used to make the hydrogel of Louguet, and thus, would allow for amphiphilic degradation products (having PEG ends and methacrylate ends), it meets the limitation of applicant’s claim 52.
Claims 9, 10, 24, 28, 29, 33 and 68 in addition to Claims 1-2, 4, 23, 25, 26, 27, 30-31, 34, 52-55, 60-62, 64, and 66 are rejected under 35 U.S.C. 103 as being unpatentable over Louguet et al (Acta Biomaterialia, 2014, volume 10, pages 1194-1205); Cai US 20080305007 and Frechet US 20060223776 (previously cited) as evidenced by Gillies et al (Journal of the American Chemical Society, 2004, volume 126, pages 11936-11943) and as evidenced by Runarsdottir thesis (Use of modified PEG as a solubility enhancer for poorly soluble drugs: possible dosage forms and taste masking evaluation, Faculty of Pharmaceutical Sciences, School of Health Sciences, University of Iceland, May 2017).
Louguet and Cai teach the claims as discussed above. As indicated above, Louguet provides for carrying drug with the hydrogel and the use of acetal group, or more generally, hydrolyzable crosslinkers.
Louguet and Cai do not teach drug types of claim 24, the self emulsifying or spontaneous micelle forming lipid solution of claims 28 and 29, a drug of aqueous solubility of claim 33 or a triethylene glycol di(ethyl-1-methacryloyloxy poly(ethylene glycol) acetal of claim 41 (also for claims 47, 49 and 51).
Frechet teaches various entrapped bioactive materials including DNA, growth factors, hormones, antivirals, antibacterials, anti-cancer and others in its microgels (paragraphs 89-91). Frechet teaches “Untreated cells as well as those incubated with plasmid DNA show a low level of about 300-400 pg/mL of secreted IL-6. When DNA was mixed with Lipofectamine 2000, the IL-6 level is increased to about 2000 pg/mL of IL-6. Lipofectamine 2000 (Invitrogen Corporation, Carlsbad, Calif.) is a commercially available transfection agent that forms micelles around the DNA, protecting it from nucleases in the serum and facilitating cellular delivery. Therefore, this shows that naked DNA requires a transfection agent, such as Lipofectamine, in order to produce an immune response.” (paragraphs 233 and 236). Lipofectamine is a lipid-micelle forming substance. Frechet teaches two drugs with the water solubility range of the claims. Frechet teaches paclitaxel with solubility in water of 0.3 ug/ml and taxitere with solubility in water of 7ug/ml (paragraph 13). Thus, using these types of drugs based on water solubility in hydrogels is known in the art. Frechet teaches using bisacrylamide polyethylene glycol acetal crosslinker as its crosslinking agent (paragraph 27 and figure 6 and example 4), which is a polyethylene glycol acrylic acetal crosslinker with acetal groups. Frechet teaches bisacryloyl acetal crosslinker (paragraphs 73-74). Frechet teaches hydrolysis of the crosslinker for hydrogels and microgels (paragraphs 69-74). Frechet teaches the hydrolyzing of the crosslinker at pH 5 being 5-30 minutes (paragraph 74).
One of ordinary skill in the art before the time of filing would have included various types of other drugs (anti-infectives (hormones, antibacterials or antivirals, etc,), drugs having water solubility in the range of 0.01 ug/ml to 120 ug/ml, lipid micelle forming agents like lipofectamine if required for drug delivery and altered hydrolysable crosslinking agent in hydrogel microspheres of Louguet and Cai based on teachings of Frechet as these were seen as other acceptable pharmaceuticals/actives, drug carrier needs (lipid micelle forming agents in Frechet) and hydrolysable crosslinkers of the prior art in making hydrogels that can carry an active agent. There would be a reasonable expectation of success in having produced applicant’s claimed hydrogels by the teachings of the prior art teaching the claimed drugs, components and groups for use in hydrogel compositions.
Response to Applicant’s Arguments over the Maintained Rejections under USC 103
Applicant argues that Louguet is to degradable hydrogel particles for embolization while Cai is toward hydrogel coatings for biosensors that need to be biostable to avoid loss of analyte binding molecules. Thus, applicant asserts Louguet is for an opposite purpose and function than that of Cai. The use of Cai is as a secondary reference to provide suitable hydrogel monomers for medical materials where Louguet provides for a degradable hydrogel with hydrolytic links, polyethylene glycol, and methacrylate. Note that paragraph 20 (also paragraph 22 that provides for mix of methacrylate and methyl methacrylate) of Cai teaches that monomers for copolymers for hydrogels include methyl methacrylate. Cai does not indicate that methyl methacrylate or its other hydrogel monomers cannot be used in degradable polymeric hydrogel materials, and thus, does not teach away from the use of methyl methacrylate in other types of hydrogels of the art. Additionally, a reference is analogous art if it is to a same field of endeavor (MPEP 2141.01(a)), which in this case is methacrylate-based hydrogel materials for medical use. Thus, one of ordinary skill in the art would seek to look toward methyl methacrylate in Cai as a hydrogel monomer in hydrogels that also incorporate methacrylate compounds.
Applicant argues that MDO appears to be necessary in Louguet, and thus, is not replaceable. It should be noted that applicant’s claims use “comprising” for transition phrases, and therefore, would allow other monomers or agents of the prior art. Thus, methyl methacrylate can still be incorporated without necessarily replacing MDO. Note that the examiner stated “One of ordinary skill in the art before the time of filing would have observed methyl methacrylate as an acceptable polymer for making hydrogel along with methacrylate as they are both acrylates for this purpose by the teachings of Cai”. There was no indication that MDO had to be substituted rather that Louguet recognizes the use of hydrophobic monomers in its hydrogels.
Applicant repeats that Cai is to maximize stability and minimizing swelling of hydrogels. However, as noted above, Cai is used to teach other monomers that are useful to make hydrogels with methacrylates. Louguet is the hydrogel of the primary reference that is being modified with addition of other known hydrogel monomers of the prior art.
Applicant argues that other references that were cited do not cure the deficiencies, however, as the rejection over Louguet and Cai is maintained, the references are still applicable. It should be noted that Gillies and Runarsdottir are evidentiary references where Gillies evidences that lowering pH leads to increased hydrolysis of hydrolysable polymers and Runarsdottir evidences that PEG is a soluble enhancer for lipophilic compounds, thus, the release of units with PEG from a hydrogel motivated by Louguet and Cai will be expected to solubilize lipophilic drugs to some extent based on the PEG of the degraded units and the polymers of the hydrogel will degrade based on pH based on the hydrolysable groups present in Louguet’s formulations. Louguet recognizes the ability of its units to degrade to break up the polymers. Thus, this is an adjustable parameter in the prior art to control hydrogel degradation via pH. As noted by applicant, Frechet teaches drugs used in hydrogels. It is still applicable for these teachings.
Applicant argues that the resulting product of the degradation of the links will be polymethacrylate/alky methacrylate chains with pendent PEG groups. Only claim 37 after amendment has a limitation toward this particular functionality. This resulted in the claim being removed from the rejection over Louguet and Cai, however, a new search was conducted to address the new limitation as claimed. The new search was also conducted in light of new claim 54.
Applicant argues that dependent claims 4 and 34 cannot be taught by the prior art with evidence from Gillies. It is true that Gillies might not provide for hydrogels, but it is relevant to polymers with hydrolytically degradable linkages that make up the hydrogels and provides evidence that they can degrade quicker when subjected to low pH.
Applicant argues that Louguet does not provide for the hydrolytically degradable functional groups of claims 9 and 10 (and now claim 68). This is noted based on applicant’s argument over the MDO, however, the maintained rejection with Frechet does allow for acetal linkages in a hydrogel polymer that is hydrolytically degradable where Louguet provides for a hydrogel polymer with hydrolysable linker that can carry drugs. Thus, these claim limitations are still taught in the prior art with a motivation to use hydrolytically degradable linkers in a hydrogel and Frechet further provides its hydrolytically degradable linkers allow for release of entrapped molecules like drugs, which makes them useful for this purpose in the prior art (MPEP 2144.06).
Applicant argues the limitations of claims 56, 57 and 63. The examiner is withdrawing these claims from these rejections. However, in searching new claim 54, the examiner found art that would also teach claim 56 as well as teaching new claim 54. Claims 57 and 63 were reconsidered and would make an allowable claim if either was incorporated into independent claim 54 as being the cross-linkers. Kim teaches a central PEG segment with terminal hydroxyl groups bound to an acetal group with a PEG methacrylate and provides for 6 ethylene glycols on each side of the acetal in one form of figure 1 of Kim. This would meet limitations of claim 56 as 6 ethylene glycols is about 370 g/mol in addition to the methacrylate groups adding molecular weight.
Applicant may consider importing claims 57 or 63 noted as allowable when imported into claim 54 with its limitations. Applicant may file an after final rejection to make such an amendment. Either of these limitations of claim 57 or 63 incorporated into independent claims 1 and 37 would have similar effect. This is one possibility for allowable claims, but applicant may consider other alternatives after consideration of this response.
Maintained Rejection – Modified As Necessitated by Amendment
Non-Statutory Type Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-2, 4, 9, 10, 27, 30-31, 34, 37, 52, 54-56, 60-62, 64, 66, and 68 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6, 7, 11, 16, 19, and 22-24 of copending Application No. 18/548,816 (reference application) in view of Frechet. Although the claims at issue are not identical, they are not patentably distinct from each other because each claim set provides for compositions with claimed polymer structures and crosslinkers along with containing a drug (in ‘816 solid fulvestrent is a hormone treatment). ‘816 does not provide for hydrogel. ‘816 provides for overlapping ranges of hydrophobic monomers and crosslinkers. ‘816 provides for amounts of fulvestrent and that it should be therapeutically effective allowing for optimization for treatment. Frechet as taught above provides for a hydrogel with polymer structures having hydrolytic linkers than can be hydrolyzed to separate the polymer backbone chains. Therefore, one of ordinary skill in the art would provide the polymer composition of ‘816 as a hydrogel as being an acceptable form for such a polymer backbone formulation.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Applicant’s Arguments
Applicant does not provide a terminal disclaimer or arguments to this double patenting rejection at this time. As the copending application ‘816 has a later patent term date, then at the time of allowance, the rejection will be withdrawn at that appropriate time if ‘816 has not yet issued as a patent. Therefore, this rejection is maintained.
Conclusion
No claims are allowed. Claims 57 and 63 are objected to.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARK V STEVENS whose telephone number is (571)270-7080. The examiner can normally be reached on M-F 9:00 am to 6:00 pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian-Yong Kwon can be reached on (571)272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/MARK V STEVENS/Primary Examiner, Art Unit 1613