Notice of Pre-AlA 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 .
DETAILED ACTION
This Office Action is in response to Applicants’ Amendment and Remarks filed on 11/11/2025 in which claim 24 is cancelled and claim 21 is amended. No claims are newly added.
Claims 1-5, 7-9, 11, 12, 14, 18, 20-23, 25, 26 and 29 are pending in the instant application and are examined on the merits herein.
Priority
This application is a National Stage Application of PCT/CN2021/088989, filed on 4/22/2021. The instant application claims foreign priority to PCT/CN2020/086487 filed on 4/23/2020. Acknowledgment is made of applicant's claim for foreign priority under 35 U.S.C. 119(a)-(d). The certified copy has been filed in the instant application on 10/27/2011.
Withdrawn Rejections
All rejection(s) of record for claim(s) 24 is/are hereby withdrawn due to the cancellation of said claim(s) rendering said rejection(s) moot.
Applicant’s amendment, filed on 3/25/2013, with respect to the rejection of claims 1-5, 7-9, 11, 18, 20-23, 25, 26 and 29 under 35 U.S.C. 102(a)(1) as being anticipated by Chau et al. (US 2015/0087725A1), as evidenced by Plitt et al. (US 2022/0062151A1, filed 2019) and claim 14 under 35 U.S.C. 102(a)(1) as being anticipated by Chau et al. (US 2015/0087725A1), as evidenced by Plitt et al. (US 2022/0062151A1, filed 2019), as evidenced by Miyata et al. (U6,387,413 B1, 2000), has been fully considered and is persuasive. Chau does not disclose a composition where a first polymer concentration is at most 5 mg/mL. The rejections are hereby withdrawn.
Maintained Rejection
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 1-5, 7-9, 11, 12, 14, 18, 20-23, 25, 26 and 29 are rejected under 35 U.S.C. 112(a), as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated that, “To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the invention, with all its claimed limitations, not that which makes it obvious,” and by using “such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 48 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated that, “A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials.” Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) (“In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...”) Regents of the University of California v. Eli Lilly & Co., 43 USPQe2d 1398.
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP § 2163. The MPEP does state that for a generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitute a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad generic. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient.” MPEP § 2163.
In the instant case, the claims are drawn to a composition comprising a first polymer bearing a first reactive group and a second polymer bearing a second reactive group, where the first polymer has an intrinsic viscosity of at least 500 mL/g and the second polymer has an intrinsic viscosity less than 1800 mL/g.
Partial structure: The partial structure provided is that the hydrogel forming composition comprises a first polymer derivative and a second polymer derivative wherein the first polymer derivative is capable of reacting with a second polymer derivative. The hydrogel forming polymer is defined by its physicochemical properties, including an intrinsic viscosity. No structural limitations are provided for the claimed hydrogel forming polymer other than the fact that said hydrogel forming polymer comprises a first polymer derivative and a second polymer derivative wherein the first polymer derivative is capable of reacting with a second polymer derivative. The genera of the first polymer derivative and second polymer derivative are vast and embrace any polymeric backbone with the disclosed intrinsic viscosity. However, there is no known or disclosed structure/function relationship within the specification that elucidates which polymers yield the claimed properties and which polymers lie outside this window.
As described in MPEP § 2163, for a generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP §2163 states that if the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. In the present case, there are two working examples in the instant specification wherein the claimed hydrogel forming polymer is prepared by reacting thiol derivatized hyaluronic acid or a thiol derivatized dextran with a vinyl sulfone derivatized hyaluronic acid. In the instant case, only two species of polymer (hyaluronic acid and dextran) from the broad genus of polymers embodied in the claims are employed within the working embodiments, and said distinct polymer further comprises distinct chemical modifications. Moreover, only two chemical groups (vinyl sulfone and thiol) are studied in the working examples relative to the broad genus of possible chemical groups embodied in the claims. As such, the specification does not provide descriptive support for the entire genus of polymeric derivatives claimed, as the hydrogel forming polymer described is not closely related in structure to the genera claimed and the specification does not show the variance embraced by the claims.
Physical and/or chemical properties and Functional characteristics:
The hydrogel forming polymer is described by its physical and chemical properties, specifically its intrinsic viscosity. However, there is no known or disclosed structure/function relationship within the specification that elucidates which polymeric derivatives yield the claimed properties and which polymeric derivatives lie outside this window.
Method of making the claimed invention:
Methods of crosslinking polymers together, in general, are known to the artisan, however methods of making the myriad of hydrogel forming polymers embraced by the instant claims is beyond the skill of the artisan, particularly when various elements including first polymer derivative and second polymer derivative, as well as their chemical modifications are merely described partially. As stated previously, the MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic. It is unquestionable that the claims are broad and generic, with respect to all possible polymers encompassed by the claims. The possible structural variations are limitless. Although the claims may recite some functional characteristics and chemical properties, the claims lack written description because there is no disclosure of a correlation between the chemical properties and function with the structure of the hydrogel forming polymer beyond the one working example in the specification. Moreover, as stated above, the specification lacks sufficient variety of species to reflect this variance in the genera disclosed above. Thus, the specification does not provide sufficient descriptive support for the myriad of hydrogel forming polymers embraced by the claims.
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”) Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Response to Arguments
Applicants’ arguments with respect to the rejection under 35 U.S.C. § 112(a) for lack of written description, have been fully considered but they are not persuasive.
Applicant argues that the specification provides a detailed description of the claimed polymers at ¶0089-00105, with respect to polymer types, polymer intrinsic viscosity ranges, intrinsic viscosity ratios, etc. Applicants’ argument is not persuasive because the cited sections do not rise to the level of providing a sufficient number of representative examples. The scope of the claims encompasses any combination of any two polymers where each polymer is derivatized with any reactive group. The cited ¶0089-00105 do not represent claim scope sufficiently. For instance, claim scope covers a composition comprising modified DNA combined with modified polystyrene, which is not a combination envisioned by the specification. There are numerous other examples of modified polymer combinations encompassed by the claims but not sufficiently represented by the written description. Thus, the specification does not support that the inventors were in possession of the invention as claimed.
Applicant further argues that the specification presents data demonstrating: 1) the superior stability of the claimed polymer combinations where the second polymer has an intrinsic viscosity less than 1800 ml/g, in comparison with polymer combinations where the second polymer has an intrinsic viscosity more than 1800 ml/g (Example 4) and 2) that examples 5, 6, 9 and 10 demonstrate superior rheological and drug release properties for the claimed polymer combination, such that the specification shows adequate structure-function relationships supporting claim scope. Applicants’ argument is not persuasive because while the exemplified data demonstrates structure-function relationships for HA-VS/HA-SH, PEG-SH /HA-VS or Dex-SH/Dex-VS polymer combinations, this data only represent three polymer pairs and two reactive group choices, which is insufficient to represent structure-function relationships for any two polymers independently modified with any reactive groups.
The rejection is still deemed proper and is maintained.
Modified Rejections
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 of this title, 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.
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.
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.
Claims 1-5, 7-9, 11, 12, 18, 20-23, 25, 26 and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Chau et al. (US 2015/0087725A1, reference of record), as evidenced by Plitt et al. (US 2022/0062151A1, filed 2019, reference of record), in view of Gravett et al. (WO 2012/145439, reference of record).
Chau et al. exemplifies compositions comprising: 1) vinyl sulfone derivatized hyaluronic acid (HA-VS), with molecular weight of 29 kDa or 108 kDa and degree of modification of 18%, 20%, 39% and 2) thiol derivatized hyaluronic acid (HA-SH), with molecular weight of 29 kDa or 108 kDa and degree of modification of 18%, 20%, 39%. (¶0071, 0081, 0109, 0114, 0124, 0127), where the polymer concentration in the composition was at 2%, 4% or 10%. Given that the molecular weights and concentrations of both the HA-VS and HA-SH are in identical ranges, the molar ratio, the molecular weight ratio and the mass ratio of HA-VS:HA-SH includes the value of 1:1 for all ratios. Moreover, a concentration of 4% meets the limitation of “about 5 mg/mL”.
Chau does not disclose the intrinsic viscosity of the polymers in the composition.
Plitt et al. discloses compositions comprising hyaluronic acid and derivatives thereof and that the Mark-Houwink equation gives a relation between intrinsic viscosity (n) and molecular weight (Mn) and allows determination of the molecular weight of a polymer from data on the intrinsic viscosity and vice versa:
[n] = K x (Mn)^a,
with [n]=intrinsic viscosity in m3/kg, Mn =viscosity average molecular weight, K=2.26x10^-5, and a=0.796. (¶0064-0065)
Gravett et al. discloses that vinyl sulfone derivatized hyaluronic acid (HA-VS) used to form hydrogels with thiol-modified polymers, may have a molecular weight in the range 10-2000 kDa; that the HA-VS has a concentration of 10-300 mg/mL and the thiol-modified polymer has a concentration of 4-300 mg/mL. (¶047, 0102; Claim 7)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to look to Gravett for guidance on art-accepted molecular weight ranges and concentrations for HA-VS polymers and thiol modified polymers used in forming hydrogels by crosslinking. In considering Gravett and Chau, one would recognize that they are both directed to similar goals of formulating crosslinked hydrogels by reacting HA-VS with thiol modified polymers. Therefore the molecular weights and concentrations of polymers in Gravett would be an obvious way to modify the hydrogels of Chau.
It would be further prima facie obvious that one could employ the Mark-Houwink equation of Plitt to covert the molecular weights of Chau/Gravett into intrinsic viscosities. Upon performing the conversion and given that the molecular weights and concentrations of both the HA-VS and HA-SH are in overlapping ranges, the ratio of the intrinsic viscosities would include the value of 1:1.
Accordingly, the instant claims are prima facie obvious over the teachings of the prior art.
Response to Arguments
Applicants’ response with respect to the rejection over Chau/Plitt/Gravett, has been fully considered but is not persuasive.
Applicant argues that the Mark-Houwink equation of Plitt is improperly applied to Chau because the “K” and “a” values in the equation are specific to polymer type. Applicants’ argument is not persuasive because Plitt is concerned with hyaluronic acid polymers, thus it is reasonable to assume that the constants employed by Plitt would be applicable to the hyaluronic acid based polymers of Chau.
Applicant further argues that Chau does not specifically disclose a molecular weight range but only discloses two distinct molecular weight data points. Applicants’ argument is not persuasive because a range does not have to be explicitly disclosed in a reference for a range to be obvious. When two data points are disclosed within a reference, or multiple references, relating to a property for the same compound, it is reasonable for one of ordinary skill in the art to assume that the values between the two endpoints are also relevant to the disclosure, implying a range. MPEP § 2144.05(I) - Iron Grip Barbell Co., Inc. v. USA Sports, Inc., 392 F.3d 1317, 1322, 73 USPQ2d 1225, 1228 (Fed. Cir. 2004)
Applicant further argues that Gravett is primarily directed to polymer concentrations higher than that claimed, such as 20-200 mg/mL. Applicants' argument is not persuasive because Gravett teaches a broader polymer concentration range, 4-300 mg/mL, overlapping that claimed. A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005)
Applicant further argues that the specification presents evidence of unexpected results regarding the stability of the claimed polymer combinations. Applicants' argument is not persuasive because the scope of the instant claims includes any two polymers independently modified with any reactive groups. In contrast, the evidence of unexpected results demonstrates superior stability only for HA-VS/HA-SH, PEG-SH /HA-VS or Dex-SH/Dex-VS polymer combinations. 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)(MPEP § 716.02(d)) Applicants’ arguments of unexpected results are not commensurate in scope with that of the claimed invention.
The rejection is still deemed proper and is maintained.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Chau et al. (US 2015/0087725A1, reference of record), as evidenced by Plitt et al. (US 2022/0062151A1, filed 2019, reference of record), in view of Gravett et al. (WO 2012/145439, reference of record), as evidenced by Miyata et al. (US 6,387,413 B1, 2000, reference of record).
The disclosure of Chau/Plitt/Gravett is referenced as discussed above. The combined prior art does not disclose the radius of gyration of the polymers in the composition.
Miyata discloses that for hyaluronic acid compositions the radius of gyration is related to the molecular weight by the following equation:
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132
230
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Greyscale
, wherein M is the molecular weight, <S2> is the mean square radius of gyration, K is an optical constant, R(theta) is the reduced excess scattering intensity, c is the polymer concentration, P(theta) is the particle scattering function, A is the wavelength of the laser beam in the solution, and A2 is the second virial coefficient, 0.002 ml·mol/g2 for hyaluronic acid. c is calculated from the output of a differential refractometer, based on the differential refractive index increment of a hyaluronic acid aqueous solution (dn/dc: 0.153 ml/g). (Col. 5)
One could employ the equation of Miyata to covert the molecular weights of Chau/Gravett into radium of gyration. Upon performing the conversion and given that the molecular weights and concentrations of both the HA-VS and HA-SH are in overlapping ranges, the ratio of the radium of gyration would include the value of 1:1.
Accordingly, the instant claims are prima facie obvious over the teachings of the prior art.
Response to Arguments
Applicant argues that the combined prior art does not render the independent claims prima facie obvious for the reasons outlined above, thus the rejection of dependent claims that reply on the teachings of said combined prior art, should be withdrawn. Applicants' arguments are not persuasive because the rejection of the independent claims is maintained as prima facie obvious over said combined prior art, as per the response to arguments above.
The rejection is still deemed proper and is maintained.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new and/or modified 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 extension fee 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.
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/DALE R MILLER/Primary Examiner, Art Unit 1693