DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . 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 (i.e., changing from AIA to pre-AIA ) 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.
Priority
The instant application is a 371 of PCT/EP2021/051394 filed on 01/21/2021, which claims foreign priority to European application no. EP20305051.3 filed on 01/22/2020. The certified copy for EP20305051.3 has been filed on 06/28/2022 in the instant application.
Status of the Claims
The claim amendments and remarks filed on 05/19/2026 is acknowledged. Claims 21-22, 25, and 37 are amended. Claims 1-20, 24, 30-36, and 38 are cancelled.
Accordingly, claims 21-23, 25-29, and 37 are pending and being examined on the merits herein.
Withdrawn Objections/Rejections
The objection to the specification is withdrawn because the suggested amendments “between 105 and 4 x 105 …” and “between 5 x 105 and 2 x 106 Da” has been implemented.
The 35 USC 112(b) rejection over claim 25 is withdrawn because it now clear that the recited molecular weight range is between 5 x 105 and 2 x 106 Da.
The 35 USC 103 rejection over Daar in view of Molliard for claims 21, 25-29, 31, and 35, further in view of Willey for claim 22, and further in view of Hunter for claims 23 and 36-38 are withdrawn because the amended claims now require a limitation of the ionizing radiation at a dose of 8 kGy to 50 kGy as well as new amount ranges for the molecule weight of the hyaluronic acid and the amount polyol, which were not considered in the previously applied rejections.
The following grounds of rejection are new as necessitated by Applicant’s amendments.
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 21-23, 25-29, and 37 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, 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.
Claim 21 recites a method for protecting hyaluronic acid against degradation induced by ionizing radiation comprising preparing a composition comprising hyaluronic acid and at least one polyol and/or carboxymethyl cellulose, and subjecting the composition to ionizing radiation at a dose of 8 kGy to 50 kGy, wherein the hyaluronic acid has a molecular weight between 105 and 107 Da and is present in the composition in an amount comprised between of 0.05% to 1% of the total weight of the composition, wherein the polyol is present in the composition in an amount between 1.0% to 75% of the total weight of the composition, and wherein the carboxymethyl cellulose is present in the composition in an amount between 1% and 5% of the total weight of the composition.
The instant claims recite subjecting a composition comprising hyaluronic acid and at least one polyol and/or carboxymethyl cellulose to ionizing radiation at a dose of 8 kGy to 50 kGy to perform the function of protecting the hyaluronic acid against degradation induced by the ionizing radiation.
The disclosure, however, does not provide a structure-function relationship or a representative
number of species which would allow an ordinary skilled artisan to identify which polyol compound at the recited amount as well as what type of ionizing radiation is needed to perform the recited function of protecting the hyaluronic acid against degradation induced by the ionizing radiation.
MPEP 2173.05(g) states that “A claim term is functional when it recites a feature “by what it
does rather than by what it is” and that “Unlimited functional claim limitations that extend to all means
or methods of resolving a problem may not be adequately supported by the written description or may
not be commensurate in scope with the enabling disclosure, both of which are required by 35 U.S.C.
112(a) and pre-AIA 35 U.S.C. 112, first paragraph.”
Furthermore, MPEP 2163 II.A.3.(a).ii. states that “Satisfactory disclosure of a "representative
number" depends on whether one of skill in the art would recognize that the inventor was in possession
of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which
embraces widely variant species cannot be achieved by disclosing only one species within the genus.”
Applicant has demonstrated in the disclosure and in the Declaration filed on 08/07/2025 several different hyaluronic acid (HA) formulations that protected the HA from ionizing radiation at doses ranging 8-50 kGy.
Applicant demonstrates the effect of beta irradiation on hyaluronic acid using five different HA compositions shown on page 13 and below:
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Applicant demonstrates these compositions containing either a polyol compound or CMC retained higher molecular weights of the hyaluronic acid in comparison to hyaluronic acid alone, indicating better protection and less degradation shown on page 15 and below:
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Applicant further shows in the declaration of Mr. Yannis Guillemin filed on 08/07/2025 additional tests that demonstrate that three different HA compositions comprising a polyol and/or carboxymethylcellulose has an effect in protecting hyaluronic acid from damage caused by ionizing radiation as shown below:
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Applicant demonstrates that these compositions were irradiated at 25-50 kGy, and shows that the compositions containing glycerol and/or CMC had higher molecular weights after irradiation in comparison to hyaluronic acid alone, indicating less hyaluronic acid is degraded and better protected shown below:
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While Applicant has demonstrated unexpected results in which eight different HA compositions were effective in causing less degradation of the HA when subjected to beta ionizing radiation at a dose of 8-50 kGy, these unexpected results are not commensurate in scope with the claimed invention, and Applicant has not demonstrated or provided further guidance that any polyol compound at the recited amounts as well as any type of ionizing radiation will result in the same effect.
The state of the art indicates polyols were not known to protect hyaluronic acid from ionizing radiation degradation, and further shows that there are various types of polyol compounds that will have different structures and properties. Furthermore, the state of the art indicates that gamma and beta irradiation can different effects / results.
RU’154 (RU2051154C1 in PTO-892, an English translation is provided) discloses a method for preventing depolymerization of hyaluronic acid (HA) solutions during sterilization with ionizing radiation (paragraph 0001).
RU’154 discloses that there are known to methods to protect HA from depolymerization during long-term storage by adding various compounds such as glycerin (glycerol) and others, however these compounds do not stabilize the structure during sterilization by autoclaving or gamma-radiation (paragraph 0004).
Findl (US20130338240A1 in PTO-892) discloses a viscoelastic fluid for producing a medicinal product for surgical eye treatment comprising at least one viscosity-increasing polymer such as hyaluronic acid, carboxymethyl cellulose, polyethylene glycol, and others (claim 1).
Findl discloses that their product is sterilized in a single terminal sterilization step via heat or hot steam (paragraph 0056), and further discloses that terminal sterilization with ionizing rays is inappropriate as it results in an uncontrolled degradation of the viscosity-increasing polymers in the fluid and the product no longer displays the necessary viscoelastic properties after sterilization (paragraph 0057).
Furthermore, Saleh (Construction and Building Materials, 2019 in PTO-892) discloses that polyols are compounds possessing two or more hydroxyl functional groups, and that there are different polyol groups based on the type of monomer that makes them similar to polyester polyols, polyether polyols, aromatic, or aliphatic polyols. Alternatively, polyols may be grouped based on their end use like high molecular weight polyols and lower molecular weight polyols (last paragraph left column page 741). Saleh discloses and shows in Table 3 (page 743) the structure of common types of polyols and a variation of the properties of polyurethanes due to different types of polyols (first paragraph right column page 741).
The teachings of RU’154, Findl, and Saleh suggest that it would not be predictable to an ordinary skilled artisan to determine what polyol compound is required in order to perform the recited protection function because the teachings of RU’154 indicate that a polyol compound (glycerol) was not known in the art to prevent HA degradation induced by ionizing radiation, and the teachings of Findl indicate that products that contain polymers such as hyaluronic acid, carboxymethyl cellulose, polyethylene glycol are not suitable for ionizing radiation sterilization as it results in uncontrollable degradation of the polymers. Furthermore, the teachings of Saleh indicate that there are different classes of polyols depending on their structures and molecular weight which can have different functional properties.
Montanari (Jounral of Controlled Release, 2003 in PTO-892) discloses that ionizing radiation is mainly used for the sterilization of heat sensitive materials and products (first paragraph right column page 281), and that raw materials or final products are typically sterilized using gamma-rays from a nuclear source or by electron beam (beta) (second paragraph left column page 282). Montanari discloses that while the main interaction with matter is basically the same for gamma-rays and high energy electrons, minor differences between the two modes remain (third paragraph left column page 282). Montanari discloses that gamma rays are a form of electromagnetic radiation characterized by high penetration into matter but at a very low dose rate (kGy/h), and on the contrary, beta rays are a form of corpuscular radiation characterized by low penetration into matter, but at a very high dose rate (kGy/s) (third paragraph left column page 282). Montanari discloses that these differences between gamma and beta rays can modify the performance of irradiated drug delivery systems, and that for the same administered radiation dose, beta ray treatment may cause an overheating of the material while gamma ray treatment could prolong the peroxidative radiolitic mechanism due to the exposure time (third paragraph left column page 282). Montanari discloses that previous research has conflicting results in regards to the effect of gamma irradiation on poly(lactide-co-glycolide) microspheres intended for parenteral use depending on the active ingredient used, and that no information is available at the moment on the effects of beta irradiated microparticulate systems made up of such copolymers (fourth paragraph left column page 282). Montanari further demonstrates that bupivacaine (BU) loaded microspheres were shown to be more stable against beta irradiation than gamma irradiation (Abstract). The teachings of Montanari suggest that it would not be predictable to an ordinary skilled artisan to determine what type of ionizing radiation is required to perform the recited protection function because Montanari indicates that there are differences between beta and gamma irradiation, and that at the same administered radiation dosages, the resulting effects can differ between the two types of ionizing radiation as described above.
It is not evident by the disclosure or the prior art, that the Applicant was in possession of using
any polyol compound at the recited amounts as well as any type of ionizing radiation for providing the function of protecting the hyaluronic acid from degradation induced ionizing radiation a dose of 8-50 kGy. Furthermore, as described above, there is no disclosed or art recognized correlation for what polyol compound at the recited amounts are needed to provide the protection function, and Applicant has only demonstrated eight specific HA compositions that were effective in causing less degradation of the HA when subjected to beta ionizing radiation at a dose of 8-50 kGy.
Therefore, the instant claims do not meet the written description requirement under 35 USC 112(a).
Response to Arguments
Applicant’s arguments filed on 05/19/2026 have been fully considered in so far as they apply to the rejections of the instant office action, but were not persuasive.
Applicant presents several arguments in regards to the previous prior art rejections, however no prior art rejections have been made in the instant Office Action, rendering Applicant’s arguments moot.
Conclusion
21-23, 25-29, and 37 are rejected.
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.
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/D.H.C./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner
Art Unit 1693
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