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 .
Claims 1 and 3-19 are pending.
Claims 11-18 are withdrawn.
Claim 1 is amended.
Note, rejections and objections not reiterated from previous office actions are hereby withdrawn. The following rejections or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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 (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.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 19 are rejected under 35 U.S.C. 103 as being unpatentable over HIEMTSRA (Rapidly in Situ-Forming Degradable Hydrogels from Dextran Thiols through Michael Addition. Biomacromolecules. 2007.).
Regarding claim 19, HIEMSTRA teaches a composition comprising a hydrogel comprising crosslinking a dextran polymer substituted with thiols and a dextran polymer substituted with vinyl sulfone groups (abstract). The substitutions allowed for an elastic hydrogel that rapidly form in situ under physiological conditions, had adjustable degradation times to match a particular biomedical application, and the thiol groups in particular can allow for incorporation of thiol-containing bioactive molecules, such as proteins and peptides. (page 1555, paragraph 4).
HIEMSTRA does not teach adding thiol groups to the second dextran polymer, but rather only to the first.
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate thiol groups into the second dextran polymer. The person of ordinary skill in the art would have been motivated to make those modifications, because it would allow for more bioactive molecules to be added, such as proteins and peptides for further pharmaceutical purposes, and reasonably would have expected success because both thiol and vinyl groups are taught to be added to polymers and substitutions are frequently made in the art to achieve various pharmaceutical purposes.
The reference does not specifically teach the percentage of vinyl sulfone and thiol substitutions as claimed by the Applicant. The percentage of vinyl sulfone and thiol substitutions is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of the ordinary skill to determine the optimal percentage of vinyl sulfone and thiol substitutions in order to best achieve desired results, such as adjustable degradation times to match a particular biomedical application, and a suitable amount of locations for incorporation of other bioactive molecules such as proteins and peptides, since both of these benefits are correlated to the amount of substitution present on the dextran polymers. Thus, absent of some demonstration of unexpected results from the claimed parameters, this optimization of the percentage of vinyl sulfone and thiol substitutions would have been obvious at the time of Applicant’s invention.
Claim 1, 3-10 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over HIEMTSRA (Rapidly in Situ-Forming Degradable Hydrogels from Dextran Thiols through Michael Addition. Biomacromolecules. 2007.) in view of LEE (Indocyanine green-loaded injectable alginate hydrogel as a marker for precision cancer surgery. Quantitative Imaging in Medicine and Surgery. 2020.) and LYM (Sulfamethazine-based pH-sensitive hydrogels with potential application for transcatheter arterial chemoembolization therapy. Acta Biomaterilia. 2016.).
HIEMTSRA teaches Applicant’s invention as discussed above.
HIEMTSRA does not teach loading the hydrogel with a water-soluble fluorescent dye and fat-soluble contrast material.
Regarding claims 1, 4, 5, and 8, LEE teaches hydrogels that are loading with indocyanine green (ICG) (abstract), which is a water soluble, cyanine-based fluorescent dye. This allowed imaging of specified parts of the body for biological sites of interest (abstract). 1.5 mg of ICG was dissolved in 3mL of DI water and then 1 mL of that solution was added to 42.89 of hydrogel, which equals 0.011 mg/mL of ICG is present tin the composition (page 780, paragraph 6).
Regarding claims 1, 6 and 7, LYM teaches adding Lipidol, a long-lasting X-ray contrast agent that is a fat-soluble iodized oil, to a hydrogel (abstract). 10% Lipidol was added (page 256, paragraph 5). Lipiodol allowed for visualization of the specific region of interest after administration (abstract).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate ICG. The person of ordinary skill in the art would have been motivated to make those modifications, because it allows imaging of specified parts of the body for diagnostic/medical purposes, and reasonably would have expected success because the references are in the same field of endeavor, such as hydrogels. Furthermore, HIEMTSRA teaches that the hydrogels described are very promising for use in biomedical applications (page 1555, paragraph 4).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate Lipidol. The person of ordinary skill in the art would have been motivated to make those modifications, because it allows for visualization of the specific region of interest after administration, and reasonably would have expected success because the references are in the same field of endeavor, such as hydrogels. Furthermore, HIEMTSRA teaches that the hydrogels described are very promising for use in biomedical applications (page 1555, paragraph 4).
Regarding claims 3, The reference does not specifically teach the percentage of vinyl sulfone and thiol substitutions as claimed by the Applicant. The percentage of vinyl sulfone and thiol substitutions is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of the ordinary skill to determine the optimal percentage of vinyl sulfone and thiol substitutions in order to best achieve desired results, such as adjustable degradation times to match a particular biomedical application, and a suitable amount of locations for incorporation of other bioactive molecules such as proteins and peptides, since both of these benefits are correlated to the amount of substitution present on the dextran polymers. Thus, absent of some demonstration of unexpected results from the claimed parameters, this optimization of the percentage of vinyl sulfone and thiol substitutions would have been obvious at the time of Applicant’s invention.
Regarding claim 9, the intended use of “labeling lung lesions” in the composition claims is met by the prior art, because the prior art compositions would be at least capable of performing said use.
Regarding claim 10, note, even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process. In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). HIEMTSRA, LEE and LYM teach the composition of instant claim 1 and there is no evidence on the record that the method of making recited in claim 10 has effects on the final product.
Response to Arguments
Applicant argues, Hiemstra makes its hydrogels from two separate polymers. One is a dextran bearing only vinyl sulfone groups (dex-VS). The other is a separate dextran bearing only thiol groups (dex-SH). The hydrogel forms when the vinyl sulfone groups on one polymer react with the thiol groups on the other polymer. The two functional groups are on different polymers. Hiemstra does not disclose a single dextran polymer that carries both vinyl sulfone groups and thiol groups. Amended Claim 1 requires the second dextran polymer itself to carry both vinyl sulfone groups and thiol groups. Kyungpook has no functional groups at all, and Hiemstra puts the two groups on separate polymers. Neither reference discloses the claimed second dextran polymer and combining them does not produce it.
The examiner does not find the argument persuasive because as discussed above, although HIEMSTRA does not teach adding thiol groups to the second dextran polymer, but rather only to the first.
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate thiol groups into the second dextran polymer. The person of ordinary skill in the art would have been motivated to make those modifications, because it would allow for more bioactive molecules to be added, such as proteins and peptides for further pharmaceutical purposes, and reasonably would have expected success because both thiol and vinyl groups are taught to be added to polymers and substitutions are frequently made in the art to achieve various pharmaceutical purposes.
Applicant argues, none of the references teaches loading a water-soluble fluorescent dye and a fat-soluble contrast material together in one hydrogel. Lee has a water-soluble dye in an alginate gel, and Hohn separately has an iodized oil. The present application addresses the difficulty that these two materials have very different physical properties, one water-soluble and one fat-soluble, and shows that they can be held together in a single dextran-based hydrogel. As shown in the specification, a hydrogel loading indocyanine green together with iodized oil retained both materials over twenty-four hours, and in animal models both imaging signals stayed localized at the lung lesion. The references do not disclose this configuration or give any reason to arrive at it.
The examiner does not find the argument persuasive because as discussed above, LEE teaches hydrogels that are loading with indocyanine green (ICG) (abstract) and LYM teaches adding Lipidol, a long-lasting X-ray contrast agent (abstract) that is a fat-soluble iodized oil, to a hydrogel (abstract).
Both would be obvious to combine with the hydrogels of HIEMTSRA as discussed above for imaging purposes, especially since HIEMTSRA teaches that the hydrogels described are very promising for use in biomedical applications (page 1555, paragraph 4).
It would be inherent that the hydrogel described by the prior art would have the same chemical/physical properties as instantly claimed unless proven otherwise.
Conclusion
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 SAMANTHA L. MEJIAS whose telephone number is (703)756-5666. The examiner can normally be reached M-F.
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, MICHAEL HARTLEY can be reached at (571) 272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/S.L.M./ Examiner, Art Unit 1618 /JAKE M VU/Primary Examiner, Art Unit 1618
Prosecution Insights