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 view of the appeal brief filed on 3/2/2026, PROSECUTION IS HEREBY REOPENED. For the reasons set forth below.
To avoid abandonment of the application, appellant must exercise one of the following two options:
(1) file a reply under 37 CFR 1.111 (if this Office action is non-final) or a reply under 37 CFR 1.113 (if this Office action is final); or,
(2) initiate a new appeal by filing a notice of appeal under 37 CFR 41.31 followed by an appeal brief under 37 CFR 41.37. The previously paid notice of appeal fee and appeal brief fee can be applied to the new appeal. If, however, the appeal fees set forth in 37 CFR 41.20 have been increased since they were previously paid, then appellant must pay the difference between the increased fees and the amount previously paid.
A Supervisory Patent Examiner (SPE) has approved of reopening prosecution by signing below:
/Michael G. Hartley/ Supervisory Patent Examiner, Art Unit 1618
Election/Restrictions
Claim 3 is additionally withdrawn by the examiner for pertaining to an unelected species of triblock copolymer. Applicants elected a diblock copolymer PEG-PGA in their response to restriction requirement filed 7/24/2024.
Claim Rejections - 35 USC § 112
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 1-2,4,8-13,17-21,23-26,40-44 and 46 are rejected under 35 U.S.C. 112, 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(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 recites the limitation, “derivative” in reference to chitosan used in the complex. Applicant has not described the claimed genus of "derivative" in a manner that would indicate they were in possession of the full scope of this genus, or even to describe what this genus is comprised of. The instant specification does not describe these derivatives or their methods of preparation. Applicant has not described the claimed genus "derivative" in a manner that would indicate they were in possession of the full scope of this genus.
Regarding the requirement for adequate written description of chemical entities, Applicant's attention is directed to the MPEP §2163. In particular, Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568 (Fed. Cir. 1997), cert. denied, 523 U.S. 1089, 118 S. Ct. 1548 (1998), holds that an adequate written description requires a precise definition, such as by structure, formula, chemical name, or physical properties, "not a mere wish or plain for obtaining the claimed chemical invention." Eli Lilly, 119 F.3d at 1566. The Federal Circuit has adopted the standard set forth in the Patent and Trademark Office ("PTO") Guidelines for Examination of Patent Applications under the 35 U.S.C. 112.1 "Written Description" Requirement ("Guidelines"), 66 Fed. Reg. 1099 (Jan. 5, 2001), which state that the written description requirement can be met by "showing that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics," including, inter aria, "functional characteristics when coupled with a known or disclosed correlation between function and structure..." Enzo Biochem, Inc. v. Gen-Probe Inc., 296 F.3d 316, 1324-25 (Fed. Cir. 2002) (quoting Guidelines, 66 Fed. Reg. at 1106 (emphasis added)). Moreover, although Eli Lilly and Enzo were decided within the factual context of DNA sequences, this does not preclude extending the reasoning of those cases to chemical structures in general. Univ. of Rochester v. G.D. Searle & Co., 249 Supp. 2d 216, 225 (W.D.N.Y. 2003).
In the instant case, the claimed "derivative" encompasses any chitosan that contains what could be considered a chitosan core, with a differing of substituents quoted for the identical purpose. Applicants describe no "derivative" in the specification. Therefore, it is not described adequately enough to allow one skilled in the art to ascertain that Applicant is in possession of the entire scope of that genus. Applicants have not described this genus in a manner that would allow one skilled in the art to immediately envisage the compounds contemplated for use. As such, the claims lack adequate written description for the claimed "derivative." Claims 2,4,8-13,17-21,23-26,40-44 and 46 incorporate the written description deficiency by dependency.
The examiner suggests deleting the recitation of “derivative” in claim 1.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-2,4,8-13,17-21,23-26,40-44 and 46 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The recitation of "derivatives " found in claim 1 when referring to the type of chitosan renders the claim indefinite. The term “derivatives” is not defined by the claims, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear what is encompassed and excluded by the limitation "derivative”. The Merriam-Webster' s Dictionary defines “derivative” as “a chemical substance related structurally to another substance and theoretically derivable from it” ([online], retrieved on 12/9/2015, at: http://www.merriamwebster.com /dictionary/derivative. Hence, one of ordinary skill would clearly recognize that derivatives or analogues of the chitosan claimed in claim 1, would read on any of those compounds having any widely varying groups that possibly substitute the compound claimed. One of ordinary skill could not ascertain and interpret the metes and bounds of the patent protection desired as to these terms. Thus, it is unclear and indefinite as to how the “derivative” herein are encompassed thereby. Claims 2,4,8-13,17-21,23-26,40-44 and 46 incorporate the indefinites by dependency.
Regarding claim 42, this claim depends upon a canceled claim rendering it indefinite.
Regarding claim 46, this claim depends upon itself, rendering it indefinite.
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(s) 1-2,4,8-13,17-21,23-26,40-44 and 46 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gao et al. (2016/0235863) in view of Lou et al. “Fabrication of chitosan based nanocomposite with legumain sensitive properties using charge driven self-assembly strategy”, J Mater Sci: Mater Med 29, 142 (2018),cited previously, in view of Lollo et al. “Polyglutamic acid–PEG nanocapsules as long circulating carriers for the delivery of docetaxel”, European Journal of Pharmaceutics and Biopharmaceutics, Vol. 87, 2014, pages 47-54, cited previously.
Gao teaches derivatized chitosan nanoparticles featuring chitosan functionalized with cationic amino acid, including arginine, complexed with a nucleic acid, including DNA, for gene delivery, the amine to phosphate ratio (N:P) is particularly between 2 to 15, (2:1 to 15:1) higher than the lower limit recited in claim 1,12. See entire disclosure, especially abstract and claims, specially 1 and 12-17. Regarding claims 19-20, Gao teaches the use of excipients including surfactants, trehalose and mannitol. [0133]-[0135].
Gao is silent with respect to the elected species of PEG-PGA and the excipients of claim 21.
Lou is used primarily for the disclosure within that PEG-PGA was well known before the time of the claimed invention to form polyelectrolyte complexes (PEC) with charged amino acid modified chitosan with the anionic carboxylic acid on PGA ionically bound to the positively charged amino acid on chitosan with PEG extending from the core forming a shell (considered to read on outer coating). See entire disclosure especially abstract and Fig 1. The molecular weight of the PEG used was 5,000 Da, within the range recited in claims 9-10. See page 142 lft col. 1st full ¶. Regarding the number of repeat units of polypeptide recited in claim 11, Lou teaches how to add PGA by ring opening polymerization to PEG and adjusting the amount of starting material. Thus, the preparation of copolymer having variable amount of monomer with varying molecular weight is within the level of skill of one having ordinary skill in the art at the time of the invention. Regarding the ratio of amino to anion recited in claims 1 and 13, Lou teaches the size and zeta potential of CPNC could be rapidly controllable regulated by simply changing the ratio of CS and PEG-PGA in CPNC. Lou noted that such a strategy can be an easy way to prepare CS based NPs with good biocompatibility. See page 142 rt/ col 1st full ¶ and last ¶ page 142. Thus, adjusting the ratio of amino to anion is within the level of skill for one in this field of endeavor at the time of the invention. It has also been held that the mere selection of proportions and ranges is not patentable absent a showing of criticality. See In re Russell, 439 F.2d 1228 169 USPQ 426 (CCPA 1971).
Lollo is used for the disclosure within that PEG-PGA had noted advantages as carriers for therapeutic agents, including good blood compatibility, low complement activity and ability to remain in the blood stream for long periods of time. See entire disclosure, especially abstract and conclusion on page 53 rt. col. Lollo is also used for the disclosure that surfactants such as poloxamer and stabilizing excipients were well known to be useful in PEG-PGA particles. See page 48 lft col 2nd full ¶-1st ¶ rt col.
Since Lou teaches how to form complexes between PEG-PGA and amino acid functionalized chitosan and Gao teaches use of chitosan nanoparticle peptide delivery vehicles one of ordinary skill would have a high expectation of success in forming a complex between the nanoparticle and an outer shell or coating of PEG-PGA. Since Lollo teaches surfactants and stabilizers were useful in making similar PEG-PGA nanoparticles one of ordinary skill would also have a high expectation of success in using them in the particle of Lou. Reason to make such a modification would be to combine the advantages of the biodegradable polymers for biomedical application including good blood compatibility, low complement activity and prolonged longevity in the blood stream. Thus, the claimed invention would have been prima facie obvious since all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention.
Regarding claim 46, which recites a specific MW of PEG, PGA, N:P molar ratio and N:A molar ratio, the combined references are silent with respect to the specific values recited. However, the preparation of PEG chitosan nanoparticles having variable ratios between polymers with varying molecular weight is within the level of skill of one having ordinary skill in the art at the time of the invention. As noted above, Gao and Lou both present teachings on why one of ordinary skill would adjust these values by doing no more than following the teachings and suggestions within each. It has also been held that the mere selection of proportions and ranges is not patentable absent a showing of criticality. See In re Russell, 439 F.2d 1228 169 USPQ 426 (CCPA 1971).
Claim(s) 1-2,4,8-13,17-21,23-26,40-44 and 46 is/are rejected under 35 U.S.C. 103 as being unpatentable over Gao et al. (US 2016/0235863) in view of Cao et al. “Layer-by-Layer Assembled Multilayer Films of Methoxypoly(ethylene glycol)-block-poly-
(α,L-glutamic acid) and Chitosan with Reduced Cell Adhesion”, Macromol. Biosci. 2011, 11, 1211–1217, in view of Lollo et al., cited above.
Gao is disclosed above. Gao is silent with respect to the elected species of PEG-PGA and the excipients of claim 21.
Cao is used for its disclosure that PEG-PGA was already known at the time of the claimed invention to be used as a polyelectrolyte coating (film) over chitosan, bound through ionic bonds between the positively charged chitosan and the negatively charged PGA. See entire disclosure, especially abstract and Fig. 7. Cao teaches PEG has good biocompatibility, lacks toxicity and immunogenicity while PGA is biodegradable, has non-toxic features and provides a charge to PEG for fabricating biocompatible polyelectrolyte films. See ¶ bridging pages 1211-1212 and 1st full ¶ page 1212. The MW of PEG used was 3,000 Da and PGA was formed by ring opening polymerization using PEG-NH2. See page 1212 left col, last ¶-rt col 2nd full ¶. Regarding the limitation on N:A molar ratio, Cao uses a 1:1 ratio of chitosan to PEG-PGA and from Fig. 7 the interfacial layer contains 1 moiety on chitosan for every negatively charged carboxylic acid on PGA. Regardless one of ordinary skill in the art would know how to measure and calculate the percentage of reactive functional groups and adjust them to around 1:1, such that a film with desirable properties is produced. Regarding the number of repeat units of polypeptide recited in claim 11, Lou teaches how to add PGA by ring opening polymerization to PEG and adjusting the amount of starting material. Thus the preparation of a nanoparticle with varying ratios of reactive ionic groups and copolymer having variable amount of monomer with varying molecular weight is within the level of skill of one having ordinary skill in the art at the time of the invention. It has also been held that the mere selection of proportions and ranges is not patentable absent a showing of criticality. See In re Russell, 439 F.2d 1228 169 USPQ 426 (CCPA 1971).
Lollo is used for the disclosure within that PEG-PGA had noted advantages as carriers for therapeutic agents, including good blood compatibility, low complement activity and ability to remain in the blood stream for long periods of time. See entire disclosure, especially abstract and conclusion on page 53 rt. col. Lollo is also used for the disclosure that surfactants such as poloxamer and stabilizing excipients were well known to be useful in PEG-PGA particles. See page 48 lft col 2nd full ¶-1st ¶ rt col.
Since Cao teaches how to form complexes between PEG-PGA and chitosan and Gao teaches use of arginine functionalized chitosan in the peptide delivering nanoparticles one of ordinary skill would have a high expectation of success in forming a complex between the nanoparticle and outer shell or coating of PEG-PGA. Since Lollo teaches surfactants and stabilizers were useful in making similar PEG-PGA nanoparticles one of ordinary skill would also have a high expectation of success in using them in the particle of Gap. Reason to make such a modification would be to combine the advantages of the biodegradable polymers for biomedical application including good blood compatibility, low complement activity and prolonged longevity in the blood stream. Thus, the claimed invention would have been prima facie obvious since all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention.
Regarding claim 46, which recites a specific MW of PEG, PGA, N:P molar ratio and N:A molar ratio, the combined references are silent with respect to the specific values recited. However, the preparation of PEG chitosan nanoparticles having variable ratios between the polymer functional groups and polymers with varying molecular weight is within the level of skill of one having ordinary skill in the art at the time of the invention. As noted above, Gao and Cao both present teachings on how one of ordinary skill could adjust these values by doing no more than following the teachings and suggestions within each. It has also been held that the mere selection of proportions and ranges is not patentable absent a showing of criticality. See In re Russell, 439 F.2d 1228 169 USPQ 426 (CCPA 1971).
Response to Arguments
Applicant’s arguments with respect to claim(s) 1-2,4,8-13,17-21,23-26,40-44 and 46 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAMES W ROGERS whose telephone number is (571)272-7838. The examiner can normally be reached 9:30-6:00 PM.
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.
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/JAMES W ROGERS/ Primary Examiner, Art Unit 1618
Prosecution Insights