DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 17-32 are pending in the present application.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 25 March 2025 was filed before the mailing of an Office action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claims 17 and 22 are objected to because of the following informalities: claim 17, line 14, the term “andthen” should be amended to “and then”; claim 22, line 2, the comma in the recitation of “60°C,;” should be deleted. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claim 21 is 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.
Regarding claim 21, the phrase "more specifically" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 103
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.
Claims 17-26 and 28-32 are rejected under 35 U.S.C. 103 as being unpatentable over Ma et al. (CN 101376708 A) in view of Bentley et al. (US 5,990,237).
Ma et al. teach throughout a synthetic method for a propionaldehyde-terminated polyalkyl ether polymer, in particular to the synthetic method for a propionaldehyde-terminated polyethylene glycol polymer.
Regarding claim 17, Ma et al. teach that the synthetic method comprises the following steps: (1) the polyalkyl ether polymer and good leaving group substituted dimethoxy (or ethoxy) propionaldehyde acetal carries out the reaction in organic solvent in the presence of alkali, so as to obtain dimethoxy (or ethoxy) propionaldehyde acetal substituted polyalkyl ether polymer; (2) the propionaldehyde acetal substituted polyalkyl ether polymer is hydrolyzed in acidic aqueous solution, so as to obtain the propionaldehyde-terminated polyalkyl ether polymer. The molecular weight of the polyalkyl ether polymer is 200-80,000, preferably 2000-50,000 (Abstract; Examples; Claim 1).
Ma et al. do not explicitly disclose the small molecule acetal derivative I-2, as instantly claimed.
However, Ma et al. teach small molecule dimethoxy (or ethoxy) propionaldehyde acetal that is reacted with the polyalkyl ether polymer to obtain dimethoxy (or ethoxy) propionaldehyde acetal substituted polyalkyl ether polymer.
Bentley et al. teach PEG aldehyde hydrates that can be used in solution to form conjugates by reductive amination with a range of biologically active molecules, including proteins, peptides, polysaccharides, oligonucleotides, and small drug molecules (col. 3, ln. 2-9). Bentley et al. teach linking a PEG polymer with a functional group that can be converted to an aldehyde hydrate moiety, wherein the suitable functional group includes a 2-alkyl-1,3-dioxolane (equivalent to the claimed small molecule acetal derivative I-2) (Claim 1).
Also, Ma et al. do not explicitly disclose dissolving the small molecule acetal in an organic solvent followed by activating it with NaOH or KOH, instantly claimed.
However, Ma et al. teach carrying out the reaction in the presence of an alkali, such as NaOH. Ma et al. teach combining the small molecule acetal and PEG compound in an organic solvent followed by addition of the alkali (Examples 1-2).
It would have been prima facie obvious for a person of ordinary skill in the art prior to the effective filing date of the instant claims to change the order of addition steps according to Ma et al. such that the small molecule acetal is dissolved in organic solvent, addition of the alkali, and then addition of the PEG in an organic solvent. The order of combining the small molecule acetal, PEG, alkali and organic solvent is obvious to one of ordinary skill in the art, wherein Ma et al. teach that the reaction occurs after all components are combined at 90 °C for 24 hours. See also MPEP 2144.04(I)(C).
Also, it would have been prima facie obvious for a person of ordinary skill in the art prior to the effective filing date of the instant claims to substitute a cyclic acetal, such as the 1,3-dioxolane compounds according to Bentley et al., in the place of the dimethoxy or diethoxy acetal according to Ma et al., wherein the resulting cyclic acetal would be functionally equivalent to the dimethoxy or diethoxy acetals of Ma et al.
Regarding claims 18-19, Ma et al. teach mPEG2K, mPEG10K, mPEG20K and mPEG30K (Examples).
Regarding claim 20, Ma et al. teach that the functional groups between the PEG and the acetal include OH and methanesulfonates (Claim 1).
Therefore, it would have been prima facie obvious to prepare a PEG functionalized with a methanesulfonyl group and a cyclic acetal with an OH group, wherein the two compounds can be reacted to form a PEG-cyclic acetal derivative.
Regarding claim 21, Ma et al. teach that the organic solvent includes toluene, dioxane, N,N-dimethylformamide (DMF) and dimethyl sulfoxide (DMSO), preferred N,N-dimethylformamide and dimethyl sulfoxide (DMSO) (Claim 5).
Regarding claims 22-24, Ma et al. teach that the reaction temperature of the first step is 50-110 °C and the reaction time is 24-48 hours (Claims 7-8).
A person of ordinary skill in the art would have been able to determine through routine experimentation the optimum reaction conditions for the reaction to occur between the PEG and acetal compounds comprising a sulfonyl and OH reactive groups. It is common in organic synthesis to adjust reaction temperatures and times in order to optimize the amount of desired product.
Regarding the molar ratio of small molecule acetal to alkali reagent, Ma et al. teach that the amount of base used is more than one time, and preferably two to four times the amount of the good leaving group-containing acetal (Claim 6).
Regarding the molar ratio of PEG containing a sulfonyl functional group to small molecule acetal derivative containing OH functional group being from 1:10 to 1:160, Ma et al. teach that the ratio of the amount of the acetal substance to the PEG compound is greater than 6, including 8-12 (Claims 1, 4).
Regarding claim 25, Ma et al. teach the reaction under the protection of Ar gas (Examples 1-6).
Regarding claim 26, Ma et al. teach addition of the small molecule acetal to the PEG in organic solvent, and after reaction completion the product is precipitated in cold ether (Examples 1-6).
Regarding claims 28-30, Ma et al. teach that the acetal-substituted PEG is hydrolyzed under acidic conditions to obtain an aldehyde-substituted PEG (Claim 1).
Bentley et al. teach converting the acetal to an active aldehyde by hydrolysis in an aqueous solution at an acid pH, wherein the acid includes acetic acid, phosphoric acid, and trifluoroacetic acid (col. 5, ln. 45-67; Examples 2, 6; Claim 2).
Therefore, a person of ordinary skill in the art would have been motivated to use acetic acid or trifluoroacetic acid as suitable acids for hydrolyzing the acetal to obtain the aldehyde, as reasonably suggested by Bentley et al.
Regarding claims 31-32, Ma et al. teach modifying proteins with the PEG aldehyde compounds, wherein the amino group of the protein reacts with the aldehyde of the PEG aldehyde compound (Technical field and Background technique).
Claim 27 is rejected under 35 U.S.C. 103 as being unpatentable over Ma et al. (CN 101376708 A) in view of Bentley et al. (US 5,990,237) as applied to claims 17-26 and 28-32 above, further in view of Weng et al. (CN 106967213 A).
The teachings of Ma et al. and Bentley et al. are discussed above.
Regarding claim 27, Ma et al. teach precipitation in cold ether, but does not explicitly disclose recrystallization in a mixture of isopropanol and n-hexane in a volume ratio from 2:1 to 5:1, as instantly claimed.
Weng et al. teach preparation of an eight-arm polyethylene glycol functionalized with a bio-related substance (Abstract). Weng et al. teach coupling a small molecule reagent containing an acetal structure and the deprotection of the acetal. For example, by polyethylene glycol amine with 2,2-diethoxyacetic acid, 3,3-diethoxypropionic acid, 4,4-diethoxybutyric acid, 5,5-diethoxyvaleric acid. After the amidation reaction, the acetal protection is removed to give the corresponding -C(=O)-(CH2)0-3CHO aldehyde derivatives (pg. 66). Weng et al. further teach recrystallization in isopropanol/n-hexane 2:1 (v:v) (Examples 1-3).
It would have been prima facie obvious for a person of ordinary skill in the art prior to the effective filing date of the instant claims to recrystallize the product according to Ma et al. in a solvent mixture of isopropanol and n-hexane in a ratio of 2:1 (v:v), as taught by Weng et al.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nathan W Schlientz whose telephone number is (571)272-9924. The examiner can normally be reached 10:00 AM to 6:00 PM, Monday through Friday.
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, Sue Liu can be reached at (571) 272-5539. 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.
/N.W.S/Examiner, Art Unit 1616
/SUE X LIU/Supervisory Patent Examiner, Art Unit 1616
Prosecution Insights