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 .
The examiner acknowledges receipt of amendment and remarks filed 03/16/2026.
Claims 2 and 3 are canceled.
Claims 1, 4, 7 and 9 are amended.
Claims 1 and 4-22 are pending.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-13, in the reply filed on 11/03/2025 is acknowledged.
Claims 14-22 stand withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/03/2025.
Claims 1 and 4-13 are under consideration after the cancelation of claims 2 and 3.
Priority
This application claims benefit of 63/342,292 filed 05/16/2022.
Response to Arguments
The rejection of claim 9 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in light of the amendment to claim 9.
For rejection under 35 U.S.C. 102, the amendment moving claim 3 into claim 1 overcomes the rejection as claim 3 was not rejected under 35 U.S.C. 102. However, amended claim 1 will be rejected under 35 USC 103 below.
For the rejection under 35 U.S.C. 103, applicant argues that polylactide polymers are inherently linear citing Ranakoti et al., Table 3, Fig. 2a; and Naser et al. Polymers, 2021, 13, 4271, section 1.1 and Fig. 1; further, polylactide polymers exemplified in the Examples of the specification as filed teaching PURASORB PDL20, PD24 or PL24 polymers obtained from Cobion Purac are known to be linear. Applicant then argues that a) Mathiowitz uses nanoparticles of PLA to encapsulate GLP-1 or a related analogue to treat a mammal, b) paragraph [0250] of Mathiowitz shows that PLA is prepared into microparticles encapsulating GLP-1 by combining PLA and GLP-1 in methylene chloride and then rapidly pouring into light petroleum ether to form microspheres ranging in size of from 0.1-10 microns according to paragraph [0183] of Mathiowitz; c) the form of nanoparticles in Mathiowitz is different from the claimed polymer because, Mathiowitz shows in Fig. 7 that the use of PLA nanoparticles on non-GLP-1-containing particles were not effective to lower blood glucose levels and that this is in contrast to the claimed method utilizing polymer consisting of at least 15-200 DL-lactide and/or L-lactide monomer units which shows that polylactide polymers of various lengths (e.g. 20L-lactide units and 24 lactide units (see Fig. 5b), and 38 lactide units and 65 L-lactide units citing Fig.7e were effective to lower blood levels in comparison to control and lower molecular weight L-lactide polymers; and that the polymers of at least 15 L-lactide units are required to achieve the blood glucose-lowering effect and that Mathiowitz does not suggest this requirement, d) With regards to claims 6 and 8-10, applicant argues that the additional references Talasniemi, Borisovich and Pyo Kang do not overcome the deficiencies of Mathiowitz.
Response: The examiner appreciates applicant’s acknowledgement that polylactide polymers are inherently linear. a and b) The claims have not excluded nanoparticles. Applicant’s specification at paragraph [0048] reduces polymer to fine powder. c) Mathiowitz is not limited to PLA because, Mathiowitz teaches poly-L-lactide, poly-D-lactide, poly-D,L-lactide and that the polyesters lactic acid units such as poly-L-lactic acid, poly-D-lactic acid, poly-D,L-lactic, poly-L-lactide, poly-D-lactide, poly-D,L-lactide are collectively referred to as “PLA” (paragraph [0082]). Thus, reference to PLA in fig one is representative of poly-lactide and poly-lactic. Further also, contrary to applicant’s assertion, results in Fig. 7 shows that GLP-1/PLA reduced blood glucose (see paragraph [0279] and Fig. 7, PIN/PLA GLP-1). d) Tayama Kenji was relied upon as evidentiary reference for teaching that PEG is known to be non-digestible (example 2, JP 2001204440 A1, PE2E Trans). Kyung Pyo Kang was relied upon for teaching that D-lactate dehydrogenase metabolizes D-lactate (second full paragraph of left column of page 54 of Kyung Pyo Kang). Talasniemi was relied upon for teaching that D-Lactate concentration is significantly increased in the blood of diabetic animals and patients leading to acidosis, first full paragraph, left column of page 1100. Borisovich was relied upon for teaching that the accumulation of lactic acid leads to D-lactate acidosis (lines 7 and 8 of the first full paragraph at page 7 of the Eng translation). The claims are not limited to 24, 38, and/or 65 lactide unit but rather to 15-200 lactide units. The as filed specification does not specify lactide monomer units in PURASORB PDL20, PD24 or PL24 polymers.
Therefore, the rejection of the claims is maintained below with modification to address the amendment.
Modified Rejections
Necessitated by Amendment
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.
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, 4, 5, 7 and 11-13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mathiowitz et al., (US 20210162013 A1). The rejection is a modification in light of the amendment.
Claim 4 is amended to depend on claim 1. Claims 2 and 3 are canceled
Claim 1 lowers blood glucose by administering linear polymer consisting of 15-200 DL-lactide and/or L-lactide monomer units to a mammal. The “which inhibits or at least reduces D-lactate transport across the intestinal barrier” is the effect of the administered composition comprising the L-lactate monomer. L-lactate monomer is defined poly-DL-lactide or poly-L-lactide as per claim 5.
Mathiowitz discloses administering GLP-1 or analogues, which meets the limitation of therapeutic agent of claim 11 and GLP-1 of claim 12, to a mammal to reduce fasting blood glucose (see the whole document with emphasis on the abstract; paragraphs [0201]-[0204], [0232]-[0235]); the GLP-1 or the GLP-1 analogue is entrapped in one or more biodegradable polyesters namely poly-L-lactic acid, poly-D-lactic acid, poly-D,L-lactic acid, poly-L-lactide, poly-D-lactide, and poly-D,L-lactide (paragraphs [0009], [0082]), which meets the limitation of lactate monomer of claim 1 and specific monomer of claim 5. Mathiowitz teaches that GLP-1 encapsulated in PLA, PIN/PLA GLP-1) is effective in reducing blood glucose levels in diabetic mice (paragraph [0088]). With regards to “which inhibits or at least reduces D-lactate transport across the intestinal barrier,” it is the administered composition that effects the inhibition or reduction of the D-lactate transport across.
Mathiowitz teaches that the average molecular weight of the polymer ranges from about 1 kDa to about 200 kDa and up to specific polymers having molecular weights of about, 1 kDa, 2 kDa, 3 kDa, 4 kDa, 5 kDa, 6 kDa, 7 kDa, 8 kDa, 9 kDa, 10 kDa, 11 kDa and 12 kDa (paragraph [0091]). Molecular weight of lactide is 144.12 g/mole or Da
(https://en.wikipedia.org/wiki/Lactide#:~:text=All%20lactides%20are%20colorless%20or%20white%20solids.,has%20the%20formula%20%5BCH(CH%203)CO%202%5D%202)
Thus, for a 7 kDa, the number of units of lactide is 7000/144.12 = about 48 monomers; for a 9 kDa, the number of lactides units of lactide is 9000/144.12 = about 62 monomers; for a 5 kDa, the number of lactides units of lactide is 5000/144.12 = about 35 monomers. Therefore, for example, lactides monomers in the polylactide of Mathiowitz ranges from about 21 (3 kDa) to 83 (12 kDa) and these ranges are points within the claimed range.
Mathiowitz differs from claims 1 and 4 and 5 in that Mathiowitz does not specifically state the number of units of lactide monomers of the polylactide. However, before the effective date of the invention the artisan guided by the teachings of Mathiowitz would reasonably expect that the number of the lactide units of the disclosed polylactides would be calculated to predictably lie within the claimed range.
For claim 7, Mathiowitz teaches that polymer concentrations in the composition is at 0.01 to about 50% (paragraph [0092]). Mathiowitz differs from claim 7 by not teaching the amount of the polymer administered with respect to the weight of the mammalian subject. However, it is reasonable to expect that the artisan would use the polymer in effective amounts in relation to the wight of the mammalian subject (paragraph [0203]) that would be predictably sufficient to alleviate symptoms.
For claims 11 and 12, administration of GLP-1 (examined claims 11 and 12) encapsulated in poly-D,L-lactide and/or poly-L-lactide (examined claims 1 and 5) reduces or lowers blood glucose thereby teaching the elements of the claims.
For claim 13, Mathiowitz contemplates using hydrogel (paragraph [0108]).
Therefore, Mathiowitz renders claims 1, 4, 5, 7 and 11-13 prima facie obvious.
Claim(s) 1 and 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mathiowitz et al., (US 20210162013 A1), as applied to claim 1, and as evidenced by Tayama Kenji (JP 2001204440 A1, PE2E Trans, using PE2E translation).
Claim 6 depends on claim 1. Mathiowitz has been described above to render claim 1 has prima facie obvious.
Mathiowitz teaches that the polymers also include copolymers of polyethylene glycol (PEG) and the polyester and PLA-PEG is named as pegylated polymer (paragraph [0085]). Mathiowitz does not identify PEG as non-digestible. However PEG is known to be non-digestible as evidenced by example 2 of Tayama Kenji (JP 2001204440 A1, PE2E Trans). The composition of Mathiowitz is in particulate form comprising polymeric particles encapsulating the GLP-1 and the particles are microparticles ranging in sizes of less than 1000 micron (paragraphs [0024], [0029]-[0039]). It is the non-digestible microparticles that promote dwell time in the intestinal lumen.
Therefore, before the effective date of the invention the artisan would reasonably expect that the pegylated polyester PLA-PEG, which is PLA bound to nondigestible moiety, administered to the mammalian subject would reasonably promote dwell time in the intestinal lumen as it is the non-digestible microparticles that promote dwell time in the intestinal lumen.
Thus, Mathiowitz as evidenced by Tayama Kenji renders claim 6 prima facie obvious.
Claim(s) 1 and 8-10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mathiowitz et al., (US 20210162013 A1), as applied to claim 1, in view of Talasniemi et al., “Analytical investigation: Assay of D-lactate in diabetic plasma and urine” in Clinical Biochemistry 41 (2008) 1099-1103 (submitted in 1449), and Borisovich (RU 2736783 CI) and Kyung Pyo Kang et al., “D-Lactic Acidosis in Humans: Review of Update” in Electrolyte and blood pressure 4:53-56, 2006.
Claim 8 depends of claim 1. Claims 9 and 10 depend on claim 8.
Mathiowitz has been described above to render claim 1 prima facie obvious.
For claim 8, Mathiowitz does not teach that the composition used to lower/reduce blood glucose level in diabetic patients contains an agent that promotes metabolism of D-lactate.
Claim 10 narrows the agent in claim 8 to D-lactate metabolizing enzyme. Claim 9 narrows the agent in claim 8 to D-lactate dehydrogenase.
Talasniemi teaches that D-Lactate concentration is significantly increased in the blood of diabetic animals and patients leading to acidosis, first full paragraph, left column of page 1100.
Borisovich teaches that the accumulation of lactic acid leads to D-lactate acidosis (lines 7 and 8 of the first full paragraph at page 7 of the Eng translation).
Kyung Pyo Kang teaches that D-lactate dehydrogenase metabolizes D-lactate (second full paragraph of left column of page 54 of Kyung Pyo Kang).
Therefore, before the effective date of the invention, the ordinary skilled artisan would be motivated to include D-lactate dehydrogenase to the composition of Mathiowitz with the reasonable expectation of predictably metabolizing D-lactate to relieve D-lactate acidosis; D-lactate accumulates in diabetic patients causing acidosis. D-lactate dehydrogenase is a D-lactate metabolizing enzyme meeting the limitation of claims 10 and 8 and the D-lactate dehydrogenase enzyme of claim 9.
Therefore, Mathiowitz in combination with the teachings of Talasniemi, Borisovich and Kyung Pyo Kang renders claims 8-10 prima facie obvious.
No claim is allowed.
The amendment to claim 1 necessitated the modification of the rejections using the same prior art cited in the office action mailed 12/15/2025.
THIS ACTION IS MADE FINAL. 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.
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BLESSING M FUBARA whose telephone number is (571)272-0594. The examiner can normally be reached 7:30 am-6 pm (M-T).
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/BLESSING M FUBARA/Primary Examiner, Art Unit 1613
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