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 .
The amendment filed May 6, 2026, has been received and entered.
Claims 2, 4-9, 11, 13, and 15-19 are cancelled.
Claims 1, 3, 10, 12, 14, and 20-22 are pending and examined on the merits.
Notice Re: Prior Art Available Under Pre-AIA and 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.
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 1 is rejected under 35 U.S.C. 103 as being unpatentable over Murray (Molecular Genetics and Metabolism. 2015. 114: 217-225. Listed on IDS filed 8/18/23) in view of Schuchman `934 (US 2005/0153934. Previously cited), Zhou (Nature Communications. 2016. 7:13082. 10 pages. Previously cited), and Nyborg (Biochem. J. 2004. 381: e3-e4. Previously cited), and as evidenced by Wasserstein (Molecular Genetics and Metabolism. 2015. 116: 88-97. Listed on IDS filed 8/18/23).
Murray discloses performing safety studies in which recombinant human acid sphingomyelinase (rhASM) was administered to animals (abstract; page 218, right column, last three paragraphs). According to Wasserstein, the recombinant human acid sphingomyelinase of Murray is olipudase alfa. See page 89, left column, first paragraph of Wasserstein which refers to reference number 9, which is Murray, as teaching olipudase alfa, i.e. recombinant human acid sphingomyelinase. Murray discloses that lyophilized rhASM was resuspended in sterile water prior to use (page 218, right column, second paragraph). As such, Murray meets limitations of the claimed invention by disclosing a composition comprising a recombinant human acid sphingomyelinase, wherein the composition is a lyophilized composition comprising olipudase alfa.
Murray differs from the invention of instant claim 1 in that Murray does not expressly disclose that the lyophilized composition (lyophilized rhASM) comprises 4-7% w/w olipudase alfa (i.e., rhASM), 3-7% w/w sodium phosphate, 15-25% w/w L-methionine, and 65-75% w/w sucrose, wherein the composition contains no detectable amount of mannitol or chelating agents.
Murray discloses that the vehicle control in their studies contained 20 mM sodium phosphate, 5% sucrose, 100 mM methionine, and 0.1 mM ethylenediaminetetraacetic acid, pH 6.5 (page 218, right column, second paragraph).
Schuchman `934 discloses wild-type recombinant acid sphingomyelinase (ASM) as part of enzyme replacement therapy (paragraph [0025]). For lyophilization of ASM enzyme and small molecule active site-specific chaperones (ASSC) preparations, the enzyme concentration can be 0.1-10 mg/mL (paragraph [0088]). Additionally, Schuchman `934 teaches that possible cryoprotectants, such as disaccharides and amino acids, can be added to the lyophilization mixture (paragraph [0088]). Buffers can also be added to the lyophilization mixture (paragraph [0088]).
Before the effective filing date of the claimed invention, it would have been obvious to the person of ordinary skill in the art to prepare the lyophilized rhASM of Murray by including sodium phosphate, methionine, and sucrose with rhASM (i.e. olipudase alfa) and water to obtain an aqueous liquid composition comprising 20 mM sodium phosphate, 5% sucrose, 100 mM methionine, with a pH of 6.5, which is thereafter lyophilized. One of ordinary skill in the art would have been motivated to include these components with the rhASM to prepare the lyophilized rhASM of Murray because they are included in the vehicle control taught in Murray serving as the counterpart of lyophilized recombinant human acid sphingomyelinase resuspended in water, thus describing the composition of the reconstituted composition (when the lyophilized rhASM is resuspended in sterile water) in the absence of the enzyme itself. Furthermore, it would have been obvious to include sodium phosphate (which is directed to a buffer), sucrose, and methionine, in the lyophilized rhASM of Murray because Schuchman `934 teaches the inclusion of buffers and cryoprotectants such as disaccharides and amino acids in a lyophilized composition comprising acid sphingomyelinase. The composition rendered obvious by Murray in view of Schuchman `934 is directed to a composition containing no detectable amount of mannitol, meeting a claimed limitation.
Therefore, the lyophilized rhASM rendered obvious by Murray, Schuchman `934, Zhou, and Nyborg (as evidenced by Wasserstein) meets claimed limitations since it is directed to a composition comprising a recombinant human acid sphingomyelinase, wherein the composition is a lyophilized composition comprising olipudase alfa, sodium phosphate, L-methionine, and sucrose. The references differ from instant claim 1 in that they do not expressly disclose the claimed concentrations: 4-7% w/w olipudase alfa, 3-7% w/w sodium phosphate, 15-25% w/w L-methionine, and 65-75% w/w sucrose. However, it would have been an obvious matter of routine optimization to vary the concentrations of the rhASM (i.e. olipudase alfa), sodium phosphate, L-methionine, and sucrose in the lyophilized rhASM rendered obvious by Murray, Schuchman `934, Zhou, and Nyborg, including varying to the concentrations of instant claim 1, so that the rhASM is sufficiently protected in its lyophilized form; the concentrations of each of the rhASM (i.e. olipudase alfa) and the additional components relative to one another would have been recognized by the skilled artisan as results-effective parameters, the result being the stabilization of the rhASM in its lyophilized form. It is noted that “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Regarding the claimed limitation of the composition containing no detectable amount of chelating agents:
Zhou discloses that biological characterizations have revealed that proper function of human acid sphingomyelinase (ASM) requires zinc ions (page 2, left column, third paragraph). In particular, zinc ions are prerequisites for the two forms of ASM, an intracellular form and an extracellular secreted form (page 2, left column, third paragraph). Zhou investigated two crystal structures of recombinant human ASM, olipudase alfa, to observe how co-factor zinc ions and a product phosphocholine are coordinated by the enzyme (page 2, left column, second-to-last paragraph; page 2, right column, first paragraph for defining the enzyme as olipudase alfa). Zinc binding in the active site was observed, in which two neighboring zinc ions were identified in the center of the cleft of the catalytic domain (page 4, right column, second and third paragraphs). The human ASM structures reported in Zhou illustrate how the co-factor zinc ions activate the enzyme (page 6, left column, first paragraph).
Nyborg discloses that EDTA is a very potent zinc-chelating agent (abstract).
Though the vehicle control of Murray includes EDTA (directed to a chelating agent), before the effective filing date of the claimed invention, one of ordinary skill in the art would have been motivated to exclude EDTA when preparing the lyophilized rhASM rendered obvious by Murray and Schuchman `934. One of ordinary skill in the art would have been motivated to do this because human acid sphingomyelinase, including recombinant human acid sphingomyelinase (i.e., olipudase alfa), require zinc ions for its proper function, as indicated in Zhou. Since EDTA is a potent zinc-chelating agent according to Nyborg, then the skilled artisan would have expected that it would have been desirable to omit EDTA for the composition of rendered obvious by Murray and Schuchman `934 to ensure that the zinc binding to the active site of the rhASM is not interfered. Additionally, it would have been obvious to the person ordinary skill in the art to exclude EDTA because Schuchman `934 does not disclose EDTA or any other chelating agent amongst the materials for lyophilization of acid sphingomyelinase (paragraph [0088]). Therefore, Murray in view of Schuchman `934, Zhou, and Nyborg renders obvious a composition containing no detectable amount of chelating agents.
Additionally, it would have been obvious to include L-methionine as the methionine in the composition rendered obvious by Murray, Schuchman `934, Zhou, and Nyborg because it would have been a matter of simple substitution of one known form of methionine for another for the predictable result of providing an amino acid for lyophilization of acid sphingomyelinase as taught in Schuchman `934 (paragraph [0088]).
As such, Murray in view of Schuchman `934, Zhou, and Nyborg (as evidenced by Wasserstein) renders obvious instant claim 1.
Claims 3, 10, 12, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Murray, Schuchman `934, Zhou, and Nyborg, as evidenced by Wasserstein as applied to claim 1 above, and further in view of Schuchman `559 (US 2011/0052559. Previously cited) and Given (US 2007/0232671. Previously cited).
As discussed above, Murray in view of Schuchman `934, Zhou, and Nyborg (as evidenced by Wasserstein) renders obvious claim 1.
The references differ from claim 3 in that they do not expressly disclose a lyophilized composition consisting essentially of 5.5% w/w olipudase alfa (i.e. rhASM), 2.3% w/w sodium phosphate dibasic heptahydrate, 2.6% w/w sodium phosphate monobasic monohydrate, 20.5% w/w L-methionine, and 68.6% w/w sucrose.
The references differ from claim 10 in that they do not disclose a vial containing a lyophilized composition consisting essentially of 21.2 mg olipudase alfa (i.e. rhASM), 9.0 mg sodium phosphate dibasic heptahydrate, 10.0 mg sodium phosphate monobasic monohydrate, 79 mg L-methionine, and 265 mg sucrose. The references differ from claim 14 in that they do not expressly disclose an article of manufacture comprising the vial of claim 10 and a vial containing sterile water, 0.9% sodium chloride, or phosphate-buffered saline for reconstituting the lyophilized composition.
The references differ from claim 12 in that they do not disclose a vial containing a lyophilized composition consisting essentially of 4.8 mg olipudase alfa (i.e. rhASM), 2.0 mg sodium phosphate dibasic heptahydrate, 2.3 mg sodium phosphate monobasic monohydrate, 17.9 mg L-methionine, and 60 mg sucrose.
Regarding instant claims 10, 12, and 14, Schuchman `559 discloses a pharmaceutical product comprising a unit dosage form of acid sphingomyelinase (ASM) in an appropriate vessel or container, such as a glass vial (paragraph [0178]). In some embodiments, the unit dosage form is a lyophilized form of ASM, and under those circumstances, the pharmaceutical product may contain a second container with sterile saline or sterile water for reconstituting the lyophilized form of ASM (paragraph [0178]). Before the effective filing date of the claimed invention, it would have been obvious to the person of ordinary skill in the art to provide the lyophilized rhASM rendered obvious by Murray in view of Schuchman `934, Zhou, and Nyborg (as evidenced by Wasserstein) in a first vial, and further provide sterile water in a second vial. One of ordinary skill in the art would have been motivated to do this to facilitate reconstituting the lyophilized rhASM, as supported by the teaching of Schuchman `559.
Further still, Given discloses a buffer agent mixture such as sodium phosphate monobasic monohydrate and sodium phosphate dibasic anhydrous to improve drug stability in tablets of a drug (paragraph [0088]). Also, Given teaches a lyophilized powder comprising sodium phosphate dibasic heptahydrate and sodium phosphate monobasic monohydrate (paragraph [0134]).
Before the effective filing date of the claimed invention, it would have been obvious to substitute the sodium phosphate with a mixture of sodium phosphate dibasic heptahydrate and sodium phosphate monobasic monohydrate in the lyophilized rhASM composition rendered obvious by Murray in view of Schuchman `934, Zhou, and Nyborg (as evidenced by Wasserstein) in further view of Schuchman `559. It would have been a matter of simple substitution of sodium phosphate with other sodium phosphates for the predictable result of buffering the composition to obtain the desired pH of 6.5. There would have been a reasonable expectation of buffering the composition with a mixture of sodium phosphate dibasic heptahydrate and sodium phosphate monobasic monohydrate since Given teaches a buffer agent mixture of specifically sodium phosphate dibasic heptahydrate and sodium phosphate monobasic monohydrate for a lyophilized formulation.
Further still, it would have been a matter of routine optimization to vary the concentrations and amounts of the rhASM (i.e. olipudase alfa), sodium phosphate dibasic heptahydrate, sodium phosphate monobasic monohydrate, L-methionine, and sucrose in the lyophilized rhASM composition rendered obvious by Murray in view of Schuchman `934, Zhou, and Nyborg (in light of Wasserstein) in further view of Schuchman `559 and Given, specifically to the concentrations recited in instant claim 3, the amounts recited in instant claim 10 in the first vial, and the amounts recited in instant claim 12 in the first vial, so that the rhASM is sufficiently protected in its lyophilized form; the concentrations of each of the rhASM and the additional components relative to one another would have been recognized by the skilled artisan as results-effective parameters, the result being the stabilization of the rhASM in its lyophilized form. It is noted that “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Additionally, it would have been obvious to include the sodium phosphate dibasic heptahydrate, sodium phosphate monobasic monohydrate, L-methionine, and sucrose as the only additional components since it would have been obvious to include any combination of the agents recognized in the references for a lyophilized formulation. Therefore, instant claims 3, 10, 12, and 14 (sterile water) are rendered obvious.
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Murray, Schuchman `934, Zhou, and Nyborg, as evidenced by Wasserstein as applied to claim 1 above, and further in view of Jalkanen (US 2017/0246254. Previously cited).
As discussed above, Murray in view of Schuchman `934, Zhou, and Nyborg (as evidenced by Wasserstein) renders obvious claim 1. The references differ from claim 20 in that they do not expressly disclose that the lyophilized rhASM (directed to the claimed lyophilized composition) comprises no more than 0.1%, 0.2%, 0.3%, 0.4%, or 0.5% moisture.
Jalkanen discloses a pharmaceutical formulation in a lyophilized form, which comprises pharmacologically effective amount of interferon beta-1a (abstract), which is a protein based pharmaceutical (paragraph [0003]). The lyophilized formulation comprises interferon beta-1a as the active ingredient; a bulking agent which can be sucrose; disodium phosphate dihydrate, sodium dihydrogen phosphate dihydrate, trisodium citrate dihydrate, and any combination thereof as a buffering agent; a surfactant which can be polysorbate; and methionine as an antioxidant (paragraphs [0060]-[0065]). In one embodiment to the invention, the lyophilized formulation comprises 50-80 weight-% of disaccharides (e.g. sucrose) per vial, based on the total weight of the lyophilized formulation (paragraph [0047]). Jalkanen also teaches that the lyophilized formulation is prepared from an aqueous solution having a pH of 5.5-7.5 comprising the components (paragraphs [0072]-[0077]).
Also, Jalkanen teaches that the content of residual moisture of their lyophilized formulation may not be more than 5% by weight for promoting storage stability of the lyophilized formulation (paragraph [0059]).
Before the effective filing date of the claimed invention, it would have been obvious to the person of ordinary skill in the art to have adjusted the residual moisture of the lyophilized rhASM rendered obvious by Murray in view of Schuchman `934, Zhou, and Nyborg (as evidenced by Wasserstein) (see rejection of instant claim 1) to not more than 5% by weight, which necessarily includes residual moisture falling in the ranges of no more than 0.1%, 0.2%, 0.3%, 0.4%, or 0.5%, since doing so would have promoted storage stability of the lyophilized rhASM, based on the teaching for lyophilization of another protein in Jalkanen. Therefore, instant claim 20 is rendered obvious.
Claims 21 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Murray, Schuchman `934, Zhou, Nyborg, Wasserstein, Schuchman `559, and Given as applied to claims 3, 10, 12, and 14 above, and further in view of Jalkanen (US 2017/0246254. Previously cited).
As discussed above, Murray in view of Schuchman `934, Zhou, and Nyborg (as evidenced by Wasserstein) and in further view of Schuchman `559 and Given renders obvious claims 3, 10, 12, and 14. The references differ from claims 21 and 22 in that they do not expressly disclose that the lyophilized rhASM (directed to the claimed lyophilized composition) comprises no more than 0.1%, 0.2%, 0.3%, 0.4%, or 0.5% moisture.
Jalkanen discloses a pharmaceutical formulation in a lyophilized form, which comprises pharmacologically effective amount of interferon beta-1a (abstract), which is a protein based pharmaceutical (paragraph [0003]). The lyophilized formulation comprises interferon beta-1a as the active ingredient; a bulking agent which can be sucrose; disodium phosphate dihydrate, sodium dihydrogen phosphate dihydrate, trisodium citrate dihydrate, and any combination thereof as a buffering agent; a surfactant which can be polysorbate; and methionine as an antioxidant (paragraphs [0060]-[0065]). In one embodiment to the invention, the lyophilized formulation comprises 50-80 weight-% of disaccharides (e.g. sucrose) per vial, based on the total weight of the lyophilized formulation (paragraph [0047]). Jalkanen also teaches that the lyophilized formulation is prepared from an aqueous solution having a pH of 5.5-7.5 comprising the components (paragraphs [0072]-[0077]).
Also, Jalkanen teaches that the content of residual moisture of their lyophilized formulation may not be more than 5% by weight for promoting storage stability of the lyophilized formulation (paragraph [0059]).
Before the effective filing date of the claimed invention, it would have been obvious to the person of ordinary skill in the art to have adjusted the residual moisture of the lyophilized rhASM rendered obvious by Murray in view of Schuchman `934, Zhou, and Nyborg (as evidenced by Wasserstein) and further in view of Schuchman `559 and Given (see rejection of instant claims 10 and 12) to not more than 5% by weight, which necessarily includes residual moisture falling in the ranges of no more than 0.1%, 0.2%, 0.3%, 0.4%, or 0.5%, since doing so would have promoted storage stability of the lyophilized rhASM, based on the teaching for lyophilization of another protein in Jalkanen. Therefore, instant claims 21 and 22 are rendered obvious.
Response to Arguments
The rejections under 35 U.S.C. 103 of claims 4-9, 11, and 13 have been rendered moot by the cancelling of claims 4-9, 11, and 13 in the amendment filed August 28, 2025.
However, Applicant’s arguments are unpersuasive with respect to the rejections under 35 U.S.C. 103 of claims 1, 3, 10, 12, 14, and 20-22 which are maintained above. Applicant argues that for routine optimization, a person of ordinary skill in the art must have a starting point to optimize from. Applicant further points out that Murray provides no information on the amount of the enzyme to be reconstituted or the volume of water used for the reconstitution which Applicant argues would not permit one to fathom through back-calculation the relative w/w ratios of the enzyme, sodium phosphate, methionine, and sucrose in Murray’s lyophilized composition based on the vehicle control. The Examiner respectfully disagrees as a starting point is not a criteria as set forth in MPEP 2144.05(II) which discusses routine optimization. Since the components claimed are rendered obvious by the references, then it would have been within the purview of the skilled artisan to optimize the concentrations of the components in the lyophilized component based on the concentrations in the liquid composition.
Applicant further argues against the Examiner’s contention that it would have been obvious to exclude chelating agents from an rhASM composition based on Zhou and Nyborg. Applicant argues that while ASM needs zinc ions to exert its enzymatic function, a person of ordinary skill in the art would not have necessarily inferred from these references that an rhASM composition could not contain any chelating agent. However, the basis of the rejection is not whether the rhASM composition could not contain any chelating agent, and instead, it is that there would have been motivation to exclude EDTA from the composition rendered obvious by Murray and Schuchman `934 based on Zhou which showed that co-factor zinc ions activate recombinant human ASM, i.e. olipudase alfa. Since EDTA is a potent zinc-chelating agent according to Nyborg, then the skilled artisan would have expected that it would have been desirable to omit EDTA from the composition rendered obvious by Murray and Schuchman `934 to ensure that the zinc binding to the active site of the rhASM is not interfered.
Additionally, Applicant argues that it is possible that the enzyme itself during recombinant production already chelates the requisite zinc ions as part of the protein and having a chelating agent in an rhASM composition therefore would not affect the enzyme’s activity. However, Applicant has not provided evidence to support this argument. Applicant points out that Murray includes 0.1 mM EDTA in the vehicle control, which according to the Examiner, reflects the excipients of the water-reconstituted lyophilized rhASM, yet Murray shows that its rhASM composition was enzymatically active, and Murray raises no concern about using EDTA in rhASM formulations, so the skilled artisan would not have found it important to remove EDTA from an rhASM composition. However, Murray does not expressly disclose that the lyophilized rhASM comprises EDTA. Also, Murray does not disclose that EDTA is required for rhASM formulations. The only instance that EDTA is mentioned is with respect to the vehicle control. Even though Murray does not express concern about using EDTA in rhASM formulations, the teachings of Zhou would have motivated the skilled artisan to exclude EDTA from them.
Applicant also refers to Qiu which was cited by the Examiner in the Response to Arguments of the last Office Action. Applicant argues that Qiu studies the activity of rhASM, not its formulation or long-term storage stability. However, Qiu was cited by the Examiner in response to Exhibits 3 and 4 filed August 28, 2025, which Applicant previously asserted as indicating that chelating agents are needed for biological activity, not their formulation or long-term storage stability, of two other enzymes, trypsin and clostripain (see page 8, second-to-last paragraph of the response filed August 28, 2025). Applicant points out that Qiu discloses that some forms of ASM are found to be “cation-independent” because zinc is “already tightly associated with” such forms of ASM, making exogenous zinc unnecessary. It appears Applicant is referring to a passage on page 32744, right column, last paragraph of Qiu. However, this is in reference to the lysosomal form of ASM, as opposed to the recombinant ASM secreted from cells. That paragraph of Qiu also states that lysosomal and secretory forms can be inactivated by the zinc-specific chelator 1,10-phenanthroline – this provides motivation to modify Murray to exclude the known zinc-chelating agent EDTA.
Furthermore, Applicant asserts that the claimed lyophilized compositions demonstrate unexpected results. Applicant asserts that the present data demonstrate the claimed lyophilized olipudase alfa composition—with the specific weight ratios of the four components—exhibits superior stability over a period of six months, with minimal protein aggregation and an excellent cake morphology, citing paragraph [0088] of the original specification as an example. Also, Applicant cites paragraph [0089] of the specification for disclosing that decreased amounts of methionine in the lyophilized composition would lead to “dimpled and collapsed” composition, which Applicant asserts the cited art would not have predicted. However, paragraphs [0088]-[0089] of the specification are in Example 1 of the specification which discloses the concentrations of the components in the liquid composition instead of the lyophilized composition (paragraph [0085] disclosing 4 mg/ml olipudase alfa and 20 mM sodium phosphate; paragraph [0086] disclosing 5% w/v sucrose; paragraph [0087]). Paragraphs [0088] and [0089] evaluated methionine as a bulking agent by determining the effect of the addition of 100 mM L-methionine to the liquid composition. There is no teaching in Example 1 of the concentrations of the components in the lyophilized composition, so it cannot be concluded that Example 1, including its paragraphs [0088]-[0089], corresponds to the claimed lyophilized compositions. As pointed out in MPEP 716.02(d), “Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the ‘objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support.’” Since it cannot be concluded that the results of Example 1 are commensurate in scope with the claimed invention, then Applicant’s assertion of unexpected results is unpersuasive.
Furthermore, paragraph [0088] indicates that “…the addition of 100 mM L-methionine neither improved nor negatively impacted the liquid stability of olipudase alfa at 5ºC,” and “No changes in activity or aggregation were observed over the course of six months of storage at 5ºC.” Therefore, there does not appear to be a superior stability over a period of six months or minimal protein aggregation as argued by Applicant.
Conclusion
No claims are allowed.
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.
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Sef
/SUSAN E. FERNANDEZ/Examiner, Art Unit 1651
/DAVID W BERKE-SCHLESSEL/Primary Examiner, Art Unit 1651
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