DETAILED CORRESPONDENCE
Application Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant’s amendment to the claims filed on 06/08/2026 in response to the Non-Final Rejection mailed on 02/09/2026 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
3. Claims 4-5, 9, 24, 34, and 39 are cancelled.
4. Claims 1, 14, 17, 20, 23, 27-29, 32, and 41-44 are pending.
5. Applicant’s remarks filed on 06/08/2026 in response to the Non-Final Rejection mailed on 02/09/2026 have been fully considered and are deemed persuasive to overcome at least one of the rejections and/or objections as previously applied.
The text of those sections of Title 35 U.S. Code not included in the instant action can be found in the prior Office Action.
Claim Rejections - 35 USC § 112(a)
6. The written description rejection of claims 1, 4-5, 9, 14, 17, 20, 23-24, 27-29, 32, 34, 39, and 41-44 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph is withdrawn in view of applicants’ amendment to the claims to cancel claims 4-5, 9, 24, 34, and 39 and to recite “an agent that increases GMP de novo synthesis selected from the group consisting of IMP, XMP, GDP, GTP, cGMP, guanine, IMP dehydrogenase, GMP synthase, and combinations thereof.”
7. The scope of enablement rejection of claims 1, 4-5, 9, 14, 17, 20, 23-24, 27-29, 32, 34, 39, and 41-44 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph is withdrawn in view of applicants’ amendment to the claims to cancel claims 4-5, 9, 24, 34, and 39 and to recite “an agent that increases GMP de novo synthesis selected from the group consisting of IMP, XMP, GDP, GTP, cGMP, guanine, IMP dehydrogenase, GMP synthase, and combinations thereof.”
Claim Rejections - 35 USC § 101
8. The rejection of claims 1, 4-5, 9, 14, 17, 20, 23-24, 27-29, 32, 34, 39, and 41-44 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception without significantly more is withdrawn in view of applicants’ amendment to the claims to recite “contacting the cell culture medium with GMP at a final concentration of 1 mM to 25 mM”, which upon further consideration of the claims in view of applicants’ remarks is sufficient to transform the claimed invention into something that is markedly different in structure from a natural process. The concentration of GMP is well above the concentration of GMP that would be naturally found inside the cell and therefore, transforms the process into something that is markedly different from a process that is naturally occurring.
Claim Rejections - 35 USC § 102
9. The rejection of claims 1, 4-5, 17, 20, 24, 27-29, 32, 39, 41, 42, and 43-44 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Collins et al. (US Patent Application Publication 2012/0277165 A1; cited on IDS filed on 04/09/2024) is withdrawn in view of applicants’ amendment to the claims to cancel 4-5, 9, 24, and 39 and to recite “a final concentration of 1 mM to 25 mM”.
Claim Rejections - 35 USC § 103
10. The rejection of claims 9, 14, 23, and 34 under 35 U.S.C. 103 as being unpatentable over Collins et al. (US Patent Application Publication 2012/0277165 A1; cited on IDS filed on 04/09/2024) is withdrawn in favor of the new rejection set forth below, which is necessitated by applicants’ amendment to the claims to incorporate limitations of now cancelled claim 9.
11. Claims 1, 14, 17, 20, 23, 27-29, 32 and 41-44 are newly rejected under 35 U.S.C. 103 as being unpatentable over Collins et al. (US Patent Application Publication 2012/0277165 A1; cited on IDS filed on 04/09/2024). This new grounds of rejection is necessitated by applicants’ amendment to the claims.
12. As amended, claims 1, 14, 17, 20, 23, 27-29, 41 and 43 are drawn to a method of reducing a high mannose glycan content of a protein expressed during a mammalian cell culture process, comprising: (1) establishing a mammalian cell culture expressing the protein in a cell culture medium;, and (2) contacting the cell culture medium with GMP at a final concentration of 1 mM to 25 mM or an agent that increases GMP de novo synthesis selected from the group consisting of IMP, XMP, GDP, GTP, cGMP, guanine, IMP dehydrogenase, GMP synthase, and combinations thereof, wherein the HMG is Man 5, and wherein the HMG content of the protein is reduced by at least 1% compared to the HMG content of the protein expresses in an essentially same cell culture except that the essentially same cell culture is not contacted with the GMP or the agent that increases de novo synthesis.
As amended, claims 32, 42, and 44 are drawn to a cell culture medium for reducing HMG content of a protein expressed during a mammalian cell culture process, comprising GMP at a final concentration of 1 mM to 25 mM, or an agent that increases GMP de novo synthesis selected from the group consisting of IMP, XMP, GDP, GTP, cGMP, guanine, IMP dehydrogenase, GMP synthase, and combinations thereof, wherein the GMP or the agent that increases GMP de novo synthesis is at a final concentration sufficient to reduce the HMG content of the protein by at least 1% compared to the protein expressed in an essentially same cell culture medium except that the essentially same cell culture medium does not include GMP or the agent that increases GMP de novo synthesis.
13. With respect to claim 1, Collins et al. teach a method of reducing high mannose glycan content of protein expressed during a mammalian cell culture process comprising: establishing a mammalian cell culture expressing the protein, and contacting the cell culture with guanosine 5’-monophosphate or another inhibitor to decrease levels of GDP-mannose and subsequently high mannose glycans [see Abstract; paragraphs 0004, 0009-0010, 0079]. Although Collins et al. does not explicitly teach that the HMG is Man 5, given that GDP-mannose is the basis for high mannose glycosylation of proteins, it is the examiner’s position that absent evidence otherwise, a reducing in GDP-mannose levels would inherently result in reducing Man 5. Since the Office does not have the facilities for examining and comparing applicants’ method with the method of the prior art, the burden is on the applicant to show a novel or unobvious difference between the claimed method and the method of the prior art (i.e., that the method of the prior art does not possess the same material structural and functional characteristics of the claimed method). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
With respect to claim 4, Collins et al. teach the method wherein step 2 comprises contacting the cell culture with GMP [see Abstract; paragraphs 0004, 0009-0010, 0079, 0122, 0133].
With respect to claim 5, Collins et al. teach the method wherein the agent that increases GMP de novo synthesis is guanosine diphosphate (GDP) [see paragraphs 0079 and 0133]. Although Collins et al. does not teach that the agent increases GMP de novo synthesis, given that Collins teaches an identical agent in identical methods, it is the examiner’s position that the increase GMP de novo synthesis is an inherent feature of the GDP agent taught by Collins. Since the Office does not have the facilities for examining and comparing applicants’ method with the method of the prior art, the burden is on the applicant to show a novel or unobvious difference between the claimed GDP and the GDP of the prior art (i.e., that the GDP of the prior art does not possess the same material structural and functional characteristics of the claimed GDP). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
With respect to claims 14 and 23, Collins et al. teach a method and cell cultures of reducing high mannose glycan content of protein expressed during a mammalian cell culture process comprising: establishing a mammalian cell culture expressing the protein, and contacting the cell culture with guanosine 5’-monophosphate or another inhibitor to decrease levels of GDP-mannose and subsequently high mannose glycans [see Abstract; paragraphs 0004, 0009-0010, 0079].
With respect to claim 17, Collins et al. teach the method wherein the cell culture is maintained by perfusion and teach selecting a time at which cell cultures are started or stopped, and selecting a time at which cell culture parameters are changed (interpreted as partial or entire period) [see paragraphs 0607-0608].
With respect to claim 20, Collins et al. teach the method wherein the cell culture is maintained by fed batch and teach selecting a time at which cell cultures are started or stopped, and selecting a time at which cell culture parameters are changed (interpreted as partial or entire period) [see paragraphs 0607-0608].
With respect to claims 24 and 27-29, Collins et al. teach the method wherein the high mannose glycan content of the protein is reduced 10%, 20%, and 30% [see paragraphs 0008-0009].
With respect to claim 32, Collins et al. teach a cell culture medium for reducing HMG content of a protein expressed during a mammalian cell culture process, comprising GMP, wherein the GMP concentration is sufficient to reduce HMG content of the protein by at least 1% [see Abstract; paragraphs 0004, 0008-0010, 0079].
With respect to claim 39, Collins et al. teach wherein the agent that increases GMP de novo synthesis is guanosine diphosphate (GDP) [see paragraphs 0079 and 0133]. Although Collins et al. does not teach that the agent increases GMP de novo synthesis, given that Collins teaches an identical agent in identical methods, it is the examiner’s position that the increase GMP de novo synthesis is an inherent feature of the GDP agent taught by Collins. Since the Office does not have the facilities for examining and comparing applicants’ culture medium with the culture medium of the prior art, the burden is on the applicant to show a novel or unobvious difference between the claimed GDP and the GDP of the prior art (i.e., that the GDP of the prior art does not possess the same material structural and functional characteristics of the claimed GDP). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
With respect to claim 41, Collins et al. teach the method wherein the mammalian cell culture is a CHO cell culture medium [see paragraph 0053].
With respect to claim 42, Collins et al. teach the mammalian cell culture is a CHO cell culture medium [see paragraph 0053].
With respect to claim 43, Collins et al. teach the method wherein the protein is a monoclonal antibody [see paragraph 0066].
With respect to claim 44, Collins et al. teach the cell culture medium wherein the protein is a monoclonal antibody [see paragraph 0066].
Although Collins et al. does not explicitly teach the methods and cell culture medium of wherein the GMP is at a final concentration of 1-25 mM; the method of claim 14, wherein the GMP is added to the cell culture between 3 and 15 days after the cell culture is established; and the method of claim 23, wherein the cell culture is maintained by combinations of perfusion and fed batch for a partial or entire period of the cell culture, Collins et al. does teach that production parameters than can be selected include addition or removal of media including when and how often media is harvested; increasing or decreasing speed at which cell cultures are agitated; increasing or decreasing temperature; adding or removing media such that cell culture density is adjusted; selecting a time at which cell cultures are started or stopped; and selecting a time at which cell culture parameters are changed and such parameters can be selected for any of the batch, fed-batch, perfusion and continuous culture conditions [see paragraph 0608]. As such, before the effective filing date of the claimed invention, it would have been obvious for one of ordinary skill in the art to optimize these parameters using the teachings of Collins et al., and one of ordinary skill in the art would desire to do so in order to maximize the condition desired by Collins et al., either decreased high mannose or increased high mannose. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
RESPONSE TO REMARKS: Beginning on p. 7 of applicants’ remarks, applicants in summary contend that reducing Man 5 specifically and the office’s position that this result is inherent is speculative. Furthermore, applicants contend that Collins does not teach the claimed concentration range and such range provides unexpected results that rebut any prima facie case of obviousness.
These arguments are found to be not persuasive in view of the new rejection set forth above. Furthermore, MPEP 2145.II states “[m]ere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979) (Claims were directed to grooved carbon disc brakes wherein the grooves were provided to vent steam or vapor during a braking action. A prior art reference taught noncarbon disc brakes which were grooved for the purpose of cooling the faces of the braking members and eliminating dust. The court held the prior art references when combined would overcome the problems of dust and overheating solved by the prior art and would inherently overcome the steam or vapor cause of the problem relied upon for patentability by applicants. Granting a patent on the discovery of an unknown but inherent function (here venting steam or vapor) "would remove from the public that which is in the public domain by virtue of its inclusion in, or obviousness from, the prior art." 596 F.2d at 1022, 201 USPQ at 661.); In re Baxter Travenol Labs., 952 F.2d 388, 21 USPQ2d 1281 (Fed. Cir. 1991) (Appellant argued that the presence of DEHP as the plasticizer in a blood collection bag unexpectedly suppressed hemolysis and therefore rebutted any prima facie showing of obviousness. However, the closest prior art utilizing a DEHP plasticized blood collection bag inherently achieved same result, although this fact was unknown in the prior art.). "The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious." Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985) (The prior art taught combustion fluid analyzers which used labyrinth heaters to maintain the samples at a uniform temperature. Although appellant showed that an unexpectedly shorter response time was obtained when a labyrinth heater was employed, the Board held this advantage would flow naturally from following the suggestion of the prior art.). See also Lantech Inc. v. Kaufman Co. of Ohio Inc., 878 F.2d 1446, 12 USPQ2d 1076, 1077 (Fed. Cir. 1989), cert. denied, 493 U.S. 1058 (1990) (unpublished — not citable as precedent) ("The recitation of an additional advantage associated with doing what the prior art suggests does not lend patentability to an otherwise unpatentable invention.").” In the instant case, the decrease in Man 5 as a result of GMP treatment is a latent property that flows from the teachings of Collins.
Even assuming arguendo, that GMP reducing Man 5 is an unexpected result, this argument is found to be not persuasive because the argument of unexpected results must be commensurate in scope with the claimed invention. MPEP 716.02(d) states “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.” In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980)”. In the instant case, the alleged unexpected property occurred in CHO cell lines; however, the claims are unlimited with respect to the type of mammalian cell. Accordingly, the alleged unexpected result is not commensurate in scope with the claimed invention.
Conclusion
14. Status of the claims:
Claims 1, 14, 17, 20, 23, 27-29, 32, and 41-44 are pending.
Claims 1, 14, 17, 20, 23, 27-29, 32, and 41-44 are rejected.
No claims are in condition for an allowance.
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 PAUL J HOLLAND whose telephone number is (571)270-3537. The examiner can normally be reached Monday to Friday from 8AM to 5PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached at 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL J HOLLAND/Primary Examiner, Art Unit 1656
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