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 .
Status of Application, Amendments and/or Claims
The amendment and Applicant’s arguments, filed 09 June 2026, have been entered in full. Claims 12, 14 and 15 are withdrawn from consideration as being drawn to a non-elected invention. Claims 2, 3, 5, 13, 16, 17 and 22 are canceled. Claims 1 and 4 are amended. Claims 1, 4, 6-11, 18-21 are under examination.
The Rosenkranz Declaration under 37 CFR 1.132, filed 09 June 2026, has been entered in full.
Claim Rejections-35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 4, 6-11, 18-20 remain rejected under 35 U.S.C. 102(a1) and 35 U.S.C. 102(a2) as being anticipated by Larson et al. (US 2015/0071925; published 12 March 2015) as evidenced by de Villiers et al. (Drug Development and Industrial Pharmacy, 25(8), 967-972; 1999).
The basis for this rejection is set forth originally at pages 5-6 of previous Office Action (15 October 2025) and pages 3-8 of previous Office Action (09 February 2026).
APPLICANT’S ARGUMENT ONE: Applicant disagrees with the arguments/response of the Examiner in the previous Office Action.
Applicant submits that under the doctrine of inherency, patent law requires that the element for which inherency is being relied must inevitably/necessarily happen always in the prior art for the legal crutch of inherency to be properly applied. Applicant argues that it is not adequate that the prior art is generic enough to "encompass" something that may happen, which appears to be the Office Action's approach. Applicant cites case law and MPEP 2112.
Applicant argues that the Office Action fails to provide a reasonable basis for the presumption that the missing portion of the prima facie case inherently is present. Applicant argues that Larson provides a plethora of undifferentiated viscosity-reducing agents and generally suggests that any combinations may be employed, and mentions nothing regarding viscosity reduction as in the claims herein.
Applicant argues that data are provided in the form of a Declaration that establish that there is no inherency in the present case, as even a single showing is adequate to overcome a rejection based on inherency as such clearly demonstrates that the missing portion of the prima facie case is NOT inherently/always/necessarily present. Applicant cites Ex parte Watanabe, No. 2016-5113, 2017 BL 311735 (P.T.A.B. August 25, 2017) holding that even one example is sufficient to fully rebut an inherency rejection.
Applicant argues that the submitted data demonstrate that combinations possible within Larson's disclosure do not possess the allegedly inherent property, therefore rendering the basis of this rejection inoperable. Applicant submits that in other words, prior-art combinations equally disclosed in Larson as the combinations recited in the claims herein fail to provide the claimed effect and fail to exhibit the synergistic viscosity reduction achieved by the claimed combinations. Applicant argues that one of the embodiments tested in the declaration concerns camphorsulfonic acid in combination with pyridoxine, the latter of which is even more clearly guided toward than claimed embodiments as pyridoxine is disclosed in Table 32 with accompanying data about its viscosity lowering effect. Applicant submits that the data show that synergy is not always observed with combinations of excipients taught by, e.g., Larson, for viscosity reduction.
Applicant argues that data are also submitted with regard to phenylalanine, which is taught in Shenoy's paragraph [[0282]).
Applicant maintains that the data provided show the opposite, i.e., that the viscosity reduction is not even additive, but rather lower than what one would expect. The expected viscosity of the combination leads to lower absolute viscosities than what was actually observed in each of the cases tested. Applicant submits that an allegation of inherency has been countered by clear evidence to the contrary. As such, the rejection cannot rely on the doctrine of inherency to establish that each element of the claim was met by the cited references.
Applicant’s arguments have been fully considered but are not found persuasive for the following reasons:
1. The Examiner has clearly stated a reasonable basis for the presumption that the missing portion of the prima facie case inherently is present. See the previous Office Action (09 February 2026; specifically at pages 7-8).
2. The Examiner understands that evidence might be presented in a Rule 132 Declaration to rebut the Examiner’s position of inherency in the prior art relevant to anticipation under 35 U.S.C. 102.
The Rosenkranz Declaration under 37 CFR 1.132 attempts to overcome the instant 102 rejections by showing that synergy is not always observed by showing data using a combinations of excipients.
3. The Rosenkranz Declaration states that equally taught cationic excipient(s) by the references (Larson teaching pyridoxine in Table 32 with accompanying data about its viscosity lowering effect, and Shenoy teaching pyridoxine in paragraphs [0044], [0209] and [0227] and phenylalanine in paragraph [[0282]), as those recited in the claims are shown herein to not lead to a synergistic viscosity reducing effect.
However, the Examiner notes that pyridoxine and phenylalanine are not recited in the instant claims.
Instant/independent claim 1 is drawn to a method for reducing the viscosity of a liquid composition comprising any protein in the amount range of at least 50 mg/ml up to 300 mg/ml, with any concentration of camphorsulfonic acid and any concentration of at least one cationic excipient selected from the group consisting of meglumine or ornithine, at any pH.
The data disclosed in the Declaration teaches a method for reducing the viscosity of a liquid composition comprising: the antibody infliximab at a specific amount of 150 mg/ml with a specific concentration of 75 mM phenylalanine and 75 mM camphorsulfonic acid, at a specific pH of 7.2 OR the antibody infliximab at a specific amount of 150 mg/ml with a specific concentration of 75 mM pyridoxine and 75 mM camphorsulfonic acid, at a specific pH of 7.2 OR the antibody evolocumab at a specific amount of 190 mg/ml with a specific concentration of 75 mM pyridoxine and 75 mM camphorsulfonic acid, at a specific pH of 5.0.
Thus, the data disclosed in the Rosenkranz Declaration and discussed by Applicant is not commensurate in scope with the claimed invention, as currently recited.
APPLICANT’S ARGUMENT TWO: Applicant maintains that the art is unpredictable as one could not tell which combinations lead to synergistic effect, additive effect or lower effect than additive without actually testing the combinations. Applicant argues that a person of ordinary skill would not even have had a reasonable expectation that selecting the claimed combinations would yield the claimed performance. As such, there is also no obviousness in the present case. Applicant argues that a vast generic disclosure as in the reference to Larson does not suggest a far narrower claim as recited in this application, as a matter of law, and particularly where there is no direction to one of ordinary skill to make the selections necessary to arrive at the claimed subject matter. Applicant asserts that this is not at all a case of a choice from among 20 specifically disclosed embodiments.
Applicant argues that in the Larson reference, N-methylglucamine appears exactly once in the disclosure buried in the lists of potential ingredients. Applicant cites Larson at paragraph [0295]. Applicant argues that camphorsulfonic acid appears at several locations in the disclosure of Larson, but argues that nowhere is camphorsulfonic acid and meglumine taught together in one combination, and furthermore in a viscosity reducing amount as recited in the claims.
Applicant argues that for anticipation, it is well established that a generic disclosure, to anticipate, must be directed to a recognizable small class of compounds, In re Schaumann, 572 F.2d 312,197 USPQ 5 (CCPA 1978) and that there can be no anticipation where a reference does not highlight the specific choices which must be made, among many dozen disclosed, In re Kollman, 595 F2d 48, 201 USPQ 193 (CCPA 1979) or where one of ordinary skill in the art would have to choose judiciously from a genus of possible combinations, without direction. In re Sivaramakrishnan, 673 F.2d 1382, 213 USPQ 441 (CCPA 1982). Applicant argues that when a reference does not highlight the choices necessary to arrive at a later claim, among "many dozen" disclosed, or where one of ordinary skill in the art must choose judiciously from a genus of possible combinations without guidance leading the artisan to a later claimed area, there is no anticipation. In re Kollman, 595 F2d 48, 201 USPQ 193 (CCPA 1979); In re Sivaramakrishnan, 673 F.2d 1382, 213 USPQ 441 (CCPA 1982).
Applicant argues that one skilled in the art would not be able to at once envision the specific combination of selections required to arrive at the claimed invention. Applicant argues that "envisage" means in view of numerous precedents that the scope is SO small that, in essence, the reference is particularly pointing out selection of these specific compounds. Applicant maintains that the scope of Larson is in no way small relative to the selections needed to arrive at Applicants' claims.
Applicant’s arguments have been fully considered but are not found persuasive for the following reasons:
1. The Examiner takes no issue with Applicant's general comments regarding the recited case law. However, the Examiner notes the following:
The instant claims fail to recite a particular concentration or a particular amount of camphorsulfonic acid, meglumine or ornithine that gives a “synergistic effect or additive effect” in the method.
The instant claims fail to recite a particular “viscosity reducing amount” of camphorsulfonic acid, meglumine or ornithine.
The instant claims fail to recite a particular concentration with a “viscosity reducing effect” for combined camphorsulfonic acid and meglumine.
The instant claims fail to recite a particular concentration with a “viscosity reducing effect” for combined camphorsulfonic acid and ornithine.
2. The Examiner maintains that Larson et al. is not a generic disclosure.
Larson et al. teach that an object of the present invention is to provide concentrated low-viscosity liquid formulations of proteins, especially high-molecular-weight proteins, such as mAbs. Larson et al. teach that it is also an object of the present invention to provide methods for making low-viscosity formulations of proteins, especially high-molecular-weight proteins, such as mAbs (paras 0016-0021).
Larson et al. teach that the term "viscosity-lowering agent," as used herein, refers to a compound which acts to reduce the viscosity of a solution relative to the viscosity of the solution absent the viscosity-lowering agent. The viscosity-lowering agent may be a single compound, or may be a mixture of one or more compounds.
Larson et al. teach that when the viscosity-lowering agent is a mixture of two or more compounds, the listed concentration refers to each individual agent, unless otherwise specified. For example, a formulation containing about 0.25 M camphorsulfonic acid arginine as the viscosity-lowering agent is a solution having camphorsulfonic acid at a concentration of 0.25 M, and arginine at a concentration of 0.25 M (para 0074). Larson et al. teach that in preferred embodiments, the viscosity-lowering agent is camphorsulfonic acid (para 0292).
Larson et al. teach in certain embodiments, the viscosity-lowering agent includes an organic base. Exemplary organic bases include N-methylglucamine, morpholine, piperidine, and primary, secondary, tertiary, and quaternary amines, substituted amines, and cyclic amines. Particularly preferred organic bases are arginine, histidine, lysine..” (para 0297).
The Examiner notes that camphorsulfonic acid is not only taught as a preferred viscosity-lowering agent, it is also employed in the Examples of Larson et al.
The Examiner notes that while the Examples of Larson et al. do not employ organic base N-methylglucamine (i.e. meglumine), the Examples employ other organic bases such as arginine and lysine. The Examples teach combinations of camphorsulfonic acid and organic base arginine; and combinations of camphorsulfonic acid and organic base lysine (nonetheless, disclosed examples and preferred embodiments do not constitute a teaching away from a broader or non-preferred embodiment).
The Examiner maintains that the Larson reference anticipates the invention, as currently claimed: a method for reducing the viscosity of a liquid composition comprising any protein in the amount range of at least 50 mg/ml up to 300 mg/ml, with any concentration of camphorsulfonic acid and any concentration of at least one cationic excipient selected from the group consisting of meglumine and ornithine.
The Examiner maintains that one of ordinary skill in the art would at once envisage the claimed subject matter from the Larson reference.
3. The Examiner has copied the teachings from MPEP 2131.02.
“A genus does not always anticipate a claim to a species within the genus. However, when the species is clearly named, the species claim is anticipated no matter how many other species are additionally named. See Ex parte A, 17 USPQ2d 1716 (Bd. Pat. App. & Inter. 1990) (The claimed compound was named in a reference which also disclosed 45 other compounds. The Board held that the comprehensiveness of the listing did not negate the fact that the compound claimed was specifically taught. The Board compared the facts to the situation in which the compound was found in the Merck Index, saying that "the tenth edition of the Merck Index lists ten thousand compounds. In our view, each and every one of those compounds is ‘described’ as that term is used in [pre-AIA ] 35 U.S.C. 102(a), in that publication."). Id. at 1718.
In the instant case, Larson et al. teach in certain embodiments, the viscosity-lowering agent includes an organic base. Organic bases would be the genus, wherein types of organic bases would be the species. Larson et al. teach exemplary organic bases include N-methylglucamine. The Examples teach preferred embodiment viscosity-lowering agent camphorsulfonic acid in combination with organic base arginine and in combination with organic base lysine.
Rosenkranz Declaration Under 1.132: The Declaration states that the Office Action alleges that the claim recited "viscosity reduction is achieved that is greater than the sum of the actions of the camphorsulfonic acid and the at least one cationic excipient" is inherent from the teachings of the cited references Larson US 2015/0071925 and Shenoy US 2018/0333493. The Declaration states that this affidavit provides supportive evidence countering the allegation of a synergistic viscosity reducing effect being inherent by the combination camphorsulfonic acid and at least one cationic excipient.
The Declaration states that equally taught cationic excipient(s) by the references (Larson teaching pyridoxine in Table 32 with accompanying data about its viscosity lowering effect, and Shenoy teaching pyridoxine in paragraphs [0044], [0209] and [0227] and phenylalanine in paragraph [[0282]), as those recited in the claims are shown herein to not lead to a synergistic viscosity reducing effect.
The Declaration states that as such, the allegation of inherency must fall in view of evidence to the contrary as inherency requires that the property being tested be necessarily present, i.e., inevitably present in all combinations. The Declaration states that the following experiments were conducted by a Merck KGaA internal team within the liquid formulation R&D Department in Germany. Experiments were performed in accordance with the described procedures in the original applications.
The Declaration submits that the data provided shows that synergy is not always observed with combinations of excipients. The Declaration states that one of ordinary skill in the art would consider this art unpredictable in this regard. The Declaration states that these data herein show the opposite, i.e., that the viscosity reduction is not even additive, but rather lower than what one would expect. The expected viscosity of the combination leads to lower absolute viscosities than what was observed in each of the cases above. The Declaration maintains that an allegation of inherency has been countered by clear evidence to the contrary. As such, the rejection cannot rely on the doctrine of inherency to establish that each element of the claim was met by the cited references.
The Rosenkranz Declaration under 37 CFR 1.132 has been fully considered but is not found persuasive.
The Rosenkranz Declaration under 37 CFR 1.132 filed 09 June 2026 is insufficient to overcome the rejection of claims 1, 4, 6-11, 18-20 under 35 U.S.C. 102(a1) and 35 U.S.C. 102(a2) as being anticipated by Larson et al. (US 2015/0071925; published 12 March 2015) as evidenced by de Villiers et al. (Drug Development and Industrial Pharmacy, 25(8), 967-972; 1999) AND the rejection of claims 1, 4, 6-11, 18-21 under 35 U.S.C. 102(a2) as being anticipated by Shenoy (US 2018/0333493; published 22 November 2018, priority date 16 May 2017) as evidenced by de Villiers et al. (Drug Development and Industrial Pharmacy, 25(8), 967-972; 1999), as set forth in the last Office action for the following reasons:
1. The Examiner understands that evidence might be presented in a rule 132 declaration to rebut the Examiner’s position of inherency in the prior art relevant to anticipation under 35 U.S.C. 102.
The Rosenkranz Declaration under 37 CFR 1.132 attempts to overcome the instant 102 rejections by showing that synergy is not always observed by showing data using a combinations of excipients.
2. As was stated above, the data disclosed in the Rosenkranz Declaration is not commensurate in scope with the claimed invention, as currently recited.
The Declaration states that equally taught cationic excipient(s) by the references (Larson teaching pyridoxine in Table 32 with accompanying data about its viscosity lowering effect, and Shenoy teaching pyridoxine in paragraphs [0044], [0209] and [0227] and phenylalanine in paragraph [[0282]), as those recited in the claims are shown herein to not lead to a synergistic viscosity reducing effect.
As was stated above, pyridoxine and phenylalanine are not recited in the instant claims. Instant/independent claim 1 is drawn to a method for reducing the viscosity of a liquid composition comprising any protein in the amount range of at least 50 mg/ml up to 300 mg/ml, with any concentration of camphorsulfonic acid and any concentration of at least one cationic excipient selected from the group consisting of meglumine or ornithine, at any pH.
The data disclosed in the Declaration teaches a method for reducing the viscosity of a liquid composition comprising: the antibody infliximab at a specific amount of 150 mg/ml with a specific concentration of 75 mM phenylalanine and 75 mM camphorsulfonic acid, at a specific pH of 7.2 OR the antibody infliximab at a specific amount of 150 mg/ml with a specific concentration of 75 mM pyridoxine and 75 mM camphorsulfonic acid, at a specific pH of 7.2 OR the antibody evolocumab at a specific amount of 190 mg/ml with a specific concentration of 75 mM pyridoxine and 75 mM camphorsulfonic acid, at a specific pH of 5.0.
Thus, the Declaration is not commensurate in scope with the claimed invention.
The scientific reasoning and evidence as a whole indicates that the rejection should be maintained.
Claims 1, 4, 6-11, 18-21 remain rejected under 35 U.S.C. 102(a2) as being anticipated by Shenoy (US 2018/0333493; published 22 November 2018, priority date 16 May 2017) as evidenced by de Villiers et al. (Drug Development and Industrial Pharmacy, 25(8), 967-972; 1999).
Applicant and the Rosenkranz Declaration under 37 CFR 1.132 incorporates their response to the rejection to claims 1, 4, 6-11, 18-20 under 35 U.S.C. 102(a1) and 35 U.S.C. 102(a2) as being anticipated by Larson et al. as evidenced by de Villiers et al., in response to the instant rejection to claims 1, 4, 6-11, 18-21 under 35 U.S.C. 102(a2) as being anticipated by Shenoy as evidenced by de Villiers et al.
Applicant’s arguments and the Rosenkranz Declaration under 37 CFR 1.132
have been fully considered but are not found to be persuasive for the reasons discussed above and reasons of record.
The scientific reasoning and evidence as a whole indicates that the rejection should be maintained.
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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/R.M.D/Examiner, Art Unit 1647 8/11/2026
/BRIDGET E BUNNER/Primary Examiner, Art Unit 1647
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