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 the Claims
Claims 1-78 were originally filed February 8, 2021.
The amendment received February 10, 2021 canceled claims 1-78 and added new claims 79-100.
The amendment received April 27, 2021 changed the status identifiers only.
The amendment received September 7, 2021 is a duplicate of the claims received April 27, 2021.
The amendment received August 10, 2022 amended claims 82, 85, 97, and 99 and canceled claims 96, 98, and 100.
The amendments received January 17, 2023 and May 5, 2023 amended claims 79, 81, 91-93, 95, and 97 and canceled claim 99.
The amendment received December 22, 2023 amended claims 79 and 97. Please note: present claim 97 has a status identifier of “Previously Presented” while the correct status identifier is “Currently Amended”.
The amendment received December 20, 2024 amended claims 79 and 97 and added new claims 101 and 102.
The amendment received July 2, 2025 amended claims 79 and 97 and cancelled claims 101 and 102.
The amendment received March 2, 2026 amended claims 79 and 97.
Claims 79-95 and 97 are currently pending.
Claims 79, 82-85, 87-93, and 97 are currently under consideration.
Please note: any addition of new claims may require a new Restriction/Species requirement.
Election/Restrictions
Applicants elected, without traverse, Group I (claims 79-95, 97, and 99) in the reply filed on August 10, 2022.
Applicants elected, without traverse, of mat-rVWF, at least 95% mature rVWF and less than 5% rVWF-PP, pH of at least 7, antibody column flow-through solution derived from a FVIII immunoaffinity step and an anion exchange chromatography step and pretreated with furin, citrate, NaOH, ion exchange chromatography, at least two wash buffers, at least one loading buffer, wash buffer, and elution buffer, acetate citrate, Na+, and citrate3- as the species in the reply filed on August 10, 2022. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Please note: applicants focused on the process for the election of species, the only election related to the final product is “at least 95% mature rVWF and less than 5% rVWF-PP”.
Please note: election of a subgenus, does not necessarily encompass other subgenus (e.g. pH of at least 7 does not necessarily encompass a pH of at least 7.1). In addition, if a subgenus is elected, only a subgenus is searched and not a single, specific species.
Claims 80, 81, 86, 94, and 95 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species, there being no allowable generic or linking claim.
Please note: applicants have already elected the Group and species without traverse. A traversal may not be presented after the initial election without traverse. If applicants believe that any withdrawn claim was withdrawn in error then applicants are invited to point out why a specific claim reads on the elected species. The subgenus example regarding the pH was an example only. This correlates to other elections (i.e. election of two wash buffers is not a specific species of wash buffer). Again, applicants may not alter the original election (i.e. election by original presentation).
Priority
The present application is a DIV of 16/359,939 filed March 20, 2019 (now U.S. Patent 10,934,340) which claims the benefit of 62/646,109 filed March 21, 2018.
Specification
The lengthy 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.
Claim Interpretation
Present independent claim 79 requires a final composition of (a) at least 95% mature VWF wherein mature VWF comprises ultra-large multimers (ULMs) over 40 subunits and at least 10,000 kDa, (b) less than 5% VWF-PP, and (c) a pharmaceutically acceptable buffer. Present independent claim 97 requires a final composition of (a) at least 95% mature VWF wherein mature VWF comprises ultra-large multimers (ULMs) over 40 subunits and at least 10,000 kDa and (b) less than 5% VWF-PP. Please note: recombinantly produced VWF is not considered distinct from non-recombinantly produced VWF. If applicants disagree, applicants should clearly state on the record how the recombinantly produced VWF differs from non-recombinantly expressed VWF and provide evidence. The cleavage by recombinant furin is no different than cleavage in vivo by furin. See Brehm, 2017, Von Willebrand factor processing, Hamostaseologie, 1: 59-72.
See MPEP § 2113 regarding product-by-process claims. Claims 79 and 97 are considered product-by-process claims and claims 82-85 and 87-93 refer to the process only (i.e. limitations of the claims are not part of the final product).
Functional limitations do not necessarily alter the product, particularly if the function is inherent to the product.
Arguments and Response
Applicants contend that recombinant VWF is distinct from WT/plasma VWF.
This is not found persuasive because the claims do not recite the specific structure that applicants are relying on to distinguish rVWF from non-recombinant VWF. In fact, the Gritsch et al. reference (2022, bio-protocol) provided by applicants specifically states that “VWF is released into the circulation from its storage granules as ultra-large VWF with ultra-high molecular weight (UHMW)” multimers (see Background, lines 7 and 8). Even though UHMW multimers are rapidly cleaved by ADAMTS13, UHMW VWF is present naturally (i.e. first secreted into the plasma prior to cleavage; in Weibel-Palade bodies in endothelial cells, a-granules of megakaryocytes, and platelets – see Stockschlaeder et al., 2014, Update on von Willebrand factor multimers: focus on high-molecular-weight multimers and their role in hemostasis, Blood Coagulation and Fibrinolysis, 25: 206-216). Gritsch et al. also states that naturally occurring VWF includes “multimers with apparent molecular masses between 500 kDa and 20,000 kDa” (see Background, lines 6 and 7). Thus, naturally occurring VWF meets the structural requirements of the present claims. Therefore, the inclusion of recombinant does not alter the structure of the claims (i.e. comprises ultra-large multimers (ULMs), wherein the ULMs comprise over 40 subunits and are at least 10,000 kDa). Furthermore, the examiner of record indicated that rVWF is not different from naturally occurring VWF structurally and/or functionally from the presently claimed structure. In addition, in Figure 3 of Gritsch et al. (2022, J Blood Medicine) provided by applicants shows that high MW bands are present. Figure 4 shows “background” on a low-resolution gel of 12.3% in the ultra large band area for plasma VWF. Moreover, the present claims with the exception of new claims 101 and 102 do not require a specific percentage of ultra-large multimers. Therefore, any ultra-high VWF reads on the present claims.
New Rejections Necessitated by Amendment
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 79, 82-85, 87-93, and 97 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection. Support in the originally filed specification was not found for “wherein the ratio of VWF-PP antigen to VWF antigen is below 1.0 ng/mg”.
Applicants pointed to Examples 4-6 and Figures 18, 30, and 32 for support of the new claim limitation.
Examples 4-6 do not teach “wherein the ratio of VWF-PP antigen to VWF antigen is below 1.0 ng/mg”. In fact, a ratio is never discussed in examples 4-6.
Example 4 refers to Figures 10-12. Figures 10-12 do not refer to a “ratio of VWF-PP antigen to VWF antigen is below 1.0 ng/mg”.
Example 5 refers to Figures 13 and 14. Figures 13 and 14 do not refer to a “ratio of VWF-PP antigen to VWF antigen is below 1.0 ng/mg”.
Example 6 refers to Figures 15 and 16. Figures 15 and 16 do not refer to a “ratio of VWF-PP antigen to VWF antigen is below 1.0 ng/mg”.
Figure 18 does not refer to a “ratio of VWF-PP antigen to VWF antigen is below 1.0 ng/mg”.
Figure 30 does not refer to an open-ended range of “below 1.0 ng/mg”. Figure 30 refers to specific individual vWF-PP/vWF ng/mg of 0.34, 1.10, 0.94, 163.3, 0.78, 0.34. and 0.62.
Figure 32 does not refer to an open-ended range or “below 1.0 ng/mg”. Figure 30 refers to specific individual vWF-PP/vWF ng/mg of less than 0.11 and 0.73.
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.
Claims 79, 82-85, 87-93, and 97 are 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. One of skill in the art would not be able to determine the scope of the present claims. For example, it is unclear how VWF compares to VWF antigen and how VWF-PP compares to VWF-PP.
Claims 79, 82-85, 87-93, and 97 are 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. One of skill in the art would not be able to determine the scope of the present claims. For example, it is unclear how “wherein the ratio of VWF-PP antigen to VWF antigen is below 1.0 ng/mg” correlates to “0.85 IU VWF Ristocetin/IU VWF antigen” (e.g. activity is typically related to concentration, the open ended ranges appear that a direct correlation is not present).
Claim 1 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.
Claim 1 recites the limitation "the ratio" in line 8. There is insufficient antecedent basis for this limitation in the claim.
Claim 97 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.
Claim 97 recites the limitation "the ratio" in line 8. There is insufficient antecedent basis for this limitation in the claim.
Maintained and/or Modified* Rejections
*wherein the modification is due to amendment
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 79, 82-85, 87-93, and 97 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
With regard to the written description requirement, the attention of the Applicant is directed to The Court of Appeals for the Federal Circuit which held that a “written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials.” University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1405 (1997), quoting Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993) (bracketed material in original) [The claims at issue in University of California v. Eli Lilly defined the invention by function of the claimed DNA (encoding insulin)] (the case is referred to herein as “Lilly”).
Additionally, it is noted that written description is legally distinct from enablement: “Although the two concepts are entwined, they are distinct and each is evaluated under separate legal criteria. The written description requirement, a question of fact, ensures that the inventor conveys to others that he or she had possession of the claimed invention; whereas, the enablement requirement, a question of law, ensures that the inventor conveys to others how to make and use the claimed invention.” See 1242 OG 169 (January 30, 2001) citing University of California v. Eli Lilly & Co.
Although directed to DNA compounds, this Eli Lilly holding would be deemed to be applicable to any compound or a generic of compounds; which requires a representative sample of compounds and/or a showing of sufficient identifying characteristics; to demonstrate possession of the compound or generic(s). In this regard, applicant is further referred to University of California v. Eli Lilly & Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997); “Guidelines for Examination of Patent Applications Under the 35 USC 112, first paragraph, ‘Written Description’ Requirement” published in 1242 OG 168-178 (January 30, 2001); and Univ. Of Rochester v G. D. Searle and Co. 249 F. Supp. 2d 216 (W.D.N.Y. 2003) affirmed by the CAFC on February 13, 2004 (03-1304) publication pending.
Additionally, Lilly sets forth a two part test for written description:
A description of a genus of cDNA’s may be achieved by means of a recitation of:
a representative number of cDNA’s, defined by nucleotide sequence, falling within the scope of the genus OR of a recitation of structural features common to the members of the genus.
See Regents of the University of California v. Eli Lilly & Co. 119 F.3d 1559 (Fed. Cir. 1997) at 1569.
Finally, University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404, 1405 held that:
...To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.
Additionally, Cf. University of Rochester v G.D. Searle & Co., Inc., Monsanto Company, Pharmacia Corporation, and Pfizer Inc., No. 03-1304, 2004 WL 260813 (Fed. Cir., Feb. 13, 2004) held that:
Regardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to that subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.
The present claims are drawn to a pharmaceutical composition comprising a high purity free mat-rVWF comprising ultra-large multimers comprising over 40 subunits and at least 10,000 kDa with a function of a specific activity of at least 0.85 IU VWF Ristocetin/IU VWF antigen wherein the ratio of VWF-PP antigen to VWF antigen is below 1.0 ng/mg and a pharmaceutically acceptable buffer (independent claim 79) or a pharmaceutical composition comprising a high purity free mat-rVWF comprising ultra-large multimers comprising over 40 subunits and at least 10,000 kDa with a function of a specific activity of at least 0.85 IU VWF Ristocetin/IU VWF antigen wherein the ratio of VWF-PP antigen to VWF antigen is below 1.0 ng/mg (independent claim 97). Independent claims 79 and 97 also have various product-by-process limitations wherein it is unclear from the specification how the process alters the final product. Dependent claims 82-85 and 88-93 are drawn to product-by-process steps only. The claims do not specifically require a structure necessary for the function of a specific activity of at least 0.85 IU VWF Ristocetin/IU VWF antigen.
In the present instance, the specification discloses “variations” 1-2140 (see Tables 3-9) without disclosing what exactly is in the “variations” or which variations have the function of at least 0.85 IU VWF Ristocetin/IU VWF antigen or the ratio of VWF-PP antigen to VWF antigen is below 1.0 ng/mg. The claims do not recite sufficient structural features which are common to members of the genus sufficient to demonstrate possession of the genus. The instant claims primarily “define” the product with process steps and not the actual final product. The claimed “high purity free mat-rVWF comprising ultra-large multimers comprising over 40 subunits and at least 10,000 kDa” is defined by a functional property (i.e. “specific activity of” “at least 0.85 IU VWF Ristocetin/IU VWF antigen”). The CAFC held that a functional definition is insufficient to adequately describe a product, therefore, an adequate written description not based on a functional definition is necessary.
The Examiner further notes the present claims stated by Applicant are broader in scope that those that were held to be impermissible in Lilly because, unlike Lilly, Applicants’ claims encompass a vast number of “variations” (e.g. at least the 2140 different variations disclosed in the specification). The scope of these claims include a vast number of pharmaceutical compositions because the specification and claims do not place a limit on the components required for the function of a specific activity of at least 0.85 IU VWF Ristocetin/IU VWF antigen. Therefore, Applicant is using an inadequately described “high purity free mat-rVWF” to inadequately describe the claimed “pharmaceutical composition”. In addition, the specific activity of at least 0.85 IU VWF Ristocetin/IU VWF antigen claim language further exacerbates this problem because the conditions under which the high purity free mat-rVWF will have the function are not specified. Consequently, there is no teaching that would allow a person of skill in the art to determine a priori that the Applicant was in possession of the full scope of the claimed invention at the time of filing because there is no common structural attributes that can link together all of the claimed high purity free mat-rVWF will have the function of a specific activity of at least 0.85 IU VWF Ristocetin/IU VWF antigen.
While the general knowledge and level of skill in the art for making VWF is high, this knowledge and level of skill does not supplement the omitted description because specific, not general, guidance is needed for the pharmaceutical composition comprising a high purity free mat-rVWF comprising ultra-large multimers comprising over 40 subunits and at least 10,000 kDa with a function of a specific activity of at least 0.85 IU VWF Ristocetin/IU VWF antigen. Since the disclosure fails to describe the common attributes or characteristics that identify all of the members of the genus or even a substantial portion thereof, and because the genus is vast and highly variant (e.g. at least the 2140 variations), the limited examples in the specification are insufficient to teach the entire genus.
The specification discloses only limited examples that are not representative of the claimed genus which has the function of a specific activity of at least 0.85 IU VWF Ristocetin/IU VWF antigen; nor do the claims recite sufficient structural feature(s) which is(are) common to members of the genus sufficient to demonstrate possession of the genus. Therefore, the teachings in the specification are general teachings relating without guidance as to the individual components of the product. In addition, there are numerous pharmaceutical compositions that could be employed in the invention with little direction or guidance for one of skill in the art to practice the claimed invention. The expedient statements in the specification do not relate to an adequate disclosure or how to make and use the claimed invention. Consequently, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to adequately describe the vast genus. Thus, Applicant does not appear to be in possession of the claimed genus.
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 112(a) (written description), for claims 79, 82-85, 87-93, and 97 were considered but are not persuasive for the following reasons.
Applicants contend the process for making the product as claimed negates the rejection. Applicants point to Gritsch et al. Applicants state that Gritsch et al. is filed as Exhibit A. It is respectfully noted that Gritsch et al. was filed with the IDS received March 2, 2026. All evidence should be filed as an Exhibit (see MPEP 42.63).
Applicants’ arguments are not convincing since applicants have not disclosed the composition of the at least 2140 different variations disclosed in the specification or which of the compositions have at least 95% mature rVWF verses less than 5% rVWF which have ultra-large multimers having over 40 subunits and a MW of at least 10,000 kDa. Applicants have also not disclosed which of the 2140 different variations have the functions as claimed (e.g. at least 0.85 IU VWF ristocetin/IU VWF antigen). In addition, an open-ended range of at least 0.85 IU VWF ristocetin/IU VWF antigen was not disclosed in the originally filed specification. Applicants have also not disclosed which of the 2140 different variations have the concentration as claimed (i.e. a ratio of VWF-PP antigen to VWF antigen is below 1.0 ng/mg). In addition, an open-ended ratio of below 1.0 ng/mg for VWF-PP antigen to VWF antigen was not disclosed in the originally filed specification. Therefore, applicants have not adequately described how to make the presently claimed product since it appears from the specification that at least 2140 different variations can be made with the same process and with unknown composition and functions.
Gritsch et al. does not provide a method of making the VWF products, but only refers to where the four products were manufactured (i.e. Table I).
It is unclear how comparing lot A and lot B of vonicog alfa (i.e. applicants assert that this is the same as the presently claimed pharmaceutical composition) to commercially available VWF negates the written description rejection. Written description must be present in the originally filed specification. Post-filing date data cannot be utilized to withdraw a written description rejection. Moreover, it is unclear how lot A and lot B of vonicog alfa were produced.
Applicants state that Gritsch et al. shows that lot A and lot B of vonicog alfa have activity above 1.0 while all other samples are below .80. It is respectfully noted that Figure 1 of Gritsch et al. shows that other VFW formulations are .80 (see Wilate®) and some are .79 which includes 0.80 when looking at the standard deviation (see Willfact®, Voncento®, Wilate®).
Moreover, individual experiments with more narrow method steps and products with more narrow components than those presently claimed cannot provide written description for products more broadly claimed.
The function of a specific activity of at least 0.85 IU VWF Ristocetin/IU VWF antigen is NEW MATTER and cannot be relied on to support written description.
While the specification discloses many “variations” (i.e. 1-2140; see Tables 3-9), the specification fails to disclose what exactly is in the “variations” or which variations have the function of at least 0.85 IU VWF Ristocetin/IU VWF antigen or the ratio of VWF-PP antigen to VWF antigen which is below 1.0 ng/mg.
Figure 11 is exactly the issue with the written description. ELU1 A10-C1 has the presently claimed function, but the exact components of the composition are unknown. In addition, it is unclear if ELU4 F11-I4 (<1.80) reads on the present claims or not since a range is provided instead of a specific data point. Furthermore, it is unclear how ELU2 C2-D1 and ELU3 D2-F6 which do not meet the functional requirement differ in structure from ELU1 A10-C1. Please also refer to Figures 6, 7, 14, 16, 18, etc. for other compositions that do not meet the functional requirement.
Tables 3 is labeled “Exemplary embodiments for the specific activity of rVWF found in the compositions and used in the methods provided herein” and provides variations 1-133 with concentrations.
Table 4 is labeled “Exemplary embodiments for the distribution of rVWF oligomers found in the compositions and used in the methods provided herein” and provides variations 458-641 with specific subunits.
The other Tables are similar in nature.
In addition, it is unclear how the variations discussed in the various Tables correlate to the various elutions (i.e. ELU) in the Figures.
Claims 79, 82-85, 87-93, and 97 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
Applicants previously pointed to Figures 11 (Example 4) and 14 (Example 5) for support of the amendments to independent claims 79 and 97 (i.e. wherein the specific activity of the mat-rVWF composition is at least 0.85 IU VWF Ristocetin/IU VWF antigen). It is respectfully noted, that Figures 11 and 14 do not contain open ended ranges (i.e. at least 0.85 IU VWF Ristocetin/IU VWF antigen) and therefore do not support the amendment in claims 79 and 97.
Paragraph 326 in the originally filed specification refers to at least 85 mU/mg (VWF:Ristocetin assay) and paragraph 332 in the originally filed specification refers to ratios of rFVIII procoagulant activity to rVWF Ristocetin cofactor activity.
Please note: applicants should utilize the same units as disclosed in the originally filed specification for the same assay as disclosed in the originally filed specification.
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 112(a) (new matter), for claims 79, 82-85, 87-93, and 97 were considered but are not persuasive for the following reasons.
Applicants contend that specific data points provide support for an open-ended range of at least 0.85 IU VWF ristocetin/IU VWF antigen.
Applicants’ arguments are not convincing since the Again, applicants are referring to specific data points to provide written description for a composition with an open-ended range of at least 0.85 IU VWF ristocetin/IU VWF antigen. Specific data points cannot provide written description for a composition with an open-ended range of at least 0.85 IU VWF ristocetin/IU VWF antigen.
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.
Claims 79, 82-85, 87-93, and 97 are 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. One of skill in the art would not be able to determine the scope of the presently claimed pharmaceutical composition. For example, it is unclear what structure is necessary for the function of a specific activity of at least 0.85 IU VWF Ristocetin/IU VWF antigen. This is particularly important since several “variations” of unknown composition in the specification do not have this function (see Table 3 and 8 – different assays, different functions). Furthermore, Figure 11 (Example 4) and Figure 14 (Example 5) which were provided as support for the amendment of a specific activity of at least 0.85 IU VWF Ristocetin/IU VWF antigen does not provide any structural information regarding the pharmaceutical composition.
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 112(b) (indefinite), for claims 79, 82-85, 87-93, and 97 were considered but are not persuasive for the following reasons.
Applicants contend that the process of making the composition provides the function. Applicants attempt to incorporate by reference several NPLs from the response received March 2, 2026 (see paragraph spanning pages 16 and 17).
Applicants’ arguments are not convincing since applicants disclose at least the 2140 variations of the composition made by the same method without disclosing what is in each composition or the functions of each of the compositions. In addition, the open-ended range of at least 0.85 IU VWF Ristocetin/IU VWF antigen is new matter (i.e. not even disclosed in the originally filed specification). It is not a matter of if one of skill in the art could test the 2140 variations provided by the present specification, but rather if the specification is clear as to which if the 2140 variations would possess the presently claimed function.
Incorporation by reference is not allowed after the filing date of the application. The incorporation by reference must be at the time of filing. In addition, anything that is necessary for patentability, must be incorporated by reference to a U.S. Patent or U.S. Patent Application Publicartion. See MPEP § 608.01(p) and § 2163.07(b).
Claims 79, 82-85, 87-93, and 97 are 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. One of skill in the art would not be able to determine the scope of the presently claimed pharmaceutical composition. For example, it is unclear what percentage of the pharmaceutical composition comprises ultra-large multimers of VWF.
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 112(b) (indefinite), for claims 79, 82-85, 87-93, and 97 were considered but are not persuasive for the following reasons.
Applicants contend that the inclusion of ratio of VWF-PP antigen to VWF antigen is below 1.0 ng/mg negates the rejection.
Applicants’ arguments are not convincing since the inclusion of a ratio of VWF-PP antigen to VWF antigen is below 1.0 ng/mg does not negate the rejection. It is unclear how the VWF antigen relates to the VWF and how the VWF-PP relates to the VWF-PP antigen. It is unclear how the ratio of VWF-PP antigen to VWF antigen is below 1.0 ng/mg relates to the at least 0.85 IU VWF Ristocetin/IU VWF antigen.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 79, 82-85, 87-93, and 97 are rejected under 35 U.S.C. 101 because the claimed invention is directed to mature VWF with or without VWF-PP without significantly more. The claims recite a “pharmaceutical composition comprising” “at least 95% mature rVWF” wherein mature VWF comprises ultra-large multimers (ULMs) comprising over 40 subunits and at least 10,000 kDa and less than 5% rVWF-PP” wherein a proportion of VWF multimers lower than hexamers in mature VWF is lower than in plasma derived VWF with or without a “pharmaceutically acceptable buffer” (see claim 79 and claim 97 - without) and a specific activity of at least 0.85 IU VWF Ristocetin/IU VWF antigen and a ratio of VWF-PP antigen to VWF antigen is below 1.0 ng/mg. This judicial exception is not integrated into a practical application because the present claims are drawn to products. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because pharmaceutically acceptable buffers are generically recited in the claims and are routine, well-understood, and conventional in the art. Furthermore, recombinant VWF or VWF-PP is not significantly different from naturally occurring VWF or VWF-PP. See Turecek et al., 2002, In vivo and in vitro processing of recombinant pro-von Willebrand factor, Histochem Cell Biol, 117: 123-129. The present specification also acknowledges that naturally occurring VWF comprises multimers of 500-20,000 kD made from 250 kD subunits (i.e. 2mers to 80mers; see paragraph 6). In addition, it is respectfully noted that ultra-large (UL) VWF forms prior to enzymatic cleavage and release of small VWF into plasma. See Brehm, 2017, Von Willebrand factor processing, Hamostaseologie, 1: 59-72. Furthermore, several disease states have UL-VWF which is not cleaved due to mutations in enzymes (e.g. wherein the enzyme ADAMTS-13 which cleaves UL-VWF is mutated causing either lower activity or no activity). See Nusrat et al., 2023, Hereditary Thrombotic Thrombocytopenic Purpura, Genes, 14: 1956 (14 pages). Furthermore, Stockschlaeder et al. teach that 100% of the VWF stored in Weibel-Palade bodies in endothelial cells and a-granules of megakaryocytes are ultra-high multimers of VWF and platelets have a large portion of ultra-high multimers of VWF (please refer to the abstract; Introduction; Biology of von Willebrand factor: synthesis and size distribution of multimers; Table 1; Figure 1; Stockschlaeder et al., 2014, Update on von Willebrand factor multimers: focus on high-molecular-weight multimers and their role in hemostasis, Blood Coagulation and Fibrinolysis, 25: 206-216).
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 101 as being drawn to a judicial exception for claims 79, 82-85, 87-93, and 97 were considered but are not persuasive for the following reasons.
Applicants contend that the presently claimed pharmaceutical composition has markedly different characteristics (i.e. both structural and functional) due to the “specific activity of the mat-rVWF composition is at least 0.85 IU VWF Ristocentin/IU VWF antigen” and a “ratio of VWF-PP antigen to VWF antigen is below 1.0 ng/mg” claim limitations. Applicants contend that the only form of VWF found naturally is in the plasma which has been cleaved by ADAMTS13. Applicants contend that there are additional elements and practical integration (i.e. via a composition prepared by a method that successfully reduces the existence of non-covalently associated mat-rVWF/rVWF-PP complex in a furin-processed pro-rVWF mixture).
Applicants’ arguments are not convincing since Stockschlaeder et al. teach that 100% of the VWF stored in Weibel-Palade bodies in endothelial cells and a-granules of megakaryocytes are ultra-high multimers of VWF and platelets have a large portion of ultra-high multimers of VWF (please refer to the abstract; Introduction; Biology of von Willebrand factor: synthesis and size distribution of multimers; Table 1; Figure 1). Stockschlaeder et al. also teach that ultra-high molecular weight multimers have the greatest activity in terms of hemostasis (i.e. binding capacity for collagen and the platelet receptors glycoprotein (GP) Ib and IIb/IIIa, and platelet aggregation under conditions of high fluid shear; please refer to the entire reference particularly the abstract; Introduction; Physiology of von Willebrand factor high-molecular-weight multimers: role in hemostasis and importance of multimer size; Figures 1, 3). See also Moake et al., 1986, Involvement of Large Plasma von Willebrand Factor (vWF) Multimers and Unusually Large vWF Forms Derived from Endothelial Cells in Shear Stress-induced Platelet Aggregation, J Clin Invest, 78: 1456-1461 which teach unusually large vWF multimers which have increased shear-stress induced platelet aggregation (please refer to the entire reference particularly the abstract; Introductions, Methods, Figures 2, 3). Additionally, Arya, 2002, Ultralarge multimers of von Willebrand factor form spontaneous high-strength bonds with the platelet glycoprotein Ib-IX complex: studies using optical tweezers, Blood, 99(11): 3971-3977 teach that ultralarge multimers of vWF have higher binding (please refer to the entire reference particularly the abstract; Introduction, Preparation of VWF and VWF-coated beads, Figures 1, 7).
It is also respectfully noted that the limitations applicants are relying on are new matter.
VWF is not only found in plasma, but also in endothelial cells, megakaryocytes, and platelets (see Stockschlaeder et al.). VWF found in endothelial cells and megakaryocytes have not been cleaved by ADAMTS13 and platelets include ultra-high multimers of VWF (see Stockschlaeder et al.).
The only additional elements present in the claims and the final composition are a pharmaceutically acceptable buffer in independent claim 79 and all dependent claims thereof. Pharmaceutically acceptable buffers are well understood, routine, and conventional in the art.
The present claims are drawn to a product, therefore a practical application (e.g. method) is not present.
Furthermore, it is respectfully noted that the present specification also acknowledges that naturally occurring VWF comprises multimers of 500-20,000 kD made from 250 kD subunits (i.e. 2mers to 80mers; see paragraph 6).
Regarding Grisch et al., it is respectfully noted that UL multimers must be present, but a specific amount is not required by the present claims. If a different property is present, the scope of the claims must be the same. Regarding the ratio of VWF-PP antigen to VWF antigen is below 1.0 ng/mg, this is new matter and it is unclear how the VWF antigen and VWF-PP antigen relate to VWF and VWF-PP.
The location of the VWF is immaterial since the present claims are drawn to a product and not a method of utilizing the product.
As evidenced by the present specification, not all compositions made by the presently claimed method have the presently claimed properties. See, at least, Figures 11, 14, 16, 18, etc.
A more narrow method of making cannot be utilized to overcome the present composition which requires a more broad method of making. In addition, it appears that the method of making can produce compositions that do not meet the presently claimed function and/or concentration (see Figures 11, 14, 16, 18, etc.).
Regarding Figure 30, it appears that only Examples 8 and 9 which are somehow “optimized” have the presently claimed ratio. It is unclear how Examples 8 and 9 differ from Examples 1-3.
Regarding Figure 32, a specific chelator (i.e. citrate) is not required by the present claims.
Claim Rejections - 35 USC § 102/Claim Rejections - 35 USC § 103
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.
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.
Claims 79, 82-87, 93, and 97 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Moake et al., 1986, Involvement of Large Plasma von Willebrand Factor (vWF) Multimers and Unusually Large vWF Forms Derived from Endothelial Cells in Shear Stress-induced Platelet Aggregation, J Clin Invest, 78: 1456-1461.
For present claims 79, 82-87, 93, and 97, Moake et al. teach compositions comprising unusually large (i.e. ultra large) VWF and a buffer (please refer to the entire reference particularly the abstract; Methods; Figures 2, 3). Please refer to the gels for an approximation of the percentage.
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[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." See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results) and In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution). See Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent") and In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.").
Therefore, the teachings of Moake et al. anticipate the presently claimed pharmaceutical composition.
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 102(a)(1) as being anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Moake et al. for claims 79, 82-87, 93, and 97 were considered but are not persuasive for the following reasons.
Applicants contend that Moake et al. do not teach all of the claimed elements. Applicants contend that there are unexpected results.
Applicants’ arguments are not convincing since the teachings of Moake et al. anticipate the product of the instant claims. Moake et al. teach a specific method to purify vWF multimeric forms and show gels of vWF purified from endothelial cell supernatant showing unusually large vWF forms wherein the lower bands are absent (please refer to the entire specification particularly methods, Figures 2 and 3).
The present claims are drawn to a product and not a method of making the product or a method of determining the specific activity of the product. Thus, the specific method steps for purifying the ULVWF are not required and the specific assay for determining the specific activity is not required.
Compositions comprising the same components would necessarily have the same function. Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. See In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "Products of identical chemical composition can not have mutually exclusive properties." See In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. See MPEP § 2112.01.
It is respectfully noted that the present specification acknowledges that naturally occurring VWF comprises multimers of 500-20,000 kD made from 250 kD subunits (i.e. 2mers to 80mers; see paragraph 6).
Unexpected results must be commensurate in scope with the present claims. Applicants are referring to a more narrow method of making the presently claimed product.
Claims 79, 82-87, 93, and 97 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Arya et al., 2002, Ultralarge multimers of von Willebrand factor form spontaneous high-strength bonds with the platelet glycoprotein 1b-IX complex: studies using optical tweezers, Blood, 99(11): 3971-3977.
For present claims 79, 82-87, 93, and 97, Arya et al. teach compositions comprising ultralarge VWF and a buffer (please refer to the entire reference particularly the abstract; Methods; Figure 1). Please refer to the gels for an approximation of the percentage.
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[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." See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results) and In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution). See Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent") and In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.").
Therefore, the teachings of Arya et al. anticipate the presently claimed pharmaceutical composition.
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 102(a)(1) as being anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Arya et al. for claims 79, 82-87, 93, and 97 were considered but are not persuasive for the following reasons.
Applicants contend that Arya et al. do not teach all of the claimed elements. Applicants contend that there are unexpected results.
Applicants’ arguments are not convincing since the teachings of Arya et al. anticipate the product of the instant claims. Arya et al. teach a specific method to purify vWF multimeric forms and show gels of vWF purified from endothelial cell supernatant showing unusually large vWF forms wherein the lower bands are absent (please refer to the entire specification particularly Preparation of VWF and VWF-coated beads, Figure 1).
The present claims are drawn to a product and not a method of making the product or a method of determining the specific activity of the product. Thus, the specific method steps for purifying the ULVWF are not required and the specific assay for determining the specific activity is not required.
Compositions comprising the same components would necessarily have the same function. Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. See In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "Products of identical chemical composition can not have mutually exclusive properties." See In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. See MPEP § 2112.01.
It is respectfully noted that the present specification acknowledges that naturally occurring VWF comprises multimers of 500-20,000 kD made from 250 kD subunits (i.e. 2mers to 80mers; see paragraph 6).
Unexpected results must be commensurate in scope with the present claims. Applicants are referring to a more narrow method of making the presently claimed product.
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.
Claims 79, 82-93, and 97 are rejected under 35 U.S.C. 103 as being unpatentable over Moake et al., 1986, Involvement of Large Plasma von Willebrand Factor (vWF) Multimers and Unusually Large vWF Forms Derived from Endothelial Cells in Shear Stress-induced Platelet Aggregation, J Clin Invest, 78: 1456-1461 and Bossard et al. WO 2008/082669 published July 10, 2008.
For present claims 79, 82-87, 93, and 97, Moake et al. teach compositions comprising unusually large (i.e. ultra large) VWF and a buffer (please refer to the entire reference particularly the abstract; Methods; Figures 2, 3). Please refer to the gels for an approximation of the percentage.
For present claims 88-92, Bossard et al. teach VWF including ultra large VWF and buffers including HEPES and MES wherein cations may be added including sodium and potassium and utilizing acetate (please refer to the entire specification particularly paragraphs 47, 51-58, 63, 64, 163, 179, 181, 184, 208, 227-229).
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[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." See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results) and In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution). See Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent") and In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.").
The claims would have been obvious because the substitution of one known element (i.e. genus of buffer) for another (i.e. HEPES or MES buffer with cations and/or anions) would have yielded predictable results (i.e. suspension of VWF in buffer) to one of ordinary skill in the ar6t at the time of the invention. The claims would have been obvious because a particular known technique (i.e. optimizing buffers) was recognized as part of the ordinary capabilities of one skilled in the art. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 103 as being unpatentable over Moake et al. and Bossard et al. for claims 79, 82-93, and 97 were considered but are not persuasive for the following reasons.
Applicants argue the prior art separately.
Applicants’ arguments are not convincing since the teachings of Moake et al. and Bossard et al. render the pharmaceutical composition of the instant claims prima facie obvious.
Moake et al. teach a specific method to purify vWF multimeric forms and show gels of vWF purified from endothelial cell supernatant showing unusually large vWF forms wherein the lower bands are absent (please refer to the entire specification particularly methods, Figures 2 and 3).
Compositions comprising the same components would necessarily have the same function. Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. See In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "Products of identical chemical composition can not have mutually exclusive properties." See In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. See MPEP § 2112.01.
It is respectfully noted that the present specification acknowledges that naturally occurring VWF comprises multimers of 500-20,000 kD made from 250 kD subunits (i.e. 2mers to 80mers; see paragraph 6).
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Bossard et al. is utilized to teach the buffer components only.
The claims would have been obvious because the substitution of one known element (i.e. genus of buffer) for another (i.e. HEPES or MES buffer with cations and/or anions) would have yielded predictable results (i.e. suspension of VWF in buffer) to one of ordinary skill in the ar6t at the time of the invention. The claims would have been obvious because a particular known technique (i.e. optimizing buffers) was recognized as part of the ordinary capabilities of one skilled in the art. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Claims 79, 82-93, and 97 are rejected under 35 U.S.C. 103 as being unpatentable over Arya et al., 2002, Ultralarge multimers of von Willebrand factor form spontaneous high-strength bonds with the platelet glycoprotein 1b-IX complex: studies using optical tweezers, Blood, 99(11): 3971-3977 and Bossard et al. WO 2008/082669 published July 10, 2008.
For present claims 79, 82-87, 93, and 97, Arya et al. teach compositions comprising ultralarge VWF and a buffer (please refer to the entire reference particularly the abstract; Methods; Figure 1). Please refer to the gels for an approximation of the percentage.
For present claims 88-92, Bossard et al. teach VWF including ultra large VWF and buffers including HEPES and MES wherein cations may be added including sodium and potassium and utilizing acetate (please refer to the entire specification particularly paragraphs 47, 51-58, 63, 64, 163, 179, 181, 184, 208, 227-229).
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[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." See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results) and In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution). See Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent") and In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.").
The claims would have been obvious because the substitution of one known element (i.e. genus of buffer) for another (i.e. HEPES or MES buffer with cations and/or anions) would have yielded predictable results (i.e. suspension of VWF in buffer) to one of ordinary skill in the ar6t at the time of the invention. The claims would have been obvious because a particular known technique (i.e. optimizing buffers) was recognized as part of the ordinary capabilities of one skilled in the art. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 103 as being unpatentable over Arya et al. and Bossard et al. for claims 79, 82-93, and 97 were considered but are not persuasive for the following reasons.
Applicants argue the references individually.
Applicants’ arguments are not convincing since the teachings of Arya et al. and Bossard et al. render the pharmaceutical composition of the instant claims prima facie obvious.
Arya et al. teach a specific method to purify vWF multimeric forms and show gels of vWF purified from endothelial cell supernatant showing unusually large vWF forms wherein the lower bands are absent (please refer to the entire specification particularly Preparation of VWF and VWF-coated beads, Figure 1).
The present claims are drawn to a product and not a method of making the product or a method of determining the specific activity of the product. Thus, the specific method steps for purifying the ULVWF are not required and the specific assay for determining the specific activity is not required.
Compositions comprising the same components would necessarily have the same function. Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. See In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "Products of identical chemical composition can not have mutually exclusive properties." See In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. See MPEP § 2112.01.
It is respectfully noted that the present specification acknowledges that naturally occurring VWF comprises multimers of 500-20,000 kD made from 250 kD subunits (i.e. 2mers to 80mers; see paragraph 6).
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Bossard et al. is utilized to teach the buffer components only.
The claims would have been obvious because the substitution of one known element (i.e. genus of buffer) for another (i.e. HEPES or MES buffer with cations and/or anions) would have yielded predictable results (i.e. suspension of VWF in buffer) to one of ordinary skill in the ar6t at the time of the invention. The claims would have been obvious because a particular known technique (i.e. optimizing buffers) was recognized as part of the ordinary capabilities of one skilled in the art. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 79, 82-85, 87-93, and 97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 8,058,411 in view of Arya et al., 2002, Ultralarge multimers of von Willebrand factor form spontaneous high-strength bonds with the platelet glycoprotein 1b-IX complex: studies using optical tweezers, Blood, 99(11): 3971-3977 and Bossard et al. WO 2008/082669 published July 10, 2008.
U.S. Patent No. 8,058,411 claims compositions comprising at least 99% mature VWF compared to VWF pro-peptide.
Arya et al. teach compositions comprising ultralarge VWF and a buffer (please refer to the entire reference particularly the abstract; Methods; Figure 1).
Bossard et al. teach VWF including ultra large VWF and buffers including HEPES and MES wherein cations may be added including sodium and potassium and utilizing acetate (please refer to the entire specification particularly paragraphs 47, 51-58, 63, 64, 163, 179, 181, 184, 208, 227-229).
See MPEP § 2113 regarding product-by-process claims.
The claims would have been obvious because the substitution of one known element (mat-VWF) for another (mat-VWF with ultralarge multimers) would have yielded predictable results (i.e. better activity) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because the substitution of one known element (i.e. genus of buffer) for another (i.e. HEPES or MES buffer with cations and/or anions) would have yielded predictable results (i.e. suspension of VWF in buffer) to one of ordinary skill in the ar6t at the time of the invention. The claims would have been obvious because a particular known technique (i.e. optimizing buffers) was recognized as part of the ordinary capabilities of one skilled in the art. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over U.S. Patent No. 8,058,411 in view of Arya et al. and Bossard et al. for claims 79, 82-85, 87-93, and 97 were considered but are not persuasive for the following reasons.
Applicants incorporate the arguments for the rejections above.
Applicants’ arguments are not convincing since the claimed invention of U.S. Patent No. 8,058,411 in view of Arya et al. and Bossard et al. renders obvious the pharmaceutical composition of the instant claims. In addition, while a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP § 714.02).
The response to the arguments from above are hereby incorporated.
Claims 79, 82-85, 87-93, and 97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 6,465,624 in view of Arya et al., 2002, Ultralarge multimers of von Willebrand factor form spontaneous high-strength bonds with the platelet glycoprotein 1b-IX complex: studies using optical tweezers, Blood, 99(11): 3971-3977 and Bossard et al. WO 2008/082669 published July 10, 2008.
U.S. Patent No. 6,465,624 claims purified VWF.
Arya et al. teach compositions comprising ultralarge VWF and a buffer (please refer to the entire reference particularly the abstract; Methods; Figure 1).
Bossard et al. teach VWF including ultra large VWF and buffers including HEPES and MES wherein cations may be added including sodium and potassium and utilizing acetate (please refer to the entire specification particularly paragraphs 47, 51-58, 63, 64, 163, 179, 181, 184, 208, 227-229).
See MPEP § 2113 regarding product-by-process claims.
The claims would have been obvious because a particular known technique (i.e. making compositions comprising high levels of mature VWF) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because the substitution of one known element (mat-VWF) for another (mat-VWF with ultralarge multimers) would have yielded predictable results (i.e. better activity) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because the substitution of one known element (i.e. genus of buffer) for another (i.e. HEPES or MES buffer with cations and/or anions) would have yielded predictable results (i.e. suspension of VWF in buffer) to one of ordinary skill in the ar6t at the time of the invention. The claims would have been obvious because a particular known technique (i.e. optimizing buffers) was recognized as part of the ordinary capabilities of one skilled in the art. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over U.S. Patent No. 6,465,624 in view of Arya et al. and Bossard et al. for claims 79, 82-85, 87-93, and 97 were considered but are not persuasive for the following reasons.
Applicants incorporate the arguments to the above rejections.
Applicants’ arguments are not convincing since the claimed invention of U.S. Patent No. 6,465,624 in view of Arya et al. and Bossard et al. renders obvious the pharmaceutical composition of the instant claims. In addition, while a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP § 714.02).
The response to the above arguments are hereby incorporated.
Claims 79, 82-85, 87-93, and 97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-51 of U.S. Patent No. 6,579,723 in view of Arya et al., 2002, Ultralarge multimers of von Willebrand factor form spontaneous high-strength bonds with the platelet glycoprotein 1b-IX complex: studies using optical tweezers, Blood, 99(11): 3971-3977 and Bossard et al. WO 2008/082669 published July 10, 2008.
U.S. Patent No. 6,579,723 claims purified VWF.
Arya et al. teach compositions comprising ultralarge VWF and a buffer (please refer to the entire reference particularly the abstract; Methods; Figure 1).
Bossard et al. teach VWF including ultra large VWF and buffers including HEPES and MES wherein cations may be added including sodium and potassium and utilizing acetate (please refer to the entire specification particularly paragraphs 47, 51-58, 63, 64, 163, 179, 181, 184, 208, 227-229).
See MPEP § 2113 regarding product-by-process claims.
The claims would have been obvious because a particular known technique (i.e. making compositions comprising high levels of mature VWF) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because the substitution of one known element (mat-VWF) for another (mat-VWF with ultralarge multimers) would have yielded predictable results (i.e. better activity) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because the substitution of one known element (i.e. genus of buffer) for another (i.e. HEPES or MES buffer with cations and/or anions) would have yielded predictable results (i.e. suspension of VWF in buffer) to one of ordinary skill in the ar6t at the time of the invention. The claims would have been obvious because a particular known technique (i.e. optimizing buffers) was recognized as part of the ordinary capabilities of one skilled in the art. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over U.S. Patent No. 6,579,723 in view of Arya et al. and Bossard et al. for claims 79, 82-85, 87-93, and 97 were considered but are not persuasive for the following reasons.
Applicants incorporate the above arguements.
Applicants’ arguments are not convincing since the claimed invention of U.S. Patent No. 6,579,723 in view of Arya et al. and Bossard et al. renders obvious the pharmaceutical composition of the instant claims. In addition, while a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP § 714.02).
The response to the above arguments are hereby incorporated.
Claims 79, 82-85, 87-93, and 97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 9,315,560 in view of Arya et al., 2002, Ultralarge multimers of von Willebrand factor form spontaneous high-strength bonds with the platelet glycoprotein 1b-IX complex: studies using optical tweezers, Blood, 99(11): 3971-3977 and Bossard et al. WO 2008/082669 published July 10, 2008.
U.S. Patent No. 9,315,560 claims purified VWF.
However, U.S. Patent No. 9,315,560 does not specify mature VWF.
Arya et al. teach compositions comprising ultralarge VWF and a buffer (please refer to the entire reference particularly the abstract; Methods; Figure 1).
Bossard et al. teach VWF including ultra large VWF and buffers including HEPES and MES wherein cations may be added including sodium and potassium and utilizing acetate (please refer to the entire specification particularly paragraphs 47, 51-58, 63, 64, 163, 179, 181, 184, 208, 227-229).
See MPEP § 2113 regarding product-by-process claims.
The claims would have been obvious because a particular known technique (i.e. making compositions comprising high levels of mature VWF) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because the substitution of one known element (mat-VWF) for another (mat-VWF with ultralarge multimers) would have yielded predictable results (i.e. better activity) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because the substitution of one known element (i.e. genus of buffer) for another (i.e. HEPES or MES buffer with cations and/or anions) would have yielded predictable results (i.e. suspension of VWF in buffer) to one of ordinary skill in the ar6t at the time of the invention. The claims would have been obvious because a particular known technique (i.e. optimizing buffers) was recognized as part of the ordinary capabilities of one skilled in the art. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over U.S. Patent No. 9,315,560 in view of Arya et al. and Bossard et al. for claims 79, 82-85, 87-93, and 97 were considered but are not persuasive for the following reasons.
Applicants incorporate the above arguments.
Applicants’ arguments are not convincing since the claimed invention of U.S. Patent No. 9,315,560 in view of Arya et al. and Bossard et al. renders obvious the pharmaceutical composition of the instant claims. In addition, while a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP § 714.02).
The response to the arguments is hereby incorporated.
Claims 79, 82-85, 87-93, and 97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 11,191,813 in view of Arya et al., 2002, Ultralarge multimers of von Willebrand factor form spontaneous high-strength bonds with the platelet glycoprotein 1b-IX complex: studies using optical tweezers, Blood, 99(11): 3971-3977 and Bossard et al. WO 2008/082669 published July 10, 2008.
U.S. Patent No. 11,191,813 claims purified VWF.
However, U.S. Patent No. 11,191,813 does not specify mature VWF.
Arya et al. teach compositions comprising ultralarge VWF and a buffer (please refer to the entire reference particularly the abstract; Methods; Figure 1).
Bossard et al. teach VWF including ultra large VWF and buffers including HEPES and MES wherein cations may be added including sodium and potassium and utilizing acetate (please refer to the entire specification particularly paragraphs 47, 51-58, 63, 64, 163, 179, 181, 184, 208, 227-229).
See MPEP § 2113 regarding product-by-process claims.
The claims would have been obvious because a particular known technique (i.e. making compositions comprising high levels of mature VWF) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because the substitution of one known element (mat-VWF) for another (mat-VWF with ultralarge multimers multimers) would have yielded predictable results (i.e. better activity) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because the substitution of one known element (i.e. genus of buffer) for another (i.e. HEPES or MES buffer with cations and/or anions) would have yielded predictable results (i.e. suspension of VWF in buffer) to one of ordinary skill in the ar6t at the time of the invention. The claims would have been obvious because a particular known technique (i.e. optimizing buffers) was recognized as part of the ordinary capabilities of one skilled in the art. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over U.S. Patent No. 11,191,813 in view of Arya et al. and Bossard et al. for claims 79, 82-85, 87-93, and 97 were considered but are not persuasive for the following reasons.
Applicants incorporate the above arguments.
Applicants’ arguments are not convincing since the claimed invention of U.S. Patent No. 11,191,813 in view of Arya et al. and Bossard et al. renders obvious the pharmaceutical composition of the instant claims. In addition, while a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP § 714.02).
The response to the arguments are hereby incorporated.
Claims 79, 82-85, 87-93, and 97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 11,191,837 in view of Arya et al., 2002, Ultralarge multimers of von Willebrand factor form spontaneous high-strength bonds with the platelet glycoprotein 1b-IX complex: studies using optical tweezers, Blood, 99(11): 3971-3977 and Bossard et al. WO 2008/082669 published July 10, 2008.
U.S. Patent No. 11,191,837 claims purified VWF.
However, U.S. Patent No. 11,191,837 does not specify mature VWF.
Arya et al. teach compositions comprising ultralarge VWF and a buffer (please refer to the entire reference particularly the abstract; Methods; Figure 1).
Bossard et al. teach VWF including ultra large VWF and buffers including HEPES and MES wherein cations may be added including sodium and potassium and utilizing acetate (please refer to the entire specification particularly paragraphs 47, 51-58, 63, 64, 163, 179, 181, 184, 208, 227-229).
See MPEP § 2113 regarding product-by-process claims.
The claims would have been obvious because a particular known technique (i.e. making compositions comprising high levels of mature VWF) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because the substitution of one known element (mat-VWF) for another (mat-VWF with ultralarge multimers) would have yielded predictable results (i.e. better activity) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because the substitution of one known element (i.e. genus of buffer) for another (i.e. HEPES or MES buffer with cations and/or anions) would have yielded predictable results (i.e. suspension of VWF in buffer) to one of ordinary skill in the ar6t at the time of the invention. The claims would have been obvious because a particular known technique (i.e. optimizing buffers) was recognized as part of the ordinary capabilities of one skilled in the art. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over U.S. Patent No. 11,191,837 in view of Arya et al. and Bossard et al. for claims 79, 82-85, 87-93, and 97 were considered but are not persuasive for the following reasons.
Applicants incorporate the above arguments.
Applicants’ arguments are not convincing since the claimed invention of U.S. Patent No. 11,191,837 in view of Arya et al. and Bossard et al. renders obvious the pharmaceutical composition of the instant claims. In addition, while a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP § 714.02).
The above response to the arguments are hereby incorporated.
Claims 79, 82-85, 87-93, and 97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 11,197,916 in view of Arya et al., 2002, Ultralarge multimers of von Willebrand factor form spontaneous high-strength bonds with the platelet glycoprotein 1b-IX complex: studies using optical tweezers, Blood, 99(11): 3971-3977 and Bossard et al. WO 2008/082669 published July 10, 2008.
U.S. Patent No. 11,197,916 claims purified VWF.
However, U.S. Patent No. 11,197,916 does not specify mature VWF.
Arya et al. teach compositions comprising ultralarge VWF and a buffer (please refer to the entire reference particularly the abstract; Methods; Figure 1).
Bossard et al. teach VWF including ultra large VWF and buffers including HEPES and MES wherein cations may be added including sodium and potassium and utilizing acetate (please refer to the entire specification particularly paragraphs 47, 51-58, 63, 64, 163, 179, 181, 184, 208, 227-229).
See MPEP § 2113 regarding product-by-process claims.
The claims would have been obvious because a particular known technique (i.e. making compositions comprising high levels of mature VWF) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because the substitution of one known element (mat-VWF) for another (mat-VWF with ultralarge multimers) would have yielded predictable results (i.e. better activity) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because the substitution of one known element (i.e. genus of buffer) for another (i.e. HEPES or MES buffer with cations and/or anions) would have yielded predictable results (i.e. suspension of VWF in buffer) to one of ordinary skill in the ar6t at the time of the invention. The claims would have been obvious because a particular known technique (i.e. optimizing buffers) was recognized as part of the ordinary capabilities of one skilled in the art. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over U.S. Patent No. 11,197,916 in view of Arya et al. and Bossard et al. for claims 79, 82-85, 87-93, and 97 were considered but are not persuasive for the following reasons.
Applicants incorporate the above arguments.
Applicants’ arguments are not convincing since the claimed invention of U.S. Patent No. 11,197,916 in view of Arya et al. and Bossard et al. renders obvious the pharmaceutical composition of the instant claims. In addition, while a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP § 714.02).
The above response to the arguments is hereby incorporated.
Claims 79, 82-85, 87-93, and 97 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,529,395 in view of Arya et al., 2002, Ultralarge multimers of von Willebrand factor form spontaneous high-strength bonds with the platelet glycoprotein 1b-IX complex: studies using optical tweezers, Blood, 99(11): 3971-3977 and Bossard et al. WO 2008/082669 published July 10, 2008 .
U.S. Patent No. 11,529,395 claims rVWF.
However, U.S. Patent No. 11,529,395 does not specify mature VWF.
Arya et al. teach compositions comprising ultralarge VWF and a buffer (please refer to the entire reference particularly the abstract; Methods; Figure 1).
Bossard et al. teach VWF including ultra large VWF and buffers including HEPES and MES wherein cations may be added including sodium and potassium and utilizing acetate (please refer to the entire specification particularly paragraphs 47, 51-58, 63, 64, 163, 179, 181, 184, 208, 227-229).
See MPEP § 2113 regarding product-by-process claims.
The claims would have been obvious because a particular known technique (i.e. making compositions comprising high levels of mature VWF) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because the substitution of one known element (mat-VWF) for another (mat-VWF with ultralarge multimers) would have yielded predictable results (i.e. better activity) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because the substitution of one known element (i.e. genus of buffer) for another (i.e. HEPES or MES buffer with cations and/or anions) would have yielded predictable results (i.e. suspension of VWF in buffer) to one of ordinary skill in the ar6t at the time of the invention. The claims would have been obvious because a particular known technique (i.e. optimizing buffers) was recognized as part of the ordinary capabilities of one skilled in the art. See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over U.S. Patent No. 11,529,395 in view of Arya et al. and Bossard et al. for claims 79, 82-85, 87-93, and 97 were considered but are not persuasive for the following reasons.
Applicants incorporate the above arguments.
Applicants’ arguments are not convincing since the claimed invention of U.S. Patent No. 11,529,395 in view of Arya et al. and Bossard et al. renders obvious the pharmaceutical composition of the instant claims. In addition, while a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP § 714.02).
The above response to the arguments is hereby incorporated.
Conclusion
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.
Future Communications
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/AMBER D STEELE/Primary Examiner, Art Unit 1658
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