The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This office action is in response to Applicants’ amendments/remarks received July 10, 2025.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.
Claims 19, 23 are canceled. Claims 1-17, 24 are withdrawn. Claims 18, 20-22, 25-28 are under consideration.
Priority: This application is a 371 of PCT/EP2020/085094, filed December 8, 2020, which claims benefit to foreign application EP 19214919.3, filed December 10, 2019. A copy of the foreign priority document has been received in the instant application on June 6, 2022 and is in the English language.
Objections and Rejections
Claims 18, 20-22, 25-28 are objected to because of the following informalities: the independent claim(s) should recite an indefinite article such as “a” or “an” at the beginning of the claim(s) and the dependent claim(s) should recite a definite article such as “the” at the beginning of the claim(s). Appropriate correction is requested.
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 18, 20-22, 25-26 are rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter. The instant claims recite a nature-based product, i.e. a human fibrinogen. The fibrinogen recited in the instant claims is not markedly different from naturally occurring fibrinogen.
Claims 18, 20-22, 25-26 are product-by-process claims. MPEP 2113 notes that "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. In the instant case, there is no evidence of record that the process by which the protein concentrate or isolate is made sufficiently transforms the protein concentrate or isolate into something that is markedly different from its natural counterpart. The claims recite fibrinogen protein that is structurally the same as naturally occurring fibrinogen. The claims are directed to a statutory category, i.e. a composition of matter (step 1: YES).
Since the claims recite a nature-based product, i.e. human fibrinogen, the claims are analyzed to determine whether it is directed to any judicial exception. The markedly different characteristics analysis is performed by comparing the nature-based product limitation in the claim to its naturally occurring counterpart to determine if it has markedly different characteristics from the counterpart. The recited human fibrinogen protein is compared to its closest naturally occurring counterpart to determine if it has markedly different characteristics. Here, the closest natural counterpart is naturally occurring human fibrinogen protein. When the claimed fibrinogen is compared to this counterpart, the comparison indicates that there are no differences in structure, function, or other characteristics. Human fibrinogen is naturally occurring and is found in plasma (application publication paragraphs 0002-0003). Human fibrinogen isolated from plasma does not have markedly different characteristics due to their purification or human manufacture. Therefor, the human fibrinogen does not have markedly different characteristics from what occurs in nature and is a “product of nature” exception. Accordingly, the claims are directed to an exception (step 2A: YES). Next, the claims as a whole are analyzed to determine whether any additional element, or combination of elements, is sufficient to ensure that the claim amounts to significantly more than the exception(s). The claims recite the fibrinogen preparation comprises a buffer system. The incorporation of a protein into a composition is not only well-understood, routine and conventional activity already engaged in by the scientific community, it is also required for using the protein. The claims recite the composition at such a high level of generality that it merely tells a scientist to use whatever general buffer (i.e. claim 18) and/or excipient (i.e. claim 21) to form a composition comprising the protein. The dependent claims also recite naturally occurring buffers and amino acids which are systems well-understood and routinely incorporated for maintaining proteins. The claims do not recite anything significantly different than the natural product, i.e. the claims do not recite elements or features that demonstrate that the claimed human fibrinogen is markedly different from what exists in nature. Therefore, the claims as a whole add nothing significantly more to the "product of nature" itself (Step 2B: NO), and thus, the claims do not qualify as eligible subject matter.
Therefore, the claimed human fibrinogen does not have markedly different characteristics from what exists in nature and is a “product of nature” exception. See also Funk Brothers Seed Co., V. Kalo Inoculant Co., 333 U.S. 127, (1948) and Association for Molecular Pathology v. Myriad Genetics, Inc. 569 U.S., 133 S. Ct. 2107, 2116, 106 USPQ 2d. 1972 (2013).
Reply: Applicants’ amendments/remarks have been considered but they are not persuasive.
Applicants assert that claim 18 is amended to recite a buffer system and claim 21 is amended to recite at least one pharmaceutical buffer.
Applicants’ remarks are not persuasive. As noted in the 101 rejection above, the claims as a whole are analyzed to determine whether any additional element, or combination of elements, is sufficient to ensure that the claim amounts to significantly more than the exception(s). While the claims recite the fibrinogen preparation comprises a buffer system, it is known that the incorporation of a protein into a composition is not only well-understood, routine and conventional activity already engaged in by the scientific community, it is also required for using the protein. The claims recite the composition at such a high level of generality that it merely tells a scientist to use whatever general buffer (i.e. claim 18) and/or excipient (i.e. claim 21) to form a composition comprising the protein. The dependent claims also recite naturally occurring buffers and amino acids which are systems and components well-understood and routinely incorporated for maintaining proteins. The claims do not recite anything significantly different than the natural product, i.e. the claims do not recite elements or features that demonstrate that the claimed human fibrinogen is markedly different from what exists in nature. Therefore, the claims as a whole add nothing significantly more to the "product of nature" itself, and thus, the claims do not qualify as eligible subject matter.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 18, 20-22, 25-28 are rejected under 35 U.S.C. 103 as being unpatentable over Nogre et al. (US 20080207878). The instant claims are product-by-process claims. As previously noted, MPEP 2113 notes that "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.”
Nogre et al. disclose a process for separating proteins fibrinogen, Factor XIII (FXIII) and biological glue from a plasma fraction and preparing highly purified lyophilized concentrates of the said proteins (at least abstract, paragraphs 0001, 0020, see also example). Nogre et al. disclose that at least one part of the recovered amount of biological glue eluate is subjected to a treatment in order to separate the FXIII accompanying the fibrinogen; this separation is carried out by precipitating the FXIII; thus, a precipitate of FXIII and a supernatant highly enriched in fibrinogen are separated (at least paragraph 0031, also example paragraphs 0061-0063). Nogre et al. disclose the obtained fibrinogen solution is concentrated to attain 15 g/l to 25 g/l (at least paragraphs 0033, 0063) and a FXIII:Ag 2.6 ± 0.9 (U/ml) and a FXIII activity 1.3 ± 0.6 (U/ml) (p. 5 Table). Nogre et al. disclose the fibrinogen solution comprises the mixture of a diafiltration buffer (mixture A) comprising trisodium citrate (10-12 g/l), lysine (1-5 g/l), glycine (1-5 g/l), Tris salt (2-5 g/l), arginine (25-50g/l), isoleucine (5-15 g/l), pH 7.4 (at least paragraphs 0030, 0047, 0059, 0064).
MPEP 2144.05 notes that a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Further, 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.
In this instance, it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that Nogre et al. disclose a composition comprising a human plasmatic fibrinogen and a buffer system, wherein the FXIII concentration FXIII:Ag (2.6 ± 0.9 U/ml) and/or FXIII activity (1.3 ± 0.6 U/ml) in the fibrinogen composition of Nogre et al. is similar to the recited FXIII concentration 0.5-2.0 FXIII:Ag (% of norm) and/or FXIII activity of less than 16 FXIII:Ac (% of norm) and/or arrive at the recited FXIII concentration and/or activity by routine optimization because Nogre et al. disclose separating FXIII from fibrinogen to obtain a pure fibrinogen composition and a pure FXIII composition (instant claims 18, 20-22, 25-28). One of ordinary skill would have a reasonable expectation of success because Nogre et al. disclose that FXIII accompanying fibrinogen can be separated to obtain a fibrinogen that is highly purified and free of coprecipitated proteins and unwanted contaminants (at least paragraphs 0018-0020).
Regarding claims 20 and 25, the fibrinogen composition having no detectable content of D-dimer and a maximum clot firmness of 20 to 30 mm, it is noted that Nogre et al. do not explicitly teach the content of D-dimer and the maximum clot firmness of the fibrinogen composition resulting from the method. It is submitted that these features and/or properties would be naturally present in the fibrinogen composition produced by the method employed by both Applicant and Nogre et al. Nogre et al. disclose the process to isolate and enrich fibrinogen from a fibrinogen-containing source (blood plasma) by ion exchange chromatography to bind fibrinogen to the ion exchange chromatography material, washing unbound components from the ion exchange chromatography material, and eluting the fibrinogen from the ion exchange chromatography material and then precipitating out the entire amount of FXIII (Nogre et al. example). Since the office does not have the facilities for examining and comparing the D-dimer content or maximum clot firmness of Applicants’ fibrinogen preparation with the D-dimer content or maximum clot firmness of the fibrinogen preparation of the prior art, the burden is on the applicant to show a novel or unobvious difference between the claimed product and the product of the prior art (i.e., that the fibrinogen preparation of the prior art does not possess the same material structural and functional characteristics of the claimed fibrinogen preparation). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
Regarding instant claims 21, 26, as noted above, Nogre et al. disclose the fibrinogen solution that is free of accompanying FXIII, comprises the mixture of a diafiltration buffer (mixture A) comprising trisodium citrate (10-12 g/l), lysine (1-5 g/l), glycine (1-5 g/l), Tris salt (2-5 g/l), arginine (25-50g/l), isoleucine (5-15 g/l), pH 7.4 (at least paragraphs 0030, 0047, 0059, 0064).
Regarding instant claim 22, Nogre et al. disclose the fibrinogen solution comprising the buffer noted above is freeze-dried (at least paragraph 0047, see also example).
Regarding instant claims 27-28, Nogre et al. disclose the obtained fibrinogen solution is concentrated to attain 15 g/l to 25 g/l (at least paragraphs 0033, 0063) and comprises the mixture of a diafiltration buffer (mixture A) comprising trisodium citrate (10-12 g/l), lysine (1-5 g/l), glycine (1-5 g/l), Tris salt (2-5 g/l), arginine (25-50g/l), isoleucine (5-15 g/l), pH 7.4 (at least paragraphs 0030, 0047, 0059, 0064). Therefore, it would have been obvious to arrive at the recited concentrations of 12-25 g/l fibrinogen, 20-65 mmol arginine, 2-10 mmol citrate, pH 6.5-7.5, by routine optimization.
Reply: In view of Applicants’ amendments/remarks, the previous 102 rejection as being anticipated by Gehringer has been withdrawn. However, in view of Applicants’ amendments to the claims, the claims remain unpatentable under a new 103 rejection over Nogre et al. for the reasons noted above. Nogre et al. disclose separating FXIII accompanying human fibrinogen to obtain a highly purified human fibrinogen composition (at least paragraph 0031, also example). Nogre et al. disclose the obtained fibrinogen solution is concentrated to attain 15 g/l to 25 g/l (at least paragraphs 0033, 0063) and a FXIII:Ag 2.6 ± 0.9 (U/ml) and a FXIII activity 1.3 ± 0.6 (U/ml) (p. 5 Table). Therefore, Nogre et al. can be deemed to disclose a FXIII concentration and/or activity similar to the recited FXIII concentration 0.5-2.0 FXIII:Ag (% of norm) and/or FXIII activity of less than 16 FXIII:Ac (% of norm) and/or arrive at the recited FXIII concentration and/or activity by routine optimization because Nogre et al. disclose separating FXIII from fibrinogen to obtain a pure fibrinogen composition and a pure FXIII composition.
Claims 18, 20-22, 25-28 are rejected under 35 U.S.C. 103 as being unpatentable over Nogre et al. (US 20080207878) in view of Smith et al. (2013 Thromb Haemost 11: 993-995). The teachings of Nogre et al. are noted above. As noted above, Nogre et al. disclose separating FXIII accompanying human fibrinogen to obtain a highly purified human fibrinogen composition (at least paragraph 0031, also example). Nogre et al. disclose the obtained fibrinogen solution is concentrated to attain 15 g/l to 25 g/l (at least paragraphs 0033, 0063) and a FXIII:Ag 2.6 ± 0.9 (U/ml) and a FXIII activity 1.3 ± 0.6 (U/ml) (p. 5 Table). While Nogre et al. can be deemed to disclose a human fibrinogen composition comprising a FXIII concentration and/or activity similar to the recited FXIII concentration 0.5-2.0 FXIII:Ag (% of norm) and/or FXIII activity of less than 16 FXIII:Ac (% of norm), Nogre et al. do not explicitly teach a FXIII activity of 0.
Smith et al. disclose obtaining FXIII-free human fibrinogen (at least p. 993). Smith et al. disclose that any additional FXIII activity in a fibrinogen composition can be removed by ammonium sulfate precipitation or IF-1 antibody affinity chromatography (at least p. 993-994).
It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the ammonium sulfate precipitation or IF-1 antibody affinity chromatography of Smith et al. into the teachings of Nogre et al. to thereby arrive at a composition comprising a human plasmatic fibrinogen and a buffer system, wherein the fibrinogen is completely FXIII-free and has no detectable FXIII activity (instant claims 18, 20-22, 25-28) because there was interest in obtaining FXIII-free fibrinogen compositions. One of ordinary skill would have a reasonable expectation of success because the prior art disclose successfully separating FXIII accompanying fibrinogen to obtain FXIII-free fibrinogen.
Regarding claims 20 and 25, the fibrinogen composition having no detectable content of D-dimer and a maximum clot firmness of 20 to 30 mm, it is noted that Nogre et al. and Smith et al. do not explicitly teach the content of D-dimer and the maximum clot firmness of the FXIII-free fibrinogen composition resulting from the method. It is submitted that these features and/or properties would be naturally present in the fibrinogen composition produced by the method employed by both Applicant and Nogre et al. in view of Smith et al. Nogre et al. disclose the process to isolate and enrich fibrinogen from a fibrinogen-containing source (blood plasma) by ion exchange chromatography to bind fibrinogen to the ion exchange chromatography material, washing unbound components from the ion exchange chromatography material, and eluting the fibrinogen from the ion exchange chromatography material and then precipitating out the entire amount of FXIII (Nogre et al. example) and Smith et al. disclose that any additional FXIII activity in a fibrinogen composition can be removed by ammonium sulfate precipitation or IF-1 antibody affinity chromatography (at least p. 993-994). Since the office does not have the facilities for examining and comparing the D-dimer content or maximum clot firmness of Applicants’ fibrinogen preparation with the D-dimer content or maximum clot firmness of the fibrinogen preparation of the prior art, the burden is on the applicant to show a novel or unobvious difference between the claimed product and the product of the prior art (i.e., that the fibrinogen preparation of the prior art does not possess the same material structural and functional characteristics of the claimed fibrinogen preparation). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
Regarding instant claims 21, 26, as noted above, Nogre et al. disclose the fibrinogen solution that is free of accompanying FXIII, comprises the mixture of a diafiltration buffer (mixture A) comprising trisodium citrate (10-12 g/l), lysine (1-5 g/l), glycine (1-5 g/l), Tris salt (2-5 g/l), arginine (25-50g/l), isoleucine (5-15 g/l), pH 7.4 (at least paragraphs 0030, 0047, 0059, 0064).
Regarding instant claim 22, Nogre et al. disclose the fibrinogen solution comprising the buffer noted above is freeze-dried (at least paragraph 0047, see also example).
Regarding instant claims 27-28, Nogre et al. disclose the obtained fibrinogen solution is concentrated to attain 15 g/l to 25 g/l (at least paragraphs 0033, 0063) and comprises the mixture of a diafiltration buffer (mixture A) comprising trisodium citrate (10-12 g/l), lysine (1-5 g/l), glycine (1-5 g/l), Tris salt (2-5 g/l), arginine (25-50g/l), isoleucine (5-15 g/l), pH 7.4 (at least paragraphs 0030, 0047, 0059, 0064). Therefore, it would have been obvious to arrive at the recited concentrations of 12-25 g/l fibrinogen, 20-65 mmol arginine, 2-10 mmol citrate, pH 6.5-7.5, by routine optimization.
Reply: In view of Applicants’ amendments/remarks, the previous 102 rejection as being anticipated by Gehringer has been withdrawn. However, in view of Applicants’ amendments to the claims, the claims remain unpatentable under a new 103 rejection over Nogre et al. in view of Smith et al. for the reasons noted above.
No claim is allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/Marsha Tsay/Primary Examiner, Art Unit 1656
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