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 .
DETAILED ACTION
The instant application is in response to the papers filed on February 10, 2025 of which claims 1-19 are currently pending. Therefore, claims 1-19 are currently under examination to which the following grounds of rejection are applicable.
Priority
The instant application claims foreign priority 35 U.S.C. 119(a)-(d) to Chinese Patent Application No. 202510035666.9 filed on January 8, 2025. Receipt is acknowledged of untranslated certified copies of papers required by 37 CFR 1.55. Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e). Failure to provide a certified translation may result in no benefit being accorded for the non-English application
Thus, the earliest possible priority for the instant application is January 8, 2025.
Claim Objections
Claims 9, 14-19 are objected to because of the following informalities:
Claim 9 is objected for the recitation of “The platelet transfusion stock solution according to claim 4, physiological saline is used as a solvent” as the proper recitation is “The platelet transfusion stock solution according to claim 4, comprising physiological saline as a solvent” because the claim is missing the transitional phrase, and moreover should maintain the same language used in claims 10-13. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1, 6, and 14 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.
Claim 1 recites the limitations “to first heating”, “to second heating”, “to third heating”, “to fourth heating”, “to fifth heating”, and “to sixth heating”. There is insufficient antecedent basis for these limitations in the claim. The proper amendments is using the article “a/an” appropriately, and then using the article “the” thereafter.
Claim 1 is indefinite for the language of “preparing a lyophilized platelet”, “a first platelet”, “a second platelet”, “a third platelet”, “a fourth platelet”, “a fifth platelet”, “a sixth platelet”, “a seventh platelet”, and “the LP”, as the language suggests the composition is entirely composed of a single platelet with no other members despite the disclosure teaching the lyophilization of platelets of which can be combined with a platelet transfusion stock solution that contains other members. The appropriate language is following “platelet” with “product”.
Claims 6 and 14 are indefinite as it is unclear if all the listed platelet activators are to be included in the solution, or rather are merely listing the concentrations of each if they were to be included. Altogether, the claim should clearly state if the solution contains a particular activator, and the respective concentration.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 4-19 are rejected under 35 U.S.C. 103 as being unpatentable over Gear et al. (Blood, The Journal of the American Society of Hematology 97.4 (2001): 937-945) in view of Ho et al. (US Patent No. 8,486,617 B2).
Regarding claims 4 and 5 Gear teaches the treatment of platelets with chemokine SDF-1 and with low levels of ADP or thrombin can serve as strong stimuli for activating platelet function stating that “Such activation may serve as a dynamic link between chemokines produced during inflammation and activation of hemostatic events.” (abstract, p 938, col 1, par 1). Gear teaches platelets at 2 x 108 platelets/mL are stimulated with SDF-1 over a range of concentrations (0, 0.005, up to 5 g/mL) in the presence of ADP (0.05, 0.1 µM, up to 10µM) or thrombin (0.005 U/mL, 5 U/mL) to induce aggregation. “The traces presented in Figure 1D and 1E reveal that SDF-1, at even lower levels of ADP (0.05 M) or with very low levels of thrombin (0.005 U/mL, approximately 0.5 nM), was able to induce aggregation at rates that began to approach those caused by maximal doses of the primary agonists.” (p 938, col 2- p 939, col 2; Fig. 1).
Ho teaches a method of lyophilizing platelets and the product of such method; and states thrombin activates platelets by converting fibrinogen to insoluble strands of fibrin which when cross-linked forms clots. Ho states thrombin can preactivate platelets prior to loading and lyophilization. Furthermore, Ho teaches the agonist ristocetin at 1 mg/mL can be added to reconstituted freeze-dried platelets for aggregation to occur (Table 1, Example 10).
It would have been prima facie obvious for one of ordinary skill in the art at the time of the effective filing date to have modified the lyophilized platelets taught by Ho et al. to include a platelet activator, e.g. thrombin, adenosine diphosphate (ADP), or ristocetin, and stromal cell-derived factor (SDF-1), to activate the platelet aggregation (as taught by Gear et al.) because it would have been obvious to combine prior art elements according to known methods to yield predictable results.
Gear teaches the inclusion of SDF-1 with ADP or thrombin are shown to be highly effective to induce aggregation of platelets, and moreover found only low levels of these platelet activators are required with SDF-1 (Fig. 1A, E) for such outcomes to be observed. Therefore, the inclusion with the lyophilized platelets (LPs) would have led to predictable results with a reasonable expectation of success because Ho teaches the process to obtain LPs, and also teaches thrombin and another platelet activator, ristocetin, can be combined with LPs for aggregation occur. Altogether, the combined reference teaching would have made it obvious to have incorporated platelet activator(s) with SDF-1 and LPs based on the combination capable of aggregating the included LPs.
Regarding claim 6, Gear teaches wherein the thrombin has a concentration of 1 U/mL based on teaching a range that encompasses this value, e.g. 0.005 U/mL, 0.01 U/mL, 5 U/mL, (Fig. 1, 2). Gear teaches the platelet activator of ADP, wherein the ADP has a concentration of 0.05, 0.1 µM, or up to 10µM, and states low levels of ADP (50-100 nM) are sufficient when combined with SDF-1 to induce aggregation. Ho teaches the ristocetin at 1 mg/mL can be added to reconstituted freeze-dried platelets for aggregation to occur (Table 1, Example 10). In view of the claimed concentrations, it would be obvious to include a higher concentration of a platelet activator in order to improve overall aggregation and the rate at which it occurs in view of using the composition for transfusion for subjects in need based on low concentrations of thrombin and ADP being observed as sufficient to induce aggregation when combined with SDF-1.
Regarding claim 7, Gear teaches SDF-1 has a concentration of 150 ng/mL based on teaching a range that encompasses this value, e.g. 0, 5 ng/mL, 500 ng/mL, and 5000 ng/mL (Figs. 1, 2, p 938, col 2, par 4).
Regarding claim 8, Gear teaches the platelet count as platelet count as 3.41 + 0.2 x 1011 platelets/L (p 938, col 1), and Ho teaches the platelet concentration of 1.25 x 1012 platelets/L (Example 2).
Regarding claims 9-13, Gear teaches the composition as comprising physiological saline as a solvent based on teaching the platelets as being resuspended in HEPES-based suspension buffer (p 938, col 1). Furthermore, Ho teaches using the same buffer in which saline was added to of reconstituted freeze-dried platelets (Example 10).
Regarding claims 14-19, the claims rejections to claims 4-13 are applied herein based on the compositions claimed being similar, with the difference being that these claims recite a hemostatic product, comprising a traumatic hemostatic product, wherein the traumatic hemostatic product comprises the platelet transfusion stock solution according to claim 4. Therefore, due to no other limitations or elements being claimed, the rejections set forth above are applied herein.
Allowable Subject Matter
Claims 1-3 would be allowable if rewritten or amended to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action. The method for preparing a lyophilized platelet (LP) as recited in claims 1-3 are free of the prior art because the prior art does not teach the combination of elements recited in the process. The art teaches the general process of lyophilization wherein the steps are divided between freezing, primary drying, and secondary drying wherein the target temperatures claimed are reached, wherein negative pressure is applied during primary drying, and wherein platelets are held or maintained at freezing temperatures for a period of time prior to the heating steps. Ho et al. (US 8,486,617 B2) teaches a lyophilization protocol for platelets as outlined below:
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As shown above, Ho teaches the freezing step as involving reaching -45° C that is maintained then followed by heating under pressure in small increments. The methods are different than the instant claims wherein the heating steps involve maintaining the temperature for periods of time, e.g. 60 minutes, before increasing temperature by around 10-12 ° C then holding temperature again, all of which is repeated until the target temperature of 20° C is reached.
Similarly, Fan et al. (Journal of Zhejiang University-SCIENCE A 10.5 (2009): 697-703) teaches freezing platelets at -60° C for 2 h with a cooling rate of about 10 °C/min, the primary heating is −40 °C at a rate of 1.5 °C/min under 1 Pa of pressure for 16 hours, and then secondary drying at 22 °C at a rate of 0.2 °C/min and then kept at that temperature for about 16 hours (p 698, col 2).
Wolkers et al. (Cell preservation technology 1.3 (2002): 175-188) teaches a lyophilization protocol wherein “One-milliliter aliquots of platelet solution were transferred to siliconized glass vials (diameter, 22 mm), which were placed on the shelves of the lyophilizer and frozen from 22°C to -5°C at a rate of 5°C/min, and then cooled further from -5 to -60°C at a rate of 2°C/min. After 15 min at -60°C the absolute pressure of the lyophilization chamber was reduced to 50 mTorr. The shelves were then heated at a rate of 0.75°C/min to -30°C where they were kept for approximately 4 h. The sample temperature was approximately -31°C. The shelves were subsequently heated to 20°C at a rate of approximately 0.2°C/min and kept at that temperature and under vacuum overnight.” (p 177, col 1, par 2).
Zhou et al. (CryoLetters 27(1), 43-50 (2006)) teaches a lyophilization protocol wherein “1ml platelet suspensions were transferred to glass vials (diameter, 25 mm) and frozen on the shelf of the freeze-drier precooled to -5°C, with a cooling rate of 10°C/min approximately. The suspensions were maintained below -40°C for 2 h to allow sufficient time for all samples to freeze completely. Subsequently, the primary drying was conducted for 18h with a shelf temperature of -38ºC, a condenser temperature of below -60ºC and a vacuum chamber pressure of 2 Pa. Then the shelf was heated to 20°C at a rate of 0.2°C/min approximately and kept at that temperature for 15 h.” (p 46, par 1).
In summary, it can be seen that the prior art does not teach breaking up the heating wherein at the end of each step the platelet samples are maintained at the end temperature for a period of time before continuing into the next heating step. The prior art merely teaches the heating with a gradual ramp up, e.g. 0.2 ºC/min until a target temperature is reached as opposed to breaking up the heating as claimed. Therefore, the methods recited in claims 1-3 are free of the prior art.
Conclusion
Claims 1-19 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL A RIGA whose telephone number is (571)270-0984. The examiner can normally be reached Monday-Friday (8AM-6PM).
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/MICHAEL ANGELO RIGA/Examiner, Art Unit 1634
/TERESA E KNIGHT/Primary Examiner, Art Unit 1634
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