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 Claims
Claims 1-17 are pending.
Priority
Claims 1-17 have priority to foreign filed application TAIWAN 11150999 filed on December 30, 2022.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on August 18, 2023, was filed before the mailing of the First Office Action on January 17, 2026. The Non-Patent Literature is in compliance with the provisions of 37 CFR 1.97 and are being considered by the examiner.
Specification
The disclosure is objected to because of the following informalities: Paragraphs [0052] and [0053] contain grammatical errors as it relates to the adjusted platelet concentration. In both paragraphs, the adjusted platelet concentration is stated as 109/mL, and it should read 109/mL.
Appropriate correction is required.
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 14 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is not nearly connected, to make and/or use the invention.
Nature of the Invention:
Claim 14 is directed to a method of preparing a platelets-containing composition wherein “sterile hot spring water” is used a substitute for water for injection in quantifying or adjusting platelet concentration.
Breadth of Claim:
Claim 14 broadly encompasses the use of any “sterile hot spring water”, without limitation as to source, mineral composition, ionic strength, osmolarity, pH, or trace elements.
Amount of direction or guidance present in the application:
The specification provides no guidance regarding the chemical composition, acceptable parameters, or functional requirements of “hot spring water”. It does not describe how the “hot spring water” is to be selected, modified, or tested to ensure compatibility with the platelets. The specification also does not disclose how the “sterile hot springs water” acts a substitute for water for injection.
Presence or absence of working examples:
The specification provides no working examples demonstrating the use of sterile hot spring water in place of water for injection, nor does it provide experimental data showing platelet stability, activation behavior, or growth factor retention following such exposure to the referenced water.
Relative skill in the art:
It is argued that the relative skill in the art, is that of a scientist with several years’ experience in the field, but that the Art itself is a recognition of what is understood by the Artisan, and thus, as seen below, does not make the breadth of the claim more predictable.
Predictability or lack thereof in the art:
The behavior of platelets in response to variations in ionic strength, mineral content, and osmolarity is unpredictable. Hot spring water varies widely in calcium, magnesium, sulfate, bicarbonate, and trace metal concentrations which are dependent on location. These variables can affect or cause unpredictable variations in activating, aggregating, or causing platelets to lyse. Given this, the effect of sterile hot spring water on platelet function cannot be reliably predicted. This is further reinforced given there are no articles discussing the use of sterile hot spring water as a substitute for water for injection for platelet-rich plasma, or other pharmaceutical type uses. Given this, such experimentation would be undue.
Conclusion:
Given this, the specification fails to provide sufficient disclosure to allow one of ordinary skill in the art to make and use the claimed invention as it relates to “sterile hot spring water” for use as a substitute for water for injection without undue experimentation.
Claims 2, 4, and 10 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.
Claim 2 uses the generic phrase “requirement of use” as it relates to a platelet-containing composition where an additive is added where the platelet-containing composition is used in colloid or liquid form.
Claim 4 uses the generic phrase “requirement of use” as it relates to a platelet-containing composition where an additive is added where the platelet-containing composition is used in colloid or liquid form. The same generic scope of “requirement of use” is present in each of the dependent claims, i.e. Claim 10.
The specification provides antecedent basis for “requirement of use” as it relates to an additive being added to the claimed platelet-containing composition [¶ 0051].
The specification states “in step 7, the platelets-containing composition 100 can be added with an additive 3 according to requirement of use, so that the platelets-containing composition 100 can be used in colloid or liquid form” [¶ 0051]. There is no further mention of “requirement of use” in the specification. In [¶ 0020], the specification recites essentially the same statement in more generic terminology. In [¶ 0022], again, the specification states an additive can be added to the platelet-containing composition according to the “use requirement” where the platelets-containing composition can be used as a colloid or liquid. In [¶ 0027], the specification gives the example of an “actual requirement” that includes making a gel that is suitable for use in irregular wounds or repairing and/or protecting bone. [¶ 0083] and [¶ 0095] refer to the platelet-containing composition being suitable for irregular wounds and a suitable shape and thickness prepared according to “requirements”. However, the specification provides no other definition, guidance, or method for determining the “requirement of use”. The specification also does not provide numerical ranges, thresholds, or other criteria for making such determination. The examples provided are only directed towards colloid or liquid form. Because of this and the generic use of “requirements of use”, it would be difficult for a person of ordinary skill in the art to determine what constitutes “requirement of use”. This is made more difficult given existing art makes no reference to “requirement of use” other than to direct an artisan how platelet-rich plasma can be used as a therapeutic treatment.
Given the generic scope of “requirements of use” as it relates to an additive being added to the platelet-containing composition that results in a colloid or liquid, and the absence of teaching of what other “requirements of use”, the Artisan would not understand Applicant to be in possession of the generic scope of “requirements of use” as it pertains to adding an additive to the platelets-containing composition according to “requirement of use” where the platelet-containing composition is used as a colloid or liquid.
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 2-17 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 2 recites “wherein the platelets-containing composition is added with an additive”. This statement is unclear. Is the platelets-containing composition being added to an additive, or is an additive being added to the composition? Or, is both the platelets-containing composition and the additive being added to a third medium. As written, the statement is vague and be difficult for an Artisan to determine what is being added to what.
Claim 2 recites “according to requirement of use”. This phrase is unclear given there is no objective guidance regarding what constitutes a “requirement” and leaves the boundaries of the claim uncertain. How would a skilled artisan determine what additives and what conditions signify what specific additive to use?
Claim 3 recites a series of steps without the use of “and” or “or”, leaving it unclear whether the septs are intended to be performed in combination, alternatively, or optionally. Because of this, a person of ordinary skill would not be able to determine the scope of the claim. For purposes of substantive examination, all claim limitations have been fully considered. However, even if only a single step or limitation were relied upon, the claim is still properly rejected, in the interest of compact prosecution.
Claims 4-17 are also rejected based on dependency to claim 3.
Claim 3 recites “completing preparation of the platelets-containing composition”. It is unclear what steps or criteria constitute “completion” of the preparation. As written, a person of ordinary skill would not understand what is meant by “completing preparation of the platelets-containing composition”.
Claims 4-17 are also rejected based on dependency to claim 3.
Claim 3 recites “the platelets-containing composition is added with an additive”. This statement is unclear. Is the platelets-containing composition being added to an additive, or is an additive being added to the composition? Or, is both the platelets-containing composition and the additive being added to a third medium. As written, the statement is vague and be difficult for an Artisan to determine what is being added to what.
Claims 4-17 are also rejected based on dependency to claim 3.
Claim 4 recites “the platelet containing composition is added with an additive”. This statement is unclear. Is the platelets-containing composition being added to an additive, or is an additive being added to the composition? Or, is both the platelets-containing composition and the additive being added to a third medium. As written, the statement is vague and be difficult for an Artisan to determine what is being added to what.
Claims 5-10 are also rejected based on dependency to claim 4.
Claim 4 recites “according to requirement of use”. This phrase is unclear given there is no objective guidance regarding what constitutes a “requirement” and leaves the boundaries of the claim uncertain. How would a skilled artisan determine what additives and what conditions signify what specific additive to use?
Claims 5-10 are also rejected based on dependency to claim 4.
Claim 5 recites “the additive is in the range of 0.01~10% Ca2+”. As written, this is unclear as to what the percentage is referring to. Is it referring to the final composition or is it referring to the concentration of the additive solution. Is the percentage in w/v, v/v, or molar? A person of ordinary skill would not be able to determine the scope of the claimed invention.
Claim 6 recites “the additive added per milliliter (mL) of the platelets-containing composition is in the range of 0.05 ~ 9.75% Ca2+”. As written, this statement is ambiguous. To start, the percentage is a relative measure while the mL suggests an absolute volumetric basis. Is the percentage in w/v, v/v, or molar? How is the percentage calculated per milliliter? Is the percentage referring to the final Ca2+ concentration in the final platelet composition, or is it referencing the concentration of the additive solution being added, or is it the percentage of Ca2+ added per milliliter of the platelets-containing composition? Based on this, it would be difficult for a person of ordinary skill to determine whether a given composition falls inside or outside the claimed range.
Claim 7 recites “the additive added per milliliter (mL) of the platelets-containing composition is in the range of 0.1 ~ 9% Ca2+”. As written, this statement is ambiguous. To start, the percentage is a relative measure while the mL suggests an absolute volumetric basis. Is the percentage in w/v, v/v, or molar? How is the percentage calculated per milliliter? Is the percentage referring to the final Ca2+ concentration in the final platelet composition, or is it referencing the concentration of the additive solution being added, or is it the percentage of Ca2+ added per milliliter of the platelets-containing composition? Based on this, it would be difficult for a person of ordinary skill to determine whether a given composition falls inside or outside the claimed range.
Claim 8 recites “wherein the additive added per milliliter (mL) of the platelets-containing composition is the group consisting of…”. The claim then states a Markush listing of percentages ranging from 0.01% to 10%. Based on the same analysis for the rejections in claims 6 and 7, claim 8 fails to specify whether one or more additives are selected from the group, the basis for the recited percentages, or how the percentage ranges relate to the “per milliliter” limitation. Given this, a person of ordinary skill could not reasonably ascertain the meets and bounds of the claim. Additionally, the claim, as written, is grammatically incorrect. The claim states “the additive added per milliliter…is the group consisting of…”. Is there one concentration selected or are there multiple concentrations selected? Or, are all of the concentrations selected?
Claim 9 recites the limitation "the gel" in Line 1. There is insufficient antecedent basis for this limitation in the claim.
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.
Claims 1-17 are rejected under 35 U.S.C. §103 as being unpatentable over Shiga et al. [Freeze-dried human platelet-rich plasma retains activation and growth factor expression after an eight-week preservation period, Asian Spine J., 2017], in view of Godoi et al. [Platelet-rich plasma gel matrix (PRP-GM): description of a new technique, Bioengineering, Dec. 19, 2022], in view of Ralsonics Surface Engineering Solutions (Hereinafter Ralsonics) [Using Sonicators in the Pharma Industry, 2018], in view of Emerson [WO 2016 153590 A2, 2016].
For claim 1 where a platelet containing composition comprises platelet-rich plasma and is mixed with platelet-poor plasma and then freeze-dried and sterilized, Shiga et al. teaches every element of claim 1 except the mixing with the platelet-rich plasma back with the platelet-poor plasma.
For claim 1 where the platelet-poor plasma is mixed back with the platelet-rich plasma, Godoi et al. teaches that the platelet-rich plasma can be mixed back with the platelet-poor plasma where it can be used to form a plasma gel [2.1 Obtaining Leukocyte-rich PRP ¶ 3].
For claim 2 where the platelet-containing composition is added to a form a colloid or liquid, Shiga et al. discloses two different scenarios for activation where in one example 100 microliters of calcium chloride and 100 microliters of thrombin solution are added to platelet-rich plasma where, initially, a liquid is formed prior to formation of fibrin [4. Platelet activation]. The other example includes adding buffered saline to platelet-rich plasma resulting in a liquid [5. Assessment of platelet activation via flow cytometry ¶ 1]. Here, it would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of claimed invention to modify the systems and methods of Shiga et al. where researchers studied retained activation and growth factor expression of lyophilized platelet-rich plasma with the additional teachings of Godoi et al. where it was taught the platelet-rich plasma could be mixed back with the platelet-poor plasma where the lyophilized platelet-rich plasma composition, through the addition of activators, could be reconstituted into the form of a liquid by using activators such as calcium chloride or buffered saline. Based on this there is a reasonable expectation that a person of ordinary skill would know to combine the teachings of both Shiga et al. with the teachings of Godoi et al. in order to reconstitute lyophilized, i.e. freeze-dried, platelet-rich plasma composition.
For claim 3, Godoi et al teaches every limitation except Godoi et al. does not teach freeze drying, performing sterilization, and completing the preparation of platelets-containing composition, e.g. elements 5-7. However, Shiga et al. discloses the use of lyophilization and sterilization on platelet-rich plasma [Methods, Discussion ¶ 4]. Shiga et al. further discloses activating the lyophilized platelet-rich plasma using a calcium chloride solution [4. Platelet activation ¶ 1].
For claim 4 where an additive is added to the platelet-containing composition, again Shiga et al. discloses the use of calcium chloride as an additive resulting in a colloid and/or liquid [Id.]. Therefore, there is a reasonable expectation of success to combine the teachings of both Godoi et al. and Shiga et al. in order to prepare a platelet-rich plasma composition following the steps the result in a lyophilized platelet-containing composition where an additive such as calcium chloride or platelet-poor plasma is used as an additive resulting in a liquid or colloid formation. Given this, it would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the claimed invention to modify the systems and methods of Godoi et al. where the authors developed a platelet-rich plasma gel matrix with the additional teachings of Shiga et al. that discussed freeze-drying platelet-rich plasma and then activating said platelet-rich plasma with the addition of an additive.
For purposes of examination, claims 5-8 are being interpreted to mean the concentration of the Ca2+ as it relates to the platelet concentration per milliliter.
For claims 5-8 where the additive is in the range of 0.01 ~ 10% Ca2+, Shiga et al. discloses a 100 microliters of calcium chloride for 10-15mL of platelet-rich plasma, the calcium chloride represents roughly 0.66 to 0.99% [4. Platelet activation ¶ 1].
For claim 9 where a gel is prepared in shape and thickness for irregular wounds or bone repair/protection, Godoi et al. discloses the use of platelet-rich plasma where it has been evaluated and established in numerous musculoskeletal conditions that include osteoarthritis, tendinopathies, and osteonecrosis, as well as stimulating wound healing in patients. Furthermore, it would have been obvious to a person of ordinary skill in the art that platelet-rich plasma compositions, e.g. gels, used for wound healing are typically molded or shaped to conform to the dimensions of the specific wound site to ensure optimal coverage and contact with the relative tissue. Such shaping would have been routine and predictable practice in the art and would be considered prima facie obvious to a skilled artisan applying platelet-rich plasma composition gels for therapeutic purposes.
For claim 10 where the additive is a solvent and the platelet composite solution is formed, Shiga et al. discloses the use where lyophilized platelet-rich plasma can be incorporated into artificial bone after being dissolved in water [Discussion ¶ 4].
For claims 11 and 12, Emerson, teaching a method for platelet rich plasma and bone marrow aspirate cell separation, discloses the use of both gamma radiation and e-beam radiation as methods for sterilization of platelet-rich plasma [¶ 0042].
For claim 13 where the quantifying platelet-rich plasma is through centrifugation and adding water for injection to adjust platelet concentration, Shiga et al. discloses the use of centrifugation as a method for concentrating platelets [Introduction ¶ 1]. Furthermore, it would have been obvious to a person of ordinary skill in the art at the time of the claimed invention to dilute platelet-rich plasma using a sterile, pharmaceutically acceptable diluent such as water for injection, as the use of such diluents for adjusting the volume or concentration of biologically active suspensions was well known and routine. Furthermore, it would have been routine for a skilled artisan to determine the appropriate platelet concentration for a particular therapeutic application through standard experimentation, including diluting and measuring platelet counts, without undue experimentation. Based on this, there is a reasonable expectation of success to combine platelet-rich plasma with a well-known diluent, e.g. water for injection, for the purpose of adjusting platelet concentration to a desired level and would have been within the ordinary skill of the art and thus, prima facie obvious.
For claim 14 where quantification is achieved using a certain substitute for water for injection, Shiga et al. discloses the use of buffered saline for purposes of activation. However, it would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the claimed invention to dilute platelet-rich plasma with a pharmaceutically acceptable diluent, e.g. normal saline or isotonic saline to adjust the volume of concentration of biologically active suspensions given these methods are well known in the art and would have allowed a skilled artisan the ability to determine an appropriate platelet concentration for a particular therapeutic application.
For claim 15 where the platelet-rich plasma composition is activated by adding an activator, Shiga et al. discloses the use of calcium chloride as an activator [4. Platelet activation ¶ 1].
For claim 17 where activating the platelet-rich plasma is activated through the use of ultrasonic vibration to mix the HCPP and the platelet-poor plasma, Ralsonics, discussing using sonicators in the pharmaceutical industry, discloses the use of ultrasonic vibration as a means for mixing solutions and accelerating the dissolution process [Particle Agitation].
Here, it would have prima facie obvious to a person of ordinary skill in the art prior to the filing of the claimed invention to modify the systems of methods of Godoi et al. where the authors developed a platelet-rich plasma gel matrix with the additional teachings of Shiga et al. that discussed freeze-drying platelet-rich plasma and then activating said platelet-rich plasma with the addition of an additive with the additional teachings of Ralsonics where sonication is disclosed for use in mixing, agitating, and/or accelerating the dissolution process for pharmaceutical compounds. Given this, there is a reasonable expectation of success that a skilled artisan would recognize the teachings of Godoi et al. with the additional teachings of Shiga et al. and Ralsonics for creating platelet-rich plasma composition from lyophilized platelet-rich plasma where it is mixed with an activator using sonication, i.e. ultrasonic vibration, as a means of mixing.
The Supreme court has acknowledged:
When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable varition..103 likely bars its patentability…if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond that person’s skill. A court must ask whether the improvement is more than the predictable use of prior-art elements according to their established functions…
…the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results (see KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 U.S. 2007) emphasis added.
In KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme Court reaffirmed "the conclusion that when a patent 'simply arranges old elements with each performing the same function it had been known to perform' and yields no more than one would expect from such an arrangement, the combination is obvious." Id. at 417 (quoting Sakraida v. Ag Pro, Inc., 425 U.S. 273,282 (1976)). The Supreme Court also emphasized a flexible approach to the obviousness question, stating that the analysis under 35 U.S.C. § 103 "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at 418; see also id. at 421 ("A person of ordinary skill is... a person of ordinary creativity, not an automaton.").
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claims allowed.
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/JOHN DAVID MOORE/Examiner, Art Unit 1638
/ROBERT M KELLY/Primary Examiner, Art Unit 1638