DETAILED ACTION
Examiner acknowledges receipt of the reply filed 11/13/2025, in response to the nonfinal office action mailed 8/13/2025.
Claims 26, 30-34, 36, and 39-41 are pending. Claims 27, 29, 37, 38, and 42 have been canceled. Claims 33, 36, and 39-41 remain withdrawn from further consideration for the reasons made of record.
Claims 26, 30-32, and 34 are being examined on the merits in this office 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 .
Trademark in the Specification- withdrawn
The objection to the specification for inclusion of trademarks is withdrawn in view of the amendment filed 11/13/2025.
Claim Objections- withdrawn
The objection of claims 26 and 27 is withdrawn in view of the amendment filed 11/13/2025.
Claim Rejections - 35 USC § 112- withdrawn
The rejection of claim 34 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in view of the amendment filed 11/13/2025.
Claim Rejections - 35 USC § 102- withdrawn
The rejection of claims 26 and 30-32 under 35 U.S.C. 102(a)(1) as being anticipated by CN 107674860 (hereinafter referred to as “the ‘860 application” – previously cited), is withdrawn in view of the amendment filed 11/13/2025.
Claim Rejections - 35 USC § 103- withdrawn
The rejection of claims 26, 27, and 30-32 under 35 U.S.C. 103 as being unpatentable over CN 107674860 (hereinafter referred to as “the ‘860 application” – previously cited), in further view of Shin et al (U.S. 2015/165000- cited in IDS filed 03/11/2022), is withdrawn in view of the amendment filed 11/13/2025.
Response to Arguments
Applicant's arguments and amendment filed 11/13/2025 with respect to the above objections and rejections have been fully considered and are persuasive. The objections and rejections have been withdrawn.
Applicant’s arguments filed 11/13/2025 have been fully considered but they are not persuasive with respect to the maintained rejections.
Upon further consideration, a new grounds of objection and rejection is made in view of the claims filed 11/13/2025.
An action on the merits is set forth herein.
Maintained Rejections
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.
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.
Claim(s) claims 26 and 30-32 remain/are rejected under 35 U.S.C. 103 as being unpatentable over Shin et al (U.S. 2015/165000- previously cited), and further in view of Percival et al (Int Wound J 15:749-755 (June 2018)- previously cited). This rejection is maintained from the office action mailed 8/13/2025, but has been amended to reflect claims filed 11/13/2025.
Shin et al teach that albumin is a protein which is very abundant in the blood and is made in the liver. Structurally, human serum albumin (HSA) is composed of 585 amino acids (66,438 Da), 17 disulfide bridges and one free cysteine (Cys34) (paras. [0003]). Albumin functions to maintain and restore the volume of plasma, and is coupled with a variety of ligands such as water, calcium, sodium and potassium cations, fatty acids, hormones, bilirubin, drugs, etc. to adjust the colloid osmotic pressure of blood and to deliver the ligand, and plays a role as an amino acid source in the case of poor nutrition. Human serum albumin (HAS) is used to treat hypoalbuminemia caused due to albumin loss and albumin synthesis dysfunction, including surgical operations, hemorrhagic shock or burns and nephrotic syndromes. Albumin is used as a drug additive for supplementing a medium for use in the growth of higher eukaryotic cells and for mixing a therapeutic protein. Serum albumin is supposed to act as an oxygen carrier which is adsorbed to or desorbed from oxygen depending on the partial pressure of oxygen, like hemoglobin. In emergency cases, albumin may be administered in lieu of hemoglobin. Id. The term “human serum albumin formulation” refers to a concept including all formulations made of human serum albumin, which may be formulated in the form of being administrable to a subject including human, and may include commercially available albumin formulations, and formulations prepared to replace them, having components, functions and efficacies similar to the commercially available albumin formulations (para. [0028]). In order for the human serum albumin to be prepared in the form of a formulation which may be administered to the human body, it is necessary for a process of a thermal treatment to prevent virus contamination and/or other infections. However, human serum albumin, like typical proteins, may be structurally changed or agglutinated and thus denatured upon treatment at high temperature. Hence, an additive is required to stabilize the albumin (para. [0029]). Shin et al teach a stable human serum albumin formulation comprising a fatty acid selected from the group consisting of C16 to C22 fatty acids or a pharmaceutically acceptable salt thereof (abstract; claims 1-18). C16 to C22 fatty acids include palmitic acid and palmitoleic acid as C16 fatty acids, stearic acid (octadecanoic acid), oleic acid, linoleic acid and linolenic acid as C18 fatty acids, eicosapentaenoic acid (EPA) as a C20 fatty acid, docosahexaenoic acid (DHA) as a C22 fatty acid, and combinations thereof (para. [0031]-[0046], claims 3 and 8). The molar ratio of long-chain fatty acid to albumin is between 1:0.5 to 1:2 (paras. [0044]-[0048], claims 5 and 10). The fatty acids improve the thermal stability of albumin and reduce denaturing from heat treatment (abstract, paras. [0005], [0008], [0029], 0060], [0069]-[0071], Ex 6-9). The appropriate concentration of the human serum albumin formulation is not particularly limited so long as it is adapted for a human serum albumin formulation, and may be set to 50 to 200 mg/mL (para. [0076]). Shin et al teach that the prepared albumin formulations may be administered to a subject including a human by means of any device able to deliver an active material to a target cell. The preferable administration mode and formulation may be provided in the form of an injection, including intravenous injection, subcutaneous injection, intradermal injection, muscular injection, drop injection, etc. (para. [0077]). The formulations can further comprise an emulsifier, a buffer a buffer for adjusting pH, a preservative for suppressing growth of microorganisms, etc. Id.
Although, Shin et al teach that the human serum albumin formulations may include an emulsifier, the reference does not explicitly teach a composition comprising a poloxamer.
Percival et al teach that surfactants are widely used as detergents, emulsifiers, wetting agents, foaming agents, and dispersants in both the food and oil industry. Their use in a clinical setting is also common, particularly in wound care. Complicated or chronic wounds show clinical signs of delayed healing, persistent inflammation, and the production of non-viable tissue. These types of wounds also present challenges such as infection and potentially house antimicrobial-tolerant biofilms. The use of wound cleansers to aid cleaning and debridement of the wound is essential. A large proportion of skin and wound cleansers contain surfactants but there is only a small amount of data that shows the effectiveness of them in the enhancement of wound closure (abstract). Percival et al teach the use and mode of action of surfactants in wound healing, in particular Poloxamer 188 (Pluronic F-68) and Poloxamer 407 (Pluronic F-127), and also the potential mechanisms behind the enhancement of wound healing and comparison to other surfactants used in wound care. Id. Percival et al teach that Poloxamer 108 (P108), Poloxamer 188 (P188), and Tetronic 1107 (T1107) are efficient as additives to suppress aggregation of and to facilitate refolding of heat-denatured albumin in solution (p. 751). The reduction of protein aggregation by Poloxamer 188 has also been effectively demonstrated and, therefore, presents interesting opportunities in biomedical sectors where the refolding of denatured proteins is problematic (p. 753). Percival et al further teach that the non-ionic surfactant Pluronic F68 (Poloxamer 188) is safe to use on mammalian cells, demonstrating multiple functions when incorporated in wound dressings, including reduction of pain, swelling, and inflammation (p. 752).
It would been obvious to one of ordinary skill in the art to have included a poloxamer in the albumin formulations of Shin et al. comprising a long-chain fatty acid. Shin et al taught that albumin formulations are used in situations of albumin loss and albumin synthesis dysfunction, including surgical operations, hemorrhagic shock or burns and nephrotic syndromes. In emergency cases, albumin may be administered in lieu of hemoglobin. Shin et al further taught that for administration to the human body, it is necessary for a process of a thermal treatment to prevent virus contamination and/or other infections. However, human serum albumin, like typical proteins, may be structurally changed or agglutinated and thus denatured upon treatment at high temperature. Hence, an additive is required to stabilize the albumin. Shin et al teach that a long-chain fatty acid of C16 to C22 helps to thermally stabilize the albumin from denaturation/aggregation. Shin et al taught that the albumin formulations could include additional components, emulsifiers/surfactants. The skilled artisan would have recognized from Percival et al that poloxamers were also useful in suppressing aggravation/denaturation of protein such as albumin. The prior art further taught that poloxamers enhanced wound care healing.
"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted). See M.P.E.P. § 2144.06. The prior art taught that albumin and poloxamer were useful in formulations for wound care. The prior art further taught that long-chain fatty acids and poloxamers stabilized albumin from denaturation/aggregation. Thus, it would have been obvious to the skilled artisan to have prepared a composition comprising human albumin, a long-chain fatty acid, and a poloxamer.
The U.S. Federal Circuit has explicitly stated that in order to make a prima facie case of obviousness, the suggestion and motivation to combine the references need not be explicitly stated in the text of the references. In DyStar Textilfarben GmbH & Co. Deutschland KG v. C.H. Patrick Co., 80 USPQ2d 1641 (Fed. Cir. 2006), the Court writes, “the suggestion test is not a rigid categorical rule. The motivation need not be found in the references sought to be combined, but may be found in any number of sources, including common knowledge, the prior art as a whole, or the nature of the problem itself. In re Dembiczak, 175 F.3d 994, 999 [50 USPQ2d 1614] (Fed. Cir. 1999). As we explained in Motorola, Inc. v. Interdigital Tech. Corp., 121 F.3d 1461, 1472 [43 USPQ2d 1481] (Fed. Cir. 1997), ‘there is no requirement that the prior art contain an express suggestion to combine known elements to achieve the claimed invention. Rather, the suggestion to combine may come from the prior art, as filtered through the knowledge of one skilled in the art.’” See Dystar at 1645. “Our suggestion test is in actuality quite flexible and not only permits, but requires, consideration of common knowledge and common sense.” See Dystar at 1650.
In this case, Shin et al taught compositions comprising albumin and a long-chain fatty acid, wherein the fatty acid improved thermal stability of the albumin. Shin et al teach that the molar ratio of long-chain fatty acids to albumin between 1:0.5 to 1:2 (paras. [0044]-[0048], claims 5 and 10). Percival et al further taught that poloxamer is could be used to stabilize albumin. Thus, the motivation to combine can be found in the common knowledge of the art and common sense of its skilled practitioners. The skilled artisan would have had a reasonable expectation of success because albumin formulations (as taught by Shin et al), as well poloxamers (as taught by Percival et al), were taught in the art as being useful in wound care. Shin et al teach that the molar ratio of long-chain fatty acids to albumin between 1:0.5 to 1:2 (paras. [0044]-[0048], claims 5 and 10). Examiner further notes that Shin et al taught inclusion of additional excipients within the albumin formulations, e.g., a surfactant such as a poloxamer. The optimization of a result effective parameter (e.g., ratio of poloxamer to human albumin) is obvious as being within the skill of the artisan. The optimization of known effective amounts of known active agents is considered well within the competence level of an ordinary skilled artisan in pharmaceutical science, involving merely routine skill in the art. It has been held that it is within the skill in the art to select optimal parameters, such as amounts of ingredients, in a composition in order to achieve a beneficial effect (e.g., stabilization of the albumin protein from aggregation/denaturation). See In re Boesch, 205 USPQ 215 (CCPA 1980).
Accordingly, instant claim 26 is rendered obvious.
Regarding claims 30 and 31, teach Poloxamer 188 and Poloxamer 407 for use in wound care compositions (abstract, pp. 749-754). The reference also teaches that the poloxamer reduce protein aggregation and denaturation of proteins such as albumin. Regarding claim 32, Shin et al teach that the long-chain fatty acids include C16 to C22 fatty acids or a pharmaceutically acceptable salt thereof (abstract; claims 1-18). C16 to C22 fatty acids include palmitic acid and palmitoleic acid as C16 fatty acids, stearic acid (octadecanoic acid), oleic acid, linoleic acid and linolenic acid as C18 fatty acids, eicosapentaenoic acid (EPA) as a C20 fatty acid, docosahexaenoic acid (DHA) as a C22 fatty acid, and combinations thereof (para. [0031]-[0046], claims 3 and 8).
Accordingly, claims 26 and 30-32 are obvious in view the teachings of the cited references.
Response to Arguments
Applicant traversed the rejection at pp. 10-12 of the reply filed 11/13/2025. Applicant asserts that claim 26 was amended to recite “the content of the poloxamer in the medical product is 10-500 µg poloxamer / 1 g human albumin” [incorporate limitations of claim 29] (p. 10). Applicant asserts that the cited reference Percival does not disclose this claim limitation (reply at p. 11). Applicant asserts unexpected results that poloxamer improved stability of the recombinant human albumin (pp. 11-12). Applicant asserts that greater than 500 µg poloxamer 188 /1 g human albumin decreases stability of human albumin (pp. 11-12). Applicant asserts that the cited references, either alone or in combination, do not teach all of the cited claim limitations (p. 12).
Examiner has reviewed and considered applicants arguments, but is not persuaded.
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).
Even if applicant did properly establish unexpected results, recent caselaw reiterated the principle from Newell Cos. v. Kenny Mfg. Co., 9 USPQ2d 1417, 1426 (Fed. Cir. 1988) that the mere presence of secondary considerations does not necessarily overcome a strong case of obviousness. See Pfizer Inc. v. Apotex Inc., 82 U.S.P.Q.2d 1321, 1338-39 (Fed. Cir. 2007) (quoting In re Chupp, 816 F.2d 643, 646 (Fed. Cir. 1987)). Secondary considerations are only one factor in determining obviousness. The cited art establishes that the skilled artisan would have expected improved stability of albumin.
In this case, Shin et al taught compositions comprising albumin and a long-chain fatty acid, wherein the fatty acid improved thermal stability of the albumin. Shin et al teach that the molar ratio of long-chain fatty acids to albumin between 1:0.5 to 1:2 (paras. [0044]-[0048], claims 5 and 10). Percival et al further taught that poloxamer is could be used to stabilize albumin. Thus, the motivation to combine can be found in the common knowledge of the art and common sense of its skilled practitioners. The skilled artisan would have had a reasonable expectation of success because albumin formulations (as taught by Shin et al), as well poloxamers (as taught by Percival et al), were taught in the art as being useful in wound care. The optimization of a result effective parameter (e.g., ratio of poloxamer to human albumin) is obvious as being within the skill of the artisan. The optimization of known effective amounts of known active agents is considered well within the competence level of an ordinary skilled artisan in pharmaceutical science, involving merely routine skill in the art. It has been held that it is within the skill in the art to select optimal parameters, such as amounts of ingredients (a content of poloxamer 10-500 µg poloxamer /1 g human albumin), in a composition in order to achieve a beneficial effect (e.g., stabilization of the albumin protein from aggregation/denaturation). See In re Boesch, 205 USPQ 215 (CCPA 1980).
The rejection is maintained for at least these reasons, and those previously made of record. Please see the above rejection for full details.
Claim(s) claims 26, 30-32 and 34 remain/are rejected under 35 U.S.C. 103 as being unpatentable over Shin et al (U.S. 2015/165000- previously cited), and Percival et al (Int Wound J 15:749-755 (June 2018)- previously cited).as applied to claims 26 and 30-32 above, and further in view of Yu et al (J. Pharma Sci 73: 82-86 (1984)- previously cited). This rejection is maintained from the office action mailed 8/13/2025, but has been amended to reflect claims filed 11/13/2025.
The teachings of Shin et al and Percival et al are set forth above. The references do not explicitly teach human albumin containing medical product comprising sodium caprylate and/or an N-acetyltryptophan.
Yu et al teach that N-acetyltryptophan was a common stabilizer used in human albumin therapeutic products (abstract, pp. 82, 85-86). Yu et al teach that to human albumin products are heated to and activate hepatitis viruses, and to minimize changes in the protein during the heating procedure stabilizers are added (p. 82).
"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted). See M.P.E.P. § 2144.06. The prior art taught that albumin and poloxamer were useful in formulations for wound care. The prior art further taught that long-chain fatty acids, poloxamers, and N-acetyl tryptophan stabilized albumin from denaturation/aggregation. Thus, it would have been obvious to the skilled artisan to have prepared a composition comprising human albumin, a long-chain fatty acid, a poloxamer, and N-acetyltryptophan, in the claimed molar ratios and weight contents.
Accordingly, claim 34 is rendered obvious.
Claims 26, 30-32 and 34 are obvious in view the teachings of the cited references.
Response to Arguments
Applicant traversed the rejection at pp. 10-12 of the reply filed 11/13/2025. Applicant provided the arguments set forth above.
Examiner refers applicant to the above rebuttal arguments that apply to this rejection, and are incorporated herein.
The rejection is maintained for at least these reasons, and those previously made of record.
New Objections/ Rejections
Claim Objections- New
Claims 26 and 34 are objected to because of the following informalities:
Claim 26 should be amended to recite
“product is 0.2-3.0:1.0[[,]]; and
wherein a”.
Claim 34 should be amended to recite “sodium caprylate, , or combination thereof”.
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 26, 30-32, and 34 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.
This is a new rejection necessitated by the amendment filed 11/13/2025.
Claim 26 recites the limitation "the medical product" at lines 2, 5, and 6. There is insufficient antecedent basis for this limitation in the claim.
Because claims 30-32, and 34 are depend from indefinite claim 26 and do not clarify the point of confusion, they must also be rejected under 35 U.S.C. 112, second paragraph.
To overcome this rejection, claim 26 should be amended to recite “the albumin-containing medical product”.
Claim 34 recites the limitation ""the medical product" at line 2. There is insufficient antecedent basis for this limitation in the claim. To overcome this rejection, claim 26 should be amended to recite “the albumin-containing medical product”.
Relevant Art not Relied Upon
Ginsberg et al (U.S. 2005/0164908- previously cited) teach a pharmaceutical composition useful in treating cerebral ischemia and cerebral injury. The pharmaceutical composition is also useful as a prophylactic treatment during surgical procedures wherein the potential for ischemic tissue damage is present (abstract). Ginsberg et al teach a pharmaceutical composition comprising a therapeutically effective amount of albumin [human] and a polyunsaturated fatty acid for mitigating ischemic and hemrrohagic tissue damage and a suitable pharmaceutical carrier (paras. [0010], [0019]-[0022], claims 1-18). The polyunsaturated fatty acid can be docosahexaenoic acid (reads on long-chain fatty acid) (para. [0002], claims 5-7, 11, 15-18).
CN 107674860 (hereinafter referred to as “the ‘860 application” – previously cited) teaches a composition comprising human albumin, poloxamer 188, linoleic acid, oleic acid, and palmitic acid (claims 1, 4, 7; paras. [0009], [0015], [0066]-[0068], [0183]-[0185]). Examiner refers to the English machine translation of the ‘860 application that was previously cited. The ‘860 application teaches that the compositions are in the field of biomedicine [reads on human albumin containing medical product]. The ‘860 application does not explicitly teach or suggest the claimed molar ratio of long-chain fatty acids to albumin, or the recited weight ratio poloxamer: human albumin.
Conclusion
No claims are allowed.
Claims 26, 30-34, 36, and 39-41 are pending. Claims 33, 36, and 39-41 are withdrawn.
Claims 26, 30-32, and 34 are rejected.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTINA M HELLMAN whose telephone number is (571)272-2836. The examiner can normally be reached M-F 9:00 am-5:30 pm.
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/KRISTINA M HELLMAN/ Examiner, Art Unit 1654
/JULIE HA/ Primary Examiner, Art Unit 1654