DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . Applicant should note that the examiner assigned to this case has changed.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114 was filed in this application after a decision by the Patent Trial and Appeal Board, but before the filing of a Notice of Appeal to the Court of Appeals for the Federal Circuit or the commencement of a civil action. Since this application is eligible for continued examination under 37 CFR 1.114 and the fee set forth in 37 CFR 1.17(e) has been timely paid, the appeal has been withdrawn pursuant to 37 CFR 1.114 and prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant’s submission filed on 6/27/2025 has been entered.
Response to Amendments
Applicant's amendments filed 6/27/2025 to claim 15 have been entered. Claims 2-4, 11-14, and 21 are canceled. Claims 24-30 have been added. Claims 1, 5-10, 15-20, and 22-30 remain pending, of which claims 1, 5-10, 15, and 22-30 are under consideration on the merits. Claims 16-20 remain withdrawn at this time. References not included with this Office action can be found in a prior action.
In view of the decision by the Patent Trial and Appeal Board decision dated 12/27/2024, the following rejections are withdrawn: 1) the 35 U.S.C. § 112(a) rejections of claims 8 and 15, 2) The 35 U.S.C. § 112(b) rejection of claim 15, and 3) the 35 U.S.C. § 103 rejections of claims 1, 5-10, 15, and 21-23 over Werber in view of Koob. New grounds of rejection are set forth below.
Any other rejections of record not particularly addressed below are withdrawn in light of the claim amendments and/or applicant’s comments.
Claim Rejections - 35 USC § 112
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.
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, 5-10, 15, and 22-30 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 limitation "the portion of an intact intermediate layer" in 3. There is insufficient antecedent basis for this limitation in the claim. Correction is required.
The term “substantially” in claims 10 and 29 is a relative term which renders the claim indefinite. The term “substantially” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Correction is required.
Claim 15 and 23 recite an “intact” intermediate layer scaffold membrane “portion”. It is unclear how the membrane can be “intact” while also being a “portion”. A “portion” of a membrane, is not a complete or “intact” membrane. Furthermore, while it appears that applicant might be interpreting the term “portion” to mean component, the term “portion” could mean a piece of the membrane, and therefore this term further renders the claim indefinite. If applicant intended to claim that a portion of the membrane remains intact, the examiner suggests amending the claims to reflect this. It is noted that applicant’s amendment to independent claim 1 overcame the rejection of this claim under 35 U.S.C. 112(b) in reference to this issue, however, applicant did not also incorporate these amendments into independent claim 15.
Claim 15 recites “human biological membrane portion” in lines 5-6. It is unclear if this limitation refers to (1) the “intact intermediate layer scaffold membrane portion” in line 2, or (2) if it is referring to a new human biological membrane portion. Since the phrase “human biological membrane portion” can refer to other types of membrane portions besides an intact intermediate layer scaffold membrane portion, it is not clear what this phrase is in reference to.
Because claims 5-10, 22, and 24-30 depend from either claim 1 or claim 23 and do not resolve the point of confusion, these claims must be rejected with claims 1 and 23 as indefinite.
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 1, 5-10, 15, and 22-30 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural product without significantly more.
Claims 1, 5-7, 15, 22-26, and 30 recite a combination of two natural products: 1) plasma, and 2) human amniotic membrane. These natural products occur naturally in vivo as taught by Malhotra et al. (World J Transplant (2014 June 24); 4(2): 111-121; Reference U) and together as part of fetal membranes, wherein the endogenous fetal membrane comprises an outer and vascular chorion (i.e. comprising blood and so the plasma fraction of blood) in contact with the uterine wall and an inner amniotic membrane which is avascular and comprises epithelium, basement membrane (i.e. extracellular matrix), and stroma and is contact with the amniotic fluid (e.g. a species of plasma when read in light of claim 5) (Figure 1 and page 112, subheading “Structure of Fetal Membranes”). At this time, there is no evidence of record that the two judicial exceptions, i.e. the natural products comprising plasma and an intact human amniotic membrane, in the claimed composition otherwise imparts any markedly difference characteristic compared to the natural product of vascular fetal membrane comprising an amniotic membrane. See M.P.E.P. § 2106.04(c)(I). Dependent claims 8, 9, 27, and 28 only recite limitations inherent to human plasma/serum, which inherently comprises growth factors such as EGF as taught by Lev-Ran et al. (Am J Physiol. (1990), 259 (3 Pt 2): R545-548; Reference V). Dependent claims 10 and 29 read on the embodiment of amniotic fluid which does not comprises fibrin or fibrinogen as taught by Benzie et al. (AJOG (1974), 119(6), 798-810; Reference W) (see Table IV on pages 802-803).
This judicial exception is not integrated into a practical application and does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims are only directed towards the natural product itself or inherent/latent properties therein as set forth above, and without any clear indication the claimed composition possesses any markedly different characteristic as compared to its nearest natural counterpart. Incidental change(s) that might result from isolating a product of nature is generally insufficient, by itself, to make a product of nature markedly different to its naturally occurring counterpart in the natural state; see M.P.E.P. § 2106(II) and particularly M.P.E.P. § 2106(II)(C)(2).
Therefore, claims 1, 5-10, 15, and 22-30 are rejected as patent ineligible under 35 U.S.C. § 101.
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.
Claims 1, 5, 6, 8, 9, 15, 22-25, 27, 28, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Mahmoudi-Rad et al. (Clinical and Experimental Dermatology (2013), 38, 646-651; Reference X) in view of Llames et al. (Transplantation (2004), 77(3), 350-355; Reference U2) and as evidenced by Lev-Ran et al. (Am J Physiol. (1990), 259 (3 Pt 2): R545-548; Reference V).
Mahmoudi-Rad teaches an intact acellular human amniotic membrane, obtained from mothers who had given birth at full term via caesarean section, to prevent any possible contamination during normal vaginal delivery and who tested negative for HIV, hepatitis B and C, and syphilis (page 647, subheading “Preparation of amniotic membrane” and Figure 2), reading in-part on claims 1, 15, and 23, and reading on claims 22 and 30. Mahmoudi-Rad teaches seeding fibroblasts on the acellular human amniotic membrane to generate a skin substitute (pages 647-648, subheading “Preparation of skin substitute”), reading in-part on claims 1, 15, and 23. Mahmoudi-Rad teaches that human plasma, formulated as clotted plasma-based matrix, as a known scaffold for fibroblasts and keratinocytes in skin substitute compositions and citing in-part the teachings of Llames (the paragraph spanning pages 648-649), reading in-part on claims 5, 6, 8, 9, 24, 25, 27, and 28.
Regarding claims 1, 15, and 23, Mahmoudi-Rad does not teach an intact acellular human amniotic membrane further comprising plasma. Regarding claims 1 and 15, Mahmoudi-Rad does not teach an intact acellular human amniotic membrane further comprising plasma at the claimed concentration ranges. Regarding claims 5 and 24, Mahmoudi-Rad does not teach human plasma. Regarding claims 6 and 25 Mahmoudi-Rad does not teach plasma comprising extracellular matrix. Regarding claims 8, 9, 27, and 28, Mahmoudi-Rad does not teach plasma comprising the embodiment of at least one growth factor.
Llames teaches a human plasma composition, formulated as clotted plasma-based matrix as a scaffold for the culturing of keratinocytes and fibroblasts and generation of a dermal equivalent composition (Abstract; Materials and Methods on pages 350-351), reading on claims 1, 5, 15, 23, and 24. Llames teaches a final volume of the human plasma composition formulated as clotted plasma-based matrix composition of 23 ml prior to the addition of 8-9 x 104 keratinocytes (page 351, subheadings “Preparation of Plasma-Based Dermal Equivalent” and “Keratinocyte Expansion on the Plasma-Based Dermal Equivalent”), reading in-part on the plasma concentrations of claims 1 and 15. Llames teaches that plasma-based dermal equivalent composition successfully regenerates skin when transplanted into subjects (Figure 2 and page 352, paragraph starting “The regeneration performance…” through paragraph ending “…C, E, and F).”, reading on claims 1, 5, 6, 8, 9, 15, 23-25, 27, and 28. Llames teaches that plasma-based dermal equivalent composition comprises collagen (Fig. 2G and the paragraph starting “Immunostaining of…” on page 353), reading on the embodiment of collagen for claims 6 and 25.
Regarding claims 8, 9, 27, and 28, Llames is silent regarding the presence of at least one growth factor in the human plasma. However, Lev-Ran teaches that human serum and plasma inherently comprises epidermal growth factor (EGF) (Abstract). Therefore, the teachings of Llames as evidenced by Lev-Ran reads on claims 8, 9, 27, and 28 (see M.P.E.P. § 2112).
Regarding the plasma of claims 1, 5, 6, 8, 9, 15, 23-25, 27, and 28, it would have been obvious to a person of ordinary skill in the art before the invention was filed to add the human plasma composition formulated as clotted plasma-based matrix of Llames to the intact acellular human amniotic membrane of Mahmoudi-Rad as evidenced by Lev-Ran. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Mahmoudi-Rad and Llames are directed in-part towards skin equivalent/substitute compositions further comprising dermal cells and because The skilled artisan would have been motivated to do so because Mahmoudi-Rad expressly cites the teachings of Llames as pertinent art. The skilled artisan would have been motivated to do so because Llames teaches that the addition of human plasma composition formulated as clotted plasma-based matrix would be predictably advantageous to improve the skin equivalent/substitute composition of Mahmoudi-Rad as a substrate for keratinocyte culture and to successfully regenerates skin when transplanted into subjects when administered to subjects in need of treatment thereof.
Regarding the plasma concentrations of claims 1 and 15, optimization within prior art conditions or through routine experimentation will generally not support patentability absent a showing of criticality of the claimed range to the contrary. See M.P.E.P. § 2144.05, particularly subsections II and III. In this case, Llames makes clear that the plasma concentration is necessarily result-effective with respect to the concentration of added keratinocytes in vitro and the ability of the plasma-based dermal equivalent composition to successfully regenerates skin when transplanted into subjects in vivo. Thus, the burden is shifted back to establish criticality of the claimed plasma concentration range by objective evidence.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claims 1, 5, 7, 10, 15, 22-24, 26, 29, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Mahmoudi-Rad et al. (Clinical and Experimental Dermatology (2013), 38, 646-651; Reference X) in view of Thakoersing et al. (Tissue Engineering: Part A (2010), 16(4), 1433-1441; Reference V2).
Mahmoudi-Rad teaches an intact acellular human amniotic membrane, obtained from mothers who had given birth at full term via caesarean section, to prevent any possible contamination during normal vaginal delivery and who tested negative for HIV, hepatitis B and C, and syphilis (page 647, subheading “Preparation of amniotic membrane” and Figure 2), reading in-part on claims 1, 15, and 23, and reading on claims 22 and 30. Mahmoudi-Rad teaches seeding fibroblasts on the acellular human amniotic membrane to generate a skin substitute (pages 647-648, subheading “Preparation of skin substitute”), reading in-part on claims 1, 15, and 23. Mahmoudi-Rad teaches that human plasma, formulated as clotted plasma-based matrix, as a known scaffold for fibroblasts and keratinocytes in skin substitute compositions and citing in-part the teachings of Llames (the paragraph spanning pages 648-649), reading in-part on claims 5, 6, 8, 9, 24, 25, 27, and 28
Regarding claims 1, 15, and 23, Mahmoudi-Rad does not teach an intact acellular human amniotic membrane further comprising plasma. Regarding claims 1 and 15, Mahmoudi-Rad does not teach an intact acellular human amniotic membrane further comprising plasma at the claimed concentration ranges. Regarding claims 5 and 24, Mahmoudi-Rad does not teach human plasma. Regarding claims 7 and 26, Mahmoudi-Rad does not teach amniotic plasma. Regarding claims 10 and 29 and in view of the indefiniteness rejection above, Mahmoudi-Rad does not teach a composition lacking fibrin or fibrinogen.
Thakoersing teaches generating dermal equivalent compositions by culturing fibroblasts and keratinocytes on collagen gels under submerged conditions and further adding 200 μL amniotic fluid (page 1434, paragraph starting “Generated on dermal equivalents…” through paragraph ending “…as the collagen HSEs.”), reading on the embodiment of amniotic plasma for claims 1, 5, 7, 15, 23, 24, 26, and 29 and reading in-part on the plasma concentrations of claims 1 and 15. Thakoersing does not teach fibrin or fibrinogen as part of the amniotic fluid-treated human skin equivalent (HSE) compositions (page 1434, paragraph starting “Generated on dermal equivalents…” through paragraph ending “…as the collagen HSEs.”), reading on the negative limitations of claims 10 and 29. Thakoersing teaches adding 0.5-1.0 x 106 cells per collagen gel (page 1434), reading in-part on the plasma concentrations of claims 1 and 15. Thakoersing teaches that the amniotic fluid-treated human skin equivalents (AF) have a similar morphology to human skin equivalents cultured on collagen and submerged (SM) and cultured on collagen and air-exposed (AE) and contain all epidermal cell layers and resemble the morphology of human skin (Figure 1, the bottom row as compared to “Collagen SM” and Collagen AE”; page 1435, paragraph starting “To determine whether all the epidermal layers…” through the paragraph spanning pages 1435-1436), reading in-part on the plasma concentrations of claims 1 and 15.
Regarding the embodiment of human amniotic plasma of claims 1, 5, 7, 10, 23, 24, 26, and 29, "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. In this case, the human amniotic membrane of Mahmoudi-Rad and the human amnionic plasma of Thakoersing are taught as useful for the same purpose as starting reagents to generate human skin equivalent compositions, and so their combination must be held prima facie obvious absent any persuasive showing of nonobviousness to the contrary.
Regarding the plasma concentrations of claims 1 and 15, optimization within prior art conditions or through routine experimentation will generally not support patentability absent a showing of criticality of the claimed range to the contrary. See M.P.E.P. § 2144.05, particularly subsections II and III. In this case, Thakoersing makes clear that the plasma concentration is necessarily result-effective to generating human skin equivalent compositions having similar morphology to human skin. Thus, the burden is shifted back to establish criticality of the claimed plasma concentration range by objective evidence.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
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 1, 5-10, 15, and 22-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of copending Application No. 16/043,505 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because both are drawn to an acellular product comprising a plasma portion and a biological membrane portion, wherein the biological membrane portion is impregnated with the plasma portion or a method of making said product. The methods of the copending ‘505 application necessarily make the claimed composition
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Claims 1, 5-10, 15, and 22-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 16/794,051 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because both are drawn to an acellular product comprising a plasma portion and a biological membrane portion, wherein the biological membrane portion is impregnated with the plasma portion. In addition, please note that the instant claims encompass and/or are encompassed by the ‘051 claims.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Claims 23 and 25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, and 9 of U.S. Patent No. 12,551,509 (Reference A).
Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of the ‘509 recites a composition comprising cellular placental product comprising a human amniotic plasma portion and an intact intermediate layer scaffold membrane portion; said intermediate layer being isolated from human amniotic membrane; said intact intermediate layer scaffold membrane portion being impregnated with said human amniotic plasma portion, and thus reading on instant claim 1. Claim 6 of the ‘509 patent reads on instant claims 8 and 9 as intact human amniotic membrane inherently comprises collagen and hyaluronic acid as evidenced by Malhotra (page 112-113, subheading “Basement membrane” and “Anti-fibrotic and anti-inflammatory properties”). Claim 6 of the ‘509 patent reads on instant claim 25.
Response to Arguments
Applicant's arguments on pages 4-6 of the reply have been fully considered, but are not found persuasive of error. Applicant’s arguments are moot in-part because the new ground(s) of rejection do not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument, and the rejections reversed by the Patent Trial and Appeal board in the decision dated 12/27/2024 are withdrawn.
It is noted that Applicant did not make any specific arguments over the 35 U.S.C. § 112(b) rejections of record for claims 1, 5-10, 15, 22, and 23 that were affirmed on appeal.
In so much that the case is not in condition for allowance, Applicant’s arguments regarding the nonstatutory double patenting rejections on page 5 of the reply are not found persuasive.
Conclusion
No claims are allowed. No claims are free of the art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN C BARRON whose telephone number is (571)270-5111. The examiner can normally be reached 7:30am-3:30pm EDT/EST (M-F).
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/Sean C. Barron/Primary Examiner, Art Unit 1653
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