DETAILED 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 .
Claims 1-2,10,13-16,21,27-32,77,79, and 121-126 are under examination.
Response to Examiner’s Amendment/Arguments
The examiner has decided to add additional references to the former rejection. The prior art does not teach a dehydrated product comprising a population of uncultured amniotic cells obtained from filtered amniotic fluid, wherein the product is substantially free of both red blood cells and also urea, and wherein the product comprises hyaluronic acid obtained from amniotic fluid. The limitation that makes claims 2,10,13,21,121-122, and 125 allowable is the absence of urea because the prior art does not teach such a product where the urea has been removed. The references that are discussed by applicants’ remarks and maintained in the rejections are listed below each specific rejection.
Claim Objections
Claim 15 is objected to because of the following informalities: TIMP is –tissue inhibitor metalloproteinase—instead of “tissue inhibitor metallopeptidase”. Furthermore, IL-1Rα stands for –interleukin-1 receptor antagonist—not “interleukin 1A receptor.” Appropriate correction is required.
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.
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 1,14-16,27-28,30-32,77,79,123-124, and 126 are rejected under 35 U.S.C. 103 as being unpatentable over Harrell (US 20140336600) in view of Horton (US 20130084314), Won (WO2008062998), Tseng (US 20150342998), and Yu et al. “Freeze-drying of Human Red Blood Cells: Influence of Carbohydrates and Their Concentrations” Cell Preservation Technology, Volume 2, Number 4, 2004
Harrell teaches in paragraph 23 an amniotic fluid that is filtered using a filter with a pore size of 100 µm. This would produce a filtrate containing small cells/stem cells and hyaluronic acid (hyaluronic acid is inherently present) in amniotic fluid. The hyaluronic acid is so small that it would be able to flow through the filter and remain in the amniotic fluid solution. Horton discloses that high concentrations of hyaluronic acid exist naturally in amniotic fluid (Paragraph 8 of Horton). Won teaches that hyaluronic acid is such a small molecule that can easily pass thorough a filter with pore sizes of 100 µm (hyaluronic acid can easily pass through filters with pore sizes of 0.2 µm) (Paragraph 11 of Won). Using a filter with a pore size of 100 µm would allow cells, hyaluronic acid, growth factors, glycoproteins, glycosaminoglycans, polycarbohydrates, cytokines, proteins having a molecular weights less than or greater than 600 kDa to successfully pass through as in instant Claims 1,14-15, and 123-124.
Harrell does not expressly state that its composition is in a lyophilized form without blood cells. However, Tseng teaches that amniotic fluid and tissue (composed of cells) derived from amniotic fluid can be used for therapeutic purposes (Paragraphs 4-6,25,31, and 38); Tseng also teaches that it is desirable to use stem cells in a therapy since they promote tissue regeneration and assist with wound care (Paragraph 4 of Tseng). Paragraph 31 of Tseng teaches that such a composition can be lyophilized and reconstituted at a later date.
It would have been obvious to an artisan of ordinary skill at the time of effective filing to have used in the amniotic fluid taught in Harrell in a lyophilized therapy. An artisan would have been motivated to have used amniotic fluid because Tseng teaches that amniotic fluid and cells derived from amniotic fluid can be used in therapies to successfully treat ocular damage, burns, necrosis, skin damage, nerve conditions, wound, etc applications (Paragraph 84 of Tseng). Furthermore, an artisan would have been motivated to have lyophilized the product as taught by Tseng because it allows for easier storage (Paragraph 32 of Tseng). Because lyophilized amniotic fluid/cells can be used therapeutically, there would have been a high expectation for success (Paragraph 84 of Tseng).
Tseng teaches lyophilization of amniotic fluid materials. Yu teaches that red blood cell viability and survival after the lyophilization process is poor without adding specifical cryoprotectants to protect the red blood cells from such processes (Abstract of Yu). Tseng does not take special precautions to protect the red blood cells during the lyophilization process, thus, it would be expected that the amounts red blood cells and hemoglobin (a component of red blood) cells would be expected to be non-existent and/or extremely low as in instant Claims 1 and 16.
Dependent Claim taught by Harrell
Using a filter with pore sizes of 100 µm would allow electrocytes, growth factors, carbohydrates, lipids, proteins, amino acids, lactate, pyruvate, enzymes, hormones to pass through into the filtrate. This protein fraction would include proteins having a molecular weight of less than 600 kDa and greater than 600 kDa as in instant Claims 14-15. Harrell teaches that the product can be sterile filtered (Paragraphs 23 of Harrell) as in instant Claim 32.
Dependent Claims taught by Tseng
Tseng teaches wherein the serum of the donor of the sample of amniotic fluid is negative for one or more antibodies to HIV-1, HIV-2, HBV, HCV, HTLV-1 (Claim 27) as in instant Claim 27. Tseng teaches wherein the product is lyophilized (Paragraphs 27 and 32) as in instant Claim 28. Tseng teaches a dry lyophilized form in a powder form (Paragraphs 31-32) as in instant Claim 30. Tseng teaches wherein the product has a residual moisture content of about 2% to about 15% (Paragraph 32) as in instant Claim 31. Tseng teaches wherein the product is sterile (Paragraph 27 of Tseng) as in instant Claim 32. Tseng teaches a pharmaceutical composition comprising the product of claim 1 and a pharmaceutically acceptable carrier (Paragraphs 42-66) as in instant Claim 77. Tseng teaches a kit comprising a product of claim 1 and a pharmaceutically acceptable carrier (Paragraphs 42-66) as in instant Claim 79. Tseng teaches that an acceptable carrier includes collagen, water, and hyaluronic acid (Paragraph 33) as in instant Claim 123. Tseng teaches the composition can be in the form of a cream, ointment, or lotion (Paragraph 33) as in instant Claims 124 and 126.
Harrell teaches a product containing filtered amniotic fluid containing cells which inherently has hyaluronic acid present. Harrell does not teach that such a composition can be lyophilized into a treatment pharmaceutical in which blood cells are removed. However, Tseng teaches that such a composition can be treated by lyophilization to produce a therapeutic composition for healing. An artisan would have been motivated to have lyophilized Harrell’s product since Tseng teaches that cells derived from amniotic fluid and amniotic fluid itself can successfully be used in a composition to treat individuals for a large range of conditions listed in paragraph 84 of Tseng. Yu teaches that the lyophilization process itself can destroy red blood cells. Therefore, it would be expected that compositions undergoing lyophilization would be lacking in red blood cells and hemoglobin. Given the teachings of the cited references and the level of skill of an artisan at the time of applicants’ invention, it must be considered absent evidence to the contrary that the ordinary skilled artisan would have had a reasonable success in practicing the claimed invention.
All of the claimed elements were known in the prior art, and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention (See KSA International Co. V. Teleflex Inc., 82 USPQ 2D 1385 (U.S. 2007). People of ordinary skill in the art will be highly educated individuals, posing advanced degrees, including M.D.s and Ph.D.s. They will be medical doctors, scientists, or engineers. Thus, these people most likely will be knowledgeable and well-read in the relevant literature and have the practical experience in molecular biology, cryopreservation, cell culture, and placental therapeutics.
Claims 1,14-16,27-32,77,79,123-124, and 126 are rejected under 35 U.S.C. 103 as being unpatentable over Harrell (US 20140336600) in view of Horton (US 20130084314), and Won (KR20080046821) in view of Tseng (US 20150342998), Yu et al. “Freeze-drying of Human Red Blood Cells: Influence of Carbohydrates and Their Concentrations” Cell Preservation Technology, Volume 2, Number 4, 2004, and Koop (US 20150064274)
Harrell, Horton, Won, Tseng, and Yu apply as above to teach claims 1,14-16,27-28,30-32,77,79,123-124, and 126. Although Tseng teaches that the placental products can be lyophilized. None of the references above teach the appropriate particle size for the lyophilized product. Koop teaches that placental material can be micronized into a particle size such as .1 µm to 400 µm (Paragraphs 101-102). It would have been obvious to an artisan of ordinary skill at the time of effective filing to have treated the placental material into such a lyophilized formation as taught in Koob. An artisan would have been motivated to have lyophilized the product of Harrell according to the specifications of Koob in order to generate a product that was able to successfully maintain useful growth factors and chemokines that have wound healing and bioactive properties (Paragraph 137 of Koop). Because Koop teaches that a lyophilized placental composition can successfully maintain wound healing characteristics, there would have been a high expectation for success forming lyophilized particles with the dimensions taught by Koop as in instant Claim 29.
Dependent Claims taught by Koob
Koob teaches that many growth factors, cytokines, and chemokines can be included in a therapeutic placental product (Paragraph 137 of Koob). Koob further teaches that the lyophilized product can have a moisture content of less than 15% of the entire weight of the construct (Paragraph 131 of Koob) as in instant Claim 31.
Harrell teaches a product containing filtered amniotic fluid containing cells which inherently has hyaluronic acid present. Harrell does not teach that such a composition can be lyophilized into a treatment pharmaceutical in which blood cells are removed. However, Tseng teaches that such a process can be treated by lyophilization in a treatment that can successfully be used for wound healing and rejuvenation. An artisan would have been motivated to have used such a Harrell’s product since Tseng teaches that cells derived from amniotic fluid and amniotic fluid itself can successfully be used in a composition to treat individuals. Yu teaches that the lyophilization process itself can destroy red blood cells. Koob teaches methods of lyophilization that can create therapeutic lyophilized product with the desired particle size in which such particles can adequately provide therapeutic benefits. Given the teachings of the cited references and the level of skill of an artisan at the time of applicants’ invention, it must be considered absent evidence to the contrary that the ordinary skilled artisan would have had a reasonable success in practicing the claimed invention.
All of the claimed elements were known in the prior art, and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention (See KSA International Co. V. Teleflex Inc., 82 USPQ 2D 1385 (U.S. 2007). People of ordinary skill in the art will be highly educated individuals, posing advanced degrees, including M.D.s and Ph.D.s. They will be medical doctors, scientists, or engineers. Thus, these people most likely will be knowledgeable and well-read in the relevant literature and have the practical experience in molecular biology, cryopreservation, cell culture, and placental therapeutics.
Response to Applicants Arguments
Applicants argue that Tseng does not teach a population of “amniotic/amnion cells.” Applicants state, “To be sure, the phrases “amnion cells” or “amniotic cells” appear nowhere in Tseng. Contrary to the Examiner’s assertions, when properly viewed as a whole, Tseng describes compositions of amniotic membrane tissue and umbilical cord tissue…” The tissue described by Tseng is composed of cells. The instant set of claims do not recite that the cells must be individually isolated, nor are more specific types of cells recited in the instant claims. Applicants further argue that the tissue in Tseng is morselized and thus Tseng cannot be used to teach the claimed invention which requires uncultured cells. As argued above, the morselized(homogenized) tissue is still composed of cells even if some are disrupted. There is no limitation presented in the claims that precludes the cells from being morselized. The claims recite “a population of uncultured amniotic cells obtained from filtered amniotic fluid.” The term “amniotic cells” are so broad that they encompass amniotic cells that are individually isolated, cells present in a tissue structure, and/or cells present in a portion of organ. Furthermore, the exact degree of cell viability is not a current limitation. The claim language is so broad that the cells can be completely intact or they can be morselized.
The arguments concerning Roubelakis, Sundberg, Nyman are moot since those references have since been removed.
Applicants argue that Koob does not teach or suggest a product comprising a population of uncultured amniotic cells obtained from filtered amniotic fluid and the growth factors, each obtained from amniotic fluid. Koob is not being relied upon to teach growth factors from amniotic fluid; Harrell is relied upon to teach that limitation and the cells (present in tissue). The claims recite “filtered amniotic fluid” and limitations that state that components such as hyaluronic and several factors are obtained from amniotic fluid. Examiner is interpreting the term “amniotic fluid” broadly as not necessarily being the same solution as the “filtered amniotic fluid” mentioned in claim 1 for example. If it is the intent of applicants for the amniotic fluid to be the same as “the filtered amniotic fluid” from which the cells are derived from, then applicant needs to make that particular amendment in the claims.
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 1-2,13-14,16,21,29,32,77,79, and 121 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3,7-9, and 23-24 of U.S. Patent No. 11,559,553 in view of Nyman “Hyaluronic acid, an important factor in the wound healing properties of amniotic fluid: In vitro studies of re-epithelialization in human skin wounds” J Plastic Surg Hand Surg, 2013,; 47: 89-92 and Sundberg (5,494,044)
Patent 11,559,553 teaches a population of uncultured amniotic cells obtained from amniotic fluid, wherein the product is substantially free of red blood cells like instant claim 1. Unlike instant claim 1, Patent 11,559,553 does not teach the inclusion of hyaluronic acid from amniotic fluid. However, it would have been obvious to an artisan of ordinary skill at the time of effectively filing to have included hyaluronic acid derived from amniotic fluid with the claimed composition of Patent 11,559,553. An artisan would have been motivated to have included hyaluronic acid from amniotic fluid with the claimed composition in the patent because it promotes wound healing as discussed in the abstract of Nyman. The claims of Patent 11,559,553 do not specifically state that amnion cells are harvested by filtering amniotic fluid. However, Sundberg teaches that amniotic cells can be successfully harvested from amniotic fluid.
Instant claim 2 corresponds to claim 3 of Patent 11,559,553. Instant claim 13 corresponds to claim 2 of Patent 11, 559, 553. Instant claim 14 corresponds to claim 9 of Patent 11,559,553. Instant claim 16 corresponds to claim 1 of Patent 11,559,553. Instant claim 21 corresponds to claim 3 of Patent 11,559,553. Instant claim 29 corresponds to claim 1 of Patent 11,559,553 because claim 1 of the Patent states that the product is lyophilized. Claim 32 corresponds to claim 7 of Patent 11,559,553. Claim 77 corresponds to claim 23 of Patent 11,559,553. Claim 79 corresponds to claim 24 of Patent 11,559,553. Claim 121 corresponds to claim 8 of Patent 11,559,553.
Response to Applicants Remarks
Applicant requests that the double patenting rejection be held in abeyance. Since a terminal disclaimer has not been filed yet, the double patenting rejection is maintained.
Conclusion
All claims stand rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAUREN K VAN BUREN whose telephone number is (571)270-1025. The examiner can normally be reached M-F:9:30am-5:40pm; 9:00-10:00pm.
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LAUREN K. VAN BUREN
Examiner
Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638