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 .
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.
Election/Restrictions
Applicant's election with traverse of Group I, claims 21-30 in the reply filed on 21 August 2026 is acknowledged. The traversal is on the ground(s) that there is no lack of unity because the instant claims do not lack an inventive step in view of the prior art cited in the restriction requirement mailed on 23 June 2026. The examiner finds this persuasive. Nevertheless, the restriction requirement has not been withdrawn. The examiner presents the following rationale in support of this position.
As set forth in Rule 13.1 of the Patent Cooperation Treaty (PCT), "the international application shall relate to one invention only or to a group of inventions so linked as to form a single general inventive concept.” Moreover, as stated in PCT Rule 13.2, "where a group of inventions is claimed in one and the same international application, the requirement of unity of invention referred to in Rule 13.1 shall be fulfilled only when there is a technical relationship among those inventions involving one or more of the same or corresponding special technical features." Furthermore, Rule 13.2 defines "special technical features" as "those technical features that define a contribution which each of the claimed inventions, considered as a whole, makes over the prior art."
The inventions listed as Groups I-II do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons:
The special technical feature of Group I is a method for producing artificial organs. The method of claim 21 lacks an inventive step in view of the combination of Orlando et al. (US 2015/0238656 A1) in view of Hoffmann et al. (Journal of Biomedical Materials Research Part A, Vol. 84A, 2008, pages 614-621), which is explained in greater detail in the obviousness rejection below. As such, Group I does not share a special technical feature with the instant claims of Group II. Therefore, the claims are not so linked within the meaning of PCT Rule 13.2 so as to form a single inventive concept, and unity between Groups I-II is broken.
The requirement is still deemed proper but is not made final because the rationale behind the examiner’s finding of lack of unity has changed in this office action as compared with the rationale presented in the office action mailed on 23 June 2026.
Claim Interpretation
Claim 21 recites the term “aptamer.” As best understood by the examiner, the scope of this term includes both DNA aptamers as well as RNA aptamers.
Claim 21 recites “wherein the aptamer is used for coating blood vessels of a decellularized organ.” The examiner understands this limitation to require that the step of treating with aptamers would have resulted in the aptamer coating the blood vessel of a decellularized organ.
Claim 22 is understood to require all of steps (a), (b), and (c).
In regard to claim 23, the examiner understands this claim to require either d-1, d-2, or d-3.
In regard to claim 26, the phrase “don’t eat me” signal appears to be a term of art and is therefore not indefinite. See e.g. Wu et al. (US 2019/0338028 A1), paragraph 0006.
In regard to claim 28, the examiner understands that a prior art reference teaching the recited sequence of Seq. ID 1 plus additional nucleotides would read on the claimed invention. This determination is made in view of the transitional phrase “comprising” which is recited by claim 28. The transitional term "comprising", which is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See MPEP 2111.03(I). Additionally, the phrase “base sequence” in claim 28 would appear to indicate that the recited sequence is the base from which the full sequence is obtained, and is therefore less than the full sequence. As such, the examiner understands that the recited sequence requires all of the nucleotides of claim 28 but does not exclude additional nucleotides.
Claim Interpretation – Issues Under 35 U.S.C. 112(f)
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
For the purposes of examination under prior art, the examiner has invoked 35 U.S.C. 112(f) in the interpretation of claims 21-23.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
Claim Rejections - 35 USC § 103 – Obviousness
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.
Claim(s) 21-27 is/are rejected under 35 U.S.C. 103 as being unpatentable over Orlando et al. (US 2015/0238656 A1) in view of Hoffmann et al. (Journal of Biomedical Materials Research Part A, Vol. 84A, 2008, pages 614-621).
Orlando et al. (hereafter referred to as Orlando) is drawn to organ decellularization and recellularization, as of Orlando, title and abstract, wherein the product of this method is described as a bio-artificial organ, as of Orlando, paragraph 0260. Orlando teaches treating the decellularized organ with anti-CD31 antibody, as of Orlando, at least paragraphs 0216, 0218, 0292, and 0299 wherein parts of paragraph 0299 are reproduced below.
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Orlando appears to teach that reendothelialization occurs on cell vasculature in paragraph 0202, which would have motivated the skilled artisan to have applied anti-CD31 antibodies to blood vessels. The examiner notes that paragraph 0216 appears to teach failures of re-reendothelialization; however, these failures appear to have been solved by the teachings of Orlando and are not understood to be teaching away.
Orlando differs from the claimed invention because Orlando teaches anti-CD31 antibodies rather than the required anti-CD31 aptamers.
Hoffmann et al. (hereafter referred to as Hoffmann) is drawn to the use of DNA aptamers as attractors for endothelial precursor cells, as of Hoffmann, page 614, title and abstract. Hoffmann teaches that endothelial precursor cells have cell-specific markers such as CD31, as of Hoffmann, page 614, right column, bottom paragraph. Hoffmann thereby uses DNA aptamers against CD31, as of Hoffmann, page 616, right column, bottom paragraph. Hoffmann teaches the following as of page 620, left column, first paragraph in “Conclusion” section, relevant text reproduced below.
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The examiner notes that anti-CD31 aptamer is an aptamer against endothelial precursor cells (abbreviated as “EPCs” above).
Hoffmann differs from the claimed invention because Hoffmann teaches coating a device with the anti-CD31 aptamer rather than coating blood vessels of a decellularized organ with the anti-CD31 aptamer.
It would have been prima facie obvious for one of ordinary skill in the art to have substituted the anti-CD31 aptamer of Hoffmann in place of the anti-CD31 antibody of Orlando in the method of Orlando. The method of Orlando entails treatment of the cell vasculature of a decellularized organ to promote reendothelialization. Hoffmann teaches that attachment of anti-CD31 aptamers promotes attachment of endothelial cells or precursors thereof. As such, the skilled artisan would have been motivated to have substituted the anti-CD31 aptamer of Hoffmann in place of the anti-CD31 antibody to have predictably promoted the attachment of endothelial cells or precursors thereof with a reasonable expectation of success. The simple substitution of one known element (e.g. anti-CD31 aptamers of Hoffmann) in place of another (e.g. anti-CD31 antibodies of Orlando) in order to achieve predictable results (attachment of endothelial cells or precursors thereof, as taught by both Orlando and Hoffmann) is prima facie obvious. See MPEP 2143, Exemplary Rationale B.
As to claim 21, the claim requires that the aptamer is used for coating blood vessels of a decellularized organ. Orlando appears to teach that reendothelialization occurs on cell vasculature in paragraph 0202, which would have motivated the skilled artisan to have applied anti-CD31 antibodies to blood vessels.
As to claim 22 steps (a) and (b), Orlando teaches decellularization of tissues and organs in multiple locations in the reference including but not limited to paragraphs 0045-0046. As to claim 22(c), Orlando teaches treating the decellularized organ with CD-31 antibodies, and the skilled artisan would have been motivated to have substituted anti-CD31 aptamers in place of the anti-CD31 antibodies, as explained above.
As to claim 23, Orlando teaches vascular endothelial cells as of paragraphs 0006, 0203, 0292, and claim 4 of Orlando. Orlando teaches a parenchymal cell source in paragraph 0309.
As to claim 24, Orlando teaches induced pluripotent stem cells that provide an autologous source for whole organ engineering, as of paragraph 0309. The examiner understands this to teach stem cells that differentiate into the type of cells used in the relevant organ.
As to claim 25, Orlando teaches induced pluripotent stem cells, as of paragraph 0309.
As to claim 26, Orlando appears to teach HLA genes removed in paragraph 0017.
As to claim 27, Hoffmann teaches an anti-CD31 aptamer, as of Hoffmann, page 616, right column, bottom paragraph.
Claim(s) 28-30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Orlando et al. (US 2015/0238656 A1) in view of Hoffmann et al. (Journal of Biomedical Materials Research Part A, Vol. 84A, 2008, pages 614-621), the combination further in view of Kim et al. (KR 20160133670 A).
As an initial matter, Kim et al. (KR 20160133670 A) is written in Korean. The examiner has provided an English language translation through Google Patents. This translation was obtained from https://patents.google.com/patent/KR20160133670A/en?oq=KR+20160133670A on 8 September 2026. All page and line citations are made to the translation unless otherwise noted, and the material cited therein is understood by the examiner to have been present in the original Korean document.
Orlando is drawn to treating decellularized organs with anti-CD31 antibodies to promote reendothelialization and formation of an artificial organ. Hoffmann is drawn to the use of CD31 aptamers for the attachment of endothelial cell precursors. See the rejection above over Orlando in view of Hoffmann.
None of the above references teach the sequence required by claim 28.
Kim et al. (hereafter referred to as Kim) is drawn to a CD31 aptamer, as of Kim, page 1, title and abstract, wherein said aptamer is specific for endothelial progenitor cells, as of Kim, title. Kim teaches the following, as of the last page of the original document, reproduced below with annotation by the examiner.
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The portion of the above-reproduced sequence in the box drawn by the examiner would appear to read on the claimed sequence of Seq. ID #1, which is reproduced below.
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Kim differs from the claimed invention because Kim does not teach producing an artificial organ.
It would have been prima facie obvious for one of ordinary skill in the art to have used the aptamer of Kim as the aptamer in the method of Hoffmann, whether by itself or in view of Orlando. Hoffmann is drawn to treatment of a material with an anti-CD31 aptamer for attachment of endothelial cells or progenitors thereof. Hoffmann appears to be silent regarding the genetic sequence of the aptamer. However, Kim teaches the genetic sequence of an aptamer used to attach to epithelial cells or progenitors thereof. As such, the skilled artisan would have been motivated to have used the aptamer of Kim as the anti-CD31 aptamer in the method of Hoffmann, by itself or in view of Orlando, for predictable attachment of endothelial cells or progenitors thereof with a reasonable expectation of success. Generally, it is prima facie obvious to select a known material (e.g. the aptamer of Kim) for incorporation into a composition (that used in the method of Orlando), based on its recognized suitability for its intended use (attachment to CD31 as well as being specific for endothelial progenitor cells). See MPEP 2144.07.
As to claim 28, the sequence of Kim is understood to read on the required sequence. See the explanation provided above.
As to claims 29-30, Kim and Hoffmann appear to be silent regarding the expression of integrin beta 3, phosphorylated Akt, and cleaved caspase-3. Nevertheless, the sequence of Kim appears to be the same as that required by the instant claims. As such, the skilled artisan would have expected that the sequence of Kim would have inherently increased the expression of integrin beta 3 and phosphorylated Akt, and decreased the expression of caspase-3 even though this feature was not taught by the prior art. Something which is old (e.g. the sequence of Kim) does not become patentable upon the discovery of a new property (that the sequence increases the expression of integrin beta 3 and phosphorylated Akt, and decreases the expression of caspase-3), and this feature need not have been recognized at the time of filing. See MPEP 2112(I & II), also see MPEP 2112.01(I & II).
Additionally as to claims 29-30, once a reference teaching a product appearing to be substantially identical is made the basis of a rejection, and the examiner presents evidence or reasoning to show inherency, the burden of production shifts to the applicant. See MPEP 2112(V). In this case, the product of Seq. ID 3 of Kim appears to be substantially identical to the sequence recited by instant claim 28. These sequences are also being used in the same manner; namely, to promote attachment of endothelial cells or progenitors thereof. This would appear to be sufficient to shift the burden to applicant in accordance with the guidance in MPEP 2112(V).
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ISAAC SHOMER whose telephone number is (571)270-7671. The examiner can normally be reached 7:30 AM to 5:00 PM Monday Through Friday.
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ISAAC . SHOMER
Primary Examiner
Art Unit 1612
/ISAAC SHOMER/ Primary Examiner, Art Unit 1612
Prosecution Insights