US 7846728

Here's a concise summary of US patent 7846728:

US Patent: 7846728

• Title: Tissue engineering in vivo with vascularized scaffolds
• Assignee: BioStruxs LLC
• Inventors: Mai Nguyen Brooks, James P Watson
• Filing Date: October 9, 2007
• Issue Date: December 7, 2010
• Abstract: The patent describes a novel method for producing tissue or an organ in a mammal by implanting a three-dimensional biodegradable scaffold in vivo. These scaffolds are designed to overcome the limitations in developing large organs using tissue engineering by addressing issues such as a lack of well-developed vascular supply, tissue resorption, loss of cell function, and untoward side effects.

Plain-Language Overview of Independent Claims:

• Independent Claim 1: This claim describes a physical implant. It consists of a three-dimensional scaffold shell with an interior and an exterior. Inside this shell is a tissue matrix. This tissue matrix is unique because it includes multiple folds of vascularized omentum (a fatty tissue in the abdomen) combined with excised fat tissue that is specifically inserted between these omentum folds. A key aspect is that the scaffold material is distinct from the tissue matrix it contains.
• Independent Claim 5: This claim describes a method for creating an implant using a three-dimensional scaffold shell to contain a tissue matrix. The method involves several steps:
  1. Providing a cell mixture: Cells harvested from an organ are prepared, ensuring they are immunocompatible with the patient.
  2. Identifying a growth site: A location within the patient is chosen that has existing vascular tissue with intact arterial and venous blood flow, and the capacity to support the growth of the cell mixture.
  3. Introducing the scaffold: A three-dimensional scaffold shell is placed into this identified growth site. The vascular tissue at the site is positioned within the scaffold's interior, maintaining its connection and blood flow with the patient.
  4. Introducing the cell mixture: The prepared cell mixture is then introduced into the scaffold's interior, where it interacts with the vascular tissue.
  5. Incubation: The scaffold, containing the vascularized tissue and cell mixture, is allowed to remain and grow within the patient's body at the growth site until it forms the desired implant and tissue matrix.
  6. Removal: Once the implant has formed, it is removed from the initial growth site.

CAFC 2026 Dockets:
A search of CAFC 2026 dockets did not reveal any active cases specifically citing US patent 7846728 as of April 26, 2026.

I am unable to find any known litigation specifically involving US patent 7846728 based on the conducted searches through general web channels, including those typically indexing patent litigation and legal news. My search did not return any cases listing plaintiff(s), defendant(s), jurisdiction, case number, filing date, or outcome/current status for this particular patent.

Proceedings overview

There are no AIA trial proceedings on file for US7846728.

Strategic summary

As of the current date, US patent 7846728 has no recorded AIA trial proceedings (Inter Partes Review, Post-Grant Review, or Covered Business Method review) at the USPTO Patent Trial and Appeal Board. This means all claims of the patent (claims 1-10) remain untested by these particular administrative challenges. Consequently, there is no estoppel landscape established through PTAB proceedings that would limit future challenges or assertions.

The absence of PTAB activity could imply several things. It might suggest that the patent has not been extensively asserted, or that prior art challenging its claims under §§ 102, 103, or 112 has not been identified as sufficiently strong to warrant a petition. For a defendant, this means that all prior art grounds remain available for potential invalidity arguments in district court litigation or for a future IPR filing, should circumstances change.

Recommended next steps

Since no PTAB activity exists for US7846728, a defendant facing assertion of this patent would not be constrained by any prior PTAB decisions. Recommended next steps would include:

• Conducting a comprehensive prior art search: Given the absence of IPRs, a thorough search for prior art relevant to §§ 102 and 103 could uncover grounds for a strong invalidity defense in litigation or support a new IPR petition.
• Monitoring for future PTAB filings: Keep an eye on the USPTO PTAB E2E system for any newly filed petitions against US7846728 by other parties. Such filings could offer insights into potential invalidity arguments and may influence defensive strategies.
• Evaluating the asserted claims: Carefully analyze which claims of US7846728 are being asserted by the patent owner. This analysis will guide targeted prior art searches and potential invalidity contentions.

Inventors

• Mai Nguyen Brooks (Employer not specified in patent text at time of filing)
• James P Watson (Employer not specified in patent text at time of filing)

Original assignee

The original assignee on the issued patent US7846728 is BioStruxs LLC. The patent itself describes "a novel method for producing tissue or organ in a mammal by implanting in vivo a novel three dimensional biodegradable scaffold" and mentions applications like "autologous breast implant engineering" and "autologous long bone engineering." It is unclear from the patent text or general web searches whether BioStruxs LLC shipped a product embodying the claims. The current status of BioStruxs LLC is unclear from readily available public information.

Assignment timeline

• 2007-10-08 (executed) / recorded 2007-10-12 — Reel 020044/0838

  • Conveyance: Assignment
  • Assignor: Brooks, Mai Nguyen; Watson, James P
  • Assignee: BCN Biosciences LLC
  • Correspondent: Not specified in the provided patent text.
  • Context: Transfer of inventors' interest to a new entity.

• 2008-09-26 (executed) / recorded 2008-10-10 — Reel 021678/0919

  • Conveyance: Assignment
  • Assignor: BCN Biosciences LLC
  • Assignee: Royal Vista Capital LLC
  • Correspondent: Not specified in the provided patent text.
  • Context: Transfer of patent ownership between entities.

• 2009-09-01 (executed) / recorded 2009-09-01 — Reel 023178/0623

  • Conveyance: Assignment
  • Assignor: Royal Vista Capital LLC
  • Assignee: BioStruxs LLC
  • Correspondent: Not specified in the provided patent text.
  • Context: Transfer of patent ownership, returning to the original assignee listed on the patent.

Timeline diagram

timeline
    title Ownership of US 7846728
    2007 : Inventors assigned to BCN Biosciences LLC
    2008 : BCN Biosciences assigned to Royal Vista Capital LLC
    2009 : Royal Vista Capital assigned to BioStruxs LLC
    2010 : Patent Issued

NPE / troll-pattern signals

1. Shell-entity transfer — unclear. While the assignees BCN Biosciences LLC and Royal Vista Capital LLC could potentially be shell entities, there is no concrete evidence from the provided text (e.g., registered-agent addresses, single-purpose LLC indication, or confirmation of no products) to definitively make this call. The eventual return of the patent to BioStruxs LLC also complicates a simple shell-entity transfer narrative.
2. Known asserter in the chain — not present. None of the listed assignees (BCN Biosciences LLC, Royal Vista Capital LLC, BioStruxs LLC) are identified as known NPEs or patent asserters in the provided context.
3. Repeat correspondent across the chain — not present. The correspondent information was not specified in the provided patent text for any of the assignment records, therefore, no recurrence can be identified.
4. Cascading transfers — present. There are three assignments recorded within a span of approximately two years (October 2007 to September 2009). The transfers from BCN Biosciences LLC to Royal Vista Capital LLC and then to BioStruxs LLC (Reel 020044/0838, Reel 021678/0919, Reel 023178/0623) demonstrate consecutive assignments within a short timeframe.
5. Pre-litigation transfer — not present. There is no litigation information provided to establish a comparison.
6. Bankruptcy fire-sale — not present. There is no information provided about any of the assignees undergoing bankruptcy proceedings.
7. Privateering — not present. There is no information to suggest privateering.
8. Defensive aggregator (anti-NPE) — not present. The chain does not terminate at any known defensive aggregators.

Verdict

Insufficient data. While there is a signal of "cascading transfers" (three assignments between October 2007 and September 2009, prior to the patent's issue date in December 2010), the lack of information regarding the business activities of the assignees, the identity of the correspondents, and any litigation history prevents a confident determination of NPE status. The patent ultimately reverted to BioStruxs LLC, the original assignee, which further complicates the interpretation of the interim transfers.
The assignment records can be verified on the USPTO Assignment Center: https://assignmentcenter.uspto.gov/

The following prior art references were cited in US patent 7846728. For each reference, the full citation, publication/filing date, a brief description, and the claim(s) it potentially anticipates under 35 U.S.C. § 102 are provided.

Patent Citations for US7846728:

1. US5759830A

   • Full Citation: US5759830A, "Three-dimensional fibrous scaffold containing attached cells for producing vascularized tissue in vivo" by Vacanti et al., assigned to Massachusetts Institute Of Technology.
   • Publication Date: 1998-06-02. Priority Date: 1986-11-20.
   • Brief Description: This patent describes a three-dimensional fibrous scaffold containing attached cells for producing vascularized tissue in vivo. It teaches implanting sheets of cell-matrix structure adjacent to vascularized tissues such as mesentery, omentum, or peritoneum.
   • Potential Anticipation (35 U.S.C. § 102): This patent broadly anticipates aspects of Claim 5 by disclosing a method of generating an implant using a three-dimensional scaffold, a cell mixture, and a vascular tissue like omentum in an in vivo growth site for tissue formation. However, it does not explicitly disclose a "scaffold shell" where the vascular tissue is placed into its interior with intact arterial and venous flow, nor does it specify "multiple folds of vascularized omentum in combination with excised fat tissue inserted between said folds" as required by Claim 1.

2. US5770193A

   • Full Citation: US5770193A, "Preparation of three-dimensional fibrous scaffold for attaching cells to produce vascularized tissue in vivo" by Vacanti et al., assigned to Massachusetts Institute Of Technology Children's Medical Center Corporation.
   • Publication Date: 1998-06-23. Priority Date: 1986-11-20.
   • Brief Description: This patent describes the preparation of a three-dimensional fibrous scaffold for attaching cells to produce vascularized tissue in vivo. It also discusses implanting sheets of cell-matrix structure adjacent to mesentery, omentum, or peritoneum tissue.
   • Potential Anticipation (35 U.S.C. § 102): Similar to US5759830A, this patent potentially anticipates aspects of Claim 5 by detailing methods involving three-dimensional scaffolds, cells, and the use of omentum for in vivo vascularization. It lacks the specific "scaffold shell" with internally placed vascular tissue and intact flow, and the "multiple folds of vascularized omentum with excised fat" as defined in US7846728.

3. US5804178A

   • Full Citation: US5804178A, "Implantation of cell-matrix structure adjacent mesentery, omentum or peritoneum tissue" by Vacanti et al., assigned to Massachusetts Institute Of Technology.
   • Publication Date: 1998-09-08. Priority Date: 1986-11-20.
   • Brief Description: This patent describes the implantation of cell-matrix structures adjacent to mesentery, omentum, or peritoneum tissue.
   • Potential Anticipation (35 U.S.C. § 102): This patent is highly relevant to Claim 5 as it directly teaches the use of omentum as a site for vascularization of cell-matrix structures in vivo. The distinction lies in US7846728 specifying that the vascular tissue (e.g., omentum) is placed into the interior of a scaffold shell while its arterial and venous flow remain intact, as opposed to placing a cell-matrix structure adjacent to the omentum. It does not appear to disclose the specific implant structure of Claim 1.

4. US5716404A

   • Full Citation: US5716404A, "Breast tissue engineering" by Vacanti et al., assigned to Massachusetts Institute Of Technology.
   • Publication Date: 1998-02-10. Priority Date: 1994-12-16.
   • Brief Description: This patent proposes placing dissociated cells into a biodegradable matrix to be implanted with a tissue expander device into the breast for breast tissue engineering.
   • Potential Anticipation (35 U.S.C. § 102): This patent directly addresses "breast tissue engineering." Therefore, it potentially anticipates Claim 2 (an implant that is a breast implant) and Claim 6 (a method where the organ is a breast). However, it does not describe the specific scaffold-omentum-fat configuration of Claim 1 or the method steps of Claim 5 involving intact vascular flow of omentum placed inside a scaffold shell.

5. US20020022883A1

   • Full Citation: US20020022883A1, "Tissue engineering composite" by Burg Karen J.L.
   • Publication Date: 2002-02-21. Priority Date: 2000-06-13.
   • Brief Description: This patent application describes a biocompatible composite with viscous fluid for injection into defects.
   • Potential Anticipation (35 U.S.C. § 102): This reference describes a fluidic composite rather than a structured three-dimensional scaffold shell designed to accommodate vascular tissue or multiple layers of omentum and fat tissue. Therefore, it does not appear to anticipate any claims of US7846728.

6. US20040052768A1

   • Full Citation: US20040052768A1, "Vascularised tissue graft" by Morrison Wayne A.
   • Publication Date: 2004-03-18. Priority Date: 2000-08-21.
   • Brief Description: The title suggests a vascularized tissue graft. No further specific description is provided within US7846728.
   • Potential Anticipation (35 U.S.C. § 102): While generally related to vascularized tissue, without more detailed information, it is not possible to determine if this patent discloses the specific elements of Claim 1 (scaffold shell, multiple folds of omentum, excised fat) or the precise method steps of Claim 5 (placing vascular tissue into the interior of a scaffold shell with intact arterial/venous flow).

7. US20070299508A1

   • Full Citation: US20070299508A1, "Vascularized tissue graft" by Victorian Tissue Engineering Centre Pty Ltd.
   • Publication Date: 2007-12-27. Priority Date: 2000-08-21.
   • Brief Description: Similar to US20040052768A1, the title indicates a vascularized tissue graft. No further specific description is provided within US7846728.
   • Potential Anticipation (35 U.S.C. § 102): Similar to US20040052768A1, without further details, it is difficult to assess direct anticipation of US7846728's specific claims.

8. US20020119180A1

   • Full Citation: US20020119180A1, "Methods and compositions for culturing a biological tooth" by Yelick et al., assigned to President And Fellows Of Harvard College.
   • Publication Date: 2002-08-29. Priority Date: 2000-11-29.
   • Brief Description: This patent application describes the construction of a biodegradable polymer scaffold molded in the shape of a tooth and placed onto the omentum of rats.
   • Potential Anticipation (35 U.S.C. § 102): This reference is relevant to Claim 5 as it discloses the use of a biodegradable polymer scaffold placed onto the omentum for tissue engineering. The key differentiating aspect for US7846728 is the explicit requirement for a "scaffold shell" with the vascular tissue placed into its interior and maintaining intact arterial/venous flow, which is not clearly disclosed by placing a scaffold onto the omentum. It does not describe the specific "multiple folds of vascularized omentum in combination with excised fat tissue inserted between said folds" of Claim 1.

9. US20030129751A1

   • Full Citation: US20030129751A1, "Tissue-engineered organs" by Grikscheit Tracy C.
   • Publication Date: 2003-07-10. Priority Date: 2001-05-16.
   • Brief Description: This patent application describes a method for high-density seeding of a polymer scaffold with organoid units. The disclosed scaffolds are collagen-coated polyglycolic acid tubes that are sutured to a rat's omentum to make new colonic tissue.
   • Potential Anticipation (35 U.S.C. § 102): This is a highly relevant reference that potentially anticipates aspects of Claim 5. It explicitly teaches a method using a polymer scaffold (tubes), seeded cells (organoid units), and omentum (vascular tissue) in an in vivo setting for tissue engineering. The description "sutured to the rat's omentum" may be distinguished from US7846728's specific requirement of placing the omentum into the interior of a scaffold shell while maintaining intact arterial/venous flow. However, the core concept of omentum-based vascularized scaffold tissue engineering is strong. It does not describe the "multiple folds of vascularized omentum in combination with excised fat tissue inserted between said folds" of Claim 1.

10. US20070059293A1

    • Full Citation: US20070059293A1, "Tissue engineered construct for supplementing or replacing a damaged organ" by Atala, assigned to Children's Medical Center Corporation.
    • Publication Date: 2007-03-15. Priority Date: 2002-02-05.
    • Brief Description: This patent application describes seeding autologous bladder cells on a biodegradable bladder-shaped scaffold made of collagen and polyglycolic acid, which was then implanted covered with omentum into patients.
    • Potential Anticipation (35 U.S.C. § 102): This is another highly relevant reference that potentially anticipates aspects of Claim 5. It discloses a method involving a biodegradable scaffold of a specific shape, seeded with autologous cells, and implanted covered with omentum. Similar to the Grikscheit patent, the phrase "implanted covered with omentum" might be distinguished from US7846728's requirement of placing the vascular tissue into the interior of a scaffold shell with intact arterial and venous flow. However, the overall concept of using omentum to vascularize a scaffold for organogenesis with autologous cells is strongly suggested. It does not describe the specific "multiple folds of vascularized omentum in combination with excised fat tissue inserted between said folds" of Claim 1.

11. US20070100358A2

    • Full Citation: US20070100358A2, "A Biomimetic Synthetic Nerve Implant" by Joe Javio63 th (as listed in US7846728), assigned to Texas Scottish Rite Hospital For Children.
    • Publication Date: 2007-05-03. Priority Date: 2002-08-01.
    • Brief Description: This patent application describes a biomimetic biosynthetic nerve implant (BNI) utilizing a hydrogel-based, transparent, multi-channel matrix as a three-dimensional substrate for nerve repair. It details novel scaffold casting devices for creating grafts with micro-conduits for nerve growth in vivo.
    • Potential Anticipation (35 U.S.C. § 102): This patent focuses on synthetic nerve implants and multi-channel scaffolds for nerve repair. It does not involve the omentum or the specific combination with excised fat tissue as described in US7846728, nor does it discuss placing vascular tissue with intact arterial/venous flow into the interior of a scaffold shell. Therefore, it is less likely to directly anticipate any claims of US7846728.

12. US20040126405A1

    • Full Citation: US20040126405A1, "Engineered scaffolds for promoting growth of cells" by Sahatjian et al., assigned to Scimed Life Systems, Inc.
    • Publication Date: 2004-07-01. Priority Date: 2002-12-30.
    • Brief Description: This patent application proposes a three-dimensional cell scaffold that can be configured as a sheet or a tube in various shapes.
    • Potential Anticipation (35 U.S.C. § 102): This reference broadly discloses three-dimensional cell scaffolds in various shapes, which is a general element of US7846728. However, it does not specify the use of omentum or excised fat tissue, particularly the "multiple folds of vascularized omentum in combination with excised fat tissue inserted between said folds" for Claim 1. For Claim 5, it lacks the specificity of using vascular tissue like omentum placed into the interior of a scaffold shell with intact arterial/venous flow, and the subsequent steps for implant formation and removal.

Under 35 U.S.C. § 103, an invention is considered obvious if "the differences between the claimed invention and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which the subject matter pertains." This analysis considers the scope and content of the prior art, the differences between the prior art and the claims, the level of ordinary skill in the art, and any secondary considerations of non-obviousness.

The core problem addressed by US7846728, as explicitly stated in its background, is the significant limitation of developing large organs or tissues (greater than a few millimeters) using tissue engineering due to the "lack of a well developed vascular supply for organogenesis," [cite: A short list of persistent problems in this area include:] leading to issues like "tissue resorption" [cite: A short list of persistent problems in this area include:] and "loss of cell function." [cite: A short list of persistent problems in this area include:] The patent emphasizes the need for a "vascularized scaffold with a complete vascular bed." [cite: In an effort to design a three dimensional biodegradable scaffold which could overcome the barrier of developing large organs with tissue engineering, the present inventors hypothesized that a vascularized scaffold with a complete vascular bed would be needed to overcome this barrier.]

A person having ordinary skill in the art (PHOSITA) in tissue engineering would be aware of these fundamental challenges and the known properties of various tissues and scaffolds.

Obviousness of Claim 1:
Claim 1 describes "An implant comprising: a three dimensional scaffold shell having an interior and an exterior; and a tissue matrix deposited in the interior of said scaffold shell comprising multiple folds of vascularized omentum in combination with excised fat tissue inserted between said folds of said omentum, wherein said scaffold is comprised of a material that is different from said tissue matrix."

1. Three-dimensional scaffold shell: Prior art clearly teaches the use of three-dimensional scaffolds. For instance, Sahatjian et al. (US Pat. appl. 20040126405) proposed "a three dimensional cell scaffold either as a sheet or a tube configured into various shapes." [cite: a later application] Similarly, Yelick et al. (US Pat. appl. 20020119180 A1) constructed a "biodegradable polymer scaffold molded in the shape of a tooth." [cite: Yelick et al.] Atala et al. (US Pat. appl. 20070059293 A1) also used a "biodegradable bladder-shaped scaffold." [cite: Recently, a successful human clinical trial has been reported]
2. Vascularized omentum: The use of omentum as a source of vasculature for tissue engineering was well-established in the prior art. Vacanti et al. (U.S. Pat. No. 5,804,178, U.S. Pat. No. 5,770,193, and U.S. Pat. No. 5,759,830) reported "implanting sheets of cell-matrix structure adjacent to mesentery, omentum, or peritoneum tissue." [cite: Vacanti et al. also reported the idea of implanting sheets of cell-matrix structure adjacent to mesentery, omentum, or peritoneum tissue] Yelick et al. placed scaffolds "onto the omentum of rats," [cite: Yelick et al.] and Grikscheit et al. (US Pat. appl. 20030129751) used scaffolds "sutured to the rat's omentum to make new colonic tissue." [cite: a later application] Atala et al. implanted scaffolds "covered with omentum." [cite: Recently, a successful human clinical trial has been reported] The patent itself acknowledges this, stating: "In all of the above studies, the omentum was used as a single layer attached to one side of a flat scaffold, or wrapped around a three-dimensional scaffold." [cite: Recently, a successful human clinical trial has been reported]
3. Excised fat tissue: The problem of fat graft resorption due to inadequate vascularization was a known issue. The patent's background states that "fat grafts larger than a few mm in diameter are well documented of undergoing resorption over time. Except for small volume fat grafting transferred into multiple well vascularized tunnels, most fat grafts undergo partial resorption." [cite: a list of the tissues which have been autografted with well documented resorption over time] This clearly highlights the need for improved vascularization for fat tissue.
4. "Multiple folds of vascularized omentum in combination with excised fat tissue inserted between said folds of said omentum": Given the prior art's recognition of omentum as a vascular source and the explicit problem of fat graft resorption due to lack of vascularization, a PHOSITA would be motivated to maximize the vascular supply to the fat tissue. The prior art demonstrates methods of placing scaffolds adjacent to or wrapped with omentum. To improve upon these methods and enhance vascularization for larger tissue constructs or fat grafts prone to resorption, a PHOSITA would find it obvious to increase the surface area of contact between the omentum and the fat cells. Creating "multiple folds" of omentum and inserting fat tissue between these folds within a scaffold would be an obvious engineering design choice to achieve maximal intimate contact and, thus, superior vascularization, directly addressing the stated problems of limited tissue size and resorption. The patent itself articulates this motivation by stating that "The scaffold interior is designed in order to accommodate multiple layers of omentum, in contact with autologous cells suspended in nutrient-containing matrix." [cite: the present invention thus provides a novel three dimensional biodegradable scaffold capable for use in developing large organs with tissue engineering.]
5. Scaffold material different from tissue matrix: This is inherent in combining a synthetic or naturally derived scaffold (e.g., polymer, collagen as taught by Grikscheit and Atala) with biological tissue (omentum, fat).

Combination: A PHOSITA would be motivated to combine the three-dimensional scaffold teachings of Sahatjian et al. or Yelick et al. with the extensive teachings on using omentum for vascularization from Vacanti et al., Yelick et al., Grikscheit et al., and Atala et al. The well-known problem of fat graft resorption, as discussed in the patent's background, would further motivate this combination. The need to overcome the "barrier of developing large organs with tissue engineering" [cite: the field of the present invention] by enhancing vascular supply would lead a PHOSITA to design a scaffold system that maximizes the interaction between the omentum and the tissue to be vascularized (e.g., fat). Inserting the fat tissue between multiple folds of the vascularized omentum within the scaffold is an obvious optimization to achieve this goal, with a reasonable expectation of success given the known properties of omentum and the physiological need for vascularization.

Obviousness of Claim 2:
Claim 2 specifies the implant as a "breast implant."
Motivation: Vacanti et al. (U.S. Pat. No. 5,716,404) explicitly proposed "breast tissue engineering" by "implanting a tissue expander device into the breast" with dissociated cells in a biodegradable matrix. [cite: The Harvard University group led by Vacanti proposed placing dissociated cells into a biodegradable matrix to be implanted with a tissue expander device into the breast] While that method had issues due to lack of vascularization, the patent also highlights ongoing problems with "autologous fat grafting for cosmetic breast augmentation" due to "fat necrosis" and difficulties in "future cancer detection." [cite: As a consequence, fat grafting for breast augmentation may make future cancer detection difficult. For this reason, autologous fat grafting for cosmetic breast augmentation has been discouraged by the FDA, radiological societies, and the plastic surgery community.] A PHOSITA would be highly motivated to apply the vascularized scaffold system of Claim 1 to breast augmentation or reconstruction to overcome these documented deficiencies and produce a more viable and safer breast implant. The patent itself notes, "For example, for a breast, the shape may resemble that of a standard breast implant." [cite: the outer shape of the scaffold]

Combination: The breast tissue engineering concept of Vacanti et al. (U.S. Pat. No. 5,716,404) combined with the vascularized scaffold and fat tissue integration of Claim 1 (as made obvious by Sahatjian et al., Yelick et al., Grikscheit et al., Vacanti et al. (omentum use), and the general knowledge of fat graft limitations).

Obviousness of Claim 3:
Claim 3 specifies the fat tissue as "a mixture of fat cells harvested from an organ and a nutrient."
Motivation: The patent itself mentions "autologous cells suspended in nutrient-containing matrix" [cite: The scaffold interior is designed in order to accommodate multiple layers of omentum, in contact with autologous cells suspended in nutrient-containing matrix.] and cites PuraMatrix (Becton Dickinson) as being used in 10% sucrose solution with harvested fat tissue in Example 1. [cite: This fat tissue was then manually mixed with PuraMatrix (Becton Dickinson, Bedford, Mass.) in 10% sucrose solution.] The concept of mixing harvested cells with nutrients for viability and growth is fundamental to "Cell culture technology," which the patent acknowledges as a "well-established technique that is very successful in vitro." [cite: Cell culture technology has become a well-established technique that is very successful in vitro under ideal laboratory conditions.]

Combination: General knowledge of cell culture techniques and the use of nutrient media for cell viability and growth, which is a common practice in the art.

Obviousness of Claim 4:
Claim 4 specifies the scaffold is "comprised of a polymer."
Motivation: This is explicitly taught in the prior art. Yelick et al. describes a "biodegradable polymer scaffold." [cite: Yelick et al.] Grikscheit et al. used "polyglycolic acid tubes," [cite: a later application] which are polymers, and Atala et al. used a scaffold "made of collagen and polyglycolic acid." [cite: Recently, a successful human clinical trial has been reported]

Combination: The polymer scaffold teachings of Yelick et al. (US Pat. appl. 20020119180 A1), Grikscheit et al. (US Pat. appl. 20030129751), or Atala et al. (US Pat. appl. 20070059293 A1).

Obviousness of Claim 5:
Claim 5 outlines a method for generating an implant comprising a 3D scaffold shell containing a tissue matrix, involving providing immunocompatible cells from an organ, identifying a vascular growth site, introducing a 3D scaffold, placing vascular tissue into the scaffold's interior while maintaining intact flow, introducing the cell mixture to associate with the vascular tissue, incubating, and then removing the implant.

1. Providing immunocompatible cells from an organ: The patent refers to "autologous cells," [cite: The scaffold interior is designed in order to accommodate multiple layers of omentum, in contact with autologous cells suspended in nutrient-containing matrix.] which are inherently immunocompatible. Harvesting cells from organs is a standard procedure in tissue engineering.
2. Identifying a vascular growth site with intact arterial/venous flow: The prior art extensively uses the omentum as a highly vascularized tissue for tissue engineering (Vacanti, Yelick, Grikscheit, Atala), implicitly relying on its intact vascular supply for successful tissue growth. The patent further lists specific anatomical "Growth Chamber Site[s]" with their corresponding "Vascular Scaffold (Blood supply)," [cite: Potential sites for such a subcutaneous chamber would include the following, listed with their proposed vascular scaffold named by their blood supply:] demonstrating that identifying such sites is known in the art.
3. Introducing 3D scaffold into growth site and placing vascular tissue into its interior with intact flow: Yelick et al. placed a "biodegradable polymer scaffold... onto the omentum of rats." [cite: Yelick et al.] Grikscheit et al. sutured "polyglycolic acid tubes... to the rat's omentum." [cite: a later application] Atala et al. implanted scaffolds "covered with omentum." [cite: Recently, a successful human clinical trial has been reported] While these may not explicitly describe placing the omentum into the interior of the scaffold, the motivation to maximize vascular contact to overcome prior art limitations (as discussed for Claim 1) would lead a PHOSITA to design an internal configuration. The concept of an "intra-abdominal growth chamber" where "the omentum would be pulled into the growth chamber" [cite: In this model, the growth chamber would be inserted between the posterior rectus sheath and the anterior parietal peritoneum. This could be done using laparoscopic techniques. Through one port in the growth chamber, the omentum would be pulled into the growth chamber using laparoscopic instruments.] is described in the patent, indicating this as a logical extension of prior art. Maintaining intact arterial and venous flow is essential for any vascularized tissue transfer or growth, making it an inherent requirement known to a PHOSITA.
4. Introducing cell mixture into scaffold interior to associate with vascular tissue: This is a direct application of the general principle of seeding cells onto or within scaffolds that are then vascularized by the omentum, as demonstrated by Grikscheit et al. (high-density seeding of polymer scaffold with organoid units) [cite: a later application] and Atala et al. (autologous bladder cells seeded on a scaffold which was then covered with omentum). [cite: Recently, a successful human clinical trial has been reported]
5. Incubating to form implant: This is a standard and expected step in all in vivo tissue engineering described in the prior art (e.g., Yelick, Grikscheit, Atala).
6. Removing implant: The patent explicitly discusses this, stating that a "resorbable chamber would allow the developing organ to be left in its 'manufacturing site' but then could be transferred with the omental vessels using free microvascular tissue transfer techniques." [cite: The resorbable chamber would allow the developing organ to be left in its “manufacturing site” but then could be transferred with the omental vessels using free microvascular tissue transfer techniques.]

Combination: A PHOSITA would be motivated to combine the known methods of creating 3D scaffolds (e.g., Sahatjian et al., Yelick et al.) with the established use of omentum for vascularization (e.g., Vacanti et al., Yelick et al., Grikscheit et al., Atala et al.) and cell seeding techniques (e.g., Grikscheit et al., Atala et al.). The explicit problems of poor vascularization, size limitations, and resorption in the prior art would provide ample motivation to develop a method that maximizes vascular contact between the omentum and the cell mixture within a scaffold. Placing the vascular tissue into the interior of the scaffold to directly associate with the cell mixture would be an obvious way to achieve the improved vascularization necessary for successful growth of larger, functional tissues, with a reasonable expectation of success building upon the established foundational techniques. The transfer of the developed organ is also explicitly described as a feature of the invention, addressing the final placement of the engineered tissue.

Obviousness of Claim 6:
Claim 6 specifies the organ as a "breast."
Motivation: Same as for Claim 2, drawing on Vacanti et al. (U.S. Pat. No. 5,716,404) for breast tissue engineering.

Combination: The method of Claim 5 applied to breast tissue engineering as known from Vacanti et al., motivated by the need for better vascularization in breast augmentation.

Obviousness of Claim 7:
Claim 7 specifies the vascularized tissue comprises "omentum of a said patient."
Motivation: This is directly and broadly taught in the prior art. "The omentum has been used by various investigators as a source of vasculature for tissue engineering purposes" [cite: The omentum has been used by various investigators as a source of vasculature for tissue engineering purposes:]. Specific examples include Vacanti et al., Yelick et al., Grikscheit et al., Atala et al., and others mentioned in the patent's background.

Combination: This is directly disclosed by a multitude of prior art references concerning the use of omentum for tissue vascularization.

Obviousness of Claim 8:
Claim 8 specifies the cell mixture comprises "a mixture of fat cells and a nutrient."
Motivation: Same as for Claim 3. Combining harvested cells (like fat cells) with a nutrient solution is a basic tenet of cell culture and tissue engineering, acknowledged as "well-established" [cite: Cell culture technology has become a well-established technique that is very successful in vitro under ideal laboratory conditions.] by the patent itself and exemplified in Example 1. [cite: This fat tissue was then manually mixed with PuraMatrix (Becton Dickinson, Bedford, Mass.) in 10% sucrose solution.]

Combination: General knowledge of cell culture and the patent's own description.

Obviousness of Claim 9:
Claim 9 specifies the growth site is selected from "mid-abdomen region, an inguinal region, an axillary region, a medial thigh region, and the substernal region."
Motivation: The patent itself proposes these specific sites as suitable "growth chambers," explicitly listing their "Vascular Scaffold (Blood supply)" [cite: Potential sites for such a subcutaneous chamber would include the following, listed with their proposed vascular scaffold named by their blood supply:] and discussing their suitability for different types of tissue engineering (e.g., substernal for esophageal and tracheal, intra-abdominal for breast, bone, cartilage). [cite: The present inventors propose a substernal vascularized growth chamber which may be the best model for esophageal and tracheal tissue engineering., The present inventors hypothesize that this may be the best model for tissue engineering the following organs:] These are anatomically recognized sites with known vascularity suitable for tissue flaps and growth, and their selection would be routine for a PHOSITA aiming to establish a vascularized growth chamber.

Combination: General anatomical and surgical knowledge of vascularized sites, reinforced by the patent's own disclosure of these specific locations as optimal growth chambers.

Obviousness of Claim 10:
Claim 10 specifies the three-dimensional scaffold shell is "bioresorbable."
Motivation: The use of biodegradable/bioresorbable scaffolds is extensively taught in the prior art. Yelick et al. uses a "biodegradable polymer scaffold." [cite: Yelick et al.] Grikscheit et al. uses "polyglycolic acid tubes," [cite: a later application] which are biodegradable. Atala et al. uses a "biodegradable bladder-shaped scaffold made of collagen and polyglycolic acid." [cite: Recently, a successful human clinical trial has been reported] The patent also discusses "resorbable plate and screw technology" in craniofacial surgery, noting that "These biopolymers are easily shaped with heat and can be easily made into chambers." [cite: Today, craniofacial surgery is done with resorbable plates that take 18 months to absorb (Macropore, Lactosorb, etc.). These biopolymers are easily shaped with heat and can be easily made into chambers.]

Combination: The bioresorbable scaffold teachings of Yelick et al. (US Pat. appl. 20020119180 A1), Grikscheit et al. (US Pat. appl. 20030129751), or Atala et al. (US Pat. appl. 20070059293 A1), reflecting well-established practice in the field.