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 .
Applicant’s claims filed on 6/10/2026 in response to the Non-Final Rejection mailed on 3/11/2026 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
Claims 81-100 are pending.
Claim 1-80 are canceled.
Applicant’s remarks filed on 6/10/2026 in response to the Non-Final Rejection mailed on 3/11/2026 have been fully considered and are not deemed persuasive to overcome at least one of the rejections and/or objections as previously applied.
It is noted that the 112b rejection over the recitation ‘under conditions inducing protein synthesis’ within the instant application claim 100 would be withdrawn in view of Applicant’s remarks that one of ordinary skill in the art would ascertain the conditions for inducing protein synthesis. However, the 112b rejection over claim 100 is maintained as said claim is dependent upon claim 81, which is rejected under 112b due to the recitation ‘essentially cross-linker-free.’
The text of those sections of Title 35 U.S. Code not included in the instant action can be found in the prior Office Action.
Maintained Claim Rejection - 35 USC § 112a
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—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 or joint inventor of carrying out the invention.
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 rejection of claims 96-98 under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, as based on a disclosure which is not enabling is maintained. The disclosure does not enable one of ordinary skill in the art to practice the invention without a conclusion one can come to after "preparing the plurality of microparticles of claim 81” and , which is/are critical or essential to the practice of the invention but not included in the claim(s). See In re Mayhew, 527 F.2d 1229, 188 USPQ 356 (CCPA 1976). In paragraph 0010 of the instant application specification, Applicant recites ‘where the plurality of microparticles is essentially or substantially cross-linker-free; and where the plurality of microparticles is water insoluble’ (Instant Application Specification, para 0010). Regarding claim 96 (claims 97 dependent thereof), the preamble states “microparticle of claim 81” but the end result is a “microparticle comprising size-reduced cross linked foam.” There is no recitation of any foam in claim 81. Regarding claim 98, the end result is not a microparticle but a “plurality of cross-linked foam or hydrogel particles.” The entire method including the preamble and the steps involved do not convey to one skilled in the art as to what this method is all about and its purpose. While claims can be broad it cannot be so broad such that its boundaries are not clear. The test is so broad such that one of skill in the art cannot envision the four corners of the breadth. Appropriate correction is suggested.
RESPONSE TO REMARKS: Beginning on p. 6 of Applicant’s remarks, Applicant contends that the rejection has been addressed. In summary, Applicant contends that the claims are fully enabled and are commensurate with the disclosure. Applicant contends that the fact that claim 96 recites formation of a "cross-linked foam or hydrogel block" does not create an enablement issue simply because claim 81 does not itself recite "foam." Applicant contends that the specification describes that "the cross-linked protein can be stabilized into, for example, a foam, into a confluent hydrogel, or into fibers," and further explains that the enzyme may subsequently be removed "by, for example, washing the enzyme out of the particles or inactivating the cross-linker or crosslinking enzyme." Specification [0047]. The specification also expressly describes "reducing in size the lyophilized cross-linker-free foam or block ... to form a plurality of cross-linked foam or block particles." Specification [0064]. Thus, the method steps and the resulting microparticles are directly and repeatedly described. Applicant contends that the specification also provides details sufficient to make and use the claimed subject matter.
This argument is found to be not persuasive. Examiner contends, in the instant case, there is a disconnect between the preamble and the end result of the method as the preamble of the instant application claim 81, upon which claims 96 and 98 depend, recites ‘a plurality of microparticle.’ The end result of claims 96 and 98 is cross- linked foam, not a plurality of microparticles, as recited in the preamble of the instant application claim 81. Additionally, based on Applicant’s recitation within the instant application claim 81, upon which claims 96 and 98 depend, it is unclear whether or not the claimed plurality of microparticles encompass a plurality of microparticles comprising size-reduced cross- linked foam and/or size-reduced cross-linker-free foam as there is no prior recitation of ‘cross-linked foam and/or size-reduced cross-linker free foam’; within the instant application claim 81. Applicant’s assertion that ‘cross-linked foam’ is stated within the instant application specification does not necessitation withdrawal of the 112a rejection as Applicant is reminded that the claims are read in-light of the specification. Additionally, Examiner contends that the entire method including the preamble and the steps involved do not convey to one skilled in the art as to what this method is all about and its purpose. While claims can be broad it cannot be so broad such that its boundaries are not clear.
Maintained Claim Rejections - 35 USC § 112(b)
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.
The rejection of claims 81-100 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 is maintained. The rejection has been modified to withdrawn the 112b rejection over the recitation ‘under conditions inducing protein synthesis,’ of the instant application claim 100.
The phrase “essentially cross-linker-free” in claim 81 (claims 82-100 dependent thereof) is a relative term which renders the claim indefinite. The term “essentially” 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. The term "essentially” is a relative term that renders the claim indefinite because it is unclear whether it is broad or limited. See MPEP § 2173.05(b) III A. Appropriate correction is suggested.
Regarding claim 84, the recitation of the phrase ‘engineered protein’ is indefinite because it is unclear what the scope of the phrase is intended to encompass structurally. It is unclear what the ‘engineered protein’ is intended to encompass. It is unclear from the claims and specification what the phrase ‘engineered protein’ is referring to structurally and functionally. In addition, the recitation “any engineered polymer comprising a RGD motif” scope is unclear as it is substantially broader than the recitation “the engineered protein.” Accordingly, the metes and bounds upon which patent protection is sought cannot be ascertained from this phrase.
Claim 96 (claims 97-98 dependent thereof) recite the phrases ‘reducing in size.’ The term "reducing" is a relative term which renders the claim indefinite. The term "reducing" is a term of degree, and there is no indication what the percentage is being compared. Accordingly, the metes and bounds upon which patent protection is sought cannot be ascertained from the claims. It is suggested that applicant clarify the meaning of the claims. See Supplementary Examination Guidelines for Determining Compliance with 35 U.S.C. §112 and for Treatment of Related Issues in Patent Applications, 76 FR 7162 (Feb. 9, 2011), page 7165.
Additionally, there is a disconnect between “the preamble of the claim and the end result of the method”.
Regarding claim 99, the recitation of the phrase ‘body contouring’ is indefinite because it is unclear what the scope of the phrase is intended to encompass structurally. It is unclear what the ‘body contouring’ is intended to encompass. It is unclear from the claims and specification what the phrase ‘body contouring is referring to structurally and functionally. Accordingly, the metes and bounds upon which patent protection is sought cannot be ascertained from this phrase.
RESPONSE TO REMARKS: Beginning on p. 7 of Applicant’s remarks, Applicant contends that the rejection has been addressed. In summary, Applicant contends that the phrase "essentially cross-linker-free" in claim 81 is not indefinite because the specification provides an expressed standard for the term. Applicant contends that the specification stating ‘that the final microparticles comprise "proteins previously cross-linked or pre-cross-linked proteins, where the cross-linked proteins have been washed to remove any cross-linkers, such that the final microparticle or plurality of microparticles comprising cross-linked proteins is cross-linker-free or essentially or substantially cross-linker-free." See, Specification at [0048], provides a concrete, functional boundary, i.e., absent cross-linker or only nominal amounts that do not affect the function or use of the microparticles.
The argument is not persuasive. Examiner contends that the term ‘essentially’ is rejected under 112b as the specification does not provide enough guidance for a skilled person to distinguish essential ingredients from trace impurities. Examiner contends that Applicant has not ‘clearly’ defined the phrase "essentially cross-linker-free" in a quantitative or measurable manner in the specification such that it would be clear to one of skill in the arts as to how to determine if the composition is free of cross-linker. Examiner contends that the specification stating that the final microparticles comprise ‘proteins previously cross-linked or pre-cross-linked proteins, where the cross-linked proteins have been washed to remove any cross-linkers, such that the final microparticle or plurality of microparticles comprising cross-linked proteins is cross-linker-free or essentially or substantially cross-linker-free’ does not clearly define the recitation "essentially cross-linker-free.” Examiner acknowledges Applicant’s attempt to define ‘essentially’ as being nominal. However, said term must be further defined to obtain patentable weight.
Applicant contends that the phrase "engineered protein" of claim 84 is a closed list of protein alternatives, including gelatin, collagen, tropoelastin, elastin, casein, albumin, engineered protein thereof, an engineered polymer comprising an RGD motif, and combinations thereof.
The argument is not persuasive. Examiner contends that the phrase "engineered protein" fails to clearly define the protein's structural boundaries or functional limits, leaving a person skilled in the art unable to determine with reasonable certainty what the claim covers. Examiner contends a closed list of protein alternatives, including gelatin, collagen, tropoelastin, elastin, casein, albumin, engineered protein thereof, an engineered polymer comprising an RGD motif, and combinations thereof does not clearly define the phrase "engineered protein."
Applicant contends that the phrase "reducing in size" in claim 96, is expressly identified as being the formed cross-linked foam or hydrogel block, the cross-linker-free foam or hydrogel block, or combinations thereof. Applicant contends that the specification identifies exemplary operations for reducing in size, including "cutting," "dicing," "chopping," "meshing," "sieving," "compression," breakers," "pulverizers," "mills," and "grinders," and states that the reduction may form particles in specified size ranges. See, e.g., Specification at [0063]. Applicant contends that the specification further explains that particle size may be measured using standard techniques, including particle size analyzers, image particle analysis, laser diffraction, dynamic light scattering, acoustic spectroscopy, and sieve analysis. See, e.g., Specification at [0050].
The argument is not persuasive. Examiner contends that the recitation "reducing in size" is a vague relative limitation lacking objective boundaries. Examiner contends that Applicant has not properly defined the parameters of “reducing in size.” Examiner contends that the specification identifying exemplary operations for reducing in size, including "cutting," "dicing," "chopping," "meshing," "sieving," "compression," breakers," "pulverizers," "mills," and "grinders" do not necessitate withdrawal of the 112b rejection as it remains unclear the degree upon which Applicant is measuring “reducing in size” as Applicant is reminded that the specification in read in-light of the claims.
Applicant contends that claim 81 need not recite "foam" for claim 96 to define a more specific process for making claim-81-compliant microparticles.
Examiner contends that MPEP 2173.05€ states “a claim is indefinite when it contains words or phrases whose meaning is unclear. In re Packard, 751 F.3d 1307, 1314, 110 USPQ2d 1785, 1789 (Fed. Cir. 2014). The lack of clarity could arise where a claim refers to "said lever" or "the lever," where the claim contains no earlier recitation or limitation of a lever and where it would be unclear as to what element the limitation was making reference. Similarly, if two different levers are recited earlier in the claim, the recitation of "said lever" in the same or subsequent claim would be unclear where it is uncertain which of the two levers was intended. A claim which refers to "said aluminum lever," but recites only "a lever" earlier in the claim, is indefinite because it is uncertain as to the lever to which reference is made. Obviously, however, the failure to provide explicit antecedent basis for terms does not always render a claim indefinite. If the scope of a claim would be reasonably ascertainable by those skilled in the art, then the claim is not indefinite. Ex parte Porter, 25 USPQ2d 1144, 1145 (Bd. Pat. App. & Inter. 1992) ("controlled stream of fluid" provided reasonable antecedent basis for "the controlled fluid"). Inherent components of elements recited have antecedent basis in the recitation of the elements themselves. For example, the limitation "the outer surface of said sphere" would not require an antecedent recitation that the sphere has an outer surface. See Bose Corp. v. JBL, Inc., 274 F.3d 1354, 1359, 61 USPQ2d 1216, 1218-19 (Fed. Cir 2001) (holding that recitation of "an ellipse" provided antecedent basis for "an ellipse having a major diameter" because "[t]here can be no dispute that mathematically an inherent characteristic of an ellipse is a major diameter").” As such, Examiner contends that the phrase “the formed cross-linked foam” lacks antecedent basis. It is recommended that Applicant amend the claim to recite “a formed cross-linked foam.”
Applicant contends that the recitation of "body contouring" in claim 99 is not indefinite due to the specification stating the injectable use of the microparticle composition in "therapeutic and/or aesthetic applications," including injection into "the subcutaneous layer," "soft tissue," and "mammalian glands." See, e.g., Specification at [0093]. The specification further states that the implant can act as a filler for "body contouring, reconstruction, breast augmentation," and may provide skin lifting or expansion through biomechanical scaffold strength. See, e.g., Specification at [0095].
The argument is not persuasive. Examiner contends that Applicant has not properly defined the phrase ‘body contouring.’ Examiner contends that body contouring is not limited to the injectables described by Application in the instant application specification para 0093.
Maintained Claim Rejections - 35 USC § 102
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.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
The rejection of claims 81-84, 86-94 under 35 U.S.C. 102(a)(1/2) as being anticipated by Attar et al (US 2018/0256641 A1, Date of Publication: Sep. 13, 2018, cited on PTO-892 dated 3/11/2026) {herein Attar} as evidenced by Asim et al (2023, Adv Healthc mater, cited on PTO-892 dated 3/11/2026) {herein Asim} is maintained. See MPEP 2131.01 regarding multiple reference 102 rejections.
Claims 81-84, 86-94 are drawn to a plurality of microparticles, comprising:(a) a cross-linked protein, wherein said cross-linked protein comprises at least one RGD (Arg- Gly-Asp) motif; wherein the plurality of microparticles is essentially cross-linker-free; wherein the plurality of microparticles is water insoluble.
With respect to claims 81-84, 86-9, 92, 94, Attar teaches a composition of a plurality of microparticles comprising cross-linkable protein that comprises gelatin that is mixed with cross-linker transglutaminase (para 0169) and dissolved in water to form a cross-linked foam (para 0323, 0324, 0325) at 37C (para 0182) or a hydrogel (para 0127). Evidentiary reference of Asim is recited to demonstrated that gelatin is natively comprised of RGD sequences (page 4, para 2). As such, absent evidence otherwise, it is the Examiner’s position that the cross-linkable protein (gelatin) comprises at least one RGD motif, as recited in the instant application claim 81. Attar further teaches the a carrier binds the cross-linking enzyme (para 0080). Furthermore, Attar teaches the composition of the invention is a substantially dry gelatin configured to form a foam (para 0122). In some embodiments, the particle size is between 2-250 microns (para 0126). Absent evidence otherwise, it is the Examiner’s position that the plurality of particles taught by Attar would inherently be comprised of at least two different particle sizes as the particle size ranges between 2-250 microns. Attar further teaches the carrier is purified from solution (para 0139). Absent evidence otherwise, it is the Examiner’s position that the carrier is wet as Attar teaches its purification from solution (para 0139).
With respect to claim 93, Attar teaches the carrier comprised hyaluronic acid, (para 0234) which is known by those of ordinary skill in the art to be the same as hyaluronan polymers, of which, absent evidence otherwise, is the Examiner’s position that hyaluronic acid (hyaluronan) it native form is un-crosslinked hyaluronan polymers as Attar does not teach it to be modified.
For the reasons stated herein, the teachings of Attar anticipate claims 81-84, 86-94.
The rejection of claims 96-97, 99-100 under 35 U.S.C. 102(a)(1/2) as being anticipated by Attar et al (US 2018/0256641 A1, Date of Publication: Sep. 13, 2018, cited on PTO-892 dated 3/11/2026) {herein Attar} as evidenced by Asim et al (2023, Adv Healthc mater, cited on PTO-892 dated 3/11/2026) {herein Asim} is maintained. See MPEP 2131.01 regarding multiple reference 102 rejections.
Claims 96-97 are drawn to a method of preparing the plurality of microparticles of claim 81, comprising:(a) mixing a cross-linkable protein solution and a cross-linker solution, wherein the cross-linkable protein solution comprises dissolving a cross- linkable protein comprising at least one RGD (Arg-Gly-Asp) motif in a liquid; wherein the cross-linker solution comprises dissolving a cross-linker in a liquid; (b) forming a cross-linked foam or hydrogel block comprising the mixed cross-linkable protein solution and cross-linker solution of (a); (c) removing the cross-linker from the cross-linked foam or hydrogel block of (b) to form a cross-linker-free foam or hydrogel block; and (d) reducing in size: the formed cross-linked foam or hydrogel block of (b), the cross- linker-free foam or hydrogel block of (c), or combinations of the formed cross- linked foam or hydrogel block of (b) and the cross-linker-free foam or hydrogel block of (c), to form a plurality of microparticles comprising size-reduced cross- linked foam of (b) and/or size-reduced cross-linker-free foam of (c).
Claim 99 is drawn to a method of treating a subject in need of body contouring, comprising administering the composition of claim 82 at a site of the subject in need of body contouring.
Claim 100 is drawn to a method of producing a cell-free protein, comprising: growing a plurality of protein-producing cells in a cell culture comprising the plurality of microparticles of claim 81 and culture medium, wherein growing occurs under conditions inducing protein synthesis, thereby producing a cell-free protein.
With respect to claims 96-97, 99-100, Attar teaches a method wherein cross-linkable protein that comprises gelatin is mixed with cross-linker transglutaminase (para 0169) and dissolved in water to form a cross-linked foam (para 0323, 0324, 0325) at 37C (para 0182). Evidentiary reference of Asim is recited to demonstrated that gelatin is natively comprised of RGD sequences (page 4, para 2). As such, absent evidence otherwise, it is the Examiner’s position that the cross-linkable protein (gelatin) comprises at least one RGD motif, as recited in the instant application claim 81. Attar further teaches cells containing the gelatin mix were seeded on tissue culture treated plastic (para 0375) Subsequently, the cells were separated from the gelatin composition (para 0385). Absent evidence otherwise, it is the Examiner’s position that said composition is cell-free gelatin as Attar teaches the cells were separated from the composition (para 0385). Absent evidence otherwise, it is the Examiner’s position that the crosslinker transglutaminase and cross-linkable protein gelatin would necessarily have to be ‘whipped’ together to form the foam as it is known by those of ordinary skill in that art that foam is made by ‘whipping’ component together. Additionally, it is the Examiner’s position that a hydrogel is necessarily formed by the reaction of the gelatin and transglutaminase as it is known by those of ordinary skill in that art that the cross-linking of natural fibers such as gelatin form stable structures. Attar further teaches that cross-linking enzyme is purified from carrier proteins (para 0139). Absent evidence otherwise, it is the Examiner’s position that the cross-linker transglutaminase, would necessarily be removed from the cross-linked foam, forming a cross-linker free foam, as Attar teaches the cross-linker is eluted from the carrier proteins that are within the gelatin composition. Absent evidence otherwise, it is the Examiner’s position that the formed cross-linked foam would necessarily be reduced in size as Attar teaches a method of preparing a plurality of microparticles by utilizing gelatin and a crosslinker enzyme of transglutaminase to form a foam size-reduced cross-linked foam (para 0169, 0323, 0324, 0345, 0084). Furthermore, said composition can be used for facial contouring (para 0280).
For the reasons stated herein, the teachings of Attar anticipate claims 96-97, 99-100.
RESPONSE TO REMARKS: Beginning on p. 10 of Applicant’s remarks, Applicant contends that the rejection has been addressed. In summary, Applicant contends that Attar does not disclose the claimed "plurality of microparticles" comprising a "cross-linked protein," where the plurality of microparticles is both "essentially cross-linker-free" and "water insoluble," as recited in independent claim 81. Applicant contends that Attar's disclosure of gelatin powder particle sizes as "rapidly dissolving dry protein of non-crosslinked protein," are expressly non-crosslinked and rapidly dissolving, not water-insoluble cross-linked protein microparticles that are essentially cross-linker-free as claimed. Applicant contends that Attar does not expressly disclose a plurality of microparticles that are already cross-linked, water- insoluble, and essentially cross-linker-free, as required by claim 81. Applicant contends that Attar's passage concerns purification of transglutaminase solutions to remove fermentation residue, carrier proteins and/or carbohydrates, endotoxin, or microbes from the transglutaminase solution. See, e.g., Attar at [0139]. The cited purification passage does not disclose removing cross-linker from a formed cross-linked foam or hydrogel block and does not disclose forming a plurality of essentially cross-linker-free cross-linked protein microparticles.
The argument is not persuasive. Examiner contends that Attar teaches cross-linked and non-crosslinked gelatin in cold temperatures to form foam (para 0122). Since the plurality of microparticles (cross-linked and non cross-linked gelatin) are in cold liquids, said composition would inherently be water soluble as it is well-known in the art that at low temperature, gelatin is insoluble. Since the Office does not have the facilities for examining and comparing Applicants’ gelatin with the gelatin of the prior art, the burden is on the applicant to show a novel or unobvious difference between the claimed product and the product of the prior art (i.e., that the microparticles of the prior art does not possess the same mineral composition of the claimed microparticles). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
Additionally, Examiner contends that since Attar teaches cross-linked gelatin, then said microparticle is inherently water insoluble because chemical bonds tie its individual protein chains into a giant, permanent 3D network wherein water can enter and swell this mesh, but it cannot break the covalent bonds holding the massive network together, thereby preventing the molecules from separating and dissolving. Examiner contends that Attar teaches a method wherein cross-linkable protein that comprises gelatin is mixed with cross-linker transglutaminase (para 0169). Attar further teaches that cross-linking enzyme is purified from carrier proteins (para 0139). It remains the Examiner’s position that the cross-linker transglutaminase, would necessarily be removed from the cross-linked foam during the purification process, thereby forming an essentially cross-linker free foam, as Attar teaches the cross-linker is eluted from the carrier proteins that are within the gelatin composition. Examiner contends that Applicant’s remarks that Attar does not expressly disclose a plurality of microparticles that are already cross-linked, water- insoluble, and essentially cross-linker-free, as required by claim 81, is not a required limitation of the claim as Applicant does not recite such a limitation. However, to advance prosecution, Attar does in-fact teach the utilization of pre-crosslinked gelatin at paragraph 128 (para 0128). Furthermore, Applicant’s recitation of ‘comprising’ within the instant application claim 81, does not further limit the claim language as the term ‘comprising’ is broad.
Applicant contends that the cited passages of Attar do not disclose the claimed sequence of method steps. Applicant contends that the cited Attar passages describe jet milling or pulverizing gelatin before crosslinking. See, e.g., Attar at [0126], [0325]. Thus, in those passages, size reduction is performed on non- crosslinked gelatin powder, rather than on an already formed cross-linked foam or hydrogel block or on a cross-linker-free foam or hydrogel block.
The argument is not persuasive. Examiner contends that Attar teaches the milling of pre-crosslinked gelatin to reduce its size (para 0127 and 0128).
Applicant contends that Attar's foam examples do not disclose removing cross-linker from the formed foam before reducing the foam in size.
The argument is not persuasive. Examiner contends that Attar teaches removal of the cross-linker by purification methods before milling to reduce the size of the gelatin (para 0122, 0127, 0128).
Applicant contends that Asim does not supply the claimed microparticle structure, water insolubility, or essentially cross-linker-free character. Applicant contends that the evidentiary reference of Cytiva does not teach or suggest modifying the cited Attar process to form a cross-linked foam or hydrogel block, remove cross-linker from the formed block, lyophilize the resulting cross-linker-free foam or hydrogel block, and then reduce the lyophilized cross-linker-free foam or hydrogel block in size to form the plurality of cross-linked foam or hydrogel particles recited in claim 98.
The argument is not persuasive. Examiner contends that the evidentiary reference of Asim is recited to demonstrated that gelatin is natively comprised of RGD sequences (page 4, para 2). Examiner contends that Asim was not relied upon to teach the limitations of independent claim 81. Additionally, the evidentiary reference of Cytia was cited to provide support for why it would be obvious to one of ordinary skill in the art to freeze-dried and lyophilized cross-linker free foam as it would extend the shelf-life of the gelatin.
Maintained 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 rejection of claims 85, 95 under 35 U.S.C. 103 as being unpatentable over Attar et al (US 2018/0256641 A1, Date of Publication: Sep. 13, 2018, cited on PTO-892 dated 3/11/2026) {herein Attar} as evidenced by Asim et al (2023, Adv Healthc mater, cited on PTO-892 dated 3/11/2026) {herein Asim} is maintained.
Claim 85 is drawn to the composition of claim 82, wherein the cross-linked protein comprises the RGD motif in a range of 0.1 µg/mg - 50 µg/mg.
Claim 95 is drawn to the composition of claim 83, wherein the composition comprises a concentration of the plurality of microparticles in the carrier of: 1 mg/ml or greater, 300 mg/ml or less, or 1 mg/ml - 300 mg/ml.
The teachings of Attar as applied to claims 81-84, 86-94 are set forth in the 102a1a2 rejection above.
However, Attar does not teach wherein the cross-linked protein comprises the RGD motif in a range of 0.1 g/mg - 50 µg/mg (claim 85). Attar does not teach wherein the composition comprises a concentration of the plurality of microparticles in the carrier of: 1 mg/ml or greater, 300 mg/ml or less, or 1 mg/ml - 300 mg/ml (claim 95).
With respect to claims 85, 95, although the reference of Attar does not explicitly teach the limitations of claim 85 (wherein the cross-linked protein comprises the RGD motif in a range of 0.1 µg/mg - 50 µg/mg)—These units are incorrectly quoted here. These are NOT claim limitations. and claim 95 (wherein the composition comprises a concentration of the plurality of microparticles in the carrier of: 1 mg/ml or greater, 300 mg/ml or less, or 1 mg/ml - 300 mg/ml), MPEP 2144.05 states"[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144.05 IIA)." One of ordinary skill would desire to optimize the RGD motif and plurality of microparticles depending on the particular application. It would be routine for one to arrive at the RGD motif and plurality of microparticles for the application they intend on using the composition. Therefore, the above invention would have been prima facie obvious.
The rejection of claim 98 as being unpatentable over Attar et al (US 2018/0256641 A1, Date of Publication: Sep. 13, 2018, cited on PTO-892 dated 3/11/2026) {herein Attar} as evidenced by Asim et al (2023, Adv Healthc mater, cited on PTO-892 dated 3/11/2026) {herein Asim} is maintained.
Claim 98 is drawn to the method of claim 96, further comprising: (e) freezing the cross-linker-free foam or hydrogel block of (c) or plurality of particles of (d); (f) lyophilizing the frozen cross-linker-free foam or hydrogel block of (e); and (g) reducing in size the lyophilized cross-linker-free foam or hydrogel block of (f) to form a plurality of cross-linked foam or hydrogel particles.
The teachings of Attar as applied to claims 96-97, 99-100 are set forth in the 102a1 rejection above.
However, Attar does not teach (e) freezing the cross-linker-free foam or hydrogel block of (c) or plurality of particles of (d); (f) lyophilizing the frozen cross-linker-free foam or hydrogel block of (e); and (g) reducing in size the lyophilized cross-linker-free foam or hydrogel block of (f) to form a plurality of cross-linked foam or hydrogel particles (claim 98).
With respect to claim 98, it would be obvious to one of ordinary skill in the art to freeze-dry and lyophilize the cross-linker-free foam as doing so would increase the shelf-life of the composition. Furthermore, it would be obvious to one of ordinary skill in the art that the freeze-dried and lyophilized cross-linker free foam would necessarily for a plurality of cross-linker foam as it is known by those of ordinary skill in the art that when a composition is freeze-dried and lyophilized, it would necessarily form a plurality of particles as the composition is a dried and free of moisture. Supporting the Examiner’s position is the evidentiary reference of Cytiva (2024, cytiva, Examiner cited) which recites the low temperature dehydration process of freeze drying maximizes product or sample stability and shelf-life, maintains chemical or biological function and enables easier transportation and storage or samples (page 1, para 1).-
Before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to modify the composition of the cross-linker free foam to that which will prolong its shelf-life. Especially since it is well-known in the industry that freeze-drying and lyophilizing protein compositions is effective at maintaining its quality and activity over an extended period of time.
One of ordinary skill in the art would be motivated, have had a reasonable expectation of success, a reasonable level of predictability to freeze-dry and lyophilize the plurality of microparticles to help maintain its activity and reduce the need for specialized storage. Furthermore, one of ordinary skill in the art would be motivated to freeze-dry and lyophilize the plurality of microparticles as doing so would reduce the probability of microbial contamination and would allow for the production and storage of the plurality of microparticles for its subsequent utilization over an extended period of time. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
RESPONSE TO REMARKS: Beginning on p. 12 of Applicant’s remarks, Applicant contends that the rejection has been addressed. In summary, Applicant contends that the cited passages of Attar and Asim do not disclose the plurality of microparticles recited in independent claim 81, including microparticles comprising cross-linked protein that are water insoluble and essentially cross-linker-free. Applicant contends that the cited passages of Attar do not disclose the method steps or their order recited in claim 96, including forming a cross-linked foam or hydrogel block, removing cross-linker from the cross-linked foam or hydrogel block to form a cross-linker-free foam or hydrogel block, and reducing in size the formed cross-linked foam or hydrogel block and/or the cross-linker-free foam or hydrogel block. The cited Attar passages describe size reduction of gelatin before crosslinking, rather than reducing in size an already formed cross-linked foam or hydrogel block or a cross-linker-free foam or hydrogel block.
The argument is not persuasive. Examiner contends that Attar teaches cross-linked and non-crosslinked gelatin in cold temperatures to form foam (para 0122). Since the plurality of microparticles (cross-linked and noncross-linked gelatin) are in cold liquids, said composition would inherently be water soluble as it is well-known in the art that at low temperature, gelatin is insoluble. Since the Office does not have the facilities for examining and comparing Applicants’ gelatin with the gelatin of the prior art, the burden is on the applicant to show a novel or unobvious difference between the claimed product and the product of the prior art (i.e., that the microparticles of the prior art does not possess the same mineral composition of the claimed microparticles). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
Examiner contends that Attar teaches cross-linked and non-crosslinked gelatin in cold temperatures to form foam (para 0122). Since the plurality of microparticles (cross-linked and noncross-linked gelatin) are in cold liquids, said composition would inherently be water soluble as it is well-known in the art that at low temperature, gelatin is insoluble. Since the Office does not have the facilities for examining and comparing Applicants’ gelatin with the gelatin of the prior art, the burden is on the applicant to show a novel or unobvious difference between the claimed product and the product of the prior art (i.e., that the microparticles of the prior art does not possess the same mineral composition of the claimed microparticles). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594. Additionally, Examiner contends that Attar does in-fact teach the utilization of pre-crosslinked gelatin at paragraph 128 (para 0128).
Maintained Nonstatutory 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.
The rejection of claims 81-95 on the grounds of nonstatutory double patenting as being unpatentable over claims 1, 3, 17 of U.S. Patent No. US 11331412 B2 which are commonly owned and have common inventors and filed before the instant application is maintained. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are drawn to a composition, wherein the pores of the foam scaffold are from 1 to 500 microns in diameter, the composition comprising: a cross-linkable protein comprising at least one RGD (Arg-Gly-Asp) motif; and a cross-linker which induces cross-linking of the cross linkable protein.
The instant application claims 81-85, 91, 93-95 are not patentably distinct from claim 1 of ‘412 because claim 1 of ‘412 recites ‘the composition comprising: a cross-linkable protein comprising at least one RGD (Arg-Gly-Asp) motif; and a cross-linker which induces cross-linking of the cross linkable protein,’ which is not patentably distinct from the instant application claims 81-85, 91, 93-95.
The instant application claims 87-90, 92 are not patentably distinct from claim 2 of ‘412 because claim 2 of ‘412 recites ‘wherein the cross-linkable protein is introduced into the composition as a micronized protein powder, having an average particle size between 5 to 200 microns’ which is not patentably distinct from the instant application claims 87-90, 92.
The instant application claim 86 is not patentably distinct from claim 3 of ‘412 because claim 3 of ‘412 recites ‘wherein the cross-linkable protein is selected from the group consisting of collagen and
gelatin’ which is not patentably distinct from the instant application claim 86.
RESPONSE TO REMARKS: Beginning on p. 14 of Applicant’s remarks, Applicant contends that the rejection has been addressed. In summary, Applicant contends that the cited claims recite compositions containing scaffold- or foam-forming materials and cross-linking components, whereas pending claim 81 requires a finished plurality of water-insoluble, essentially cross-linker-free microparticles comprising cross-linked protein. Applicant contends that the Examiner does not establish that the cited patent claims render obvious this claimed combination of features. Applicant contends that nor do the additional cited features, including micronized protein powder or gelatin powder, eliminate this distinction. Those features relate to materials used in scaffold or foam compositions, not to a plurality of water-insoluble, essentially cross-linker-free microparticles comprising cross-linked protein as presently claimed.
The argument is not persuasive. Examiner contends that claim 1 of ‘412 which recites ‘the composition comprising: a cross-linkable protein comprising at least one RGD (Arg-Gly-Asp) motif; and a cross-linker which induces cross-linking of the cross linkable protein,’ is not patentably distinct from the instant application claims 81-85, 91, 93-95 as said claim limitation is not patentably distinct from the recitation ‘a plurality of microparticles, comprising:(a) a cross-linked protein, wherein said cross-linked protein comprises at least one RGD (Arg- Gly-Asp) motif; wherein the plurality of microparticles is essentially cross-linker-free; wherein the plurality of microparticles is water insoluble’ of the instant application claim 81, upon which all claims of the instant application depend upon. Regarding the recitation ‘wherein the plurality of microparticles is essentially cross-linker-free; wherein the plurality of microparticles is water insoluble’ of the instant application claim 81. Since the plurality of microparticles (cross-linked and noncross-linked gelatin) are in cold liquids, said composition would inherently be water soluble as it is well-known in the art that at low temperature, gelatin is insoluble. Since the Office does not have the facilities for examining and comparing Applicants’ gelatin with the gelatin of the prior art, the burden is on the Applicant to show a novel or unobvious difference between the claimed product and the product of the prior art (i.e., that the microparticles of the prior art does not possess the same mineral composition of the claimed microparticles). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
Regarding the recitation ‘essentially cross-linker free,’ since Applicant has not clearly defined the term ‘essentially,’ it is the Examiner’s position that the composition recited by ‘412 is ‘essentially’ free of cross-linker as some of cross-linker could be unbound to the microparticles (collagen).
The rejection of claims 81-95 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5 of U.S. Patent No. US10596194 which are commonly owned and have seven common inventors and filed before the instant application is maintained. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are drawn to a composition, comprising: a closed-cell foam; wherein the composition comprises: a. cross-linkable gelatin; b. a cross-linker; and c. a liquid, wherein the composition is a porous scaffold, having a pore size from 2 to 500 microns.
The instant application claims 81-95 are not patentably distinct from claims 1, 5 of ‘194 because claims 1, 5 of ‘194 recites ‘a composition, wherein the composition comprises: a. cross-linkable gelatin; b. a cross-linker; and c. a liquid, having a pore size from 2 to 500 microns,’ which is not patentably distinct from the instant application claims 81-95.
RESPONSE TO REMARKS: Beginning on p. 14 of Applicant’s remarks, Applicant contends that the rejection has been addressed. In summary, Applicant contends that the cited claims recite compositions containing scaffold- or foam-forming materials and cross-linking components, whereas pending claim 81 requires a finished plurality of water-insoluble, essentially cross-linker-free microparticles comprising cross-linked protein. Applicant contends that the Examiner does not establish that the cited patent claims render obvious these claimed combination of features. Applicant contends that nor do the additional cited features, including micronized protein powder or gelatin powder, eliminate this distinction. Those features relate to materials used in scaffold or foam compositions, not to a plurality of water-insoluble, essentially cross-linker-free microparticles comprising cross-linked protein as presently claimed.
The argument is not persuasive. Examiner contends that claims 1 and 5 of ‘194 which recites ‘a composition, wherein the composition comprises: a. cross-linkable gelatin; b. a cross-linker; and c. a liquid, having a pore size from 2 to 500 microns,’ is not patentably distinct from the instant application claims 81-95 as said claim limitation is not patentably distinct from the recitation ‘a plurality of microparticles, comprising:(a) a cross-linked protein, wherein said cross-linked protein comprises at least one RGD (Arg- Gly-Asp) motif; wherein the plurality of microparticles is essentially cross-linker-free; wherein the plurality of microparticles is water insoluble’ of the instant application claim 81, upon which all claims of the instant application depend upon. Regarding the recitation ‘herein the plurality of microparticles is essentially cross-linker-free; wherein the plurality of microparticles is water insoluble’ of the instant application claim 81, the limitation of ‘water insoluble’ is inherent to the structure of a cross-linked gelatin composition. Since the plurality of microparticles (cross-linked and noncross-linked gelatin) are in cold liquids, said composition would inherently be water soluble as it is well-known in the art that at low temperature, gelatin is insoluble. Since the Office does not have the facilities for examining and comparing Applicants’ gelatin with the gelatin of the prior art, the burden is on the Applicant to show a novel or unobvious difference between the claimed product and the product of the prior art (i.e., that the microparticles of the prior art does not possess the same mineral composition of the claimed microparticles). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594. Regarding the recitation ‘essentially cross-linker free,’ since Applicant has not clearly defined the term ‘essentially,’ it is the Examiner’s position that the composition recited by ‘194 is ‘essentially’ free of cross-linker as some of cross-linker could be unbound to the microparticles (collagen).
Conclusion
Status of claims
Claims 81-100 are pending.
Claim 1-80 are canceled.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERICA NICOLE JONES-FOSTER whose telephone number is (571)270-0360. The examiner can normally be reached mf 7:30a - 4:30p.
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/ERICA NICOLE JONES-FOSTER/ Examiner, Art Unit 1656
/MANJUNATH N RAO/ Supervisory Patent Examiner, Art Unit 1656
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